(Amino)(Carboxy) Radicals

UNIVERSITY OF CALIFORNIA, SAN DIEGO

Experimental and Theoretical Investigations into the Stabilization of Captodative (Amino)(Carboxy) Radicals

A dissertation submitted in the partial satisfaction of the requirements for the degree of Doctor of Philosophy

Chemistry

Janell Kathryn Mahoney

Committee in charge:

Professor Guy Bertrand, Chair Professor Adah Almutairi Professor Joshua Figueroa Professor Michael Tauber Professor William Trogler

2017

The Dissertation of Janell Kathryn Mahoney is approved, and it is acceptable in quality and form for publication on microfilm and electronically:

Chair

University of California, San Diego

2017

iii

DEDICATION

This thesis is dedicated to my family and fiancé.

TABLE OF CONTENTS

Signature Page ...... iii

Dedication ...... iv

Table of Contents ...... v

List of Abbreviations ...... vii

List of Figures ...... viii

List of Schemes ...... xii

List of Tables ...... xiii

Acknowledgments ...... xiv

Vita...... xviii

Abstract of the Dissertation ...... xx

General Introduction ...... 1

Chapter 1: Bottleable (Amino)(Carboxy) Radicals Derived from Cyclic (Alkly)(Amino) Carbenes

...... 15

Introduction ...... 16

(A) A monomeric (amino)(carboxy) radical ...... 17

(B) Di- and tri-(amino)(carboxy) radicals ...... 20

Conclusion ...... 23

Appendix: Experimental Section ...... 24

Chapter 2: Air-Persistent (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino)

Carbenes ...... 32

Introduction ...... 33

(A) Computational analysis ...... 34

(B) Experimentally obtained (amino)(carboxy) radicals ...... 37

Conclusion ...... 44

Appendix: Experimental Section ...... 45

Chapter 3: The Suitability of Stable Acyclic Carbenes as Building Blocks for Capto-dative C-

Centered Radicals ...... 71

Introduction ...... 72

(A) Cyclic and acyclic N-heterocyclic carbenes ...... 74

(B) Acyclic (amino)(alkyl) carbene ...... 81

Conclusion ...... 86

Appendix: Experimental Section ...... 87

Chapter 4: A Redox Bistable Molecular Switch Built from (Amino)(Carboxy) Radical Architecture

...... 96

Introduction ...... 97

(A) A molecular switch ...... 100

(B) Tuning redox bistability as a function of the carbene ligand ...... 106

Conclusion ...... 117

Appendix: Experimental Section ...... 118

Conclusion ...... 139

References ...... 145

LIST OF ABBREVIATIONS

Bz: Benzoyl

Bn: Benzyl

CAAC: Cyclic (alkyl)(amino) carbene

DDQ: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

DIPP: 2,6-iPr2(C6H3)

DFT: Density functional theory

ERP: Electron paramagnetic resonance iPr: Isopropyl

LUMO: Lowest unoccupied molecular orbital

Me: Methyl

MES: 2,4,6-Me3(C6H2)

NHC: N-heterocyclic carbene

Ph: Phenyl

RDE: Rotating disk electrode

SOMO: Singly occupied molecular orbital

TDAE: Tetrakis(dimethylamino)ethylene

THF: Tetrahydrofuran

ZORA: Zeroth order regular approximation

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LIST OF FIGURES

Figure I.1: Gomberg’s radical...... 3

Figure I.2: Modified tri(phenyl)methyl radicals...... 4

Figure I.3: Poly-radicals related to the tri(phenyl)methyl radical...... 5

Figure I.4: Phenalenyl radical and its σ-dimer (left) and the SOMO (right)...... 6

Figure I.5: The 2,5,8-tri-tert-butylphenalenyl radical and its π-dimer...... 6

Figure I.6: Nitrogen containing phenalenyl radicals...... 7

Figure I.7: Cyclopentadienyl radicals...... 8

Figure I.8: The singlet and triplet carbene electronic states ...... 9

Figure I.9: A stable cyclic (alkyl)(amino) carbene (CAAC)...... 10

Figure I.10: Carbene supported paramagnetic metal complexes...... 11

Figure I.11: Selected examples of carbene stabilized main group paramagnetic species. .... 12

Figure I.12: Organic radicals derived from carbenes...... 13

Figure 1.1: Examples of captodative substituted radicals and carbene derived organic radicals...... 16

Figure 1.2: Cyclic voltammogram of 1.2a. Potentials referenced with respect to Fc+/Fc...... 18

Figure 1.3: X-ray structure of 1.2a and 1.3a. Hydrogen atoms, solvent molecules and the chloride anion (for 1.2a) were omitted for clarity...... 18

Figure 1.4: Left: Representation of the SOMO of 1.3a (isosurfaces at 0.05au). Right: X-band EPR spectra of 1.3a in benzene at room temperature...... 19

Figure 1.5: Cyclic voltammogram of 1.2b (top) and 1.2c (bottom). Corrected with respect to the Fc+/Fc...... 21

Figure 1.6: X-ray crystal structure of 1.2b. Hydrogens, solvent molecules, and chloride anions are omitted for clarity...... 21

Figure 1.7: X-ray crystal structures of 1.3b (right) and 1.3c (left). Hydrogen atoms and solvent molecules as well as the isopropyl, ethyl, and methyl substituents of 1.3c, are omitted for clarity...... 22

Figure 1.8: X-band EPR spectra of 1.3b (right) and 1.3c (left) in benzene at room temperature...... 22

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Figure 1.9: a) X-band EPR spectra of 1.3b at half-field and at temperatures ranging from 4-10 K; the triplet oxygen signal was subtracted out of the spectrum for visual purposes. b) I*T versus T (I = intensity; T = temperature) points for the EPR measurements (□) and a fitting plot with the Bleany-Blowers equation (inset)...... 23

Figure 2.1: The tri(aryl) radical 2.A, per-chlorinated tri(phenyl)methyl radical 2.B, and assorted (amino)(carboxy) radicals 2.C-E...... 34

3 Figure 2.2: Plot of the enthalpy of the reaction of O2 with model (amino)(carboxy) radicals against the Hammett parameter σp of R (top) and the Mulliken spin density on C2 (bottom). R- groups which will be investigated experimentally are given in red...... 35

Figure 2.3: Calculated Mulliken spin densities for model (amino)(carboxy) radicals with increasing Hammett parameters σp from the bottom to the top...... 36

Figure 2.4: Plot of the ratios of Mulliken spin density on C2 and O1 against σp. R groups investigated experimentally are given in red...... 37

Figure 2.5: Cyclic voltammograms of 2.2a-e. Insets illustrate the reversibility of the first reduction wave for 2.2a and 2.2c-e. Spectra are referenced to Fc+/Fc...... 39

Figure 2.6: Solid-state structures of 2.3a-b and 2.3d-f. Hydrogen atoms, solvent molecules and the counter-anion and isopropyl groups of 2.3f are omitted for clarity...... 40

Figure 2.7: Optimized structures of 2.3a’ (left) and 2.3a’’ (right). Calculated at the B3LYP/6- 311g** level of theory...... 41

Figure 2.8: Top: Experimental EPR spectra of (amino)(carboxy) radicals 2.3b-f in dichloromethane. Bottom: Simulated spectra using isotropic hyperfine coupling constants given in Table 2.1...... 42

Figure 2.9: The X-band EPR spectra of 2.3a at 5.0 mW (left) and 63.0 mW (right)...... 42

Figure 2.10: Energy of model radical 2.3f’ as a function of dihedral angles θ1 and θ2, geometry being optimized on all other internal coordinates (B3LYP/6-31G*)...... 43

Figure 2.11: Decay of radicals 2.3b-f in solution after exposure to air or after exposure to water (x) and air (□)...... 44

Figure 3.1: a) Dimerization of (amino)(carboxy) radical 3.A. b) General synthesis of monomeric representatives 3.2 from stable (amino)carbenes 3.1...... 72

Figure 3.2: Stable carbenes 3.1a-h and the corresponding captodative radicals 3.2a-h...... 73

Figure 3.3: a) Cyclic voltammogram of 3.3 before (black) and after (red) electrolysis. b) UV-Vis monitoring (1 scan every 50 seconds) of the electrochemical reduction of 3.3 on a reticulated vitreous electrode at -1.40 V. c) Rotating disk electrode voltammetry (RDE; 10 mV/s; 600 rpm) of 3.3. d) RDE after exhaustive electrolysis...... 75

Figure 3.4: a) Cyclic voltammogram of 3.4 before (black) and after (red) electrolysis. b) UV-Vis monitoring (1 scan every 50 seconds) of the electrochemical reduction of 3.4 on a reticulated vitreous electrode at -1.50 V. c) Rotating disk electrode voltammetry (RDE; 10 mV/s; 600 rpm) of 3.4. d) RDE after exhaustive electrolysis...... 76

Figure 3.5: Isotropic X-band EPR spectra of 3.2b, 3.2g, 3.5 and 3.7 (top) and the corresponding simulated band shapes with the following isotropic hyperfine coupling constants: 3.2b, a(15N) = 6.6 and 5.4 MHz, a(1H) = 10.66 (2), 8.30 (2), 1.49, 2.08, and 3.21 MHz; 3.2g, a(15N) = 11.6 and 6.0 MHz, a(1H) = 8.9, 6.1, 7.9, 3.9, 3.2 MHz; 3.5, a(15N) = 20.6 MHz, a(1H) = 22.8 MHz; ect.. 77

Figure 3.6: Representation of the optimized geometries of 3.2g, 3.2g’, and 3.2g’’ at the B3LYP/TZVP level of theory. The majority of the isopropyl hydrogens have been removed for clarity...... 78

Figure 3.7: X-ray crystal structure of dimer 3.6. Hydrogens removed for clarity. Selected bond lengths [pm] and angles [deg]: C2-C2’: 153.8(3); C1-C2: 153.4(4); C1-O1: 122.4(3); N1-C2-C1: 113.6(2)...... 80

–1 –1 Figure 3.8: CV curves of 3.8 (1.0 mmolL ) in CH3CN + (n-Bu)4NPF6 0.1 molL (carbon electrode, Φ = 3 mm; E vs Fc+/Fc). Scan rates: (a) v = 0.2 V s–1; (b) v = 6.4 V s–1...... 82

Figure 3.9: Representations of the optimized geometry of 3.2b, 3.2g and 3.2h at the B3LYP/TZVP level of theory; top: front view; middle: view along the C1-C2 axis; bottom: view along the N1-C2 axis. The isopropyl groups of 3.2b have been removed for clarity...... 85

Figure 4.1: Systems characterized by magnetic bistability...... 97

Figure 4.2: Molecular switches characterized by redox bistability...... 98

Figure 4.3: Isolated bi-radical 4.J and proposed bi-radical 4.K...... 99

Figure 4.4: Potential di-radical modifications...... 100

- Figure 4.5: a) Cyclic voltammogram curve of 4.2a2BF4 in CH3CN + 0.1 M NBu4PF6 at a scan rate of 0.1 V·s-1 at room temperature. Spectrum referenced with respect to Fc*+/Fc*. b) UV-Vis - spectra of 4.2a2BF4 and 4.3a in dichloromethane...... 101

- Figure 4.6: X-ray crystal structure of 4.2a2BF4 . Hydrogen atoms, solvent molecules, and anions have been removed for clarity. Selected bond lengths [pm] and angles [deg]: C1-O1: 120.9(3); C1-C2: 152.9(3); C2-N1: 128.6(3); C4-O2: 120.2(3); C4-C5: 153.3; C5-N2: 128.9(3); N1-C2-C1: 124.9(2); C4-C5-N2: 125.5(2)...... 102

Figure 4.7: X-ray crystal structure of 4.3a. Hydrogen atoms and isopropyl groups have been removed for clarity. Selected bond lengths [pm] and angles [deg]: O1-C5: 147.27(15); O1-C1: 141.72(15); C1-C2:134.66(19); C1-C3: 152.63(19); C2-N1: 143.40(17); O2-C4: 120.67(17); C4- C5: 151.61(19); C5-N2: 142.93(17); C1-O1-C5: 113.20(10)...... 102

Figure 4.8: Square scheme of the redox induced structural changes to 4.2a...... 103

Figure 4.9: Cyclic voltammetry data for 4.3a at room temperature with a sweep rate range of -1 -1 0.2-12.8 Vs (a) and at -40 ˚C with a sweep rate range of 0.1-2.0 Vs (b) in CH3CN + 0.1M + NBu4PF6. Spectra referenced with respect to Fc* /Fc*...... 104

Figure 4.10: Computational square scheme of 4.2a...... 105

Figure 4.11: Possible isomers of 4.3a...... 106

Figure 4.12: Cyclic voltammograms of 4.2b (A) and 4.2c (C). Inset B demonstrates the reversibility of the first 4.2b reduction wave. Spectra referenced with respect to Fc+/Fc...... 108

Figure 4.13: Carbenes 4.1f-i...... 108

Figure 4.14: Proposed molecular switch systems, where L is an arbitrary linking group...... 109

Figure 4.15: Optimized geometry of 4.16...... 112

Figure 4.16: Cyclic voltammogram of 4.17a. Spectrum referenced with respect to Fc+/Fc. . 113

Figure 4.17: Proposed nitroso-based molecular switch...... 114

Figure 4.18: Azodioxy dimers 4.34a-b...... 116

Figure C.1: Stable monomeric (amino)(carboxy) radical and related bi- and tri- radicals. .... 140

Figure C.2: (Amino)(carboxy) radicals bearing succesively more electron withdawing R-acyl substituents...... 141

Figure C.3: (Amino)(carboxy) radicals C.5-6 derived from acyclic carbenes and enolate C.7...... 142

Figure C.4: Future C-centered radicals ...... 142

Figure C.5: Molecular switch system characterized by redox bistability...... 143

Figure C.6: Stable carbenes to be considered as molecular switch synthons...... 143

Figure C.7: Molecular switches with alternate linking moieties...... 144

Figure C.8: Further modifications to the initial molecular switch framework...... 144

LIST OF SCHEMES

Scheme I.1: First isolable carbenes...... 8

Scheme I.2: Fukuzumi’s radical...... 12

Scheme 1.1: Synthesis of iminium precursor 1.2a and a stable monomeric (amino)(carboxy) radical 1.3a starting from free carbene 1.1...... 17

Scheme 1.2: Synthesis of bi- and tri- (amino)(carboxy) radicals 1.3b and 1.3c starting from free carbene 1.4...... 20

Scheme 2.1: The synthesis of iminium precursors 2.2a-e and radicals 2.3a-e starting from carbene 2.1a, and 2.5 and 2.3f starting from carbene 2.1b...... 38

Scheme 3.1: Synthesis of radicals 3.2b and 3.2g...... 74

Scheme 3.2: Decomposition of radical 3.2g...... 80

Scheme 3.3: Synthesis of enol 3.10...... 81

- Scheme 4.1: Synthesis of 4.2a2BF4 and 4.3a...... 100

Scheme 4.2: Experimental results for synthesizing molecular switches from carbenes 4.1b-e...... 107

Scheme 4.3: Proposed synthetic pathway to 4.10 (top). Experimentally obtained α- amino(ketone) 4.11 (bottom)...... 110

Scheme 4.4: Formation of acyl chloride 4.13a...... 110

Scheme 4.5: Proposed synthetic pathway to 4.10 from acyl chloride 4.13b (top). Experimentally obtained adduct 4.14(bottom)...... 111

Scheme 4.6: Synthesis of 4.11 by addition of phosgene to carbene 4.1i...... 111

Scheme 4.7: Synthesis of 4.12 from acyl chloride 4.13a...... 111

Scheme 4.8: Synthesis of di-(amino)(carboxy) radicals 4.17a-b...... 113

Scheme 4.9: The isodesmic reaction of 4.18a-b and 4.19a-b...... 115

Scheme 4.10: Synthesis of acyl chloride 4.25 by irradiation of diazo 4.24...... 115

Scheme 4.11: Proposed synthesis of 4.28 from 2-nitrosobenzaldehyde 4.26 (top). Compound 4.29 was isolated from the crude reaction mixture (bottom)...... 116

Scheme 4.12: Proposed synthesis of 4.28 from 4.32...... 116

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LIST OF TABLES

Table 1.1: Computed Mulliken spin density and isotropic hyperfine coupling constants aN (MHz) for 1.3a...... 19

Table 2.1: Structural parameters, redox potentials, EPR hyperfine coupling constants and Mulliken spin densities of radicals 3a-f (calculated valuesa are in parenthesis)...... 38

Table 3.1: Calculated zero-point energies (Hartree) and isotropic hyperfine coupling constants (MHz) of 3.2g, 3.2g’ and 3.2g’’...... 78

Table 3.2: Key structural parameters of 3.2g, 3.2g’, and 3.2g’’...... 78

Table 3.3: Calculated Mulliken spin densities for conformers 3.2g, 3.2g’ and 3.2g’’...... 79

Table 3.4: Experimental measures of the electronic properties of carbenes 3.1a-h and the corresponding radicals 3.2a-h...... 83

Table 3.5: Calculated Radical Stabilization Energy (RSE) of representative radicals (relative to  H3C ) and Deviation from Additivity of RSE (DARSE) for the corresponding captodative radicals...... 84

Table 3.6: Select calculated geometric parameters of radicals 3.2b, 3.2e and 3.2g-h at the B3LYP/TZVP level of theory...... 85

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ACKNOWLEDGEMENTS

Firstly, I would like to thank Prof. Adah Almutairi, Prof. Joshua Figueroa, Prof. Michael

Tauber and Prof. William Trogler for taking the time to evaluate this work.

To my advisor, Prof. Guy Bertrand. Thank you for taking me into your group within your first year here at UCSD. The work that I have done here in your group has helped me grow as a scientist, and I cannot thank you enough for that. I would also like to thank you for supporting my ambitions to go to France. It was an amazing experience and I learned a lot about both electrochemistry and your wonderful country. Thanks again and all the best.

I am also extremely grateful to Prof. David Martin, who not only was my mentor during his time here at the University of California, San Diego, but also my hosting professor during the short time I spent in Grenoble, France. He introduced me to the lab, and helped me with any tricky experiments when I was first starting out. Since then, he has continually assisted me and helped me grow as a scientist, and has always made time to meet with me and discuss science.

He encouraged me to apply to the Chateaubriand fellowship, and became my hosting professor when I got it. I would like to thank him for helping both prepare for my trip, especially with the visa and housing, and for looking after me while I was there. Thank you for all the hiking, the

French cuisine, and for having me over for dinner with your amazing family. I wish him all the best with his career in France, and hope that I get to come back and visit someday.

I would also like to thank Mo for all his assistance though out the years. From helping me analyze my CV spectra, to helping me obtain EPR spectra from my first paper he has always been willing to put aside a couple of minutes to help me. No matter how lost I was on a subject or concept, Mo would patiently walk me though it until I understood. So, I would like to thank him for his help and patience throughout the years.

I would also like to thank Michelle for all her help and assistance throughout the years.

You always made sure that the lab was up and running and always told me to order the chemicals I needed instead of laboring through the difficult synthesis. Thanks for all your help and for all the discussions on both chemistry and French culture.

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Rudy, although a new addition to the team, has been a huge help to me. Whether I need to discuss science and ideas for my project or simply needed some advice on the papers

I was writing, Rudy was always there to help me and give me his honest opinion. Thanks for helping me become a better writer and scientist.

I have also seen a number of talented scientist pass through the lab who have touched me in a number of ways. My thoughts go out to Bastien, Caleb, Conor, David, Daniel, Desiree,

Domenik, Dominik, Eder, Erik, Fabian, Glen, Jesse, Jiaxang, Jing, Liu, Mael, Martin, Robert,

Steffen and Xingbang.

To Gael Ung, who took me under his wing when I first arrived in the lab, and helped me through the synthesis of my first carbene, I would like to thank you for all your support. I wish you the best with your new position at the University of Connecticut.

I would also like to thank Cory, who started his Ph.D. at the same time I did. While he was always extremely busy, he was always there to listen to problems I was having and offer up good advice on how to fix it. He has always inspired me with his love of chemistry and teaching. Thanks for everything and I wish you the best in your future endeavors.

I would also like to thank Fatme Dahcheh who did a short stint in our lab during her

Ph.D. and then joined our lab again as a post doc. You became my good friend, and I enjoyed talking to you about chemistry, life and the future over coffee. I had an awesome time over

Easter. I wish you all the best in Canada and hope to see you again soon.

To Pauline, who became my good friend. When your first walked into lab for your rotation with us, I instantly knew that I wanted you to join. I know that you had a lot of other options, so I was really excited when you joined us and got put in my lab. You livened up the lab and were always there to support me in lab. I also enjoyed all of our swimming expeditions and still miss you in the pool. I wish you all the best with your future, whether that be joining another lab or heading out into the work force.

I would also like to thank Max Hansmann, who helped me interpret very old pieces of

German literature and figure out how to get their reactions actually working. I would also like to

xv thank you for helping me figure out how to do calculations here at UCSD when I got back from

France.

In the last year of my Ph.D. I got the opportunity to do a fellowship in Grenoble, France.

I met a number of amazing people and I would like to thank everyone in the CIRE lab for all their help and support they gave me even though I was only there a short time.

I would especially like to thank Vianney, a Ph.D. student studying under the direction of

David Martin. Not only did he continually help me in the lab, by both showing me where everything was or how to do new techniques, but he also became my good friend over lunch, mid-afternoon coffee, cheese sampling and hiking. He was also my French mentor, and while I have still not mastered the French “r” sound, he continually helped me with my pronunciation and would always have a story handy about French culture or sayings. I hope that I adequately returned the favor by telling him about American culture. I would like to thank him for his friendship and I wish him all the best with his Ph.D and future endeavors.

I would also like to thank Prof. Guy Royal for all his help in electrochemistry. He personally helped me with some of the experiments, and explained the theory about what we were doing while sitting there. He really helped me gain a deeper understanding of electrochemistry and for that I am very grateful.

I would also like to say thank you to Florian Molton who assisted me in acquiring EPR data at low temperatures.

X-ray crystallography was an integral piece of my research, and therefore I would like to thank Dr. Arnold Rheingold and Dr. Curtis Moore for both training me to use the equipment and for helping me solve any issues I might have had with my structures. I would also like to thank Anthony Mrse for both training me to use the NMR facilities and helping me with any new techniques I needed to use.

This material is based upon research supported by the Chateaubriand Fellowship of the

Office for Science & Technology of the Embassy of France in the United States.

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Lastly, I would like to thank my family, fiancé and friends who have stood by me and encouraged me throughout my Ph.D.

Chapter 1 has been adapted from materials published in Mahoney, J. K.; Martin, D.;

Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2013, 135, 18766-18769. The dissertation author was the primary investigator of this paper.

Chapter 2 has been adapted from materials published in Mahoney, J. K.; Martin, D.;

Thomas, F.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2015, 137, 7519-

7525. The dissertation author was the primary investigator of this paper.

Chapter 3 has been adapted from materials currently being prepared for submission.

Mahoney, J. K.; Jazzar, R.; Royal, G.; Martin, D.; Bertrand, G. The dissertation author was the primary investigator of this paper.

Chapter 4 has been adapted from materials currently being prepared for submission.

Mahoney, J. K.; Royal, G.; Moore, C. E.; Rheingold, A. L.; Martin, D.; Bertrand, G. The dissertation author was the primary investigator of this paper.

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VITA

Education

UC San Diego San Diego, CA Ph.D. Chemistry March 2017 Chateaubriand Fellowship recipient (2015)

UC San Diego San Diego, CA M.S. Chemistry June 2014

University of Nevada, Reno Reno, NV B.S. Chemistry with Honors May 2012 Westfall Scholar Award recipient (2012)

Core Qualifications

. Synthesis of air and water sensitive materials (Shlenk and glove box techniques). . Nuclear Magnetic Resonance (NMR; 1H, 13C, 19F and 31P), high resolution mass spectroscopy (HRMS), UV-Vis spectroscopy and fluorescence spectroscopy. . Electrochemistry: cyclic voltammetry (CV), rotating disk electrode (RDE) voltammetry and potentiostatic coulometry. . Electron Paramagnetic Resonance (EPR) . X-Ray crystallography . Recrystallization: single and multiple solvent, diffusion, slow evaporation and hot filtration . Column Chromatography: basic silica . Software: ChemDraw, Gaussian, GaussView, Olex, Mercury, POV-Ray, and Matlab

Research Experience

UC San Diego San Diego, CA Graduate Researcher with Prof. Guy Bertrand 2012-present . Collaborator: David Martin, Université Joseph Fourier. Grenoble, France. . Prepared oxygen and water sensitive materials using standard Shlenk techniques. . Characterized materials by NMR, MS, UV-Vis and X-ray crystallography. . Investigated paramagnetic materials through electrochemical techniques, including CV, RDE and potentiostatic coulometry, and EPR. . Analyzed and modeled EPR data using Matlab. . Interpreted technical material for non-technical audiences at multiple conferences.

University of Nevada, Reno Reno, NV Undergraduate Researcher with Prof. Vincent Catalano 2010-2012 . Investigated the structure, bonding and optical properties of polymetallic complexes. Developed a new synthetic pathway to imidazole ligands with extended pi-systems using a metal template. . Analyzed complexes using X-ray crystallography and fluorescence spectroscopy techniques.

Publications

. Janell K. Mahoney, Guy Royal, Curtis E. Moore, Arnold L. Rheingold, David Martin and Guy Bertrand. “A Redox Bistable Molecular Switch Built from (Amino)(Carboxy) Radicals Architecture.” In preparation.

. Janell K. Mahoney, Rodolphe Jazzar, Guy Royal, David Martin, and Guy Bertrand. “On the Advantage of Cyclic over Acyclic Carbenes to Access Isolable Stable Captodative C-Centered Radicals.” Chem. Eur. J., Accepted for publication.

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. Janell K. Mahoney, David Martin, Fabrice Thomas, Curtis E. Moore, Arnold L. Rheingold, and Guy Bertrand. “Air-Persistent Monomeric (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino) Carbenes.” J. Am. Chem. Soc. 2015, 137, 7519- 7525.

. Janell K. Mahoney, David Marin, Curtis E. Moore, Arnold L. Rheingold, and Guy Bertrand. “Bottleable (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino) Carbenes.” J. Am. Chem. Soc. 2013, 135, 18766-18769.

Conference Presentations

. Janell Mahoney (June 2015) Air-Persistent Monomeric (Amino)(Carboxy) Radicals. Presentation at Semaine d’Etudes en Chimie Organique (French organic chemistry student conference), Sulniac, France.

. Janell Mahoney (May 2015) Air-Persistent Monomeric (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino) Carbenes. Invited seminar at the Université Joseph Fourier. Grenoble, France.

. Janell Mahoney (March 2015) Bottleable (Amino)(Carboxy) Radials Derived from Cyclic (Alkyl)(Amino) Carbenes. Presentation at the national meeting of the American Chemical Society (ACS). San Diego, CA.

Awards

Chateaubriand Fellowship ($6,500) April 2016-July 2016 . Competitive fellowship supporting Americans who wish to conduct research in France.

Westfall Scholar Award May 2012 . Awarded for the highest GPA in the chemistry division of the College of Science

Teaching Experience

UC San Diego San Diego, CA Teaching Assistant September 2012-March 2016 . Instructed introductory general and organic chemistry laboratory courses and discussion sections. . Assisted faculty members with classroom instruction, exams and record keeping . Facilitated set up and clean-up of laboratory experiments and ensured adherence to safe laboratory practices. . Developed pertinent examples and problems to compliment lecture material.

University of Nevada, Reno Reno, NV Teaching Assistant May 2012-July 2012 . Instructed a general chemistry laboratory class. . Provided students with basic laboratory skills, and reinforced lecture material during experiments. . Provided clear safety instructions to mitigate risk to students . Assisted the faculty member with instruction, exams, grading and record keeping.

Supplemental Instructor January 2012-May 2012 . Developed lesson plans and group activities designed to enhance comprehension and retention of class material.

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ABSTRACT OF THE DISSERTATION

Experimental and Theoretical Investigations into the Stabilization of Captodative (Amino)(Carboxy) Radicals

Janell Kathryn Mahoney

Doctor of Philosophy in Chemistry

University of California, San Diego, 2017

Professor Guy Bertrand, Chair

Remarkable advances in the field of radical chemistry have been made since the seminal isolation of tri(phenyl)methyl radical by Gomberg in 1900. However, carbon centered radicals are still primarily considered as observable, but non-isolable species. Two key factors have inhibited the isolation of these species, namely their inclination to dimerize due to a high

C-C bond dissociation energy, and their proclivity to react with oxygen to form peroxides and other derivatives. Herein, we will demonstrate stable monomeric C-centered (amino)(carboxy) radicals, and even related bi- and tri-radical species, can be successfully synthesized by utilizing stable carbenes as building blocks. We will also establish that simple modifications to the acyl

R-substituent of these paramagnetic species can lead to highly air persistent variants. Indeed bulky and electron-withdrawing acyl substituents lead to ambidentate C,O-radicals with life- times ranging from several hours to days in the most favorable case. We will then highlight the importance of subtle steric factors, which not only affect the susceptibility of these systems

toward undesired reactions, but also control the intrinsic stability of the paramagnetic species, in a comparative study on (amino)(carboxy) radicals constructed from cyclic and acyclic carbenes. Lastly, we will discuss a di-iminium with a flexible linking acyl moiety which undergoes spontaneous intramolecular cyclization upon a two-electron reduction. Importantly, this system exhibits two requirements of a molecular switch, specifically bistability and reversibility.

xiv

GENERAL INTRODUCTION

Radicals are sub-valent compounds which are typically considered as transient species that rapidly undergo dimerization, hydrogen abstraction, or disproportionation. These reactivity pathways are thermodynamically favored, and occur with little to no activation barrier.1 However, it is evident that certain types of molecular architectures can lead to the isolation of stable and highly useful radicals. Indeed, paramagnetic species have been investigated in synthetic chemistry,2 particularly as co(catalysts) for the oxidation of alcohols to carbonyl compounds,3 polymer synthesis,4 as antioxidants,5 and as synthons for materials. 6 Additionally, several techniques, including spin labeling,7 spin trapping8 and electron paramagnetic resonance (EPR) imaging,9 have successfully incorporated stable radicals as reporter molecules in biological systems with the goal of obtaining structural, dynamic, and reactivity information.

A) Carbon-Centered Radicals

When considering the plethora of stable radicals available, it is clear that most are heteroatom (nitroxides, thiazyls and verdazyls) and not carbon based.10 Two debilitating factors have inhibited the isolation of C-centered radicals. Firstly, they have a propensity to dimerize due to the strength of the C-C bond (80 kcalmol-1 compared to 30-40 kcalmol-1 for O-O and N-

N bonds).11 Secondly their proclivity to react with oxygen leads to the formation of peroxide radicals and related derivatives. Despite these disadvantages, a number of notable C-centered radicals can be identified throughout the literature. For the purposes of this discussion, and in accordance to Ingold’s definitions, stable radicals are herein defined as species which can be isolated as a pure compound; those paramagnetic species which are long-lived enough to be observed by spectroscopy but are non-isolable will be considered as persistent.12

Gay-Lussac first reported the formation of cyanogen (the dimer of CN) upon heating mercury cyanide in 1815.13 This experiment, and several other investigations by Bunsen,14

Frankland,15 and Wurtz16 suggested the existence of carbon centered radicals, but there was little interest in these paramagnetic species within the scientific community until 1900 when

Gomberg isolated the tri(phenyl)methyl radical upon treatment of triphenylmethyl chloride with

either silver or zinc metal.17-18 While the tri(phenyl)methyl radical monomer could be observed in solution, a dimer formed in the solid state despite the steric protection of the phenyl groups, which adopt a propeller conformation (twist angle = 30˚).19 Several different dimers were initially proposed,20 but spectroscopic data20f eventually confirmed the formation of the

“Jacobson” structure, which consists of a σ-bond between the central carbon of one monomer and the para carbon of another.20c Gomberg’s radical was also found to be sensitive to oxygen, with a crystal structure by Gildwell confirming the formation of the “head to head” peroxide.21-22

Since then, Ayers and coworkers have demonstrated that the formation of the initially formed peroxy radical is reversible.23

Figure I.1: Gomberg’s radical.

Further modifications to the original tri(phenyl)methyl framework have led to increasingly stable variants. For example, Schlenk et al. demonstrated that substitution at the para position of all three phenyl rings results in a monomeric, albeit air sensitive, radical.24 An ortho substituted tri(phenyl)methyl radical by Kahr et al. was also shown to be monomeric in solution, and react very slowly with oxygen.25 Perhaps the most successful illustration is the perchlorinated radical developed by Ballester et al. which is considered to be essentially inter to air, with an estimated life-time of decades.26 The extreme stability of this radical stems from the increased twist angle of the phenyl groups ( 50˚)27 which both localizes the electron density at the central carbon and kinetically protects the radical from both dimerization and small molecule reactivity. Interestingly, Ballester28 and Domingo29 were also able to incorporate

carboxylate groups at the para positions of the perchlorinated tri(phenyl)methyl radical. The resultant paramagnetic species were found to form supramolecular assemblies via hydrogen bonding30 and bind to metals in both discrete metal complexes31 and metal-organic frameworks.32 Consequently, the extreme stability of the perchlorinated tri(phenyl)methyl radical, and other related derivatives, have led to their utilization in the design of multifunctional materials.33

Figure I.2: Modified tri(phenyl)methyl radicals.

The extension of the tri(phenyl)methyl molecular architecture towards the synthesis of poly-radicals was also investigated as early as 1904 by Thiel.34 This early example, the tetraphenyl-para-xylylene, structurally characterized by X-ray diffraction, has been shown to have some degree of di-radical character. Several related examples of extended linear polyaromatics by Tschitchibabin35 and Schmidt36 have displayed magnetic behavior, with the latter being recognized as a true di-radical. However, reports by Schlenk37 and Leo38 on the

first stable bi- and tri-radical species, respectively, are considered to mark the beginning of the study of “high spin” molecules with particular interest in their use as molecular magnets.39

Figure I.3: Poly-radicals related to the tri(phenyl)methyl radical.

Another molecular architecture which is well-known to yield persistent paramagnetic species is the phenalenyl radical which was first discovered by Reid40 and independently detected by Calvin.41 This molecule is both the smallest neutral odd-alternate π-conjugated hydrocarbon radical with a fused polycyclic structure and the smallest open shell graphene.42

The spin density in the phenalenyl radical is mainly distributed over the six α-carbons, with small contributions on the β-carbons, and no electron density localized on the central carbon. In dilute de-oxygenated solutions, the monomer persists indefinitely, while higher concentrations lead to the formation of a σ-dimer which has been calculated to have a bond dissociation enthalpy of

16 kcalmol-1.43 Additionally, further thermal decomposition of the dimer yields highly fused polycyclic hydrocarbons. Thus, while Haldon initially proposed this radical as a component for molecule-based conductors,44 the kinetic instability of this system has limited its applications.

Figure I.4: Phenalenyl radical and its σ-dimer (left) and the SOMO (right).

Efforts to sterically prevent dimerization through the inclusion of tert-butyl groups at the

β-positions were later made by Nakasuji.45 Importantly, these substituents had no effect on the electronics of the system, and thus, the 2,5,8-tri-tert-butylphenalenyl radical is considered to be the most electronically fundamental radical in the phenalenyl series. Interestingly, while the σ- dimerization pathway was effectively blocked, this molecule was still found to π-dimerize. The two molecules in the dimer are stacked anti-parallel to each other in order to minimize steric interactions, and are separated by 3.2 Å, a distance which is smaller than the sum of the van der Waals radius of the carbon atom (3.4 Å).43,46 Additional evidence for the formation of the π- dimer was given by both NMR data and a long wavelength transition in the UV-Vis spectrum.43,47

Haddon also determined that this dimer is diamagnetic at room temperature indicating a strong spin pairing between the two radical units.48 Several other phenalenyl radical derivatives featuring alkoxy,49a hydroxyl,49b-c amino,49b-c and N-S-N49d groups, and even a perchlorinated version, have since been realized.50

Figure I.5: The 2,5,8-tri-tert-butylphenalenyl radical and its π-dimer.

The phenalenyl framework was also modified by incorporation of nitrogen atoms. The first attempts by Nakasuji substituted two nitrogen atoms into the α-positions of the 2,5,8-tri-tert-

butylphenalenyl radical to form the 2,5,8-tri-tert-butyl-1,3-diazaphenalenyl.51 Interestingly, crystals of this radical show no apparent decomposition in air over a period of several years, and exhibited thermochromatic behavior. X-ray diffractometry studies at various temperatures revealed the coexistence of a σ- and π- dimer, with the ratio between the two being directly tied to temperature.52 Substitutions at the β-position with one and three nitrogens were also performed by Rubin, and astoundingly the later showed no dimerization in solution despite the lack of steric protection. 53-54

Figure I.6: Nitrogen containing phenalenyl radicals.

The last noteworthy framework which has successfully yielded several C-centered radicals is the cyclopentadienyl radical. While the transient unsubstituted “pristine radical” has only been observed at low temperatures,55 Sitzmann prepared the stable, but air sensitive, pentaisopropyl derivative and reported its crystal structure.56 Radical units within the crystal structure were separated by 5.28 Å, indicating no π-dimerization. Further efforts by Rubin yielded a robust pentakis(trialkylsilylenthynyl) substituted radical which was purified by column chromatography, and found to survive for days and even weeks under air in solution and the solid state, respectively.57 Lastly, Wasserman58 and Wudl59 have incorporated the cyclopentadienyl radical into C60 and monoaza-C60. However, the instability of these systems has prevented isolation, and therefore, the electronics of these radicals have only been studied in solution.60

Figure I.7: Cyclopentadienyl radicals.

B) Radicals derived from carbenes.

In 1988, Bertrand and co-workers reported the first isolable carbene, a

(phosphino)(silyl) carbene, which was generated by the photolysis of the corresponding diazo compound.61 Three years later, in 1991, Arduengo et al. isolated the first N-heterocyclic carbene

(NHC), which was generated by the simple deprotonation of the corresponding iminium chloride salt and fully characterized by X-ray crystallography.62 Since this ground breaking discovery by

Ardugeno, numerous derivatives, with varying heteroatoms, and diverse steric and electronic properties have been reported.63

Scheme I.1: First isolable carbenes.

Carbenes can exist in two different electronic states, namely the singlet and triplet states. Singlet carbenes feature a filled sp2 orbital and an empty p-orbital, the latter of which can effectively participate in π-backbonding, while triplet carbenes are characterized by two degenerate singly occupied orbitals (Figure I.8). Therefore, singlet carbenes display ambiphilic reactivity while triplet carbenes are best characterized as bi-radicals. In this way, the carbene ground state has a huge impact on both stability and reactivity. This is best exemplified by the large number of stable singlet carbenes which can be found the literature. By comparison, triplet carbenes are short lived species.64

Figure I.8: The singlet and triplet carbene electronic states

The (phosphino)(silyl) carbene is stabilized by push-pull effects wherein the phosphorus center donates electron density into the empty carbene p-orbital (push), while the silicon accepts electron density from the carbene lone pair into a low lying σ*-orbital (pull). Comparatively, the

NHC has two nitrogen substituents, both of which are σ- withdrawing and π- donating, which serve to stabilize the singlet state. These heteroatoms simultaneously stabilize both the occupied σ-oribital by inductively removing electron density, and the empty p-orbital through the mesomeric donation of electron density. Thus, while NHCs have been described as potent nucleophiles,65 their electrophilicty is diminished by the two nitrogens which donate electron density into the empty carbene p-orbital.

However, in 2005 Bertrand et al. demonstrated that carbenes could be both potent nucleophiles and electrophiles with the isolation of the cyclic (alkyl)(amino) carbene (CAAC).66

This carbene features one nitrogen substituent and one quaternary carbon, which is σ- and not

π-donating. This leads to enhanced σ-donation and π-accepting properties as demonstrated through both spectrochemical and electrochemical data67-69 as well as reactivity studies.70 For example, CAACs have been shown to mimic transition metals71 by splitting dihydrogen and ammonia under mild conditions, reactivity which has not been observed with the NHC.72 Further examples of small molecule activation by CAACs provides additional evidence for the ambiphilic nature of these carbenes.73

Figure I.9: A stable cyclic (alkyl)(amino) carbene (CAAC).

These stable carbenes have become important synthons in numerous fields such as catalysis,74 materials75 and even metallopharmaceuticals.76 They have also become extremely useful ligands for the isolation of highly reactive species such as metals in previously unknown oxidations states, and previously unrealized main-group species.77 In recent years, stable singlet carbenes have also emerged as useful tools for the design of stable paramagnetic species. Specifically, CAACs, as a result of their energetically accessible LUMO, have even led to the isolation of numerous transition metal complexes in their zero-oxidation state. These include complexes of manganese,78 iron,79 cobalt,79-80 nickel,81 copper,82 zinc,83 and gold.84

Figure I.10: Carbene supported paramagnetic metal complexes.

A number of groups have also utilized carbenes in the synthesis of stable main-group paramagnetic species.85 For instance, in 2009 Gabbaï isolated the first neutral boron radical which was stabilized by an NHC.86 Additionally, while phosphorus radicals had been previously observed in solution, it wasn’t until 2010 that Bertrand et al. utilized a CAAC to isolate the first structurally characterized monomeric phosphorus radical.87 Furthermore, stable carbenes have been used to isolate new silyl radicals, a class of paramagnetic species which, aside from a few exceptions, are rare.88 Robinson89 and Bertrand90 have also used carbenes to synthesize less prevalent arsenic and antimony radicals, respectively.

Figure I.11: Selected examples of carbene stabilized main group paramagnetic species.

Finally, carbenes have been successfully employed as building blocks for organic radicals. The first example, reported by Fukuzumi et al. in 1997,91 involved the synthesis of

(amino)(carboxy) radicals from thiazolylidene carbenes.92 These compounds were generated by reacting the carbene with an aldehyde to generate an enolate which could then be electrochemically oxidized by one electron to the corresponding radical. These species were studied by EPR and found to decay within hours at room temperature.

Scheme I.2: Fukuzumi’s radical.

Since then, several examples of organic radicals derived from carbenes have emerged.

For example, in 2013, Bertrand reported the synthesis of an oxygen centered air stable oxyllyl radical93 which was synthesized from an anti-Bredt N-heterocyclic carbene.94 Following this, both Bertrand95 and Roesky96 independently reported the synthesis of CAAC supported

cumulene radical cations in 2014. Interestingly, the latter was synthesized by air oxidation of the corresponding cumulene, and both were found to be stable towards oxygen and moisture for extended periods of time. Bertrand then isolated a C-centered CAAC-pyridyl radical by reduction of the corresponding iminium salt in 2015.97 Remarkably, calculations indicate that primary spin density carrier in this radical is the CAAC carbene carbon (41%). Lastly, in a more recent example, Bertrand also demonstrated that a carbene based hetero-dimer could be successfully oxidized to the corresponding stable radical cation.98

Figure I.12: Organic radicals derived from carbenes.

These recent results suggest that carbenes are excellent synthons for the synthesis of organic paramagnetic species. With this in mind, we will investigate using carbenes in the synthesis of new (amino)(carboxy) radicals, which are analogous to those first reported by

Fukuzumi. Chapter 1 will focus on the synthesis and characterization of the first stable monomeric C-centered (amino)(carboxy) radical and related bi- and tri- radical species, which were constructed from CAACs. Chapter 2 will then explore air persistency of these

(amino)(carboxy) radicals as a function of the electronic properties of the acyl substituent R. We will then present a comparative study cyclic and acyclic derived of (amino)(carboxy) radicals,

and further explore the requirement for isolating stable versions of these paramagnetic species in Chapter 3. Finally, in Chapter 4, a cyclizing bi-radical built from (amino)(carboxy) radical architecture, which displays two of the essential requirements for a molecular switch, namely reversibility and bistability, will be investigated.

Chapter 1 :

Bottleable (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino) Carbenes

Adapted from: Mahoney, J. K.; Martin, D.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2013, 135, 18766-18769.

INTRODUCTION

Persistent organic paramagnetic species have found numerous applications in

synthetic chemistry (radial polymerization, oxidative catalysis), medicine, and material

science.6-10 However, when considering the plethora of stable radicals available, it is obvious

that most are heteroatom and not carbon-based. Apart from a few noteworthy exceptions,

such as the triarylmethyl radicals or the highly π-delocalized phenalenyl systems, C-centered

radicals are considered as observable, but non-isolable species.1 Two main debilitating factors

have led to the limited number of monomeric C-centered radicals available in the literature:

their propensity to dimerize due to a large C-C (83 kcal·mol-1) bond strength when compared

to N-N, O-O or S-S (35, 38, 54 kcal·mol-1, respectively) bonds,11 and their proclivity to react

with oxygen to form peroxides and related derivatives.

It has been recognized since the 1960’s that captodative stabilization99-101 can weaken

the dimer C-C bond up to the point where trace amounts of the corresponding radical can be

detected in solution. Perhaps the most classical example is 2-oxomorpholin-yl radical 1.A .

Although the captodative association of amino and carboxy groups is optimal, only the dimeric

form 1.B could be isolated. Nevertheless, small amounts of the radical were observed with

dissociation constants of up to 10-9 M in de-gassed solution.102-104 Note that dimerization of

glycyl radicals 1.C can be prevented when they are sheltered in enzymes.105-106

Figure 1.1: Examples of captodative substituted radicals and carbene derived organic radicals.

Carbenes have emerged as efficient tools for the preparation of main group

paramagnetic species,63,85-90 and recently our group ventured into purely organic radicals.

Using an anti-Bredt diaminocarbene,94 we synthesize the air stable oxyallyl radical cation 1.D,

in which oxygen is the main spin density carrier.95 Interestingly, Fukuzumi et al. also reported

the observation of thiazolyildene carbene-based radicals 1.E by EPR. These radicals were

generated in situ by the electrochemical oxidation of the corresponding enolate. However,

degradation of radicals 1.E occurred within hours at room temperature.91 Based on these

results, we decided to investigate the stability of radicals built on CAACs. Herein we report the synthesis and structural studies of a monomeric (amino)(carboxy) radical. We will then extend our synthetic method to the synthesis of stable bi- and tri- radicals.

A) A monomeric (amino)(carboxy) radical.

A suitable iminium precursor was readily synthesized by addition of benzoyl chloride to a THF solution of 1.1 at -78 ˚C. After work-up, 1.2a was isolated in 81% yield and was fully characterized, including a single crystal diffraction study. The cyclic voltammogram (CV) of 1.2a

+ is characterized by two reversible reduction waves (E1/2 = -0.93 and -1.86 V, against Fc /Fc) indicating the formation of the radical and enolate species, respectively (Figure 1.2). Addition of

107 half an equivalent of TDAE (E1/2 ≈ -1.2 V) to a dichloromethane solution of 1.2a yielded, after workup, 1.3a in 94% yield as deep red crystals.

Scheme 1.1: Synthesis of iminium precursor 1.2a and a stable monomeric (amino)(carboxy) radical 1.3a starting from free carbene 1.1.

Figure 1.2: Cyclic voltammogram of 1.2a. Potentials referenced with respect to Fc+/Fc.

A single crystal X-ray diffraction study of 1.3a revealed that the N1, C1, C2 and O1 atoms are coplanar, as expected for a captodative π-system (Figure 1.3). This conjugate π- system is orthogonal to the phenyl group, which is this is in contrast to 1.2a, in which the iminium moiety is orthogonal to the benzoyl group. Additionally, reduction of 1.2a to 1.3a results in a shortening of the C1-C2 [1.2a: 1.521(2), 1.3a: 1.429(2) Å] bond and a lengthening of the C2-N1

[1.2a: 1.292(2), 1.3a: 1.3601(19) Å], O1-C1 [1.2a: 1.217(2), 1.3a: 1.2587(18) Å] and C1-C3 bonds [1.2a: 1.465(2), 1.3a: 1.507(2) Å].

Figure 1.3: X-ray structure of 1.2a and 1.3a. Hydrogen atoms, solvent molecules and the chloride anion (for 1.2a) were omitted for clarity.

The SOMO of 1.3a (B3LYP/6-311** level of theory) is a bonding combination of the

π*(CO) molecular orbital and the LUMO of the carbene with significant electron density on all the conjugate atoms (Figure 1.4). The C1 atom is the principal spin density carrier with 41.9% of the electron density (values calculated on the optimized structure at the B3LYP/TZVP level with ZORA). The remaining spin density is distributed over O1 (28%), N1 (24.6%), C2 (5.4%)

and the Ph group (2%). Importantly, the spin density distribution over the captodative system is almost insensitive to the geometry and level of theory (Table 1.1).

Figure 1.4: Left: Representation of the SOMO of 1.3a (isosurfaces at 0.05au). Right: X-band EPR spectra of 1.3a in benzene at room temperature.

The X-band EPR spectra of 1.3a at room temperature features a triplet with a g-value of 2.0039 and isotropic hyperfine coupling constant to nitrogen of 15.4 MHz (Figure 1.4). This data is also concurrent with delocalization of the unpaired spin over the conjugate π-system.

The computed hyperfine coupling constant a(15N) for 1.3a, at several different levels of theory, ranged from 11 to 18 Hz and are in fair agreement with the experimental value (Table 1.1).

Table 1.1: Computed Mulliken spin density and isotropic hyperfine coupling constants aN (MHz) for 1.3a.

Isotropic hyperfine Spin Density Method coupling a(15N) (Hz) N1 C1 C2 O1 Phenyl B3LYP/6-31g* a 18.3 24.1 40.8 5.7 28.3 1.0 B3LYP/6-311g** a 10.9 24.2 41.5 5.4 27.9 1.0 B3LYP/6-311g** b 10.9 24.7 39.2 6.1 29.6 0.2 B3LYP/6-311g** c 10.8 23.7 40.1 5.3 28.7 1.1 B3LYP/EPR-II d 13.3 25.0 39.7 6.9 26.7 1.2 B3LYP/EPR-II c 13.3 24.9 39.3 7.0 27.3 1.0 a Optimized geometry. b Experimental geometry (molecule 1). c Experimental geometry (molecule 2). d Optimized geometry at the B3LYP/6-311g** level of theory.

A) Bi- and tri- (amino)(carboxy) radicals.

In principal, our synthetic strategy affords an easy entry into a plethora of

(amino)(carboxy) radicals, including poly-radicals, from the corresponding acyl chlorides. In order to demonstrate this versatility, we reacted carbene 1.4 with terephthoyl and trimesoyl chlorides, respectively. The resulting di- and tri- iminium salts 1.2b and 1.2c were isolated in

67% and 58% yields. The CV of 1.2b features three one -electron reduction waves, to the mono- and bi- radicals (E1/2 = -0.56 V and -0.81 V), and an enolate species, (E1/2 = -1.84 V) respectively (Figure 1.5). The small difference in potentials between the two radical reductions makes the isolation of a radical-cation impossible. The CV of iminium 1.2c features three reduction waves to a tri-radical (E1/2 = -0.43 V, -0.57 V and -0.75V), with one additional reduction wave to an enolate species (E1/2 = -1.90 V). Reduction with TDAE afforded the corresponding bi- and tri- radicals 1.3b and 1.3c in 87% and 90% yield as purple and brown crystals respectively.

Scheme 1.2: Synthesis of bi- and tri- (amino)(carboxy) radicals 1.3b and 1.3c starting from free carbene 1.4.

Figure 1.5: Cyclic voltammogram of 1.2b (top) and 1.2c (bottom). Corrected with respect to the Fc+/Fc.

X-ray diffraction studies were conducted on single crystals of 1.2b (Figure 1.6) and

1.3b-c (Figure 1.7). The crystal structure of 1.2b displays similar features to 1.2a, in that the carbenes are orthogonal to the central linking moiety. The structures of 1.3b-c feature conjugate

O1-C1-C2-N1 captodative systems with orthogonal phenyl linkers, features which parallel 1.3a.

Furthermore, the O1-C1 [1.3b:1.266(8); 1.3c:1.293(4) Å], C1-C2 [1.3b:1.435(9); 1.3c:1.401(5)

Å], and C2-N1 [1.3b:1.388(8); 1.3c:1.378(4) Å] bond lengths compare well with those of 1.3a.

Finally, steric hindrance around the phenyl moiety of 1.3c leads to the inversion of one of the

(amino)(carboxy) radical units.

Figure 1.6: X-ray crystal structure of 1.2b. Hydrogens, solvent molecules, and chloride anions are omitted for clarity.

Figure 1.7: X-ray crystal structures of 1.3b (right) and 1.3c (left). Hydrogen atoms and solvent molecules as well as the isopropyl, ethyl, and methyl substituents of 1.3c, are omitted for clarity.

Figure 1.8: X-band EPR spectra of 1.3b (right) and 1.3c (left) in benzene at room temperature.

The room temperature X-band EPR spectra of 1.3b-c (Figure 1.8) are comparable to that of 1.3a. They feature a triplet with close g-values (2.0040 and 2.0040, respectively) and isotropic hyperfine coupling constants with nitrogen [a(15N) = 16.8 and 16.8 MHz respectively].

This data is in line with the expected weak electron exchange coupling in polyradicals which feature non-conjugate spacers and large separations between the radical units (C1-C1’ distances range from 6.60 to 7.40 Å).108

A low temperature X-band ERP analysis of 1.3b was also conducted in order to determine the ground state of this system. At 4K, the EPR spectrum at half-field is characterized by a singlet, which gradually disappears upon warming the sample to 10K. It is important to note that the triplet oxygen signal, which is also found in this region, has been subtracted from the original EPR signal for visualization purposes only (Figure 1.9). An analysis using the Bleany-

Blowers equation109 (Figure 1.9 inset), wherein -2J is the energy separation between the singlet

and triplet states, indicates that the ground state of 1.3b is a triplet, with a singlet-triplet gap no larger than 200 J.

CONCLUSION

In summary, we were able to synthesize (amino)(carboxy) radicals in two easy steps.

These radicals do not dimerize and could be characterized for the first time by X-ray crystallography. Radicals 1.3a-c have been stored at room temperature under an inert atmosphere for several years with no apparent decomposition. These results suggest that

(amino)(carboxy) radicals should now be considered as stable monomeric paramagnetic building blocks, similarly to verdazyl and nitroxyl radicals.

Chapter 1 has been adapted from materials published in Mahoney, J. K.; Martin, D.;

Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2013, 135, 18766-18769. The dissertation author was the primary investigator of this paper.

APPENDIX: EXPERIMENTAL SECTION

1) General Considerations

Experiments were performed under an atmosphere of dry argon using standard Schlenk techniques. Solvents were dried by standard methods and distilled under argon. Benzoyl chloride was purified by distillation and terephtaloyl chloride and trimesoyl chloride were recrystallized prior to use. 1H and 13C NMR spectra were recorded on Varian Inova 500 and

Bruker 300 MHz spectrometers. NMR multiplicities are abbreviated as follows: s = singlet, d = doublet, t = triplet, sept = septet, m = multiplet, br = broad signal. Melting points were measured with an Electrothermal MEL-TEMP apparatus. Electrochemical experiments were performed with an analyzer from CH Instruments (Model 620E) with a platinum working and auxiliary electrodes. The reference electrode was built from a silver wire inserted in a small glass tube fitted with a porous Vycor frit and filled with an AgNO3 solution in acetonitrile (0.01 M). Ferrocene was used as a standard, and all reduction potentials are reported with respect to the E1/2 of the

Fc+/Fc couple. EPR spectra were obtained using an X-band Bruker E500 spectrometer. Field calibration was accomplished by using a standard of solid 2,2-diphenyl-1-picrylhydrazyl

(DPPH), g = 2.0036.

2) Synthetic Procedures

Stable cyclic (alkyl)(amino) carbenes: The synthesis of CAAC 1.4 was already reported.66

The CAAC 1.1 was synthesized from 2-ethylbutanal following the same procedure. mp: 63-66

1 ˚C. H NMR (C6D6, 300 MHz): δ = 7.22 (t, J = 6 Hz, 1H), 7.14 (d, J = 6 Hz, 2H), 3.16 (sept., J =

6 Hz, 2H), 1.83 (m, 4H), 1.50 (s, 2H), 1.24 (d, J = 9 Hz, 6H), 1.18 (d, J = 6 Hz, 6H), 1.11 (s, 6H),

13 1.11 (t, J = 6 Hz, 6H) ppm. C NMR (C6D6, 75 MHz): δ = 317.1 (C), 146.1 (C), 138.3 (C), 127.7

(CH), 123.8 (CH), 81.8 (C), 66.6 (C), 44.7 (CH2), 29.5 (CH3), 26.3 (CH), 21.9 (CH3) ppm.

Iminium chloride 1.2a: Benzoyl chloride (334 mg, 2.38 mmol) was added to a stirred solution of carbene 1.1 (790.2 mg, 2.42 mmol) in hexane (10 mL). A heavy white precipitate immediately

appeared. After stirring for 30 minutes, the supernatant was removed by filtration, and the resulting solid was washed with diethyl ether (2 x 20 mL). Colorless crystals were obtained by slow diffusion of diethyl ether in a dichloromethane solution of 1.2a. Yield: 914 mg (81%). mp:

+ + 1 180-182 °C. MS (m/z): [M ] calc. for C30H40NO , 430.3110; found, 430.3104. H NMR (CDCl3,

300 MHz): δ =8.53 (d, J = 6 Hz, 2H), 7.67 (m, 3 H), 7.40 (t, J = 3 Hz, 1H), 7.20 (d, J = 6 Hz, 2H),

3.13 (b s, 3H), 2.41 (b s, 2H), 1.82-1.78 (m, 2H), 1.76 (s, 6H), 1.43-1.66 (m, 5H), 1.31 (d, J = 6

13 Hz, 6H), 1.04 (m, 2H), 0.79 (b s, 6H) ppm. C NMR (CDCl3, 75 MHz): δ = 197.3 (C), 186.0 (C),

146.2 (C), 137.2 (CH), 132.1 (CH), 131.8 (CH), 130.1 (CH), 127.6 (C), 126.4 (CH), 86.1(C), 57.1

(C), 42.0 (CH2), 35.5 (CH2), 29.6 (CH3), 29.3 (CH), 27.0 (CH3), 25.0 (CH3), 24.4 (CH2), 21.8

(CH2) ppm.

Radical 1.3a: Tetrakis(dimethylamino)ethylene (TDAE, 23.0 μL, 0.099 mmol) was added to a dichloromethane (10.0 mL) solution of 1.2a (92.5 mg, 0.198 mmol). The mixture was stirred for

10 minutes and the solvent removed in vacuo. Extraction with toluene (1 x 10mL) and removal of volatiles afforded 1.3a as an orange powder. Single crystals were grown by cooling a saturated toluene solution of 1.3a at -30 °C. Yield: 80.2 mg (94%). mp: 135-137 °C.

Bis(Iminium chloride) 1.2b was synthesized from carbene 1.4 (841 mg, 2.68 mmol) and terephtaloyl chloride (262 mg, 1.29 mmol), following the previous procedure. Colourless crystals were obtained by slow diffusion of diethyl ether into a dichloromethane solution of 1.2b. Yield:

+ 2+ 2+ 1.37 g (67%). mp: 187-189 °C. MS (m/z): [M ] calc. for C52H74N2O2 , 379.2870 [M ]; found,

1 379.2868. H NMR (CD3CN, 300 MHz): δ = 8.49 (s, 4 H), 7.52 (t, J = 6 Hz, 2 H), 7.36 (d, J = 6

Hz, 4 H), 2.94 (sept, J = 6 Hz, 2 H), 2.74 (s, 4 H), 2.38 (b s, 12 H), 2.26-2.02 (m, 8 H), 1.70 (s,

13 12 H), 1.33 (d, J = 6 Hz, 12 H), 0.88 (t, J = 6 Hz, 12 H) ppm. C NMR (CD3CN, 75 MHz): δ =

196.6 (C), 187.0 (C), 187.0 (C), 145.8 (C), 137.3 (C), 132.6 (CH), 131.0 (CH), 128.1 (C), 127.2

(CH), 87.0 (C), 60.1 (C), 44.3 (CH2), 29.6 (CH), 29.0 (CH3), 26.3 (CH3), 24.8 (CH3), 8.5 (CH3) ppm.

Tris(Iminium chloride) 1.2c was synthesized similarly from carbene 1.4 (1.7 g, 5.43 mmol) and trimesoyl chloride (467 mg, 1.76 mmol). Crystals were obtained by slow diffusion of diethyl ether in an acetonitrile solution of 1.2c. Yield: 1.23 g (58%). mp: 180-183 °C (dec.). MS (m/z): [M+]

3+ 3+ 1 calc. for C75H108N3O3 , 366.2797 [M ]; found, 366.2788. H NMR (CD3CN, 300 MHz): δ = 8.62

(s, 3 H), 7.53 (t, J = 8 Hz, 2 H), 7.33 (br m, 6 H), 3.41 (q, J = Hz, 12 H), 2.66 (br m, 6 H), 2.18

(br m, 6 H),1.66 (br s, 18 H), 1.23 (br m, 18 H), 1.11 (t, J = Hz, 18 H), 1.01 (br m, 18 H) ppm.

13 C NMR (CD3CN, 75 MHz): δ = 195.7 (C), 185.3 (C), 139.3 (CH), 134.8 (C), 133.6 (CH), 128.4

(C), 128.0 (CH), 88.6 (C), 61.0 (C), 44.2 (CH2), 31.3 (br, CH2), 31.3 (br, CH2), 30.2 (br, CH),

29.6 (br, CH3), 26.6 (CH3), 25.2 (CH3), 9.7 (CH3) ppm.

Biradical 1.3b was synthesized from TDAE (91.5 μL, 0.395 mmol) and 1.2b (300mg,

0.395mmol), following the previous procedure. Single crystals were grown by cooling a saturated dichloromethane solution of 1.3b at -30 °C. Yield: 262 mg (87%). mp: 140-142 °C.

Triradical 1.3c was synthesized similarly in acetonitrile from TDAE (57.0 μL, 0.249 mmol) and

1.2c (200 mg, 0.166 mmol). Single crystals were grown by cooling a saturated dichloromethane solution of 1.3c at -30 °C. Yield: 164.9mg (90%) yield. mp: 132-134 °C.

3) Crystallographic Data

Crystal data and structure refinement for Compound 1.2a

Empirical Formula C30H41NO1.50Cl Formula Weight 475.09 Temperature/K 100 K Crystal System Triclinic Space group P1 a/Å 9.8938(11) b/Å 11.3371(13) c/Å 24.318(3) Å α/˚ 86.787(7) β/˚ 83.279(6)° ϒ/˚ 80.303(6)° Volume/Å3 2668.4(5)

Z 4 3 Ρcalcmg/mm 1.183 Absorption coefficient/mm-1 0.167 F(000) 1028 Crystal size/mm3 0.251 x 0.183 x 0.125 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 0.844 to 26.423 Index ranges -12<=h<=12, -14<=k<=13, -30<=l<=24 Reflections collected 31505

Independent reflections 10902 (Rint = 0.0391) Data/restrains/parameters 0.332 and -0.217 Goodness-of-fit on F2 1.027

Final R indexes [I>2σ (I)] R1 = 0.0415, wR2 = 0.0879

Final R indexes [all data] R1 = 0.0623, wR2 = 0.0986 Largest diff. peak/hole/e Å-3 0.332 to -0.217

Crystal data and structure refinement for Radical 1.3a

Empirical Formula C30H40NO Formula Weight 430.63 Temperature/K 100 K Crystal System Monoclinic

Space group P21/n a/Å 12.4627(12) b/Å 14.7071(18) c/Å 27.878(3) α/˚ 90.00 β/˚ 95.428(5) ϒ/˚ 90.00 Volume/Å3 5086.9(9) Z 8 3 Ρcalcmg/mm 1.125 Absorption coefficient/mm-1 0.066 F(000) 1880 Crystal size/mm3 0.317 x 0.113 x 0.085 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 3.186 to 26.388 Index ranges -15<=h<=13, -18<=k<=18, -34<=l<=34 Reflections collected 39359

Independent reflections 10371 (Rint = 0.0586)

Data/restrains/parameters 10371 / 0 / 589 Goodness-of-fit on F2 1.007

Final R indexes [I>2σ (I)] R1 = 0.0477, wR2 = 0.0944

Final R indexes [all data] R1 = 0.0853, wR2 = 0.1086 Largest diff. peak/hole/e Å-3 0.246 and -0.193

Crystal data and structure refinement for Bis(iminium) dichloride 1.2b

Empirical Formula C56H82N2O2Cl10 Formula Weight 1169.73 Temperature/K 100 K Crystal System Triclinic Space group P1 a/Å 10.3069(8) b/Å 13.2296(11) c/Å 13.2731(10 α/˚ 108.688(2) β/˚ 108.688(2) ϒ/˚ 106.689(2) Volume/Å3 1537.7(2) Z 4 3 Ρcalcmg/mm 1.263 Absorption coefficient/mm-1 0.493 F(000) 618 Crystal size/mm3 0.20 x 0.18 x 0.10 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 1.730 to 28.744 Index ranges -13<=h<=13, -13<=k<=17, -17<=l<=17 Reflections collected 17143

Independent reflections 7079 (Rint = 0.0370) Data/restrains/parameters 7079 / 0 / 352 Goodness-of-fit on F2 1.034

Final R indexes [I>2σ (I)] R1 = 0.0487, wR2 = 0.1063

Final R indexes [all data] R1 = 0.0838, wR2 = 0.1207 Largest diff. peak/hole/e Å-3 0.295 and -0.353

Crystal data and structure refinement for Bi-radical 1.3b

Empirical Formula C56H82N2O2Cl8 Formula Weight 1098.83

Temperature/K 100 K Crystal System Monoclinic Space group C2/c a/Å 14.936(8) b/Å 11.904(8) c/Å 34.07(2) α/˚ 90.00 β/˚ 96.695(14) ϒ/˚ 90.00 Volume/Å3 6017(6) Z 4 3 Ρcalcmg/mm 1.213 Absorption coefficient/mm-1 0.414 F(000) 2336 Crystal size/mm3 0.113 x 0.085 x 0.052 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 1.805 to 25.406 Index ranges -15<=h<=15, -14<=k<=14, -41<=l<=39 Reflections collected 23643

Independent reflections 4895 (Rint = 0.0793) Data/restrains/parameters 4895 / 81 / 398 Goodness-of-fit on F2 1.310

Final R indexes [I>2σ (I)] R1 = 0.1220, wR2 = 0.3416

Final R indexes [all data] R1 = 0.1869, wR2 = 0.3818 Largest diff. peak/hole/e Å-3 0.594 and -0.418

Crystal data and structure refinement for Tri-radical 1.3c

Empirical Formula C80H118N3O3Cl10 Formula Weight 1524.27 Temperature/K 100 K Crystal System Monoclinic

Space group P21/n a/Å 11.6366(5) b/Å 29.7863(13) c/Å 23.7121(10) α/˚ 90.00 β/˚ 90.466(2) ϒ/˚ 90.00 Volume/Å3 8218.6(6)

Z 4 3 Ρcalcmg/mm 1.232 Absorption coefficient/mm-1 0.386 F(000) 3252 Crystal size/mm3 0.351 x 0.217 x 0.143 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 1.849 to 25.431 Index ranges -13<=h<=12, -35<=k<=35, -28<=l<=28 Reflections collected 65716

Independent reflections 15044 (Rint = 0.0732) Data/restrains/parameters 15044 / 27 / 935 Goodness-of-fit on F2 1.025

Final R indexes [I>2σ (I)] R1 = 0.0716, wR2 = 0.1785

Final R indexes [all data] R1 = 0.1290, wR2 = 0.2135 Largest diff. peak/hole/e Å-3 1.025 and -1.177

4) Cartesian Coordinates

Cartesian coordinates of 1.3a calculated at the B3LYP/6-31g* level of theory

------H -0.76495 3.39826 0.929251 Atom X Y Z C -1.39733 1.421713 0.135399 ------C -3.90246 -2.63117 -1.87871 O 0.212407 -1.83231 -0.95808 H -4.33592 -2.873 -2.84581 N 0.879884 0.679294 0.120903 C -2.66751 -1.98742 -1.81492 C 1.014362 -2.66288 2.304765 H -2.13156 -1.74253 -2.72772 H 0.582759 -2.88155 1.324618 C -2.26085 1.281687 1.426338 H 0.257885 -2.85276 3.077066 H -2.82739 0.348493 1.362147 H 1.842018 -3.3628 2.471212 H -1.61487 1.196107 2.308146 C 1.508195 -1.20039 2.384251 C -3.26126 2.435816 1.617265 H 0.628974 -0.55909 2.284752 H -3.86644 2.238756 2.511486 C 2.449286 -0.90916 1.215766 H -2.72879 3.3773 1.812299 C 2.077363 -0.14005 0.086754 C -4.16617 2.609529 0.389032 C -0.41822 0.256241 -0.07026 H -4.83254 3.470854 0.524998 C -0.69919 -1.07195 -0.54733 H -4.81049 1.724161 0.287681 C -2.09742 -1.64871 -0.57773 C -3.33215 2.77112 -0.88989 C -2.77011 -2.02155 0.594259 H -2.77675 3.719303 -0.84866 H -2.31578 -1.82092 1.560629 H -3.98911 2.837633 -1.76641 C -4.00136 -2.68029 0.532609 C -2.35985 1.5943 -1.07283 H -4.50501 -2.96867 1.451788 H -1.76853 1.725687 -1.98843 C -4.57609 -2.97675 -0.70353 H -2.94432 0.678462 -1.20586 H -5.53553 -3.48487 -0.75285 C 1.213597 2.16504 2.126333 C 2.134134 -0.93039 3.76601 H 0.447499 1.636353 2.69817 H 2.979627 -1.5993 3.962853 H 1.215857 3.211936 2.450278 H 1.392957 -1.1055 4.555157 H 2.188235 1.736261 2.375345 H 2.495317 0.09837 3.864547 C 2.070507 2.906525 -0.08499 C 0.961612 2.101288 0.606765 H 3.060378 2.483346 0.109375 C -0.42958 2.635496 0.222053 H 2.058878 3.929868 0.307121 H -0.36615 3.117373 -0.76057 H 1.91842 2.961375 -1.16487

C 2.89942 -0.10391 -1.06698 H 1.332961 -1.30678 -2.93658 C 2.440089 0.496228 -2.3952 C 4.138166 -0.75286 -1.02125 H 1.526953 1.068811 -2.2086 H 4.78002 -0.73203 -1.89729 C 3.475236 1.439972 -3.03615 C 4.553699 -1.44471 0.111759 H 3.785553 2.241211 -2.35757 H 5.523255 -1.9357 0.129203 H 3.055504 1.901331 -3.93827 C 3.701234 -1.53878 1.205091 H 4.377421 0.898352 -3.34284 H 4.003833 -2.12852 2.065692 C 2.068291 -0.63268 -3.3821 ------H 2.952965 -1.22207 -3.65289 H 1.65457 -0.20792 -4.3058

Cartesian coordinates of 1.3a calculated at the B3LYP/6-311g** level of theory.

------C -3.1958 2.637965 1.338367 Atom X Y Z H -3.75297 2.5794 2.279101 ------H -2.66597 3.597632 1.360394 O 0.222091 -1.97469 -0.59763 C -4.16199 2.618623 0.147088 N 0.875995 0.688764 -0.00167 H -4.82242 3.491143 0.180456 C 1.03859 -2.17632 2.751366 H -4.80677 1.733806 0.219217 H 0.609319 -2.57352 1.831062 C -3.39943 2.574187 -1.18309 H 0.282274 -2.21558 3.542127 H -2.8542 3.515393 -1.32582 H 1.862463 -2.83266 3.047037 H -4.10238 2.498434 -2.01881 C 1.535828 -0.72731 2.555284 C -2.42967 1.383481 -1.22839 H 0.660044 -0.11347 2.343767 H -1.89051 1.364225 -2.18141 C 2.465941 -0.65952 1.346507 H -3.01302 0.462322 -1.17878 C 2.080257 -0.11754 0.099972 C 1.25297 2.529621 1.678601 C -0.41757 0.23299 -0.1134 H 0.513834 2.115895 2.363348 C -0.69215 -1.15656 -0.35646 H 1.250516 3.61675 1.794382 C -2.09414 -1.72566 -0.34048 H 2.238473 2.165028 1.971513 C -2.79461 -1.93102 0.851677 C 2.031599 2.843885 -0.65752 H -2.36173 -1.6074 1.791108 H 3.032001 2.487607 -0.40607 C -4.02907 -2.58105 0.850108 H 2.005138 3.922509 -0.47981 H -4.55491 -2.73935 1.785419 H 1.854458 2.675193 -1.71871 C -4.57855 -3.03587 -0.34504 C 2.888176 -0.29771 -1.04606 H -5.53945 -3.53813 -0.34761 C 2.412221 0.031058 -2.45907 C 2.171543 -0.20429 3.855853 H 1.494651 0.615674 -2.37563 H 3.010086 -0.82967 4.173745 C 3.427928 0.849149 -3.27725 H 1.43501 -0.21651 4.664963 H 3.73301 1.763697 -2.76466 H 2.54123 0.817898 3.75228 H 2.994434 1.128846 -4.24218 C 0.955759 2.178303 0.209292 H 4.331606 0.27037 -3.48665 C -0.44969 2.6219 -0.22747 C 2.053608 -1.27052 -3.20809 H -0.41783 2.910197 -1.28184 H 2.94778 -1.87861 -3.37566 H -0.77495 3.498163 0.333219 H 1.620135 -1.03694 -4.18616 C -1.40387 1.408822 -0.06416 H 1.341981 -1.86346 -2.63367 C -3.8762 -2.85817 -1.53714 C 4.129461 -0.91875 -0.89111 H -4.28943 -3.22449 -2.47057 H 4.762105 -1.06196 -1.75928 C -2.63925 -2.22181 -1.53144 C 4.558183 -1.38285 0.344521 H -2.08399 -2.10551 -2.45531 H 5.528616 -1.85675 0.443543 C -2.19314 1.473196 1.278098 C 3.71827 -1.27482 1.442204 H -2.74843 0.540928 1.393207 H 4.030934 -1.69259 2.392171 H -1.50112 1.531109 2.122662 ------

Chapter 2 :

Air-Persistent (Amino)(Carboxy) Radicals Derived from Cyclic (Alkyl)(Amino) Carbenes

Adapted from: Mahoney, J. K.; Martin, D.; Thomas, F.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2015, 137, 7519-7525.

INTRODUCTION

The discovery of the tri(aryl)methyl radical 2.A by Gomberg in 1900 is a major landmark of organic chemistry.17-18 Further alterations to this radical framework have led to extremely stable variants. Of particular interest is the per-chlorinated version 2.B, which due to extensive steric shielding, is considered to be essentially inert to air with an estimated life-time of decades.26 Thus, 2.B and related derivatives have found a number of applications in the design of multifunctional materials.33 However, 2.B remains a novelty in the realm of C-centered radicals, with dimerization and oxidation being the biggest challenges faced when considering the isolation of this class of paramagnetic species.

As previously pointed out, captodative substitution, which disfavors the formation of C-

C dimers up to the point where trace amount of the monomeric radical can be observed in solution, can effectively stabilize C-centered radicals.99-101 Among the most noteworthy examples of compounds featuring this substitution pattern are the 2-oxomorpholin-3-yl radical

2.C,102-103 which has a dissociation constant of 10-9 M at room temperature, and several enzymes which harbor glycyl radicals 2.D.105-106 These results suggest that a combination of electronic and steric factors could be used to prevent the dimerization of C-centered radicals.

Indeed, by taking advantage of the peculiar properties of CAACs, we were able to synthesize a captodatively stabilized monomeric (amino)(carboxy) radical 2.E and related bi- and tri- radicals.110

While 2.E is extremely stable under an inert atmosphere, both in solution and the solid state, it was found to rapidly degrade upon exposure to air. Interestingly, it has been noted that radicals of type 2.C could be considered as air-stable if the rate of dimerization, which is at best a millisecond at room temperature, is faster than their reaction with oxygen.102 Additionally, glycyl enzymes 2.D, which catalyze anaerobic process, are air sensitive, thereby suggesting that steric hindrance alone may not be sufficient to prevent the oxidation of these captodative carboradicals.103

Figure 2.1: The tri(aryl) radical 2.A, per-chlorinated tri(phenyl)methyl radical 2.B, and assorted (amino)(carboxy) radicals 2.C-E.

Herein we report a theoretical and experimental study on the influence of electronic effects upon the reactivity of (amino)(carboxy) radicals with dioxygen. We will demonstrate that it is possible to rationally design air-persistent variants, with half-lives, in well aerated solutions, of several hours and even days in the most favorable case.

A) Computational analysis

In order to design air-persistent radicals, we analyzed the reaction of triplet oxygen with a representative set of (amino)(carboxy) radicals at the B3LYP/6-311g** level of theory. We considered a series of (amino)(carboxy) radicals with the carboxy moiety substituents R covering a broad range of electronic properties. A good correlation was found with the enthalpy

111 of the reaction and the Hammett parameter σp of R (Figure 2.2, top). The formation of the corresponding peroxide radicals is favored for radicals bearing electron donating groups (low

σp). Conversely, the reaction becomes less exothermic as R becomes more electron withdrawing. Indeed, the reaction is endothermic for the most electron-withdrawing groups (σp

> 0.2-0.3).

Intuitively, it can be assumed that the propensity of these radicals to react with oxygen increases as they become more C-centered. Indeed, a good correlation was found with the

Mulliken spin density on C2 and the enthalpy of the reaction (Figure 2.2, bottom). Interestingly, the electronic properties of R essentially effect only the spin density localized on the C2 and O1 atoms, with the spin density on C1 and N1 (25-33%) being only slightly influenced (Figure 2.3).

With electron donating R substituents, the majority of the spin density is localized on the C2

(50%) position with only 15% localized on O1. As the substituent becomes increasingly electron- withdrawing, the spin density shifts from C2 to O1. However, a plateau is reached around σp =

0.2, and therefore, the electron density is approximately 30-35% on both C2 and O1 in the case of the most electron withdrawing R groups (Figure 2.4).

Figure 2.3: Calculated Mulliken spin densities for model (amino)(carboxy) radicals with increasing Hammett parameters σp from the bottom to the top.

These calculations indicate that (amino)(carboxy) radicals transition from C-centered to

C,O-ambidentate radicals as the electron withdrawing properties of R increase. This is paralleled with a thermodynamic protection of the radical from dioxygen as the reaction becomes endothermic with the most electron withdrawing substituents (σp > 0.2-0.3). It is also important to note that the formation of the peroxide should also be kinetically disfavored for molecules with high σp by virtue of the Hammond postulate.

Figure 2.4: Plot of the ratios of Mulliken spin density on C2 and O1 against σp. R groups investigated experimentally are given in red.

A) Experimentally obtained air-persistent (amino)(carboxy) radicals

In order to experimentally ascertain the influence of electronic effects on the persistency of (amino)(carboxy) radicals, we considered a series of radicals 2.3a-f with carbonyl moieties featuring increasingly electron withdrawing properties: t-butyl, phenyl, 3,5- bis(trifluoromethyl)phenyl, perfluorophenyl, heptafluoropropyl, and 2H-pyrroliumyl. The iminium precursors 2.2a-c and 2.2e were readily prepared by addition of the appropriate acyl chloride to a hexane solution of carbene 2.1a. Iminium 2.2d was obtained by addition of 2,3,4,5,6- pentafluorobenzaldehyde to CAAC 2.1a, followed by an oxidation of the resulting α-

(amino)ketone 2.4 with DDQ and treatment with tetraphenylborate. Lastly, following the procedure previously established for the “anti-Bredt” NHC,93 iminium 5 was synthesized by addition of excess CO to a THF solution of 2.1b at -78 ˚C followed by the addition of one equivalent of hydrogen chloride and a subsequent anion exchange with sodium tetrafluoroborate. In this instance, CAAC 2.1b had to be used instead of 2.1a, since sterically hindered CAAC’s and other electrophilic carbenes with bulky substituents have been shown to form ketenes when reacted with CO.112

Scheme 2.1: The synthesis of iminium precursors 2.2a-e and radicals 2.3a-e starting from carbene 2.1a, and 2.5 and 2.3f starting from carbene 2.1b. Table 2.1: Structural parameters, redox potentials, EPR hyperfine coupling constants and Mulliken spin densities of radicals 3a-f (calculated valuesa are in parenthesis).

2.3a 2.3b 2.3c 2.3d 2.3e 2.3f

t 3,5- R Bu Ph C6F5 C3F7 2H-pyrroliumyl (CF3)2(C6H3) Bond lengths (pm) O1-C1 124.7 125.9/125.8b (125.1) 125.0 125.8 126.0 C1-C2 145.6 142.9/142.8 b (143.2) 142.2 142.9 142.6 C2-N1 138.6 136.0/136.5 b (136.9) 136.2 135.3 136.1 angle (deg) C1-C2-N1 128.5 121.7/120.6 b (121.2) 121.4 119.3 120.0 Torsion (deg) O1-C1-C2-N1 155.6 2.3/8.8 b (7.4) 2.7 3.9 4.5 + E1/2 vs Fc /Fc I+/I -1.13 -0.93 -0.65 -0.41 -0.30 +0.25 I/I- -2.02 -1.86 -1.74c -1.73c -1.51c -1.03 g-factor --- 2.0039 2.0043 2.0031 2.0032 2.0032 Isotropic hyperfine coupling (MHz) A(14N) --- 15.4 17.1 17.2 17.3 8.9 (average)d (1 nucleus)e --- (14.4) (14.8) (14.9) (14.5) (13.2 and 3.7) A(19F) ------8.2 30.8 --- (2 nuclei)e ------(7.3) (35.5) --- Mulliken spin density e on O1 (22.4)f (28.0) (28.9) (30.5) (32.7) (35.5) on C1 (3.4)f (5.4) (6.7) (6.8) (10.0) (14.8) on C2 (52.9)f (41.9) (38.8) (36.6) (31.4) (18.7) on N1 (21.5)f (24.6) (25.4) (25.7) (25.0) (23.0) a Calculations at the B3LYP/TZVP level of theory. b Values given for each of the two independent molecules in the unit cell. c Irreversible. d Assuming a fast exchange between two equivalent conformers, see text. e Values calculated on optimized structure at the B3LYP/TZVP lever with ZORA. f Values are calculated for 2.3a’.

The cyclic voltammograms of 2.2a-e feature two one-electron reduction waves to the radical and enolate species, respectively (Figure 2.5). As expected, stronger electron withdrawing groups R positively shifted the first reduction potential. Therefore, while 2.2a-c were

107 reduced to 2.3a-c with one half equivalent of TDAE (E1/2  -1.20 V), the synthesis of 2.3d-e

114 required the addition of one equivalent of decamethylferrocene (FcCp*2; E1/2 = -0.59 V) to electron poor iminiums 2.2d-e. Lastly, 2.3f was synthesized by addition of potassium ferricyanide to 2.5, a procedure adapted from that reported by Mayer et al. for the production of

2,4,6-tri-tert-butylphenoxy radical from the corresponding phenol.114 The cyclic voltammogram of 2.3f features a reversible 1-electron oxidation and reduction at +0.25 V and -1.03 V, respectively. Not surprisingly, these values are the highest of the series.

Figure 2.5: Cyclic voltammograms of 2.2a-e. Insets illustrate the reversibility of the first reduction wave for 2.2a and 2.2c-e. Spectra are referenced to Fc+/Fc.

Radicals 2.3a-f were isolated in 54-94% yields and single crystals of 2.3a-b and 2.3d-f were subjected to X-ray diffraction studies which revealed the expected monomeric structure

(Figure 2.6). Importantly, in 2.3b and 2.3d-f, the O1, C1, C2 and N1 atoms are nearly planar, with torsion angles ranging from 2-9˚. These features are indicative of a conjugate captodative

π- system. Additionally, as previously observed for 2.E,103 the second substituent (CAAC unit or aryl ring) is twisted away from coplanarity (torsion 57˚-85˚).

Figure 2.6: Solid-state structures of 2.3a-b and 2.3d-f. Hydrogen atoms, solvent molecules and the counter-anion and isopropyl groups of 2.3f are omitted for clarity.

Interestingly, while 2.3b-f were stable in solution, samples of 2.3a were found to degrade over time at room temperature. Nevertheless, it was possible to obtain a single crystal by cooling a freshly prepared sample of 2.3a in toluene to -40˚C. The X-ray diffraction study revealed a monomeric structure with a large longer C1-C2 and N1-C2 bonds and a shorter C2-

O2 bond than 2.3b-f. Additionally, this structure varies significantly from the rest of the series in that the oxygen and nitrogen atoms are anti to each other with a O1-C1-C2-N1 torsion angle of

155.6˚. Calculations at the B3LYP/6-311g** level of theory predict that the anti-conformation

2.3a’ (N1-C2-C1-O1 = 159˚) is thermodynamically favored over the syn-conformation 2.3a’’

(N1-C2-C1-O1 = 13˚) by a mere 0.6 kJmol-1.

Figure 2.7: Optimized structures of 2.3a’ (left) and 2.3a’’ (right). Calculated at the B3LYP/6- 311g** level of theory.

The room temperature X-band EPR spectra of 2.3a-e (Figure 2.8) were recorded in dry dichloromethane under an inert atmosphere of argon, and feature similar g-values (2.0031-

2.0043) and similar isotropic hyperfine coupling constants to nitrogen [a(15N) = 15-17 MHz]. In the case of 2.3d and 2.3e there is additional isotropic hyperfine coupling to two equivalent fluorine atoms [a(19F) = 8.2 and 30.8 MHz, respectively]. DFT calculations estimate these values fairly well (Table 2.1). The EPR spectrum of crystals of 2.3a features an unsymmetrical shoulder on the left side of the signal. This shoulder almost disappears upon saturation of the EPR signal, thus indicating that two different paramagnetic species, 2.3a and a paramagnetic impurity, are present in solution (Figure 2.9). Lastly, the EPR spectra of 2.3f features a quintet, with a relatively small isotropic hyperfine coupling constant to nitrogen [a(15N) = 8.9 MHz] when compared to 2.3b-e. Calculations identified two different isotropic hyperfine coupling constants to nitrogen [a(15N) = 13.2 and 3.7 MHz], with the average [a(15N) = 8.5 MHz] being very close to the experimental value. This implies that a dynamic exchange process, which is faster than the

EPR time scale, is occurring. In fact, a preliminary conformational study, performed at the

B3LYP/6-31G* level of theory, on a simple model 2.3f’, found two symmetrical local minima

(Figure 2.10). The Gibbs free energy associated with the exchange of the magnetic environments was approximated at 11 kJ·mol-1.

Figure 2.8: Top: Experimental EPR spectra of (amino)(carboxy) radicals 2.3b-f in dichloromethane. Bottom: Simulated spectra using isotropic hyperfine coupling constants given in Table 2.1.

Figure 2.9: The X-band EPR spectra of 2.3a at 5.0 mW (left) and 63.0 mW (right).

Figure 2.10: Energy of model radical 2.3f’ as a function of dihedral angles θ1 and θ2, geometry being optimized on all other internal coordinates (B3LYP/6-31G*).

Mulliken spin densities follow the same trends previously observed at lower levels of calculation with simpler models (Table 2.1). Again, increasing the electron withdrawing groups mainly effect the spin density on C2 and O1, while leaving C1 (5-15%) and N1 (22-26%) essentially unchanged. Radical 2.3a has 53% spin density on C2 with only 22% on O1. This difference slowly diminishes as R becomes more electron-withdrawing. While 2.3b (C2: 42%;

O1: 28%), 2.3c (C2: 38.8%; O1: 28.9%) and 2.3d (C2: 36.6%; O1: 30.5%) can still be considered as C- centered radicals, 2.3e has an equal distribution of spin density on C2 (31.4%) and O1 (32.7%). In the extreme case, radical cation 2.3f features significantly more electron density on O1 (36%) than on C2 (19%).

The persistency of 2.3b-f in air was then evaluated by vigorously bubbling air into each

EPR sample over the course of one minute (Figure 2.11). It is important to note that 2.3b is so air sensitive that no EPR signal was observed following this procedure. Therefore, in order to monitor its decomposition, a sample was briefly exposed to air (a few seconds). Even under these conditions, 2.3b decayed rapidly with pseudo first-order kinetics and a half-life of

approximately one minute at room temperature. Radicals 2.3c and 2.3d have longer half-lives of about 13 minutes and 1.5 days, respectively in well-aerated dichloromethane. It is interesting to note that washing an aerated dichloromethane solution of 2.3d with water does not increase the rate of decay, indicating that it is more sensitive to oxygen than water. Surprisingly, while

2.3e is remarkably air persistent (half-life of 3 hours), it is more oxygen sensitive than 2.3d despite having a more electron withdrawing per(fluoro)-n-propyl substituent. This clearly indicates that steric hindrance plays a role in protecting (amino)(carboxy) radicals from oxygen.

Indeed, 2.3f, which has the strongest and bulkiest 2H-pyrroliumyl substituent, has a life-time of one week in technical dichloromethane and can be stored in an oxygenated environment for more than a year in the solid state.115

Figure 2.11: Decay of radicals 2.3b-f in solution after exposure to air or after exposure to water (x) and air (□).

CONCLUSION

As with many C-centered radicals, (amino)(carboxy) radicals have been considered undego dimerization and to be highly reactive species towards oxygen. However, we have demonstrated that (amino)(carboxy) radicals can not only exist as monomeric species, but can

also be sufficiently protected from oxidative decay. Electron withdrawing R substituents extended the life-time of these radicals to hours and even days in the most extreme case. These half-lives could also be further prolonged with sterically hindering substituents, as was demonstrated by 2.3d (R = C6F5, σp = +0.26) which has an exception half-life of three hours despite only having a moderate electron withdrawing group.

Chapter 2 has been adapted from materials published in Mahoney, J. K.; Martin, D.;

Thomas, F.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2015, 137, 7519-

7525. The dissertation author was the primary investigator of this paper.

APPENDIX: EXPERIMENTAL SECTION

1) General Considerations

All manipulations were performed under an inert atmosphere of dry argon, using standard Schlenk and drybox techniques. Commercially available 3,5- bis(trifluoromethane)benzoyl chloride was distilled before use. Heptafluorobutyryl chloride was first distilled and then subjected to ten freeze-pump-thaw cycles to remove any excess hydrochloric acid. Compounds 2.1a-b, 2.2a and 2.3a were previously reported.66,110 NMR spectra (1H, 13C, 19F and 11B) were recorded on Bruker Avance 300, Varian VX 500 and Jeol

ECA 500 spectrometers. All spectra were obtained at 25°C in the solvent indicated. Chemical

1 13 shifts are given relative to SiMe4 and referenced to the residual solvent signal ( H, C) or

11 . 19 relative to an external standard ( B: BF3 Et2O, F: F3COOH). Melting points were measured with an Electrothermal MEL-TEMP apparatus. Electrochemical experiments were performed with an analyzer from CH Instruments (Model 620E) with platinum working and auxiliary electrodes. The reference electrode was built from a silver wire inserted in a small glass tube fitted with a porous Vycor frit and filled with an AgNO3 solution in acetonitrile (0.01 M). Ferrocene was used as a standard, and all reduction potentials are reported with respect to the E1/2 of the

Fc+/Fc redox couple. EPR spectra were obtained using an X-band Bruker E500 spectrometer.

Field calibration was accomplished by using a standard of solid 2,2-diphenyl-1-picrylhydrazyl

(DPPH), g = 2.0036.

2) Synthetic Procedures

Synthesis 2.2a: Trimethylacetylchloride (0.26 mL, 2.16 mmol), was added to hexane solution of 2.1a (616 mg, 2.16 mmol). After stirring for 10 minutes, the solvent was removed in vacuo, and the precipitate washed with diethyl ether (2 x 20mL). Yield: 0.6868 g (71%). mp: 163-165

+ + 1 ᵒC. MS (m/z): [M ] calc. for C28H44NO , 410.3417; found, 410.3418. H NMR (CDCl3, 500 MHz):

δ = 0.94 (s, 9H), 1.18 (d, J = 6 Hz, 6H), 1.27 (d, J = 6 Hz, 6H), 1.49-1.56 (m, 5H), 1.72 (bs, 6H),

1.80 (bs, 3H), 2.21 (bs, 2H), 2.78 (bs, 1H) 2.69 (bs, 1H), 2.87 (bs, 2H), 7.31 (d, J = 9 Hz, 2H),

13 7.51 (t, J = 9 Hz, 1H) ppm. C NMR (CDCl3, 125 MHz): δ = 204.0 (C), 196.8 (C), 145.4 (C),

132.6 (CH), 129.3 (C), 127.3 (CH), 87.3 (C), 57.2 (C), 44.2 (C), 43.1 (CH2), 35.7 (CH2), 29.7

(CH3), 29.6 (CH), 26.5 (CH3), 26.0 (CH3), 24.3 (CH2), 21.4 (CH2) ppm.

Iminium chloride 2.2c: 3,5-bis(trifluoromethane)benzoyl chloride (0.44 mL, 2.42 mmol), was added to hexane solution of CAAC 2.1a (582 mg, 2.42 mmol), resulting in the immediate formation of a heavy white precipitate. After stirring for 10 minutes, the solvent was removed in vacuo, and the precipitate was washed with diethyl ether (3 x 20mL). Yield: 807 mg (55 %). mp:

+ + 1 168-170 ᵒC. MS (m/z): [M ] calc. for C32H38F6NO , 566.2853; found, 566.2851. H NMR (CDCl3,

300 MHz): δ = 8.76 (s, 2H), 8.15 (s, 1H), 7.43 (t, J = 3 Hz, 1H), 7.22 (d, J = 3 Hz, 2H), 3.08 (bs,

2H), 3.26 (bs, 2H), 2.72 (bs, 2H), 1.80-1.83 (m, 3H), 1.78 (s, 6H), 1.49-1.59(m, 5H), 1.32 (d, J

13 = 3 Hz, 6H), 0.80 (s, 6H) ppm. C NMR (CDCl3, 125 MHz): δ = 194.5 (C), 184.9 (C), 145.8 (C),

2 144.4 (C), 133.9 (C), 133.6 (C, q, JC-F = 35 Hz), 132.3 (CH), 131.6 (C), 131.2 (CH), 129.9 (CH),

1 127.3 (C), 126.6 (CH), 125.1 (C), 122.1 (C, q, JC-F = 272.5 Hz), 87.6 (C), 57.5 (C), 41.5 (CH2),

19 35.3 (CH2), 29.5 (CH3), 29.3 (CH), 26.7 (CH3), 25.0 (CH3), 24.3 (CH2), 22.6 (CH2) ppm. F NMR

(CDCl3, 282 MHz): δ = -62.63 (CF3) ppm.

Compound 2.4: 2,3,4,5,6-Pentafluorobenzaldehyde (1.89 g, 9.68 mmol) in THF was slowly added via cannula to a THF solution of CAAC 2.1a (3.15 g, 9.68 mmol). After 20 minutes, the solution was opened to air and left to stir for 1 hour. The solvent was then removed by vacuum.

Column chromatography using a 5:95 ethyl acetate: hexanes solution yielded 2.4 as an orange

+ 1 oil. Yield: 3.81 g (76 %). MS (m/z): [M ] calc. for C30H35F5NO, 520.2633; found, 520.2630. H

NMR (CDCl3, 300 MHz): δ = 7.19 (t, J = 6 Hz, 1H), 7.10 (d, J = 6 Hz, 2H), 4.68 (s, 1H), 4.08

(sept., J = 6 Hz, 1H), 3.16 (sept., J = 6 Hz, 1H), 3.28 (d, J = 12 Hz, 1H), 2.02 (bs, 1H), 1.97 (bs,

1H), 1.95 (d, J = 12 Hz, 1H), 1.62 (bs, 4H), 1.52 (s, 3H), 1.42 (m, 3H), 1.26 (d, J = 6 Hz, 6H),

13 1.17 (d, J = 6 Hz, 3H), 0.99 (d, J = 6 Hz, 6H) ppm. C NMR (CDCl3, 125 MHz): δ = 198.7 (C),

152.4(C), 149.0 (C), 140.1 (C), 126.8 (CH), 124.6 (CH), 124.4 (CH), 86.1 (CH), 64.3 (C), 51.7

(CH2), 47.8 (C), 42.2 (CH2), 34.5 (CH2), 32.1 (CH3), 28.0 (CH), 27.9 (CH3), 27.4 (CH), 25.8

19 (CH2), 25.7 (CH3), 25.3 (CH3), 25.0 (CH3), 24.9 (CH3), 24.3 (CH2), 23.6 (CH2) ppm. F NMR

(C6D6, 282 MHz): δ = -138.7 (d, J = 16.9 Hz, 2F), -149.9 (t, J = 19.7 Hz, 1F), -160.2 (m, 2F) ppm.

Iminium tetraphenylborate 2.2d: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (423 mg, 1.86 mmol) dissolved in ether was added, via addition cannula, to an ether solution of 2.4 (970 mg,

1.86 mmol). The mixture was allowed to stir overnight. The solvent was then removed via filtration and the purple precipitate washed with ether (3 x 20 mL). The solid was then dissolved in dichloromethane and added to an aqueous solution of sodium tetraphenylborate (1.273 g,

3.72mmol). The biphasic mixture was stirred vigorously for 1 hour. The layers were then separated. The organic layer was washed with brine (3 x 20 mL) and subsequently dried with magnesium sulfate. The solvent was removed by vacuum and the product recrystallized through diffusion of ether and dichloromethane. The 2.2d was obtained as a yellow solid. Yield: 503 mg

+ + 1 (32 %). mp: 151-153ᵒC. MS (m/z): [M ] calc. for C30H35F5NO , 520.2633; found, 520.2637. H

NMR (CDCl3, 300 MHz): δ = 7.46 (bm, 9H), 7.26 (d, J = 6 Hz, 2H), 7.05 (t, J = 6 Hz, 8H), 6.91

(t, J = 6 Hz, 4H), 2.49 (sept, J = 3 Hz, 2H), 1.95 (s, 2H), 1.91 (d, J = 9 Hz, 2H), 1.73 (bd, J = 9

Hz, 3H), 1.55 (bt, J = 9 Hz, 3H), 1.34 (m, 2H), 1.29 (d, J = 3 Hz, 6H), 1.21 (s, 6H), 1.01 (d, J =

13 3 Hz, 6H) ppm. C NMR (CDCl3, 125 MHz): δ = 189.9 (C), 177.3 (C), 164.3 (q, C, JC-B = 48.8

Hz), 148.1 (C), 146.0 (C), 145.3 (C), 139.3 (C), 137.2 (C), 136.4 (CH), 133.0 (CH), 127.0 (CH),

125.6 (CH), 121.7 (CH), 87.1 (C), 57.8 (C), 43.3 (CH2), 35.1 (CH2), 29.6 (CH), 29.0 (CH3), 26.0

19 (CH3), 25.4 (CH3), 24.1 (CH2), 21.3 (CH2) ppm. F NMR (CDCl3, 282 MHz): δ = -134.0 (bs, 2F),

11 -134.5 (bs, 1F), -155.7 (t, 2H, J = 16.9 Hz) ppm. B NMR (CDCl3, 96 MHz): δ = -7.77 (s) ppm.

Iminium chloride 2.2e: Heptafluorobutyryl chloride (0.20 mL, 1.31 mmol) was added to a hexane solution of CAAC 2.1a (0.340 g, 1.19 mmol), resulting in the immediate formation of a yellow solid. After stirring for 20 minutes, the solvent was removed in vacuo and the precipitate washed with pentane (4 x 10 mL). This compound decomposes in solvent (CHCl3, CH2Cl2,

CH3CN) over time at room temperature. However, diffusion of chloroform and pentane at -40˚C yielded 2.2e as yellow crystals. Yield: 345 mg (52%). mp: 112-114 ᵒC. MS (m/z): [M+] calc. for

+ 1 C27H35F7NO , 552.2607; found, 522.2599. H NMR (CDCl3, 300 MHz): δ = 7.57 (t, J = 6 Hz, 1H),

7.34 (d, J = 6 Hz, 2H), 3.12 (s, 2H), 2.60 (sept, J = 6 Hz, 2H), 2.23 (bs, 1H), 2.19 (bs, 1H), 1.87

(bs, 3H), 1.84 (s, 6H), 1.68-1.53 (m, 4H), 1.48 (s, 1H), 1.30 (d, J =6 Hz, 6H), 1.12 (d, J = 6 Hz,

13 6H) ppm. C NMR (CDCl3, 125 MHz): δ = 189.1 (C), 181.2 (C, t, J = 36 Hz)), 145.0 (C), 133.3

1 2 (CH), 127.7 (C), 127.3 (CH), 116.7 (C, qt, JC-F =287.5 Hz, JC-F = 32.5 Hz), 108.0 (C, t,sext.,

1 2 1 2 JC-F =268.8 Hz, JC-F = 32.5 Hz), 107.1 (C, tt, JC-F =287.5 Hz, JC-F = 32.5 Hz), 90.8 (C), 58.1

(C), 43.9 (CH2), 34.4 (CH2), 29.8 (), 29.7 (CH3), 26.5 (CH), 25.0 (CH3), 24.2 (CH2), 21.0 (CH2)

19 ppm. F NMR (CDCl3, 282 MHz): δ = -80.5 (t, J = 8.46 Hz, 3H), -115.0 (s, 2H), -125.3 (s, 2H) ppm.

Radical 2.3a: TDAE (28 μL, 0.121 mmol) was added to a chloroform solution of iminium chloride

2.2a (0.100g, 0.242 mmol). The solution was stirred for 10 minutes, and the solvent removed in vacuo. Extraction with toluene (1 x 10 mL) and removal of the solvent yielded a red oil. Yield:

87.4 mg (96%).

Radical 2.3c: TDAE (31 μL, 0.133 mmol) was added to a dichloromethane (3.0mL) solution of the iminium chloride 2.2c (200 mg, 0.332 mmol). The mixture was stirred for 10 minutes and

the solvent removed in vacuo. Extraction with toluene (1 x 5.0mL) and removal of solvent in vacuo yielded 2.3c as a red solid. Yield: 122 mg (81 %). mp: 145-147 ˚C.

Radical 2.3d: Iminium tetraphenylborate 2.2d (58 mg, 0.069 mmol) and decamethylferrocene

(22.6 mg, 0.069 mmol) were combined under argon. Dichloromethane (5.0 mL) was added to the flask and the solution stirred for 30 minutes. Removal of the solvent in vacuo and extraction with hexanes yielded 2.3d as an orange powder. Single crystals were obtained by cooling a concentrated toluene solution to -40˚C. Yield: 24 mg (67 %). mp: 186-189˚C.

Radical 2.3e: Iminium chloride 2.2e (100 mg, 0.179 mmol) and decamethylferrocene (58.4 mg,

0.179 mmol) were combined under argon, and dichloromethane was added to the flask. The solution allowed to stir for 20 minutes and the solvent was removed in vacuo. Extraction with toluene and removal of the solvent in vacuo yielded the product as a yellow powder. Single crystals were grown by cooling a concentrated hexane solution of 2.3e to -40 ˚C. Yield: 87.9 mg

(94 %). mp: 128-130˚C.

Iminium tretrafluoroborate 2.5: CO(g) was bubbled through a cooled solution (-78ᵒC) of 2.1b

(1.03 g, 3.59 mmol) in THF (20.00 mL) for 1 hour. Trifluoromethanesulfonic acid (0.24 mL, 1.80 mmol) was then added to the flask while at-78ᵒC and stirred for 10 minutes before warming to room temperature. The resulting product was then extracted with chloroform (3 x 10 mL) and washed with water (3 x 10 mL). Sodium tetrafluoroborate (0.98 g, 8.98 mmol) in water was added to the organic phase. The mixture was stirred vigorously for one hour before the layers were separated and the organics washed with brine and dried over magnesium sulfate.

Removal of the solvent yielded a red solid. Single crystals of 2.5 were obtained though diffusion of dichloromethane and diethyl ether. Yield: 0.819 g (66 %). mp: 182-185ᵒC. MS (m/z): [M+]

+ 1 calc. for C41H63N2O , 599.4940; found, 599.4935. H NMR (CDCl3, 500 MHz): δ = 7.24 (t, J =

7.7 Hz, 2H), 7.14 (d, J = 7.7 Hz, 2H), 7.04 (d, J = 7.7 Hz, 2H), 2.75 (sept., J = 6.5 Hz, 2H), 2.49

(sept., J = 6.5 Hz, 2H), 2.47 (d, J = 13.5 Hz, 2H), 2.30 (d, J = 13.5 Hz, 2H), 2.08 (s, 6H), 1.75

(s, 6H), 1.34 (s, 6H), 1.31 (d, J = 6.5 Hz, 6H), 1.22 (d, J = 6.5 Hz, 6H), 1.16 (s, 6H), 1.09 (d, J =

13 6.5 Hz, 6H), 0.24 (d, J = 6.5 Hz, 6H) ppm. C NMR (CDCl3, 125 MHz): δ = 176.3 (C), 146.1

(C), 144.0 (C), 135.2 (C), 129.2 (CH), 125.4 (CH), 125.0 (CH), 118.13 (C), 72.2 (C), 58.4 (CH2),

46.4 (C), 32.8 (CH3), 30.7 (CH3), 30.6 (CH3), 29.9 (CH), 28.9 (CH), 28.7 (CH3), 28.3 (CH3), 25.0

19 11 (CH3), 24.7 (CH3), 23.6 (CH3) ppm. F NMR (CDCl3, 470 MHz): δ = -154.08 (s) ppm. B NMR

(CDCl3, 160 MHz): δ = -1.05 (s) ppm.

Radical 2.3f: CO(g) was bubbled through a cooled solution of 2.1b (336 mg, 0.24 mmol) in toluene (5 mL) for 1h. Then, a solution of HCl in diethyl ether (2M, 0.06 mL, 0.12 mmol) was added dropwise and the solution warmed to room temperature. A solution of potassium ferricyanide (198 mg, 0.6 mmol) in water was added to the flask. The biphasic mixture was stirred vigorously for 10 minutes. The phases were then separated and the organic phase washed with brine (3 x 10 mL) and dried with magnesium sulfate. After removing the solvent, the blue powder was dissolved in water and a solution of saturated sodium tetraflouroborate was added to the reaction flask. After stirring for 20 minutes, the product was extracted with dichloromethane. The organic phase was washed with water (3 x 10 mL), dried over magnesium sulfate, and the solvent removed under reduced pressure. Suitable single crystals were grown through diffusion of diethyl ether into a dichloromethane solution of the product. Yield: 116 mg

+ + (84%). mp: 220-222 ˚C. MS (m/z): [M ] calc. for C41H62N2O , 598.4812; found, 598.4854.

Decay of Radicals 3b-f in Aerobic Conditions: An EPR sample of the radical in distilled dichloromethane was poured into an open-to-air vial. The volume of the solution was filled to 3 mL, and air was vigorously bubbled over 1 min; an aliquot was taken and the evolution of the concentration of the radical was monitored by EPR. In the case of 2.3d, the remaining solution was steadily washed with water over a minute. The organic phase was recovered and a sample was monitored by EPR.

3) Crystallographic Data

Crystal data and structure refinement for Radical 2.3a Empirical Formula C28H44NO Formula Weight 410.64 Temperature/K 100K

Crystal System Monoclinic Space group Cc a/Å 13.5085(7) b/Å 13.2349(7) c/Å 14.1300(7) α/˚ 90 β/˚ 99.2550(19) ϒ/˚ 90 Volume/Å3 2493.3(2) Z 4 3 Ρcalcmg/mm 1.094 Absorption coefficient/mm-1 0.064 F(000) 908.0 Crystal size/mm3 0.27 x 0.25 x 0.16 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 2.92 to 61.088 Index ranges -19<=h<=19, -18<=k<=18, -20<=l<=20 Reflections collected 20341

Independent reflections 6991 (Rint = 0.0387, Rsima = 0.0390) Data/restrains/parameters 6991/2/281 Goodness-of-fit on F2 1.051

Final R indexes [I>2σ (I)] R1 = 0.0370, wR2 = 0.0923

Final R indexes [all data] R1 = 0.0923, wR2 = 0.0951 Largest diff. peak/hole/e Å-3 0.31/-0.21

Crystal data and structure refinement for Radical 2.3d

Empirical Formula C37H43F5NO Formula Weight 612.72 Temperature/K 100 K Crystal System Orthorhombic

Space group Pca21 a/Å 21.875(4) b/Å 8.1455(13) c/Å 18.299(3) α/˚ 90.00 β/˚ 90.00 ϒ/˚ 90.00 Volume/Å3 3260.6(9) Z 4 3 Ρcalcmg/mm 1.248

Absorption coefficient/mm-1 0.093 F(000) 1300.00 Crystal size/mm3 0.5 x 0.3 x 0.2 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 4.338 to 52.76 Index ranges -27<=h<=27, -6<=k<=10, -22<=l<=22 Reflections collected 21716

Independent reflections 6570 (Rint = 0.0586, Rsima = 0.0661) Data/restrains/parameters 6570/1/404 Goodness-of-fit on F2 1.011

Final R indexes [I>2σ (I)] R1 = 0.0434, wR2 = 0.0802

Final R indexes [all data] R1 = 0.0702, wR2 = 0.0911 Largest diff. peak/hole/e Å-3 0.18 and -0.00

Crystal data and structure refinement for Radical 2.3e

Empirical Formula C27H35F7NO Formula Weight 522.56 Temperature/K 100 K Crystal System Monoclinic

Space group P21/c a/Å 8.8071(4) b/Å 24.8008(12) c/Å 11.5922(5) α/˚ 90.00 β/˚ 90.095(3) ϒ/˚ 90.00 Volume/Å3 2532.0(2) Z 4 3 Ρcalcmg/mm 1.371 Absorption coefficient/mm-1 0.118 F(000) 1100.00 Crystal size/mm3 0.2 x 0.1 x 0.1 Radiation MoKα (λ = 0.71073) 2θ Range for data collection/˚ 3.514 to 51.996 Index ranges -10<=h<=9, -30<=k<=30, -14<=l<=14 Reflections collected 19172

Independent reflections 4920 (Rint = 0.0354, Rsima = 0.0291) Data/restrains/parameters 4920/0/332 Goodness-of-fit on F2 1.031

Final R indexes [I>2σ (I)] R1 = 0.0669, wR2 = 0.1821

Final R indexes [all data] R1 = 0.0779, wR2 = 0.1923 Largest diff. peak/hole/e Å-3 0.74 and -0.37

Crystal data and structure refinement for Radical 2.3f

Empirical Formula C41H62BF4N2O Formula Weight 685.73 Temperature/K 100 K Crystal System Monoclinic

Space group P21/c a/Å 17.1080(11) b/Å 14.0937(8) c/Å 16.0726(11) α/˚ 90.00 β/˚ 102.341(5) ϒ/˚ 90.00 Volume/Å3 3785.8(4) Z 4 3 Ρcalcmg/mm 1.203 Absorption coefficient/mm-1 0.677 F(000) 1484.0 Crystal size/mm3 0.3 x 0.2 x 0.2 Radiation CuKα (λ = 1.54178) 2θ Range for data collection/˚ 5.288 to 136.564 Index ranges -20<=h<=20, -16<=k<=16, -19<=l<=19 Reflections collected 10098

Independent reflections 10098 (Rint = ?, Rsima = 0.0914) Data/restrains/parameters 10098/1/513 Goodness-of-fit on F2 1.043

Final R indexes [I>2σ (I)] R1 = 0.0744, wR2 = 0.1843

Final R indexes [all data] R1 = 0.1284, wR2 = 0.2194 Largest diff. peak/hole/e Å-3 0.28 and -0.26

Crystal data and structure refinement for Iminium 2.5

Empirical Formula C42H65BCl2F4N2O Formula Weight 771.67 Temperature/K 100 K Crystal System Monoclinic

Space group P21/c a/Å 12.3686(5) b/Å 10.8693(5)

c/Å 31.8290(12) α/˚ 90.00 β/˚ 100.487(3) ϒ/˚ 90.00 Volume/Å3 4207.6(3) Z 4 3 Ρcalcmg/mm 1.218 Absorption coefficient/mm-1 1.805 F(000) 1656.0 Crystal size/mm3 0.1 x 0.04 x 0.02 Radiation CuKα (λ = 1.54184) 2θ Range for data collection/˚ 5.648 to 137.732 Index ranges -14<=h<=14, -13<=k<=13, -38<=l<=37 Reflections collected 31283

Independent reflections 7582 (Rint = 0.0476, Rsima = 0.0415) Data/restrains/parameters 7582/64/526 Goodness-of-fit on F2 1.052

Final R indexes [I>2σ (I)] R1 = 0.0704, wR2 = 0.1942

Final R indexes [all data] R1 = 0.0948, wR2 = 0.2148 Largest diff. peak/hole/e Å-3 0.60 and -0.61

4) Cartesian coordinates of 2.3a-f.

Cartesian coordinates of 2.3a’ calculated at the B3LYP/TZVP level of theory.

------C -1.98745 -0.57944 0.466011 Atom x y Z C -2.98929 0.277413 1.290009 ------C -2.72963 -1.25226 -0.72886 C -0.55256 1.20636 -1.04407 C -4.26077 -0.48997 1.692952 O 0.565934 1.283087 -1.58618 H -3.29504 1.147592 0.711272 C -1.55789 2.365916 -1.40551 H -2.4907 0.665125 2.182971 C -2.9508 1.9435 -1.91527 C -3.99011 -2.0198 -0.29915 H -3.57255 1.464771 -1.1624 H -3.01361 -0.50124 -1.4636 H -3.48802 2.836106 -2.25006 H -2.03172 -1.92644 -1.23473 H -2.86995 1.271725 -2.77425 C -4.95687 -1.12118 0.480902 C -0.91575 3.187911 -2.54483 H -4.94175 0.195836 2.207366 H -1.57447 4.024495 -2.79789 H -4.01886 -1.27621 2.417661 H 0.057784 3.583739 -2.26015 H -4.48231 -2.42834 -1.18768 H -0.7704 2.579568 -3.43959 H -3.71646 -2.88195 0.321529 C -1.69769 3.300206 -0.17987 H -5.83309 -1.69274 0.803137 H -0.72169 3.693828 0.113953 H -5.32869 -0.3276 -0.17968 H -2.3384 4.15208 -0.43101 C 0.156378 -0.52209 2.995516 H -2.13037 2.800918 0.686914 H -0.222 -1.13983 3.815043 C -0.72949 0.166399 -0.03607 H 1.188769 -0.26229 3.226161 C 0.064231 -1.31272 1.675226 H -0.4305 0.397065 2.963893 C -1.38346 -1.70098 1.359704 C 0.961086 -2.54931 1.794798 H -1.3868 -2.6489 0.816129 H 2.002858 -2.27994 1.975623 H -1.95384 -1.85921 2.27533 H 0.615563 -3.14895 2.641559

H 0.913089 -3.17181 0.902351 H 1.185023 -4.25662 -2.23139 N 0.399932 -0.44691 0.4934 C 1.236463 -1.60864 -3.08819 C 1.789022 -0.31449 0.08964 H 0.512669 -2.20886 -3.64932 C 2.633026 0.646794 0.685452 H 2.185751 -1.63377 -3.63216 C 2.307444 -1.24443 -0.84344 H 0.894948 -0.57421 -3.0551 C 4.002634 0.596571 0.402888 C 2.115797 1.820489 1.511573 C 3.680109 -1.24358 -1.09513 H 1.054022 1.658469 1.698662 C 4.531616 -0.34783 -0.46243 C 2.241972 3.128038 0.700586 H 4.662252 1.327799 0.856001 H 1.764924 3.026132 -0.2742 H 4.089507 -1.95027 -1.8076 H 1.777347 3.959058 1.241267 H 5.59703 -0.37018 -0.66372 H 3.292643 3.384442 0.535532 C 1.41502 -2.17246 -1.66253 C 2.825159 1.977843 2.869194 H 0.429814 -2.18528 -1.19405 H 2.799983 1.060532 3.461631 C 1.921437 -3.62487 -1.72565 H 3.875138 2.254413 2.73994 H 2.853484 -3.70262 -2.29185 H 2.350395 2.771024 3.454433 H 2.103298 -4.04406 -0.73304 ------

Cartesian coordinates of 2.3a’’ calculated at the B3LYP/TZVP level of theory.

------C 0.210117 -0.68981 3.002023 Atom X Y Z H 0.808258 -0.45033 3.885701 ------H -0.809 -0.87069 3.339855 C 0.819234 -1.05082 -1.45165 H 0.599822 -1.6137 2.572557 O 1.762273 -0.86661 -2.23944 C -0.44096 1.696383 2.564586 C -0.19273 -2.18269 -1.82376 H -1.49827 1.499712 2.741658 C -0.47032 -3.07195 -0.59846 H 0.015344 1.967081 3.520623 H -0.89081 -2.50944 0.231046 H -0.36325 2.556717 1.898878 H -1.1701 -3.87172 -0.85937 N -0.21387 0.069926 0.625841 H 0.454326 -3.5419 -0.2503 C -1.48008 0.573564 0.124436 C 0.475116 -3.06007 -2.90374 C -2.71192 0.0163 0.561682 H -0.19836 -3.88248 -3.16519 C -1.49071 1.670046 -0.78209 H 0.694846 -2.4857 -3.80309 C -3.90671 0.556204 0.074291 H 1.416292 -3.48552 -2.54883 C -2.71747 2.138139 -1.26017 C -1.49758 -1.62561 -2.4309 C -3.92142 1.596698 -0.83948 H -1.27616 -1.00175 -3.30102 H -4.84743 0.133868 0.407422 H -2.12525 -2.45585 -2.77147 H -2.72572 2.963376 -1.96261 H -2.07839 -1.03162 -1.72974 H -4.86118 1.985571 -1.21537 C 0.847287 -0.30139 -0.19781 C -0.24478 2.417948 -1.25131 C 0.295351 0.478904 1.998242 H 0.616555 1.992926 -0.74477 C 1.769804 0.824876 1.711427 C -0.3012 3.912034 -0.87248 H 1.853568 1.8992 1.525204 H -1.08787 4.439838 -1.41832 H 2.394455 0.605885 2.577912 H -0.4881 4.054775 0.194777 C 2.206277 0.053981 0.444029 H 0.648793 4.395963 -1.11774 C 2.989194 -1.25722 0.764046 C -0.00224 2.259538 -2.76419 C 3.135616 0.95455 -0.42476 H 0.9034 2.798376 -3.05744 C 4.367824 -1.02158 1.399815 H -0.83518 2.667324 -3.34448 H 3.124432 -1.79473 -0.17926 H 0.132481 1.214298 -3.04221 H 2.390141 -1.90412 1.411022 C -2.84437 -1.16891 1.517733 C 4.490194 1.221564 0.250733 H -1.84514 -1.54961 1.717984 H 3.292393 0.466447 -1.38474 C -3.66158 -2.32505 0.904111 H 2.635709 1.905413 -0.63145 H -3.28272 -2.61576 -0.07555 C 5.233525 -0.08528 0.549585 H -3.61819 -3.2007 1.558529 H 4.869089 -1.98589 1.534909 H -4.71464 -2.05495 0.78912 H 4.2539 -0.59643 2.404974 C -3.48023 -0.76175 2.862506 H 5.094271 1.857665 -0.40479 H -4.50436 -0.40678 2.718306 H 4.353373 1.786277 1.182093 H -3.52031 -1.62068 3.539405 H 6.18371 0.118508 1.054364 H -2.92618 0.034434 3.36288 H 5.478902 -0.58148 -0.39757 ------

Cartesian coordinates of 2.3c calculated at the B3LYP/TZVP level of theory.

------C 4.848081 0.93832 -2.67443 Atom X Y Z H 5.546572 1.208301 -3.45735 ------C 4.179636 -0.27283 -2.7238 O 0.609459 1.147001 -1.34347 H 4.344621 -0.93467 -3.56456 N 2.281013 -0.19163 0.497208 C 3.6988 1.49619 -0.61303 C 2.932614 -0.89255 1.663062 C 2.466906 -1.92441 -1.93938 C -4.18558 0.381474 -0.74013 H 1.888813 -2.11163 -1.03606 C -3.52395 1.542179 -0.3394 C 0.45848 -0.76 1.931388 C 1.801226 -0.86346 2.698237 C -0.21892 -2.15024 1.758859 H 1.849753 -1.72936 3.355772 H 0.451317 -2.83858 1.240695 H 1.920662 0.022922 3.32482 H -1.09398 -2.02999 1.119902 C 0.11595 0.482752 -0.4048 C -0.51973 0.157625 2.707912 C -2.14425 1.555799 -0.19687 H -1.41686 0.323299 2.110874 C -1.39526 0.396718 -0.42228 H -0.05487 1.136208 2.857395 C -0.68344 -2.76703 3.08567 C 4.587293 1.819789 -1.63761 H 0.179533 -3.03106 3.70546 H 5.070162 2.788693 -1.63282 H -1.20298 -3.70594 2.87618 C 4.576893 3.215754 1.069561 C 3.358065 -2.32407 1.298223 H 5.23701 2.47555 1.523106 H 2.530194 -2.9272 0.931442 H 5.166079 3.785888 0.348469 H 4.140494 -2.31369 0.540472 H 4.261103 3.913052 1.849539 H 3.762666 -2.81218 2.187016 C 2.471945 3.663028 -0.24436 C 3.083694 0.225946 -0.63885 H 3.037405 4.217852 -0.99704 C 4.171169 -0.15821 2.18235 H 1.601851 3.226296 -0.7323 H 4.955374 -0.10504 1.427044 H 2.135622 4.377788 0.511741 H 3.934581 0.849686 2.515223 C 1.459935 -1.72681 -3.09032 H 4.567754 -0.70874 3.03791 H 1.97832 -1.6163 -4.04559 C 3.346677 2.573868 0.407699 H 0.800629 -2.59535 -3.17049 H 2.745671 2.110606 1.190247 H 0.85284 -0.83521 -2.93821 C 0.916275 -0.15266 0.597857 H -1.63891 2.467374 0.091561 C -2.05414 -0.75281 -0.84372 H -5.26059 0.373835 -0.85386 C -0.94615 -0.44584 4.052435 H -1.48711 -1.64372 -1.0787 H -1.63949 0.23812 4.548966 C -4.33315 2.793179 -0.10742 H -0.08022 -0.53924 4.716405 C -4.1203 -2.03826 -1.41425 C 3.332252 -3.16605 -2.20963 F -4.72915 3.357834 -1.27173 H 3.878267 -3.07498 -3.15076 F -5.45865 2.536021 0.598535 H 4.063155 -3.34213 -1.41959 F -3.64325 3.731907 0.571422 H 2.699995 -4.0539 -2.28785 F -3.46209 -2.65478 -2.42069 C 3.277808 -0.65028 -1.72699 F -5.38822 -1.84205 -1.82434 C -1.59987 -1.81794 3.863611 F -4.17138 -2.92649 -0.3886 H -2.54024 -1.69526 3.314509 ------H -1.85951 -2.253 4.832363 C -3.44128 -0.75832 -1.00061

Cartesian coordinates of 2.3d calculated at the B3LYP/TZVP level of theory.

------C -3.94665 -1.51584 -0.99572 Atom X Y Z C 0.969804 2.727227 -0.86784 ------H 0.950638 3.761665 -0.53014 F -1.9732 -1.30552 -2.23109 H 1.005161 2.746898 -1.95895 F -1.96223 -0.35688 2.402251 C -0.36755 -0.69209 0.04673 F -5.92442 -1.7166 0.27679 C -2.59622 -1.20398 -1.04678 F -4.60269 -1.89766 -2.09686 C -1.88782 -0.78343 0.074349 F -4.59209 -0.93491 2.520649 C -1.53642 3.897506 0.674936 O 0.204412 -1.78669 0.230702 H -0.75293 4.638906 0.487136 N 1.685352 0.602669 -0.1352 H -2.02472 4.204755 1.603719 C 2.21526 2.000571 -0.34141 C 2.733058 2.613084 0.968756 C -4.6237 -1.4233 0.213462 H 1.972371 2.640158 1.746507

H 3.593016 2.060339 1.343191 C 3.116709 -1.20534 -1.01556 H 3.055425 3.638226 0.775712 C 2.345866 -0.26119 2.657889 C 2.609823 -0.4954 0.093726 H 1.664787 0.532847 2.356766 C 3.352833 2.050118 -1.36488 C -0.27779 1.926237 -0.41923 H 4.221642 1.482345 -1.03204 C -0.9157 2.508181 0.875384 H 3.038095 1.673425 -2.33541 H -0.17626 2.540297 1.677748 H 3.660113 3.090098 -1.49275 H -1.69742 1.826335 1.213837 C 2.547375 -1.07638 -2.42479 C -1.34204 1.956685 -1.54374 H 1.874285 -0.21924 -2.44091 H -2.17109 1.30022 -1.28249 C 0.32129 0.537951 -0.16365 H -0.90794 1.565609 -2.46713 C -2.59107 -0.71849 1.271177 C 4.116722 -2.15136 -0.79151 C -1.91391 3.36266 -1.76649 H 4.519323 -2.70447 -1.63048 H -2.66072 3.322548 -2.56385 C 3.624392 -0.85366 -3.49958 H -1.12952 4.041925 -2.11699 H 4.266435 -0.00191 -3.2718 C 3.329242 0.324636 3.684464 H 4.265845 -1.73034 -3.60879 H 3.97917 -0.44788 4.10073 H 3.154241 -0.67572 -4.46981 H 3.968541 1.096999 3.254896 C 1.704132 -2.31876 -2.77415 H 2.779069 0.766997 4.518393 H 2.336922 -3.20644 -2.85029 C 3.024896 -0.80611 1.405611 H 0.94736 -2.50939 -2.01493 C -2.53911 3.915687 -0.48252 H 1.207032 -2.17913 -3.73757 H -3.40974 3.305198 -0.21595 C 1.491431 -1.36036 3.320513 H -2.91015 4.93111 -0.64525 H 2.124287 -2.15804 3.71705 C -3.94336 -1.02217 1.354239 H 0.919916 -0.94192 4.152868 C 4.591128 -2.414 0.483142 H 0.797428 -1.80389 2.608689 H 5.373388 -3.14833 0.63367 ------C 4.030757 -1.76039 1.56738 H 4.364621 -2.01105 2.566205

Cartesian coordinates of 2.3e calculated at the B3LYP/TZVP level of theory.

------H 0.162721 -2.30419 2.024232 Atom x y z H 1.32934 -3.13074 3.056811 ------H 0.268775 -1.90009 3.747018 F -2.36551 -0.10249 -1.79287 C 2.814295 2.037524 1.742626 F -2.72903 0.698217 0.220133 H 1.979151 1.987245 2.437903 F -2.4355 -2.01865 1.177337 H 3.545871 1.282548 2.024908 F -2.60143 -2.60782 -0.94207 H 3.28736 3.015304 1.853124 O -0.13066 -1.55522 -0.30481 C 1.480334 -1.51199 -3.25762 N 1.622348 0.570482 0.070884 H 1.97555 -2.44704 -3.5304 F -4.7796 -0.76689 1.099382 H 0.628965 -1.75796 -2.62526 F -4.94521 -2.71055 0.160961 H 1.113689 -1.04805 -4.17699 F -4.91123 -0.92015 -1.06616 C -2.1012 -0.30956 -0.46493 C 2.359817 -0.68441 0.043029 C 3.635606 1.955186 -0.5925 C -0.06473 2.252479 -0.00731 H 4.363749 1.183588 -0.34349 C 2.868938 -1.14838 -1.1888 H 3.397748 1.886408 -1.65118 C 2.606204 -1.3841 1.241916 H 4.102856 2.926587 -0.41793 C 4.014186 -2.92385 0.002405 C -0.71837 2.643533 1.353347 H 4.668746 -3.78701 -0.0112 H -1.61288 2.044145 1.505602 C 3.702122 -2.26636 -1.17641 H -0.03939 2.394775 2.170958 H 4.100666 -2.63836 -2.11158 C 3.658408 -0.26223 -3.45812 C -0.57404 -0.38924 -0.23929 H 4.400597 0.375988 -2.97705 C 0.275637 0.752694 -0.06329 H 4.164822 -1.17762 -3.77076 C 3.452809 -2.49299 1.192184 H 3.313966 0.240453 -4.36511 H 3.655277 -3.04276 2.102465 C 1.337503 2.89659 -0.15179 C 2.380712 1.861495 0.279129 H 1.506612 3.154346 -1.19912 C 2.462954 -0.56579 -2.53913 H 1.436701 3.814625 0.423799 H 1.933742 0.370597 -2.36078 C 2.855841 -0.94215 3.752316 C 1.897229 -1.08245 2.558215 H 3.346824 -1.89009 3.981718 H 1.359955 -0.14179 2.447155 H 3.637072 -0.20177 3.576267 C 0.847223 -2.17033 2.859638 H 2.301431 -0.64174 4.64461

C -0.95731 2.738772 -1.17932 C -1.10228 4.128421 1.434677 H -0.45401 2.515864 -2.12394 H -1.63508 4.301635 2.373646 H -1.90145 2.203767 -1.19523 H -0.20381 4.75295 1.478641 C -2.84556 -1.62992 -0.05247 C -1.96213 4.568289 0.246684 C -4.40974 -1.4888 0.036465 H -2.17141 5.639567 0.310253 C -1.27482 4.236743 -1.08095 H -2.92977 4.056388 0.288212 H -0.36038 4.831509 -1.17942 ------H -1.91555 4.519205 -1.92037

Cartesian coordinates of 2.3f calculated at the B3LYP/6-311g** level of theory.

------H 3.549701 4.353933 1.136833 Atom x y z C -3.83632 1.543908 -2.15119 ------H -4.29427 1.366793 -3.11669 O -0.12144 0.370696 -0.8216 C -3.7957 2.83473 -1.64861 N 2.400765 -0.63032 -0.37185 H -4.23593 3.652631 -2.20707 N -2.30783 -0.40596 0.658558 C -0.48272 3.115775 1.142786 C -1.17745 -1.15382 0.610708 H 0.110904 2.48151 0.486498 C -2.70473 0.722399 -0.18903 H 0.111462 3.356003 2.028287 C -1.32832 -2.38054 1.526166 H -0.68714 4.051841 0.616184 C -0.04709 -0.70701 -0.18043 C -1.7536 -3.63794 0.724457 C 1.307558 -1.36763 -0.40188 H -2.72133 -3.50189 0.245782 C 2.608389 1.795034 -0.91619 H -1.84114 -4.48545 1.409504 C -3.34338 -0.94052 1.650094 H -1.0507 -3.91138 -0.05583 C 2.811576 1.037112 1.429049 C -2.56945 3.3266 2.53259 C -1.7959 2.42225 1.554064 H -2.73444 4.319981 2.108493 H -1.52289 1.504917 2.079485 H -1.99134 3.463217 3.45069 C -2.59509 2.040235 0.310061 H -3.54377 2.919182 2.804309 C 2.959867 3.076403 -0.48499 C -2.29122 -0.84016 -3.3472 H 2.998459 3.877522 -1.21211 H -2.66133 -0.16358 -4.12164 C -3.29012 0.464773 -1.44994 H -2.18462 -1.83131 -3.79806 C 2.564762 0.767679 0.0636 H -1.30889 -0.48229 -3.03698 C 2.646712 0.03786 2.573772 C 3.909753 -0.09914 3.447133 H 2.421618 -0.94446 2.156174 H 4.801288 -0.32879 2.862386 C 2.275657 1.642311 -2.40368 H 3.773234 -0.89734 4.181624 H 2.092875 0.585806 -2.6118 H 4.110746 0.819948 4.002242 C 3.656725 -1.41114 -0.82708 C 0.564147 -2.93964 -2.23511 C 1.587537 -2.72795 -1.10096 H -0.44282 -3.12152 -1.86102 C -2.50391 -1.95632 2.43406 H 0.866767 -3.80765 -2.82665 H -3.09677 -2.81435 2.754349 H 0.523727 -2.076 -2.90045 H -2.11275 -1.47614 3.334101 C 1.455971 0.450932 3.464148 C -3.26838 -0.8912 -2.15307 H 1.640159 1.419446 3.934532 H -2.89043 -1.63934 -1.45424 H 1.306824 -0.27809 4.265364 C -3.16026 3.074984 -0.44008 H 0.531821 0.535643 2.889078 H -3.08757 4.0916 -0.07371 C 0.991772 2.413408 -2.78291 C 2.993116 -2.478 -1.69579 H 0.133717 2.087372 -2.20344 H 3.585272 -3.39209 -1.74184 H 0.775564 2.258382 -3.84396 H 2.89717 -2.09503 -2.71469 H 1.129088 3.487641 -2.63309 C 3.171101 2.343268 1.781585 C 1.656888 -3.99759 -0.21736 H 3.374757 2.569166 2.820863 H 2.401934 -3.91925 0.573312 C -0.10118 -2.67163 2.405472 H 1.957512 -4.82399 -0.86564 H 0.792332 -2.91664 1.837754 H 0.711691 -4.27347 0.233447 H -0.31644 -3.52509 3.054421 C -4.65427 -1.35979 -2.63531 H 0.125392 -1.81849 3.043082 H -5.38804 -1.38713 -1.8286 C 3.416166 2.143867 -3.31972 H -4.5832 -2.36422 -3.06198 H 3.472898 3.234858 -3.30607 H -5.04707 -0.70554 -3.41695 H 3.217395 1.848885 -4.3535 C -3.8863 0.141055 2.589976 H 4.399629 1.766911 -3.04029 H -3.09991 0.610705 3.177697 C 3.262258 3.352213 0.839479 H -4.44028 0.9084 2.049794

H -4.57847 -0.34005 3.285619 H 5.16896 -2.65067 0.067097 C -4.55211 -1.55103 0.919714 C 4.646625 -0.57424 -1.63009 H -5.22164 -1.98852 1.663488 H 4.225166 -0.23153 -2.5703 H -5.10744 -0.77788 0.388042 H 5.019126 0.280429 -1.0652 H -4.28631 -2.32987 0.20921 H 5.500624 -1.21457 -1.8648 C 4.391865 -1.96168 0.404695 ------H 4.881262 -1.15452 0.947971 H 3.74297 -2.49519 1.096685

Cartesian coordinates of 2.3f’ calculated at the B3LYP/6-31g* level of theory.

------C -4.28527 0.970932 -1.55881 Atom x y z H -4.93354 0.606815 -2.35007 ------C -4.17972 2.341405 -1.33973 O -0.54552 -0.36581 -1.25468 H -4.73896 3.035566 -1.96051 N 2.289018 -0.70132 -0.7206 C -0.71243 3.481625 1.123674 N -2.07538 -0.34937 1.144119 H -0.06423 2.991167 0.392385 C -0.89699 -1.01409 1.005317 H -0.08827 3.830423 1.954423 C -2.74787 0.565517 0.24182 H -1.15031 4.365512 0.646624 C -0.68201 -1.90702 2.240278 C -1.22085 -3.33194 1.95508 C -0.13188 -0.90442 -0.18871 H -2.28572 -3.31863 1.700971 C 1.235285 -1.46227 -0.54527 H -1.09584 -3.95892 2.844885 C 2.153388 1.674545 -1.34956 H -0.69637 -3.8153 1.127946 C -2.73886 -0.64745 2.430792 C -2.68034 3.222069 2.697059 C 3.178568 1.032898 0.816411 H -3.19349 4.09135 2.27135 C -1.79982 2.522382 1.641094 H -2.06644 3.575611 3.533264 H -1.28153 1.693306 2.135945 H -3.45056 2.554509 3.100012 C -2.64202 1.948305 0.503537 C -3.4695 -1.81515 -2.49822 C 2.436837 3.011622 -1.04259 H -4.21453 -1.38434 -3.17597 H 2.179132 3.78178 -1.76232 H -3.50648 -2.90344 -2.62504 C -3.57798 0.052265 -0.77661 H -2.4831 -1.45837 -2.80859 C 2.495988 0.706793 -0.37642 C 5.251393 -0.21684 1.536548 C 3.740246 -0.00579 1.78433 H 5.467612 -0.51223 0.504482 H 3.235842 -0.96057 1.599117 H 5.642908 -0.994 2.20257 C 1.579643 1.346212 -2.72798 H 5.80769 0.706037 1.733202 H 1.314424 0.286678 -2.75223 C 0.211108 -3.38275 -1.9012 C 3.361304 -1.38352 -1.51145 H -0.5966 -3.60146 -1.19636 C 1.461052 -2.84634 -1.18961 H 0.466206 -4.31406 -2.41773 C -1.60889 -1.22096 3.276739 H -0.1666 -2.66863 -2.63688 H -1.96011 -1.91933 4.041164 C 3.511266 0.362742 3.263384 H -1.07239 -0.40862 3.780303 H 4.154505 1.192224 3.575001 C -3.75175 -1.4414 -1.0307 H 3.754782 -0.49028 3.905554 H -3.02051 -1.97867 -0.41705 H 2.475927 0.657988 3.460644 C -3.3675 2.820541 -0.31749 C 0.285671 2.125995 -3.02815 H -3.30191 3.890742 -0.14484 H -0.47636 1.935496 -2.26939 C 2.607696 -2.52367 -2.18485 H -0.11579 1.811884 -3.99786 H 3.241806 -3.39186 -2.38042 H 0.465353 3.205384 -3.08394 H 2.190542 -2.18343 -3.13859 C 1.970347 -3.87336 -0.14613 C 3.427752 2.389041 1.060851 H 2.877984 -3.53362 0.364565 H 3.942244 2.677247 1.971409 H 2.211438 -4.80374 -0.67024 C 0.756138 -1.96207 2.762884 H 1.221029 -4.10958 0.610105 H 1.443235 -2.4541 2.070195 C -5.15549 -1.9178 -0.60384 H 0.782717 -2.53122 3.698952 H -5.35714 -1.69677 0.450682 H 1.134099 -0.95896 2.971002 H -5.25581 -2.99938 -0.75056 C 2.632037 1.608918 -3.82753 H -5.93555 -1.42717 -1.19647 H 2.897922 2.670524 -3.8771 H -3.17945 0.266103 2.833907 H 2.233753 1.320009 -4.80638 H -3.55396 -1.36232 2.259043 H 3.560519 1.049406 -3.66234 H 3.801015 -0.65889 -2.1972 C 3.053946 3.37085 0.15015 H 4.14018 -1.71897 -0.82014 H 3.264412 4.415385 0.360608 ------

Cartesian coordinates of 2.3f’ transition state calculated at the B3LYP/6-31g* level of theory.

------H -4.41283 -1.77965 2.461234 Atom X Y Z C -3.79783 -2.9831 0.799023 ------H -4.22482 -3.8945 1.207315 O 0.012975 -0.63819 -0.04478 C -0.73766 -2.91411 -2.35275 N 2.248373 0.567456 0.880482 H -0.00499 -2.64814 -1.58719 N -2.25573 0.581018 -0.86507 H -0.24105 -2.90342 -3.32994 C -1.12871 1.273764 -0.70307 H -1.07503 -3.94022 -2.16876 C -2.7077 -0.65753 -0.24218 C -1.68618 3.796349 -0.81373 C -1.18599 2.549198 -1.58317 H -2.64131 3.612051 -0.31013 C 0.002873 0.626754 -0.00701 H -1.83915 4.610517 -1.52981 C 1.118205 1.258981 0.719802 H -0.97884 4.152373 -0.06651 C 2.613068 -1.86164 0.961299 C -2.92442 -2.281 -3.46832 C -3.19851 1.221858 -1.81424 H -3.34384 -3.28183 -3.31827 C 3.380088 -0.56447 -1.00108 H -2.42796 -2.27346 -4.44512 C -1.91897 -1.9242 -2.35371 H -3.76605 -1.57941 -3.51124 H -1.50181 -0.93709 -2.58211 C -3.04979 0.538237 3.256402 C -2.60129 -1.84987 -0.99042 H -3.67966 -0.15413 3.824612 C 3.181037 -3.00343 0.39036 H -3.08306 1.504698 3.771752 H 3.109551 -3.95059 0.916448 H -2.02358 0.157092 3.294774 C -3.36091 -0.59686 1.003903 C 5.01648 1.22435 -1.7389 C 2.716344 -0.6543 0.237525 H 5.374929 1.359602 -0.71214 C 3.552264 0.738611 -1.77628 H 5.118232 2.180759 -2.26429 H 2.938139 1.509313 -1.2972 H 5.682586 0.503417 -2.2254 C 1.914752 -1.9672 2.314273 C -0.15843 2.795064 2.350897 H 1.499211 -0.98417 2.562931 H -0.97273 3.068266 1.678253 C 3.177885 1.19437 1.850866 H -0.01763 3.625388 3.051994 C 1.164149 2.520103 1.619804 H -0.47643 1.921761 2.927565 C -2.28782 2.145738 -2.60504 C 3.063999 0.610178 -3.23212 H -2.80747 3.016639 -3.01198 H 3.698569 -0.06825 -3.81189 H -1.841 1.596041 -3.44079 H 3.092211 1.585989 -3.73 C -3.54052 0.690319 1.803726 H 2.040136 0.223778 -3.27875 H -2.93236 1.474181 1.338579 C 0.729207 -2.9512 2.272675 C -3.15436 -3.00696 -0.43581 H 0.007893 -2.66196 1.504553 H -3.08038 -3.94312 -0.98084 H 0.219803 -2.96423 3.243249 C 2.256937 2.104172 2.646191 H 1.064758 -3.97346 2.065205 H 2.770231 2.970219 3.071227 C 1.670321 3.776889 0.870033 H 1.803268 1.54126 3.469389 H 2.62895 3.598124 0.3711 C 3.933618 -1.74377 -1.51953 H 1.818122 4.583035 1.596235 H 4.456001 -1.71011 -2.47058 H 0.968957 4.141166 0.121035 C 0.130897 2.834954 -2.32074 C -5.00822 1.166424 1.7774 H 0.947695 3.106614 -1.65037 H -5.3695 1.318717 0.754005 H -0.01811 3.669977 -3.01448 H -5.11566 2.11196 2.320995 H 0.449351 1.96738 -2.90589 H -5.66832 0.43163 2.251188 C 2.904776 -2.35492 3.432171 H -3.68541 0.447442 -2.40851 H 3.321162 -3.35426 3.264746 H -3.97322 1.747425 -1.24382 H 2.396948 -2.36687 4.403103 H 3.659287 0.411336 2.438569 H 3.7489 -1.65831 3.50035 H 3.958837 1.730869 1.299146 C 3.836274 -2.95034 -0.83736 ------H 4.275131 -3.85004 -1.25882 C -3.89901 -1.7907 1.505037

5) Cartesian coordinates of the calculated mono-radicals (B3LPY/6-311G**).

R= NO2 ------H 2.137559 2.206851 1.212976 Atom x y z H 2.488513 2.361619 -0.52127 ------H 0.818478 2.571555 0.06966 C -0.92228 0.61557 -0.03735 H 3.050373 -0.35766 1.090617 O -1.13681 1.813807 -0.15634 H 3.459817 0.074369 -0.57754 C 1.744617 2.024194 0.205509 N -2.1802 -0.28968 0.041792 N 1.508778 0.598762 0.018612 O -2.0687 -1.4088 0.541221 C 2.079846 -1.64352 -0.40232 O -3.21226 0.198829 -0.36733 H 2.593778 -2.50043 0.033325 H 0.446704 -1.94135 1.034353 H 2.153166 -1.72047 -1.48988 H -0.07131 -2.10988 -0.62248 C 0.603011 -1.55232 0.023524 ------C 0.32633 -0.0643 0.014669 C 2.662653 -0.30944 0.063806

R = CN ------C 2.324808 -0.4183 0.116033 Atom x y z H 1.956329 2.226407 0.999784 ------H 2.196576 2.221445 -0.76058 C -1.25152 0.59449 -0.03431 H 0.567222 2.514048 -0.08233 O -1.44304 1.828788 -0.11621 H 2.71076 -0.40944 1.144469 C 1.495888 1.965499 0.039694 H 3.140611 -0.12526 -0.54973 N 1.215762 0.536608 -0.00232 C -2.4052 -0.30533 0.011404 C 1.679828 -1.75904 -0.25326 N -3.33084 -0.9972 0.046845 H 2.14855 -2.60249 0.253663 H 0.023032 -1.87318 1.176437 H 1.760016 -1.92324 -1.33032 H -0.49194 -2.12387 -0.48372 C 0.203125 -1.56176 0.140177 ------C 0.009526 -0.06733 0.021972

R = (CO)Me ------H -2.12488 2.324492 -1.11101 Atom x y z H -2.42018 2.421831 0.637359 ------H -3.12031 -0.19148 -1.13629 C 0.915237 0.501192 0.042008 H -3.52935 0.186124 0.544262 O 1.129495 1.738984 0.151786 C 2.117481 -0.41642 -0.04707 C -1.71349 2.078773 -0.12434 O 2.03418 -1.61857 -0.23715 N -1.5459 0.636097 -0.00665 C 3.454505 0.277108 0.09823 C -2.23712 -1.59161 0.308828 H 3.565003 1.049923 -0.66625 H -2.775 -2.39978 -0.18743 H 3.513389 0.793059 1.060043 H -2.3538 -1.72134 1.387656 H 4.248917 -0.46315 0.012579 C -0.74162 -1.5486 -0.05743 H -0.55735 -1.92783 -1.06882 C -0.39753 -0.07575 -0.00714 H -0.11024 -2.14281 0.5982 C -2.74307 -0.20901 -0.10434 ------H -0.75061 2.560816 0.006747

R = C3F7 ------F -3.08207 -0.941 -1.26342 Atom x y z F -4.09907 0.51045 -0.01386 ------F -3.123 -1.20188 0.894923 F -0.45346 -1.01065 1.235746 C 3.611229 1.964919 -0.13888 F -0.41527 -1.11704 -0.95915 C 2.290679 -1.55322 -0.14151 F -1.72261 1.374123 -1.04613 C 0.857064 0.638234 0.093595 F -1.87284 1.297263 1.158286 C 2.094586 -0.05514 -0.02469 O 0.718188 1.871675 0.219475 C 4.410188 -0.41951 -0.17733 N 3.312095 0.543365 -0.03792 C -0.41183 -0.24105 0.098469

C 3.770499 -1.74708 0.23589 H 4.375458 2.22604 0.599063 H 3.866714 -1.88365 1.315694 H 5.249464 -0.11926 0.455412 H 4.227625 -2.6051 -0.25739 H 4.762626 -0.43321 -1.21828 C -1.74076 0.561789 0.03471 H 2.104429 -1.86524 -1.17525 C -3.03515 -0.30074 -0.09027 H 1.609295 -2.11879 0.491007 H 4.0031 2.194613 -1.13745 ------H 2.706924 2.536911 0.039383

R = (CO)H ------C 2.329649 -0.45246 0.125465 Atom x y z H 0.673668 2.532651 -0.04915 ------H 2.038818 2.171571 1.04539 C -1.21651 0.684828 -0.05279 H 2.301262 2.186478 -0.71115 O -1.30959 1.94045 -0.14332 H 2.704379 -0.4594 1.158061 C 1.579147 1.947739 0.075501 H 3.158718 -0.16955 -0.52825 N 1.244492 0.53092 0.006347 C -2.50619 -0.07635 -0.00315 C 1.658317 -1.77162 -0.26286 H -3.36562 0.620982 -0.08642 H 2.088594 -2.62838 0.256014 O -2.6594 -1.27461 0.120041 H 1.765517 -1.93941 -1.33727 H -0.05863 -1.86799 1.105283 C 0.176486 -1.53644 0.087108 H -0.52081 -2.05997 -0.56246 C 0.02152 -0.03407 0.006013 ------

R = C6F5 ------H -4.59933 -1.52197 0.257342 Atom x y z H -5.11517 -0.05714 1.10875 ------C 0.37142 0.291541 -0.31454 C -1.06091 0.649506 -0.67227 C 0.906567 -0.97048 -0.55219 O -1.23305 1.492781 -1.57552 C 1.246127 1.275041 0.146553 C -4.07494 0.86862 -1.24015 C 2.248112 -1.26054 -0.3377 N -3.42696 0.190126 -0.128 C 2.591295 1.011984 0.371429 C -3.26831 -0.96589 1.913747 C 3.093994 -0.26076 0.12468 H -3.50093 -1.91684 2.393627 F 0.795208 2.506929 0.411555 H -3.3003 -0.18293 2.675161 F 3.405902 1.967844 0.832178 C -1.89802 -0.96219 1.210352 F 4.385977 -0.52236 0.337779 C -2.09369 0.010313 0.068409 F 2.730349 -2.48571 -0.57806 C -4.23993 -0.62388 0.779971 F 0.117067 -1.9613 -1.00971 H -3.34483 1.483427 -1.75678 H -1.08019 -0.67382 1.871856 H -4.49734 0.134086 -1.93783 H -1.65881 -1.95572 0.813295 H -4.89081 1.48954 -0.85869 ------

R = 4-NO2(C6H4) ------H 5.018356 1.682795 -0.05025 Atom x y z H 4.755526 -1.40704 0.807327 ------H 5.270564 -0.70787 -0.73587 C 1.204402 0.92055 0.100724 C -0.24181 0.514616 0.074658 O 1.464437 2.14646 0.123544 C -0.75299 -0.64101 0.684037 C 4.203956 1.394171 0.620849 C -1.14184 1.407899 -0.53008 N 3.563405 0.191127 0.109369 C -2.11431 -0.91762 0.665684 C 3.441741 -1.94063 -0.86836 H -0.09483 -1.31888 1.210784 H 3.692299 -2.99032 -0.7128 C -2.50057 1.139415 -0.56912 H 3.461788 -1.73913 -1.9422 H -0.74682 2.319603 -0.95871 C 2.070855 -1.55287 -0.28407 C -2.97097 -0.02785 0.027915 C 2.232191 -0.0797 0.032204 H -2.52252 -1.79807 1.141807 C 4.39543 -0.98886 -0.14385 H -3.20082 1.811271 -1.04546 H 3.472537 2.193386 0.673888 N -4.41561 -0.32234 -0.00366 H 4.628958 1.198795 1.613759 O -4.79811 -1.3552 0.533714

O -5.14792 0.481368 -0.56737 H 1.886594 -2.12355 0.635204 H 1.240019 -1.7522 -0.96011 ------

R = CCH ------C 2.330155 -0.47259 0.122385 Atom x y z H 0.657003 2.499849 -0.08688 ------H 1.986134 2.163363 1.055013 C -1.22638 0.627374 -0.04803 H 2.311289 2.177179 -0.69167 O -1.35382 1.871139 -0.14649 H 2.703178 -0.47807 1.156737 C 1.565778 1.926579 0.069306 H 3.164933 -0.20256 -0.53032 N 1.249802 0.508451 -0.01207 C -2.40706 -0.21759 0.015803 C 1.657006 -1.79636 -0.25683 C -3.4147 -0.87748 0.068195 H 2.103781 -2.65318 0.248368 H -4.31025 -1.44718 0.115356 H 1.74047 -1.95661 -1.33452 H -0.01089 -1.87841 1.161243 C 0.182947 -1.56439 0.127775 H -0.52094 -2.10666 -0.5035 C 0.02179 -0.06655 0.012499 ------

R = CH=CH(CO)H ------H 2.934532 2.140927 1.069055 Atom x y z H 3.232089 2.160115 -0.68238 ------H 3.664909 -0.47825 1.179866 C -0.27991 0.582101 -0.06432 H 4.130416 -0.17313 -0.50043 O -0.36879 1.829905 -0.17372 C -1.49466 -0.24837 0.007749 C 2.499414 1.907398 0.089974 C -2.736 0.276504 -0.02486 N 2.195574 0.483628 0.014202 H -1.39243 -1.32586 0.101942 C 2.663588 -1.80722 -0.25576 H -2.87862 1.347944 -0.11317 H 3.117219 -2.65836 0.252319 C -3.92014 -0.57664 0.056927 H 2.769008 -1.95941 -1.33244 O -5.06617 -0.1789 0.033865 C 1.178944 -1.60887 0.10357 H -3.69973 -1.66586 0.14577 C 0.982233 -0.1084 0.006704 H 0.974263 -1.94404 1.128033 C 3.299978 -0.4738 0.143536 H 0.514489 -2.16556 -0.55677 H 1.583764 2.471717 -0.05351 ------

R = H ------C 0.252401 -0.55008 -0.04228 Atom x y z C -1.61519 0.874276 -0.08705 ------H 1.714845 1.622985 0.106604 C 1.59123 -1.01951 0.002472 H 0.576431 2.41712 -1.01318 O 2.623999 -0.33083 0.103861 H 0.383888 2.638888 0.739431 C 0.681087 1.926134 -0.03643 H 1.665793 -2.12311 -0.05972 N -0.16298 0.745885 0.032225 H -1.88827 1.172044 -1.11063 C -2.12184 -0.53335 0.256306 H -1.98466 1.647831 0.592515 H -3.06682 -0.76997 -0.23404 H -1.08212 -1.74148 -1.23781 H -2.26874 -0.61694 1.335989 H -0.87881 -2.35792 0.39917 C -0.95814 -1.44148 -0.18881 ------

R = Ph ------H 2.926567 -2.83262 -0.55721 Atom x y z H 2.588983 -1.6704 -1.84822 ------C 1.170653 -1.53648 -0.20727 C 0.067902 0.857443 0.044184 C 1.1879 -0.0408 0.032597 O 0.209954 2.100815 -0.00408 C 3.430309 -0.74742 -0.0849 C 3.00387 1.635187 0.573634 H 2.207206 2.371277 0.541179 N 2.492572 0.362344 0.091282 H 3.381137 1.530812 1.60018 C 2.577782 -1.82044 -0.76567 H 3.83246 1.956834 -0.06445

H 3.811989 -1.08269 0.891497 H -2.00733 1.933526 -1.16204 H 4.287472 -0.42272 -0.68166 C -4.01247 -0.53787 0.039147 C -1.3309 0.304152 0.046019 H -3.34604 -2.12662 1.327771 C -1.72618 -0.83422 0.759648 H -4.37447 1.174718 -1.21489 C -2.31007 1.029896 -0.64768 H -5.04644 -0.86452 0.034515 C -3.05617 -1.25044 0.757889 H 1.033339 -2.07767 0.737917 H -1.004 -1.38376 1.350698 H 0.367188 -1.84738 -0.87447 C -3.63359 0.607379 -0.66212 ------

R = Me ------H -0.27983 2.449159 -0.1423 Atom x y z H 1.0022 2.47353 1.094992 ------H 1.436069 2.638743 -0.6204 C -1.56139 0.098742 -0.03053 H 2.508241 0.196127 1.155096 O -2.02253 1.250109 -0.16279 H 2.904981 0.577543 -0.52843 C 0.742763 2.155923 0.075084 C -2.52391 -1.08204 0.075371 N 0.855658 0.713183 -0.0553 H -2.53392 -1.67091 -0.84886 C 1.910612 -1.37634 -0.25369 H -2.2723 -1.76187 0.894844 H 2.592829 -2.06196 0.250357 H -3.52431 -0.68192 0.236962 H 2.028762 -1.51088 -1.33178 H -0.06801 -2.32119 -0.48401 C 0.435224 -1.58232 0.142527 H 0.356674 -1.93962 1.17866 C -0.16353 -0.19931 0.016534 ------C 2.166771 0.088682 0.113744

R = cyclopropyl ------H 2.505191 2.42787 -0.60603 Atom x y z H 3.197795 -0.12091 1.161576 ------H 3.644117 0.190556 -0.52377 C -0.84119 0.35974 -0.04819 C -1.96762 -0.62311 0.108165 O -1.11351 1.566805 -0.22931 C -3.2478 -0.11586 0.748311 C 1.729887 2.057867 0.071582 C -3.22078 -0.39054 -0.72089 N 1.633787 0.612948 -0.05438 H -1.70904 -1.65466 0.309936 C 2.38799 -1.60384 -0.23751 H -3.23353 0.923074 1.052919 H 2.966929 -2.37466 0.272673 H -3.78638 -0.79485 1.398681 H 2.487404 -1.76086 -1.3144 H -3.7403 -1.26158 -1.10242 C 0.898289 -1.6004 0.156612 H -3.18969 0.467952 -1.38019 C 0.496171 -0.14687 0.017693 H 0.769442 -1.93608 1.194452 C 2.845124 -0.18718 0.120596 H 0.303272 -2.26637 -0.47011 H 0.768496 2.498146 -0.17391 ------H 2.007452 2.338412 1.09751

R = OMe ------H 0.372076 2.509599 -0.17689 Atom x y z H 1.542788 2.353626 1.153129 ------H 2.126202 2.533895 -0.51666 C -1.13548 0.293192 -0.04723 H 2.885905 -0.01726 1.16046 O -1.54 1.443992 -0.19188 H 3.352253 0.30423 -0.51889 C 1.337602 2.09823 0.103009 O -2.00332 -0.76776 0.087067 N 1.319503 0.658871 -0.08725 C -3.39029 -0.42346 0.03473 C 2.154243 -1.53401 -0.24481 H -3.64502 0.034131 -0.92397 H 2.763016 -2.27804 0.270491 H -3.92964 -1.36091 0.161554 H 2.266958 -1.68903 -1.32076 H -3.6509 0.275752 0.832413 C 0.661766 -1.59154 0.141564 H 0.533308 -1.93646 1.176302 C 0.219185 -0.15832 0.006338 H 0.078721 -2.2668 -0.4859 C 2.555374 -0.09821 0.112737 ------

R = OH ------C 2.13611 0.231108 0.102757 Atom x y z H -0.47643 2.411826 -0.17967 ------H 0.71653 2.479059 1.13778 C -1.56494 -0.03043 -0.03305 H 1.242225 2.743924 -0.54013 O -2.17301 1.028848 -0.17194 H 2.456707 0.373443 1.146694 C 0.54973 2.181619 0.092164 H 2.843901 0.764132 -0.53808 N 0.784913 0.759961 -0.08577 O -2.25175 -1.21835 0.098724 C 1.988343 -1.25469 -0.24796 H -3.18448 -0.97059 0.043367 H 2.720868 -1.87908 0.264936 H 0.473063 -1.92562 1.187019 H 2.119068 -1.39191 -1.32425 H 0.070859 -2.33934 -0.47067 C 0.531819 -1.56974 0.149766 ------C -0.15417 -0.23613 0.012847

R = NH2 ------C 2.143572 0.193295 0.104886 Atom x y z H -0.41471 2.429625 -0.13655 ------H 0.750644 2.423381 1.211344 C -1.57562 0.006748 -0.04997 H 1.320178 2.736215 -0.44422 O -2.10613 1.104912 -0.26077 H 2.466037 0.303761 1.153 C 0.599697 2.16882 0.151236 H 2.864734 0.725373 -0.52173 N 0.804718 0.749276 -0.0776 N -2.3752 -1.13809 0.078443 C 1.970339 -1.28035 -0.27937 H -2.04566 -1.88943 0.666207 H 2.696875 -1.9304 0.209858 H -3.34978 -0.90748 0.209831 H 2.084235 -1.39382 -1.36011 H 0.47251 -1.96451 1.156446 C 0.512151 -1.57839 0.126239 H 0.043134 -2.32882 -0.51517 C -0.15778 -0.23037 0.022205 ------

R = NMe2 ------H 2.578114 2.464758 0.128116 Atom x y z H 3.121998 -0.43222 1.084459 ------H 3.590439 0.250967 -0.4826 C -0.865 0.510789 -0.17968 N -1.99383 -0.32811 -0.08283 O -0.99778 1.701252 -0.49917 C -2.1579 -1.23375 1.047016 C 1.714822 1.978566 0.590118 H -1.19709 -1.58008 1.417313 N 1.593775 0.62907 0.069991 H -2.67987 -0.73916 1.881108 C 2.260532 -1.50884 -0.6182 H -2.74764 -2.10735 0.751461 H 2.833143 -2.39435 -0.33827 C -3.24896 0.266727 -0.52345 H 2.311346 -1.39543 -1.70403 H -3.69504 0.91581 0.244194 C 0.788636 -1.56516 -0.15992 H -3.0753 0.872019 -1.41007 C 0.429249 -0.10713 0.005896 H -3.95673 -0.53356 -0.7571 C 2.772491 -0.23378 0.05797 H 0.726296 -2.11386 0.790695 H 0.813841 2.534277 0.345462 H 0.131382 -2.07535 -0.86661 H 1.864461 1.972287 1.680569 ------

6) Cartesian coordinates of calculated peroxides (B3LYP/6-311G**).

R = NO2 ------N -1.30272 -0.82473 -0.34494 Atom x y z C -2.76208 0.919301 0.221569 ------H -3.53722 1.245301 0.915828 C 0.780776 -0.09599 0.805099 H -2.9542 1.374649 -0.75232 O 0.764514 -0.35413 1.960176 C -1.35093 1.272113 0.709191 C -0.84306 -2.18573 -0.5689 C -0.46687 0.254168 -0.03431

C -2.68566 -0.60107 0.084815 H -1.0289 2.291291 0.501369 H -0.82462 -2.77473 0.359658 O 0.010819 0.886215 -1.32923 H -1.51655 -2.67953 -1.27355 O 0.86422 1.855292 -1.07626 H 0.153321 -2.1749 -1.0057 O 2.158205 -0.96591 -0.91566 H -2.88944 -1.10475 1.042398 O 3.104133 0.308094 0.576863 H -3.37942 -1.00217 -0.65944 N 2.157663 -0.24327 0.067565 H -1.25577 1.087549 1.781415 ------

R = CN ------H -0.18163 -2.76351 0.123831 Atom x y z H -0.98607 -2.67382 -1.45567 ------H 0.62027 -1.98273 -1.26286 C 1.007267 -0.06084 0.858466 H -2.53075 -1.3614 0.880021 O 0.922727 -0.20442 2.051283 H -2.98635 -1.22844 -0.8295 C -0.33775 -2.13239 -0.76309 H -1.15351 0.977477 1.773322 N -0.94848 -0.85194 -0.45016 H -1.00636 2.22549 0.527024 C -2.5879 0.702405 0.155211 O 0.302584 0.977729 -1.25505 H -3.4121 0.914462 0.837018 O 1.10712 1.96299 -0.90995 H -2.80017 1.179857 -0.80396 C 2.287226 -0.32953 0.181656 C -1.23296 1.174607 0.702167 N 3.297045 -0.59978 -0.30586 C -0.22465 0.272074 -0.01752 ------C -2.35502 -0.79562 -0.04811

R = (CO)Me ------H 0.070125 -2.24954 -0.77743 Atom x y z H -2.94557 -0.98058 1.190024 ------H -3.45892 -1.02013 -0.50667 C 0.788777 -0.00724 0.740327 H -1.24566 1.262631 1.684377 O 0.767117 -0.04392 1.947576 H -1.06056 2.33754 0.286866 C -0.93405 -2.22006 -0.35853 O -0.09046 0.761877 -1.43493 N -1.37448 -0.84155 -0.23204 O 0.884989 1.633294 -1.31106 C -2.80769 0.96376 0.193797 C 2.112216 -0.34845 0.015263 H -3.56107 1.357355 0.877426 O 2.114203 -1.20199 -0.84025 H -3.02601 1.332243 -0.81112 C 3.339622 0.34467 0.536717 C -1.37854 1.344664 0.602955 H 4.223673 -0.05296 0.040473 C -0.52246 0.251325 -0.0505 H 3.252503 1.418109 0.345913 C -2.74793 -0.56459 0.189561 H 3.407928 0.207469 1.618548 H -0.93856 -2.74632 0.607426 ------H -1.60289 -2.75354 -1.03983

R = C3F7 ------H -4.20677 -2.08851 -0.79764 Atom x y z H -3.01003 0.417018 1.886519 ------H -3.42171 1.73101 0.775075 C -0.72266 0.333698 0.742185 O -2.00995 1.16052 -1.23118 O -0.68387 0.127214 1.924169 O -1.62306 2.362419 -0.8607 C -1.4406 -2.02928 -1.00169 C 0.643756 0.640172 0.031939 N -2.39508 -1.05555 -0.49996 C 1.801211 -0.2555 0.575069 C -4.41043 -0.21614 0.344579 C 3.092398 -0.25744 -0.29855 H -5.19229 -0.35279 1.092602 F 0.576538 0.453749 -1.31392 H -4.85884 0.222388 -0.54976 F 0.970094 1.929954 0.268209 C -3.25554 0.657426 0.850845 F 1.365232 -1.54199 0.640766 C -2.07286 0.228485 -0.03149 F 2.146812 0.153504 1.808323 C -3.69675 -1.51883 -0.01511 F 4.071082 -0.87163 0.375214 H -1.01016 -2.65328 -0.2068 F 3.480218 0.991865 -0.57257 H -1.9495 -2.6852 -1.71233 F 2.894493 -0.91446 -1.44569 H -0.63486 -1.53193 -1.53784 ------H -3.58667 -2.17558 0.861848

R = (CO)H ------H 0.412745 2.782358 0.530617 Atom x y z H 0.920943 2.791476 -1.17072 ------H -0.65887 2.132846 -0.73846 C -0.99316 -0.13668 0.891344 H 2.660337 1.231346 0.952766 O -0.89557 -0.15828 2.094725 H 2.982114 1.280679 -0.79008 C 0.376503 2.220046 -0.41375 H 1.24946 -1.16846 1.648408 N 0.968621 0.899508 -0.28761 H 1.039325 -2.28311 0.287273 C 2.617037 -0.7414 0.003008 O -0.26486 -0.85527 -1.33929 H 3.471722 -1.04128 0.610632 O -1.18672 -1.75802 -1.09155 H 2.770605 -1.10814 -1.01448 H -3.18493 -0.41791 0.862328 C 1.283119 -1.2569 0.559737 C -2.39226 0.124103 0.312077 C 0.258939 -0.2697 -0.01201 O -2.62161 0.925174 -0.55417 C 2.400868 0.772996 -0.0142 ------

R = C6F5 ------H -4.84353 -0.77523 -0.88605 Atom x y z H -2.61416 2.110287 0.56077 ------H -1.9064 2.077009 -1.0668 C -0.86268 0.192118 0.983396 O -1.45902 -0.4702 -1.364 O -1.11704 0.370548 2.14389 O -0.63224 0.312538 -2.02329 C -3.05089 -1.98192 0.740779 C 0.57859 0.078382 0.525026 N -3.11837 -0.58807 0.342395 C 1.149236 -1.15337 0.237504 C -3.95559 1.231484 -0.9336 C 1.38297 1.20866 0.455936 H -4.65736 2.050947 -0.77457 C 2.487929 -1.2694 -0.10992 H -3.88817 1.049446 -2.00769 C 2.722285 1.121133 0.102677 C -2.55723 1.547554 -0.37324 C 3.274114 -0.12451 -0.17802 C -2.0117 0.151294 -0.05478 F 0.398948 -2.26498 0.305511 C -4.37345 -0.05779 -0.20252 F 3.023494 -2.46334 -0.37423 H -3.85139 -2.19516 1.454725 F 4.560699 -0.22117 -0.51229 H -3.15215 -2.66695 -0.11145 F 3.480544 2.217604 0.02709 H -2.10204 -2.18823 1.234929 F 0.857226 2.415994 0.706364 H -5.07946 0.132441 0.615056 ------

R = 5-NO2(C6H5) ------H 3.482636 1.842368 0.029879 Atom x y z H 3.249432 1.250883 1.683062 ------O 1.784208 -0.80208 1.295732 C 0.972881 1.037328 -0.23953 O 1.318454 -0.13505 2.331154 O 1.221854 2.132801 -0.6922 C -0.46393 0.593896 -0.11646 C 1.930913 -1.51178 -1.75578 C -0.88174 -0.70934 0.188924 N 2.70227 -0.61486 -0.91711 C -1.43231 1.577055 -0.37601 C 4.565843 -0.02222 0.43 C -2.2349 -1.02598 0.22481 H 5.51628 0.495597 0.296321 H -0.16136 -1.48119 0.412751 H 4.662671 -0.68768 1.289993 C -2.78447 1.27677 -0.3307 C 3.394412 0.948429 0.646951 H -1.09847 2.57748 -0.6171 C 2.195728 0.145436 0.138411 C -3.16431 -0.02755 -0.03245 C 4.15306 -0.8263 -0.81444 H -2.57598 -2.02511 0.455843 H 2.426694 -1.6065 -2.72588 H -3.54198 2.023521 -0.5224 H 1.830684 -2.51845 -1.32614 N -4.60851 -0.36319 0.01295 H 0.933741 -1.11195 -1.93952 O -4.9109 -1.52143 0.26173 H 4.642905 -0.46854 -1.72854 O -5.40365 0.539947 -0.20312 H 4.389477 -1.89201 -0.70799 ------

R = CCH ------H -0.343 -2.73551 -0.16872 Atom x y z H -1.09616 -2.47685 -1.75768 ------H 0.53815 -1.88911 -1.46479 C 0.992946 -0.29869 0.821347 H -2.57079 -1.37368 0.677879 O 0.798722 -0.76896 1.92113 H -3.05422 -0.9764 -0.98382 C -0.44194 -2.02846 -1.00628 H -1.1078 0.713506 1.891683 N -0.99259 -0.7463 -0.60523 H -0.89272 2.136316 0.857753 C -2.5487 0.770422 0.261337 O 0.339264 1.111918 -1.11699 H -3.36379 0.916817 0.971313 O 1.054376 2.117305 -0.65483 H -2.73485 1.397063 -0.61401 C 2.30413 -0.32559 0.208553 C -1.17275 1.083819 0.866611 C 3.404446 -0.39269 -0.27284 C -0.2076 0.257419 0.009044 H 4.376681 -0.43627 -0.70157 C -2.38759 -0.68855 -0.16543 ------

R = CH=CH(CO)H ------H -0.10951 -1.62532 -1.71101 Atom x y z H -3.07025 -1.78235 0.673575 ------H -3.7442 -1.30741 -0.89889 C 0.320094 -0.12543 0.62982 H -1.8188 0.380156 1.987385 O 0.312766 -0.70478 1.695096 H -1.92418 1.917309 1.111866 C -1.00815 -1.94814 -1.18172 O -0.79025 1.315589 -1.0801 N -1.71202 -0.80136 -0.63669 O -0.17832 2.373055 -0.58864 C -3.39958 0.369263 0.489251 C 1.586962 0.129702 -0.11583 H -4.16069 0.317452 1.268762 C 2.772565 -0.22483 0.39785 H -3.75486 1.038662 -0.29768 H 1.531977 0.611469 -1.08425 C -2.03741 0.837862 1.020631 H 2.842513 -0.69893 1.371719 C -1.04472 0.264872 0.003528 C 4.029908 0.016041 -0.33687 C -3.06155 -0.99962 -0.10138 H 3.910917 0.51826 -1.32055 H -0.71935 -2.68112 -0.41374 O 5.118784 -0.30245 0.079478 H -1.65203 -2.44829 -1.90868 ------

R = H ------C 2.085905 -0.17106 0.002542 Atom x y z H 1.103795 2.550801 -0.22155 ------H 1.804677 1.919612 -1.72839 C -1.25375 0.94517 0.601228 H 0.057829 2.082063 -1.58471 O -1.05237 1.420236 1.686883 H 2.486443 0.42212 0.840203 C 0.965729 1.823302 -1.03514 H 2.869858 -0.25228 -0.75646 N 0.88949 0.451605 -0.56675 H 0.159167 -0.74663 1.950354 C 1.567324 -1.5277 0.482162 H -0.5556 -2.0199 0.94554 H 2.179942 -1.95855 1.275136 O -1.06656 -0.70174 -1.18157 H 1.536261 -2.23184 -0.35254 O -2.26211 -1.08823 -0.7837 C 0.144746 -1.18541 0.9492 H -2.10593 1.25433 -0.03288 C -0.29571 -0.08817 -0.0234 ------

R = Ph ------C -1.23545 -0.2145 0.103188 Atom x y z C -3.25338 0.718451 -0.75807 ------H -1.55368 1.939868 -2.46312 C 0.08097 -0.91621 -0.3618 H -1.12431 2.680333 -0.90894 O -0.05817 -1.96161 -0.96178 H -0.04752 1.490308 -1.6698 C -1.09079 1.747839 -1.49059 H -3.68962 0.478681 -1.736 N -1.78853 0.654916 -0.84205 H -3.59021 1.726583 -0.48545 C -3.61824 -0.31623 0.320601 H -2.34602 -1.98171 -0.32712 H -4.50925 -0.89066 0.063851 H -2.21435 -1.64757 1.407096 H -3.8039 0.185872 1.272086 O -0.96214 0.577522 1.408988 C -2.36254 -1.19584 0.427282 O -0.49738 -0.19294 2.370005

C 1.453851 -0.34608 -0.15173 H 2.300805 -2.11659 -1.00558 C 1.732251 0.914507 0.397028 C 4.099911 0.553583 0.078675 C 2.525543 -1.14719 -0.57991 H 3.247634 2.335673 0.929827 C 3.04711 1.359375 0.503788 H 4.650477 -1.33723 -0.79483 H 0.932762 1.547003 0.752552 H 5.122539 0.902088 0.171295 C 3.83508 -0.70452 -0.46334 ------

R = Me ------H -1.35595 -2.24754 -1.85385 Atom x y z H 0.358822 -1.90996 -1.66746 ------H -2.50288 -1.17655 0.701577 C 1.234803 -0.56228 0.616019 H -3.02318 -0.51647 -0.86266 O 1.027096 -1.2355 1.598634 H -0.66609 0.513375 2.005493 C -0.5928 -1.94249 -1.13387 H -0.32973 2.028102 1.144242 N -0.92847 -0.62792 -0.61827 O 0.538306 1.137456 -1.09163 C -2.19445 0.977829 0.527884 O 1.288207 2.113427 -0.62646 H -2.93082 1.143203 1.315572 C 2.589187 -0.48538 -0.04401 H -2.34739 1.727896 -0.25168 H 2.514177 -0.61109 -1.12663 C -0.7499 1.028107 1.046248 H 3.236218 -1.24536 0.391636 C 0.02421 0.205076 0.011802 H 3.016917 0.50724 0.120069 C -2.27265 -0.42603 -0.07153 ------H -0.53008 -2.70948 -0.34792

R = cyclopropyl ------H -2.61959 -1.67611 0.896704 Atom x y z H -3.38034 -1.28727 -0.65953 ------H -1.23933 0.528992 1.983837 C 0.803374 -0.10528 0.530013 H -1.37045 2.012277 1.022455 O 0.856527 -0.56072 1.654476 O -0.40136 1.241621 -1.1993 C -0.67979 -2.02601 -1.03882 O 0.200679 2.351116 -0.82326 N -1.32455 -0.81831 -0.55695 C 2.006493 0.020764 -0.3311 C -2.91353 0.465887 0.591803 C 3.306928 0.419688 0.361926 H -3.62603 0.481871 1.417759 C 3.133714 -0.98182 -0.10005 H -3.30378 1.092672 -0.21367 H 1.858832 0.388199 -1.33525 C -1.51108 0.932297 1.006611 H 3.229253 0.609021 1.425057 C -0.59649 0.275619 -0.03043 H 3.960666 1.083824 -0.18897 C -2.64146 -0.94559 0.071803 H 3.670732 -1.31596 -0.9793 H -0.37986 -2.70659 -0.22714 H 2.943133 -1.73531 0.653821 H -1.37091 -2.56046 -1.69522 ------H 0.203699 -1.77648 -1.62777

R = OMe ------H 0.984815 2.233415 -1.6487 Atom x y z H -0.50672 2.223622 -0.69302 ------H 2.776268 1.37937 1.201133 C -1.10759 -0.16159 0.584372 H 3.028221 1.229689 -0.54317 O -1.40797 -0.53795 1.68683 H 1.002715 -1.12136 1.847998 C 0.579102 2.200559 -0.62825 H 1.028264 -2.2172 0.461555 N 1.013255 1.016359 0.095799 O 0.252947 -0.66066 -1.43069 C 2.639454 -0.68911 0.451245 O -0.42859 -1.77566 -1.5684 H 3.370445 -0.95397 1.216116 O -1.96609 0.388468 -0.28586 H 2.973563 -1.1162 -0.49653 C -3.33867 0.456023 0.152351 C 1.227936 -1.19582 0.783584 H -3.88148 0.914641 -0.67041 C 0.333528 -0.2101 0.03887 H -3.71638 -0.5472 0.351585 C 2.458408 0.832101 0.305475 H -3.42088 1.058628 1.057725 H 0.912949 3.096056 -0.09581 ------

R = OH ------H 1.119765 2.991401 0.00008 Atom x y z H 0.94238 2.198983 -1.58165 ------H -0.46672 2.415226 -0.52958 C -1.40459 0.101374 0.670057 H 2.708767 0.935159 1.133469 O -1.72115 -0.25882 1.771479 H 2.843534 0.815905 -0.62618 C 0.598778 2.194579 -0.53839 H 0.557949 -1.26389 1.785422 N 0.85669 0.921752 0.117944 H 0.337113 -2.28233 0.357896 C 2.183489 -1.04871 0.326752 O -0.24917 -0.52841 -1.42888 H 2.889278 -1.46326 1.047451 O -1.11279 -1.50911 -1.5705 H 2.401918 -1.48802 -0.64868 O -2.20477 0.833531 -0.12898 C 0.721518 -1.32536 0.708996 H -3.03686 0.95889 0.352821 C -0.02221 -0.16946 0.0485 ------C 2.257861 0.486259 0.240469

R = NH2 ------H -0.64401 -2.69806 -0.47944 Atom x y z H -1.36366 -2.09909 -1.99582 ------H 0.354202 -1.85702 -1.68641 C 1.242907 -0.62566 0.573989 H -2.52051 -1.15018 0.66656 O 1.03205 -1.41421 1.47676 H -3.01835 -0.39184 -0.85995 C -0.62938 -1.8825 -1.2158 H -0.59963 0.432345 2.034741 N -0.92829 -0.59234 -0.62141 H -0.23566 1.972901 1.231946 C -2.13846 1.00079 0.602008 O 0.560289 1.168415 -1.06965 H -2.85869 1.145118 1.408429 O 1.312065 2.139271 -0.59306 H -2.28336 1.79369 -0.13571 N 2.448951 -0.47296 -0.02684 C -0.68529 0.989621 1.099847 H 3.227411 -0.96079 0.389631 C 0.04581 0.189307 0.020838 H 2.63736 0.307823 -0.63292 C -2.26476 -0.36915 -0.06683 ------

R = NMe2 ------H -2.78676 1.702519 -0.47481 Atom x y z H -3.24405 1.061745 1.115586 ------H -1.41059 -0.20207 -2.01594 C 0.829411 0.176825 -0.72359 H -1.34018 -1.82113 -1.30317 O 0.79856 0.539063 -1.89176 O -0.31684 -1.3485 0.959245 C -0.57358 2.101307 0.913108 O 0.223295 -2.42259 0.430161 N -1.19761 0.81992 0.620473 N 1.983616 0.154172 0.003734 C -2.87827 -0.47489 -0.42303 C 2.141038 -0.16112 1.420726 H -3.7067 -0.44131 -1.13194 H 2.537717 -1.17249 1.55604 H -3.10352 -1.22918 0.334722 H 2.844961 0.553088 1.858269 C -1.53098 -0.76979 -1.09286 H 1.199779 -0.09657 1.955995 C -0.52849 -0.21667 -0.07837 C 3.235027 0.436146 -0.69541 C -2.61766 0.879392 0.237481 H 3.026772 0.565818 -1.75339 H -0.50637 2.750242 0.026844 H 3.695326 1.349369 -0.3031 H -1.16872 2.61679 1.670683 H 3.933488 -0.39474 -0.55391 H 0.427704 1.968141 1.319218 ------

Chapter 3 :

The Suitability of Stable Acyclic Carbenes as Building Blocks for Captodative C-Centered Radicals

INTRODUCTION

In recent years, stable N-heterocyclic carbenes63 have emerged as powerful tools for the design of stable paramagnetic species, including complexes of metals79-85, main-group derivatives86-91 and organic radicals.93,95-98 They have also allowed for an insightful reinvestigation into the stabilization of C-centered radicals by the synergistic combination of electron donating and electron withdrawing substituents, or so-called captodative substitution.99-

101 Such effects have long been known to afford paramagnetic species that are long-lived enough to perform intermolecular reactions and to be observed by EPR spectroscopy.101a

However, while captodative stabilization weakens the C–C dimer up to the point where a small amount of the radical can be observed, the dimer usually remains thermodynamically favored.102-104 For instance, (dimethylamino)(carboxy) radical 3.A exists in the solid state as the diamagnetic dimer 3.B (Figure 1). However, sufficient amounts of the radical are formed in solution at 140 °C, which allowed for both the detection of the EPR signal of 3.A and a measurement of the C–C dimer dissociation bond enthalpy (25 kcal.mol-1; 70–80 kcal.mol-1 for typical C–C bonds).104b

Figure 3.1: a) Dimerization of (amino)(carboxy) radical 3.A. b) General synthesis of monomeric representatives 3.2 from stable (amino)carbenes 3.1.

Increased steric bulk should disfavor the dimer formation and shift the equilibrium towards the monomers. Consequently, stable N-heterocyclic carbenes, such as 3.1a-f, are evident precursors for such radicals because they are readily-engineered reactive synthons with

bulky amino groups. As early as 1997, Fukuzumi et al. first synthesized captodative

(amino)(carboxy) radicals 3.2d93 by reacting thiazolylidene carbenes 3.1d92 with an aldehyde and then performing a one-electron electrochemical oxidation on the resulting enolate. Species

3.2d were studied by EPR and found to decay within hours at room temperature. More recently, we demonstrated that a cyclic (alkyl)(amino) carbene (CAAC)66 3.1e could allow for a simple two-step synthesis of the first structurally characterized monomeric C-centered

(amino)(carboxy)radical 3.2e, as well as related bi- and tri-radicals.110 These molecules were found to be perfectly stable at room temperature in both solution and the solid state. Even more, we found that highly electronegative R substituents significantly enhanced the electron- withdrawing capabilities of the acyl moieties, resulting in remarkably air- persistent radicals.116

Figure 3.2: Stable carbenes 3.1a-h and the corresponding captodative radicals 3.2a-h.

Hudnall et al. also recently reported (amino)(carboxy) radicals 3.2a, 3.2c and 3.2f,117 which are similarly based on stable cyclic carbenes, namely imidazolylidene 3.1a,118 (amido)(amino) carbene 3.1c,119 and diamidocarbene 3.1f,120 respectively.

Strikingly, only cyclic carbenes have been considered so far. However, acyclic carbenes differ from their cyclic analogs in terms of electronic properties, and exhibit original behaviors due to their flexibility.121 Importantly, known transient captodative C-centered radicals do not feature cyclic amino frameworks. Therefore, the conceptual bridge between this iconic class of reactive intermediates and their stable monomeric representatives 3.2a-f is missing. Herein, we report a comparative study of cyclic and acyclic stable carbenes as building blocks for

(amino)(carboxy)radicals and further explore the requirements for stable versions of these paramagnetic species.

A) Cyclic and acyclic N-heterocyclic carbenes.

Using the same strategy previously employed,103 the saturated N-heterocyclic carbene

3.1b122 and the acyclic bis(diisopropylamino)carbene 3.1g123 were reacted with benzoyl chloride to afford iminiums 3.3 and 3.4 in 66 and 78% yield, respectively. (Scheme 3.1).

Scheme 3.1: Synthesis of radicals 3.2b and 3.2g.

The cyclic voltammograms of 3.3 and 3.4 feature two reversible one-electron reductions, for the formation of the corresponding radical (E1/2 = -1.21 and -1.26 V for 3.3 and

3.4, respectively) and enolate (E1/2 = -1.94 and -1.74 V for 3.3 and 3.4, respectively) species, respectively. Thus, we synthesized 3.2b and 3.2g by the UV-Vis monitored electrochemical reductions of 3.3 and 3.4, respectively. The stoichiometry of the electrochemical reductions

(approximately one coulomb per mole of reagent) are consistent with a one electron process, and the cyclic voltammetry following electrolysis is comparable to that of the starting material, indicating no chemical transformations occur immediately upon reduction (Figures 3.3a and

3.4a). This is also supported by rotating disk electrode (RDE) voltammetry which shows similar waveforms and Levich currents for the starting materials and the electrolyzed solutions (Figures

3.3c-d and 3.4c-d). UV-Vis spectroscopy provided further evidence for the formation of the radicals (Figures 3.3b and 3.4b). Indeed, DFT calculations reproduced the larger UV-Vis absorptions at 358 and 539 nm for 3.2b (calculated values: 352 and 516 nm) and 504 nm for

3.2g (calculated value: 496 nm). Note that the chemical reductions of 3.3 and 3.4 with a

113 stoichiometric amount of cobaltocene (Co[Cp]2; E1/2 = -1.33 V) similarly yields radicals 3.2b and 3.2g in 67 and 63% yield, respectively.

Figure 3.3: a) Cyclic voltammogram of 3.3 before (black) and after (red) electrolysis in CH3CN –1 + + 0.1 molL (n-Bu)4NPF6 (carbon electrode, Φ = 3 mm; E vs Fc /Fc). b) UV-Vis monitoring (1 scan every 50 seconds) of the electrochemical reduction of 3.3 on a reticulated vitreous

electrode at -1.40 V. c) Rotating disk electrode voltammetry (RDE; 10 mV/s; 600 rpm) of 3.3. d) RDE after exhaustive electrolysis.

Figure 3.4: a) Cyclic voltammogram of 3.4 before (black) and after (red) electrolysis in CH3CN –1 + + 0.1 molL (n-Bu)4NPF6 (carbon electrode, Φ = 3 mm; E vs Fc /Fc). b) UV-Vis monitoring (1 scan every 50 seconds) of the electrochemical reduction of 3.4 on a reticulated vitreous electrode at -1.50 V. c) Rotating disk electrode voltammetry (RDE; 10 mV/s; 600 rpm) of 3.4. d) RDE after exhaustive electrolysis.

The X-band isotropic EPR spectra of 3.2b and 3.2g were recorded in acetonitrile under an argon atmosphere (Figure 3.5). Radical 3.2b features isotropic hyperfine coupling constants to nitrogen [a(15N) = 6.6 and 5.4 MHz], the carbene backbone hydrogens [a(1H) = 10.66 (2) and

8.30 (2) MHz] and the ortho and para hydrogens of the phenyl moiety [a(1H) = 1.49, 2.08, and

3.21 MHz]. DFT calculations at the B3LYP/TZVP level of theory produce similar simulated values. For 3.3g, the isotropic hyperfine coupling constants to nitrogen [a(15N) = 11.6 and 6.0

MHz], the isopropyl hydrogens [a(1H) = 8.9, 6.1, 7.9, and 3.9 MHz] and a phenyl hydrogen [a(1H)

= 3.2 MHz] were inferred from simulation.124 The DFT calculated nitrogen isotropic hyperfine

15 15 coupling constants of 3.2g, [calculated: a( N1) = 11-13 MHz and a( N2) = 6-7 MHz] across several levels of theory, were consistent with the experimental value, whereas those to hydrogen deviated significantly. Indeed, the isotropic hyperfine coupling constants to the

isopropyl hydrogens were calculated to be fairly small at anywhere between 2.0 and 6.0 MHz.

Further calculations revealed several additional local minima geometries 3.2g’ and 3.2g’’ (Table

3.1), which are only slightly higher in energy (2-4 kcalmol-1). These conformers vary primarily in the orientation of the isopropyl groups (Figure 3.6), and importantly, the key N1-C2, N2-C2,

C2-C1, and C1-O1 bond lengths and the N1-C2-C1-O1 dihedral angle (25˚-28˚) are similar across the series (Table 3.2). While the isotropic hyperfine coupling constants to nitrogen vary slightly in 3.2g’ and 3.2g’’, those to hydrogen are significantly more dependent on orientation, and range from 2-16 MHz. Thus, the experimental hydrogen hyperfine coupling constants of

3.2g stem from an averaging of multiple geometries over the EPR time scale. Importantly, the spin density is almost insensitive to the geometry and level of theory (Table 3.3), and therefore the values calculated for 3.2g at the B3LYP/TZVP level of theory can be considered as a good estimate.

Figure 3.6: Representation of the optimized geometries of 3.2g, 3.2g’, and 3.2g’’ at the B3LYP/TZVP level of theory. The majority of the isopropyl hydrogens have been removed for clarity.

Table 3.1: Calculated zero-point energies (Hartree) and isotropic hyperfine coupling constants (MHz) of 3.2g, 3.2g’ and 3.2g’’.

Zero-Point Isotropic hyperfine coupling (MHz) Method Energy aN1 aN2 aH1 aH2 aH3 aH4 Experimental --- Conformer 3.3a B3LYP/6-311g** -966.440352 11.3 5.8 2.3 1.6 2.3 6.5 B3LYP/6-TZVP --- 12.7 6.6 2.3 1.7 2.3 6.5 B3LYP/EPRII --- 12.9 7.2 2.4 1.4 2.4 6.7 Conformer 3.3a’ B3LYP/6-311g** -966.436901 9.2 2.4 3.1 11.9 2.6 15.3 B3LYP/6-TZVP --- 10.4 3.0 3.2 11.8 2.7 15.5 B3LYP/EPRII --- 10.6 3.4 3.3 12.4 2.8 16.6 Conformer 3.3a’’ B3LYP/6-311g** -966.433884 13.9 2.7 3.1 15.2 13.0 14.0

Table 3.2: Key structural parameters of 3.2g, 3.2g’, and 3.2g’’.

3.3a 3.3a’ 3.3a’’ Bond lengths (pm) N1-C2 139.3 139.2 139.1 N2-C2 139.6 139.8 139.6 C2-C1 145.3 145.0 145.1 C2-O1 125.2 125.0 125.1 Angle (deg) N1-C1-C2 118.3 118.9 119.0 Dihedral angles (deg) N1-C2-C1-O1 25.0 25.9 27.9 N2-C2-C1-O1 149.3 148.7 144.5

Table 3.3: Calculated Mulliken spin densities for conformers 3.2g, 3.2g’ and 3.2g’’.

Spin Density Method N1 N2 C2 C1 O1 Conformer 3.3a B3LYP/6-311g** a 13.0 7.3 39.5 5.8 27.9 B3LYP/6-TZVP a 11.9 5.7 41.4 8.1 27.0 B3LYP/EPRII a 13.1 7.4 38.5 7.4 26.3 Conformer 3.3a’ B3LYP/6-311g** b 9.0 9.6 41.4 4.4 27.1 B3LYP/6-TZVP b 6.9 7.9 44.3 8.0 26.2 B3LYP/EPRII b 8.2 9.6 40.3 6.4 25.4 Conformer 3.3a’’ B3LYP/6-311g** c 13.1 6.5 39.6 5.4 26.7

With respect to stability, radical 3.2g showed slow decomposition within a few days in solution, while 3.2b, was found to be indefinitely stable in solution and in the solid state. Attempts to obtain a crystal of 3.2g from a cooled concentrated solution in hexane led to characterization of the diketone 3.6 (Figure 3.7), or the C-C dimer of the (amino)(carboxy) radical 3.5.

Interestingly, this dimer features a longer C2-C2’ bond [153.8 pm] than that of the parent dimer

3.B [152.4 pm]. We hypothesize that 3.2g undergoes a H 1,3-migration and subsequent disproportionation to yield 3.5 and N-isopropylacetonimine; facile dimerization of 3.5 would then result in the formation of 3.6 (Scheme 3.2). Interestingly, crystallized 3.6 had a strong isotropic

X-band EPR absorption at room temperature indicating dissociation of the dimer to 3.5 (Figure

3.5). The spectrum is characterized by a quartet with isotropic hyperfine coupling constants to nitrogen (20.6 MHz) and the α-hydrogen (22.8 MHz). This relatively small hydrogen coupling constant is indicative of a large degree of delocalization of the unpaired electron. Additionally, it is important to note that 3.A104b was only observed under thermal conditions, whereas 3.5 was detected at room temperature. This indicates that increased steric hindrance significantly lowers the dissociation barrier of dimer 3.6. Indeed, DFT calculations at the B3LYP/6-311G** level of theory indicated a dissociation enthalpy of only 5.1 kcalmol-1 (for 3.B: 25 kcalmol-1).

Figure 3.7: X-ray crystal structure of dimer 3.6. Hydrogens removed for clarity. Selected bond lengths [pm] and angles [deg]: C2-C2’: 153.8(3); C1-C2: 153.4(4); C1-O1: 122.4(3); N1-C2-C1: 113.6(2).

Scheme 3.2: Decomposition of radical 3.2g.

Radicals 3.2b and 3.2g are air sensitive, as previously reported for 3.2a and 3.2c-f.

The decay of the latters has been attributed to a reaction with oxygen although the products of this decomposition process have never been clearly identified. Interestingly, while briefly exposing 3.2g to oxygen, we detected a paramagnetic compound. Its EPR spectrum (Figure

3.5) features a 1:1:1 triplet of 1:2:1 triplets, with isotropic hyperfine coupling constants to nitrogen (aN = 47.3 MHz) and two hydrogens (aH = 12.0 MHz). These values match those of the known di(isopropyl)nitroxyl radical 3.7.125 The formation of this compound is the first evidence

of the oxidative cleavage of N-C bonds upon the air-oxidation of such captodative stabilized radicals.

B) Acyclic (amino)(alkyl) carbene.

Next, we reacted acyclic (amino)(alkyl) carbene 3.1h126 with benzoyl chloride, and isolated iminium 3.8 in 38% yield. The cyclic voltammogram of this compound at a scan rate of

-1 +/ 200 mVs is characterized by an irreversible reduction wave at Epc = -1.30 V vs. Fc Fc, with the corresponding re-oxidation wave at Epa = -0.28 V (Figure 3.8a). This data suggests an EC

(E – electron transfer; C – chemical transformation) redox process.127 When increasing the scan rate, the reduction of 3.8 at Epc = -1.30 V turned progressively reversible (E1/2 = -1.22 V; ΔEp =

300 mV at scan rate = 6.4 Vs-1, see Figure 3.8b) indicating that the chemical rearrangements are not apparent on the CV time scale. The exhaustive electrochemical reduction of 3.8 required two coulombs per mole of iminium, which ruled out the possible formation of the desired radical

3.2h and instead indicated the formation of enolate 3.9 through a two-electron transfer process.

Extraction of the product in diethyl ether led to the isolation of enol 3.10,128 and thus identified the protonation of 3.9 as the chemical transformation that was evidenced in the cyclic voltammetry experiments. Lastly, the reversible reduction of 3.10 is observed at E1/2 = -1.76 V

(ΔEp = 110 mV) at low scan rates.

Scheme 3.3: Synthesis of enol 3.10.

–1 –1 Figure 3.8: CV curves of 3.8 (1.0 mmolL ) in CH3CN + (n-Bu)4NPF6 0.1 molL (carbon electrode, Φ = 3 mm; E vs Fc+/Fc). Scan rates: (a) v = 0.2 V s–1; (b) v = 6.4 V s–1.

C) Discussion

Among other metrics,67-69 it is widely accepted that the π-accepting properties of a carbene can be evaluated from the 31P NMR chemicals shift of 3.1PPh, or the carbene

(phenyl)phosphinidene adducts.67 Thus, acyclic (amino)carbenes 3.1g-h are known to be more

π-accepting than their cyclic counterparts 3.1a-f by orders of magnitude due to free rotation around the C-N bonds which hinders the π-donating ability of both amino groups into the carbenes empty p-orbital. It should be expected that, in agreement with Hudnall’s results,117 the redox potential of the first reduction will be positively shifted as the carbene moiety becomes more π-accepting. This trend is nicely followed for 3.2a-f, which are based on cyclic carbenes, but radicals stemming from the acyclic (amino)carbenes deviate from the series. One would expect the reductions of 3.4 and 3.8, which would yield 3.2g and 3.2h, respectively, to occur at high reduction potentials. However, on the contrary, the oxidation potential of 3.2g is

significantly lower at E1/2 = -1.24, a value which compares well with electron rich 3.2a-b rather than electron poor 3.2c-f. Additionally, radical 3.2h is thermodynamically non-existent, as iminium 3.8 undergoes a two-electron reduction to 3.9 at E1/2 = -1.32V (Table 3.4).

Table 3.4: Experimental measures of the electronic properties of carbenes 3.1a-h and the corresponding radicals 3.2a-h.

π- accepting + Carbene Radical 3.2 E1/2 (mV) of 3.2/3.2 property a 3.1a -18.9 3.2a -1.32 3.1b -10.2 3.2b -1.21 3.1c 37.7 3.2c -0.98 3.1d 57c 3.2d -0.95 3.1e 68.9 3.2e -0.93 3.1f 83 3.2f -0.48 3.1g 69.5 3.2g -1.24 3.1h 126.3 3.2h -1.32b a As defined by the 31P NMR chemical shift (in ppm) of the carbenePPh adduct according to ref. [28a]. b The radical is not thermodynamically stable and the potential is given for 3.2-/3.2+. c Value is given for a related carbene with minor differences in the amino substitution pattern.

We then performed DFT calculations to further evaluate 3.2g-h, particularly with respect to their cyclic counterparts 3.2b and 3.2e. There is no unambiguous way to define radical stabilization energy (RSE). However, several studies have shown that isodesmic H-transfer reactions can be used as a conceptually simple and insightful method to gain insight into the captodative effect.129 For example, isodesmic reactions (1) and (2) will provide a relative estimate for the effect of a substituent X or a set of substituents (X,Y), respectively, on the RSE.

⋅ 퐶퐻2푋 + 퐶퐻4 → 퐶퐻3푋 + ⋅ 퐶퐻3 ∆퐻 = 푅푆퐸(푋) (1)

∙ 퐶퐻푋푌 + 퐶퐻4 → 퐶퐻2푋푌 + ⋅ 퐶퐻3 ∆퐻 = 푅푆퐸(푋,푌) (2)

 As previously shown, any substitution of H3C leads to an increase in stability as indicated by the RSE values in Table 3.5. Both the π-accepting benzoyl substituent (entry 1) and the π-donating amino groups (entries 2-3) have a significant stabilizing effect (10-20 kcalmol-1), while the tert-butyl group (entry 4) has a slight stabilizing effect (3.4 kcalmol-1) due to the hyperconjugation of the σ*C-C orbitals. It is also well known that the RSE shows little

improvement from the combination of two donating groups. This is illustrated by entries 5-8 which show that di(amino) or (alky)(amino) substitution patterns are as efficient as a singular di(isopropyl)amino group. Furthermore, one could expect to have a synergistic effect when considering captodative substitution, and thus a deviation from the additivity of the RSE

(DARSE) of each substituent, as defined in equation (3):

퐷퐴푅푆퐸(푋,푌) = 푅푆퐸(푋,푌) − 푅푆퐸(푋) − 푅푆퐸(푌) (3)

As expected, parent radicals 3.A and 3.5 (entries 9-10), as well as radicals 3.2b, 3.2e and 3.2g, exhibited strong DARSE. However, the captodative combination of 3.2h has a clearly detrimental effect (entry 14).

Table 3.5: Calculated Radical Stabilization Energy (RSE) of representative radicals (relative to  H3C ) and Deviation from Additivity of RSE (DARSE) for the corresponding captodative radicals.

Entry Radical RSE (kcalmol-1) DARSE (kcalmol-1)  1 BzCH2 10.0 ---  2 (Me2N)CH2 14.4 ---  3 (iPr2N)CH2 20.9 ---  4 (t-Bu)CH2 3.4 ---

5 22.2 ---

6 20.2 ---

 7 (iPr2N)2CH2 19.7 ---  8 (iPr2N)(t-Bu)CH2 14.0 --- 9 3.A 34.2 9.8 10 3.5 37.6 6.7 11 3.2b 41.9 9.7 12 3.2e 36.5 6.3 13 3.2g 41.6 11.9 14 3.2h 21.4 -2.6

When comparing 3.2b and 3.2g, it is clear that both radicals benefit from comparable thermodynamic stabilization as exhibited by both the RSE and DARSE values. Furthermore, the O1-C1-C2-N torsion angles in both these radicals are fairly similar. Thus, the instability of

3.2g stems from having flexible amino substituents with β-hydrogens that facilitate the degradation pathway.

Figure 3.9: Representations of the optimized geometry of 3.2b, 3.2g and 3.2h at the B3LYP/TZVP level of theory; top: front view; middle: view along the C1-C2 axis; bottom: view along the N1-C2 axis. Hydrogens and the isopropyl groups of 3.2b have been removed for clarity.

Table 3.6: Select calculated geometric parameters of radicals 3.2b, 3.2e and 3.2g-h at the B3LYP/TZVP level of theory.

Radical 3.2b 3.2e 3.2g 3.2h Bond lengths (pm) O1-C1 126.0 125.1 125.2 124.2 C1-C2 143.8 143.4 145.1 147.6 C2-N 137.8; 139.1 137.4 138.9; 139.4 138.7 Torsions (˚) O1-C1-C2-N 19.8; 25.8 6.7 25.0; 30.7 42.0

Finally, the poor thermodynamic stabilization of 3.2h clearly accounts for the single two- electron reduction of 3.8. This relative destabilization is interpreted as a consequence of the excessive steric hindrance around the radical center. Indeed, the di(isopropyl)amino group of

3.2h is poorly conjugated due to the large O1-C1-C2-N1 torsion angle (Table 3.6). This results in an elongation of the C1-C2 bond (147.6 pm) and a shortening of the O1-C1 bonds (124.2 pm), when compared to 3.2e (143.4 and 125.1 pm, respectively), the latter of which features a nearly planar conjugated π-system.

CONCLUSION

We have demonstrated that stable acyclic (amino)carbenes are detrimental to the stability of the corresponding radicals 3.2g-h, but for fundamentally different reasons. Radical

3.2h is intrinsically unstable, and has no existence at equilibrium due to the disproportionation of this species into iminium 3.8 and the enolate 3.9. On the other hand, 3.2g and its cyclic counterpart 3.2b are equally stabilized as exhibited by the comparable RSE and DARSE values.

However, 3.2g underwent a disproportionation to 3.5 over the course of several days under an argon atmosphere, whereas 3.2b could be stored for several weeks with no apparent signs of degradation. Consequently, the limited lifetime of 3.2g most likely stems from having amino substituents which feature β-hydrogens, and the enhanced flexibility around the C-N bonds, which facilitates the migration-elimination process.

Thus, our study provides further insight into this class of stable radicals by bridging the gap between typical reactive captodative radicals and the recently reported stable monomeric versions. In particular, it has highlighted the importance of subtle steric factors, which not only affect the susceptibility of these radicals towards undesired reactions, including dimerization, but also control the overall stability of the species. Indeed, steric factors can inhibit the optimal

π-donation required for fully conjugated amino groups, which leads to the electronic destabilization of the radical. Therefore, this work also suggests general guidelines for the future design of highly persistent radicals which are derived from stable carbenes, especially by emphasizing the key advantages of cyclic patterns which enforce strong mesomeric substituent effects.

Chapter 3 has been adapted from materials currently being prepared for submission.

Mahoney, J. K.; Jazzar, R.; Royal, G.; Martin, D.; Bertrand, G. The dissertation author was the primary investigator of this paper.

APPENDIX: EXPERIMENTAL SECTION

1) General Considerations

All manipulations were performed under an inert atmosphere of dry argon, using standard Schlenk and drybox techniques. Dry and oxygen-free solvents were employed.

Benzoyl chloride was purified by distillation before use. Carbenes 3.1b,122 3.1g,123 and 3.1h,126 were prepared as previously reported. NMR spectra (1H, 13C, and 19F) were recorded on Bruker

Advance 300, Varian VX 500 and Jeol ECA 500 spectrometers. All spectra were obtained at

25°C in the solvent indicated. Chemical shifts are given relative to SiMe4 and referenced to the

1 13 19 residual solvent signal ( H, C) or relative to an external standard ( F: CFCl3). Melting points were measured with Büchi Melting Point B – 545 apparatus. Electrochemical experiments were carried out with a Bio-logic SP-300 potentiostat. Potentials were referred to an Ag/0.01M AgNO3 reference electrode in CH3CN + 0.1M [Bu4N]PF6. The working electrode was a vitreous carbon disk (3 mm in diameter) and the auxiliary electrode was a platinum wire in CH3CN + 0.1M

[Bu4N]PF6. Ferrocene was used as a standard, and all reduction potentials are reported with

+ respect to the E1/2 of the Fc /Fc redox couple. Electrochemical reductions were performed using reticulated vitreous carbon electrode, and were monitored with a Zeiss MCS 501 UV-NIR Plus spectrometer. EPR spectra were obtained using an X-band Bruker EMX Plus spectrometer.

2) Synthetic Procedures

Synthesis Iminium 3.3: Benzoyl chloride (0.37 mL, 3.17 mmol) was added slowly to a toluene solution of carbene 3.1b (1.027 g, 2.88 mmol). The mixture was stirred for 20 minutes, filtered and the solid washed with hexanes (3 x 20mL). Recrystallization by diffusion of diethyl ether into a dichloromethane solution of the product yielded 3.3 as colorless crystals. Yield: 942 mg

ᵒ + + (66 %). mp: 261 – 263 C. MS (m/z): [M ] calc. for C34H43N2O , 495.3375; found, 495.3372. λmax

1 (ε) = 269 nm (12,285). H NMR (CDCl3, 300 MHz): δ = 7.96 (d, J = 6 Hz, 2H), 7.62 (t, J = 6Hz,

1H), 7.45 (t, J = 6 Hz, 2H), 7.32 (t, J = 6 Hz, 2H), 7.12 (d, J = 6 Hz, 4H), 5.07 (bs, 4H), 3.45

13 (sept, J = 3Hz, 4H), 1.33 (d, J = 3 Hz, 12H), 1.12 (d, J = 3 Hz, 12H) ppm. C NMR (CDCl3, 125

MHz): δ = 180.6 (C). 162.1 (C), 147.1 (C), 137.1 (CH), 131.7 (CH), 131.3 (C), 130.0 (CH), 129.9

(CH), 128.7 (C). 125.4 (CH), 55.7 (CH2), 29.4 (CH), 26.9 (CH3), 23.1 (CH3) ppm.

Synthesis Iminium 3.4: Benzoyl chloride (0.122mL, 0.965 mmol) was added to a hexane solution of carbene 3.1g (194 mg, 0.804 mmol). The mixture was stirred for 20 minutes, filtered and the solid washed with diethyl ether (2x10mL). Recrystallization by diffusion of diethyl ether into a dichloromethane solution of the product yielded 3.4 as yellow crystals. Yield: 284 mg

ᵒ + + (78%). mp: 209 – 210 C. MS (m/z): [M ] calc. for C20H33N2O , 317.2587; found, 317.2590. λmax

1 (ε) = 272 nm (12,676), 367 nm (838). H NMR (CDCl3, 400 MHz): δ = 8.11 (bd, 2H, J = 7.2 Hz),

7.70-7.61 (m, 3H), 4.19 (sept, 4H, J = 6.8 Hz), 1.41 (d, 12H, J = 6.8 Hz), 1.37 (d, 12H, J = 6.8

13 Hz) ppm. C NMR (CDCl3, 100 MHz): δ = 189.5 (C), 168.0 (C), 136.8 (CH), 133.8 (CH), 130.3

(CH), 56.9 (CH), 22.9 (CH3), 22.6 (CH3) ppm.

Synthesis Iminium 3.8: Carbene 3.1h, in THF, was prepared in situ from the corresponding amidinium salt (0.50 g, 1.64 mmol) and lithium 2,2,6,6-tetramethylpiperidine (0.24 g, 1.64 mmol). The mixture was cooled to −78 °C, and benzoyl chloride (0.20 mL, 1.99 mmol) was added dropwise to the flask. The solution was stirred at −78 °C for 30 minutes, warmed to room temperature and stirred an additional 30 minutes. The supernatant was then removed via filtration, and the solid was then washed with diethyl ether (2 x 10 mL). Extraction of the product in chloroform and removal of the solvent in vacuo yielded a white solid. Recrystallization by diffusion of diethyl ether into an acetonitrile solution of the product yielded 3.8 as white crystals.

ᵒ + + Yield: 255 mg (38 %). mp: 179 – 180 C. MS (m/z): [M ] calc. for C18H28NO , 274.2165; found,

1 274.2169. λmax (ε) = 263 nm (9,058), 268 nm (9,427). H NMR (CDCl3, 500 MHz): δ = 8.10 (bs,

1H), 7.80 (bs, 3H), 7.71 (bs, 1H), 5.32 (sept, J = 6.6 Hz, 1H), 4.62 (sept., J = 7.0 Hz, 1H), 1.88

(d, J = 6.6 Hz, 3H), 1.71 (d, J = 6.6 Hz, 3H), 1.54 (s, 9H), 1.51 (d, J = 7.0 Hz, 3H), 1.30 (d, J =

13 7.0 Hz, 3H) ppm. C NMR (CDCl3, 125 MHz): δ = 197.8 (C), 189.0 (C), 137.3 (CH), 131.9 (C),

19 130.7 (CH), 127.5 (CH), 62.4 (CH), 40.5 (C), 29.3 (CH3), 23.7 (CH3) ppm. F NMR (CDCl3, 282

MHz): δ = -78.23 (s, 3F) ppm.

Synthesis Radical 3.2b: Iminium salt 3.3 (0.400 g, 0.75 mmol) and cobaltocene (0.14 g, 0.75 mmol) were combined under argon. Dichloromethane was added to the flask, and the solution stirred for 30 minutes. Removal of the solvent in vacuo and extraction in diethyl ether yielded

3.2b as a dark purple solid. Yield: 250 mg (67 %). mp:104 – 106 ᵒC. The electrochemical reduction of iminium salt 3.3 (6.9 mg, 0.013 mmol), in 10.0 mL of acetonitrile containing 0.1M

[Bu4N]PF6, was performed on a reticulated vitreous carbon electrode at a potential of -1.50 V under an argon atmosphere. Complete electrolysis (one electron exchanged per molecule) yielded a purple solution. λmax (ε) = 242 nm (9,120), 359 nm (5,643), 541 nm (2,991).

Synthesis 3.2g: Iminium salt 3.4 (0.200 g, 0.57 mmol) and cobaltocene (0.097 g, 0.52 mmol) were combined under argon. Dichloromethane was added to the flask, and the solution stirred for 20 minutes. Removal of the solvent in vacuo and extraction in hexanes yielded 3.2g as a dark reddish-purple solid. Yield: 62 mg (63 %). Mp: 102-104 ᵒC. The electrochemical reduction of iminium salt 3.4 (3.7 mg, 0.012 mmol), in 10.0 mL of acetonitrile containing 0.1M [Bu4N]PF6, was performed on a reticulated vitreous carbon electrode at a potential of -1.40 V under an argon atmosphere. Complete electrolysis (one electron exchanged per molecule) yielded a reddish-purple solution. λmax (ε) = 236 nm (6,026), 505 nm (3,515). Crystallization of 3.2g by cooling a concentrated hexane solution yielded crystals of 3.6 as yellow blocks. mp: 109-111

ᵒC.

Electrochemical Synthesis 3.10: Iminium salt 3.8 (4.5 mg, 0.011 mmol), in 10.0 mL of acetonitrile containing 0.1M [Bu4N]PF6, was reduced on a reticulated vitreous carbon electrode at -1.60V under an argon atmosphere. Complete electrolysis (two electrons exchanged per molecule) yielded a yellow solution. Removal of the solvent in vacuo and extraction in diethyl

1 ether yielded a yellow oil. λmax (ε) = 248 nm (13,561), 394 nm (618). H NMR (C6D6, 400 MHz):

δ = 8.06 (s, 1H), 7.31-7.29 (m, 2H), 7.08-7.00 (m, 3H), 3.29 (sept, J = 6.4 Hz, 2H), 1.05 (d, J =

13 6.4 Hz, 12H), 0.95 (s, 9H) ppm. C NMR (C6D6, 100 MHz): δ = 153.5 (C), 138.8 (C), 130.3

(CH), 129.7 (CH), 129.0 (CH), 124.3 (C), 49.3 (CH), 36.5 (C), 32.7 (CH3), 22.9 (CH3), 22.6 (CH3) ppm.

Computational methods: The DFT calculations were carried out using the program package

Gaussian09.131 Structures were first calculated at the B3LYP/6-311g** level of theory, with optimized structures identified as energy minima by the calculation of vibrational frequencies.

Further calculations at the B3LYP/TZVP and B3LYP/EPR-II level of theory were then performed on the optimized structures. The solvent (acetonitrile) was taken into account for only the TD-

DFT calculations using the Polarizable Continuum Model (PCM) method.

3) Crystallographic Data

Crystal data and structure refinement for Dimer 3.6 Empirical formula C14H20NO Formula weight 218.31 Temperature/K 100 Crystal system triclinic Space group P-1 a/Å 8.4548(5) b/Å 12.2282(7) c/Å 13.7007(7) α/° 100.808(2) β/° 102.348(2) γ/° 109.950(2) Volume/Å3 1247.24(12) Z 4 3 ρcalcg/cm 1.163 μ/mm-1 0.072 F(000) 476.0 Crystal size/mm3 0.25 × 0.2 × 0.1 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 3.174 to 50.772 Index ranges -10 ≤ h ≤ 10, -14 ≤ k ≤ 14, -16 ≤ l ≤ 16 Reflections collected 9112 Independent reflections 4573 [Rint = 0.1083, Rsigma = 0.2578] Data/restraints/parameters 4573/0/297 Goodness-of-fit on F2 0.903 Final R indexes [I>=2σ (I)] R1 = 0.0574, wR2 = 0.1036 Final R indexes [all data] R1 = 0.1345, wR2 = 0.1184 Largest diff. peak/hole / e Å-3 0.21/-0.24

4) Cartesian Coordinates

Cartesian coordinates of 3.2b calculated at the B3LYP/6-311g** level of theory.

------H -2.03199 3.79719 2.038637 Atom X Y Z H -1.15667 3.885932 -1.66157 ------H -2.08718 4.705404 -0.40738 C 0.221303 -0.13122 1.246541 H -0.32092 4.758107 -0.36655 O 1.232952 0.230374 1.903854 C -3.05393 -1.32367 -2.10233 C -0.92925 -0.74174 1.973441 C -3.39098 -1.03874 -3.58149 C -1.07049 -0.43047 3.335677 C -3.90267 -2.50515 -1.59847 C -1.78046 -1.70681 1.42114 H -2.00486 -1.62382 -2.04639 C -2.05515 -1.0342 4.10727 H -2.80873 -0.20594 -3.98289 H -0.3759 0.276479 3.771486 H -3.19418 -1.9209 -4.1983 C -2.75711 -2.3233 2.199027 H -4.44794 -0.78053 -3.69487 H -1.65513 -2.00232 0.387484 H -3.72117 -2.71085 -0.54321 C -2.9066 -1.98353 3.541653 H -4.9723 -2.3138 -1.72083 H -2.15408 -0.77236 5.155205 H -3.66648 -3.40786 -2.16937 H -3.3956 -3.0826 1.760767 C 2.028694 -2.74145 -0.5637 H -3.66917 -2.46378 4.144613 C 1.751807 -3.54547 0.721593 C 0.259048 0.028263 -0.18368 C 2.442534 -3.67239 -1.71907 N 1.459626 0.165816 -0.85302 H 1.087794 -2.26767 -0.8501 C 2.756279 -0.27211 -0.39514 H 1.458979 -2.88688 1.540855 C 3.729301 0.711949 -0.13421 H 0.946998 -4.26793 0.556091 C 3.059109 -1.64527 -0.31299 H 2.639339 -4.10147 1.037329 C 5.016289 0.294494 0.20945 H 2.6199 -3.11355 -2.64225 C 4.361831 -2.01075 0.040922 H 3.359675 -4.21944 -1.48411 C 5.334687 -1.05474 0.29627 H 1.658609 -4.41064 -1.91342 H 5.777553 1.036071 0.424336 C 3.402219 2.198771 -0.16353 H 4.6159 -3.06184 0.119453 C 4.307635 2.980661 -1.13174 H 6.338904 -1.36053 0.568796 C 3.447324 2.793497 1.256824 N -0.78531 0.185 -1.09387 H 2.374532 2.296587 -0.51848 C -2.10611 0.677299 -0.77976 H 4.260332 2.572573 -2.14561 C -2.28991 1.907245 -0.10751 H 4.00199 4.030443 -1.17436 C -3.21294 -0.06293 -1.25635 H 5.35426 2.956697 -0.81502 C -3.59923 2.321261 0.156135 H 2.784456 2.23495 1.919208 C -4.49782 0.41031 -0.98226 H 4.460302 2.756194 1.669448 C -4.69482 1.581083 -0.26402 H 3.133422 3.842353 1.240953 H -3.76134 3.253341 0.684686 C 1.236096 0.208355 -2.30047 H -5.35716 -0.14867 -1.33358 H 1.4192 -0.77745 -2.74679 H -5.69998 1.925671 -0.04781 H 1.905187 0.926499 -2.77897 C -1.14657 2.846543 0.273379 C -0.23137 0.608642 -2.3974 C -1.14888 3.210699 1.768906 H -0.34684 1.692329 -2.51462 C -1.18126 4.121976 -0.59418 H -0.74754 0.118932 -3.22303 H -0.20008 2.345567 0.07403 ------H -1.13081 2.31814 2.39455 H -0.26671 3.810071 2.009388

Cartesian coordinates of calculated 3.2g at the B3LYP/6-311g** level of theory.

------H -1.86204 0.091108 1.725642 Atom X Y Z C -4.39745 -1.5838 -0.66153 ------H -2.66757 -2.18185 -1.8047 C -0.64591 -1.187 -0.42351 C -4.85121 -0.92164 0.479537 O -0.29421 -2.24628 -0.9902 H -4.27389 0.174375 2.23921 C -2.10364 -1.01527 -0.10311 H -5.1061 -2.06492 -1.32692 C -2.56991 -0.36372 1.045368 H -5.91133 -0.88471 0.704501 C -3.03727 -1.6408 -0.94239 C 0.355014 -0.19543 -0.06896 C -3.93161 -0.32084 1.336814 N 0.097964 1.176206 -0.02908

N 1.66603 -0.62138 0.130734 C 2.698089 -0.07626 -0.7902 C 0.835608 2.007403 0.962537 C 2.785009 -0.8522 -2.11976 C -0.00188 2.323724 2.215877 C 4.080349 0.119914 -0.15797 C 1.491913 3.280405 0.407672 H 2.328311 0.918172 -1.04257 H 1.645763 1.359789 1.294044 H 1.785765 -1.08004 -2.49445 H -0.39584 1.407764 2.660504 H 3.313134 -0.24793 -2.86489 H 0.633886 2.806582 2.964643 H 3.322702 -1.79486 -2.01324 H -0.83799 2.992594 2.008753 H 4.028244 0.720552 0.752808 H 2.145178 3.070132 -0.44064 H 4.566149 -0.82744 0.083056 H 0.764217 4.03389 0.101341 H 4.726138 0.642359 -0.8694 H 2.106368 3.726701 1.194398 C 1.875287 -1.83192 0.967801 C -0.82139 1.75565 -1.04632 C 2.56735 -1.48902 2.300901 C -0.08137 2.275808 -2.29399 C 2.545243 -3.02172 0.270347 C -1.81129 2.792832 -0.50454 H 0.868109 -2.16123 1.221305 H -1.42401 0.915692 -1.38651 H 2.05008 -0.67088 2.808742 H 0.601224 1.517375 -2.68352 H 2.543112 -2.36124 2.961479 H -0.81017 2.500098 -3.07875 H 3.612358 -1.20358 2.169553 H 0.485525 3.187076 -2.09927 H 1.99877 -3.28015 -0.63506 H -2.3918 2.389656 0.325407 H 3.593872 -2.83488 0.026791 H -1.32728 3.716363 -0.18147 H 2.519703 -3.88321 0.94403 H -2.51066 3.056352 -1.30228 ------

Cartesian coordinates of 3.2g’ calculated at the B3LYP/6-311g** level of theory.

------C 0.5072 1.15456 2.4787 Atom X Y Z H - 0.33258 2.78896 1.45235 ------H 1.59854 3.33723 -0.00895 C 0.5669 -1.08837 0.39778 H 2.03761 3.26236 1.69502 O 0.25924 -2.17466 0.93426 H 2.47287 1.93132 0.61156 C 2.02223 -0.84985 0.1037 H - 0.42831 0.66236 2.74829 C 2.48295 -0.1616 -1.0245 H 1.28752 0.39774 2.40783 C 2.96492 -1.46699 0.9391 H 0.77749 1.83131 3.29391 C 3.84584 -0.07294 -1.2989 C - 2.85217 -0.04928 0.66751 H 1.77265 0.29694 -1.69758 C - 3.00982 -0.81496 1.99614 C 4.32629 -1.36209 0.67864 C - 4.19241 0.08541 -0.0633 H 2.60237 -2.0412 1.7829 H - 2.52754 0.95944 0.92757 C 4.77342 -0.66308 -0.44285 H - 2.0351 -1.01064 2.44495 H 4.18316 0.4539 -2.18503 H - 3.60911 -0.22422 2.69693 H 5.04076 -1.8353 1.34345 H - 3.50732 -1.77589 1.85902 H 5.83459 -0.58926 -0.65353 H - 4.09049 0.63693 -1.00157 C - 0.46903 -0.13176 0.06078 H - 4.64468 -0.8849 -0.28259 N - 0.2747 1.25303 0.06754 H - 4.89373 0.63235 0.57237 N - 1.75948 -0.59392 -0.17971 C - 2.05323 -1.72404 -1.09997 C - 0.97301 2.05709 -0.98078 C - 2.36202 -3.07154 -0.42204 C - 0.08161 2.34289 -2.20252 C - 0.97269 -1.89896 -2.17354 C - 1.61968 3.35364 -0.47433 H - 2.95894 -1.41673 -1.63515 H - 1.7819 1.41725 -1.33195 H - 3.25922 -3.01927 0.19671 H 0.27403 1.41462 -2.65285 H - 2.54369 -3.82795 -1.19209 H - 0.66044 2.87624 -2.96335 H - 1.52458 -3.38135 0.20072 H 0.78637 2.95528 -1.95152 H - 0.72216 -0.94849 -2.65056 H - 2.26793 3.18384 0.38844 H - 0.0608 -2.34168 -1.77273 H - 0.88354 4.11609 -0.20626 H - 1.35602 -2.57036 -2.94626 H - 2.23837 3.76952 -1.27358 ------C 0.36661 1.98599 1.19932 C 1.69992 2.66372 0.84352

Cartesian coordinates of 3.2g’’ calculated at the B3LYP/6-311g** level of theory.

------H 3.447687 -1.60197 2.02672 Atom X Y Z H 3.479762 0.022289 2.712915 ------C 4.152799 -0.0033 -0.07919 C -3.84304 -0.00012 -1.39911 H 4.084239 0.463373 -1.06499 C -2.49334 -0.09415 -1.07216 H 4.879501 0.562197 0.510469 C -2.08323 -0.72238 0.110459 H 4.555391 -1.01058 -0.20789 C -3.06421 -1.27454 0.946738 O -0.36731 -1.98822 1.120873 C -4.41406 -1.16378 0.632148 N 1.690475 -0.56786 -0.15902 C -4.80975 -0.5249 -0.54309 N 0.235145 1.327221 0.004612 H -4.14116 0.480201 -2.32484 C 0.724948 2.199709 -1.10137 H -1.75191 0.318053 -1.74297 H -0.08037 2.931387 -1.23537 H -2.74008 -1.80204 1.835376 C -0.40082 2.111921 1.106239 H -5.15954 -1.5856 1.297535 H 0.216323 3.014473 1.184813 H -5.86159 -0.44678 -0.79497 C 0.88495 1.487047 -2.44483 C -0.64366 -0.95719 0.469093 H 1.112686 2.231273 -3.2126 C 0.414997 -0.05602 0.052289 H 1.699227 0.763278 -2.42386 C 1.939588 -1.82651 -0.91885 H -0.02768 0.970244 -2.74429 H 2.814027 -1.59813 -1.53978 C 1.996207 3.012725 -0.78455 C 2.298204 -3.05751 -0.06503 H 2.094566 3.82577 -1.50991 H 2.401939 -3.92645 -0.722 H 1.963797 3.466733 0.20811 H 3.247761 -2.93583 0.457158 H 2.89659 2.401294 -0.85207 H 1.512219 -3.25107 0.663254 C -0.32567 1.433436 2.475939 C 0.81147 -2.18626 -1.89414 H 0.693908 1.132086 2.720419 H 0.482485 -1.32856 -2.481 H -0.6579 2.146267 3.235526 H 1.191622 -2.93949 -2.58944 H -0.96775 0.555131 2.54425 H -0.0501 -2.61363 -1.38233 C -1.83231 2.595757 0.813271 C 2.805234 -0.0037 0.649798 H -2.55875 1.789803 0.903642 H 2.525217 1.03517 0.813343 H -2.09868 3.379081 1.529491 C 2.922582 -0.64655 2.048404 H -1.92422 3.022396 -0.18811 H 1.93457 -0.82222 2.474945 ------

Cartesian coordinates of 3.2h calculated at the B3LYP/6-311g** level of theory.

------H 1.377449 2.602114 1.340821 Atom X Y Z H 0.379939 3.777774 0.496699 ------C 1.420651 2.255709 -1.56313 C -0.66893 -0.52319 -0.75133 H 1.309947 3.319907 -1.7908 O -0.52412 -1.42833 -1.5868 H 2.45279 2.093249 -1.26079 C -2.04205 -0.33441 -0.16623 H 1.257645 1.695102 -2.48682 C -2.24365 0.095939 1.150549 N 1.662205 -0.31542 0.022915 C -3.15406 -0.71988 -0.92689 C 1.854874 -1.79979 0.130185 C -3.52856 0.172752 1.684441 H 2.749327 -1.88773 0.745842 H -1.38708 0.351025 1.763782 C 2.776061 0.436526 0.658017 C -4.43651 -0.63422 -0.39943 H 2.579527 1.484834 0.492924 H -2.98592 -1.08795 -1.93158 C 4.138361 0.152947 0.006298 C -4.62863 -0.18387 0.908081 H 4.888339 0.822822 0.436343 H -3.66964 0.500114 2.708741 H 4.483215 -0.86994 0.170489 H -5.28985 -0.92223 -1.00369 H 4.100926 0.32978 -1.07048 H -5.62923 -0.12354 1.321717 C 2.81962 0.239773 2.185267 C 0.447968 0.303048 -0.26562 H 3.084893 -0.78112 2.469244 C 0.354174 1.844748 -0.50384 H 3.570281 0.905757 2.620836 C -0.98937 2.252433 -1.16697 H 1.853097 0.47784 2.634355 H -1.84311 2.144907 -0.50196 C 2.206282 -2.46456 -1.211 H -0.92177 3.307225 -1.44689 H 2.495482 -3.50493 -1.02844 H -1.18728 1.681236 -2.07626 H 1.359277 -2.44192 -1.89055 C 0.455244 2.721661 0.77384 H 3.052554 -1.96022 -1.68265 H -0.37575 2.500132 1.447069 C 0.769497 -2.56116 0.909492

H 0.478937 -2.02127 1.813792 H 1.186095 -3.52492 1.217154 H -0.1185 -2.76025 0.314797 ------

Cartesian coordinates of 3.5 calculated at the B3LYP/6-311g** level of theory.

------H 3.601854 -2.17998 -1.75973 Atom X Y Z H 2.636225 -0.84451 -2.39594 ------H 4.09299 -0.51882 -1.43622 C -3.80829 1.399944 -0.45283 C 3.14256 -1.72892 0.952921 C -2.46745 1.024546 -0.4654 H 2.481379 -1.8117 1.817925 C -2.07579 -0.25383 -0.04271 H 3.550611 -2.72159 0.745416 C -3.0701 -1.15206 0.369541 H 3.981463 -1.0764 1.214227 C -4.40778 -0.77582 0.387771 C 2.583715 1.256237 0.248378 C -4.78351 0.503961 -0.02021 H 3.604967 0.877481 0.196387 H -4.09227 2.390274 -0.79186 C 2.431806 2.327454 -0.84148 H -1.73187 1.727487 -0.83916 H 2.603059 1.904964 -1.83332 H -2.76289 -2.14697 0.666426 H 1.43463 2.774254 -0.83011 H -5.1614 -1.48253 0.718013 H 3.156258 3.129963 -0.67939 H -5.82744 0.797008 -0.01003 C 2.376308 1.831807 1.656491 C -0.65306 -0.74725 -0.03995 H 2.507372 1.060144 2.417427 C 0.372918 0.249474 0.022698 H 3.10145 2.628087 1.844543 H 0.058017 1.273044 0.163379 H 1.376273 2.256369 1.773771 C 2.36313 -1.22987 -0.27039 O -0.44296 -1.98038 -0.0417 H 1.537811 -1.91745 -0.43575 N 1.71648 0.0795 -0.00138 C 3.225506 -1.17778 -1.53863 ------

Cartesian coordinates of 3.6 calculated at the B3LYP/6-311g** level of theory.

------C -1.53426 -3.36533 -0.9847 Atom X Y Z H -1.38156 -4.25795 -0.37083 ------H -1.87465 -3.70623 -1.96727 O 1.515649 -0.29818 -2.02842 H -2.32895 -2.77503 -0.52875 N 0.132538 -1.90259 0.150691 C -0.08022 -2.4827 2.579214 C 1.740553 -0.24515 -0.83105 H 0.209727 -1.49797 2.952373 C 3.149085 -0.00708 -0.36039 H 0.216035 -3.2246 3.327334 C 0.579164 -0.50142 0.160463 H -1.16743 -2.48841 2.49344 H 0.899016 -0.29654 1.17944 C 5.494961 0.152932 -0.96232 C 3.485763 0.318156 0.959514 H 6.275883 0.086108 -1.71146 H 2.718828 0.399401 1.718411 O -1.51587 0.298332 2.028422 C -0.2398 -2.54402 -1.12926 N -0.13255 1.902736 -0.15053 H -0.43618 -1.72785 -1.82535 C -1.74064 0.245222 0.831029 C 4.81015 0.561757 1.314413 C -3.1491 0.006961 0.360222 H 5.054041 0.819859 2.338587 C -0.57919 0.501568 -0.16038 C 4.172756 -0.07899 -1.31721 H -0.89897 0.296731 -1.17938 H 3.901445 -0.31615 -2.3383 C -3.48561 -0.31824 -0.95973 C 0.578407 -2.80834 1.231083 H -2.7186 -0.39933 -1.71857 H 0.203864 -3.79084 0.935603 C 0.239837 2.544101 1.129446 C 5.817366 0.474997 0.356605 H 0.436215 1.727896 1.825495 H 6.848866 0.659517 0.635359 C -4.80993 -0.56201 -1.31477 C 0.856319 -3.41453 -1.77797 H -5.05369 -0.82008 -2.33898 H 1.776527 -2.85387 -1.93947 C -4.17287 0.078671 1.316948 H 0.512812 -3.77426 -2.75261 H -3.90168 0.315824 2.338081 H 1.083221 -4.29423 -1.16868 C -0.57846 2.808554 -1.23085 C 2.10317 -2.95603 1.396558 H -0.20394 3.79104 -0.93531 H 2.596629 -3.17087 0.447561 C -5.81724 -0.47545 -0.35704 H 2.322354 -3.77784 2.085476 H -6.84869 -0.66011 -0.6359 H 2.556274 -2.05537 1.814904 C -0.85622 3.414633 1.778231

H -1.77645 2.854003 1.93974 H 2.328967 2.775079 0.528851 H -0.51266 3.774292 2.75287 C 0.08014 2.483045 -2.57902 H -1.0831 4.294375 1.168991 H -0.20979 1.498335 -2.95226 C -2.10323 2.95622 -1.39628 H -0.21614 3.224998 -3.32707 H -2.59668 3.17093 -0.44724 H 1.167349 2.488762 -2.49327 H -2.32246 3.778108 -2.08509 C -5.495 -0.15342 0.961927 H -2.55632 2.055604 -1.81472 H -6.276 -0.08676 1.711005 C 1.534319 3.365377 0.98487 ------H 1.381621 4.258037 0.371055 H 1.874765 3.706219 1.967449

Cartesian coordinates of 3.9 calculated at the B3LYP/6-311g** level of theory.

------C 1.36459 2.697789 -0.43651 Atom X Y Z H 1.089038 3.754567 -0.5459 ------H 2.071526 2.619776 0.391538 C -0.47161 -0.69543 0.063672 H 1.887619 2.38504 -1.34198 O -0.20269 -1.94291 0.164017 N 1.851081 0.021239 -0.0659 C -1.98419 -0.51036 0.104227 C 2.484349 -0.7259 -1.16383 C -2.66159 -0.36768 1.322928 H 3.498006 -0.3111 -1.29692 C -2.76071 -0.6999 -1.04844 C 2.491346 0.012787 1.254302 C -4.05428 -0.38639 1.386721 H 2.063992 0.878966 1.772995 H -2.08078 -0.24994 2.231679 C 4.008848 0.265527 1.189166 C -4.15233 -0.716 -0.99248 H 4.404457 0.409798 2.200576 H -2.25622 -0.83992 -1.99862 H 4.548623 -0.5763 0.745528 C -4.81035 -0.55536 0.227518 H 4.232066 1.160324 0.600596 H -4.55135 -0.2692 2.345897 C 2.179421 -1.20508 2.161123 H -4.7271 -0.85595 -1.90402 H 2.793879 -2.07202 1.902262 H -5.89503 -0.5672 0.273992 H 2.381438 -0.95497 3.21199 C 0.437831 0.345145 -0.07369 H 1.137621 -1.50182 2.042126 C 0.08804 1.861178 -0.19465 C 1.74896 -0.49287 -2.48848 C -0.86139 2.176643 -1.38067 H 2.321869 -0.94388 -3.3068 H -1.83332 1.699378 -1.26093 H 0.758901 -0.95043 -2.46127 H -1.03011 3.259818 -1.4661 H 1.627949 0.571372 -2.70011 H -0.42998 1.826581 -2.32289 C 2.651435 -2.25066 -0.94824 C -0.57033 2.425665 1.094185 H 3.343222 -2.46725 -0.13017 H -1.53113 1.949546 1.291013 H 1.67949 -2.68175 -0.70367 H 0.072486 2.253309 1.962628 H 3.06357 -2.7151 -1.8545 H -0.745 3.508249 1.009076 ------

Chapter 4 :

A Redox Bistable Molecular Switch Built from (Amino)(Carboxy) Radical Architecture

INTODUCTION

Miniaturization of silicon based electronic components has significantly increased the computing capacity of devices. However, further miniaturization of electronic components through conventional top-down lithography is quickly becoming cumbersome and economically unfeasible.131 Therefore, it has been suggested that the next frontier lies in the design of electronic devices as small as single molecules.132 These molecules could serve as information storage and processing units133 or as basic elements for more complex logic operations.134

Indeed molecular assemblies135 and even some organic based systems136 have shown improved read/write functions when compared to purely metal based systems.

Among other things, an important prerequisite for the functionality of molecular switches is bistability, or the capacity of a molecular system to be observed in two different electronic states within a certain range of external perturbations.137 Thus far, there are two forms of bistability: magnetic and redox bistability. Magnetic bistability has been primarily studied in single molecule magnets, and has been observed in discrete transition metal complexes,138 and organic radical stacks or dimers.136b-f More recently, Wang et al. also reported the first example of intramolecular bistability within discrete organic bi-radical 4.A.139

Figure 4.1: Systems characterized by magnetic bistability.

Redox bitstability has been described as a result of structural modifications observed during oxido-redox processes for a number of transition metal complexes.140 For example,

Royal et al. reported redox triggered bistability in copper cyclam complex 4.B.140e In organic

systems, this process has been widely studied in complex organic architectures such as rotaxanes (4.C) and catenanes,141 but has also been observed for smaller systems such as bicyclo[1.1.0]butane142 4.D and a methylenepyran system 4.F,143 which undergo reversible C-C dimerization to 4.E and 4.G, respectively, upon electron transfer (Figure 4.2).144 Importantly, while complex architectures have been widely studied in a number of molecular switch applications, the ultimate objective is to discover the smallest and simplest molecules which would function as components in molecular devices. Therefore, simple systems, which display redox bistability through bond making/breaking should be further explored.

Figure 4.2: Molecular switches characterized by redox bistability.

In recent years, carbenes have emerged as excellent ligands for the preparation of stable radicals and di-radicals.78-91,95,94-98 Indeed, we demonstrated that cyclic (alkyl)(amino) carbenes were efficient synthons for the formation of stable monomeric C-centered

(amino)(carboxy) radical,110 and a number of variants featuring alternate carbene ligands and R acyl substituents have since been realized.116-117 In addition, we also established that our

synthetic scheme could be expanded to the formation of stable bi- radical 4.H and a related tri- radical species. These molecules exhibited weak electron exchange108 due to a non-conjugated and rigid linking moiety.110 Following this work, we wished to determine whether di-radicals bearing a flexible non-conjugate linking moiety would be stable. With this objective in mind, we decided to first examine 4.I. If we were indeed able to isolate this paramagnetic species, we could examine the through space interactions between the two radical units. However, we also recognized that dimerization could occur, thereby leading to a new molecular switch system. In this way, 4.I is a very attractive synthetic target, as this very simple molecule should afford new information on radical stability or open the door new and exciting applications.

Figure 4.3: Isolated bi-radical 4.J and proposed bi-radical 4.K.

Herein, we would like to report a di-(amino)(carboxy) radical 4.I which undergoes spontaneous intramolecular dimerization and displays redox bistability in solution. Interestingly, simple modifications to this simple system 4.I would allow for a wide variety of molecules and new applications. Such modifications include exchange of the carbene ligand in order to tune redox potentials (varying X and Y in Figure 4.4), and alterations to the linking moiety (“spacer” and Z in Figure 4.4), which would affect spin delocalization, and through space and through bond communication between the two radical units. These changes would also allow for the incorporation of new properties into a molecular switch system if cyclization were to occur.

Given the timeframe of this work, we decided to concentrate on a few examples wherein the carbene electronics have been modified, and on structural changes to the spacer. The corresponding results will be presented and discussed.

100

Figure 4.4: Potential di-radical modifications.

A) A Molecular Switch

A di-iminium precursor was readily synthesized by addition of half an equivalent of dimethylmalonyl dichloride to a THF solution of free carbene 4.1a. Subsequent anion exchange

- with two equivalents of sodium tetrafluoroborate yielded 4.2a2BF4 in 74% yield after work-up.

- Scheme 4.1: Synthesis of 4.2a2BF4 and 4.3a.

- The cyclic voltammogram of 4.2a2BF4 is characterized by an irreversible reduction wave at -0.77 V, with the corresponding re-oxidation wave at -0.16 V (Figure 4.5a). This data indicates that a reversible chemical transformation occurs upon reduction. Furthermore, the redox bistability of the system is evidenced by the wide spacing between Epc and Epa (ΔE = Epa

-Epc = 0.61 V). The addition of two equivalents of zinc to a dichloromethane solution of

- 4.2a2BF4 yielded 4.3a in 92% yield as off white crystals, and thus identified a C,O-cyclization

101

as the chemical transformation which was observed during the CV experiments.

Characterization of 4.3a by UV-Vis spectroscopy (Figure 4.5b) revealed an absorption band at

- 314 nm, which is very similar to that of 4.2a2BF4 (308 nm). Finally, reformation of di-iminium

4.2a2OTf- was successfully achieved in 87% yield through the addition of two equivalents of

113 silver triflate (E1/2 ≈ 0.65 V) to an acetonitrile solution of 4.3a.

- Single crystals of 4.2a2BF4 were grown by slow diffusion of diethyl ether into a saturated acetonitrile solution of the compound and subjected to an X-ray diffraction study. With

110,116-117 - respect to previously isolated α-acyl formidium ions, the structure of 4.2a2BF4 features iminium moieties which are orthogonal to the linking acyl groups (Figure 4.6). Additionally, the key bonds lengths and angles are comparable to those of previously isolated iminium salts.110

An X-ray diffraction study was also performed on a single crystal of 4.3a, which was obtained by slowly evaporation of a dichloromethane solution of the compound (Figure 4.7). The crystal structure confirmed that cyclization occurs across the acyl oxygen O1 of one radical unit and the carbenic C5 position of another, and the O1-C5 dimer bond length [147.27(15) pm] was found to be longer than the O1-C1 bond [141.72(15) pm].

102

The electrochemical process of this system is best described by a classic square scheme (Figure 4.8), wherein the redox cycle involves four distinct species, that is, the two structural isomers (4.2a and 4.3a) in their two oxidation states (4.4 and 4.5). For this ECEC mechanism, the electron transfer reactions (E) are electrochemically reversible, while the chemical transformations (C) are described by the rate constants k1 and k2.

103

Figure 4.8: Square scheme of the redox induced structural changes to 4.2a.

0 0 It is well known that E 1, E 2, k1, k2 can be efficiently extracted by electrochemical methods.145 Therefore, we conducted cyclic voltammetry on an acetonitrile solution of 4.3a with a wide sweep rate range of 0.2-12.8 Vs-1 (Figure 4.9). However, no reversibility of either electrochemical wave was observed even at the highest scan rate. Similarly, lowering the temperature of the system to -40 ˚C yielded CV spectra characterized by an irreversible oxidation wave at 0.03 V and reduction wave at -0.65 V. These data indicate that the chemical rearrangement is faster than the CV timescale.

104

We then studied this process further using DFT. The computed structure of 4.2a

B3LYP/6-311g** level of theory aligns well with that of the crystal structure in that both iminium moieties are orthogonal to the central acyl linking group (Figure 4.10). The addition of two electrons to 4.2a yields di-radical 4.4 in which both iminium moieties are coplanar with the acyl group, a structural feature that has been observed in previously isolated (amino)(carboxy) radicals.110,116-117 DFT calculations also indicate that the singlet and triplet ground states of this bi-radical are essentially equal in energy. Cyclization of 4.4 to 4.3a could yield four different possible isomers depending on the stereochemistry of both the chiral center and double bond

(Figure 4.11). Interestingly, S,E-4.3a is calculated to be the lowest energy conformation and is thermodynamically preferred over the crystal structure isomer R,E-4.3a by 6.7 kcalmol-1.

Importantly, and in line with our experimental observations, S,E-4.3a is favored over the di-

105

radical by 28.9 kcalmol-1. Accordingly, no EPR signal was observed for 4.3a at room temperature. Lastly, the addition of one electron to S,E-4.3a resulted in a ring opening to radical cation 4.6. Thus, the formation of 4.5 is highly un-favorable and the last step of the square scheme would be associated with a large k2 value.

Figure 4.10: Computational square scheme of 4.2a.

106

Figure 4.11: Possible isomers of 4.3a.

B) Tuning redox bistability as a function of the carbene ligand.

Following the success of 4.2a, we decided to modulate the switching properties of the system by synthesizing iminium salts from carbenes 4.1b-e.67,125,146 As recently reported by

Hudnall et al. the redox potentials of α-acyl formamidium ions can be tailored by simple modification of the carbene fragment (i.e. the redox potential is shifted anodically by 1.0V when moving from the NHC to the more electrophilic diamidocarbene). 117 Additionally, it is reasonable to expect that the steric environment should also play a major role in the stability of the dimer, and would thus effect the spacing between the two peak potentials. Combined, these two key factors should yield a family of molecular systems with predictable and tunable redox bistability.

The addition of dimethylmalonyl dichloride to two equivalents of 4.1b-c yielded 4.2b-c in 72 and 77% yield, respectively. However, the same procedure failed to produce 4.2d-e from carbenes 4.1d-e, respectively (Scheme 4.2).

107

Scheme 4.2: Experimental results for synthesizing molecular switches from carbenes 4.1b-e.

The cyclic voltammogram of 4.2c (Figure 4.12a) is characterized by an irreversible reduction at -0.65 V and an irreversible oxidation at -0.28, and thus, 4.2c exhibits similar redox

- properties as 4.2a2BF4 . Interestingly, the spacing between Epa and Epc is much smaller in 4.2c

- - than in 4.2a2BF4 (ΔE = Epa -Epc = 0.61 V and 0.37 V for 4.2a2BF4 and 4.2c, respectively).

Treatment of 4.2c with two equivalents of zinc yielded the cyclized compound 4.3c in 60% yield.

In contrast, the cyclic voltammogram of 4.1b (Figure 4.12c) is characterized by two two-electron reductions to a bi-radical and enolate species (E1/2 = -1.24 V and -1.88 V respectively). The addition of two equivalents of cobaltocene to 4.2b yielded bi-radical 4.7, which was isolated as a brown, NMR silent solid. It is likely that the steric constraints imposed by the NHC ligand in this system prevent the intramolecular dimerization.

108

Figure 4.12: Cyclic voltammograms of 4.2b (a) and 4.2c (c). Inset B demonstrates the reversibility of the first 4.2b reduction wave. Spectra referenced with respect to Fc+/Fc.

While the importance of sterics needs to be taken into account, these results clearly suggest that the carbene electronics and effectively and predictably modulate the redox properties of these systems. Future developments could focus on smaller di-iminium precursors featuring either a smaller (4.1f-g) or unsymmetrical NHCs (4.1h-i).

Figure 4.13: Carbenes 4.1f-i.

C) Molecular switches: other models

a. Nitrogen linked molecular switches

- Our flagship molecular model 4.2a2BF4 /4.3a displayed two of requirements of a molecular switch, namely bistability and reversibility. However, to be useful molecular switches must also satisfy some additional pre-requisite properties. Firstly, the interconversion barrier between the states must be higher than the thermal energy at the working temperature.

109

Secondly, there must be a large difference in the magnitude of the initial and the final value of the given properties. In many cases, UV-Vis absorptions bands have been used to differentiate between the two states, as it is a simple and fast method of detection. However, since the

- absorption bands of 4.2a2BF4 and 4.3a are so similar, a modification to our initial design in order to introduce a larger physical change was deemed appropriate. With this in mind, we decided to explore other linker motifs (Figure 4.14).

Figure 4.14: Proposed molecular switch systems, where L is an arbitrary linking group.

- We initially attempted to exchange the central tertiary carbon of 4.2a2BF4 with a NR group, which would allow for the incorporation of a tunable handle, which could be used to integrate different physical properties (e.g. color, luminescence, pKa ect.) into the molecular system. This would allow for easier detection and the potential incorporation of additional logic operations within the switch.

To synthesize a suitable precursor, we envisaged that the reaction of 4.8 148 with two equivalents of carbene 4.1j would yield a di-α-amino(ketone) 4.9 which could then be oxidized by DDQ to the desired iminium salt 4.10 (Scheme 4.3). However, the addition of two equivalents of 4.1j to a THF solution of 4.8 yielded α-amino(ketone) 4.11 in 56% yield. Additional attempts to synthesize 4.9 under different experimental conditions (e.g. heating, longer reaction time…) consistently resulted in the isolation of 4.11.

110

Scheme 4.3: Proposed synthetic pathway to 4.10 (top). Experimentally obtained α- amino(ketone) 4.11 (bottom).

We then explored an alternative synthetic route. It has long been established that NHCs

149 react with CO2 to form the corresponding adducts. Interestingly, in 1999, Kuhn et al. also demonstrated that 4.12a could be effectively converted into acyl chloride 4.13a through the simple addition of thionyl chloride (Scheme 4.4).149a With these results in mind, we decided to extend this synthetic method to CAACs, specifically to the synthesis of 4.13b. A nitrogen nucleophile, generated by the in situ deprotonation of an amine, could then react with two equivalents of 4.13b to generate 4.10 (Scheme 4.5). Following an established procedure,150 we easily isolated 4.12b by addition of excess CO2 to a THF solution of 4.1j. However, efforts to isolate 4.13b through the addition of either thionyl chloride or PCl5 to 4.12b at room temperature failed, and instead yielded adduct 4.14 via a CO(g) elimination. This product was also formed in 71% yield upon addition of phosgene to a THF solution of carbene 4.1j (Scheme 4.6). As

4.13b was unstable at room temperature, we then generated this compound in situ at -78˚C and added a mixture of aniline and triethylamine to the flask. The reaction mixture was then stirred at -78˚C for five hours before being warmed to room temperature. However, work up of the reaction mixture still yielded adduct 4.14.

Scheme 4.4: Formation of acyl chloride 4.13a.

111

Scheme 4.5: Proposed synthetic pathway to 4.10 from acyl chloride 4.13b (top). Experimentally obtained adduct 4.14(bottom).

Scheme 4.6: Synthesis of 4.11 by addition of phosgene to carbene 4.1j.

Despite several attempts, we were not able to introduce a nitrogen functionality into our linker at this time. Furthermore, given our timeframe, we were not able to further pursue the preparation of 4.15 (Scheme 4.7), another attractive candidate which was identified for this methodology. Lastly, di-iminium precursors built from NHCs with smaller substituents (4.1f-g) or unsymmetrical NHCs (4.1h-i), should prove to be interesting targets.

˚C

Scheme 4.7: Synthesis of 4.12 from acyl chloride 4.13a.

112

b. Ferrocene as a linking moiety.

We also considered ferrocene as a linking moiety, since changes in state should be easily detectable by the UV-Vis spectroscopy. In order to determine the feasibility of this linker, we performed DFT calculations at the B3LYP/6-31g* level of theory on 4.16. Importantly, these calculations show that the cyclized product should be thermodynamically attainable with small substituents (see Figure 4.15). However, as small carbenes, such as 4.1f, are prone to the formation of “Wanzlick dimers,”151 we sought to first establish a synthetic procedure using a stable CAAC.

Figure 4.15: Optimized geometry of 4.16.

A suitable precursor was synthesized through the addition of an ether solution of 1,1’- ferrocene dicarbonyl chloride152 to carbene 4.1c. A subsequent anion exchange with sodium tetraphenylborate yielded 4.17a in 82% yield as a dark purple solid (Scheme 4.8). The cyclic voltammogram of 4.17a is characterize by two reversible reductions (E1/2 = 0.80 and 1.08 V) to the radical and bi-radical species, respectively (Figure 4.16). Additionally, there is a reversible oxidation wave at 1.01 V, which has been assigned to the Fe2+/Fe3+ redox couple. These data indicate that a di-radical will be formed upon reduction of 4.17a. Indeed, when one equivalent

107 of TDAE (E1/2 ≈ -1.2 V) was added to a dichloromethane solution of 4.17a, the corresponding di-radical 4.18a was formed as an NMR silent, brown solid in 77% yield. To reduce the sterics of the di-iminium salt, we also synthesized 4.17b from our smallest CAAC 4.1a. However, this product was found to degrade over time in the solid state, even when shielded from light.

113

Nevertheless, reduction of the crude material with two equivalents of cobaltocene yielded di- radical 4.18b as an NMR silent material.

Scheme 4.8: Synthesis of di-(amino)(carboxy) radicals 4.17a-b.

Figure 4.16: Cyclic voltammogram of 4.17a. Spectrum referenced with respect to Fc+/Fc.

These results indicate two very important problems with these systems. Firstly, the sterics of the carbene influences the stability of the di-iminium salt. This is thus far unprecedented and at present it is not clearly understood why. Secondly, reduction of the di- iminium salts 17a-b yielded di-radicals 18a-b and not cyclized species. Thus, while DFT calculations suggested that cyclization would occur with extremely small substituents, the stability of the iminium precursor would be highly questionable as 17b degraded even when under an inert atmosphere and shielded from light.

114

c. Nitroso based molecular switches

With extremely simple molecular systems in mind, we also decided to explore the idea of having an (amino)(carboxy) radical cyclize with an external functional group, such as a nitroso. This functional group features a nucleophilic nitrogen which would facilitate cyclization with an (amino)(carboxy) radical. Thus, in our proposed molecular system, the reduction of iminium 4.19 would yield the cyclized molecule 4.20 (Figure 4.17). Furthermore, detection of the two states of the molecular system would be easily accomplished by UV-Vis spectroscopy.

Figure 4.17: Proposed nitroso-based molecular switch.

In order to determine the feasibility of this molecular system, we first performed DFT calculations at the B3LYP/6-311g** level of theory. We considered the isodesmic reaction of iminium 4.21a and enol 4.22a which would lead to the formation of either (amino)(carboxy) radical 4.23a or the cyclized radical 4.24a (Scheme 4.9) Calculations predict that the cyclized product 4.24a is favored over 4.23a by 48.6 kcalmol-1. The cyclized product 4.24b was also thermodynamically favored over 4.24b when considering the isodesmic reaction of 4.21b and

4.22b, wherein the steric bulk of the amino groups had been increased from methyl to isopropyl.

However, the newly formed C-N bond of 4.24b (155.7 pm) was longer than that of 4.24a (153.1 pm), and energy gap between the open and cyclized radicals was decreased to 33.9 kcalmol-

1. These results indicate that excessive steric bulk could lead to an inversion in stability between the open radical and the cyclized product. Therefore, only small carbenes should be considered as synthons for this molecular system.

115

Scheme 4.9: The isodesmic reaction of 4.21a-b and 4.22a-b.

However, as previously stated, sterically unhindered carbenes, such as 4.1f, are prone to the formation of “Wanzlick dimers.”150 Therefore, we again sought to first establish a synthetic procedure using stable CAAC 4.1j. Our conventional synthetic method to generate iminium precursor 4.29, the reaction of a free carbene with acyl chloride 4.26, was inaccessible as 2- nitrosobenzoyl chloride has only been observed upon irradiation of 4.25 in a matrix at 10 K

(Scheme 4.10).153 Therefore we considered first forming the α-amino(keytone) 4.28, which could be subsequently oxidized to 4.29 by DDQ (Scheme 4.11). The addition of carbene 4.1j to a THF solution of 4.27 154 yielded a dark brown oil after work-up. However, an X-ray diffraction study on crystals grown from the crude mixture revealed 4.30 and no other viable product could be extracted from the crude mixture. At this time, it is unclear whether the formation of 4.30 results from a simple oxidation of 4.1j by 4.27 or if this is the product of a degradation pathway.

hν

Scheme 4.10: Synthesis of acyl chloride 4.26 by irradiation of diazo 4.25.

116

Scheme 4.11: Proposed synthesis of 4.29 from 2-nitrosobenzaldehyde 4.27 (top). Compound 4.30 was isolated from the crude reaction mixture (bottom).

In another pathway, the reaction of 4.33 with carbene 4.1j, was then envisaged to access 4.29 (Scheme 4.12). In order to synthesize a suitable precursor, 4.31155 was first oxidized to 4.32 with iron chloride, a procedure previously described by Bamberger and

Plyman.156a Compound 4.33 was then formed in 52% yield by the addition of trimethylacetyl chloride and triethylamine to a THF solution of 4.32. As previously described for 4.32,156 anhydride 4.33 was found to be in equilibrium with azodioxy dimers 4.34a-b (Figure 4.18), as determined by NMR. However, addition of carbene 4.1j to a THF solution 4.33 failed to produce any reaction.

Scheme 4.12: Proposed synthesis of 4.29 from 4.33.

Figure 4.18: Azodioxy dimers 4.34a-b.

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Thus, while DFT calculations indicated that these systems are excellent molecular switch targets, we have not been able to access compound 4.28. Importantly, we believe that the failure to attain 4.28 from 4.33 is due to the lower electophilicity of the carbonyl moiety in

4.33 when compared to that of an acid chloride or an aldehyde.

CONCLUSION

In summary, we have designed an air-stable molecular switch that exhibits redox bistability. Cyclic voltammetry experiments indicate that the chemical transformations associated with this redox process are reversible and occur at a rate which is higher than the

CV time scale. We then demonstrated that the redox properties of this switch system could be tuned by alterations to the carbene framework. Importantly, excessive steric bulk around the carbene prevented the cyclization process. Therefore, with these results in mind, it should be possible to rationally assemble a family of molecular switches by using carbenes with varying electronic properties, but small substituents, as synthons.

We also made modifications to our flagship m several different molecular systems with alternate linking moieties with the goal of modifying our flagship molecular switch would have allowed for the incorporation of an easily detectable property with a large difference in values.

Our initial work involved a nitrogen linked molecular switch. In the timeframe available to us, we were unable to isolate a working model, but several additional synthetic strategies have been proposed herein. DFT calculations also indicated that a ferrocene linked switch and a nitroso based model showed promise, but thus far we have been unable to isolate any viable molecular switch targets. In particular, the former failed to exhibit molecular switch properties. Therefore, it is important to remember that synthesis should always be utilized to verify the results of predictive modeling.

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Chapter 4 has been adapted from materials currently being prepared for submission.

Mahoney, J. K.; Royal, G.; Moore, C. E.; Rheingold, A. L.; Martin, D.; Bertrand, G. The dissertation author was the primary investigator of this paper.

APPENDIX: EXPERIMENTAL SECTION

1) General Considerations

All manipulations were performed under an inert atmosphere of dry argon, using standard Schlenk and drybox techniques. Dry and oxygen-free solvents were employed.

Dimethylmalonyl dichloride, was distilled before use. 1H and 13C, NMR spectra were recorded on Bruker Avance 300, Varian VX 500 and Jeol ECA 500 spectrometers. All spectra were obtained at 25°C in the solvent indicated. Chemical shifts are given relative to SiMe4 and referenced to the residual solvent signal (1H, 13C). Melting points were measured with an

Electrothermal MEL-TEMP apparatus. Ferrocene was used as a standard, and all reduction

+ potentials are reported with respect to the E1/2 of the Fc /Fc redox couple. Electrochemical experiments were carried out with a Bio-logic SP-300 potentiostat. Potentials were referred to an Ag/0.01M AgNO3 reference electrode in CH3CN + 0.1M [Bu4N]PF6. The working electrode was a vitreous carbon disk (3 mm in diameter) and the auxiliary electrode was a platinum wire in CH3CN + 0.1M [Bu4N]PF6. All reduction potentials are reported with respect to the E1/2 of either the Fc+/Fc or Fc*+/Fc* redox couple. Electrochemical reductions were performed using reticulated vitreous carbon electrode, and were monitored with a Zeiss MCS 501 UV-NIR Plus spectrometer.

2) Synthetic Procedures

- Di-iminium 4.2a2BF4 : Dimethylmalonyl dichloride (99 μL, 0.75 mmol) was added to a THF solution of 4.1a (0.45 g, 0.158 mmol); the solution was stirred for twenty minutes. The solvent was removed by filtration and the precipitate washed with diethyl ether (2 x 10mL). The solid was then re-dissolved in water, and an aqueous solution of sodium tetraflouroborate (0.69 g,

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6.31 mmol) was added to the flask. After stirring for one hour, the product was extracted in dichloromethane. The organics were washed with brine and dried over MgSO4 before removing

- the solvent under vacuum. Single crystals of 4.2a2BF4 were grown by slowly diffusing diethyl ether into a concentrated acetonitrile solution of the product. Yield: 272 mg (43%). mp: 146-

+ 2+ 1 148ᵒC. MS (m/z): [M ] calc. for C45H68N2O2 , 334.2635; found, 334.2637. H NMR (CDCl3,

300MHz): δ = 7.65 (t, J = 6 Hz, 2H), 7.51 (d, J = 6 Hz, 4H), 2.88 (bs, 4H), 2.70 (bs, 6H), 1.66

13 (bs, 24H), 1.25 (d, J = 6 Hz, 12H), 1.15 (d, J = 6 Hz, 12H), 0.90 (bs, 4H) ppm. C NMR (CDCl3,

125MHz): δ = 200.4 (C), 195.5 (C), 146.2 (C), 134.1 (CH), 130.3 (C), 128.8 (CH), 90.0 (C), 62.0

(C), 53.3 (C), 50.4 (CH2), 30.0 (CH3), 29.1 (CH), 27.2 (CH3), 25.4 (CH3), 20.3 (CH3) ppm.

- Molecule 4.3a: Zinc (19 mg, 0.297 mmol) and 4.2a2BF4 (100 mg, 0.134mmol) were combined under argon and acetonitrile was added to the flask. After 10 minutes, the solvent was removed in vacuo. Subsequent extraction with hexanes (5.0 mL) lead to the isolation of a white powder.

Single crystals for x-ray crystallography were isolated through slow evaporation of a dichloromethane solution of the product. Yield: 96 mg (92%). mp: 217-221ᵒC. MS (m/z): [M+]

+ 1 calc. for C54H68N2O2, 669.0336; found, [M+Na] = 691.5172 . H NMR (C6H6, 300 MHz): δ = 7.21-

7.15 (m, 3H), 7.05-6.95 (m, 3H), 4.26 (sept, J = 6 Hz, 1H), 3.84 (sept, J = 6 Hz, 1H), 3.54 (m,

2H), 2.10 (d, J = 12 Hz, 1H), 1.97 (s, 3H), 1.87 (s, 3H), 1.82 (d, J= 12 Hz, 1H), 1.77 (d, J = 6

Hz, 3H), 1.62 (d, J = 12 Hz, 1H), 1.64 (s, 3H), 1.51 (s, 3H),1.47 (d, J = 6 Hz, 3H), 1.38 (s, 3H),

1.30 (bs, 3H), 1.28 (bs, 2H), 1.26 (s, 1H), 1.24 (s, 1H), 1.22 (d, J = 3 Hz, 3H), 1.19 (d, J = 3 Hz,

3H), 1.17 (s, 1H), 1.13 (s, 3H), 1.07 (d, J = 6 Hz, 3H), 0.99 (s, 3H), 0.96 (d, J = 6 Hz, 1H), 0.91-

13 0.84 (m, 4H), 0.79 (s, 3H), 0.51 (s, 3H) ppm. C NMR (CDCl3, 125MHz): δ = 213.7 (C), 154.1

(C), 151.6 (C), 148.4 (C), 147.7 (C), 144.3 (C), 142.1 (C), 136.3 (C), 133.5 (C), 127.4 (CH),

125.8 (CH), 125.0 (CH), 124.5 (CH), 107.3 (C), 64.1 (C), 63.6 (C), 58.7 (CH2), 55.7 (CH2), 49.6

(C), 45.6 (C), 42.9(C), 32.8 (CH3), 30.5 (CH3), 29.5 (CH3), 29.3 (CH3), 28.6 (CH), 28.4 (CH3),

28.1(CH), 27.8 (CH), 27.1 (CH3), 26.8 (CH3), 26.7 (CH3), 26.6 (CH3), 26.5 (CH3), 26.4 (CH3),

26.1 (CH), 25.8 (CH3), 25.7 (CH3), 24.9 (CH3), 23.9 (CH3), 21.8 (CH3) ppm.

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Di-iminium 4.2a2OTf- from compound 4.3a: Silver triflate (68.6 mg, 0.27 mmol) and 4.3a

(100 mg, 0.13 mmol) were combined under argon. Acetonitrile (5 mL) was added to the flask and the mixture was stirred for 20 minutes. The supernatant was then removed via filtration.

The solvent was removed in vacuo and the solid washed with hexanes to yield 2. Yield: 0.121 g (87%).

Di-iminium 4.2b: Dimethylmalonyl dichloride (0.1 mL, 0.76 mmol) was added to a tetrahydrofuran solution of 4.1b (617 mg, 1.59 mmol). The mixture was stirred for 2 hours and the supernatant was removed via filtration. The solid was then washed with diethyl ether (2 x

20 mL) and dried in vacuo. Recrystallization by a slow diffusion of diethyl ether into a dichloromethane solution of the product yielded 4.2b as white crystals. Yield: 515 mg (72 %).

1 H NMR (CDCl3, 500 MHz): 8.95 (s, 4H), 7.57 (t, J = 7.8 Hz, 4H), 7.28 (d, J = 7.8 Hz, 8H), 2.12

(sept., J = 6.6 Hz, 8H), 1.17 (d, J = 6.6 Hz, 24H), 1.05 (d, J = 6.6 Hz, 24H), 0.44 (s, 6H).13C

NMR (CDCl3, 125 MHz): 192.4 (C), 145.1 (C), 133.3 (CH), 129.8 (C), 128.3 (C), 125.2 (CH),

124.8 (CH), 61.9 (C), 29.8 (CH), 27.2 (CH3), 21.5 (CH3), 19.8 (CH3).

Di-iminium 4.2c: Dimethylmalonyl dichloride (0.85 mL, 53.8 mmol) was added to a THF solution of 4.1c (438 mg, 1.35 mmol); the mixture was stirred for twenty minutes. The solvent was removed by filtration and the precipitate washed with diethyl ether (2 x 10mL). Yield: 338 mg

+ 2+ 1 (77%). mp: 175-177ᵒC. MS (m/z): [M ] calc. for C51H76N2O2 , 374.2948; found, 374.2950. H

NMR (CDCl3, 300MHz): 7.59 (t, J = 6 Hz, 2H), 7.38 (d, J = 6 Hz, 2H), 7.31 (d, J = 6 Hz, 2H),

1.78 (bs, 2H), 3.73 (sept., J = 3 Hz, 4H), 3.18 (bs, 2H), 2.50-2.39 (m, 4H), 2.21 (s, 3H), 1.97

(bs, 8H), 1.86-1.81 (m, 5H), 1.77 (bs, 3H), 1.66-1.59 (m, 3H), 1.52 (s, 6H), 1.35 (s, 6H), 1.25 (d,

13 J = 3 Hz, 12H) 1.10 (d, J = 3 Hz, 12H). C NMR (CDCl3, 125MHz): 200.8 (C), 194.2 (C), 147.1

(C), 144.5 (C), 133.58 (CH), 128.9 (C), 128.3 (CH), 127.5 (CH), 88.6 (C), 62.76 (C), 58.79 (C),

41.7 (CH2), 35.8 (CH2), 33.6 (CH2), 30.3 (CH3), 29.44 (CH), 29.0 (CH), 27.3 (CH3), 26.6 (CH3),

26.3 (CH3), 25.7 (CH3), 24.7 (CH2), 22.1 (CH2), 21.5 (CH2), 19.9 (CH3).

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Molecule 4.3c: Di-iminium 4.2c (200 mg, 0.244 mmol) and zinc (35 mg, 0.536 mmol) were combined under argon. Acetonitrile was added to the flask and the mixture was stirred overnight.

The solvent was removed in vacuo, and the product extracted with hexanes (5.0 mL). Removal of the solvent lead to the isolation of a light-yellow powder. Yield: 110 mg (60%). mp: 249-251ᵒC.

+ + 1 MS (m/z): [M ] calc. for C51H76N2O2, 748.5907; found, [M+H] = 749.5971. H NMR (CDCl3,

300MHz): δ = 7.18-7.11 (m, 3H), 7.05-6.98 (m, 3H), 4.25 (sept., J = 3 Hz, 1H), 3.86-3.81 (m,

2H), 3.54 (sept., J = 6 Hz, 1H), 3.13-3.02 (m, 3H), 2.51 (d, J = 9 Hz, 1H), 2.20 (bs, 1H), 2.17 (d,

J = 9 Hz, 2H), 2.06 (d, J = 9 Hz, 1H), 1.97 (d, J = 9 Hz, 1H), 1.93-1.87 (m, 5H), 1.83 (d, J = 3

Hz, 3H), 1.81 (s, 3H), 1.50 (s, 3H), 1.44 (d, J = 3 Hz, 3H), 1.27 (s, 3H), 1.26 (s, 3H), 1.25 (s,

3H), 1.24 (s, 5H), 1.22 (s, 3H), 1.18 (s, 2H), 1.17 (s, 2H), 1.14 (s, 3H), 1.06 (d, J = 3 Hz, 3H),

1.03 (s, 3H), 0.97 (d, J = 3 Hz, 3H), 0.85 (d, J = 3 Hz, 1H), 0.83 (s, 3H), 0.56 (s, 3H) ppm. 13C

NMR (C6D6, 125 MHz): δ = 213.5 (C), 154.0 (C), 151.2 (C), 148.2 (C), 147.4 (C), 144.6 (C),

143.0 (C), 136.7 (C), 134.9 (C), 127.4 (CH), 125.6 (CH), 125.2 (CH), 125.0 (CH), 124.8 (CH),

123.8 (CH), 108.6 (C), 64.4 (C), 63.8 (C), 54.3 (C), 51.0 (CH2), 50.7 (CH2), 48.4 (C), 45.9 (C),

37.4 (CH2), 37.1 (CH2), 35.0 (CH2), 32.3 (CH2), 32.0 (CH2), 31.0 (CH3), 29.8 (CH2), 28.6 (CH),

28.3 (CH), 28.2 (CH), 27.9 (CH3), 27.6 (CH3), 27.0 (CH3), 26.4 (CH3), 26.3 (CH3), 26.1 (CH),

26.0 (CH2), 25.6 (CH3), 25.6 (CH2), 25.1(CH3), 24.9 (CH2), 24.5(CH2), 24.4 (CH2), 24.3 (CH3),

23.7(CH3), 23.1 (CH2), 21.9 (CH3) ppm.

Di-radical 4.7: Cobaltocene (27 mg, 0.21 mmol) and 4.2b (100 mg, 0.11 mmol) were combined under argon. Dichloromethane was added to the flask, and the mixture was stirred for 30 minutes. Removal of the solvent and extraction with toluene yielded 4.4 as a dark brown NMR silent solid.

α-Amino(ketone) 4.11: A THF solution (20.0 mL) of N-formyl-N-phenylformamide (200 mg,

1.34 mmol) was added drop-wise to a THF solution (10.0 mL) of carbene 4.1j (408 mg, 1.30 mmol) at -78˚C. The solution was warmed to room temperature and stirred for two hours. The solvent was then removed by vacuum and the oil was then re-dissolved in dichloromethane and run through a plug of silica gel. Following this, the solvent was removed by vacuum, the product

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re-dissolved in a minimum amount of hexane and cooled to ˚0 C to crystallize. Yield: 347 mg

+ + 2+ 1 (56 %). MS (m/z): [M ] calc. for C30H42N2O2 , 462.3246; found, [M ] = 433.45. H NMR (CDCl3,

500 MHz): δ = 9.56 (s, 1H), 7.30 – 7.04 (m, 8H), 3.92 (s, 1H), 3.90 (sept, J = 6.9 Hz, 1H), 3.05

(sept., J = 6.9 Hz, 1H), 2.18 (d, J = 12.9 Hz, 1H), 1.95 (d, J = 12.9 Hz, 1H), 1.88 – 1.69 (m, 4H),

1.55 (s, 3H), 1.22 (d, J = 6.9 Hz, 3H), 1.17 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.9 Hz, 3H), 1.03 (s,

3H), 0.91 (t, J = 7.2 Hz, 3H), 0.70 (t, J = 7.2 Hz, 3H), 0.37 (d, J = 6.9 Hz, 3H) ppm.13C NMR

(CDCl3, 125 MHz): δ = 178.3 (C), 163.6 (CH), 152.6 (C), 150.7 (C), 139.0 (C), 135.1 (C), 130.0

(CH), 128.8 (CH), 128.3 (CH), 127.3 (CH), 125.0 (CH), 124.9 (CH), 75.0 (CH), 64.6 (C), 54.8

(CH2), 50.4 (C), 32.3 (CH3), 31.4 (CH), 28.7 (CH3), 27.8 (CH), 27.4 (CH), 27.3 (CH2), 26.5 (CH3),

25.7 (CH3), 24.8 (CH3), 24.6 (CH3), 9.7 (CH3), 9.6 (CH3) ppm.

Compound 4.12b: CO(g) was bubbled through a THF solution of carbene 4.1j (0.50 g, 1.60 mmol) for 30 minutes. The solvent was then removed, and the white solid washed with hexane

1 (2 x 10 mL) and dried in vacuo. Yield: 0.39 g (68 %). H NMR (CDCl3, 500 MHz): δ = 7.37 (t, J

= 8 Hz, 1H), 7.24 (d, J = 8 Hz, 2H), 2.79 (sept, J = 6.5 Hz, 2H), 2.22 (s, 2H), 2.10-1.96 (m, 4H),

1.47 (s, 6H), 1.37 (d, J = 6.5 Hz, 6H), 1.28 (d, J = 6.5 Hz, 6H), 1.16 (t, J = 7.5 Hz, 6H) ppm. 13C

NMR (CDCl3, 125 MHz): δ = 194.5 (C), 158.4 (C), 146.0 (C), 130.6 (CH), 125.7 (CH), 79.2 (C),

56.9 (C), 41.7(CH2), 31.8(CH2), 29.5 (CH), 29.4(CH3), 26.6(CH3), 24.5(CH3), 9.5 (CH3) ppm.

Compound 4.14: Phosgene (0.45 g, 4.55 mmol) was added to a THF solution of carbene 4.1j

(1.50 g, 4.79 mmol) at -78 ˚C. After stirring at -78 ˚C for 30 minutes, the solution was warmed to room temperature and stirred for an additional hour before filtering, washing the solid with hexanes, and removing residual solvent by vacuum. Compound 4.14 was isolated as an off-

1 white solid. Yield: 1.30 g (71%). H NMR (CDCl3, 500 MHz): δ = 7.59 (t, J = 7.5 Hz, 1H), 7.38

(d, J = 7.5 Hz, 2H), 2.82 (s, 2H), 2.50 (sept, J = 6.5 Hz, 2H), 2.10-1.96 (m, 4H), 1.69 (s, 6H),

13 1.32 (d, J = 6.5 Hz, 6H), 1.14 (d, J = 6.5 Hz, 6H), 1.13 (t, J = 6.5 Hz, 6H) ppm. C NMR (CDCl3,

125 MHz): δ = 189.8 (C), 144.3(C), 132.7 (CH), 127.6 (C), 126.4 (CH), 84.5 (C), 60.0 (C), 40.6

(CH2), 31.6 (CH2), 30.0 (CH), 29.1 (CH3), 26.2 (CH3), 23.2 (CH3), 9.0 (CH3) ppm.

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Di-iminium 4.17a: A diethyl ether solution of 1,1’ ferrocene dicarbonyl chloride (0.42 g, 1.35 mmol) was added, via cannula to a diethyl ether solution of 4.1c (0.97 g, 2.97 mmol)) shielded from light. The mixture was stirred for 20 minutes and then filtered. The resultant purple solid was then washed with additional portions of diethyl ether (2 x 30 mL) and dried in vaccuo. The material was then dissolved in dichloromethane and an aqueous solution of sodium tetraflouroborate (0.65 g, 6.44 mmol) was added to the flask. The biphasic mixture was stirred vigorously for one hour, before the layers were separated and the organics washed with brine and dried over MgSO4. Removal of the solvent by vacuum yielded 4.16a a purple material.

2+ 2+ Yield: 1.18 g (82 %). mp: 230-232 ˚C. MS (m/z): [M ] calc. for C58H78FeN2O2 , 445.2701; found,

445.2705. 1H NMR (DMSO, 500 MHz): δ = 7.47 (t, J = 7.85, 2H), 7.29 (d, J = 7.85 Hz, 4H), 5.09

(s, 4H), 4.94 (s, 4H), 2.70 (s, 4H), 2.54 (sept., J = 6.35 Hz, 4H), 2.32 (bd, 4H), 2.13 (bt, 5H),

2.00 (bd, 5H), 1.81 (bd, 2H), 1.58 (bd, 4H), 1.53 (s, 12H), 1.24 (d, J = 6.35 Hz, 12H), 0.73 (bs,

12H) ppm. 13C NMR (DMSO, 125 MHz): δ = 192.8 (C), 191.0 (C), 144.8 (C), 132.2 (C), 126.8

(CH), 126.5 (CH), 86.0 (C), 78.2 (C), 76.8 (CH), 74.8 (CH), 55.0 (C), 42.6 (CH2), 33.9 (CH2),

11 28.7 (CH3), 28.6 (CH), 26.3 (CH3), 24.9 (CH3), 24.1 (CH2), 20.8 (CH2) ppm. B NMR (DMSO,

96 MHz): δ = -0.74 (s) ppm.

Di-iminium 4.17b: Carbene 4.1a (760 mg, 2.66 mmol) was dissolved diethyl ether and cooled to -78 ˚C. An ether solution of 1,1’ ferrocene dicarbonyl chloride (380 mg, 1.22 mmol) was added to the flask via cannula. The mixture was stirred at -78 ˚C for 30 minutes and then at room temperature for 30 minutes before filtering, washing with diethyl ether (2 x 20 mL), and drying the purple solid in vacuo. Sodium tetraphenylborate (1.67 g, 4.89 mmol) and dichloromethane were then added to the flask, and the mixture was stirred overnight. The solvent was then removed in vacuo and the product was extracted in chloroform. 13C NMR (DMSO, 125 MHz): δ

= 193.7 (C), 190.4 (C), 163.0 (q, C, J = 50 Hz), 144.4 (C), 135.2 (CH), 132.7 (C), 126.2 (CH),

124.9 (CH), 124.3 (CH), 121.1 (CH), 85.7 (C), 78.8 (CH), 76.6 (CH), 74.3 (CH), 50.0 (C), 47.6

(CH2), 28.1 (CH3), 27.8 (CH), 27.2 (CH3), 25.8 (CH3), 24.6 (CH3) ppm.

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Di-radical 4.18a: Iminium 4.17a (100 mg, 0.093 mmol) was dissolved in dichloromethane, and

TDAE (20 μL,0.089 mmol) was added to the flask. The mixture was stirred for 30 minutes before removing the solvent in vacuo and extracting the product in hexanes. Yield: 61 mg (77%).

Di-radical 4.18b: Cobaltocene (39 mg, 0.41 mmol) and 4.17b (100mg, 0.23 mmol) were combined under argon. Dichloromethane (5 mL) was added to the flask, and the mixture was stirred for one hour. Removal of the solvent in vacuo, and extraction in toluene yielded 4.15b as a dark brown NMR silent solid.

Compound 4.31:155 Barium hydroxide (1.57 g, 9.16 mmol) and 2-nitrobenzoic acid (1.67 g, 10.0 mmol) were dissolved in degassed water and the mixture cooled to 0 ˚C. Ammonium chloride

(0.75 g, 14.0 mmol) was then added to the flask. Following this, zinc (1.50 g, 23.0 mmol) was added to the flask over the course of an hour, while keeping the temperature under 10 ˚C. The mixture was stirred for an additional 30 minutes, and the mixture was quickly filtered under argon into an iced flask, which has been shielded from light. The solids were washed with warm water

(30 ˚C) to extract the remaining product. A 25% solution of HCl was then added to the flask.

The precipitate was then filtered off, washed with water and dried overnight in vacuo.

Recrystallize by cooling a 50:50 ethanol: chloroform solution of the product. Yield: 1.31 g (86%).

+ - 1 mp: 180-182 ˚C. MS (m/z): [M ] calc. for C7H7NO3, 153.0426; found, 152.0354 [M-H] . H NMR

(DMSO, 300 MHz): δ = 8.95 (bs, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.45 (t, J = 7.2 Hz, 1H), 7.22 (d,

J = 8.1 Hz, 1H) 6.77 (t, J = 7.5 Hz, 1H) ppm. 13C NMR (DMSO, 125 MHz): δ = 169.4 (C), 154.1

(C), 134.6 (CH), 131.3 (CH), 118.3 (CH), 114.1 (CH), 111.8 (C) ppm.

Compound 4.32:155a Iron chloride (10.0 g, 61.7 mmol) was dissolved in degassed water and cooled to 0 ˚C. An ethanol solution of 4.31 (2.86 g, 18.7 mmol) was added slowly. The mixture was stirred at 0 ˚C for 5-10 minutes before filtering under argon. The green solid was washed with cold water and then dried overnight in vacuo. Yield: 1.15 g (41%). See literature for NMR analysis of 4.32.156

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Compound 4.33: A THF solution of 4.32 (0.100 g, 0.66 mmol) was cooled to -78 ˚C. Acetyl chloride (0.08 mL, 1.32 mmol) and triethylamine (0.10 mL, 1.32 mmol) were then added to the flask. The mixture was warmed to room temperature, and stirred for one hour, before filtering,

13 washing with diethyl ether and drying the solid in vacuo. Yield: 66 mg (52%) C NMR (CDCl3,

125 MHz): δ =165.6, 165.4, 163.0, 161.96, 159.1, 142.0, 135.5, 135.2, 133.0, 131.2, 131.1,

126.1, 123.4, 114.8, 114.0, 22.6, 22.2 ppm.

3) Crystallographic Data

- Crystal data and structure refinement for 4.2a2BF4 . Empirical formula C58H78BF4N2O2 Formula weight 922.03 Temperature/K 100.0 Crystal system Monoclinic Space group P21/n a/Å 21.3385(5) b/Å 10.2918(3) c/Å 24.6136(6) α/° 90 β/° 111.6150(10) γ/° 90 Volume/Å3 5025.3(2) Z 4 3 ρcalcg/cm 1.219 μ/mm-1 0.657 F(000) 1988.0 Crystal size/mm3 0.01 x 0.1 x 0.3 Radiation CuKα (λ = 1.54178) 2Θ range for data collection/° 4.698 to 137.024 Index ranges -25 ≤ h ≤ 23, -12 ≤ k ≤ 12, -29 ≤ l ≤ 29

Reflections collected 58547 Independent reflections 9248 [Rint = 0.0554, Rsigma = 0.0332] Data/restraints/parameters 9248/0/641 Goodness-of-fit on F2 1.022 Final R indexes [I>=2σ (I)] R1 = 0.0594, wR2 = 0.1503 Final R indexes [all data] R1 = 0.0732, wR2 = 0.1602 Largest diff. peak/hole / e Å-3 0.76/-0.69

Crystal data and structure refinement for 4.3a.

Empirical formula C45H68N2O2 Formula weight 669.01 Temperature/K 100.0

126

Crystal system tetragonal Space group I41/a a/Å 40.9002(13) b/Å 40.9002(13) c/Å 9.3346(4) α/° 90 β/° 90 γ/° 90 Volume/Å3 15615.2(12) Z 16 3 ρcalcg/cm 1.138 μ/mm-1 0.517 F(000) 5888.0 Crystal size/mm3 0.56 × 0.21 × 0.15 Radiation CuKα (λ = 1.54178) 2Θ range for data collection/° 4.32 to 136.964 Index ranges -49 ≤ h ≤ 48, -49 ≤ k ≤ 45, -11 ≤ l ≤ 11 Reflections collected 63137 Independent reflections 7154 [Rint = 0.0615, Rsigma = 0.0289] Data/restraints/parameters 7154/0/460 Goodness-of-fit on F2 1.020 Final R indexes [I>=2σ (I)] R1 = 0.0379, wR2 = 0.0884 Final R indexes [all data] R1 = 0.0532, wR2 = 0.0966 Largest diff. peak/hole / e Å-3 0.19/-0.20

4) Cartesian Coordinates

Cartesian coordinates of 4.2a calculated at the B3LYP/6-311g** level of theory.

------H -5.29799 -4.09301 -0.48007 Atom X Y Z C -5.51882 2.049141 -0.45121 ------H -5.35053 2.127625 -1.52201 C 1.146731 -1.28115 0.162226 H -6.1124 1.159205 -0.23829 O 1.063996 -1.82391 1.231493 H -6.11177 2.91544 -0.14926 C -0.09841 -0.72907 -0.57536 C -4.57304 2.124635 1.846791 C -0.87917 0.187309 0.408266 H -5.23293 1.305868 2.126491 O -0.60777 0.293182 1.574766 H -3.69812 2.108581 2.494583 C -2.05618 1.149444 0.083685 H -5.11084 3.056851 2.032418 C -1.8236 2.665415 0.102727 C -0.93689 3.114345 -1.07714 C -4.22701 2.076436 0.353396 H -0.95032 4.206004 -1.11541 C -3.26971 3.19266 -0.07774 H 0.100743 2.806905 -0.9459 H -3.44302 3.43461 -1.12879 H -1.30511 2.748689 -2.03808 H -3.43757 4.100989 0.500554 C -1.17057 3.157177 1.417152 N -3.30961 0.822424 0.098355 H -1.73159 2.8662 2.303508 C -3.85361 -0.5417 -0.03547 H -0.15161 2.787517 1.527104 C -3.93703 -1.38783 1.094854 H -1.13151 4.248176 1.380574 C -4.28995 -0.947 -1.3249 C 0.264849 0.006132 -1.86819 C -4.46074 -2.67043 0.888761 H -0.61959 0.428253 -2.34526 C -4.80211 -2.24107 -1.44562 H 0.970409 0.81218 -1.68159 C -4.8894 -3.09702 -0.35696 H 0.709781 -0.68465 -2.58635 H -4.5409 -3.34292 1.733369 C -0.95927 -1.99147 -0.87501 H -5.14291 -2.58325 -2.41469 H -1.19812 -2.53104 0.040024

127

H -1.8848 -1.71976 -1.37368 H -6.39161 0.368754 -2.53265 H -0.40897 -2.65751 -1.54183 H -5.59011 0.793458 -4.05111 C 2.555333 -1.45079 -0.44511 H -5.96139 -0.88581 -3.6873 C 2.964239 -2.82008 -0.99189 H -2.23857 -0.73948 -3.29614 C 4.916986 -1.29366 -0.73076 H -3.57209 -1.67692 -3.96564 C 4.491237 -2.77113 -0.75546 H -3.26897 -0.04194 -4.54528 H 5.034493 -3.3271 -1.51945 C -3.52482 -1.02742 2.523337 H 4.713938 -3.23249 0.209025 C -2.42332 -1.96188 3.065806 N 3.540889 -0.61979 -0.32137 C -4.73823 -1.06644 3.477716 C 2.339343 -4.01371 -0.2447 H -3.12044 -0.01517 2.532151 H 2.804781 -4.92741 -0.62165 H -1.52021 -1.94859 2.454919 H 2.511292 -3.96074 0.830119 H -2.14186 -1.6478 4.073619 H 1.265525 -4.09899 -0.41737 H -2.77501 -2.9938 3.133593 C 2.586998 -2.92027 -2.49336 H -5.58317 -0.48113 3.111266 H 1.5058 -2.97317 -2.63194 H -5.09245 -2.08979 3.620448 H 2.970954 -2.09349 -3.09026 H -4.45547 -0.67856 4.459065 H 3.007812 -3.84544 -2.89208 C 3.666771 1.932288 -2.04405 C 5.419034 -0.83053 -2.10206 C 5.055161 2.573926 -2.28548 H 5.78164 0.191877 -2.08709 C 2.630394 2.716099 -2.87426 H 6.267917 -1.46761 -2.35985 H 3.680445 0.914144 -2.43086 H 4.681012 -0.93795 -2.89573 H 5.832294 2.159774 -1.64103 C 5.973617 -1.00049 0.326288 H 5.361541 2.443147 -3.32619 H 6.907404 -1.47045 0.008791 H 5.017831 3.647327 -2.08606 H 6.161933 0.069339 0.429417 H 1.623172 2.304801 -2.80466 H 5.708518 -1.4154 1.296034 H 2.584413 3.766774 -2.58126 C 3.406045 0.729118 0.285959 H 2.919884 2.691652 -3.92743 C 3.320976 0.817104 1.701967 C 3.48541 -0.33287 2.700051 C 3.382374 1.886201 -0.53981 C 2.295176 -0.44934 3.676371 C 3.134237 2.090569 2.252912 C 4.7817 -0.15674 3.525177 C 3.189516 3.118572 0.092021 H 3.55342 -1.2756 2.153959 C 3.056492 3.227554 1.46778 H 1.33586 -0.48948 3.165349 H 3.068273 2.185926 3.328833 H 2.401992 -1.35893 4.271856 H 3.174098 4.017248 -0.51119 H 2.277483 0.391014 4.374202 H 2.923659 4.19996 1.927509 H 5.666617 -0.00526 2.907609 C -4.23408 -0.09709 -2.6001 H 4.700494 0.703605 4.193045 C -5.62928 0.056053 -3.24567 H 4.946168 -1.0386 4.149191 C -3.26715 -0.67519 -3.65481 ------H -3.8698 0.899658 -2.34288

Cartesian coordinates of 4.4 calculated at the B3LYP/6-311g** level of theory.

------C -2.74839 -3.36158 0.257463 Atom X Y Z C -2.99532 -2.6092 -1.99629 ------C -2.81875 -3.647 -1.09607 C 1.19963 1.160425 -0.69483 H -2.57351 -4.16812 0.959682 O 0.892985 0.118093 -1.28531 H -3.01895 -2.82687 -3.0576 C -0.00172 2.130686 -0.3889 H -2.71788 -4.66778 -1.44836 C -1.11536 1.219265 0.264297 C -5.87348 -0.03581 -0.18748 O -0.73448 0.25253 0.92981 H -5.75966 0.172054 -1.24956 C -2.5684 1.439906 0.151934 H -5.82115 -1.1153 -0.03595 C -3.37862 2.719911 0.473656 H -6.86881 0.300322 0.116385 C -4.82643 0.707896 0.649247 C -5.14861 0.447183 2.135527 C -4.82872 2.207491 0.329197 H -5.24419 -0.61744 2.335651 H -5.14802 2.348992 -0.70758 H -4.39584 0.853719 2.808102 H -5.52111 2.764379 0.964546 H -6.10747 0.915109 2.377443 N -3.41143 0.336608 0.284068 C -3.23768 3.950426 -0.44326 C -3.10912 -1.00814 -0.17952 H -4.00237 4.680174 -0.15687 C -2.87658 -2.0568 0.744254 H -2.27258 4.447686 -0.35111 C -3.13869 -1.28483 -1.5711 H -3.40319 3.696079 -1.4923

128

C -3.09906 3.187084 1.929106 H 2.520681 -4.52352 1.849327 H -3.11662 2.363107 2.640768 C -3.26478 -0.2233 -2.66297 H -2.12154 3.661295 2.014259 C -4.45337 -0.46415 -3.61576 H -3.85074 3.921771 2.235357 C -1.9617 -0.15377 -3.48581 C 0.304748 3.246255 0.624037 H -3.40509 0.746275 -2.18287 H -0.58239 3.849215 0.813043 H -5.40342 -0.56599 -3.0885 H 0.63863 2.831189 1.577221 H -4.54391 0.369214 -4.31933 H 1.065249 3.93079 0.257512 H -4.30983 -1.37292 -4.20658 C -0.41906 2.708312 -1.75884 H -1.08646 -0.06408 -2.84244 H -0.46119 1.913289 -2.49967 H -1.83699 -1.05844 -4.0882 H -1.3892 3.190674 -1.72875 H -1.98946 0.698087 -4.17301 H 0.304832 3.449777 -2.10138 C -2.70222 -1.86384 2.247661 C 2.616566 1.378549 -0.38959 C -1.28063 -2.26084 2.692971 C 3.480985 2.649063 -0.55541 C -3.73234 -2.66918 3.067179 C 4.903913 0.594344 -0.56133 H -2.82161 -0.80347 2.4631 C 4.802363 2.03335 -1.08292 H -0.53072 -1.72706 2.115134 H 5.670026 2.632769 -0.7975 H -1.14252 -2.02249 3.752836 H 4.766238 2.00936 -2.17542 H -1.11596 -3.33597 2.573015 N 3.452749 0.26871 -0.31835 H -4.75917 -2.51668 2.728187 C 2.990022 3.648827 -1.62097 H -3.52991 -3.74222 3.003319 H 3.802444 4.343641 -1.85671 H -3.67874 -2.39065 4.124098 H 2.708806 3.135754 -2.54325 C 3.068932 0.019929 2.636387 H 2.143689 4.250489 -1.29293 C 4.122173 -0.17973 3.743818 C 3.751938 3.414536 0.764465 C 1.691721 0.291691 3.272337 H 2.844642 3.840428 1.188729 H 3.338669 0.910712 2.07377 H 4.201343 2.777617 1.525434 H 5.110792 -0.40939 3.342833 H 4.447814 4.237302 0.569023 H 4.203704 0.727983 4.350061 C 5.773454 0.474668 0.703481 H 3.84186 -0.99292 4.418512 H 5.748093 -0.54381 1.094258 H 0.920858 0.419491 2.51258 H 6.809895 0.706099 0.44373 H 1.388845 -0.53965 3.915827 H 5.469385 1.154675 1.495967 H 1.7359 1.192181 3.894717 C 5.534883 -0.30877 -1.62813 C 2.779514 -2.12145 -2.10858 H 6.537167 0.064398 -1.85894 C 1.369371 -2.56862 -2.55182 H 5.637436 -1.33306 -1.26952 C 3.819275 -3.00909 -2.82338 H 4.951846 -0.31049 -2.54853 H 2.902152 -1.08703 -2.42725 C 3.088703 -1.02247 0.246865 H 0.599252 -2.0096 -2.02787 C 2.895301 -2.15704 -0.58385 H 1.249618 -2.40269 -3.6275 C 2.997267 -1.15241 1.657896 H 1.220357 -3.63661 -2.36497 C 2.711282 -3.40226 0.026796 H 4.847967 -2.77262 -2.55195 C 2.787948 -2.42185 2.204898 H 3.654437 -4.06627 -2.59627 C 2.669201 -3.54577 1.403932 H 3.7232 -2.89393 -3.90758 H 2.57051 -4.2758 -0.59889 ------H 2.715682 -2.5269 3.281046

Cartesian coordinates of S,E-4.3a calculated at the B3LYP/6-311g** level of theory.

------H -3.43757 4.100989 0.500554 Atom X Y Z N -3.30961 0.822424 0.098355 ------C -3.85361 -0.5417 -0.03547 C 1.146731 -1.28115 0.162226 C -3.93703 -1.38783 1.094854 O 1.063996 -1.82391 1.231493 C -4.28995 -0.947 -1.3249 C -0.09841 -0.72907 -0.57536 C -4.46074 -2.67043 0.888761 C -0.87917 0.187309 0.408266 C -4.80211 -2.24107 -1.44562 O -0.60777 0.293182 1.574766 C -4.8894 -3.09702 -0.35696 C -2.05618 1.149444 0.083685 H -4.5409 -3.34292 1.733369 C -1.8236 2.665415 0.102727 H -5.14291 -2.58325 -2.41469 C -4.22701 2.076436 0.353396 H -5.29799 -4.09301 -0.48007 C -3.26971 3.19266 -0.07774 C -5.51882 2.049141 -0.45121 H -3.44302 3.43461 -1.12879 H -5.35053 2.127625 -1.52201

129

H -6.1124 1.159205 -0.23829 C 3.134237 2.090569 2.252912 H -6.11177 2.91544 -0.14926 C 3.189516 3.118572 0.092021 C -4.57304 2.124635 1.846791 C 3.056492 3.227554 1.46778 H -5.23293 1.305868 2.126491 H 3.068273 2.185926 3.328833 H -3.69812 2.108581 2.494583 H 3.174098 4.017248 -0.51119 H -5.11084 3.056851 2.032418 H 2.923659 4.19996 1.927509 C -0.93689 3.114345 -1.07714 C -4.23408 -0.09709 -2.6001 H -0.95032 4.206004 -1.11541 C -5.62928 0.056053 -3.24567 H 0.100743 2.806905 -0.9459 C -3.26715 -0.67519 -3.65481 H -1.30511 2.748689 -2.03808 H -3.8698 0.899658 -2.34288 C -1.17057 3.157177 1.417152 H -6.39161 0.368754 -2.53265 H -1.73159 2.8662 2.303508 H -5.59011 0.793458 -4.05111 H -0.15161 2.787517 1.527104 H -5.96139 -0.88581 -3.6873 H -1.13151 4.248176 1.380574 H -2.23857 -0.73948 -3.29614 C 0.264849 0.006132 -1.86819 H -3.57209 -1.67692 -3.96564 H -0.61959 0.428253 -2.34526 H -3.26897 -0.04194 -4.54528 H 0.970409 0.81218 -1.68159 C -3.52482 -1.02742 2.523337 H 0.709781 -0.68465 -2.58635 C -2.42332 -1.96188 3.065806 C -0.95927 -1.99147 -0.87501 C -4.73823 -1.06644 3.477716 H -1.19812 -2.53104 0.040024 H -3.12044 -0.01517 2.532151 H -1.8848 -1.71976 -1.37368 H -1.52021 -1.94859 2.454919 H -0.40897 -2.65751 -1.54183 H -2.14186 -1.6478 4.073619 C 2.555333 -1.45079 -0.44511 H -2.77501 -2.9938 3.133593 C 2.964239 -2.82008 -0.99189 H -5.58317 -0.48113 3.111266 C 4.916986 -1.29366 -0.73076 H -5.09245 -2.08979 3.620448 C 4.491237 -2.77113 -0.75546 H -4.45547 -0.67856 4.459065 H 5.034493 -3.3271 -1.51945 C 3.666771 1.932288 -2.04405 H 4.713938 -3.23249 0.209025 C 5.055161 2.573926 -2.28548 N 3.540889 -0.61979 -0.32137 C 2.630394 2.716099 -2.87426 C 2.339343 -4.01371 -0.2447 H 3.680445 0.914144 -2.43086 H 2.804781 -4.92741 -0.62165 H 5.832294 2.159774 -1.64103 H 2.511292 -3.96074 0.830119 H 5.361541 2.443147 -3.32619 H 1.265525 -4.09899 -0.41737 H 5.017831 3.647327 -2.08606 C 2.586998 -2.92027 -2.49336 H 1.623172 2.304801 -2.80466 H 1.5058 -2.97317 -2.63194 H 2.584413 3.766774 -2.58126 H 2.970954 -2.09349 -3.09026 H 2.919884 2.691652 -3.92743 H 3.007812 -3.84544 -2.89208 C 3.48541 -0.33287 2.700051 C 5.419034 -0.83053 -2.10206 C 2.295176 -0.44934 3.676371 H 5.78164 0.191877 -2.08709 C 4.7817 -0.15674 3.525177 H 6.267917 -1.46761 -2.35985 H 3.55342 -1.2756 2.153959 H 4.681012 -0.93795 -2.89573 H 1.33586 -0.48948 3.165349 C 5.973617 -1.00049 0.326288 H 2.401992 -1.35893 4.271856 H 6.907404 -1.47045 0.008791 H 2.277483 0.391014 4.374202 H 6.161933 0.069339 0.429417 H 5.666617 -0.00526 2.907609 H 5.708518 -1.4154 1.296034 H 4.700494 0.703605 4.193045 C 3.406045 0.729118 0.285959 H 4.946168 -1.0386 4.149191 C 3.320976 0.817104 1.701967 ------C 3.382374 1.886201 -0.53981

Cartesian coordinates of R,E-4.3a calculated at the B3LYP/6-311g** level of theory.

------H -2.14072 -1.09544 3.284746 Atom X Y Z H -3.3398 -2.37441 3.116325 ------C 0.55741 -0.2847 0.383504 O -0.68291 -0.06709 1.021679 C 1.660974 0.815669 2.419656 C 0.282946 -0.93754 -0.96507 C 3.157617 1.069273 2.687312 C -1.75228 -0.97118 0.513288 C 3.940671 0.065203 1.830759 C -1.90794 -2.23649 1.46571 H 3.421545 2.079897 2.365754 C -3.72571 -0.59393 1.887928 H 3.404887 0.989093 3.74875 C -2.78121 -1.61272 2.56664 C 1.686764 0.124205 1.015606

130

N 3.06069 -0.03494 0.605091 C -3.61719 0.550218 -0.42822 N -3.04531 -0.35943 0.558343 C -4.50634 0.055624 -1.43277 C -3.83884 0.661542 2.767799 C -3.37738 1.954704 -0.37369 H -4.50639 1.399376 2.321465 C -5.13572 0.958599 -2.29645 H -4.26226 0.379701 3.736782 C -4.03892 2.80328 -1.2693 H -2.86808 1.121934 2.94851 C -4.92055 2.322808 -2.21963 C -5.15136 -1.14448 1.720592 H -5.81196 0.574387 -3.0507 H -5.5968 -1.30241 2.706661 H -3.85276 3.869343 -1.21475 H -5.7788 -0.42796 1.187781 H -5.4268 3.001431 -2.89765 H -5.17757 -2.09171 1.185889 C 2.843892 2.628444 -0.83707 C -0.59721 -2.798 2.029144 C 1.984097 3.335486 -1.90442 H -0.02733 -3.33132 1.264793 C 3.815911 3.666448 -0.23826 H 0.035346 -2.02918 2.454994 H 2.173306 2.294954 -0.04888 H -0.83309 -3.52198 2.815517 H 1.310885 2.648318 -2.41568 C -2.63886 -3.41502 0.790535 H 1.378695 4.114385 -1.43446 H -2.80118 -4.19139 1.544595 H 2.602771 3.823989 -2.66215 H -3.60666 -3.14394 0.379808 H 4.402738 3.263913 0.587107 H -2.04873 -3.85095 -0.01612 H 4.514889 4.026492 -0.99895 C 1.047897 -0.02648 3.559268 H 3.260095 4.53049 0.138959 H -0.01993 -0.16449 3.404711 C 4.571841 -2.32063 -0.71351 H 1.515784 -1.00457 3.666399 C 5.997105 -2.59235 -0.18227 H 1.183701 0.507121 4.505314 C 4.266678 -3.4377 -1.74087 C 0.909944 2.162119 2.422226 H 3.863455 -2.41873 0.109452 H 1.042214 2.646878 3.395858 H 6.308946 -1.90194 0.599068 H 1.290438 2.844282 1.66188 H 6.05761 -3.60582 0.226411 H -0.15507 2.017608 2.256564 H 6.727708 -2.52065 -0.99302 C 5.345607 0.608757 1.551364 H 3.330454 -3.28783 -2.27543 H 5.878907 0.690048 2.50288 H 5.062774 -3.519 -2.48588 H 5.9282 -0.03514 0.896781 H 4.210025 -4.40155 -1.2265 H 5.31739 1.597672 1.0973 C -4.83506 -1.4161 -1.6847 C 4.05812 -1.29635 2.55403 C -4.42204 -1.85445 -3.10591 H 4.756867 -1.96131 2.050443 C -6.33299 -1.73351 -1.48923 H 4.421975 -1.15045 3.575588 H -4.25532 -2.00913 -0.98543 H 3.095412 -1.80459 2.605459 H -3.37963 -1.62049 -3.31001 C 0.32435 0.033418 -2.17275 H -4.54905 -2.93633 -3.21098 H 1.34665 0.356233 -2.36101 H -5.04545 -1.37488 -3.86649 H -0.04804 -0.48846 -3.05758 H -6.70783 -1.42457 -0.51362 H -0.30326 0.910035 -2.00908 H -6.94358 -1.23762 -2.24924 C 1.135267 -2.16653 -1.30172 H -6.50162 -2.81032 -1.59013 H 2.124345 -1.84371 -1.60362 C -2.40529 2.645994 0.579835 H 1.234554 -2.84709 -0.45528 C -3.07617 3.741087 1.434477 H 0.672386 -2.70306 -2.13324 C -1.23406 3.270857 -0.19971 C -1.17801 -1.3767 -0.84207 H -1.98706 1.888787 1.23635 O -1.76376 -2.00544 -1.68623 H -3.9689 3.383682 1.948185 C 3.649179 0.145525 -0.70201 H -2.37505 4.10572 2.191542 C 3.580238 1.400315 -1.37753 H -3.36959 4.600336 0.824712 C 4.414081 -0.90812 -1.29457 H -0.64571 2.508839 -0.70865 C 4.256799 1.564691 -2.5898 H -1.58751 3.983276 -0.9502 C 5.083332 -0.66971 -2.50055 H -0.56927 3.808295 0.480792 C 5.013107 0.5492 -3.15186 ------H 4.206818 2.522296 -3.09375 H 5.669287 -1.46735 -2.94194 H 5.541173 0.70711 -4.08571

131

Cartesian coordinates of S,Z-4.3a calculated at the B3LYP/6-31g* level of theory.

------C 3.483095 3.377044 -0.39027 Atom X Y Z H 3.068377 3.697634 1.680615 ------H 3.911268 2.725682 -2.3826 O -0.08994 0.178988 -0.24446 H 3.688495 4.424281 -0.5967 C -0.71256 -1.74531 -1.53047 C 2.584401 1.323488 2.661946 C -1.40159 0.589909 -0.81494 C 1.416138 2.105855 3.289341 C -1.73115 2.987904 -0.28674 C 3.855164 1.626433 3.493046 C -2.79274 2.140828 0.436908 H 2.336297 0.268555 2.7503 H -2.80827 2.342677 1.516692 H 0.458462 1.832014 2.848557 H -3.80057 2.361938 0.055246 H 1.366848 1.886573 4.363337 C 0.370726 -1.08979 -0.65517 H 1.538997 3.189706 3.184388 C 2.179819 -2.97223 -0.50039 H 4.765285 1.224485 3.037508 C 3.167912 -3.0609 0.674856 H 3.999965 2.70881 3.591968 C 3.670748 -1.65316 1.028811 H 3.764469 1.213192 4.505126 H 2.640924 -3.47407 1.542254 C 3.629947 0.122325 -2.31373 H 3.997747 -3.74237 0.454938 C 5.099972 0.223637 -2.7779 C 1.623268 -1.52398 -0.31425 C 2.70197 0.337931 -3.52204 N 2.610505 -0.75849 0.42297 H 3.463155 -0.88952 -1.96414 C -0.53869 3.26058 0.643697 H 5.80244 0.130014 -1.94459 H 0.196504 3.91705 0.167541 H 5.322084 -0.56866 -3.50388 H -0.88056 3.755852 1.560373 H 5.300639 1.181521 -3.27128 H -0.02423 2.340371 0.915133 H 1.657537 0.174546 -3.25081 C -2.31521 4.348187 -0.7079 H 2.790436 1.353485 -3.92542 H -2.53672 4.943689 0.186389 H 2.959425 -0.36179 -4.32696 H -1.59814 4.921752 -1.30718 C -1.32141 2.041387 -1.4853 H -3.24239 4.256833 -1.27995 C -2.32327 2.206299 -2.65289 C 2.936883 -3.23696 -1.83248 H -2.1164 1.506445 -3.46257 H 2.359444 -2.94077 -2.71043 H -3.36714 2.069227 -2.36146 H 3.902674 -2.73141 -1.87859 H -2.21916 3.218181 -3.05719 H 3.143872 -4.31158 -1.91421 C 0.064125 2.355533 -2.05297 C 1.198621 -4.14477 -0.30387 H 0.866498 2.152729 -1.34921 H 1.781561 -5.04534 -0.07372 H 0.247623 1.768768 -2.95856 H 0.514192 -3.9673 0.52969 H 0.115047 3.411853 -2.34389 H 0.619719 -4.37482 -1.19814 N -2.42923 0.747864 0.178491 C 3.781701 -1.62625 2.569967 C -3.19601 -0.29157 0.819299 H 4.381329 -2.49225 2.878233 C -2.7344 -0.85062 2.039591 H 4.283524 -0.74069 2.95496 C -4.45298 -0.69826 0.291696 H 2.799677 -1.72303 3.042377 C -3.47747 -1.87231 2.64532 C 5.077344 -1.37032 0.467914 C -5.15798 -1.72011 0.941006 H 5.371593 -0.33077 0.643366 C -4.67126 -2.32215 2.095041 H 5.807489 -2.01272 0.973176 H -3.12042 -2.31008 3.573511 H 5.148903 -1.56521 -0.60308 H -6.11394 -2.04142 0.537423 C -0.28249 -2.27692 -2.91291 H -5.23288 -3.11847 2.577174 H 0.247673 -3.22637 -2.83715 C -5.12065 -0.01986 -0.9015 H -1.18125 -2.43478 -3.51688 C -6.28983 0.869786 -0.42532 H 0.359758 -1.56579 -3.43993 C -5.61461 -1.00884 -1.9737 C -1.62897 -2.81034 -0.84095 H -4.37696 0.617049 -1.37951 H -1.20184 -3.80756 -0.91016 H -5.96814 1.599504 0.325745 H -1.80741 -2.58057 0.210043 H -6.72295 1.418511 -1.27068 H -2.59425 -2.83228 -1.35538 H -7.08707 0.264871 0.023775 C -1.66838 -0.57347 -1.78083 H -4.80062 -1.64213 -2.33453 O -2.54971 -0.60304 -2.61249 H -6.42012 -1.6525 -1.60071 C 2.911377 0.639323 0.14782 H -6.01206 -0.45493 -2.83244 C 2.844933 1.62124 1.184007 C -1.5037 -0.3277 2.770217 C 3.343344 1.064483 -1.14749 C -0.48569 -1.43399 3.098598 C 3.126869 2.961775 0.88371 C -1.93176 0.415725 4.053308 C 3.598335 2.420371 -1.38782 H -1.00624 0.381052 2.106477

132

H -0.13029 -1.9233 2.186699 H -1.06071 0.843859 4.562143 H 0.383712 -1.00471 3.609848 ------H -0.9079 -2.19998 3.760187 H -2.62896 1.231175 3.829622 H -2.43118 -0.2613 4.756774

Cartesian coordinates of R,Z-4.3a calculated at the B3LYP/6-31g* level of theory.

------C -1.20602 -2.79716 -1.48946 Atom X Y Z H -0.56049 -3.40159 -2.12925 ------H -2.03608 -3.43257 -1.16404 O -0.05447 0.02333 0.271415 H -1.61557 -1.97242 -2.07993 C -0.44761 -2.28965 -0.23788 C 0.162023 -3.49509 0.522888 C -1.30373 -0.26143 1.030604 H 0.906662 -4.02028 -0.06937 C -1.06733 0.041945 2.571181 H 0.636176 -3.17459 1.453567 C -2.71056 1.672318 1.666269 H -0.64258 -4.19262 0.77539 C -1.54584 1.504454 2.658477 C -1.51122 -1.74417 0.715072 H -0.72209 2.168403 2.379582 O -2.38055 -2.43528 1.198572 H -1.84275 1.770508 3.678638 C 3.053938 0.542016 0.504473 C 0.489349 -1.08689 -0.40922 C 3.669524 -0.3052 1.474384 C 2.262971 -1.91852 -2.17099 C 2.931995 1.931258 0.780186 C 3.673425 -1.3287 -2.40255 C 4.115556 0.256246 2.67801 C 3.650028 0.133182 -1.92686 C 3.409344 2.438018 1.996351 H 4.404015 -1.88053 -1.79947 C 3.995071 1.613927 2.947065 H 3.979801 -1.42724 -3.45002 H 4.589294 -0.38698 3.414692 C 1.723356 -1.01511 -1.00076 H 3.319017 3.501983 2.19819 N 2.655479 0.059593 -0.79833 H 4.360322 2.024321 3.885008 N -2.43387 0.569259 0.676556 C -3.22942 0.414063 -0.5344 C -2.70066 3.079536 1.045058 C -4.43506 -0.36192 -0.55088 H -3.50689 3.191928 0.313689 C -2.83951 1.085927 -1.73315 H -2.86769 3.821786 1.83458 C -5.17366 -0.44424 -1.74061 H -1.7537 3.315289 0.561462 C -3.6224 0.956079 -2.8886 C -4.07771 1.539853 2.367424 C -4.78291 0.19921 -2.90423 H -4.17188 2.329852 3.121609 H -6.0848 -1.03455 -1.74827 H -4.89012 1.678236 1.650758 H -3.31218 1.469213 -3.79407 H -4.2169 0.581908 2.868389 H -5.37793 0.114316 -3.81014 C 0.397703 -0.07023 3.001626 C 3.928073 -1.80342 1.287585 H 0.751298 -1.10374 2.939469 C 3.333592 -2.65314 2.429144 H 1.056264 0.553319 2.39996 C 5.432787 -2.13454 1.17798 H 0.489278 0.237866 4.05043 H 3.444236 -2.11738 0.363608 C -1.89031 -0.86775 3.511773 H 2.278521 -2.4304 2.597334 H -1.81917 -0.46412 4.528914 H 3.423661 -3.7202 2.192772 H -2.94327 -0.94004 3.244091 H 3.861131 -2.48399 3.37493 H -1.49428 -1.88696 3.5311 H 5.913792 -1.64457 0.327395 C 1.430022 -1.76929 -3.47066 H 5.970146 -1.8275 2.082703 H 0.400619 -2.10101 -3.34035 H 5.572675 -3.21628 1.060495 H 1.396824 -0.74161 -3.83214 C 2.300703 2.923643 -0.19304 H 1.88049 -2.38222 -4.26208 C 3.304104 3.983838 -0.69188 C 2.433145 -3.43475 -1.92379 C 1.087541 3.62954 0.434353 H 3.077804 -3.84485 -2.71159 H 1.935237 2.352641 -1.04829 H 2.90943 -3.65479 -0.96405 H 4.188812 3.540099 -1.15852 H 1.489874 -3.98266 -1.97812 H 2.827554 4.63945 -1.43116 C 5.054802 0.57763 -1.49622 H 3.652919 4.617595 0.132311 H 5.714169 0.535475 -2.371 H 0.357795 2.892062 0.769914 H 5.065822 1.603172 -1.12012 H 1.371165 4.247887 1.294572 H 5.478521 -0.06351 -0.72355 H 0.603461 4.286914 -0.29818 C 3.194018 1.097277 -3.04706 C -5.03761 -1.13748 0.626387 H 3.357461 2.139349 -2.76082 C -5.18659 -2.6438 0.315449 H 3.774209 0.914053 -3.95977 C -6.42967 -0.59751 1.026724 H 2.137689 0.982971 -3.28533 H -4.36567 -1.04886 1.478125

133

H -4.2457 -3.08914 -0.00866 H -2.7004 3.867409 -1.62434 H -5.51288 -3.17574 1.217148 H -1.06097 4.041639 -2.27274 H -5.94112 -2.81983 -0.46043 H -2.36305 3.448206 -3.30574 H -6.43117 0.476505 1.225929 H -0.27316 0.39679 -2.60008 H -7.16725 -0.78472 0.237551 H -1.06755 1.308531 -3.89965 H -6.78233 -1.10924 1.930514 H 0.257875 2.041765 -2.98881 C -1.60111 1.968563 -1.87523 ------C -1.95971 3.412858 -2.28689 C -0.61653 1.387354 -2.90321 H -1.08303 1.986302 -0.91762

Cartesian coordinates of 4.6 calculated at the B3LYP/6-311g** level of theory.

------H 0.87647 -2.33818 0.01242 Atom X Y Z H -0.79794 -1.95537 0.425589 ------H -0.41414 -2.61518 -1.17106 O -0.39289 1.012206 0.740962 C -1.24247 -0.06126 -1.42155 C 0.15874 -0.518 -0.94775 O -1.68816 -0.4082 -2.48995 C -2.16678 0.853533 -0.623 C 3.718056 -0.35371 -0.58866 C -3.39671 2.794463 0.119323 C 4.10093 0.741515 -1.4071 C -4.17017 1.488414 0.375076 C 4.037426 -1.68155 -0.96904 H -4.48562 1.368693 1.410253 C 4.730474 0.471233 -2.62514 H -5.04937 1.380583 -0.26461 C 4.697121 -1.88022 -2.18619 C 0.591341 0.384028 0.234935 C 5.029238 -0.82343 -3.01893 C 1.901414 1.345608 2.231574 H 5.013803 1.296973 -3.26669 C 3.391708 1.258507 2.621572 H 4.944762 -2.88932 -2.49169 C 3.959035 0.004142 1.950539 H 5.529777 -1.00698 -3.96254 H 3.925805 2.13574 2.248265 C 3.91028 2.211498 -1.03285 H 3.527411 1.234325 3.703776 C 2.859919 2.906853 -1.9185 C 1.854208 0.507549 0.923036 C 5.235546 3.000045 -1.08321 N 3.084415 -0.07103 0.691133 H 3.551635 2.257681 -0.00691 C -2.68346 3.23465 1.412598 H 1.880132 2.436627 -1.82345 H -2.1389 4.168351 1.259803 H 2.756975 3.957407 -1.63268 H -3.42468 3.416029 2.195245 H 3.147766 2.877023 -2.97274 H -1.97684 2.487168 1.77167 H 6.024181 2.519068 -0.501 C -4.34291 3.922666 -0.31907 H 5.602885 3.109548 -2.10619 H -5.012 4.182919 0.505389 H 5.085328 4.006106 -0.68234 H -3.78312 4.826026 -0.5739 C 3.696676 -2.9303 -0.15692 H -4.96393 3.652819 -1.17389 C 4.966418 -3.6049 0.404624 C 1.001872 0.794721 3.358507 C 2.911125 -3.97481 -0.97971 H -0.04628 0.864659 3.080578 H 3.067662 -2.62628 0.681322 H 1.22519 -0.24301 3.604715 H 5.590242 -2.91954 0.980022 H 1.158406 1.390638 4.262048 H 4.69777 -4.44422 1.052154 C 1.527576 2.830031 2.011584 H 5.583454 -3.99914 -0.40677 H 1.824665 3.398666 2.898128 H 2.049857 -3.54464 -1.49117 H 2.047177 3.261088 1.153639 H 3.544091 -4.44104 -1.73799 H 0.457359 2.956139 1.870649 H 2.552513 -4.7729 -0.32393 C 5.446379 0.16403 1.635542 C -2.36983 2.337164 -0.99839 H 5.986043 0.253842 2.581591 C -3.02606 2.354976 -2.40863 H 5.854693 -0.69214 1.099007 H -2.38078 1.880861 -3.14723 H 5.645505 1.061572 1.051745 H -3.99306 1.853267 -2.43832 C 3.753285 -1.24417 2.831852 H -3.17553 3.392822 -2.70925 H 4.27894 -2.11076 2.438432 C -1.09722 3.184474 -1.0862 H 4.154439 -1.04403 3.828483 H -0.5236 3.183032 -0.1662 H 2.700149 -1.50258 2.940063 H -0.4543 2.828032 -1.89492 C 1.026428 -0.5769 -2.21591 H -1.37177 4.21344 -1.33058 H 1.949018 -1.11655 -2.04853 N -3.214 0.402173 0.021963 H 0.463893 -1.09183 -2.99433 C -3.59455 -0.98775 0.292537 H 1.274117 0.419575 -2.58276 C -3.37232 -1.51998 1.581707 C -0.06237 -1.95092 -0.37923 C -4.28232 -1.71141 -0.70847

134

C -3.7847 -2.83465 1.817226 H -4.90686 -2.9635 -3.23474 C -4.65925 -3.02416 -0.40849 H -4.61317 -1.50743 -4.17732 C -4.40676 -3.58753 0.832257 C -2.77658 -0.72413 2.73976 H -3.62393 -3.27249 2.79379 C -1.69776 -1.51227 3.504576 H -5.17747 -3.60648 -1.1598 C -3.88329 -0.28457 3.722933 H -4.71389 -4.60608 1.039535 H -2.29925 0.169191 2.332074 C -4.72129 -1.12634 -2.04733 H -0.89382 -1.84643 2.845682 C -6.23843 -0.83972 -2.0325 H -1.25959 -0.8842 4.282279 C -4.35661 -2.01952 -3.24643 H -2.11441 -2.39201 3.999844 H -4.20141 -0.18309 -2.19778 H -4.68048 0.27771 3.231527 H -6.52875 -0.19183 -1.20092 H -4.34679 -1.15332 4.197593 H -6.54073 -0.35353 -2.96399 H -3.46306 0.344026 4.512542 H -6.8121 -1.76537 -1.93921 ------H -3.28921 -2.23966 -3.26965

Cartesian coordinates of 4.16 calculated at the B3LYP/6-31g** level of theory.

------H 0.820282 4.523787 0.945219 Atom X Y Z H 2.357847 3.786508 1.448502 ------H 1.805394 3.606241 -0.22136 C 2.409161 -0.21449 -1.97434 C 0.4753 2.330111 2.623915 C 1.961589 0.730953 -0.96276 H 1.403332 2.37386 3.209198 C 2.963235 0.721442 0.092326 H -0.16274 3.170124 2.949978 C 3.98692 -0.20195 -0.27838 H -0.03982 1.39791 2.842917 C 3.643543 -0.78069 -1.54696 C -0.99117 3.77784 -1.32261 H 1.875724 -0.42788 -2.88511 H -0.67284 4.774825 -0.97049 H 2.914844 1.302382 0.993647 H -0.27277 3.416616 -2.05466 H 4.869719 -0.42579 0.300201 H -1.95121 3.902827 -1.84309 H 4.222764 -1.51516 -2.08466 C -2.11714 3.25971 0.787923 Fe 2.101706 -1.12384 -0.14447 H -1.80411 4.180892 1.312087 C 1.737338 -3.14614 0.166607 H -3.08176 3.47094 0.30604 C 2.075546 -2.49939 1.402317 H -2.27012 2.463932 1.515579 C 0.571142 -2.4988 -0.36361 C -4.66857 -0.47382 0.096416 H 2.262834 -3.97546 -0.28101 H -5.34943 -0.84565 -0.68524 C 1.118915 -1.45567 1.634314 H -4.65307 -1.19523 0.914195 H 2.900683 -2.75677 2.048397 H -5.07645 0.476834 0.468744 C 0.157649 -1.45846 0.553109 C -3.19921 0.70881 -1.49477 H 0.070553 -2.74315 -1.28722 H -3.84086 0.40184 -2.33808 H 1.10108 -0.78606 2.478447 H -3.52831 1.70066 -1.16438 C 0.609767 1.288574 -1.04687 H -2.16775 0.791631 -1.83123 O -0.0453 1.119591 -2.10519 C -3.23566 -3.16069 -0.83377 C -0.13347 1.878902 0.182695 H -3.52743 -2.48215 -1.63694 O -0.85186 0.750328 0.885083 H -2.5593 -3.92417 -1.25042 C -1.00222 -0.57874 0.401585 H -4.13427 -3.67319 -0.46266 C -2.25363 -1.04701 0.053561 C -2.13055 -3.19283 1.377463 N 0.821244 2.380656 1.196699 H -2.96827 -3.79761 1.753731 N -1.15968 2.823915 -0.22611 H -1.30292 -3.87235 1.127627 N -3.31322 -0.27195 -0.41469 H -1.79408 -2.52434 2.171041 N -2.57903 -2.4057 0.232668 ------C 1.471556 3.641489 0.819877

Cartesian coordinates of 4.21a calculated at the B3LYP/6-311g** level of theory.

------C 3.53553 0.324906 -0.07072 Atom X Y Z C 3.462669 1.551516 -0.73301 ------C 2.22246 2.130332 -0.97308 C 1.054539 1.496021 -0.53766 H 0.101803 1.991439 -0.69387 C 1.107088 0.273692 0.133778 H 4.483767 -0.16516 0.115592 C 2.374529 -0.32461 0.329066 H 4.369087 2.045586 -1.06022

135

H 2.155377 3.083696 -1.48282 H -2.78399 2.419152 1.640532 N 2.596182 -1.65163 0.860831 H -2.37378 1.060747 2.719802 O 1.671844 -2.41779 0.721688 H -1.11352 1.857001 1.753832 C -0.13434 -0.22871 0.78659 C -2.64131 -0.30078 -2.15365 O -0.20213 -0.68184 1.899117 H -3.44649 -1.03709 -2.19278 C -1.48193 -0.05945 0.024034 H -3.04731 0.686392 -1.95232 N -2.44209 0.610274 0.651803 H -2.14755 -0.27979 -3.12652 N -1.61895 -0.65688 -1.15533 C -0.70881 -1.73276 -1.59823 C -3.88366 0.360306 0.465559 H -1.31601 -2.59431 -1.88451 H -4.04681 -0.5913 -0.03092 H -0.13419 -1.3981 -2.46415 H -4.33111 0.306797 1.459251 H -0.03576 -2.04079 -0.80173 H -4.36746 1.165457 -0.09068 ------C -2.15174 1.538695 1.764638

Cartesian coordinates of 4.21b calculated at the B3LYP/6-311g** level of theory.

------C 0.442733 -2.89298 -1.94124 Atom X Y Z C 2.736545 -2.32855 -1.07562 ------H 1.328715 -0.9639 -1.8632 C 0.184139 0.077214 -0.04084 H -0.59132 -2.57404 -2.0755 N 0.664867 -1.30503 0.043248 H 0.868334 -3.06649 -2.93378 N 1.217665 1.068849 -0.08413 H 0.446066 -3.84946 -1.41321 C -0.81683 0.187671 -1.27128 H 3.365982 -1.62575 -0.53085 O -0.49263 0.182711 -2.43848 H 2.81226 -3.303 -0.59343 N -0.83289 0.345992 1.106653 H 3.155006 -2.43205 -2.08137 O -0.50924 0.60802 2.303971 C 2.487776 0.832109 0.639557 C -2.18737 0.257977 -0.74549 C 2.606851 1.374233 2.080792 C -3.4047 0.287666 -1.41899 C 3.716157 1.24511 -0.186 C -2.13984 0.405421 0.646235 H 2.513879 -0.2514 0.733374 C -4.56903 0.457862 -0.67452 H 1.708632 1.157492 2.655857 H -3.42724 0.187689 -2.49773 H 3.45629 0.881662 2.566119 C -3.29603 0.592852 1.40655 H 2.795834 2.448004 2.115824 C -4.50569 0.611603 0.721526 H 3.663369 0.854187 -1.2038 H -5.53193 0.480839 -1.17042 H 3.828884 2.330834 -0.24004 H -3.23104 0.716291 2.479064 H 4.621358 0.853256 0.287659 H -5.42528 0.751523 1.278753 C 0.779711 2.419943 -0.51777 C 0.240091 -2.18109 1.164121 C 1.390978 2.857264 -1.86063 C 1.331893 -3.16291 1.617665 C 0.908681 3.529201 0.539287 C -1.08751 -2.94326 0.956043 H -0.2952 2.330191 -0.6975 H 0.092817 -1.51295 2.009119 H 1.25374 2.079172 -2.61196 H 2.284472 -2.65769 1.784306 H 0.893963 3.76736 -2.21163 H 1.020028 -3.61356 2.563898 H 2.456072 3.076502 -1.77323 H 1.486875 -3.97815 0.908409 H 0.48001 3.222667 1.494369 H -1.88593 -2.28688 0.608762 H 1.947341 3.824303 0.700537 H -0.98582 -3.75923 0.238764 H 0.371164 4.415629 0.190142 H -1.40828 -3.37836 1.90781 ------C 1.281176 -1.83056 -1.20762

Cartesian coordinates of 4.22a calculated at the B3LYP/6-311g** level of theory.

------C 3.848562 0.889485 0.355192 Atom X Y Z C 2.84071 1.720611 0.864284 ------H 0.748005 1.942329 1.286201 C 1.516646 1.300713 0.870903 H 4.221471 -1.02572 -0.58026 C 1.12306 0.045137 0.380653 H 4.885418 1.210008 0.358934 C 2.150168 -0.76713 -0.16378 H 3.096178 2.697536 1.265559 C 3.491081 -0.3451 -0.15468 N 1.98027 -2.02397 -0.81587

136

O 0.825788 -2.37262 -1.0323 H -3.00236 2.310683 -0.76181 C -0.28561 -0.46049 0.655299 H -1.80221 2.839904 0.435835 O -0.37109 -1.47882 1.400003 C -2.99582 -1.50257 -0.27854 C -1.34335 0.246265 0.095121 H -2.73246 -1.51069 -1.33815 N -1.10393 1.322749 -0.82137 H -2.42823 -2.29675 0.225518 N -2.71153 -0.17695 0.286027 H -4.07092 -1.71619 -0.19362 C -1.08703 0.949964 -2.23529 C -3.16432 -0.10173 1.675168 H -2.09339 0.718279 -2.63549 H -4.24592 -0.29465 1.723623 H -0.67041 1.769097 -2.83776 H -2.64383 -0.81883 2.326429 H -0.45804 0.068826 -2.36007 H -2.98375 0.905904 2.05932 C -1.92721 2.499602 -0.59622 ------H -1.61214 3.310348 -1.26605

Cartesian coordinates of 4.22b calculated at the B3LYP/6-311g** level of theory.

------C 1.660235 2.545122 -1.08206 Atom X Y Z C -0.30656 2.015875 -2.57578 ------H 0.940416 0.609381 -1.60298 C 2.348822 -0.00738 1.549986 H 2.291393 2.199065 -0.26296 C 1.877742 -0.70047 0.423723 H 2.278906 2.621068 -1.98267 C 2.864732 -1.19038 -0.47806 H 1.304661 3.553217 -0.84598 C 4.234307 -1.01961 -0.20464 H -1.17878 1.378807 -2.72853 C 4.664049 -0.35498 0.928725 H -0.64433 3.052474 -2.51648 C 3.703792 0.162925 1.810472 H 0.33059 1.927134 -3.46301 H 1.618516 0.363282 2.259343 C -2.46144 -0.84259 -1.11043 H 4.930512 -1.42459 -0.93204 C -3.75637 -0.10718 -1.50659 H 5.72323 -0.23592 1.133178 C -2.54453 -2.35694 -1.37897 H 4.017075 0.686481 2.709122 H -1.68837 -0.47197 -1.7838 N 2.62414 -1.80394 -1.7329 H -3.66036 0.963402 -1.30971 O 1.44304 -1.87353 -2.08721 H -3.94903 -0.24352 -2.57772 C 0.423502 -1.09678 0.339031 H -4.63469 -0.46861 -0.96723 O 0.197735 -2.34551 0.415331 H -1.59989 -2.82132 -1.09139 C -0.55978 -0.1128 0.221014 H -3.36042 -2.83481 -0.82634 N -0.28794 1.250259 -0.12074 H -2.7257 -2.5311 -2.44594 N -1.95345 -0.4786 0.247567 C -2.41287 -1.32116 1.378199 C -0.97796 2.269446 0.684944 C -3.9363 -1.21779 1.575802 C -1.65655 3.410052 -0.0925 C -1.72512 -0.93646 2.693763 C -0.10594 2.85153 1.817226 H -2.15371 -2.36999 1.192677 H -1.79209 1.716862 1.159998 H -4.49817 -1.61668 0.730673 H -2.33099 3.021879 -0.85743 H -4.2321 -1.79201 2.460562 H -2.24736 4.013239 0.605401 H -4.2386 -0.17538 1.72329 H -0.93958 4.081184 -0.57311 H -0.66352 -1.16984 2.662592 H 0.307238 2.047151 2.426772 H -1.85401 0.128352 2.915384 H 0.726161 3.446274 1.431409 H -2.17688 -1.50842 3.511967 H -0.70761 3.495607 2.471224 ------C 0.499898 1.565845 -1.32866

Cartesian coordinates of 4.23a calculated at the B3LYP/6-311g** level of theory.

------H 1.809678 -0.96863 3.111814 Atom X Y Z H 0.512601 0.130663 2.661737 ------C 2.699612 -1.58778 0.761388 C 0.97703 -0.02543 -0.03388 H 3.477131 -1.61732 1.52991 N 1.768108 -0.505 1.091555 H 2.212727 -2.57189 0.715599 N 1.835822 0.49897 -1.05539 H 3.160226 -1.3917 -0.20388 C 1.061717 -0.7545 2.345402 C 1.205161 0.80217 -2.33541 H 0.373417 -1.61507 2.305163 H 0.530835 1.672872 -2.28982

137

H 1.990109 1.027404 -3.06048 C -2.5984 -1.28002 -0.6138 H 0.651432 -0.05836 -2.71079 C -1.3393 0.598117 0.269116 C 2.77402 1.54838 -0.6416 C -3.76981 -0.59864 -0.2962 H 3.613593 1.557907 -1.34292 H -2.61654 -2.25948 -1.07711 H 2.309765 2.542844 -0.6287 C -2.50539 1.295486 0.591929 H 3.143268 1.331296 0.357402 C -3.71386 0.674188 0.299303 C -0.00639 -1.12399 -0.58914 H -4.73322 -1.04639 -0.50799 O 0.351068 -2.16804 -1.08675 H -2.44812 2.273104 1.051145 N -0.02984 1.005035 0.483545 H -4.64009 1.184998 0.538051 O 0.299474 2.112683 1.004068 ------C -1.37935 -0.67171 -0.32808

Cartesian coordinates of 4.23b calculated at the B3LYP/6-311g** level of theory.

------C 3.263576 2.258568 0.470929 Atom X Y Z C 2.551942 0.449794 1.979647 ------H 1.514001 2.258767 1.724317 C 0.198922 0.022154 0.083876 H 3.035954 3.118514 -0.14842 N 1.07242 1.208924 -0.05344 H 3.901764 2.602802 1.288852 N 0.933841 -1.22264 0.111878 H 3.842564 1.560343 -0.13986 C -0.78046 0.173637 1.316255 H 1.763918 -0.08378 2.498752 O -0.44222 0.411378 2.453575 H 3.18089 -0.25608 1.440266 N -0.89042 0.061308 -1.08115 H 3.178891 0.938803 2.732577 O -0.65351 0.053086 -2.31136 C 2.083613 -1.40271 -0.85526 C -2.16792 0.171241 0.825087 C 1.577311 -1.72199 -2.28152 C -3.36047 0.236617 1.538028 C 3.222652 -2.31818 -0.38918 C -2.17932 0.062918 -0.56795 H 2.486791 -0.38935 -0.91313 C -4.55789 0.183825 0.829017 H 0.737767 -1.05396 -2.29275 H -3.33948 0.321051 2.618023 H 2.339353 -1.47405 -3.02021 C -3.36804 0.019608 -1.29794 H 1.284615 -2.76243 -2.3931 C -4.55312 0.076642 -0.57338 H 3.616779 -2.06433 0.595627 H -5.50215 0.227266 1.357459 H 2.950675 -3.37121 -0.37141 H -3.34728 -0.05283 -2.37699 H 4.039403 -2.21198 -1.1102 H -5.49793 0.041265 -1.10381 C 0.130232 -2.39007 0.572376 C 0.432814 2.431229 -0.66809 C 0.936313 -3.37435 1.430895 C 1.18158 2.889949 -1.93568 C -0.66453 -3.15153 -0.50701 C 0.167566 3.599415 0.298671 H -0.60633 -1.96948 1.256415 H -0.53578 2.121128 -1.03175 H 1.560704 -2.8478 2.153644 H 1.479719 2.025673 -2.529 H 0.24344 -4.01979 1.977921 H 0.51449 3.505804 -2.54653 H 1.563901 -4.01774 0.823169 H 2.059908 3.498474 -1.71418 H -1.32893 -2.49547 -1.07267 H -0.38817 3.281593 1.186517 H -0.01335 -3.65107 -1.2186 H 1.082997 4.093995 0.63022 H -1.28005 -3.91629 -0.0238 H -0.43615 4.348936 -0.21888 ------C 2.027226 1.557276 1.058351

Cartesian coordinates of 4.24a calculated at the B3LYP/6-311g** level of theory.

------H 0.512601 0.130663 2.661737 Atom X Y Z C 2.699612 -1.58778 0.761388 ------H 3.477131 -1.61732 1.52991 C 0.97703 -0.02543 -0.03388 H 2.212727 -2.57189 0.715599 N 1.768108 -0.505 1.091555 H 3.160226 -1.3917 -0.20388 N 1.835822 0.49897 -1.05539 C 1.205161 0.80217 -2.33541 C 1.061717 -0.7545 2.345402 H 0.530835 1.672872 -2.28982 H 0.373417 -1.61507 2.305163 H 1.990109 1.027404 -3.06048 H 1.809678 -0.96863 3.111814 H 0.651432 -0.05836 -2.71079

138

C 2.77402 1.54838 -0.6416 C -1.3393 0.598117 0.269116 H 3.613593 1.557907 -1.34292 C -3.76981 -0.59864 -0.2962 H 2.309765 2.542844 -0.6287 H -2.61654 -2.25948 -1.07711 H 3.143268 1.331296 0.357402 C -2.50539 1.295486 0.591929 C -0.00639 -1.12399 -0.58914 C -3.71386 0.674188 0.299303 O 0.351068 -2.16804 -1.08675 H -4.73322 -1.04639 -0.50799 N -0.02984 1.005035 0.483545 H -2.44812 2.273104 1.051145 O 0.299474 2.112683 1.004068 H -4.64009 1.184998 0.538051 C -1.37935 -0.67171 -0.32808 ------C -2.5984 -1.28002 -0.6138

Cartesian coordinates of 4.24b calculated at the B3LYP/6-311g** level of theory.

CONCLUSION

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140

We have demonstrated that stable carbenes are excellent building blocks for the synthesis of organic radicals. Indeed, we first utilized a cyclic (alkyl)(amino) carbene in the isolation of an (amino)(carboxy) radical C.1. Furthermore, we successfully extended our synthetic method to the isolation of related bi- and tri-radicals C.2 and C.3 respectively. These paramagnetic species were found to be monomeric in solution and in the solid state, and were structurally characterized for the first time by X-ray crystallography. Importantly, these radicals have been stored at room temperature under an inert atmosphere for several years without any apparent decomposition.

Figure C.1: Stable monomeric (amino)(carboxy) radical and related bi- and tri- radicals.

However, like many C-centered radicals, our flagship (amino)(carboxy) radicals C.1-3 were found to decompose when exposed to oxygen. This led us to investigate whether the electronic properties of the R acyl substituent could be modified to extend the life-time of these paramagnetic species in air. To this end, we examined a series of radicals with increasingly electron withdrawing R-substituents. We found that electron withdrawing R-substituents led to

C,O-ambidentate radicals with life-times in air of hours and even days in the most favorable case. These half-lives could also be further prolonged with sterically encumbered substitutes as demonstrated by C.4 which had an exceptional half-live of three hours despite having only a moderate electron withdrawing group. Thus, we have demonstrated that (amino)(carboxy) radicals can not only exist as monomeric species, but can also be sufficiently protected from oxidative decay.

141

Figure C.2: (Amino)(carboxy) radicals bearing successively more electron withdrawing R-acyl substituents.

We then sought to bridge the gap between our systems and previously established transient capto-dative radicals which do not feature cyclic amino patterns. In our comparative study of (amino)(carboxy) radicals derived from cyclic and acyclic carbenes, we discovered that steric factors not only affect the susceptibility of these radicals towards undesired reactions, including dimerization, but also control the overall stability of the species. In fact, excessive steric hindrance inhibits the optimal π-donation required for fully conjugated amino groups and leads to the electronic destabilization of the paramagnetic species. This was best exhibited by

(amino)(carboxy) radical C.6, which is intrinsically thermodynamically unstable as evidenced by the isolation of the corresponding enolate C.7. This inquiry provides general guidelines for the design of highly persistent radicals, which are derived from stable carbenes, with particular emphasis on the key advantages of cyclic patterns that enforce strong mesomeric substituent effects.

Figure C.3: (Amino)(carboxy) radicals C.5-6 derived from acyclic carbenes and enolate C.7.

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142

Thus, we have exhibited that C-centered (amino)(carboxy) radicals should now be considered as stable monomeric paramagnetic building blocks, similarly to heteroatom based nitroxyl or verdazyl radicals. Indeed, we have demonstrated that N-heterocyclic carbenes are excellent synthons for the generation of these species, and investigations herein have established a rough set of guidelines for the synthesis of stable and increasing air persistent variants. Importantly, the information acquired throughout these studies should be applicable to the construction of future air persistent paramagnetic species. Efforts to synthesize di-radical

C.8 are already underway in our group and one could imagine C.9 and C.10 as future targets.

Figure C.4: Future C-centered radicals.

Finally, we designed and characterized an air-stable molecular switch that exhibits redox bistability on the basis of electron transfer induced bond making/breaking. Cyclic voltammetry experiments indicate that the chemical transformations associated with this redox process are extremely fast and reversible.

Figure C.5: Molecular switch system characterized by redox bistability.

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143

Initial investigations also indicate that the redox properties of this model can be efficiently tuned by modulation of the carbene substituents. However, we also demonstrated that excessive steric environments can inhibit the cyclization process. Therefore, future modifications to our initial system should focus on using stable carbenes with varying electronic properties but small substituents. Some carbene building blocks have been identified as potential targets (Figure C.6).

Figure C.6: Stable carbenes to be considered as molecular switch synthons.

Furthermore, we attempted to synthesis molecular switch systems with alternate linking moieties in order to incorporate an easily detectable physical response into the system. We first proposed nitrogen linked switches C.11, but thus far these molecules have remained out of reach due to synthetic complications. Additional options, particularly a nitroso based switch C.12 and ferrocene linked system C.13, were also shown to be promising targets by DFT calculations.

However, in the case of the latter, only a di-radical, and not the DFT predicted cyclized product, was experimentally observed upon reduction of the corresponding iminium salt.

143

144

Figure C.7: Molecular switches with alternate linking moieties.

Finally, further modifications to our flagship bi-radical should yield molecules with new and exciting properties. These could include new linking moieties such as a cyanine mimic C.14, or alterations to Z (Figure C.8).

Figure C.8: Further modifications to the initial molecular switch framework.

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145

REFERNCES

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146

(1) Hicks, R. G. Org. Biomol. Chem., 2007, 5, 1321-1338.

(2) Radicals in Organic Synthesis, Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH Verlag GmbH; Germany, 2001.

(3) (a) Zimmer, H.; Lankin, D. C.; Horgan, S. W. Chem. Rev. 1971, 71, 229-246. (b) deNooy, A. E. J.; Besemer, A. C.; vanBekkum, H. Synthesis, 1996, 1153-1174. (c) Sheldon, R. A.; Arends, I.; Ten Brink, G. J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774-781.

(4) Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. Rev. 2001, 50, 151-216. (5) (a) Wright, J. S.; Carpenter, D. J.; McKay, D. J.; Ingold, K. U. J. Am. Chem. Soc. 1997, 119, 4245-4252. (b) Scaiano, J. C.; Martin, A.; Yap, G. P. A.; Ingold, K. U. Org. Lett. 2000, 2, 899-901. (c) Wright, J. S.; Johnson, E. R.; DiLabio, G. A. J. Am. Chem. Soc. 2001, 123, 1173-1183. (d) Font-Sanchis, E.; Aliaga, C.; Focsaneanu, K. S.; Scaiano, J. C. Chem. Commun. 2002, 1576-1577. (e) Aliaga, C.; Aspee, A.; Scaiano, J. C. Org. Lett. 2003, 5, 4145-4148.

(6) (a) Rajca, A. Chem. Rev. 1994, 94, 871-893. (b) Magnetic Properties of Organic Materials, Lahti, P. M., Ed.; Marcel Dekker: New York, 1999. (c) Rawson, J. M.; Alberola, A.; Whalley, A. J. Mater. Chem. 2006, 16, 2560-2575.

(7) Berliner, L. J. Spin Labelling: Theory and Applications, Academic Press: New York, 1979.

(8) (a) Perkins, L. J. Adv. Phys. Org. Chem. 1980, 17, 1. (b) Rehorek, Chem. Soc. Rev. 1991, 20, 341-353. (c) Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U. J. Am. Chem. Soc. 1992, 114, 4983-4992. (d) Bowry, V. W.; Ingold, K. U. J. Am. Chem. Soc. 1992, 114, 4992-4996.

(9) Zweier, J. L.; Kuppusamy, P. Proc. Natl. Acad. Sci. U. S. A. 1988, 85, 5703-5707.

(10) Stable Radicals: Fundamental and Applies Aspects of Odd-Electron Compounds; Hicks, R. C., Ed.; Wiley: Chichester, 2010.

(11) Sanderson, R. T. Chemical Bonds and Bond Energy; Academic Press: New York, 1976.

(12) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1976, 9, 13-19.

(13) Gay-Lussac, J. L. Ann. Chim. 1815, 95, 136-231.

(14) Bunsen, R. H. Justus Liebigs Ann. Chim. 1842, 42, 14-46.

(15) Frankland, E. Justus Liebigs Ann. Chim. 1849, 71, 213-216;

(16) Wurtz, C. A. Compt. Rend. 1854, 40, 1285.

(17) Gomberg, M. J. J. Am. Chem. Soc. 1900, 22, 757-771.

(18) Gomberg’s discovery was designated as a national historical chemical landmark by the ACS in 2000; see http://www.acs.org/content /acs/education/whatischemistry/landmarks/freeradicals.html.

(19) (a) Andersen, P. Acta Chem. Scand. 1965, 19, 629. (b) Andersen, P.; Klewe, B. Acta Chem. Scand. 1967, 21, 2599. (c) Kahr, B.; Vanengen, D.; Gopalan, P. Chem. Mater. 1993, 5, 729-732.

146

147

(20) (a) Heintschel, E. Ber. Dtsch. Chem. Ges. 1903, 36, 320-322. (b) Heintschel, E. Ber. Dtsch. Chem. Ges. 1903, 36, 579. (c) Jacobson, P. Ber. Dtsch. Chem. Ges. 1905, 38, 196-199. (d) McBride, J. M. Tetrahedron 1974, 30, 2009-2022. (e) Eberson, L. Chem. Intelligencer 2000, 6, 44-49. (f) Lankamp, H.; Nauta, W. T.; MacLean, C. Tetrahedron Lett. 1968, 9, 249-254.

(21) (a) Lankamp, H.; Nauta, W. T.; MacLean, C. Tetrahedron Lett. 1968, 249-254. (b) Gildewell, C.; Liles, D. C.; Walton, D. J. Acta. Cryst. Sect. B. 1979, 35, 500-502.

(22) While the “head-to-head dimer was proven to be correct, the “tail-to-head” and “tail-to-tail” peroxides were also observed with modified tri(aryl)methyl radicals. See: (a) Gomberg, M. Ber. Dtsch. Chem. Ges. 1900, 33, 3150-3163. (b) Jang, S.-H.; Goplan, P.; Jackson, J. E.; Kahr, B. Angew. Chem. Int. Ed. 1994, 33, 775-777. (c) Kahr, B.; Jackson, J. E.; Ward, D. L.; Jang, S. -H.; Blount, J. F. Acta. Cryst. Sect. B. 1992, 48, 324-329.

(23) Janzen, E. G.; Johnston, F. J.; Ayers, C. L. J. Am. Chem. Soc. 1967, 89, 1176-11783.

(24) Schlenk, W.; Weickel, T.; Herzenstein, A. Justus Liebigs Ann. Chem. 1910, 372, 1-20.

(25) Jang, S. H.; Gopalan, P.; Jackson, J. E.; Kahr, B. Angew. Chem. Int. Ed. Engl. 1994, 33, 775-777.

(26) (a) Ballester, M.; Molinet, C.; Castañer, J. J. Am. Chem. Soc. 1960, 82, 4254-4258. (b) Ballester, M.; Riera-Figueras, J.; Castañer, J.; Badfa, C.; Monso, J. M. J. Am. Chem. Soc. 1971, 93, 2215-2225. (c) Ballester, M. Acc. Chem. Res. 1985, 18, 380-387.

(27) Veciana, J.; Carilla, J.; Miravitlles, C.; Molins, E. J. Chem. Soc., Chem. Commun. 1987, 812-814.

(28) Ballester, M.; Castaner, J.; Riera, J. Ibanez, A.; Pujadas, J. J. Org. Chem. 1982, 47, 259- 264.

(29) Domingo, V. M.; Castaner, J.; Riera, J.; Labarta, A. J. Org. Chem. 1994, 59, 2604-2607.

(30) (a) Maspoch, D.; Catala, L.; Gerbier, P.; Ruiz-Molina, D.; Vidal-Gancedo, J.; Wurst, K.; Rovira, C.; Veciana, J. Chem. -Eur. J. 2002, 8, 3635-3645. (b) Maspoch, D.; Domingo, N.; Ruiz-Molina, D.; Wurst, K.; Tejada, J.; Rovira, C.; Veciana, J. J. Am. Chem. Soc. 2004, 126, 730-731. (c) Maspoch, D.; Domingo, N.; Ruiz-Molina, D.; Wurst, K.; Vaughan, G.; Tejada, J.; Rovira, C.; Veciana, J. Angew. Chem. Int. Ed. 2004, 43, 1828-1832.

(31) (a) Maspoch, D.; Ruiz-Molina, D.; Wurst, K.; Rovira, C.; Veciana, J. Chem. Commun. 2002, 2958-2959. (b) Maspoch, D.; Gomez-Segura, J.; Domingo, N.; Ruiz-Molina, D.; Wurst, K.; Rovira, C.; Tejada, J.; Veciana, J. Inorg. Chem. 2005, 44, 6936-6938.

(32) (a) Maspoch, D.; Ruiz-Molina, D.; Wurst, K.; Domingo, N.; Cavallini, M.; Biscarini, F.; Tejada, J.; Rovira, C.; Veciana, J. Nat. Mater. 2003, 2, 190-195. (b) Maspoch, D.; Ruiz- Molina, D.; Wurst, K.; Rovira, C.; Veciana, J. Chem. Commun. 2004, 1164-1165. (c) Maspoch, D.; Domingo, N.; Molina, D. R.; Wurst, K.; Hernandez, J. M.; Vaughan, G.; Rovira, C.; Lloret, F. Tejada, J.; Veciana, J. Chem. Commun. 2005, 5035-5037.

(33) Ratera, I.; Veciana, J. Chem. Soc. Rev. 2012, 41, 303-349.

147

148

(34) (a) Thiele, J.; Balhorn, H.; Ber. Dtsch. Chem. Ges. 1904, 37, 1463-1470. (b) Montgomery, L. K.; Huffman, J. C.; Jurczak, E. A.; Grendze, M. P. J. Am. Chem. Soc. 1986, 108, 6004- 6011.

(35) Tschitschibabin, A. E. Ber. Dtsch. Chem. Ges. 1907, 40, 1810-1819.

(36) Schmidt, R.; Brauer, H. -D. Angew. Chem. Int. Ed. 1971, 10, 506-507.

(37) Schlenk, W.; Brauns, M. Ber. Dtsch. Chem. Ges. 1915, 48, 661-669.

(38) Leo, M. Ber. Dtsch. Chem. Ges. 1937, 70, 1691-1695.

(39) (a) Shishlov, N. M. Russ. Chem. Revs. 2006, 75, 863-884. (b) Diradicals; Borden, W. T., Ed.; John Wiley & Sons, Inc.: New York, 1982. (c) Iwamura, H. Adv. Phys. Org. Chem. 1990, 26, 179-253. (d) Racja, A. Adv. Phys. Org. Chem. 2005, 40, 153-199.

(40) Reid, D. H. Tetrahedron, 1958, 3, 339-352.

(41) Sogo, B. P.; Nakazaki, M.; Calvin, M. J. Chem. Phys. 1957, 26, 1343-1345.

(42) For a review on early phenalenyl radicals see: Zaitsev, V.; Rosokha, S. V.; Head-Gordon, M.; Kochi, J. K. J. Org. Chem. 2006, 71, 520-526.

(43) Zaitzev, V.; Rosokha, S. V.; Head-Gordon, M.; Kochi, J. K. J. Org. Chem. 2006, 71, 520- 526.

(44) Haldon, R. C. Nature, 1975, 256, 394-396

(45) Goto, K.; Kubo, T.; Yamamoto, K.; Nakuhiro, K.; Sato, K.; Shiomi, D.; Takui, T.; Kubota, M.; Kobayashi, T.; Yakusi, K. J. Am. Chem. Soc. 1999, 121, 1619-1620.

(46) (a) Lu, J. M.; Rosokha, S. V.; Kochi, J. K. J. Am. Chem. Soc. 2003, 125, 12161-12171. (b) Small, D.; Zaitsev, V.; Jung, Y. S.; Rosokha, S. V.; Head-Gordon, M.; Kochi, J. K. J. Am. Chem. Soc. 2004, 126, 13850-13858. (c) Small, D.; Roskha, S. V.; Kochi, J. K.; Head- Gordon, M. J. Phys. Chem. A. 2005, 109, 11261-11267.

(47) Suzuki, S.; Morita, Y.; Fukui, K.; Sato, K.; Shiomi, D.; Takui, T.; Nakasuji, K. J. Am. Chem. Soc. 2006, 128, 2530-2531.

(48) Haddon, R. C.; Wudl, F.; Kaplan, M.; Marshall, J. H.; Cais, R. E.; Bramwell, F. B. J. Am. Chem. Soc. 1978, 100, 7629-7633.

(49) (a) Haddon, R. C.; Hirani, A. M.; Kroloff, N. J.; Marshall, J. H. J. Org. Chem. 1983, 48, 2115-2117. (b) Peebles, W.; Pagni, R. M.; Haddon, R. C. Tetrahedron Lett. 1989, 30, 2727-2730. (c) Pagni, R. M.; Peebles, W.; Haddon, R. C.; Chichester, S. V. J. Org. Chem. 1990, 55, 5595-5601. (d) Kaplan, M. L.; Haddon, R. C.; Hirani, A. M. Schilling, F. C.; Marshall, J. H. J. Org. Chem. 1981, 46, 675-678.

(50) (a) Haddon, R. C.; Chinchester, S. V.; Stein, S. M.; Marshall, J. H.; Mujsce, A. M. J. Org. Chem. 1987, 52, 711-712. (b) Koutentis, P. A.; Chen, Y.; Cao, Y.; Best, T. P.; Itkis, M. E.; Beer, L.; Oakley, R. T.; Cordes, A. W.; Brock. C. P.; Haddon, R. C. J. Am. Chem. Soc. 2001, 123, 3864-3871.

148

149

(51) Morita, Y.; Aoki, T.; Fukui, K.; Nakazawa, S.; Tamaki, K.; Suzuki, S.; Fuyuhiro, A.; Yamamoto, K.; Sato, K.; Shiomi, D.; Naito, A.; Takui, T. Nakasuji, K. Angew. Chem. Int. Ed. 2002, 41, 1793-1796.

(52) Morita, Y.; Suzuki, S.; Fukui, K.; Nakazawa, S.; Kitagawa, H.; Kishida, H.; Okamoto, H.; Naito, A.; Sekine, A.; Ohashi, Y.; Shiro, M.; Sasaki, K.; Shiomi, D.; Sato, K.; Takui, T.; Nakasuji, K. Nature Mater. 2008, 7, 48-51.

(53) Zheng, S. J.; Lan, J.; Khan, S. I.; Rubin, Y. J. Am. Chem. Soc. 2003, 125, 5786-5791.

(54) Zheng, S. J.; Thompson, J. D.; Tontcheva, A.; Khan, S. I.; Rubin, Y. Org. Lett. 2005, 7, 1861-1863.

(55) (a) Harrison, A. G.; Honnen, L. R.; Dauben, H. J., Jr.; Lossing, F. P. J. Am. Chem. Soc. 1960, 82, 5593-5598. (b) Ohnishi. S.; Nitta, I. J. Chem. Phys. 1963, 39, 2848-2849. (c) Zandstra, P. J. J. Chem. Phys. 1964, 40, 612-613. (d) Fessenden, R. W.; Ogawa, S. J. Am. Chem. Soc. 1964, 86, 3591-3592. (e) Liebling, G. R.; McConnell, H. M. J. Chem. Phys. 1965, 42, 3931-3934. (f) Barker, P. J.; Davies, A. G.; Fisher, J. D. J. Chem. Soc., Chem. Commun. 1979, 587-588. (g) Kira, M.; Watanabe, M.; Sakurai, H. J. Am. Chem. Soc. 1980, 102, 5202-5207. (h) Barker, P. J.: Davies, A. G.; Tse, M. -W. J. Chem. Soc., Perkin Trans. 1980, 2, 941-948.

(56) (a) Sitzmann, H.; Boese, R. Angew. Chem. Int. Ed. 1991, 30, 971-973. (b) Sitzmann, H.; Bock, H.; Boese, R.; Dezember, T.; Havlas, Z.; Kaim, W.; Moscherosh, W.; Zanathy, L. J. Am. Chem. Soc. 1993, 115, 12003-12009.

(57) Jux, N.; Holczer, K.; Rubin, Y. Angew. Chem. Int. Ed. 1996, 35, 11986-1990.

(58) Krusic, P. J.; Wasserman, E.; Keizer, P. N.; Morton, J. R.; Preston, K. F. Science, 1991, 254, 1183-1185.

(59) (a) Hummelen, J. C.; Knight, B.; Pavlovich, J.; Gonzalez, R.; Wuld, F. Science, 1995, 269, 1554-1556. (b) Keshavarz-K., M.; Gonzalez, R; Hicks, R. G.; Srdanov, G.; Vojislav, I.; Collins, T. G. Hummelen, J. C.; Bellavia-Lund, C.; Pavlovich, J.; Wuld, F.; Holczer, K. Nature, 1996, 383, 147-150. (c) Hasharoni, K.; Bellavia-Lund, C.; Keshavarz-K.; M.; Srdanov, G.; Wuld, F. J. Am. Chem. Soc. 1997, 119, 11128-11129. (d) Vostrowsky, O.; Hirsch, A. Chem. Rev. 2006, 106, 5191-5207.

(60) Radical Reactions of Fullerenes and their Derivatives; Tumanskii, B.; Kalina, O., Eds.; Kluwer Academic Publishers: Bordetcht 2001.

(61) Igau, A.; Grützmacher, H.; Baceiredo, A.; Bertrand, G. J. Am. Chem. Soc. 1988, 110, 6463-6466.

(62) Arduengo, A. J., III; Harlow, R. L.; Kline, M. A. J. Am. Chem. Soc. 1991, 113, 361-363.

(63) (a) Soleilhavoup, M.; Bertrand, G. Acc. Chem. Res. 2015, 48, 256-266. (b) Melaimi, M. Soleilhavoup, M.; Bertrand, G. Angew. Chem. Int, Ed. 2010, 49, 8810-8849. (c) Droege, T.; Glorius, F. Angew. Chem. Int. Ed. 2010, 49, 6940-6942. (d) Martin, D.; Melaimi, M.; Soleilhavoup, M.; Bertrand, G. Organometallics 2011, 30, 5304-5313. (e) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. Nature, 2014, 510, 485-496.

(64) Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275-3332.

149

150

(65) Crabtree, R. H. J. Organomet. Chem. 2005, 690, 5451-5457.

(66) (a) V. Lavallo, Y. Canac, C. Prasang, B. Donnadieu, G. Bertrand, Angew. Chem. Int. Ed. 2005, 44, 5705-5709; b) R. Jazzar, R. D. Dewhurst, J. -B. Bourg, B. Donnadieu, Y. Canac, G. Bertrand, Angew. Chem. Int. Ed. 2007, 46, 2899-2902. C) R. Jazzar, J. B. Bourg, R. D. Dewhurst, B. Donnadieu, G. Bertrand, J. Org. Chem. 2007, 72, 3492-3499. (67) The π-accepting properties (electrophilicity) of a stable carbene can be directly inferred form the 31P NMR chemical shifts of the corresponding carbenephenylphosphinidene adducts. See: (a) Back, O.; Henry-Ellinger, M.; Martin, C. D.; Bertrand, G. Angew. Chem. Int. Ed. 2013, 52, 2939-2943. (b) Rodrigues, R. R.; Dosey, C. L.; Arceneaux, C. A.; Hudnall, Chem. Commun. 2014, 50, 162-164.

(68) The π-accepting properties (electrophilicity) of a stable carbene can be directly inferred form the 77Se NMR chemical shifts of the corresponding carbeneselenium adducts (c) Liske, A.; Verlinden, K.; Buhl H.; Schaper, K.; Ganter, C. Organometallics 2013, 32, 5269- 5272. (d) Vummaleti, S. V. C.; Nelson, D. J.; Poater, A.; Gómez-Suárez, D. B.; Slawin, A. M. Z.; Nolan, S. P.; Cavallo, L. Chem. Sci. 2015, 6, 1895-1904.

(69) The Tolman electronic parameter of a carbene is a measure of its overall donor properties, which is a combination of its nucleophilicity and electrophilicity. See: (a) Tolman, C. A. Chem. Rev. 1977, 77, 313-348. (b) Lever, A. B. P. Inorg. Chem. 1990, 29, 1271-1285. (c) Lever, A. B. P. Inorg. Chem. 1991, 30, 1980-1985. (d) Fielder, S. S.; Osborne, M. C.; Lever, A. B. P.; Pietro, W. J. J. Am. Chem. Soc. 1995, 117, 6990-6993. (e) Perrin, L.; Clot, E.; Eisenstein, O.; Loch, J.; Crabtree, R. H. Inorg. Chem. 2001, 40, 5806-5811. (f) Chianese, A. R.; Li, X.; Janzen, M. C.; Faller, J. W.; Crabtree, R. H. Organometallics 2003, 22, 1663-1667. (h) Kelly, R. A., III; Clavier, H. Giudice, S.; Scott, N. M.; Stevens, E. D. Bordner, J.; Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2008, 27, 202-210. (i) Huynh, H. V.; Han, Y.; Jothibasu, R.; Yang, J. A. Organometallics 2009, 28, 5395-5404. (j) Droege, T.; Glorius, F.; Angew Chem. Int. Ed. 2010, 49, 6940-6952. (k) Liske, A.; Verlinden, K.; Buhl, H.; Schaper, K.; Ganter, C. Organometallics 2013, 32, 5269-5272. (l) Rodrigues, R. R.; Dorsey, C. L.; Arceneaux, C. A.; Hudnall, T. W. Chem. Commun. 2013, 50, 162-164.

(70) Lavallo, V.; Canac, Y.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. Angew. Chem. Int. Ed. 2006, 45, 3488-3491.

(71) Martin, D.; Soleilhavoup, M.; Bertrand, G. Chem. Sci. 2011, 2, 389-399.

(72) Frey, G. D.; Lavallo, V.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. Science, 2007, 316, 439-441.

(73) Frey, G. D.; Masuda, J. D.; Donnadieu, B. Bertrand, G. Angew. Chem. Int. Ed. 2010, 49, 9444-9447.

(74) (a) Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1290-1309. (b) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612-3676. (c) N-Heterocyclic Carbenes in Transition Metal Catalysis; Glorius, F. Ed.; Springer: Heidelberg 2007. (d) N- Heterocyclic Carbenes in Synthesis; Nolan, S. P. Ed.; Wiley: Germany 2006.

(75) (a) Lee, K. M.; Lee, C. K.; Lin, I. J. B. Angew. Chem. Int. Ed. Engl. 1997, 36, 1850-1852. (b) Poyatos, M; Mata, J. A.; Peris, E. Chem. Rev. 2009, 109, 3677-3707. (c) Boydston, A. J.; Williams, K. A.; Bielawski, C. W. A. J. Am. Chem. Soc. 2005, 127, 12496-12497. (d) Oisaki, K.; Li, Q.; Furukawa, H.; Czaja, A. U.; Yaghi, O. M. A. J. Am. Chem. Soc. 2010,

150

151

132, 9262-9264. (e) Visbal, R.; Concepcion Gimeno, M. Chem. Soc. Rev. 2014, 43, 3551- 3574.

(76) (a) Hickey, J. L. J. Am. Chem. Soc. 2008, 130, 12570-12571. (b) Hindi, K. M.; Panzner, M. J. Tessier, C. A.; Cannon, C. L.; Youngs, W. J. Chem. Rev. 2009, 109, 3859-3884.

(77) Soleilhavoup, M.; Bertrand, G. Acc. Chem. Res. 2015, 48, 256-266.

(78) Samuel, P. P.; Mondal, K. C.; Roesky, H. W.; Hermann, M.; Frenking, G.; Demeshko, S.; Meyer, F.; Stuckl, A. C.; Christian, J. H.; Dalal, N. S.; Ungur, L.; Chibotaru, L. F.; Propper, K.; Meents, A.; Dittrich, B. Angew. Chem. Int. Ed. 2013, 52, 11817-11821.

(79) Ung, G.; Rittle, J.; Soleilhavoup, M.; Bertrand, G.; Peters, J. C. Angew. Chem. Int. Ed. 2014, 53, 8427-8431.

(80) Mondal, K. C.; Samuel, P. P.; Roesky, H. W.; Carl, E.; Herbst-Irmer, R.; Stalke, D.; Schwederski, B.; Kain, W.; Ungur, L.; Chibotaru, L. F.; Hermann, M.; Frenking, G. J. Am. Chem. Soc. 2014, 136, 1770-1773.

(81) Mondal, K. C.; Samuel, P. P.; Li, Y.; Roesky, H. W.; Roy, S.; Ackermann, L.; Sidhu, N. S.; Sheldrick, G. M.; Carl, E.; Demeshko, S.; De, S.; Parameswaran, P.; Ungur, L.; Chibotaru, L. F.; Andrada, D. M. Eur. J. Inorg. Chem. 2014, 2014, 818-823.

(82) Weinberger, D. S.; Amin, N.; Mondal, K C.; Melaimi, M.; Bertrand, G.; Stückl, A. C.; Roesky, H. W.; Dittrich, B.; Demeshko, S.; Schwederski, B.; Kaim, W.; Jerabek, J.; Frenking, G. J. Am. Chem. Soc. 2014, 136, 6235-6238.

(83) Singh, A. P.; Samuel, P. P.; Roesky, H. W.; Schwarzer, M. C.; Frenking, G.; Sidhu, N. S.; Dittrich, B. J. Am. Chem. Soc. 2013, 135, 7324-7329.

(84) Weinberger, D. S.; Melaimi, M.; Moore, C. E.; Rheingold, A. L.; Frenking, G.; Jerabek, P.; Bertrand, G. Angew. Chem. Int. Ed. 2013, 52, 8964-8967.

(85) For other carbene supported main group radicals see: (a) Back, O.; Donnadieu, B.; Parameswaran, P.; Frenking, G.; Bertrand, G. Nat. Chem. 2010, 2, 369-373. (b) Kinjo, R.; Donnadieu, B.; Bertrand, G. Angew Chem. Int. Ed. 2010, 49, 5930-5933. (c) Back, O.; Donnadieu, B.; von Hopffgarten, M.; Klein, S.; Tonner, R.; Frenking, G.; Bertrand, G. Chem Sci. 2011, 2, 858-861. (d) Kinjo, R.; Donnadieu, B.; Celik, M. A.; Frenking, G.; Bertrand, G. Science 2011, 333, 610-613. (e) Percival, P. W.; McCollum, B. M.; Brodovitch, J.-C.; Driess, M.; Mitra, A.; Mozafari, M.; West,R; Xiong, Y.; Yao, S. Organometallics 2012, 31, 2709-2714. (f) Mondal, K. C.; Roesky, H. W.; Schwarzer, M. C.; Frenking, G.; Tkach, I.; Wolf, H.; Kratzert, D.; Herbst-Irmer, R.; Niepӧtter, B.; Stalke, D. Angew. Chem. Int. Ed. 2013, 52, 1801-1805. (g) Mondal, K. C.; Roesky, H. W.; Schwarzer, M. C.; Frenking, G.; Niepӧtter, B.; Wolf, H.; Herbst-Irmer, R.; Stalke, D. Angew. Chem. Int. Ed. 2013, 52, 2963-2967. (h) Mondal, K. C.; Samuel, P. P.; Tretiakov, M.; Singh, A. P.; Roesky, H. W.; Stüeckl, A. C. Niepӧtter, B.; Carl, E.; Wolf, H.; Herbst- Irmer, R.; Stalke, D. Inorg. Chem. 2013, 52, 4736-4743. (i) Martin, C. D.; Soleilhavoup, M.; Bertrand, G. Chem. Sci. 2013, 4, 3020-3030. (l) Mondal, K. C. Roesky, H. W. Stuckl, A. C.; Ehret, F.; Kaim, W.; Dittrich, B.; Maity, B.; Koley, D. Angew. Chem. Int. Ed. 2013, 52, 11804-11807. (j) Kretschmer, R.; Ruiz, D. A.; Moore, C. E.; Rheinold, A. L.; Bertrand, G. Angew. Chem. Int. Ed. 2014, 53, 8176-8179. (k) Roy, S.; Stüeckl, A. C.; Demeshko, S.; Dittrich, B.; Meyer, J.; Maity, B.; Koley, D.; Schwederski, B.; Kaim, W.; Roesky, H. W. J. Am. Chem. Soc. 2015, 137, 4670-4673.

151

152

(86) Matsumoto, T.; Gabbaï, F. P. Organometallics, 2009, 28, 4252-4253.

(87) Back, O.; Ali Celik, M.; Frenking, G.; Melaimi, M.; Donnadieu, B.; Bertrand, G. J. Am. Chem. Soc. 2010, 132, 10262-10263.

(88) Tanaka, H.; Ichinohoe, M.; Sekiguchi, A. J. Am. Chem. Soc. 2012, 134, 5540-5543.

(89) Abraham, M. Y.; Wang, Y.; Xie, Y.; Gilliard Jr., R. J.; Wei, P.; Vaccaro, B. J.; Johnson, M. K.; Schaefer, H. F. III; Schleyer, P. v. R.; Robinson, G. H. J. Am. Chem. Soc. 2013, 135, 2486-2488.

(90) Kretschmer, R.; Ruiz, D. A.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. Angew. Chem. Int. Ed. 2014, 53, 8176-8179.

(91) (a) Nakanishi, I.; Otoh, S.; Suenobu, T.; Fukuzumi, S. Chem. Commun. 1997, 1927-1928. (b) Nakanishi, I.; Otoh, S.; Fukuzumi, S. Chem. -Eur. J. 1999, 5, 2810-2818.

(92) Arduengo, A. J., III; Goerlich, J. R.; Marshall, W. J. Liebigs. Ann. 1997, 365-374.

(93) Martin, D.; Lassauque, N.; Donnadieu, B.; Bertrand, G. Angew. Chem. Int. Ed. 2013, 52, 7014-7017.

(94) Martin, D.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. Angew. Chem. Int. Ed. 2012, 51, 6172-6175.

(95) Jin, L.; Melaimi, M.; Liu, L.; Bertrand, G. Org. Chem. Front. 2014, 1, 351-354.

(96) Li, Y.; Mondal, K. C.; Samuel, P. P.; Zhu, H.; Orben, C. M.; Panneerselvam, S.; Dittrich, B.; Schwederski, B.; Kaim, W.; Mondal, T.; Koley, D.; Roesky, H. W. Angew. Chem. Int. Ed. 2014, 53, 4168-4172.

(97) Styra, S.; Melaimi, M.; Moore, C. E.; Rheingold, A. L.; Augenstein, T.; Breher, F.; Bertrand, G. Chem. Eur. J. 2015, 21, 8441-8446.

(98) Munz, D.; Chu, J.; Melaimi, M.; Bertrand, G. Angew. Chem. Int. Ed. 2016, 55, 12886- 12890.

(99) (a) Baldock, R.W.; Hudson, P.; Katritzky, A. R.; Soti, F. J. Chem. Soc., Perkin Trans. 1 1974, 1422-1427. (b) Balaban, A. T.; Caproiu, M. T.; Negotia, N.; Baican, R. Tetrahedron 1977, 33, 2249-2253. (c) Viehe, H. G.; Mértnyi, R.; Stella, L.; Janousek, Z. Angew. Chem. Int. Ed. Engl. 1979, 18, 917-932. (d) Veihe, H. G. Janousek, Z.; Mértnyi, R.; Stella, L. Acc. Chem. Res. 1985, 18, 148-154. (e) Zipse, H. Top Curr. Chem. 2006, 263, 163-189.

(100) (a) Leroy, G.; Peeters, D.; Sana, M.; Wilante, C. Substituent Effects in Radical Chemistry; Viehe, V. H., Janousek, Z.; Mertinyi, R., Eds.; Reidel: Boston, 1986; pp 1-48. (b) Katritzky, A. R.; Zerner, M. C.; Karelson, M. M. J. Am. Chem. Soc. 1986, 108, 7213-7214. (c) Pasto, D. J. J. Am. Chem. Soc. 1988, 110, 8164-8175. (d) Bordwell, F. G.; Lynch, T.-Y. J. Am. Chem. Soc. 1989, 111, 7558-7562. (e) Wright, J. S.; Shadnia, H.; Chepelev, L. L. J. Comput. Chem. 2009, 30, 1016-1026.

(101) Captodative C-centered radicals are also pivotal intermediates in organic chemistry; see: (a) Radicals in Organic Chemistry; Renaud, R., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001. (b) Easton, C. J. Chem. Rev. 1997, 97, 53-82.

152

153

(102) (a) Koch, T. H.; Olesen, J. A.; DeNiro, J. J. Am. Chem. Soc. 1975, 97, 7285-7288. (b) Himmelsbach, R. J.; Barone, A. D.; Kleyer, D. L.; Koch, T. H. J. Org. Chem. 1983, 48, 2989-2994. (c) Gaudiano, G.; Sweeney, K.; Haltiwanger, R. C.; Koch, T. H. J. Am. Chem. Soc. 1984, 106, 7628-7629. (d) Benson, O., Jr.; Gaudiano, G.; Haltiwagner, R. C.; Koch, T. H. J. Org. Chem. 1988, 53, 3036-3045. (e) Benson, O., Jr.; Demirdji, S. H.; Haltiwanger, R. C.; Koch, T. H. J. Am. Chem. Soc. 1991, 113, 8879-8886.

(103) Such radicals have been described as “dynamically stable,” see: Frenette, M.; Aliaga, C.; Font-Sanchis, E.; Scaiano, J. C. Org. Lett. 2004, 6, 2579-2582.

(104) For other related isolated dimers also see: (a) Kleyer, D. L.; Haltiwanger, R. C.; Koch, T. H. J. Org. Chem. 1983, 48, 147-149. (b) Welle, F.; Verevkin, S. P.; Keller, M.; Beckhaus, H.-D. Rüchardt, C. Chem. Ber. 1994, 127, 697-710. (c) Welle, F. M.; Beckhaus, H.-D.; Rüchardt, C. J. Org. Chem. 1997, 62, 552-558.

(105) For reviews on radical based proteins see: (a) Stubbe, J.; van der Donk, W. A. Chem. Rev. 1998, 98, 705-762. (b) Buckel, W.; Golding, B. T. Annu. Rev. Microbiol. 2006, 60, 27-49.

(106) (a) Frey, M.; Rothe, M.; Wagner, A. F.; Knappe, J. J. Biol. Chem. 1994, 269, 12432-12437. (b) Mulliez, E.; Fontecave, M.; Gaillard, J.; Reichard, P. J. Biol. Chem. 1993, 268, 2296- 2299. (c) Leuthner, B.; Leutwein, C.; Schulz, H.; Horth, P. Haehnal, W. Schiltz, E. Schägger, H.; Heider, J. Mol. Mircobiol. 1998, 28, 615-628. (d) O’Brien, J. R.; Raynaud, C. Croux, C. Girbal, L.; Soucaille, P.; Lanzilotta, W. N. Biochemistry 2004, 43, 4635-4645. (e) Martins, B. M.; Blaser, M.; Feliks, M.; Ullmann, G. M.; Buckel, W. Selmer, T. J. Am. Chem. Soc. 2011, 133, 14666-14674. (f) Jarling, R.; Sadegh, M.; Drozdowska, M.; Lahme, S.; Buckel, W.; Rabus, R.; Widdel, F.; Golding, B. T.; Wilkes, H. Angew. Chem. Int. Ed. 2012, 51, 1334-1338.

(107) Burkholder, C.; Dolbier, W. R., Jr. J. Org. Chem. 1998, 63, 5385-5394.

(108) Tri-radical 1.3c is reminiscent of some well-known hindered 1,3,6-trinitroxylbenzenes: Fujita, J.; Tanaka, M.; Suemune, H.; Koga, N.; Matsuda, K.; Iwamura, H. J. Am. Chem. Soc. 1996, 118, 9347-9351.

(109) Bleany, B.; Bowers, K. D. Proc. R. Soc. London, Ser. A. 1952, 214, 451-465.

(110) Mahoney, J. K.; Martin, D.; Moore, C. E.; Rheingold, A. L.; Bertand, G. J. Am. Chem. Soc. 2013, 135, 18766-18769.

(111) Hansh, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165-195.

(112) (a) Lavallo, V.; Canac, Y.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. Angew. Chem. Int. Ed. 2006, 45, 3488-3491. (b) Hudnall, T. W.; Bielawski, C. W. J. Am. Chem. Soc. 2009, 131, 16039-16041.

(113) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877-910.

(114) Manner, V. W.; Markle, T. F.; Freudenthal, J. H.; Roth, J. P.; Mayer, J. M. Chem. Commun. 2008, 256-258.

(115) Part of our study was performed on a sample of crystallized 2.3f, which had been synthesized in mid-2014 and stored in a regular vial under air.

153

154

(116) Mahoney, J. K.; Martin, D.; Thomas, F.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. J. Am. Chem. Soc. 2015, 137, 7519-7525. (117) Deardorff, C. L.; Sikma, E. R.; Rhodes, C. P.; Hudnall, T. W. Chem. Commun. 2016, 52, 9024-9027.

(118) (a) Arduengo, A. J., III; Harlow, R. L.; Kline, M. A. J. Am. Chem. Soc. 1991, 113, 361-363. (b) Arduengo, A. J., III; Krafczky, R.; Schmutxler, R.; Craig, H.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M. Tetrahedron, 1999, 55, 14523-14534.

(119) Blake, G. A.; Moerdyk, J. P. Bielawski, C. W. Organometallics, 2012, 31, 3373-3378.

(120) Hudnall, T. W.; Bielawski, C. W. J. Am. Chem. Soc. 2009, 131, 16039-16041.

(121) Vignolle, J.; Cattoen, X.; Bourissou, D. Chem. Rev. 2009, 109, 3333-3384.

(122) Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. J. Org. Chem. 2001, 66, 7729-7737.

(123) Alder, R. W.; Allen, P, R.; Murray, M.; Orpen, A. G. Angew. Chem. Int. Ed. 1996, 35, 1121- 1123.

(124) Experimental EPR spectra were fitted with the EasySpin simulation package: Stoll, S.; Schweiger, A. J. Magn. Reson. 2006, 178, 42-55.

(125) (a) Hudson, A.; Hussein, H. A. J. Chem. Soc. B. 1967, 1299-1300. (b) Eleveld, M. B.; Hogeveen, H. Tetrahedron Lett. 1984, 25, 785-788.

(126) Lavallo, V.; Mafhouz, J.; Canac, Y.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. J. Am. Chem. Soc. 2004, 126, 8670-8671.

(127) For this notation see: Testa, A. C.; Reinmuth, W. H. Anal. Chem. 1961, 33, 1320-1324.

(128) Martin, D.; Canac, Y.; Lavallo, V.; Bertrand, G. J. Am. Chem. Soc. 2014, 136, 3800-3802.

(129) For recent considerations on RSE, see: (a) Menon, A. S.; Henery, D. J.; Bally, T.; Radom, L. Org. Biomol. Chem. 2011, 9, 3636-3657. (b) Coote, M. L.; Lin, C. Y.; Beckwith, A. L.; Zavitsas, A. A. Phys. Chem. Chem. Phys. 2010, 12, 9597-9610. (c) Coote, M. L.; Dickerson, A. B. Aust. J. Chem. 2008, 61, 163-167.

(130) Gaussian 09. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreyen, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Ivengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gompertsm R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian, Inc., Wallingford CT, 2009.

(131) Sun, L.; Diaz-Fernandz, Y. A.; Gschneidtner, T. A.; Westerlund, F.; Lara-Avila, S.; Moth- Poulsen, K. Chem. Soc. Rev. 2014, 43, 7378-7411.

154

155

(132) Ratner, M. Nat. Nanotechnol. 2013, 8, 378-381.

(133) (a) Khan, O.; Martinez, C. J. Science, 1998, 279, 44-48. (b) Weilbel, N.; Grunder, S.; Mayor, M. Org. Biomol. Chem. 2007, 5, 2343-2353.

(134) Andreasson, J.; Pishel, U. Chem. Soc. Rev. 2010, 39, 174-188.

(135) (a) Sato, O.; Tao, J.; Zhang, Y.-Z. Angew. Chem. Int. Ed. 2007, 46, 2152-2187. (b) Camarero, J.; Coronado, E. J. J. Mater. Chem. 2009, 19, 1678-1684.

(136) (a) Haddon, R. C. Nature, 1975, 256, 394-396. (b) Fujita, W.; Awaga, K. Science, 1999, 286, 261-262. (c) Brusso, J. L.; Clements, O. P.; Haddon, R. C.; Itkis, M. E.; Leitch, A. A.; Oakley, R. T.; Reed, R. W.; Richardson, J. F. J. Am. Chem. Soc. 2004, 126, 8256-8265. (d) Beer, L.; Brusso, J. L.; Haddon, R. C.; Itkis, M. E.; Kleinke, H.; Leitch, A. A.; Oakley, R. T.; Reed, R. W.; Richardson, J. F.; Secco, R. A.; Yu, X. J. Am. Chem. Soc. 2005, 127, 18159-18170. (e) Dediu, V. A.; Hueso, L. E.; Bergenti, I.; Taliani, C. Nat. Mater. 2009, 8, 707-716. (f) Barraud, C.; Seneor, P.; Mattana, R.; Fusil, S.; Bouzehouane, K.; Deranlot, C.; Graziosi, P.; Hueso, L.; Bergenti, I.; Dediu, V.; Petroff, F.; Fert, A. Nature Phys. 2010, 6, 615-620.

(137) Kahn, O.; Launay, J. P. Chemtronics, 1988, 3, 140.

(138) (a) Sessoli, R.; Gatteschi, D.; Caneschi, A.; Novak, M. A. Nature, 1993, 365, 141-143. (b) Chibotaru, L. F.; Ungur, L.; Aronica, C.; Elmoll, H.; Pilet, G.; Laneau, D. J. Am. Chem. Soc. 2008, 130, 12445-12455. (c) Bogani, L.; Wernsdorfer, W. Nat. Mater. 2008, 7, 179- 186. (d) Mannini, M.; Pineider, F.; Sainctavit, P.; Danieli, C.; Otero, E.; Sciancalepore, C.; Talarico, A. M.; Arrio, M. -A.; Cornia, A.; Gatteschi, R.; Sessoli, R. Nat. Mater. 2009, 8, 194-197. (e) Lin, P. -H.; Burchell, T. J.; Ungur, L.; Chibotaru, L. F.; Wersdorfer, W.; Murugesu, M. Angew. Chem. Int. Ed. 2009, 48, 9489-9492.

(139) Li, T.; Tan, G.; Shao, D.; Li, J.; Zhang, Z.; Song, Y.; Sui, Y.; Chen, S.; Fang, Y.; Wang, X. J. Am. Chem. Soc. 2016, 138, 10092-10095.

(140) (a) Bernardo, M. M.; Robandt, P. V.; Schroeder, R. R.; Rorabacher, D. B. J. Am. Chem. Soc. 1989, 111, 1224-1231. (b) Cummings, D. A.; McMaster, J.; Rieger, A. L.; Rieger, P. H. Organometallics, 1997, 16, 4362-4368. (c) Pombeiro, A. J. L.; Guedes de Silva, M. F. C.; Lemos, M. A. N. D. A. Coord. Chem. Rev. 2001, 219, 53-80. (d) Ruiz-Molina, D.; Wurst, K.; Hendrickson, D. N.; Rovira, C. Adv. Funct. Mater. 2002, 12, 347-351. (e) Bucher, C.; Moutet, J.-C.; Pécaut, J.; Royal, G.; Saint-Aman, E.; Thomas, F. Inorg. Chem. 2004, 43, 3777-3779. (f) Dei, A.; Gatteschi, D.; Sangregorio, C.; Sorace, L. Acc. Chem. Res. 2004, 37, 827-835. (g) Evangelio, E.; Hendrickson, D. N.; Ruiz-Molina, D. Inorg. Chim. Acta 2008, 361, 3403-3409. (h) Evangelio, E.; Bonnet, M. -L.; Cabañas, M.; Nakano, M.; Sutter, J. -P.; Dei, A.; Robert, V.; Ruiz-Molina, D. Chem. Eur. J. 2010, 16, 6666-6677. (i) Lomoth, R. Antioxidants & Redox Signaling, 2013, 19, 1803-1814. (j) Martins, B.; Schweinfurth, D.; Ehret, F.; Stanislav, Z.; Kvapilova, H.; Fiedler, J.; Zeng, Q.; Frantisek, H.; Wolfgang, K. Organometallics, 2014, 33, 4973-4985.

(141) For reviews see: (a) Tock, C.; Frey, J.; Sauvage, J. P. Molecular Switches; Feringa, B. L.; Browne, W. R., Eds; Wiley-VCH Verlag GmbH and Co.: Germany, 2011, pp. 97-119. (b) Saha, S.; Stoddart, J. F. Functional Org. Mater. 2007, 295-327. (c) Fahrenbach, A. C.; Bruns, C. J.; Cao, D.; Stoddart, J. F. Acc. Chem. Res. 2012, 45, 1581-1592. (d) Antonio, R.; Chiacchio, U.; Corsaro, A.; Romeo, G. Curr. Org. Chem. 2012, 16, 127-160. (e) Fahrenbach, A. C.; Bruns, C. J.; Li, H.; Trabolsi, A.; Coskun, A.; Stoddart, J. F. Acc. Chem. Res. 2014, 47, 482-493.

155

156

(142) (a) Horner, M.; Hünig, S. J. Am. Chem. Soc. 1977, 99, 6120-6122. (b) Horner, M.; Hünig, S. J. Am. Chem. Soc. 1977, 99, 6122-6124.

(143) (a) Ba, F.; Cabon, N.; Robin-Le Guen, F.; Le Poul, N.; Le Mest, Y.; Golhen, S.; Caro, B. Organometallics, 2008, 27, 6396-6399. (b) Ba, F.; Robin-Le Guen, F.; Cabon, N.; Le Poul, P.; Golhen, S.; Le Poul, N.; Caro, B. J. Organomet. Chem. 2010, 695, 235-243. (c) Ba, F.; Cabon, N.; Le Poul, P.; Kahlal, S.; Saillard, J.-Y.; Le Poul, N.; Golhen, S.; Caro, B.; Robin-Le Guen, F. New. J. Chem. 2013, 37, 2066-2081. (d) Gauthier, S.; Vologdin, N.; Achelle, S.; Barsella, A.; Caro, B.; Robin-le Guen, F. Tetrahedron, 2013, 69, 8392-8399.

(144) For other bond forming/breaking redox bistable systems see: (a) Nashida, J.; Suzuki, T.; Ohkita, M.; Tsuji, T. Angew. Chem. Int. Ed. 2001, 40, 3251-3254. (b) Rathore, R.; Magueres, P. L.; Lindeman, S. V.; Kochi, J. K.; Angew. Chem. Int. Ed. 2000, 39, 809-812. (c) Lin, C. -H.; Jhang, J. -F.; Yang, D. -Y.; Org. Lett. 2009, 11, 4064-4067. (d) Nishida, J.; Miyagawa, T.; Yamashita, Y. Org. Lett. 2004, 6, 2523-2526.

(145) Savéant, J.-M. Elements of Molecular and Biomolecular Electrochemistry; Wiley- Interscience; Hoboken, 2006.

(146) (a) Arduengo, A. J., III. US patent 5 077 414, 1991. (b) Arduengo, A. J., III; Dias, H. V. R.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1992, 114, 5530-5534.

(147) Alder, R. W.; Allen, P. R.; Murray, M.; Orpen, A. G. Angew. Chem. Int. Ed. 1996, 35, 1121- 1123.

(148) Yagupolskii, L. M.; Petko, K. I.; Retchitsky, A. N.; Malentina, I. I. J. Fluor. Chem. 1996, 76, 95-98.

(149) (a) Kuhn, N.; Steimann, M.; Weyers, G. Z. Naturforsch. 1999, 54 b, 427-433. (b) Ishiguro, K.; Hirabayashi, K.; Nojima, T.; Sawaki, Y. Chem. Lett. 2002, 796-797. (c) Holbrey, J. D.; Reichert, R. D.; Tkatchenko, I.; Bouajila, E.; Walter, O.; Tommasi, I.; Rogers, R. D. Chem. Commun. 2003, 28-29. (d) Duong, H. A.; Tekavec, A. M.; Louie, J. Chem. Commun. 2004, 112-113. (e) Schmidt, A.; Merkel, L.; Eisfeld, W. Eur. J. Org. Chem. 2005, 2124-2130. (f) Tudose, A.; Demonceau, A.; Delaude, L. J. Organomet. Chem. 2006, 691, 5356-5365. (g) Tommasi, I.; Sorrentino, F. Tetrahedron Lett. 2006, 47, 6453-6456. (h) Zhou, H.; Zhand, W. -Z.; Liu, C. -H.; Qu, J.-P.; Lu, X.-B. J. Org. Chem. 2008, 73, 8039-8044. (i) Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M. Louie, J. J. Org. Chem. 2009, 74, 7935-7942. (j) Delaude, L.; Demonceau, A.; Wouters, J. Eur. J. Org. Chem. 2009, 1882- 1891.

(150) (a) Arduengo, A. J. III; Goerlich, J. R.; Marshall W. J. Liebigs Ann. 1997, 365-374. (b) Alder, R. W.; Blake, M. E. Chem. Commun. 1997, 1513-1514. (c) Alder, R. W.; Chaker, L.; Paolini, F. P. V. Chem. Commun. 2004, 2172-2173. (d) Otto, M.; Conejero, S.; Canac, Y.; Romanenko, V. D.; Rudzevitch, V.; Bertrand, G. J. Am. Chem. Soc. 2004, 126, 1016- 1017. (e) Jolly, P. I.; Zhou, S.; Thomson, D. W.; Garnier, J.; Parkinson, J. A.; Tuttle, T.; Murphy, J. A. Chem. Sci. 2012, 3, 1675-1679.

(151) Kuchenbeiser, G.; Soleilhavoup, M.; Donnadieu, B.; Bertrand, G. Chem. Asian. J. 2009, 4, 1745-1750.

(152) Saif ullah Khan, M.; Nigar, A.; Bashir, M. A.; Akhter, Z. Synth. Commun. 2007, 37, 473- 482.

156

157

(153) Tomioka, H.; Ichikawa, N.; Komatsu, K. J. Am. Chem. Soc. 1992, 114, 8045-8053.

(154) Corrie, J. E. T.; Gradwell, M. J.; Papageorgiou, G. J. Chem. Soc., Perkin Trans. 1, 1999, 2977-2982.

(155) (a) Bamberger, E.; Plyman, F. L. Chem. Ber. 1909, 42, 2317-2330. (b) Clancy, M. G.; Hesabi, M. M.; Meth-Cohn, O. J. Chem. Soc., Perkin Trans. 1, 1984, 429-434.

(156) Schaper, K. Magn. Reson. Chem. 2008, 46, 1163-1167.

157