Synthesis of Contorted Nanographenes Via Multi-Fold Alkyne Benzannulation Reactions

University of Nevada, Reno

Synthesis of contorted nanographenes via multi-fold alkyne benzannulation reactions

A dissertation submitted in partial fulfillment of the Requirements for the degree of Doctor of Philosophy in Chemistry

by Paban Sitaula Prof. Dr. Wesley. A. Chalifoux/ Dissertation Advisor:

May 2020

THE GRADUATE• SCHOOL

We recommend that the dissertation prepared under our supervision by

entitled

be accepted in partial fulfillment of the requirements for the degree of

Advisor

Committee Member

Graduate School Representative

David W. Zeh, Ph.D., Dean Graduate School

Abstract

Nanographenes (NGs) of unique shape, size and properties are always at the center of attraction because of their potential application as semiconducting materials in organo-electronic devices.

Contorted NGs have gained increased attention because of their fascinating molecular packing, reduced π-π interaction, enhanced solubility and lower band gap compared to the planar analogues.

We have synthesized a library of contorted NGs by utilizing the non-oxidative, alkyne benzannulation reaction catalyzed by indium chloride and silver bis triflimide by exploiting high energy content of carbon-carbon triple bonds of the diyne precursors under a mild-reaction conditions.

We employed two-fold InCl3/AgNTf2-catalyzed alkyne benzannulation reaction to afford a broad collection of highly functionalized, laterally π-expanded, [5]helicene-like naphtho[1,2-a]pyrene derivatives in moderate to very good yields. We were able to utilize this method to expand conjugation of the HBC core to get a variety of π-extended HBC NGs. The Suzuki cross-coupling of the halogen(s) substituted smaller polycyclic aromatic hydrocarbons with diyne boronic ester gave polyalkyne precursors, which were subjected to multi-fold alkyne benzannulation reaction to afford larger, highly soluble contorted NGs. This work also proved the applicability InCl3 and

AgNTf2 in the synthesis of up to six benzene ring in one-pot reaction condition. In most of the cases, the chiral, helically twisted skeletons were unambiguously determined through X-ray crystallography. We are also very close (two-steps away) towards the synthesis of longer pyrenacenes such as quateropyrene and quinteropyrene following our previous protocol for the synthesis of pyrene, peropyrene and teropyrene.

ii a) Chiral naphtho[1,2-a]pyrenes

b) Extended chiral HBC NGs

c) Longer functionalized chiral pyrenacenes

iii

Acknowledgements

I would like to express the most sincere appreciation to my advisor, Prof. Dr. Wesley A. Chalifoux, for his willingness and enthusiasm in helping me to become the researcher that I am today. I would also like to thank Dr. Chalifoux for always holding the bar high and helping me to grow my chemical knowledge. He has been absolutely instrumental regarding my success. He has taught me how to become a great researcher, an inspiring teacher and a good human being. Without his guidance, continuous encouragement, persistent motivation and throughout help, this dissertation would not have been possible. I would like to express my sincere thank and deep appreciation to my graduate committee members, Dr. Robert S. Sheridan, Dr. Sean Casey, Dr. Shamik Sengupta, and Dr. Mark

A. Pinsky for their guidance, time, and support during my candidacy exam and dissertation de- fense. I’m very grateful to Prof. Lawrence T. Scott for his thoughtful suggestions every week in our group meeting which really helped me to drive my research projects ahead. I would also like to thank Dr. Vincent Catalano and Dr. Stephen Spain for instrumentation training and for always being there to troubleshoot problems. I would like to acknowledgement to our collaborators Gio- vanna Longhi, Sergio Abbate, Eva Gualtieri, Andrea Lucotti, Matteo Tomassini, Roberta Frazini and Claudio Villani for their contributions in studying optical properties of our compounds.

I would like to thank my lab mates in the Chalifoux lab, particularly Dr. Wenlong Yang and Dr.

Khagendra Hamal for their help when I started working. I would like to thank Punyanuch

Sophanpanichkul, Amber Senese, Kelsie Magiera, Ryan Malone, Stephen George and for their help and support and being nice labmates. I would like to acknowledge faculties, staff, and friends in the UNR Chemistry department for helpful discussions, support and assistance when I needed it most. I would like to thank my parents, whose love and guidance and prayers are with me in whatever I pursue. I’m much grateful to my siblings Bimala and Pawana for always keeping my iv desire at highest priority than their needs. Most importantly, I wish to thank my loving and sup- portive wife, Bimala, and my son Parjanya, who provide unending inspiration.

Table of Contents

1. INTRODUCTION…………………………………………………………………………….1 1.1 Graphene……………………………………………………………………………………...1 1.2 Nanographenes (NGs)………………………………………………………………………. .2 1.3 Clar’s Rule……………………………………………………………………………………4

1.4 Classification of the NGs……………………………………………………………………..5

1.4.1 NGs with zigzag edges……………………………………………………………………...6

1.4.2 NGs with arm-chair edges…………………………………………………………………..6

1.4.3 Zigzag-armchair hybrid NGs……………………………………………………………….7

1.4.4 planar and twisted NG………………………………………………………………………8

1.5 Molecular architectures of chiral NGs……………………………….………………………..9

1.5.1 Helicenes……………………………………………………………………….……..……10

1.5.2 Twistacene……………………………………………………………………….…………10

1.5.3 Propeller-shaped NGs………………………………………………………………………11

1.5.3 Nanohoops and nanotubes (cylindrical NGs)…………………………………….………...12

1.6 Synthetic methods of NGs……………………………………………………………………13

1.7 Alkyne benzannulation reactions………………………………………………….………….16

1.8 Mechanism of electrophilic alkyne benzannulation……………………………….………….24

1.9 Conclusion…………………………………………………………………………………....25

1.10 References………………………………………………………………………………...... 25

2. SYNTHESIS, CHARACTERIZATIONS AND PROPERTIES OF [5]HELICENE-LIKE π-EXTENDED NAPHTHO[1,2-a]PYRENES………………………………………………...34

2.1 Helicenes……………………………………………………………………………………..34 vi

2.1.1 Laterally π-extended helical NGs………….……………………………………………….35

2.2 Naphtho[1,2-a]pyrenes……………………………………………………………………….37

2.2.1 Our route towards naphtho[1,2-a]pyrenes……………….…………………………………37

2.2.2 Synthesis of diyne boronic ester……………………………………………………………38

2.2.3 Synthesis of 3-bromophenantharenes………………………………………………………40

2.2.4 Two-fold alkyne benzannulation reaction………………………………….………………40

2.3 Photophysical properties……………………………………………………………………..44

2.3.1 UV-vis/fluorescence spectra………………………………………………………………..44

2.3.2 Separation of enantiomers……………………………..…………………………………...46

2.3.3 CD spectra of 2.7d and 2.7i…………………………………………………………………49

2.3.4 FTIR Spectroscopy…………………………………………………………………………51

2.3.5 Raman Spectroscopy……………………………………………………………………….52

2.4 Conclusion and future directions………………………………………..……………………54

2.5 Experimental section…………………………………………………………………………56

2.5.1. General experimental……………………………………………………………………...56

2.5.2. Synthesis and characterizations……………………………………………………………57

2.6 Reference…………………………………………………………………………………….90

3. SYNTHESIS OF HBC-BASED π-EXTENDED NANOGRAPHENES VIA ALKYNE BENZANNULATION REACTIONS………………………………………………….….…...94

3.1 Introduction…………………………………………………………………………………..94

3.2 Our design of the π-extended HBC NGs…………………………………………………….98

3.3 Synthesis of π-extended HBC NG analogues………………………………………………100

3.3.1 Mono π-extended HBC NG 3.18………………………………………………………….100 vii

3.3.1.1 Synthesis of pseudo-1-bromoHBC……………………………………………………...100

3.3.1.2 Two-fold alkyne benzannulation reaction towards HBC NG 3.13……………………..102

3.3.1.3 X-Ray crystal structure and racemization barrier of HBC NG 3.18…………………...104

3.3.2 Pseudo-1,2-π-extended HBC NG 3.19……………………………………………………105

3.3.3 Pseudo-1,4-π-extended HBC NG 3.20……………………………………………………107

3.3.3.1 Synthesis of soluble pseudo-1,4-dibromoHBC………………………………………….108

3.3.3.2 Four-fold alkyne benzannulation towards HBC NG 3.15……………………………….109

3.3.3.3 Possible isomers………………………………………………………………………...110

3.3.3.4 Crystal structures and racemization barrier studies of compound 3.20………………...113

3.3.4 UV-vis spectroscopy……………………………………………………………………...115

3.3.5 Attempted synthesis of pseudo-1,3-extended HBC NG…………………………………..116

3.3.6 Pseudo-1,3,5-extended Propeller-shaped HBC NGs……………………………………...118

3.3.6.1 Propeller-shaped NGs (PNGs)………………………………………………………….118

3.3.6.2 Our design of HBC PNG………………………………………………………………..122

3.3.6.3 Synthesis of pseudo-1,3,5-triiodoHBC 3.75…………………………………………….123

3.3.6.4 Six-fold alkyne benzannulation reaction towards HBC NGP 3.21……………………..124

3.3.6.5 Isomers of HBC PNG 3.21……………………………………………………………...125

3.3.6.6 Synthesis of soluble pseudo-1,3,5-triiodoHBC………………………………………...126

3.3.6.7 Attempted synthesis of HBC PNG starting from soluble triiodoHBC 3.88…………….128

3.4 Conclusion…………………………………………………………………………………..131

3.5 Experimental section………………………………………………………………………..132 3.5.1 General Methods………………………………………………………………………….132 3.5.2 Synthesis and characterizations…………………………………………………………..133 viii

3.6 References…………………………………………………………………………………..146

4. SYNTHESIS OF LONGER PYRENACENES…………………………………………...152

4.1 Introduction…………………………………………………………………………………152

4.2 Our design of longer pyrenacenes…………………………………………………………..156 4.3 Attempted synthesis of quateropyrene……………...………………………………………157

4.3.1 Convergent approach toward the synthesis of chiral diiodoperopyrene…………………..157

4.3.1.1 Synthesis of chiral diiodoperopyrene 4-19……………………………………………...157

4.3.1.2 Eight-fold alkyne benzannulation towards the synthesis of quateropyrene…………….163

4.3.1.3 Linear route towards chiral quateropyrene……………………………………………...165

4.4 Attempted synthesis of quinteropyrene…...………………………………………………...167

4.4.1 Synthesis of diiodoteropyrene…………………………………………………………….167

4.5 Conclusion………………………………………………………………………………….169

4.6. Experimental section……………………………………………………………………….170

4.6.1 General experimental:…………………………………………………………………….170

4.6.2 Synthesis and characterizations…………………………………………………………...171

4.7 References…………………………………………………………………………………..182

5. SYNTHESIS OF TETRASUBSTITUTED ALKENES STRARTING FROM A TMS- PROTECTED INTERNAL ALKYNES……………………………………………………...184

5.1 Introduction…………………………………………………………………………………184

5.2 Alkynes as a tetrasubstituted alkene precursors…………………………………………….186

5.3 Our strategy for the synthesis of tetrasubstituted alkenes…………………………………..189

5.4 Synthesis of bis(Z)-haloalkene 5.51………………………………………………………..191

5.5 Conclusion…………………………………………………………………………………..198 ix

5.6 References…………………………………………………………………………………..199

Appendixes……………………………………………………………………………...……..202

Appendix-1 ……………………………………………………………………………………..203

A-1.1 Synthesis of 1,2-diketo-functionalized skipped cyclohexadiene…………………………203

A-1.2 References………………………………………………………………………………..206

Appendix-2 1H and 13C NMR spectra of new compounds ……………………………………..208

List of Tables

Table 2-1: Screening of the suitable conditions for the acid-catalyzed alkyne benzannulation…42

Table 2-2: Rate constant and free energy barriers of enantiomerization…………………………48

Table 4-1: Catalyst screening for two-fold alkyne benzannulation of diiodo terphenyl………...161

Table 5-1: Screening of Sonogashira cross-coupling of vinyl halide with ethynylbenzene derivatives……………………………………………………………………………………………..193

Table 5-2: Screening of the conditions for Suzuki cross-coupling of vinyl iodide with phenyl boronic acid…………………………………………………………………………………….....195

List of Figures

Figure 1-1: Structure of graphene………………………………………………………………...1

Figure 1-2: Some common NGs/PAHs……………………………………………………………3

Figure 1.3: PAHs formed by four benzene rings showing structural diversity of NGs……………4

Figure 1-4: Clar's rule……………………………………………………………………………..5

Figure 1-5: a) Zigzag triangular-shaped NGs b) Resonance structure of phenalenyl radical

1.16………………………………………………………………………………………………...6

Figure 1-6: Arm-chair NGs……………………………………………………………………….6

Figure 1-7: Zigzag-arm-chair hybrid NGs………………………………………………..………8

Figure 1-8: a) Stacking in planar PAHs b) Minimized π-π interaction in twisted PAHs [picture adapted from ref. 58] c) Helical chirality………………………………………………………….8

Figure 1-9: Helicene NGs………………………………………………………………………..10

Figure 1-10: Twistacenes………………………………………………………………………..11

Figure 1-11: Propeller-shaped NGs……………………………………………………………...11

Figure 1-12: Cylindrical NGs……………………………………………………………………12

Figure 2-1: A)Helicene Cartesian co-ordinates B) Lateral π-extension along x-axis C) Helical π- expansion through z axis D) Lateral and helical π-expansion……………………………………35 xii

Figure 2-3: UV-vis spectra of naphtho[1,2-a]pyrenes……………………………………….....45

Figure 2-4: UV-vis and emission spectra of 2.7a…………………………………………….....46

Figure 2-5. Enantioselective HPLC of 2.7d (a) and 2.7i (b) using UV (280 nm, red traces) and

CD (300 nm, blue traces) detections……………………………………………………………...47

Figure 2-6. Comparison of calculated and experimental ECD and absorption spectra of compounds 2.7d (left) and 2.7i (right)………………………………………………………………..51

Figure 2-7. The experimental micro FT-IR spectra of compounds 2.7(b-i) across the fingerprint region…………………………………………………………………………………………….53

Figure 2-8. The experimental micro FT-Raman spectra of compounds 2.6(b-i) across the G and

D-band regions…………………………………………………………………………………...54

Figure 3-1: Hexa-peri-hexabenzocoronene (HBC) molecule…………………………….……..94

Figure 3-2: Analogous numbering/nomenclature of benzene HBC derivatives…………...……95

Figure 3-3: HBC derivatives used in organo-electronic devices………………………….…..…96

Figure 3-4: Examples of current trends of chemical modification of HBC molecules…………..97

Figure 3-5: Our design of a chiral HBC NGs……………………………………………….……99 xiii

Figure 3-6: a) Mono-extended HBC showing embedded chiral teropyrene (in magenta) b) HBC

NG 3.13 showing phenalenyl-fused on HBC……………………………………………………100

Figure 3-7: Single crystal structure of HBC NG 3.18 (left), lateral view of compound 3.18 (middle), Skewed view of compound 3.18 (right)……………………………………………….…..104

Figure 3-8: Experimental racemization route compound 3.18………………………………….105

Figure 3-9: HBC NG 3.19 showing two phenalenyl moieties fused on HBC core (left), embedded

[7]helicene-like moiety (middle), calculated structure (right)…………………………….…….105

Figure 3-10: HBC NG 3.20 showing embedded quateropyrene (left), and two phenalenyl moieties fused on HBC core in 1,4-positions (right)……………………………………………………..108

Figure 3-11: Some possible isomers of HBC NG 3.20…………………………….……………111

Figure 3-12: Predicted pathways towards chiral 3.20a and meso-3.20b products…..…………..113

Figure 3-13: a) Crystal strucures of 3.15a b) Crystal structure of 3.15b ……………………...114

Figure 3-14: Racemization study of chiral HBC NG 3.20a……………………..………………115

Figure 3-15: Combined UV-vis plots of compounds 3.18, 3.19. 3.20……………….………….116

Figure 3-16: Mode of twisting in propeller-shaped architecture (A-C)……………..…………..119

Figure 3-17: PNGs………….…………………………………………………………………..120

Figure 3-18: Propeller-shaped nanographene with HBC core A) Hexapole [7]helicene B) Hexa- pole[9]helicene C) N-doped hexapole [7]helicene……………………………………………..121

Figure 3-19: Retrosynthetic analysis of PNG 3.21……………………………………………..123 xiv

Figure 3-20: Some of the possible isomers of HBC PNG 3.21………………………………….126

Figure 4-1: Structure of pyrenacenes…………………………………...………………………153 Figure 4-2: Pyrenacenes structures and their Clar’s aromatic sextet representation…….………153 Figure 4-3: The λmax vs. pyrenacene length plot for pyrenacenes ………………………...... 154

Figure 4-3: UV-vis spectra of compound 4.19………………………………...………...…….168 Figure 5-1: Distortion from normal trigonal planar structure in tetrasubstituted alkenes………185

Figure 5-2: Biologically active natural products containing tetra-substituted alkenes…………185

Figure 5-3: Examples of tetra-substituted alkenes used in organo-electronic devices…….……186

Figure 5-4: Classical anti-dibromination of alkyne………………………..…………………...190

List of Schemes

Scheme 1-1 A) Scholl reaction B) Cyclotrimerization reaction in the synthesis of NGs C) Friedel-

Craft type of reaction yielding [6]helicene………………………………….……………………14

Scheme 1-2: APEX approach toward NGs syntheses……………………………………………15

Scheme 1-3: The Itami group's APEX polymerization toward cove type GNR…………………15

Scheme 1-4: Metal-catalyzed alkyne benzannulation reactions…………………………………17

Scheme 1-5: The Swager group’s TFA-catalyzed alkyne benzannulation reactions…………….18

Scheme 1-6: The Chalifoux group's Brønsted acid catalyzed alkyne benzannulation reaction towards A) NGs and B) AGNR…………………………………………………………………….19

Scheme 1-7: The Chalifoux group's Lewis acid-catalyzed alkyne benzannulation reaction towards

NGs syntheses……………………………………………………………………………………20

Scheme 1-8: Thermal and photochemical alkyne benzannulation reactions……………………21

Scheme 1-9: Base-catalyzed alkyne benzannulation reactions………………………………….22

Scheme 1-10: Electrochemical alkyne benzannulation reaction………………………………..22

Scheme 1-11: Radical mediated cascade alkyne benzannulation………………………………..23

Scheme 1-12: Iodine salt mediated alkyne benzannulation reactions……………………………24

Scheme 1-13: Mechanism of electrophile-catalyzed alkyne benzannulation……………………24

Scheme 2-1: Retrosynthetic analysis of pyrene-naphthalene hybrid 2.7…………………...……37 xvi

Scheme 2-2: Synthesis of diiodobromobenzene derivatives……………...……………………..38

Scheme 2-3: Synthesis of terminal alkynes……………………………………...……………....38

Scheme 2-4: Synthesis of bromodiyne boronic ester……………...……………………………..39

Scheme 2-5: Synthesis of 3-bromophenanthrenes……………………………………..………...40

Scheme 2-6: Synthesis of diyne precusors2.8……………….……...……………………………41

Scheme 2-7: Two-fold alkyne benzannulation reaction yielding naphtho[1,2-a]pyrenes ……….43

Scheme 2-8: Selective mono-benzannulation resulting 7j and 7k……………………………….44

Scheme 2.9: Future works towards π-extended helical NGs 2.23………………………………..55

Scheme 3-1: Synthesis of diphenylacetylene 3.26……………………………………………...101

Scheme 3-2: Synthesis of cyclopentadienone 3.29…………………………………………….101

Scheme 3-3: Synthesis of soluble monobromoHBC 3.32……………………………………..102

Scheme 3-4: Synthesis of chiral HBC NG 3.18……………………………………………….103

Scheme 3-5: Synthesis of pseudo-1,2-dibromoHBC 3.41……………………………………..106

Scheme 3-6: Synthesis of HBC NG 3.19………………………………………………………107

Scheme 3-7: Synthesis of soluble dibromoHBC 3.46………………………………………….109

Scheme 3-8: Synthesis of HBC NGs 3.20……………………………………………………..110

Scheme 3-9: Synthesis of cyclopentadienone 3.59……………………………………………..117

Scheme 3-10: Attempted synthesis of pseudo-1,3-dibromoHBC 3.62…………………………118 xvii

Scheme 3-11: Sygula's synthesis of corannulene PNG 3.69……………………………………120

Scheme 3-12: Wang's synthesis of seven HBC-fused PNG (figure adapted from ref. 32)…….122

Scheme 3-13: Synthesis of triiodoHBC 3.75……………………………………………………124

Scheme 3-14: Synthesis of HBC PNG 3.21 via six-fold alkyne benzannulation reaction………125

Scheme 3-15: Attempted synthesis of compound 3.90…………………………………………127

Scheme 3-16: Synthesis of soluble triiodoHBC 3.99…………………………………………..128

Scheme 3-17: Serendipitous formation of saddle-shaped NG (SNG) 3.102…………………….129

Scheme 3-18: Predicted pathways towards compound 3.102………………………………….130

Scheme 3-19: Possible mechanism for the formation of compound 3.102…………………….131

Scheme 4-1: The Chalifoux group's synthesis of pyrenacenes…………………………………155

Scheme 4-2: Our design of quateropyrene and quinteropyrene…………...……………………156

Scheme 4-3: Attempted synthesis of ditriazine tetrayne 4.25…………………………………..158

Scheme 4-4: Synthesis of ditriazine tetrayne…………………………………………………..158

Scheme 4-5: Attempted alkyne benzannulation of ditriazine tetrayne………………………….159

Scheme 4-6: MeI reaction of ditriazine 4.25 yielding diiodo analogue 428……………………160

Scheme 4-7: Synthesis of quateropyrene 4.14………………………………………………....162

Scheme 4-8: Attempted synthesis of octayne precursor via direct Suzuki cross-coupling of triazine with boronic ester……………………………………………………………………………….163 xviii

Scheme 4-9: Attempted eight-fold alkyne benzannulation reaction towards chiral quateropyrene

4 14……………………………………………………………………………………………...164

Scheme 4-10: Proposed linear route towards chiral quateropyrene 4.42……………………….165

Scheme 4-11: Attempted linear synthesis………………………………………………………166

Scheme 4-12: Methods to try in the future towards dihalo-functionalized peropyrene…………167

Scheme 4-13: Progresses towards synthesis of diiodoteropyrene 4.19…………………………169

Scheme 5-1: Carbometallation of alkynes resulting tetrasubstituted alkenes………………….187

Scheme 5-2: Ruthenium catalysed functionalization of alkyne yielding tetrasubstituted alkene…………………………………………………………………………………………...188

Scheme 5-3: Palladium-catalyzed domino-Heck double cyclization yielding tetrasubstituted alkene…………………………………………………………………………………………...... 188

Scheme 5-4: Hosomi's iron-catalyzed synthesis of tetrasubstituted alkene……………….……189

Scheme 5-5: Larock's multicomponent one-pot synthesis of tetrasubstituted alkene……….…189

Scheme 5-6: ICl addition generating bis(Z)-haloalkene and bis(E)-haloalkene………………..190

Scheme 5-7: Mechanism of syn-dihalogenation………………………………………………..191

Scheme 5-8: Synthesis of syn-dihalo-TMS-alkene starting 5.51……………………………….192

Scheme 5-9: Attempted Sonogashira cross-coupling of vinyl iodide with phenyl acetylene….192

Scheme 5-10: Attempted Suzuki cross-coupling of vinyl iodide with phenyl boronic acid…….194 xix

Scheme 5-11: Attempted Negishi cross-coupling of phenyl zinc iodide with vinyl iodide……..196

Scheme 5-12: Failed Negishi cross-coupling of decyl zinc iodide with vinyl iodide………..….196

Scheme 5-13: Failed attempt to synthesize vinyl zinc iodide…………………………………...197

Scheme 5-14: Attempted trapping of vinyl carbanion with benzaldehyde……………………..197

Scheme 5-15: Control experiment to trap vinyl carbanion with water…………………………198

Scheme A-1: Synthesis of skipped cyclo-1,4-hexadiene through Birch reduction……………...203

Scheme A-2: Synthesis of bicyclic furan via copper-catalyzed alkyne cyclization reactions…..204

Scheme A-3: Synthesis of dihydroisobenzofuran carboxaldehyde via silver catalyzed alkyne cyclization…………………………………………………………………………………………204

Scheme A-4: Synthesis of vicinal diketone functionalized skipped dienes…………………….205

Scheme A-5: Mechanism of formation of dihydroisobenzofuran carboxaldehyde (path I) and diketo skipped diene (path II)…………………………………………………………………..206

List of Abbreviations/Acronyms

NGs = Nanographenes

GNRs = Graphene nanoribbons

HPB = Hexaphenylbenzene

PNG = Propeller-shaped nanographene

PAH = Polycyclic aromatic hydrocarbon r.t. = Room temperature

T = Temperature dtbpy = 4,4′-Di-t-butyl-2,2′-dipyridyl

HOMO = Highest Occupied Molecular Orbital

LUMO = Lowest Unoccupied Molecular Orbital

Endo = Endocyclic

Dig = Diagonal

NBS = N-Bromosuccinimide

TFA = Trifluoroacetic acid

TfOH = Triflic acid

DDQ = 2,3-dichloro-5,6-dicyanobenzoquinone

DCM = Dichloromethane

PE = Petroleum ether

DMSO = Dimethyl sulfoxide

THF = Tetrahydrofuran

EtOAC = Ethyl acetate pTSA = p-Toluene sulfonic acid xxi

MSA = methyl sulfonic acid

ΔG‡ = Gibbs free energy of enantiomerization

CD = Circular dichroism

DHPLC = Dynamic high performance liquid chromatography

HPLC = High performance liquid chromatography

CSP = Chiral stationary phase

CPL = Circularly polarized luminescence

UV-vis = Ultra-violet and visible wavelength light ppm = parts per million

Equiv. = Equivalent

HRMS = High resolution mass spectroscopy

FTIR = Fourier transform infra-red h = hour(s)

Rf = Retention factor

TLC = Thin layer chromatography

ESI = Electron spray ionization

TOF = Time of flight

MALDI = Matrix-assisted laser desorption ionization xxii

APPI = Atmospheric pressure photoionization

NMR = Nuclear magnetic resonance

MHz = Megahertz 1

1. Introduction Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compound consisting of more than one aromatic rings made up of carbons and hydrogens.1-3 They are found naturally in oil, coal and tar. They have been studied as a common environmental pollutant and carcinogens as they are

4 the products of combustion of fuel. PAHs have found application in different fields such as in dyes, drugs, fluorescent and chemiluminescent reagents, and as semiconductors in electronic de-

5, 6 vices.

1.1 Graphene

The term Graphene was first introduced by Hanns-Peter Boehm in 1962 to describe mono-layered carbon foil which at present defined as a two-dimensional, one atom thick allotrope of carbon composed of planar, honeycomb like hexagonal network of sp2-hybridized carbons.7 It is a basic building block of all graphitic materials.8 Graphene has two main regions, basal planes and the edges.9, 10 The edges can exist in two major forms, zig-zag and arm-chair structure.11 The zig-zag edges have less local aromaticity arising due to the frustrated aromatic sextet. Because of this, a zig-zag edge is more reactive and less stable compared to arm-chair edges which exists in fully benzenoid form .12 13

The first discovery of graphene was done by Novose- lov and Giem et al. in 2004 by mechanical exfoliation from a lump of graphite using a scotch tape and in the following few years, it became a hottest topic in con- dense matter physics.14, 15 The pioneering work by these two scientists was recognized by the Nobel Prize Figure 1-1: Structure of graphene. 2 in physics in 2010.16 Several other methods for the efficient synthesis of graphene has been reported over the course of time. Chemical vapor deposition is another method of making high quality, polycrystalline graphene film of large surface area. It is an efficient method which can be done on transition metal surfaces.17, 18 For instances, Bae et al. have reported the synthesis of graphene monolayer of size more than 30 inches on the copper surface.19 The major limitations of this method is high cost, large energy consumption and difficulties in transferring graphene product from metal surfaces.20, 21 Epitaxial growth is another graphene fabrication technique. that can be done on SiC surfaces. This method also allows us to control the number of layers of graphene being formed.22-24

Because of the continuous conjugation arising from the alternative single and double bond throughout the sheet, graphene has interesting electronic properties such as electrical conductivity, low resistivity, better current capacity, linear dispersion Dirac-particles, and high light absorption coefficient.25-28 It has some other unusual physical properties like high elasticity, low density, and is one of the strongest material found in the world.29 Because of these properties, graphene has found applications in various filed such as electronic devices, sensing, gas and energy storage, micro and optoelectronics and military purposes. However, application of graphene as a semiconducting materials has been limited by its band gap (the energy gap between the valence and con- ducting band) as it is a zero band gap material.30 Therefore, it is necessary to open a finite band gap which can be done by various ways.

1.2 Nanographenes (NGs)

There are various mechanisms to open band gap in graphene. Synthesis of graphene nanoribbons,31 chemical functionalization of graphene,32, 33 or by synthesizing structural sub-cuts of graphene34 are major ways to induce band gap in graphitic materials. Nanographenes (NGs) (Figure 1.2), also 3 known as graphene nanodots or PAHs, are the structural fragments of the graphene sheet. They are organic compounds having more than one aromatic rings. Naphthalene is the smallest polycyclic aromatic hydrocarbon having two fused aromatic rings. Similarly, anthracene 1.1, tetracene

1.2, pentacene 1.3 phenanthrene 1.4, chrysene 1.6, etc., are larger PAHs.5, 6. PAHs made up of aromatic rings fused in the linear fashion are called linear PAHs or acenes (compounds 1.1-1.3) and those containing non-linearly fused aromatic rings are called angular PAHs (compounds 1-4 to 1-12).35-38

Figure 1-2: Some common NGs/PAHs.

NGs are intensely studied organic compounds because of their structural diversity and wide applications in material sciences. The mode of fusion of the aromatic rings can lead to the structural 4 diversity. For example, seven different structural isomers can be written with four benzene rings namely, tetracene 1.1, triphenylene 1.4, crysene 1.6, pyrene 1.7, tetraphene 1.13, benzo[c]phenanthrene 1.14, and benzo[d,e]anthracene 1.15 (Figure 1-3). If we use all the permutations and com- binations, we can draw numerous different nanographene molecules using up to ten benzene rings.

The interesting optical and electronic properties of these molecules arising because of the delocal- ization of the electrons have garnered considerable attention of scientists. The era of NGs began after the discovery of semiconducting polymer and discotic liquid crystals by Chandrasekhar in

1970’s.39-42 The combined electronic, optical and self-assembling properties of these materials have broadened the scope of their applications in light emitting diodes (LED), field-effect transistors, solar cells and liquid crystal displays (LCDs).43, 44

Figure 1.3: PAHs formed by four benzene rings showing structural diversity of NGs.

1.3 Clar’s Rule

The term aromaticity is used to explain the thermodynamic stability of cyclic conjugated system.

There are certain physical properties such as bond lengths, anisotropy, planarity, ring current, re- stricted rotations which can be used to explain aromaticity quantitatively. To explain relative qual- itative stability and aromatic character of benzenoid species, Enrich Clar in 1972 formulated a rule 5 which is known as Clar’s rule or Clar’s aromatic π-sextet rule. This rule states that the resonance structure having largest number of aromatic sextets are more favored structure because of it’s higher stability. The aromatic sextet refers to the six π-electrons localized within a benzene ring which is generally noted by a circle inside a benzene ring.45 For linear acenes such as anthracene

1.1, only one aromatic sextet results (Figure 1-4A) and thus the poly-alkene character grows as the number of rings increases. Hence, longer acenes undergo cycloaddition reaction, thereby gain- ing more aromatic sextets.46 In conjugated π-systems, in which six-membered rings are fused in an angular fashion such as in phenanthrene 1.4, more than one aromatic sextet can be written

(Figure 1-4B), indicating higher local aromaticity of angular NGs compared to linear analogues.

Figure 1-4: Clar's rule.

1.4 Classification of the NGs

Based on the edge structures, NGs can be divided into three categories, zigzag, armchair and hybrid NGs. Based on the planarity of the molecules, they can be divided into two classes, planar and contorted/twisted NGs.

1.4.1 NGs with zigzag edges

These NGs are segment of graphene with zigzag motif. They contain benzene rings fused in a triangular fashion, because of which, they have a non-Kekulé structure or open-shell character (i.e. molecules having one or more unpaired electrons). One of the simplest member of this category is phenalenyl radical 1.16 which is composed of three benzene rings. It contains an unpaired electron with spin multiplicity of 2. π-Extension of this molecule in a triangular way results in the formation of triangulene 1.17 with two unpaired electrons and sin multiplicity of 3. Further π-extension results in the formation of extended triangulene 1.18 (Figure 1-4).

Figure 1-5: a) Zigzag triangular-shaped NGs b) Resonance structure of phenalenyl radical 1.16.

1.4.2 NGs with arm-chair edges

Figure 1-6: Arm-chair NGs.

Graphene fragments of defined shape with fully arm-chair edges are called arm-chair NGs. They are closed-shell in nature because they can form all benzenoid resonance structure without any 7 isolated double bond or unpaired electron. These kind of NGs usually have high stability and relatively larger band gap. They can self-organize into columnar mesophases because of their stacking properties. This property makes them a potential candidates in electronic applications such as photosensors and photovoltaics. Hexa-peri-hexabenzocoronene (HBC) 1.19, often known as expanded superbenzene is most widely studied NGs of this class of NG which was first synthesized by Clar in 1958. Later on, the Halleux, Scmidt, Müllen and Rathore groups have made significant contribution in the synthesis of functionalized, soluble as well as in π-expansion of HBC core 1.20-

1.22 (Figure 1-7).47, 48, 49, 50

1.4.3 Zigzag-arm-chair hybrid NGs

If we cut the graphene into a rectangular fragment, it results into the NGs containing both zigzag and armchair edges (Figure 1-8). Rylenes 1.23, anthenes 1.24, and periacenes 1.25 are the most common NGs of this category. Rylenes are also known as peri-fused naphthalenes having two zigzag edges. π-Extension of rylene results into anthenes 1.24, also known as peri-fused anthracene, containing three zigzag edges and extended armchairs. Further π-extended analogues of anthenes are called periacenes 1.25, which preserves two armchair edges and extended zigzag structures. The relative stability of these kind of NGs can be predicted based on the number of Clar sextet that can be drawn for those molecules. Anthenes and periacenes are more stable compared to rylenes because they have extended Clars aromatic sextets.51-53 8

Figure 1-7: Zigzag-arm-chair hybrid NGs.

1.4.4 planar and twisted NGs

Unsubstituted PAHs adopt a planar configuration and can establish strong - interactions (Figure

1-8a) that leads to decreased solubility and difficulty in their purification and characterizations.

This low solubility also limits their utility in different solution-based processes. The - interacti-

Figure 1-8: a) Stacking in planar PAHs b) Minimized π-π interaction in twisted PAHs [picture adapted from ref. 58] c) Helical chirality. on is also responsible for the quenching of fluorescence because of excimer formation.35, 54 One of the ways to overcome this limitation is by twisting them out of planarity and breaking the - 9 stacking (Figure 1-8b).There are two more common ways to force planar NGs to nonplanar structures. First one is inducing steric strain through atom overcrowding and another is by embedding non-hexagonal rings.55, 56 Embedding non-hexagonal rings can induce two major type of twists from the planarity, positively curved (bowl-shaped) and negatively curved (saddle-shaped) structures. NGs consisting of a four- or five-membered ring generally adopt a positively curved bowl- shaped structure, while NGs having non-hexagonal (more than six-membered) rings adopt a negatively curved architecture.57 Sometimes, twisting a planar NG can result a chiral NG with a stereogenic axis making it chiral. and such chirality is also known as helical/axial chirality. Helical chirality is a property of chiral systems that do not contain chiral center (asymmetric unit where four non-equivalent points represent the vertices of a tetrahedron). For a helically chiral system, the relative stereochemistry is assigned based on the handedness of the helices. Right handed helices are represented by ‘P’ and left handed helices are represented by ‘M’ (Figure 1-8c).58

Compared to planar NGs, twisted NGs show a variety of fascinating molecular packing structures.59-61 Due to their helical structure, - interactions are minimized which makes them soluble in common organic solvents. This also leads towards some useful properties such as chiroptical properties, nonplanarity, optical rotation (OR), and dynamic behavior which make them of great interest for applications in nonlinear optics, switches, and sensors.62, 63 Recently, compounds with multi-helicity (more than one helical units within the same molecule) have garnered attention due to their plural electronic states and interesting molecular dynamics.58

1.5 Molecular architectures of chiral NGs

Because of the steric repulsion arising due to the overcrowding of atoms, chiral NGs can adopt various structural shapes.58 Some very common molecular architectures are described below. 10

1.5.1 Helicenes

Helicenes are an important class of nanographene having ortho-fused aromatic rings. Because of the steric interaction between terminal rings, they get twisted out of the planarity and assume helical configuration and is responsible for some of their the interesting photophysical properties like optical rotation and circular dichroism.64 These axially chiral molecules have a stereogenic axis that does not intersect the helical body. The general representation of these molecules is [n]helicene, where, n represents the number of aromatic rings ortho-fused making the body of the helicenes (Figure 1-9). For the helicene with n>3, the average torsional angle ranges from 19° (for n=4) to 24° (for n=16).58, 65

Figure 1-9: Helicene NGs.

Compounds 1.26-1.28 are some examples of helical NGs. Helicenes having carbon atoms in the helical skeleton are called carbohelicenes (1.27-1.28), while, if at least one carbon in helical skeleton replaced with a heteroatom are called heterohelicenes (1.26).

1.5.2 Twistacenes

Another class of twisted NGs are twistacenes (Figure 1-10), which are formed by deformation of the planar nanographene along its main molecular axis. These kind of NGs contain high degree of symmetry with edges of same length simplifying the synthesis of these molecule. PAHs 11 comprising linearly fused aromatic rings (aka acenes) are more suitable for such deformations.

Perphenylated anthracene 1.29 reported by Pascal in 1996, shows a twist of 63° in the solid state structure. Twistacene 1.30 has very large twist angle of 144° which is the largest induced twist to date. The nonatwistacene 1.31 is a stable acene derivative with π-extended ends shows average twisting of 7.1° per benzene rings.66

Figure 1-10: Twistacenes.

1.5.3 Propeller-shaped NGs

When a highly symmetric molecule gets twisted on the same direction with an equal angle along at least three axes, that molecule adopts the propeller-shape molecular architecture. Propeller- shaped NGs (PNGs) are the reminiscent of a propeller which contain the outer blade subunit fused on the central core.58 Because of the sterics, the outer blade gets twisted out of the planarity from a central core. The first PNG, cloverphene 1.32 was reported by Pascal and coworkers in 1999 which contains three-[5]helicene blades fused on the benzene core.67 Compound 1.33 is corannulene propeller containing three corannulene blades fused on a benzene core.68 Compound 1.34 is a [5]helicene propeller containing six-fold helicity reported by Gingras and coworkers (Figure 1-

11).69 12

Figure 1-11: Propeller-shaped NGs.

1.5.4 Nanohoops and nanotubes (cylindrical NGs)

Carbon-rich nanohoops (Figure 1-12) are a class of PAH having radial -conjugation having in- triguing optoelectronic properties and interesting shapes. This class of NG contains a cyclic array of carbon atoms in a pearl necklace form of benzene or a its cylindrical hoop. There are mainly two types of arene fusion observed in nano hoops. One is angular fusion of benzene rings leading to the formation of an arm-chair belt 1.35 and the other one is flank-fused benzenes resulting zigzag nanographene belt 1.37.70

Figure 1-12: Cylindrical NGs. 13

1.6 Synthetic methods of NGs

There are number of methods reported for the synthesis of NGs to date. The Scholl reaction

(Scheme 1-1A) is an efficient and well-known methods used for the synthesis of NGs of different shapes, sizes and edge structures.71-75 The Müllen group has extensively utilized Scholl chemistry in the synthesis of a library of NGs. The scopes of the Scholl reaction has been limited by several factors, including incomplete graphitization, unwanted halogenation, unexpected structural rear- rangements, low yields, and difficulties of purifications.50, 76, 77 Cyclotrimerization is another important method employed for the synthesis of NGs of smaller and larger sizes which was developed by the Diego Peña group in 1998. They synthesized tripentacene propeller 1.42 using nickel catalyzed cyclotrimerization of dibromotetracene 1.41 in 52% yield (Scheme 1-1B). In the recent years, this method has been adopted by other groups to arrive at a structurally complex, larger NGs through this single-step metal-catalyzed chemical transformation.78, 79 A Friedel-Craft type of reaction has also been reported as a powerful method for the synthesis of NGs. One representative example is the synthesis of [6]helicene reported by Newman and coworkers, wherein they started with a dicarboxylic acid 1.43 and carried out two-fold sequential Friedel-Craft acylation/reduction/hydrogen transfer reactions to arrive at [6]helicene 1.45 (Scheme 1-1C).80, 81

Scheme 1-1 A) Scholl reaction B) Cyclotrimerization reaction in the synthesis of NGs C) Friedel-

Craft type of reaction yielding [6]helicene.

Annulative π -extension (APEX) is another efficient approach that allows the rapid access of structurally uniform NGs. This is a bottom-up, ‘growth from template’ approach to afford a larger NGs starting from smaller template NGs. The Itami group has utilized this method to synthesize a variety of NGs. These APEX reactions can be carried out selectively in a specific region (bay-region, 15

K-region and L-region) of a substrate/template NGs (Scheme 1-2).82, 83

Scheme 1-2: APEX approach toward NGs syntheses.

The Itami group have also utilize the APEX polymerization (Scheme 1-3) in the synthesis of graphene nanoribbon (GNR). They heated a silicon-bridged phenanthrene monomer 1.52 in dichlo- roethane at 80 °C in the presence of palladium(II)trifluoroacetate (1 equiv.), AgSbF6 (1 equiv.), o- chloranil (2 equiv.) to arrive at a cove-type NG 1.53.84

Scheme 1-3: The Itami group's APEX polymerization toward cove-type GNR. 16

1.7 Alkyne benzannulation reactions

Alkyne annulation reactions are a powerful synthetic tool to construct a variety of important structural motifs such as five-membered rings, six-membered rings, substituted skipped dienes, and

[6,5,6] molecular scaffolds.85-88 Because of the high energy content in alkynes, they can undergo irreversible chemical transformations to yield stable lower energy products. Recent research has shown that, alkynes can undergo various chemical transformations like Friedel-Craft alkylation, acylation, Diels-Alder reaction, metal catalyzed alkyne cyclization, and radical initiated cascade reaction.89-92 The alkyne benzannulation reaction is the synthesis of a benzene ring using alkyne precursors, and has been an important tool for the construction of PAHs.93 This mild and efficient method that does not involve oxidative aryl-aryl coupling (cyclodehydrogenation) to extend the π- conjugation by synthesizing number of benzene rings in a single step starting from a readily available aromatics.

Alkyne benzannulation reactions have been reported to proceed using a variety of -Lewis acids such as gold(III), platinum(II), ruthenium(II), indium(III) and antimony(V).94-97 The Yamamoto group has reported the utilization of AuCl3-catalyzed [4+2] benzannulation reaction of o-alkynyl benzaldehydes 1.54 and alkynes 1.55 to afford keto-functionalized naphthalene derivatives 1.56.98

The Müllen group has shown an efficient use of platinum catalyst in the benzannulation of both internal and terminal alkyne substrates. One example is the platinum-catalyzed two-fold alkyne benzannulation of diyne 1.57 affording bischrysene molecule 1.58 .99 The Liu and Storch groups have utilized platinum-catalyzed alkyne benzannulation reaction for the synthesis of library of helical NGs.100, 101 The Scott group has reported a series of by Ru-catalyzed alkyne benzannulation reaction of diaryl tetraethynyl diethylenes 1.59 to afford coronene 1.60.102 Swager and coworkers 17 have reported efficient synthesis of dibenzochrysene derivatives 1.62 employing antimony-catalyzed alkyne benzannulation reactions of alkynes 1.61. The Fürstner group has reported the synthesis of substituted phenanthrenes and other heteroarenes using indium- and platinum-catalyzed alkyne benzannulation reaction.103 These reactions proves the efficiency of metal catalyzed alkyne benzannulation towards the synthesis of NGs (Scheme 1-4).

Scheme 1-4: Metal-catalyzed alkyne benzannulation reactions.

Brønsted acids such as TFA, TfOH etc. are also reported to be efficient catalysts to afford NGs through alkyne benzannulation reactions. This type of transformation was first reported by the

Swager group. Electron rich aryl substituted alkynes 1.63 and 1.64 when treated with TFA, two- fold alkyne benzannulation reactions afforded NGs 1.64 and 1.66 in excellent yields (Scheme 1-

5).104 18

Scheme 1-5: The Swager group’s TFA-catalyzed alkyne benzannulation reactions.

Later on, Chalifoux group extensively studied the utility of acid-catalyzed alkyne benzannulation reactions to synthesize a variety of NGs. In 2017, they reported the synthesis of highly soluble pyrene 1.70, peropyrene 1.71, and teropyrene 1.72 through TFA/TfOH-catalyzed two- and four- fold alkyne benzannulation reactions of precursor electron rich alkyne derivatives 1-91 (Scheme

1-6A). They were able to utilize this method for the synthesis of highly soluble arm-chair graphene nanoribbon (AGNR) 1.74 using a one-pot, multi-fold alkyne benzannulation reaction of the polyalkyne 1.73 (Scheme 1-6B).105-107

Scheme 1-6: The Chalifoux group's Brønsted acid catalyzed alkyne benzannulation reaction towards A) NGs and B) AGNR.

The scope of alkyne benzannulation was expanded by using InCl3 and AgNTf2 as a catalyst to afford highly irregular NGs. The 1,3-butadiyne 1.75 when heated in toluene with aforementioned catalyst afforded NGs of different sizes 1.77-1.80, through a regioselective domino two-fold alkyne benzannulation reactions (Scheme 1-7).108-110 20

Scheme 1-7: The Chalifoux group's Lewis acid-catalyzed alkyne benzannulation reaction towards

NGs syntheses.

Beside these methods, Some conventional methods such as thermal pyrolysis and photochemical alkyne benzannulation reactions are also reported. Thermal alkyne benzannulation approach was first reported by Musso and coworkers in 1969 where they were able to synthesize benzene 1.82 by heating dienyne 1.81. 111 Later on, This method was utilized by different other groups to make larger PAHs.112, 113 The Scott group has reported the synthesis of bowl-shaped NG corannulene

1.84 by flash vacuum pyrolysis (FVP) of diyne 1.83.114 Photochemical alkyne benzannulation are more common to synthesize smaller PAHs and barely used to synthesize larger NGs. One example of such transformation is synthesis of phenanthrene 1.86 reported by Gevorgan and Laarhoven starting from a biphenyl alkynes 1.85 (Scheme 1-8).115-117 21

Scheme 1-8: a) Thermal and b) Photochemical alkyne benzannulation reactions.

Some amine bases have also been reported to have catalytic activity to induce alkyne benzannulation reactions. The Gao group have reported the synthesis of π-extended terrylenediimide (TDI)

1.87 by utilizing DBU-catalyzed alkyne benzannulation reactions of tetrayne 1.87.118 Geng and coworkers have adopted similar approach for the synthesis of an extended thienoacenes 1.89 consisting of 13 fused aromatic rings (Scheme 1-9).119 The Alabugin group has reported the synthesis of isoquinoline derivatives 1.91 via DBU-catalyzed alkyne benzannulation of enynes 1.90 in good to excellent yields..

Scheme 1-9: Base-catalyzed alkyne benzannulation reactions.

Electrochemical reactions has been taken as a very efficient, mild and green synthetic methods in organic chemistry.120 Electrochemical alkyne cyclization reaction is rarely reported in the literature. Xu group has utilized electrochemical cascade alkyne cyclization reactions to synthesize N- doped NGs. They have synthesized N-doped NGs 1.93 starting from a urea-tethered diyne 1.92 using ferrocene as a mild redox catalyst in moderate to good yields (Scheme 1-10).121

Scheme 1-10: Electrochemical alkyne benzannulation reaction.

Radical initiated alkyne benzannulation reaction has been another kind of alkyne benzannulation reaction which can result in the formation of number of aromatic rings in a single step. Alabugin 23 and coworkers have intensely studied radical initiated alkyne benzannulation reactions for the synthesis of a library of NGs.122-124 One representative work by Alabugin group is the synthesis of helical NG 1.95. They treated compound 1.94 with AIBN and Bu3SnH to afford compound 1.95 as a racemic mixture (Scheme 1-11).

Scheme 1-11: Radical mediated cascade alkyne benzannulation.

There are plenty of examples of iodine salt-catalyzed alkyne benzannulation rection reported towards the synthesis of PAHs and NGs.125 Asensio and coworkers first reported alkyne benzannu-

125 lations reaction using electrophilic reagents I(py)2BF4 to produce iodocyclohexene products.

Following their works, the Swager group have utilized these conditions to cyclize terphenyl diyne derivative 1.96 to obtain dibenzoanthracene derivative 1.97 in excellent yields (Scheme 1-7).126

The Müllen group have used and ICl catalyzed two-fold alkyne benzannulation of the diyne 1.98 to get iodine functionalized phenanthrene derivatives 1.99 as an intermediate during the synthesis of dibenzo ovalene derivatives (Scheme 1-12).127

Scheme 1-12: Iodine salt mediated alkyne benzannulation reactions.

1.8 Mechanism of electrophilic alkyne benzannulation

The general mechanism of electrophilic alkyne benzannulation is as given in the Scheme 1-13. An electrophile coordinates to the triple bond of the alkyne 1.100, generating a three-membered transition state 1.101. This coordination might be symmetric or asymmetric depending on the nature of the electrophile used. An electrophilic attack by the activated alkyne on the neighboring aromatic ring results in the formation of arenium intermediate 1.102. Thus, formed arenium ion gets stabilized by losing one proton regaining the aromaticity yielding compound 1.103.

Scheme 1-13: Mechanism of electrophile-catalyzed alkyne benzannulation. 25

1.9 Conclusion

Synthesis of NGs and GNRs is an efficient way to mimic graphitic properties that creating a band gap. There are numerous ways reported for the synthesis of NGs and GNRs. Alkyne benzannulation reaction has been an efficient, versatile tool for the synthesis of a variety of NGs starting from a simple starting materials. This method allows the incorporation of different substituents on the

NG core that can enhance the solubility and also helps to enhance liquid crystallinity.

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2. Synthesis, Characterizations and Photophysical Properties of [5]Helicene-like π-Extended Naphtho[1,2-a]pyrenes†

2.1 Helicenes

Helicenes are an important class of nanographene having ortho-fused aromatic rings resulting in fascinating structures and applications. The first synthesis and resolution helicenes was of [6]helicene reported by Newman in the 1950s.1-3 The helical structure arises because of the interaction between the terminal rings which makes the molecule twisted out of the planarity. Typically, these molecules contain a C2-axis perpendicular to the helical axis which renders them chiral even though they do not have asymmetric carbon centers.4 With the increase in the number of ortho- fused aromatic rings, they spiral up along the helical axis with constant outer and inner pitch of the spiral/cylindrical architecture.5 Compared to the linear analogues acenes, helicenes have little loss of the local aromaticity in each ring even though these molecules exhibit a departure from planarity.6, 7 They have a relatively smaller HOMO-LUMO gap, higher stability, enhanced solubility, and reduced π-stacking properties compared to acenes.1, 6-11 Like other polycyclic aromatic hydrocarbons, they can form π-complexes with different electron deficient molecules through π- donation. Additionally, they can also exhibit fluorescence, with moderate quantum yield.12 Be- cause of the helical structure and interesting optoelectronic properties such as absorption, emission and circular dichroism, these molecules have been found to be applicable in different fields such as catalysis, cancer treatment, drug delivery, as a semiconducting material in organic field effect

† A version of this chapter is submitted for a publication (Paban Sitaula, Giovanna Longhi, Sergio Abbate, Eva Gualtieri, Andrea Lucotti, Matteo Tommasini, Roberta Franzini, Claudio Villani, Vincent J. Catalano, and Wesley A. Chalifoux* submitted in JOC).

35 transistors (OFETs), organic photovoltaics (OPVs), molecular photo switches, and liquid crystal technologies.13-28

Figure 2-1: A) [5]Helicene showing helicene Cartesian coordinates B) Lateral π-extension along x- and y-axis (indicated by blue dotted lines) C) Helical π-expansion through z-axis (indicated by red dotted lines) D) Lateral and helical π-expansion.

The helicene Cartesian coordinates and possible directions of π-extensions are shown in Figure 2-

1. The axis of coil is represented by z-axis. The two lateral directions are represented by x- and y- axis. Several approaches have been reported for the synthesis of helical NGs. Photocyclization, olefin metathesis, alkyne benzannulations, Friedel-Craft reactions, metal-catalyzed cyclization are the most common approaches used for their synthesis.3, 29-36 All of these methods are used to synthesize higher helicenes by condensing aromatic rings along the axis of coil (i.e. along the z-axis).

The largest helicene obtained by π -elongation along z-axis reported till date is [16]helicene by

Fujita and co-workers in 2015.37 They synthesized single strand of oligo(arylene-vinylene) precursor and carried out multiple photo-dehydrocyclization reactions to get [16]helicene.

2.1.1 Laterally π-extended helical NGs:

Lateral extension of the helical nanographene can result in the enhanced photophysical properties such as absorption-emission range, carrier mobility, π- π stacking, and other optical responses in the visible and near-infrared regions.38-44 However, there are only a handful of methods reported 36 toward the synthesis of laterally extended helicenes (Figure 2-2). One of the representative example is the synthesis of dibenzo[a,l]pyrene reported by Desai and coworkers. They treated enol ether functionalized chrysene with triflic acid to get dibenzo[a,l]pyrene product.45 The pyrene-naphthalene hybrid reported by them are non-functionalized and has narrow substrate scope. Collins group has reported the photochemical synthesis of pyrene-helicene hybrid 2.2 starting from a stilbene precursors 2.3 by stirring under UV light for several hours. The yield of the reaction was low (up to 42%).46 Recently, the Chalifoux group has reported the synthesis of conformationally locked-

Figure 2-2: Synthesis of laterally π-extended naphthopyrene helicene hybrids (a) Triflic acid catalyzed alkene-benzannulation (b) Photochemical synthesis of pyrene-helicene hybrid (c) One-step synthesis of naphtho[1,2-a]pyrene through two-fold alkyne benzannulation. 37 pyreno[a]pyrene-based helicene hybrids 2.4 using a Brønsted acid-catalyzed alkyne benzannulation reaction of tetrayne precursor 2.3.47 Hence, the development of synthetic methods yielding laterally π-expanded helically twisted NGs are still on demand.

2.2 Naphtho[1,2-a]pyrenes

Naphtho[1,2-a]pyrene is an example of laterally π-extended pyrene-naphthalene hybrid. It has four benzene rings ortho-fused with each other and the substituents in the cove-region makes the molecule twisted and also enhances the solubility. Furthermore, the aryl substituent in the cove-region

(indicated by bold bond in compound 2.7, Scheme 2-1) stacks over the terminal phenanthrene ring that enhances the absorption-emission properties of these molecules compared to that of [4]- and

[5]Helicenes.

2.2.1 Our Route towards naphtho[1,2-a]pyrenes

Scheme 2-1: Retrosynthetic analysis of pyrene-naphthalene hybrid 2.7.

Our approach towards a highly functionalized naphtho[1,2-a]pyrenes is the synthesis of diyne precursor 2.8. The precursor diyne 2.8 can be easily obtained by Suzuki cross-coupling of the diyne boronic ester 2.10 and 3-bromophenanthrene derivatives 2.9. Compound 2.8 when subjected to a two-fold alkyne benzannulation reaction affords target naphtho[1,2-a]pyrene. Hence, we planned 38 a synthesis of a library of the highly functionalized naphtho[1,2-a]pyrenes in concise and efficient way under mild conditions.

2.2.2 Synthesis of diyne boronic ester

We initiated the synthesis with commercially available 4-t-butyl aniline 2.11. Diiodination reaction of 2.11 with KI and hydrogen peroxide in concentrated sulfuric acid resulted aniline 2.12 which was converted to compound 2.13 using a Sandmeyer reaction (Scheme 2-2). Derivative of

2.31 having -COOEt group as R1 was synthesized following the procedure reported by Skulski and coworkers.48

Scheme 2-2: Synthesis of diiodobromobenzene derivatives.

A number of terminal alkynes 2.16 were synthesized starting from haloarenes 2.14 by cross-coupling with trimethylsilyl acetylene to get internal alkyne 2.15, which was then desilylated with

49-51 K2CO3 in methanol to get terminal alkynes 2.16 in good to excellent yields (Scheme 2-3).

Scheme 2-3: Synthesis of terminal alkynes. 39

Terminal alkynes 2.16 were cross-coupled selectively with compound 2.13 under Sonogashira conditions to get bromodiyne compound 2.17 in good to moderate yields. Thus obtained bromodiyne 2.17 was taken through lithium-halogen exchange reaction with n-BuLi followed by treating with isopropoxyboronic acid pinacol ester to get diyne boronic ester 2.10(Scheme 2-4).

Scheme 2-4: Synthesis of bromodiyne boronic ester. 40

2.2.3 Synthesis of 3-bromophenantharenes

Most of the 3-bromophenanthrene derivatives are not commercially available or very expensive and had to be synthesized. 3-bromophenanthrene derivatives were synthesized following the literature procedure using the Mallory reaction.52 Bromobenzaldehyde 2.18 was subjected into HWE olefination with 4-bromobrnzyl bromide 2.19 to get stilbene 2.20, which was then stirred with catalytic amount of iodine and THF in toluene as a solvent under UV irradiation to get 3-bromophenanthrene derivatives 2.9 (Scheme 2-5).

Scheme 2-5: Synthesis of 3-bromophenanthrenes.

2.2.4 Two-fold alkyne benzannulation reaction

Having both of the coupling partners 2.9 and 2.10 in hand, we coupled them together using a

Suzuki cross-coupling reaction under preoptimized conditions that afforded diyne precursor 2.8

(Scheme 2-6).53 The diyne 2.8 was then taken through the alkyne benzannulation reaction to afford the [5]helicene-like naphtho[1,2-a]pyrene 2.7. In our group, we have shown the efficient catalytic activities of TFA/TfOH, InCl3 and equimolar mixture of InCl3 and AgNTf2 to induce multi-fold alkyne benzannulation reactions to afford a wide variety of NGs and GNR. We screened all three catalytic conditions with diyne 8a having t-butyl group as R1, p-hexyloxyphenyl group as R2 and

3 H as R . TFA/TfOH afforded two-fold benzannulated product 7a in 54% yield and InCl3/AgNTf2 produced 7a in 74% yield. The reaction in later condition was cleaner and easier to purify. InCl3 alone afforded only the mono-benzannulated product even after heating at an elevated temperature 41 for several hours which might be because of the relatively higher activation energy of the second alkyne benzannulation and InCl3 alone could not cross that barrier.

Scheme 2-6: Synthesis of diyne precursors 2.8 ([a]compound was synthesized by different method, see experimental section). 42

Catalysts Equiv. T (oC) Solvents Product Yield (%)

TFA:TfOH 50:1 -78 to 0 CH2Cl2 2.7a 54

InCl3 0.5 90 toluene 2.7a’ 60

InCl3:AgNTf2 0.1:0.1 90 toluene 2.7a 74

Table 2-1: Screening of the suitable conditions for the acid-catalyzed alkyne benzannulation.

With this optimized conditions, nine derivatives of the naphtho[1,2-a]pyrenes were synthesized

(Scheme 2-7). The reaction worked well with t-butyl groups and methyl group as R1 (2.7a-e) in a

1 very good yields. When the R was changed to inductively electron withdrawing -CF3 groups (2.7f- g), the reaction worked in moderate to good yields. With electron withdrawing ester group as R1

(2.7h), the yield of the reaction was excellent. Substrate with electron rich ethynyl aryl groups as

R2 (2.7a-i) gave naphtho[1,2-a]pyrene in good to excellent yields. The reaction also worked in a very good yield with 6-methoxynaphthyl group as R2. We were also able to synthesized tail functionalized naphtho[1,2-a]pyrenes (electron donating -OCH3 group functionalized 7d and induc-

3 tively electron withdrawing -CF3 group functionalized 7i as R ) in moderate to good yield. Diynes with inductively electron-withdrawing p-chlorophenyl groups as R2 2.8j and electron-neutral (4-t- butylphenyl) groups 2.8k were also carried through alkyne benzannulation conditions. those substrate underwent alkyne benzannulation reaction selectively on one side, resulting in the formation of kinetic benzochrysene products 2.7j and 2.7k respectively containing the helical core (confirmed by crystal structure and NMR study), while possible formation of dibenzoanthracene 43

Scheme 2-7: Two-fold alkyne benzannulation reaction yielding naphtho[1,2-a]pyrenes. was ruled out (Scheme 2-8). We also attempted growing X-ray quality single crystals for two-fold benzannulated products 2.7(a-h) using different methods and solvents but are still not successful to get single crystal of any of those derivatives. Screening suitable conditions is under study. The diyne precursors 2.8f and 2.8m having naphthyl and hexyl group as R2 did not cyclize at all under these conditions. We tried to push the reaction by elevating the temperature from 90 °C to 110 °C 44 in toluene for another 24 hours and there was no conversion of the starting material. We also tried using some high boiling solvents such as 1,4-xylene and mesitylene, but the reaction failed to give even a mono-benzannulated product. Then, we also tried Brønsted acid (TFA/TfOH) conditions that was again unsuccessful to give the desired two-fold alkyne benzannulation reaction (even a mono-cyclization was not observed). These observations shows that, only electron rich arylalkynes undergo such type of transformations. This is because, electron rich aryls can better stabilize vinyl cation resulting after activation by Lewis or Brønsted acids.

Scheme 2.8: Selective mono-benzannulation resulting 2-7j and 2-7k.

2.3 Photophysical properties

2.3.1 UV-vis/fluorescence spectra

The UV-Vis spectra of the products were compared with that of [5]helicene. Although, there is no significant absorption for [5]helicene 1.27 past 350 nm, and [7]helicene 1.28 past 400 nm, our naphtho[1,2-a]pyrene 2.7 showed bathochromic shift with extended absorption to about 407 nm and tails up to 450 nm. The spectral difference is because of the laterally expanded conjugation. 45

UV-vis spectra of the products 2.7b, 2.7d, 2.7e, 2.7g, 2.7j, and 2.7h are given in figure 2-3. The

λmax value of all two-fold benzannulated products are about the same i.e. 407 nm, while λmax value of mono-benzannulated product 2.7j was found to be 320 nm. The [5]helicene-like helical skeleton resulting from the first cyclization is responsible for the maximum absorption of the 320 nm and the second cyclization causes the bathochromic shift to 407 nm.

1 2.7 d 2.7g 0.8 2.7e

0.6 2.7j

2.7 0.4 b 2.7

Normalizedintensity h 0.2

0 277 327 377 427 477 Wavelength (nm

Figure 2-3: UV-vis spectra of naphtho[1,2-a]pyrenes 2.7.

The UV-Vis and fluorescence spectra of compound 2.7a is given in figure 2-4. The maximum emission wavelength of 2.7a is found to be 453 nm. The Stokes shifts of 46 nm for these molecules are due to the fact that there is less rigidity that arises from the low racemization barrier.

1 0.9 0.8 0.7 0.6 Emissio 0.5 n 0.4 0.3

0.2 Normalizedintensity 0.1 0 290 390 490 590 wavelength (nm)

Figure 2-4: UV-vis and emission spectra of 2.7a.

2.3.2 Separation of enantiomers

With the help of our collaborators, we studied the chiral HPLC separations of the enantiomers of the naphtho[1,2-a]pyrene products. The twisted π-system of 2.7a-j generates conformational chirality in these molecules, and their M-P enantiomers are amenable to HPLC separation, if M and

P species are separated by a sufficiently high energy barrier. The M-P interconversion barriers of naphtho[1,2-a]pyrenes 2.7b-i and of the partially cyclized 2.7j were investigated using a variable temperature dynamic high performance liquid chromatography (DHPLC) on a chiral stationary phase (CSP) for the determination of the enantiomerization barriers.23 Preliminary experiments showed that single enantiomers of 2.7b-i and of 2.7j are prone to racemization at room temperature. However, excellent enantio-separations were achieved at lower column temperature (between

0 °C and 10 °C), using a single enantioselective HPLC column packed with an immobilized am- ylose derivative CSP, and a single mobile phase consisting of hexane/dichloromethane/methanol

90/10/1.24 Low-temperature HPLC separations of the enantiomers of 2.7d and 2.7i using ultravio- 47 let and circular dichroism detections (Figure 2-5) clearly demonstrate the enantiomeric relation- ship of the two species observed in each plot, showing equal intensity and opposite chiroptical signals.

Figure 2-5. Enantioselective HPLC of 2.7d (a) and 2.7i (b) using UV (280 nm, red traces) and

CD (300 nm, blue traces) detections.

When the HPLC column temperature was set to 0 °C, little or no on-column interconversion was detected for 2.7b-i and 2.7j. When the column temperature was raised to 10 and 20 °C, we observed temperature dependent deformations of the elution profiles and peak coalescence due to fast interconversion for the majority of the examined compounds. For 2.7d, 2.7i and 2.7j the dynamic behavior was shifted to higher temperatures, with peak coalescence observed between 40 and 60 °C. We used computer simulation of the exchange broadened chromatograms to extract the apparent rate constants for the on-column M-P interconversion process, and from these values we calculated the corresponding free energy barriers of enantiomerization (Table 2-2).25

[a] ‡ [b] [c] Compd. k’1 ΔG (T) T

b 7b Tcol0.52= 0°C (kcal/mol)19.39 (°C)10 7c 1.06 19.53 10 7d 0.41 20.48 10 7e 1.19 19.51 10 7f 0.26 19.61 10 7g 0.86 19.63 10 7h 1.92 19.72 10 7i 0.13 21.36 20 7j 0.05 20.04 10

Table 2-2: Rate constant and free energy barriers of enantiomerization. [a] retention factor of the 1st

st eluted enantiomer, defined as (t1-t0)/t0 where t1 is the elution time of the 1 eluted enantiomer and t0 is the elution time of a non-retained compound. [b] Gibbs free activation energy for the on-column enantiomerization (conversion of the 1st into the 2nd eluted enantiomer) at column temperature T, error ±0.02 kcal/mol. [c] Column temperature for the DHPLC experiments, T ±0.1°C.

The experimental Gibbs free energy of enantiomerization ΔG‡ for 2.7b-i and 2.7j are gathered in

Table 2-2, together with the retention factor of the first eluted enantiomer on the CSP. As expected, for the structurally similar 2.7b-i naphtho[1,2-a]pyrene series, enantiomerization barriers span a narrow range between 19.39 and 21.36 kcal/mol. The majority of naphtho[1,2-a]pyrenes shows interconversion barriers between 19.39 and 19.72 kcal/mol, that correspond to half-life times between 20 and 30 s at 25 °C. Conversely, 2.7d and 2.7i have interconversion energy barriers of 20.48 and 21.36 kcal/mol, respectively, and their M-P enantiomers have half-lives in the minutes range at 25 °C. Clearly, M-P interconversion barriers in 2.7b-i are mainly dependent on the presence of substituents (-OMe, 2.7d or -CF3, 2.7i) on the terminal rings of the helix. Remote functionalization at the pyrene rings with methyl, t-butyl, trifluoromethyl or ester groups has no 49 effect on the interconversion barrier. The mono-benzannulated benzo[c]chrysene 2.7j showed a barrier equal to 20.04 kcal/mol, suggesting the stereochemical stability of the whole set of compounds is controlled by the number of ortho‐condensed rings in the benzo[c]chrysene skeleton, by the size of the group on the terminal ring and by the presence of the substituted aryl ring in the cove-region. Discrete amounts of the single enantiomers of 2.7d and 2.7i were obtained by low- temperature HPLC on a semipreparative column packed with the same CSP of the analytical separations. Wet fractions containing the individual enantiomers were used for the acquisition of their circular dichroism (CD) spectra.

2.3.3 CD spectra of 2.7d and 2.7i

Comparison between Experimental CD (ECD) spectra and calculated data of compounds 2.7d and

2.7i can be carried out as for other [5]helicenes which racemize at room temperature.26 Calcula- tions have been performed considering the P enantiomer of the two compounds 2.7d and 2.7i.

Conformational analysis has been conducted considering just the most significant dihedral angles assuming for simplicity that aliphatic chains are trans-planar and also substituting-OMe groups by hexyl chains. One of the two phenyl orientation is dictated by the steric hindrance with the [4]helicene moiety, while the phenyl on the opposite side shows two possible orientations; the hexyloxy/methyloxy groups also exhibit two different orientations, giving a total of eight possible conformers for 2.7i and sixteen for 2.7d (due to the two possible conformers of -OCH3 group).

Substitution of hexyloxy chains with methoxy groups seems to have a marginal influence onto the conformer populations.

For all reported conformers, ECD spectra have been calculated: the phenyl and hexyloxy/methoxy orientations have some influence on the calculated ECD spectra particularly considering higher energy bands. Substitution of hexyloxy with methoxy group seems to play a minor role on the 50 calculated ECD spectra. The final results for the two molecules are reported in Figure 2-6 after applying a wavelength red-shift as indicated in the caption, analogous to the one used with similar level of calculations. The correspondence with the experimental spectra of the first eluted fraction is quite good for the two compounds permitting a safe assignment of the configuration, namely the

P-enantiomer for the two molecules. We notice that the succession of band signs is correctly predicted, the lowest energy bands are well reproduced and are the ones also showing low sensitivity to conformational changes, the wavelength difference among the observed features is better reproduced by the calculations based on the presence of solvent (we considered hexane for simplicity).

The low sensitivity of the lowest energy CD band to pendant conformation is strictly connected to the laterally extended π-system in comparison with carbohelicene: in this last case it is well known that the lowest energy bands correspond to forbidden transitions a fact that limits their use for optoelectronic application as opposed to the cases with helicene or heterohelicene.27, 28 In the two compounds herein considered, the extended carbon-atom backbone gives rise to dipole and rotational strength of the lowest energy transition which are non-negligible due to the pyrene moiety.

From the calculations we obtain that the electric dipole moment of the lowest energy transition

(HOMO-LUMO) is nearly parallel to the pyrene long axis, while the magnetic dipole transition moment forms an angle of about 80° pointing out of the pyrene plane, in any case enough to give good rotational strength. Computational study reveals that the HOMO and LUMO orbitals for the most populated conformer of the two molecules 2.7d and 2.7i which are localized on the pyrene- helicene backbone, justifying their sensitivity to configuration.

Figure 2-6. Comparison of calculated and experimental ECD and absorption spectra of compounds 2.7d (left) and 2.7i (right). (Calculations have been performed considering all trans-planar aliphatic chains and O-methyl substitution in the gas phase and at the iefpcm level, in all cases a Boltzmann weighted average has been performed. Red shift has been applied to calculated spectra by 40 nm for the gas phase and by 35 nm when implicit solvent model has been considered).

2.3.4 FTIR Spectroscopy

The markers of the phenyl functional groups are found in the regions highlighted by boxes 3, 5, 9 and 10 (Figure 2-7). The CO stretching vibrations from the alkoxy groups couple with phenyl vibrations in the region highlighted by box 9. The naphthyl functionalization of compound 2.7e is evidenced by the markers observed in the regions labelled by 2, 4, and 8. Similarly to modes in 52

box 9, in box 8 the vibrations of naphthyl groups are coupled with those of OCH3 functional group, as well as contributions of t-butyl R1 group. Collective C-C stretching vibrations, coupled with in- plane C-H bending vibrations of naphthyl and phenyl are assigned to boxes 2 and 3. The IR bands found in region 4 involve both naphthyl and t-butyl groups. Methyl bending modes are found in the region between 1490 and 1360 cm-1, but they do not yield evident IR signals (group I compounds exhibit the antisymmetric methyl bending at ~1464 cm-1, and the umbrella (symmetric)

-1 1 bending at ~1440 cm ). CH2-scissoring in 2.7h (R = ethyl ester) and 2.7f, 2.7i, 2.7d (bearing hexyloxy groups) is found roughly in the same region as the methyl antisymmetric bending. CH2-

-1 wagging is found in the same molecules between 1425 and 1100 cm , whereas CH2-twisting is

-1 found between 1305 and 1240 cm . As expected, CH2- rocking modes are found at lower wavenumber, in the out-of-plane bending region. Since their signal is quite weak, it is difficult to assign them to any experimental feature of the IR spectra. We found a series of collective out-of-plane

C-H bending markers in the region highlighted by box 14. These bands form a pattern which is remarkably similar across the series of compounds 2.7c, 2.7b, 2.7h, 2.7g and 2.7f. This is because such molecules share the same topology of CH-bonds at the edge of the helical nanographene core.

Interestingly, 2.7i and 2.7d slightly deviate from the previous pattern because of their functionalization at the tail of the nanographene core (R3). As expected, the naphthyl groups of compound

2.7e add significant signals in this wavenumber region, so that the pattern of the IR spectrum changes quite dramatically.

2.3.5 Raman Spectroscopy

Raman spectroscopy is an absorption spectroscopy which is used to characterize graphitic materials. The expected G and D bands of such NGs are markers of the structure of the extended π- conjugated core for all graphitic materials.54, 55 We did not observe obvious Raman markers of the 53 functional groups, with the only exception of the weak CO-stretching feature observed for compound 2.7h (slightly above 1700 cm-1, Figure 2-8). However, the pattern of the G band and the position of the D peak are remarkably sensitive to the functional groups attached to the nanographene core. 2.7c and 2.7b essentially share the same substituents (the difference between a methyl

(2.7c) and t-butyl (2.7b) substituent is not much from the point of view of the effect on π-conjugation). By consequence, the position of the D peak in the two compounds is essentially-

Figure 2-7. The experimental micro FT-IR spectra of compounds 2.7(b-i) across the fingerprint region. (The contributions from specific functional groups are highlighted with numbered boxes).

the same (1314 cm-1), and it is the same the pattern of the G band. Compared with 2.7c and 2.7b, the ethyl ester substituent of 2.7h very slightly changes the pattern of the G band and the position

-1 1 of the D peak (1317 cm ). Compounds 2.7g and 2.7f share the CF3 functionalization at R , and the p-methoxyphenyl/p-hexyloxyphenyl functionalization at R2 has the same influence on π- 54 conjugation. Therefore, as expected, 2.7g and 2.7f exhibit the same G band pattern and the same position of the D peak (1321 cm-1). The Raman spectra of 2.7i and 2.7d are rather close, from which we infer that the inductive effect caused by the trifluoromethyl and methoxy R3 substituents on the nanographene core are rather close. This observation is consistent with the similarity of the position of the π-π* electronic transitions of 2.7i and 2.7d . Finally, the G and D bands of compound 2.7e appear significantly different from the previous compounds given the sizeable contributions from the π-conjugated naphthyl substituents to the Raman spectrum.

Figure 2-8. The experimental micro FT-Raman spectra of compounds 2.6(b-i) across the G and

D-band regions (grey boxes identify similar patterns and positions of the G and D bands).

2.4 Conclusion and future directions.

In summary, we successfully synthesized highly functionalized naphtho[1,2-a]pyrene derivatives by the utilization of the two-fold alkyne benzannulation catalyzed by indium chloride and silver bistriflimide in moderate to excellent yields. Because of the relatively low racemization barriers, 55 we were unable to separate enantiomers from the racemic mixture of the products in many cases.

However, because of the elevated racemization barrier for 2.7d and 2.7i (due to -OMe and -CF3 substitution in tail of conjugated core), we were able to separate enantiomers in chiral column. The

Raman spectroscopy of all products were recorded and they have similar absorption pattern with characteristic D and G bands which are characteristics of all graphitic materials. We were also able to study the FTIR, CD and ECD of naphtho[1,2-a]pyrenes. Following the synthesis of naphtho[1,2- a]pyrenes, we can employ this method to synthesized further π-extended NGs twisted by larger angles (Scheme 2-9). We can attempt a two-fold Suzuki cross-coupling of the diyne boronic ester

2.10 to get a tetrayne precursor 2.22, that can afford π-extended [7]helicene-like pyrene-helicene hybrids 2.23. By incorporating dibromo-heteroaryl coupling cores, we can synthesize a library of heteroatom-doped helical NGs. Those NGs are expected to have high racemization barrier compared to naphtho[1,2-a]pyrenes because of the steric congestion in the fjord-region (highlighted with red) of molecule 2.23.

Scheme 2-9: Future works towards π-extended helical NGs 2.23.

2.5 Experimental section

2.5.1. General experimental

All reactions dealing with air- or moisture-sensitive compounds were carried out in a dry reaction vessel under nitrogen. All reagents and solvents were commercially obtained and used without prior purification, unless otherwise noted. Anhydrous toluene and tetrahydrofuran (THF) were obtained by passing the solvent (HPLC grade) through an activated alumina column on a PureSolv MD 5 solvent drying system. 1H and 13C NMR spectra were recorded on Varian 400 MHz or Varian 500

MHz NMR Systems Spectrometers. Spectra were recorded in deuterated chloroform (CDCl3).

Chemical shifts are reported in part per million (ppm) Coupling constants (J) are reported in Hz.

The multiplicity of 1H signals are indicated as: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad. High resolution ESI/APPI mass spectrometry was recorded using an Agilent 6230 TOF

MS. TLC information was recorded on Silica gel 60 F254 glass plates. Purification of reaction products was carried out by flash chromatography using Silica Gel 60 (230-400 mesh). A suitable crystal was mounted on a glass fiber and placed in the low-temperature nitrogen stream. A suitable crystal was mounted on a glass fiber and placed in the low-temperature nitrogen stream. Data were collected on a Bruker Apex CCD area detector diffractometer equipped with a low-temperature device, using graphite-mono-chromated Mo K radiation (λ= 0.71073 Å) and a full sphere of data was collected. Integration, data reduction and scaling were carried out with the programs SAINT and SADABS56 in the Bruker APEX3 suite of software.

2.5.2. Synthesis and characterizations

2.5.2.1 General procedure for synthesis of Compound 2.17

To the solution of 2.13 (1.0 equiv.) and the terminal alkyne 2.16 (2.5 equiv.) in Et3N and THF, were added Pd(PPh3)2Cl2 (10 mol%) and CuI (20 mol%). The resulting mixture was stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration.

The solvent was removed under reduced pressure and the residue was purified by column chromatography to afford the product 2.17 (2.17a, 2.17b, 2.17e, 2.17d, 2.17, 2.17k were synthesized following the literature procedure).53, 57, 58

2.17c

To the solution of 1-bromo-4-methyl-2,5-diiodobenzene (2.22 g, 5.26 mmol) and 4-methoxy-1- ethynylbenzene (1.73 g, 13.1 mmol) in Et3N (30 mL) and THF (80 mL), were added Pd(PPh3)2Cl2

(369 mg, 0.525 mmol) and CuI (200 mg, 1.05 mmol). The resulting mixture was stirred under a

N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration.

The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane 2:3) to afford 1.50 g (yield 66%) of the product 2.17c. Rf = 0.32

(DCM:hexane, 2:3). FTIR (neat) 2964, 2209, 1604, 1508, 1245, 1024, 832 cm-1. 1H NMR (400

MHz, CHCl3) δ 7.56 – 7.52 (m, 4H), 7.30 (s, 2H), 6.91 – 6.88 (m, 4H), 3.82 (s, 6H), 2.29 (s, 3H)

13 ppm. C NMR (400 MHz, CDCl3) δ 160.0, 136.8, 133.3, 133.0, 126.3, 124.9,115.1, 114.1, 93.9,

+ + 87.2, 55.4, 20.7 ppm. HRMS (ESI-TOF) m/z: [M+Na] calcd for [C25H19BrO2 Na] 453.0466, found 453.0426.

2.17e

To the solution of 1-bromo-4-t-butyl-2,5-diiodobenzene (3.00 g, 6.45 mmol) and 2-ethynylnaph- thalene (2.45 g, 16.1 mmol) in Et3N (100 mL) were added Pd(PPh3)2Cl2 (226 mg, 0.320 mmol) and CuI (123 mg, 0.646 mmol). The resulting mixture was stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel,

DCM:hexane 1:10) to afford 800 mg (yield 24%) of the product 2.17e. Rf = 0.21 (DCM:hexane,

–1 1 1:10). FTIR (neat) 2829, 2243, 1615, 1561, 1505 cm . H NMR (400 MHz, CDCl3) δ 8.15 (s, 59

2H), 7.87 – 7.80 (m, 8H), 7.66 (dd, J = 8.5, 1.6 Hz, 2H), 7.53 – 7.51 (m, 4H), 1.38 (s, 9H) ppm.

13 C NMR (400 MHz, CDCl3) δ 150.4, 133.2, 133.1, 131.9, 130.5, 128.5, 128.2, 128.02, 127.99,

127.0, 126.8, 126.7, 126.0, 120.3, 94.0, 89.1, 34.8, 31.2 ppm. HRMS (ESI-TOF) m/z: [M+Na]+

+ for [C34H25BrNa] 535.1037, found 535.1032.

2.17f

To the solution of 1-bromo-2,5-diiodo-4-(trifluoromethyl)benzene (6.00 g, 12.6 mmol) and 4-hexyloxy-1-ethynylbenzene (6.36 g, 31.4 mmol) in Et3N (30 mL) and THF (80 mL), were added

Pd(PPh3)2Cl2 (885 mg, 1.26 mmol) and CuI (480 mg, 2.52 mmol). The resulting mixture was stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane 1:3) to afford 7.10 g (yield 90%) of the product

–1 1 2.17f. Rf = 0.41 (DCM:hexane, 1:4). FTIR (neat) 2839, 2263, 1605, 1571, 1510 cm . H NMR

(400 MHz, CDCl3) δ 7.67 (s, 2H), 7.55 – 7.50 (m, 4H), 6.92 – 6.87 (m, 4H), 3.99 (t, J = 6.6 Hz,

4H), 1.84 – 1.77 (m, 4H), 1.51 – 1.43 (m, 4H), 1.35 (m, 8H), 0.94 – 0.89 (m, 6H) ppm. 13C NMR

2 1 (400 MHz, CDCl3) δ 160.2, 133.5, 131.7, 129.8 (q, J(C, F) = 33.6 Hz), 128.2 (q, J(C, F) = 3.5

Hz), 127.8, 123.4 (q, 3J(C, F) = 272.4 Hz), 114.8, 114.1, 96.2, 86.1, 68.3, 31.7, 29.3, 25.8, 22.7,

+ + 14.2 ppm. HRMS (ESI-TOF) m/z: [M+Na] for [C35H36BrF3O2Na] 647.1748, found 647.1774.

2.17g

To the solution of 2-bromo-1,3-diiodo-5-(trifluoromethyl)benzene (4.00 g, 8.39 mmol) and 4- methoxy-1-ethynylbenzene (2.22 g, 16.8 mmol) in Et3N (30 mL) and THF (80 mL), were added

Pd(PPh3)2Cl2 (589 mg, 0.84 mmol) and CuI (320 mg, 1.68 mmol). The resulting mixture was stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:3) to afford 2.84 g (yield 70%) of the product

–1 1 2.17g. Rf = 0.31 (DCM:hexane, 1:3). FTIR (neat) 2829, 2215, 1605, 1510 cm . H NMR (400

13 MHz, CDCl3) δ 7.67 (s, 2H), 7.56 – 7.53 (m, 4H), 6.93 – 6.90 (m, 4H), 3.85 (s, 6H) ppm. C NMR

2 1 (400 MHz, CDCl3) δ 160.5, 133.6, 131.7, 129.8 (q, J(C, F) = 33.4 Hz), 128.2 (q, J(C, F) = 3.8

Hz), 127.8, 123.4 (q, 3J(C, F) = 272.8 Hz), 114.4, 114.3, 96.1, 86.2, 55.5 ppm. HRMS (ESI-TOF)

+ + m/z: [M+H] calcd for [C25H18BrF3O2] 485.0364, found 485.0114.

2.17h

To the solution of ethyl-(2-bromo-3,5-diiodo)benzoate (2.00 g, 4.42 mmol) and 4-methoxy-1- ethynylbenzene (1.37 g, 10.4 mmol) in Et3N (30 mL) and THF (80 mL), were added Pd(PPh3)2Cl2

(146 mg, 0.208 mmol) and CuI (79 mg, 0.42 mmol). The resulting mixture was stirred under a N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:Hexane, 1:2) to afford 1.29 g (yield 63%) of the product 2.17h. Rf = 0.41

(DCM:hexane, 1:2). FTIR (neat) 3070, 2958, 2209, 1718, 1603, 1508 cm–1. 1H NMR (500 MHz,

CDCl3) δ 8.08 (s, 2H), 7.55 – 7.53 (m, 4H), 6.90 – 6.88 (m, 4H), 4.38 (t, J = 7.1 Hz, 2H), 3.82 (s,

13 6H), 1.41 (t, J = 7.2 Hz, 3H) ppm. C NMR (500 MHz, CDCl3) δ 165.0, 160.3, 133.4, 132.8,

132.5, 129.5, 127.1, 114.6, 114.2, 95.2, 86.5, 61.6, 55.4, 14.4 ppm. HRMS (ESI-TOF) m/z:

+ + [M+Na] for [C27H21BrO4Na] 511.0521, found 511.0494.

2.17j

To the solution of 1-bromo-4-(t-butyl)-2,5-diiodobenzene (3.00 g, 6.45 mmol) and 4-chloro-1- ethynylbenzene (2.20 g, 16.1 mmol) in Et3N (30 mL) and THF (80 mL), were added Pd(PPh3)2Cl2

(453 mg, 0.645 mmol) and CuI (246 mg, 1.29 mmol). The resulting mixture was stirred under a

N2 atmosphere at room temperature for 14 h. The ammonium salt was then removed by filtration.

The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, hexane) to afford 2.40 g (yield 77%) of the product 2.17j. Rf = 0.55 (hexane).

1 1 FTIR (neat) 2868, 2214, 1899, 1563, 1488, 1413 cm- . H NMR (400 MHz, CDCl3) δ 7.55 – 7.51 62

13 (m, 6H), 7.37 – 7.34 (m, 4H), 1.34 (s, 9H) ppm. C NMR (400 MHz, CDCl3) δ 150.5, 134.9,

133.1, 130.5, 128.9, 125.7, 125.4, 121.5, 92.5, 89.5, 34.8, 31.1 ppm. HRMS (ESI-TOF) m/z:

+ + [M+Na] calcd for [C26H19BrCl2Na] 502.9945, found 502.9938.

2.5.2.2 General procedure for the synthesis of compound 2.10:

To a solution of 2.17 (1 equiv.) in anhydrous THF at -78 °C was added a solution of n-butyllithium in hexanes (2.5 M, 1.2 equiv.). After stirring for 1 h at -78 °C, isopropoxyboronic acid pinacol ester (1.2 equiv.) was added, the reaction removed from the cooling bath and allowed to warm.

Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (2.17a, 2.17b, 2.17i, and 2.10k were synthesized following the literature procedure).53, 57

2.10c

To a solution of 2.17c (1.10 g, 2.51 mmol) in THF (120 mL) at -78 °C was added a solution of n- butyllithium in hexanes (1.3 mL, 2.5 M, 3.18 mmol). After stirring for 1 h at -78 °C, isopropoxyboronic acid pinacol ester (712 mg, 3.82 mmol) was added, the reaction was removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried 63

with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:1) and yielded 810 mg (yield 66%) of 2.10c as a white

–1 1 solid. Rf = 0.46 (DCM:hexane, 1:1). FTIR (neat) 2980, 2253, 1605, 1569 cm . H NMR (400

MHz, CDCl3) δ 7.47 – 7.42 (m, 4H), 7.29 (s, 2H), 6.88 – 6.84 (m, 4H), 3.82 (s, 5H), 2.31 (s, 3H),

13 1.37 (s, 10H) ppm. C NMR (400 MHz, CDCl3) δ 159.7, 139.0, 133.1, 132.2, 127.1, 115.8, 114.1,

+ + 90.2, 88.6, 84.3, 55.4, 25.1, 21.2 ppm. HRMS (ESI-TOF) m/z: [M+H] for [C31H32BO4] 479.2394, found 479.2399.

2.10d

To a solution of 2.17e (1.10 g, 2.51 mmol) in THF (120 mL) at -78 °C was added a solution of n- butyllithium in hexanes (1.3 mL, 2.5 M, 3.2 mmol). After stirring for 1 hour at -78 °C, isopropoxyboronic acid pinacol ester (712 mg, 3.82 mmol) was added, the reaction was removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:1) and yielded 810 mg (yield 66%) of 2.10d as a white

–1 1 solid. Rf = 0.46 (DCM:hexane, 1:1). FTIR (neat) 2964, 2202, 1628, 1585, 1535 cm . H NMR

(500 MHz, CDCl3) δ 8.00 (s, 2H), 7.74 – 7.70 (m, 4H), 7.60 – 7.55 (m, 4H), 7.18 (m, 2H), 7.14 –

13 7.13 (m, 2H), 3.95 (s, 6H), 1.40 (s, 12H), 1.36 (s, 9H) ppm. C NMR (500 MHz, CDCl3) δ 158.5,

152.5, 134.2, 131.4, 129.5, 129.2, 129.1, 128.7, 126.9, 126.8, 119.5, 118.6, 106.0, 90.5, 90.0, 84.4, 64

+ + 55.5, 34.8, 31.2, 25.2 ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C42H42BO4] 621.3176, found 621.3181.

2.10e

To a solution of 17e (800 mg, 2.51 mmol) in THF (50 mL) at -78 °C was added a solution of n- butyllithium in hexanes (0.8 mL, 2.5 M, 2.0 mmol). After stirring for 1 hour at -78 °C, isopropoxyboronic acid pinacol ester (580 mg, 3.12 mmol) was added, the reaction was removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:4) and yielded 349 mg (yield 40%) of 2.10e as a white

–1 1 solid. Rf = 0.26 (DCM:hexane, 1:4). FTIR (neat) 2982, 2243, 1607, 1579 cm . H NMR (400

MHz, CDCl3) δ 8.07 (s, 2H), 7.89 – 7.77 (m, 7H), 7.59 (s, 3H), 7.53 – 7.48 (m, 4H), 1.39 (s, 12H),

13 1.35 (s, 9H) ppm. C NMR (500 MHz, CDCl3) δ 150.4, 133.2, 133.1, 131.9, 130.5, 128.22,

128.02, 127.0, 126.8, 126.7, 126.0, 120.3, 94.0, 89.1, 34.8, 31.2 ppm. HRMS (ESI-TOF) m/z:

+ + [M+H] for [C40H37BO2] 560.2886, found 560.2892.

2.10f

To a solution of 2.17j (1.21 g, 2.51 mmol) in THF (120 mL) at -78 °C was added a solution of n- butyllithium in hexanes (1.3 mL, 2.5 M, 3.1 mmol). After stirring for 1 hour at -78 °C, isopropoxyboronic acid pinacol ester (700 mg, 3.80 mmol) was added, the reaction was removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:4) and yielded 800 mg (yield 61%) of 2.10f as a white

–1 1 solid. Rf = 0.21 (DCM:hexane, 1:4). FTIR (neat) 2963, 2869, 2216, 1563 cm . H NMR (400

MHz, CDCl3) δ 7.53 (s, 2H), 7.46 (d, J = 8.2 Hz, 4H), 7.32 (d, J = 8.2 Hz, 4H), 1.35 (s, 12H), 1.32

13 (s, 9H) ppm. C NMR (400 MHz, CDCl3) δ 152.6, 134.4, 132.9, 129.3, 128.8, 126.5, 122.1, 91.1,

+ + 88.9, 84.4, 34.8, 31.1, 25.1 ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C32H32BCl2O2]

529.1872, found 529.1877.

2.10h

To a solution of 2.17f (2.00 g, 3.19 mmol) in THF (120 mL) at -78 °C was added a solution of n- 66 butyllithium in hexanes (1.6 mL, 2.5 M, 4.0 mmol). After stirring for 1 h at -78 °C, isopropoxyboronic acid pinacol ester (1.19 g, 6.40 mmol) was added, the reaction was removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:4) and yielded 1.16 g (yield 55%) of 2.10h as a white

–1 1 solid. Rf = 0.2 (DCM:hexane, 1:4). FTIR (neat) 2930, 2210, 1604, 1553, 1467cm . H NMR (500

MHz, CDCl3) δ 7.66 (s, 2H), 7.46 – 7.43 (m, 4H), 6.88 – 6.86 (m, 4H), 3.97 (t, J = 6.6 Hz, 4H),

1.81 – 1.77 (m, 4H), 1.50 – 1.42 (m, 6H), 1.38 (s, 12H), 0.93 – 0.89 (m, 6H) ppm. 13C NMR (500

2 1 MHz, CDCl3) δ 159.7, 133.2, 131.7(q, J(C, F) = 33.5 Hz), 128.1, 127.4 (q, J(C, F) = 3.8 Hz),

123.5(q, 3J(C, F) = 272.6 Hz), 114.72, 114.66, 92.3, 87.0, 84.8, 68.3, 31.7, 29.3, 25.9, 25.1, 22.7,

+ + 14.2 ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C41H49BF3O4] 673.2676, found 673.3765.

2.10i

To a solution of 2.17g (835 mg, 1.73 mmol) in THF (80 mL) at -78 °C was added a solution of n- butyllithium in hexanes (0.92 mL, 2.5 M, 2.30 mmol). After stirring for 1 hour at -78 °C, isopropoxyboronic acid pinacol ester (387 mg, 2.07 mmol) was added, the reaction removed from the cooling bath and allowed to warm. Upon reaching room temperature the reaction was quenched by the addition of H2O, and then extracted with DCM. The extract was washed with water, dried 67

with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, DCM:hexane, 1:3) and yielded 598 mg (yield 65%) of 2.10i as a white

-1 1 solid. Rf = 0.15 (DCM:hexane, 1:3). FTIR (neat) 2982, 2210, 1602, 1569, 1553 cm . H NMR

(400 MHz, CDCl3) δ 7.67 (s, 2H), 7.48 – 7.45 (m, 4H), 6.90 – 6.87 (m, 4H), 3.83 (s, 6H), 1.38 (s,

13 2 12H) ppm. C NMR (400 MHz, CDCl3) δ 160.1, 133.2, 131.7(q, J(C, F) = 32.8 Hz), 128.1,

127.5(q, 1J(C, F) = 3.8 Hz), 127.4, 123.4(q, 3J(C, F) = 272 Hz), 114.9, 114.2, 92.2, 87.1, 84.8,

+ + 55.4, 25.1 ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C31H29BF3O4] 533.2111, found

531.2115.

2.5.2.3 General procedure for the synthesis of compound 2.8

52 3-Bromophenanthrenes (1.0 equiv.), 2,6-diynylphenyl borate 2.10 (1.0 equiv.) and K2CO3 (2.0 equiv.) were dissolved in THF (50 mL) and water (10 mL). Pd(PPh3)4 (0.1 equiv.) was added to the solution before degassing the mixture via bubbling nitrogen for 30 min. The resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was complete, the mixture was diluted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography to give compound 2.8.

2.8a

3-Bromophenanthrene (78 mg, 0.30 mmol), 2.10a (200 mg, 0.303 mmol) and K2CO3 (84 mg, 0.61 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.030 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, diethyl ether:hexane, 1:15) to give 118 mg (yield 55%) of 2.8a as a spongy white solid. Rf =

0.37 (diethyl ether : hexane, 1:15). FTIR (neat) 2953, 2206, 1604, 1567, 1554 cm-1. 1H NMR (400

MHz, CDCl3) δ 9.06 (s, 1H), 8.75 – 8.70 (m, 1H), 7.99 – 7.94 (m, 2H), 7.94 – 7.90 (m, 1H), 7.84

– 7.76 (m, 2H), 7.67 (s, 2H), 7.60 – 7.56 (m, 2H), 7.06 – 7.00 (m, 1.3 Hz, 4H), 6.63 – 6.56 (m,

4H), 3.84 (t, J = 6.4 Hz, 4H), 1.74 – 1.67 (m, 4H), 1.43 (s, 9H), 1.38 – 1.27 (m, 12H), 0.91 – 0.85

13 (m, 6H) ppm. C NMR (400 MHz, CDCl3) δ 159.2, 150.3, 142.7, 137.3, 132.9, 132.2, 131.4,

130.8, 129.7, 129.6, 129.5, 128.6, 127.3, 127.05, 126.96, 126.7, 126.5, 125.2, 123.4, 123.0, 115.1,

114.4, 92.6, 88.4, 68.1, 34.8, 31.7, 31.3, 29.2, 25.8, 22.7, 14.2 ppm. HRMS (APPI-TOF) m/z: [M]+

+ calcd for [C52H54O2] 740.4124, found 740.4124.

2.8b

3-Bromophenanthrene (124 mg, 0.482 mmol), 2.10b (250 mg, 0.480 mmol) and K2CO3 (131 mg,

0.948 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (56 mg, 0.048 mmol) was added and the 69

resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:15) to give 213 mg (yield 78%) of 2.8b as a spongy white solid.

–1 1 Rf = 0.3 (DCM:hexane, 1:3) FTIR (neat) 2960, 2205, 1604, 1585, 1543, 1508, cm . H NMR (400

MHz, CDCl3) δ 9.08 (s, 1H), 8.78 – 8.71 (m, 1H), 8.01 – 7.91 (m, 3H), 7.86 – 7.78 (m, 2H), 7.70

(s, 2H), 7.63 – 7.56 (m, 2H), 7.10 – 7.04 (m, 4H), 6.67 – 6.59 (m, 4H), 3.70 (s, 6H), 1.46 (s, 9H)

13 ppm. C NMR (400 MHz, CDCl3) δ 159.6, 150.4, 142.8, 137.3, 133.0, 132.3, 131.4, 130.8, 129.7,

129.5, 128.6, 127.4, 127.1, 126.9, 126.7, 126.5, 125.1, 123.4, 123.0, 115.4, 113.9, 92.5, 88.5, 55.3,

+ + 34.8, 31.3 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C42H34O2] 570.2559, found 570.2550.

2.8c

3-Bromophenanthrene (134 mg, 0.521 mmol), 2.10c (250 mg, 0.522 mmol) and K2CO3 (144 mg,

1.05 mmol) were dissolved in THF (50 mL) and distilled water (10mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (61 mg, 0.052 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography

(silica gel, DCM:hexane, 1:3) to give 334 mg (yield 63%) of 2.8c as a spongy white solid. Rf =

0.12 (DCM:hexane, 1:3). FTIR (neat) 2953, 2206, 1604, 1567, 1554 cm–1. 1H NMR (400 MHz, 70

CDCl3) δ 9.07 (s, 1H), 8.76 – 8.72 (m, 1H), 8.00 – 7.91 (m, 3H), 7.82 (m, 2H), 7.61 – 7.57 (m,

2H), 7.50 (s, 2H), 7.05 – 7.01 (m, 4H), 6.64 – 6.60 (m, 4H), 3.70 (s, 6H), 2.44 (s, 3H) ppm. 13C

NMR (400 MHz, CDCl3) δ 159.6, 142.8, 137.3, 137.1, 132.95, 132.88, 132.3, 131.4, 130.8, 129.7,

129.6, 128.6, 127.3, 127.1, 126.9, 126.7, 126.5, 125.1, 123.6, 123.0, 115.3, 113.9, 92.8, 88.1, 55.3,

+ + 20.9 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C39H28O2] 528.2089, found 528.2123.

2.8d

6-Methoxy-3-bromophenanthrene (86 mg, 0.30 mmol), 2.10a (200 mg, 0.303 mmol) and K2CO3

(83 mg, 0.60 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (58 mg, 0.050 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4.

The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:4) to give 150 mg (yield 67%) of 2.8d as a spongy white

-1 1 solid . Rf = 0.15 (DCM:hexane, 1:4). FTIR (neat) 2953, 2205, 1621, 1507 cm . H NMR (400

MHz, CDCl3) δ 9.02 (s, 1H), 8.06 (s, 1H), 7.97 (s, 2H), 7.82 (d, J = 8.7 Hz, 1H), 7.73 – 7.69 (m,

3H), 7.25 – 7.19 (m, 2H), 7.12 – 7.02 (m, 4H), 6.66 – 6.60 (m, 4H), 3.84 (t, J = 6.6 Hz, 4H), 3.79

(s, 3H), 1.75 – 1.67 (m, 4H), 1.45 (s, 9H), 1.40 – 1.26 (m, 12H), 0.94 – 0.86 (m, 6H) ppm. 13C

NMR (400 MHz, CDCl3) δ 159.2, 158.6, 150.3, 142.6, 136.7, 132.9, 132.1, 130.6, 130.0, 129.6, 71

129.5, 129.1, 127.8, 127.4, 126.7, 125.1, 124.5, 123.5, 117.5, 115.0, 114.5, 103.5, 92.8, 88.5, 68.1,

55.4, 34.7, 31.7, 31.3, 29.2, 25.8, 22.7, 14.2 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for

+ [C53H56O3] 640.4229, found 640.4250.

2.8e

3-Bromophenanthrene (55 mg, 0.21 mmol), 2.10d (132 mg, 0.21 mmol) and K2CO3 (59 mg, 0.42 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (25 mg, 0.16 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:1) to give 90 mg (yield 63%) of 2.8e as a spongy white solid. Rf = 0.37

–1 1 (DCM:hexane, 1:1). FTIR (neat) 2961, 2205, 1629, 1600 cm . H NMR (500 MHz, CDCl3) δ 9.19

(s, 1H), 8.82 (d, J = 8.0 Hz, 1H), 8.06 – 8.01 (m, 2H), 7.99 (dd, J = 7.8, 1.6 Hz, 1H), 7.87 (d, J =

8.9 Hz, 2H), 7.77 (s, 2H), 7.62 – 7.56 (m, 2H), 7.51 (s, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.24 (d, J =

8.9 Hz, 2H), 7.17 (dd, J = 8.5, 1.6 Hz, 2H), 7.04 – 6.97 (m, 4H), 3.87 (s, 6H), 1.48 (s, 9H) ppm.

13 C NMR (500 MHz, CDCl3) δ 158.3, 150.5, 143.2, 137.3, 134.1, 132.4, 131.6, 131.4, 130.9,

129.9, 129.75, 129.71, 129.4, 128.8, 128.7, 128.4, 127.7, 127.5, 127.2, 127.0, 126.8, 126.6, 123.3,

119.2, 118.1, 105.7, 93.3, 89.5, 55.3, 34.8, 31.4 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for 72

+ [C50H38O2] 670.2872, found 670.2874.

2.8f

3-Bromophenanthrene (76 mg, 0.29 mmol), 2.10h (200 mg, 0.297 mmol) and K2CO3 (83 mg, 0.60 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.03 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:4) to give 194 mg (yield 90%) of 2.8f as a spongy white solid. Rf = 0.36

–1 1 (DCM:hexane, 1:4). FTIR (neat) 2930, 2859, 2211, 1605, 1509 cm . H NMR (400 MHz, CDCl3)

δ 9.07 (s, 1H), 8.73 (dd, J = 6.3, 3.1 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.98 – 7.89 (m, 2H), 7.88

(s, 2H), 7.84 (s, 2H), 7.65 – 7.58 (m, 2H), 7.06 – 6.99 (m, 4H), 6.66 – 6.58 (m,, 4H), 3.84 (t, J =

6.6 Hz, 4H), 1.75 – 1.65 (m, 4H), 1.44 – 1.26 (m, 12H), 0.96 – 0.85 (m, 6H) ppm. 13C NMR (400

2 MHz, CDCl3) δ 159.6, 148.2, 136.2, 133.1, 132.3, 131.9, 130.7 (q, J(C, F) = 33.4 Hz),, 129.9,

129.7, 129.0, 128.7, 128.3 (q, 1J(C,F) = 3.2 Hz),, 127.7, 127.6, 126.9, 126.84, 126.78, 125.0, 124.9,

123.7 (q, 3J(C,F) = 272.6 Hz),, 123.0, 114.5, 114.3, 94.9, 86.7, 68.1, 31.7, 29.2, 25.8, 22.7, 14.1

+ + ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C49H45F3O2] 722.3371, found 722.3372.

2.8g

3-Bromophenanthrene (72 mg, 0.28 mmol), 2.10i (150 mg, 0.223 mmol) and K2CO3 (78 mg, 0.56 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (32 mg, 0.027 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:1) to give 131 mg (yield 80%) of 2.8g as a spongy white solid. Rf = 0.38

(DCM:hexane, 1:1). FTIR (neat) 2964, 2206, 1604, 1554, 1506, cm–1. 1H NMR (500 MHz,

CDCl3) δ 9.05 (s, 1H), 8.73 – 8.70 (m, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.95 – 7.91 (m, 2H), 7.88 (s,

2H), 7.86 – 7.83 (m, 2H), 7.62 – 7.60 (m, 2H), 7.04 – 7.01 (m, 4H), 6.64 – 6.61 (m, 4H), 3.71 (s,

13 6H). C NMR (500 MHz, CDCl3) δ 160.0, 148.2, 136.1, 133.2, 133.0, 132.3, 131.9, 130.6, 130.1,

129.8, 129.7, 128.8, 128.4, 128.2, 127.8, 126.9, 126.8, 125.1, 124.9, 124.8, 122.9, 114.2, 94.8,

+ + 86.8, 55.9, 55.4 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C39H25F3O2] 582.1807, found

582.1807.

2.8h

3-Phenanthrenylborolane (374 mg, 1.12 mmol), 2.17h (300 mg, 0.613 mmol) and K2CO3 (340 mg,

2.45 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (142 mg, 0.123 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography

(silica gel, DCM:hexane, 3:2) to give 210 mg (yield 58%) of 2.8h as a spongy white solid. Rf =

0.28 (DCM:hexane, 3:2). FTIR (neat) 2964, 2206, 1714, 1602, 1554 cm–1. 1H NMR (400 MHz,

CDCl3) δ 9.07 (s, 1H), 8.78 – 8.69 (m, 1H), 8.29 (s, 2H), 8.01 (d, J = 8.2 Hz, 1H), 7.96 – 7.91 (m,

2H), 7.83 (d, J = 2.8 Hz, 2H), 7.63 – 7.58 (m, 2H), 7.09 – 6.99 (m, 4H), 6.68 – 6.56 (m, 4H), 4.47

13 (q, J = 7.1 Hz, 2H), 3.71 (s, 6H), 1.48 (t, J = 7.1 Hz, 3H) ppm. C NMR (400 MHz, CDCl3) δ

165.6, 159.8, 149.0, 136.5, 133.1, 132.9, 132.3, 131.9, 130.7, 129.75, 129.69, 129.0, 128.7, 127.6,

126.89, 126.87, 126.7, 125.0, 124.4, 123.0, 114.9, 114.0, 94.0, 87.2, 61.6, 55.4, 14.5 ppm. HRMS

+ + (APPI-TOF) m/z: [M] calcd for [C41H30O4] 586.2144, found 586.2205.

2.8i

6-Trifluoromethyl-3-bromophenanthrene (98 mg, 0.30 mmol), 2.10a (200 mg, 0.297 mmol) and

K2CO3 (84 mg, 0.61 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (35 mg, 0.03 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over

Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, EtOAc:hexane, 1:20) to give 151 mg (yield 64%) of 2.8i as a spongy

-1 1 white solid. Rf = 0.32 (EtOAc:hexane, 1:20). FTIR (neat) 2930, 2859, 2211, 1605, 1508 cm . H

NMR (500 MHz, CDCl3) δ 9.10 (s, 1H), 9.00 (s, 1H), 8.04 – 8.00 (m, 2H), 7.94 (d, J = 8.8 Hz,

1H), 7.84 – 7.75 (m, 2H), 7.70 (s, 2H), 7.57 (s, 1H), 7.37 – 7.32 (m, 1H), 7.06 – 7.02 (m, 4H), 6.75

– 6.73 (m, 1H), 6.63 – 6.60 (m, 3H), 3.91 (t, J = 6.4 Hz, 2H), 3.84 (t, J = 6.6 Hz, 2H), 1.75 – 1.68

(m, 4H), 1.53 – 1.47 (m, 9H), 1.39 – 1.29 (m, 12H), 0.91 – 0.87 (m, 6H) ppm. 13C NMR (500

MHz, CDCl3) δ 159.3, 150.7, 142.1, 138.1, 134.1, 133.0, 132.9, 131.6, 130.5, 130.3, 129.7, 129.4,

129.3, 128.2, 127.6, 126.3, 125.1, 123.4, 122.4, 114.9, 114.7, 114.51, 114.46, 92.9, 88.2, 68.1,

+ + 34.8, 31.7, 31.3, 29.2, 25.8, 22.7, 14.1 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C53H53F3O2]

778.3998, Found 778.3966.

2.8j

3-Bromophenanthrene (65 mg, 0.25 mmol), 2.10g (144 mg, 0.252 mmol) and K2CO3 (70 mg, 0.50 mmol) were dissolved in THF (50 mL) and distilled water (10 ml). The solution was degassed by 76

bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (29 mg, 0.025 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:5) to give 123 mg (yield 79%) of 2.8j as a spongy white solid. Rf = 0.43

–1 1 (DCM:hexane, 1:5). FTIR (neat) 2961, 2252, 1512 cm . H NMR (500 MHz, CDCl3) δ 9.07 (s,

1H), 8.78 – 8.72 (m, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.97 – 7.93 (m, 2H), 7.87 – 7.79 (m, 2H), 7.73

(s, 2H), 7.63 – 7.57 (m, 2H), 7.16 – 7.10 (m, 4H), 7.10 – 7.04 (m, 4H), 1.46 (s, 9H), 1.23 (s, 18H)

13 ppm. C NMR (500 MHz, CDCl3) δ 151.4, 150.4, 143.2, 137.2, 132.3, 131.5, 131.3, 131.1, 130.8,

130.0, 129.7, 128.7, 127.2, 127.1, 127.0, 126.8, 126.6, 126.4, 125.2, 125.2, 123.3, 120.2, 92.7,

+ + 89.1, 34.8, 34.8, 31.4, 31.3 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C48H46] 622.36, found

622.3606.

2.8k

3-Bromophenanthrene (97 mg, 0.38 mmol), 2.10f (200 mg, 0.378 mmol) and K2CO3 (104 mg,

0.753 mmol) were dissolved in THF (50 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (44 mg, 0.038 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The 77 solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane, 1:5) to give 131 mg (yield 60%) of 2.8k as a spongy white solid.

–1 1 Rf = 0.37 (DCM:hexane, 1:5). FTIR (neat) 3384, 2963, 2248, 1584 cm . H NMR (500 MHz,

CDCl3) δ 9.02 (s, 1H), 8.72 – 8.67 (m, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.95 – 7.92 (m, 1H), 7.90

(dd, J = 8.2, 1.6 Hz, 1H), 7.86 – 7.78 (m, 2H), 7.72 (s, 2H), 7.64 – 7.54 (m, 2H), 7.08 – 7.04 (m,

13 4H), 7.03 – 6.99 (m, 4H), 1.44 (s, 9H) ppm. C NMR (500 MHz, CDCl3) δ 150.6, 143.5, 136.9,

134.2, 132.7, 132.3, 131.6, 130.6, 130.3, 130.2, 130.1, 129.7, 129.3, 128.7, 128.6, 127.5, 126.9,

126.82, 126.76, 125.1, 122.9, 121.6, 91.5, 90.5, 34.8, 31.3 ppm. HRMS (APPI-TOF) m/z: [M]+

+ calcd for [C40H28Cl2] 578.1568, found 578.1590.

2.8l

3-Bromophenanthrene (88 mg, 0.34 mmol), 2.10e (191 mg, 0.34 mmol) and K2CO3 (188 mg, 1.36 mmol) were dissolved in THF (45 mL) and distilled water (10 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (39 mg, 0.034 mmol) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 h. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, diethyl DCM : hexane, 1:4) to give 160 mg (yield 77%) of 2.8l as a pale yellow solid. Rf =

0.27 (DCM:hexane, 1:4). FTIR (neat) 2943, 2216, 1614, 1576, 1544 cm-1. 1H NMR (400 MHz,

CDCl3) δ 9.21 (d, J = 2.1 Hz, 1H), 8.83 (d, J = 8.1 Hz, 1H), 8.10 – 7.97 (m, 3H), 7.89 (d, J = 8.9

Hz, 2H), 7.81 (d, J = 2.6 Hz, 2H), 7.72 – 7.67 (m, 2H), 7.66 – 7.54 (m, 6H), 7.41 – 7.36 (m, 5H), 78

13 7.21 (dt, J = 8.5, 1.7 Hz, 2H), 1.49 (s, 9H) ppm. C NMR (400 MHz, CDCl3) δ 150.6, 143.5,

137.1, 132.9, 132.8, 132.4, 131.7, 130.8, 130.1, 129.8, 129.6, 128.7, 128.1, 127.9, 127.8, 127.7,

127.6, 127.3, 127.0, 126.9, 126.81, 126.7, 126.6, 126.4, 125.29, 125.28, 123.2, 123.1, 120.5, 93.1,

+ + 90.1, 34.8, 31.4 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C48H34] 610.2660, found

610.2669.

2.8m

3-Bromophenanthrene (108 mg, 0.420 mmol), 2.10j (200 mg, 0.419 mmol) and K2CO3 (232 mg,

1.68 mmol) were dissolved in THF (30 mL) and distilled water (5 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (48 mg, 0.042 mmol,) was added and the resulting mixture was stirred under a N2 atmosphere at 80 °C for 24 hours. After the reaction was complete, the mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography

(silica gel, diethyl DCM : hexane, 1:5) to give 171 mg (yield 77%) of 2.8m as a colorless oil. Rf

= 0.31 (DCM:hexane, 1:5). FTIR (neat) 2933, 2211, 1613, 1556, 1524 cm-1. 1H NMR (500 MHz,

CDCl3) δ 8.85 (s, 1H), 8.69 (d, J = 8.7 Hz, 1H), 7.91 – 7.86 (m, 2H), 7.78 – 7.73 (m, 3H), 7.63 –

7.56 (m, 2H), 7.52 (s, 2H), 2.11 (t, J = 7.0 Hz, 4H), 1.37 (s, 9H), 1.20 – 1.12 (m, 4H), 0.97 – 0.90

13 (m, 8H), 0.86 – 0.79 (m, 4H), 0.68 (t, J = 7.2 Hz, 6H) ppm. C NMR (500 MHz, CDCl3) δ 150.1,

143.4, 137.8, 132.3, 131.2, 130.9, 130.7, 129.7, 129.3, 129.1, 126.9, 126.4, 124.9, 123.7, 123.0,

122.8, 93.6, 80.6, 34.6, 31.3, 31.3, 28.4, 22.4, 19.5 ppm. 79

2.5.2.4 General procedure for the synthesis of compound 2.7

A flame-dried round bottom flask was charged with a magnetic stirring bar, the corresponding precursors 8 (1 equiv.), and anhydrous toluene (25 mL). 10 mol% each of InCl3 and AgNTf2 were added to the solution inside the glovebox after degassing the mixture via bubbling nitrogen for 30 min, then the resulting mixture was heated to reflux under a N2 atmosphere. After reaction completion, the solvent was removed under reduced pressure and the residue was purified by column chromatography.

2.7a

2.8a (82 mg, 0.11 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min.

InCl3 (2.6 mg, 0.011 mmol) and silver bistriflimide (4.5 mg, 0.11 mmol) was added inside a glovebox. Then the reaction mixture was heated to reflux for 15 h under nitrogen environment. After the reaction was complete, it was quenched with 5mL of a saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 2:1) to give 52 mg (yield 63%) of 2.7a as faintly yellow spongy solid. Rf = 0.3 (hexane:DCM, 2:1). FTIR (neat) 2953, 2929, 1605

–1 1 cm . H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.36 (d, J = 15.8 Hz, 2H), 8.27 (s, 1H), 8.15 (d,

J = 8.1 Hz, 1H), 8.01 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.76 – 7.7.66 (m,

4H), 7.32 – 7.7.26 (m, 1H), 7.16 (d, J = 7.0 Hz, 3H), 7.00 – 7.08 (m, 1H), 6.95 – 5.66 (br, 3H), 80

4.13 (t, J = 6.5 Hz, 2H), 3.83 (q, J = 6.2, 5.6 Hz, 2H), 1.91 (m, J = 7.5 Hz, 2H), 1.73 – 1.69 (m,

13 2H), 1.64 (s, 9H), 1.52 – 1.30 (m, 12H), 1.02 – 0.92 (m, 6H) ppm. C NMR (400 MHz, CDCl3) δ

158.9, 157.8, 149.8, 139.44, 139.38, 136.7, 133.4, 131.3, 131.2, 131.1, 130.6, 130.4, 129.6, 129.5,

129.2, 127.9, 127.5, 126.8, 126.7, 126.1, 125.62, 125.59, 125.1, 125.0, 124.3, 124.0, 122.9, 122.2,

114.6, 68.3, 68.1, 35.4, 32.0, 31.8, 31.7, 29.5, 29.2, 26.0, 25.8, 22.83, 22.76, 14.3, 14.2 ppm.

+ + HRMS (APPI-TOF) m/z: [M] calcd for [C52H54O2] 710.2124, found 710.2124.

2.7b

2.8b (213 mg, 0.373 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min.

InCl3 (8.2 mg, 0.037 mmol) and silver bistriflimide (15 mg, 0.037 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After reaction was complete, it was quenched with 5mL of saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 163 mg (yield 76%) of 2.7b as

-1. 1 faint yellow spongy solid. Rf = 0.3 (hexane:DCM, 1:1). FTIR (neat) 2960, 1608 cm H NMR

(400 MHz, CDCl3) δ 8.57 (s, 1H), 8.36 (d, J = 1.9 Hz, 1H), 8.32 (s, 1H), 8.25 (d, J = 1.8 Hz, 1H),

8.13 (m, J = 8.3, 1.3, 0.7 Hz, 1H), 7.99 (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.86 – 7.80 (m, 1H), 7.76

– 7.67 (m, 3H), 7.31 – 7.25 (m, 1H), 7.19 – 7.15 (m, 2H), 7.04 (m, J = 8.3, 7.0, 1.4 Hz, 1H), 6.90

13 – 6.15 (br, 4H), 3.98 (s, 3H), 3.69 (s, 3H), 1.64 (s, 9H) ppm. C NMR (400 MHz, CDCl3) δ 159.4, 81

158.3, 149.9, 139.4, 139.3, 136.9, 133.7, 131.4, 131.3, 131.2, 131.1, 130.6, 130.4, 129.7, 129.5,

129.2, 128.0, 127.5, 126.9, 126.7, 126.2, 125.7, 125.1, 125.0, 124.4, 124.0, 122.9, 122.2, 121.9,

+ + 114.1, 55.6, 55.4, 35.4, 32.0 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C42H34O2] 570.2559, found 570.2567.

2.7c

2.8c (334 mg, 0.63 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min.

InCl3 (13.9 mg, 0.0631 mmol) and AgNTf2 (24.5 mg, 0.0631 mmol) was added inside glovebox.

Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 257 mg (yield 77%) of 2.7c as faint

-1 1 yellow spongy solid. Rf = 0.32 (hexane:DCM, 1:1). FTIR (neat) 2926, 1739, 1620, 1506 cm . H

NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.23 (s, 1H), 8.12 (s, 2H), 8.00 (s, 1H), 7.96 – 7.90 (m,

2H), 7.83 (d, J = 8.7 Hz, 1H), 7.75 – 7.65 (m, 3H), 7.31 – 7.26 (m, 1H), 7.16 (d, J = 8.8 Hz, 2H),

7.30 – 7.26 (m, 1H), 6.85 – 6.12 (br, 4H), 3.98 (s, 3H), 3.68 (s, 3H), 2.84 (s, 3H) ppm. 13C NMR

(400 MHz, CDCl3) δ 159.4, 158.3, 139.5, 139.4, 136.9, 136.5, 133.7, 131.41, 131.36, 131.25,

131.3, 130.3, 130.1, 129.7, 129.4, 129.2, 127.54, 127.52, 126.8, 126.7, 126.3, 126.2, 125.8, 125.7,

125.2, 124.9, 124.4, 124.1, 121.9, 114.2, 55.6, 55.4, 22.2 ppm. HRMS (APPI-TOF) m/z: [M]+

+ calcd for [C39H28O2] 528.2089, found 528.2114. 82

2.7d

2.8d (68 mg, 0.092 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min.

InCl3 (2.1 mg, 0.0092 mmol) and AgNTf2 (3.5 mg, 0.0092 mmol) was added inside a glovebox.

Then the reaction mixture was heated to reflux for 15 h under nitrogen environment. After the reaction was complete, it was quenched with 5 mL of a saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 45 mg (yield 66%) of 2.7d as light yellow spongy solid. Rf = 0.33 (hexane:DCM, 1:1). FTIR (neat) 2953.07, 1608.66,

1 1 12043.31, 1174.56, 830.41 cm- . H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.32 (d, J = 8.3 Hz,

2H), 8.22 (s, 1H), 7.96 (s, 1H), 7.82 – 7.76 (m, 2H), 7.71 – 7.63 (m, 3H), 7.57 (d, J = 2.5 Hz, 1H),

7.18 – 7.12 (m, 2H), 6.94 (m, 1H), 6.57 (br, 4H), 4.16 – 4.10 (m, 2H), 3.88 – 3.75 (m, 5H), 0.99 –

0.87 (m, 2H), 1.74 – 1.67 (m, 2H), 1.62 (s, 9H), 1.49 – 1.28 (m, 12H), 0.99 – 0.87 (m, 6H) ppm.

13 C NMR (400 MHz, CDCl3) δ 159.0, 157.9, 156.6, 149.8, 139.5, 139.0, 136.5, 133.5, 131.4,

131.2, 131.16, 131.15, 130.8, 130.3, 129.6, 129.2, 127.9, 127.8, 127.1, 126.5, 126.4, 125.0, 124.8,

124.5, 124.0, 122.9, 122.1, 121.9, 116.0, 114.7, 112.8, 68.4, 68.2, 55.2, 35.4, 32.1, 31.83, 31.75,

29.6, 29.3, 26.0, 25.8, 22.83, 22.81, 14.24, 14.20 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd for

+ [C53H56O3] 640.4229, found 640.4225.

2.7e

2.8e (87 mg, 0.13 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min.

InCl3 (3.1 mg, 0.013 mmol) and AgNTf2 (5.0 mg, 0.013 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate, extracted in

DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 55 mg (yield 77%) of 2.7e as faint

-1 1 yellow spongy solid. Rf = 0.26 (hexane:DCM 1:1). FTIR(neat) 3026, 2920, 1604 cm . H NMR

(500 MHz, CDCl3) δ 8.62 (s, 1H), 8.48 (s, 1H), 8.42 (d, J = 1.8 Hz, 1H), 8.30 (d, J = 1.8 Hz, 1H),

8.22 – 8.18 (m, 2H), 8.11 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.93 – 7.85 (m, 4H), 7.81 (d, J = 8.7

Hz, 1H), 7.63 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 2.6 Hz, 1H), 7.30 – 7.27 (m, 1H), 7.08 – 7.03 (m,

2H), 6.95 (d, J = 13.1 Hz, 2H), 6.83 (s, 2H), 4.03 (s, 3H), 3.88 (s, 3H), 1.65 (s, 9H) ppm. 13C NMR

(500 MHz, CDCl3) δ 158.2, 157.5, 150.0, 139.84, 139.78, 136.7, 134.2, 133.2, 131.4, 131.3, 131.2,

131.1, 130.4, 129.9, 129.6, 129.4, 129.3, 129.24, 129.18, 128.8, 128.4, 127.64, 127.56, 126.9,

126.8, 126.7, 126.1, 125.7, 125.3, 125.0, 124.2, 124.1, 123.2, 122.5, 122.1, 119.4, 118.6, 106.0,

+ + 105.6, 55.6, 55.3, 35.5, 32.1 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C50H38O2] 670.2872, found 670.2874.

2.7f

2.8f (194 mg, 0.268 mmol) was dissolved in dry toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. InCl3 (5.9 mg, 0.027 mmol) and AgNTf2 (10 mg, 0.0258 mmol) was added inside glovebox.

The reaction mixture was heated to reflux for 15 h under nitrogen environment. After reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate, extracted in

DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:4) to give 180 mg (yield 92%) of 2.7f as faint

-1 1 yellow spongy solid. Rf = 0.07 (hexane:DCM, 1:4). FTIR (neat) 2930, 1607, 1508 cm . H NMR

(400 MHz, CDCl3) δ 8.65 (s, 1H), 8.52 (s, 1H), 8.38 – 8.29 (m, 2H), 8.10 (d, J = 7.8 Hz, 1H), 8.00

(d, J = 4.6 Hz, 1H), 7.96 – 7.92 (m, 1H), 7.90 – 7.85 (m, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.77 – 7.72

(m, 2H), 7.334 – 7.28 (m, 1H), 7.26 (s, 1H), 7.18 – 7.13 (m, 2H), 7.09 – 7.03 (m, 1H), 6.55 (s,

3H), 4.13 (t, J = 6.6 Hz, 2H), 3.85 – 3.75 (m, 2H), 1.95 – 1.86 (m, 2H), 1.75 – 1.65 (m, 2H), 1.60

– 1.54 (m, 2H), 1.46 – 1.38 (m, 6H), 1.37 – 1.30 (m, 4H), 1.00 – 0.90 (m, 6H) ppm. 13C NMR (400

MHz, CDCl3) δ 159.3, 158.2, 158.1, 141.0, 140.7, 136.0, 132.7, 131.54, 131.51, 131.49, 131.3,

131.1, 131.0, 130.0, 129.7, 129.7, 129.0, 128.4, 127.2, 126.6, 126.3, 126.13, 126.09, 125.9, 125.6,

125.2, 124.9, 124.7, 121.30, 121.26, 120.8, 120.7, 114.8, 68.4, 68.2, 31.8, 31.7, 29.5, 29.2, 26.0, 85

+ + 25.8, 22.83, 22.76, 14.2, 14.2 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C49H45F3O2]

722.3372, found 722.3372.

2.7g

2.8g (186 mg, 0.319 mmol) was dissolved in toluene (30 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. catalytic mixture of InCl3 (7.1 mg, 0.032 mmol) and AgNTf2 (12 mg, 0.031 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment.

After reaction was complete, it was quenched with 5 mL of saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM, 1:1) to give 134.0 mg (yield

72%) of 2.7g as faint yellow spongy solid. Rf = 0.38 (hexane:DCM, 1:1). FTIR (neat) 3026.27,

1 2919.55, 1604.32, 1495.09 cm-1. H NMR (500 MHz, CDCl3) δ 8.63 (s, 1H), 8.52 (s, 1H), 8.35

(d, J = 1.7 Hz, 1H), 8.33 (s, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.98 (s, 1H), 7.94 (d, J = 8.6 Hz, 1H),

7.87 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 6.6 Hz, 1H), 7.65 (d, J = 7.9 Hz, 2H), 7.33 – 7.29 (m, 1H),

7.16 (d, J = 8.8 Hz, 3H), 7.07 – 7.04 (m, 1H), 6.92 – 6.16 (br, 3H), 3.98 (s, 3H), 3.69 (s, 3H). 13C

NMR (500 MHz, 3) δ 159.7, 158.6, 140.9, 140.6, 136.2, 132.9, 131.5, 131.4, 131.1, 131.0, 130.0,

129.8, 129.6, 129.0, 128.5, 128.4, 128.2, 127.2, 126.6, 126.3, 126.12, 126.06, 125.9, 125.5, 125.1,

124.9, 124.7, 123.9, 121.3, 120.8, 114.3, 55.62, 55.60, 55.4 ppm. HRMS (APPI-TOF) m/z: [M]+

+ calcd for [C39H25F3O2] 582.1807, found 582.1807. 86

2.7h

2.8h (170 mg, 0.289 mmol) was dissolved in toluene (30 mL) in a 50 mL flame dried-round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. catalytic mixture of InCl3 (7.1 mg, 0.032 mmol) and AgNTf2 (11 mg, 0.028 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment.

1714.61, 1608.06, 1245.65, 1221.56, 1210.14, 1176.83, 1034.46, 833.67 cm-1. 1H NMR (400

MHz, CDCl3) δ 8.98 (s, 1H), 8.82 (s, 1H), 8.62 (s, 1H), 8.37 (s, 1H), 8.11 (d, J = 8.2 Hz, 1H), 8.04

(s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.69 (d, J =

8.1 Hz, 2H), 7.33 – 7.27 (m, 1H), 7.18 (d, J = 8.3 Hz, 2H), 7.09 – 7.03 (m, 1H), 6.55 (s, 4H), 4.58

13 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 3.69 (s, 3H), 1.54 (s, 3H). C NMR (400 MHz, CDCl3) δ 167.3,

159.6, 158.5, 140.2, 140.1, 136.4, 133.1, 131.44, 131.40, 131.2, 131.1, 130.9, 130.6, 130.0, 129.7,

129.1, 128.4, 128.2, 127.8, 126.6, 126.4, 126.32, 126.29, 126.2, 126.0, 125.8, 125.5, 125.3, 124.69,

+ + 124.67, 114.2, 61.5, 55.6, 55.4, 14.7 ppm. HRMS (APPI-TOF) m/z: [M] calcd for [C41H30O4]

586.2144, found 586.2158.

2.7i

2.8i (199 mg, 0.256 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. A catalytic mixture of InCl3 (5.6 mg, 0.02 mmol) and AgNTf2 (10 mg, 0.026 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment. After the reaction was complete, it was quenched with 5 mL of a saturated solution of sodium bicarbonate, extracted in DCM, dried with Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:EtOAc, 1:20) to give 98 mg (yield

49%) of 2.7i as faint yellow spongy solid. Rf = 0.30 (hexane:EtOAc, 1:20). FTIR (neat) 2953,

-1 1 1608, 1509 cm . H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 8.45 – 8.35 (m, 3H), 8.28 (s, 1H),

8.08 – 8.00 (m, 2H), 7.87 – 7.81 (m, 2H), 7.68 (d, J = 6.7 Hz, 2H), 7.46 (d, J = 8.4 Hz, 1H), 7.16

(d, J = 7.3 Hz, 2H), 6.12 (br, 4H), 4.13 (t, J = 6.5 Hz, 2H), 3.86 (t, J = 6.2 Hz, 2H), 1.96 – 1.87

(m, 2H), 1.75 – 1.69 (m, 2H), 1.65 (d, J = 1.3 Hz, 9H), 1.56 – 1.28 (m, 12H), 1.02 – 0.90 (m, 6H)

13 ppm. C NMR (400 MHz, CDCl3) δ 159.0, 158.0, 150.3, 139.3, 139.0, 135.8, 133.2, 132.9,

131.34, 131.27, 131.1, 131.0, 130.5, 130.2, 129.7, 129.3, 129.0, 128.5, 128.1, 127.2, 126.9, 126.6,

126.0, 125.9, 125.6, 125.2, 124.8, 124.0, 123.3, 122.6, 121.7, 114.7, 68.3, 68.2, 35.5, 32.0, 31.8,

31.7, 29.5, 29.2, 26.0, 25.8, 22.83, 22.77, 14.25, 14.20 ppm. HRMS (APPI-TOF) m/z: [M]+ calcd

+ for [C53H53F3O2] 778.3998, Found 778.3998.

2.7j

2.8j (123 mg, 0.197 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. catalytic mixture of InCl3 (4.4 mg, 0.019 mmol) and AgNTf2 (7.6 mg, 0.019 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment.

67%) of 2.7j as faint yellow spongy solid. Rf = 0.31 (hexane:EtOAc, 20:1). FTIR (neat) 3026,

-1 1 2919, 2224, 1604 cm . H NMR (400 MHz, CDCl3) δ 10.22 (d, J = 8.4 Hz, 1H), 8.10 (s, 1H), 8.02

(d, J = 8.7 Hz, 2H), 7.93 (s, 1H), 7.91 – 7.80 (m, 4H), 7.72 – 7.61 (m, 3H), 7.50 – 7.45 (m, 2H),

7.21 – 7.12 (m, 1H), 7.11 – 6.78 (m, 4H), 1.55 (s, 9H), 1.39 (s, 9H), 1.19 (s, 9H) ppm. 13C NMR

(400 MHz, CDCl3) δ 151.8, 149.3, 148.8, 140.8, 139.8, 133.0, 132.9, 132.3, 131.33, 131.31, 130.6,

130.1, 129.9, 128.8, 127.8, 127.7, 127.4, 127.2, 126.3, 125.7, 125.5, 125.3, 125.08, 125.05, 124.7,

124.4, 121.0, 119.5, 94.2, 92.0, 35.0, 34.8, 34.4, 31.5, 31.4, 31.3 ppm. HRMS (APPI-TOF) m/z:

+ + [M] calcd for [C48H46] 622.3599, found 622.3601.

2.7k

2.8k (138 mg, 0.238 mmol) was dissolved in toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was deoxygenated by bubbling nitrogen gas through the solution for 30 min. catalytic mixture of InCl3 (5.3 mg, 0.024 mmol) and AgNTf2 (9.3 mg, 0.024 mmol) was added inside glovebox. Then reaction mixture was heated to reflux for 15 h under nitrogen environment.

-1 1 1489 cm . H NMR (400 MHz, CDCl3) δ 10.07 (d, J = 8.7 Hz, 1H), 8.08 (s, 1H), 8.00 (d, J = 10.5

Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H), 7.88 – 7.81 (m, 3H), 7.71 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 8.3

Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 14.6 Hz, 2H), 7.06 – 6.82 (m, 4H), 1.53 (s, 9H)

13 ppm. C NMR (400 MHz, CDCl3) δ 149.1, 142.4, 138.8, 134.6, 133.3, 133.2, 132.80, 132.75,

132.2, 131.6, 131.4, 130.5, 130.4, 130.1, 129.7, 129.0, 128.9, 128.1, 127.5, 127.01, 127.0, 126.8,

125.85, 125.64, 125.6, 125.3, 125.2, 124.8, 122.3, 119.0, 93.4, 92.9, 34.9, 31.4 ppm. HRMS

+ + (APPI-TOF) m/z: [M] mass calcd for [C40H28Cl2] 578.1568, found 578.1574.

2.6 References

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3. Synthesis of HBC-based π-extended nanographenes via alkyne benzannulation reactions

3.1 Introduction

Hexa-peri-hexabenzocoronenes (HBCs) 3.1 (Figure 3-1), are a two dimensional NG with formula

C42H18. It consists of a central coronene core with an additional benzene ring fused between each adjacent pair of rings around the periphery.1 So, in total it has 13 aromatic rings fused with each other. It is a planar PAH with 42-sp2-hybridized conjugated carbon atoms. Because of it’s planar structure, it can aggregate via π-π interactions leading to disk-shaped columnar mesophases.2 The substituents around the periphery of these molecules mainly govern the liquid crystallinity and solubility. The electronic and optical properties of the HBC molecule is solely dependent on the conjugated core. Stacking properties, absorption-emission properties, band gap and other photophysical properties are mostly relied on the central conjugated core.

Figure 3-1: Hexa-peri-hexabenzocoronene (HBC) molecule 3.1.

HBC molecule can also be viewed as an expanded benzene analogue (Figure 3-2). When a benzene molecule is peri-condensed with six more benzenes, it results in the formation of coronene

3.3 which is also known as superbenzene. If six more benzene rings are peri-fused on coronene 95 molecule, the resulting molecule is called HBC (also known as expanded superbenzene). The numbering and nomenclature of the superbenzene can be done in an analogous way as for benzene derivatives. Carbons labeled as 1-6 are the less sterically hindered carbons compared to other bay- region carbons in HBC molecules and are analogous to six carbons in benzene. The mono-substituted HBC 3.7 can be named as pseudo-1-bromo expanded superbenzene or pseudo-1-bromoHBC.

Compound 3.8 can be named as pseudo-1,2-dibromoHBC or pseudo-o-dibromoHBC. Similarly, compound 3.9 can be named as pseudo-1,4-dibromoHBC or pseudo-p-dibromoHBC.

Figure 3-2: Analogous numbering/nomenclature of benzene HBC derivatives. 96

HBC molecule and it’s derivatives have gained considerable interest because of their applicability in different organo-electronic devices. 3-5 By taking advantage of the long-range structural order of the HBC derivatives, many functional materials have been developed.6-14 Researchers have reported that spin-coated thin-film of HBC have high level of lithium and sodium storage capacity.15,

16 The electrochemical studies of unsubstituted and highly fluorinated HBCs have been found to have high discharge capacity. This indicates potential application of HBC and it’s derivatives to be used as an anodic material in lithium ion batteries.17 Unsubstituted HBC 3.1 has been found to

Figure 3-3: HBC derivatives used in organo-electronic devices. have a good hole transport properties while perfluorenated HBC is a good electron transport material.18 Hence, modification of the HBC core as well as peripheral substituents can lead to diverse materials.17 In addition, HBC derivatives have found some biological applications as well. HBC chromophores 3.10 and 3.11 have been incorporated into phospholipid polyethylene glycol mi- celles for cellular imaging applications.19 Water-soluble HBC derivative 3.12 with carboxylic acid groups is used in biological sensing applications (Figure 3-3).2 97

π -Extension of the aromatic system by condensing aromatic rings is an emerging field in organic materials chemistry. Some impressive examples of π-extension include the synthesis of NGs reported by Chalifoux20, GNRs reported by Itami groups21, 22 and nanobelts reported by Jasti23 groups. HBC can be a good core to expand π-conjugation by condensing more aromatic sextets.

Most of the works on HBC that have been reported are focused on synthesis of functionalized derivatives.24-27 For instances, the Jux group have synthesized aldehyde functionalized HBC 3.13 and utilized it to afford superbenzene-porphyrin conjugates 3.14.28 Ikai and coworkers have synthesized optically active triptycene-bridged HBCs through conglomerate crystallization.29 Müllen and coworkers have synthesized very large, planar π-extended HBC super triphenylenes by Diels-

Alder reaction and subsequent cyclodehydrogenation.1 Another interesting approach to peripheral

Figure 3-4: Examples of current trend of chemical modifications of HBC molecules. 98 modification is the synthesis of star-shaped coaxial hole-transport material 3.15 by installing large alkyl aryl groups on HBC.30, 31 But, only a limited number of methods have been reported for the synthesis of contorted aromatics by modification of an HBC core. The Wang group utilized a central HBC core to make a variety of fascinating propeller-shaped soluble NGs.32 The Müllen group have synthesized insoluble extended HBC 3.16 by Scholl reaction of oligophenylene. They have also extended HBC systems into a gulf-type soluble GNR 3.17.33, 34 However, synthesis of

π-extended, soluble HBC-based contorted NGs using alkyne benzannulation reactions is not reported to date.

3.2 Our design of the π-extended HBC NGs

One of the difficulties during syntheses of HBCs and other larger PAHs is the solubility and hence, purification and characterizations of the products.35-38 The solubility of these larger NGs can be improved by inducing twisting or by incorporating solubilizing groups around the periphery. Our work is the π-extension of the HBCs in pseudo-1-, pseudo-1,2-, pseudo- 1,4-, and pseudo-1,3,5- positions (3.18-3.21) with incorporation of substituents to induce twists in the product. Thus, obtained contorted HBC NGs will be highly soluble in common organic solvents which will allow us to perform solution-based spectroscopic characterizations. In the previous chapter, we discussed the synthesis of [5]helicene-like naphtho[1,2-a]pyrene by Suzuki cross-coupling of diyne boronic ester with 3-bromophenanthrene followed by the two-fold alkyne benzannulation reaction of resulting diyne precursors. Here, we planned to replace the 3-bromophenanthrene core with halogen functionalized HBCs to afford diyne, tetrayne, and hexayne precursors, which on alkyne benzannulation condition would result in π-extended HBC-based NGs 3.18 to 3.21.

Figure 3-5: Design of a chiral HBC NGs.

100

3.3 Synthesis of π-extended HBC NG analogues

3.3.1 Mono π-extended HBC NG (3.18)

NG 3.13 was our first model target which consists of one phenalenyl unit (Figure 3-6a, phenalenyl unit shown in blue) fused on the HBC core. The aryl substituents in the cove-region makes the molecule twist out of the planarity. This NG can also be considered as a laterally π-expanded chiral teropyrene (Figure 3-6b, teropyrene structure shown in magenta). Our approach for the synthesis of this molecule is to start with the soluble, monobrominated HBC that upon Suzuki cross-coupling with boronic ester diyne 2.10c gives us a diyne precursor. The diyne precursor can be converted to compound 3.18 through a two-fold alkyne benzannulation reaction.

Figure 3-6: a) Mono-extended HBC showing embedded chiral teropyrene (in magenta) b) HBC

NG 3.13 showing phenalenyl-fused on HBC.

3.3.1.1 Synthesis of pseudo-1-bromoHBC

We initiated the synthesis of the target π-extended HBC NG 3.18 by synthesizing the monobro- moHBC 3.32. A number of synthetic methods are reported for the synthesis of the HBC core and most of then suffer from the difficulties with purification and are low yielding. Müllen and coworkers have developed an efficient method for the synthesis of symmetrically halogenated 101 soluble HBCs with alkyl substituents around the periphery. We adopted this method for the synthesis of soluble pseudo-1-bromoHBC 3.32. 4-t-butylethynylbenzene was synthesized in two-steps starting from 4-t-butyliodobenzene. Sonogashira cross-coupling of compound 3.22 with TMS- acetylene followed by the disilylation of the TMS alkyne 3.23 with potassium carbonate in

THF/MeOH mixture resulted compound 3.24 in excellent yield of 90%. Diphenylacetylene 3.26 was synthesized by Sonogashira cross-coupling of the 3.24 and 3.25 (Scheme 3-1).

Scheme 3-1: Synthesis of diphenylacetylene 3.26.

Tetra-aryl cyclopentadienone 3.30 was synthesized using a literature method starting from compound 3.26. Oxidation of compound 3.26 with iodine in DMSO at 155 °C resulted the diketo compound 3.27 in quantitative yield, which was then treated with diaryl ketone 3.28 to get compound 3.29 in 75% yield (Scheme 3-2).

Scheme 3-2: Synthesis of cyclopentadienone 3.29. 102

Compound 3.29 was taken through the Diels-Alder cyclization with compound 3.30 followed by the cheletropic extrusion of CO to get bromohexaphenylbenzene 3.31. The Scholl oxidation of

3.31 with FeCl3 yielded monobromoHBC 3.32 with five t-butyl groups around the periphery to improve solubility (Scheme 3-3).

Scheme 3-3: Synthesis of soluble monobromoHBC 3.32.

3.3.1.2 Two-fold alkyne benzannulation reaction towards HBC NG 3.13 Boronic ester diyne 2.10c was prepared as described in the Chapter 2 starting from 4-t-butylaniline in four linear steps. Having both of the coupling partners 3.32 and 2.10c in hand, we coupled them together using Suzuki cross-coupling reaction. There are several conditions reported for the

Suzuki cross-coupling of aryl halide with aryl boronic esters. Dr. Khagendra Hamal, one of my senior coworkers screened a number of conditions. I adopted his optimized conditions and 103 synthesized compound 3.33 in 75% yield (Scheme 3-4). With diyne precursor 3.33, we attempted two-fold alkyne benzannulation reaction to arrive at our target 3.18. Initially, Dr. Hamal used

Bronsted acid (TFA and triflic acid) catalyzed alkyne benzannulation that gave the target compound 3.18 in 70% yield. I revisited the reaction under Lewis acid (InCl3/AgNTf2) catalyzed conditions to get the same compound 3.18 in 82% yield. Under these conditions, reaction was much cleaner and easy to purify.

Scheme 3-4: Synthesis of chiral HBC NG 3.18.

104

3.3.1.3 X-Ray crystal structure and racemization barrier of HBC NG 3.18 The twisted structure of HBC NG 3.18 was unambiguously confirmed by X-ray crystallography of a racemic single crystal obtained by slow evaporation of a solution of compound 3.18 in benzene/MeOH. The X-ray crystal structure clearly showed a twisted π-system forcing two cove-aryl substituents out of the plane (Figure 3-7).

Figure 3-7: Single crystal structure of HBC NG 3.18 (left), lateral view of compound 3.18 (middle), and skewed view of compound 3.18 (right). (Hydrogen atoms removed for clarity. All carbons represented with grey spheres, oxygen with red).

With the help of our collaborators in Italy, we studied the racemization pathways for compound

3.18. The possible equilibration pathway is shown in Figure 3-8. One of the enantiomer of compound 3.18 was heated in decalin at 120 °C. We saw a clean racemization after 350 min with no additional peak formed (i.e. no meso- form 3.34 was observed) as observed in chiral HPLC analysis. From the rate constant, racemization barrier was calculated to be 30.3 kcal/mol. The interconversion is expected to occur via the less stable meso-form 3.34. 105

Figure 3-8: Experimental racemization route of compound 3.18.

3.3.2 Pseudo-1,2-π-extended HBC NG (3.19)

Figure 3-9: HBC NG 3.19 showing two phenalenyl moieties fused on HBC core (left), embedded

[7]helicene-like moiety (middle), calculated structure (right).

Pseudo-1,2-extended HBC NG 3.19 consists of two phenalenyl moieties fused on a central HBC core in pseudo-1,2-positions and is a laterally π-expanded [7]helicene-like molecule (Figure 3-9). 106

This molecule contains five benzene rings ortho-fused in the helical region. Two additional aryls in the fjord-region stacks on the benzene rings of phenalenyl moieties (see calculated structure,

Figure 3-9) making this molecule [7]helicene-like system.

Pseudo-1,2-dibromoHBC 3.41 was synthesized following the method reported by Shapiro and

Becker by refluxing dibenzyl ketone and benzil in ethanol in the presence of benzyl trime- thylammonium hydroxide (Scheme 3-5).39, 40 Cyclopentadienone 3.37 was heated in diphenyl ether with compound 3.39 at 250 °C to get dibromohexaphenylbenzene 3.40. An one-pot Friedel-

Craft reaction of compound 3.40 with t-butyl chloride in the presence of a catalytic amount of

FeCl3 in nitromethane followed by cyclodehydrogenation afforded dibromoHBC 3.41 in 82% yield.

Scheme 3-5: Synthesis of pseudo-1,2-dibromoHBC 3.41.

HBC 3.41 was subjected to a two-fold Suzuki cross-coupling reaction with boronic ester 2.10b to afford tetrayne 3.42 in 48% yield (Scheme 3-7). The four-fold alkyne benzannulation reaction of 107

tetrayne 3.42 with catalytic mixture of InCl3/AgNTf2 gave pseudo-1,2-extended HBC NG 3.19 in

51% yield. The lower yield of this step is understandable because of the extreme steric hindrance observed in product 3.19.

Scheme 3-6: Synthesis of HBC NG 3.19.

3.3.3 Pseudo-1,4-π-extended HBC NG 3.20

HBC NG 3.20 consists of two phenalenyl units fused on a HBC core in pseudo-1,4-positions. It can also be viewed as a laterally π-extended chiral quateropyrene (Figure 3-10). This molecule can be synthesized starting from a pseudo-1,4-dibromoHBC in an analogous way as we synthesized HBC NG 3.14.

108

Figure 3-10: HBC NG 3.20 showing embedded quateropyrene (left), and two phenalenyl moieties fused on HBC core in 1,4-positions (right).

3.3.3.1 Synthesis of soluble pseudo-1,4-dibromoHBC

The synthesis of pseudo-1,4-dibromoHBC 3.39 molecule was carried out following the literature procedure reported by Nabeshima and coworkers (Scheme 3-7).41 The tetra-arylcyclopentadi- enone 3.41 was obtained by two-fold Knoevenagel condensation of diketone 3.24 with dibromo- diaryl acetone 3.40 under reflux condition in ethanol in 60% yield. Dinenone 3.41 was then subjected to [4+2] cycloaddition with tolane at 250 °C in diphenyl ether to get dibromo hexaphenyl benzene (HPB) 3.42 in 89% yield. The Scholl reaction of 3.42 gave dibromoHBC 3.39 in 75% yield. 109

Scheme 3-7: Synthesis of soluble dibromoHBC 3.46.

3.3.3.2 Four-fold alkyne benzannulation towards HBC NG 3.15

The dibromoHBC 3.39 was coupled with the diyne boronic ester 2.10c using Suzuki cross-coupling reaction by heating in toluene and tetraethylammonium hydroxide with Pd(PPh3)4 catalyst to get tetrayne precursor 3.38 in 82% yield (Scheme 3-8). Then, the tetrayne compound 3.38 was taken through a four-fold alkyne benzannulation under preoptimized conditions to get chiral compound 3.15a and meso-compound 3.15b in 41% and 49% yield respectively. 110

Scheme 3-8: Synthesis of HBC NGs 3.20.

3.3.3.3 Possible isomers

Theoretically, there was the possibility for the formation of more than two isomers based the different possible orientations of the aryl groups in the cove-regions. Compounds 3.20a-e are some of the possible isomers that could have formed during a four-fold alkyne benzannulation reaction of tetrayne 3.47 (Figure 3-11). Isomers 3.20a and 3.20d are chiral isomers with D2 and C1 point groups while, 3.20b, 3.20c, and 3.20e are meso isomers with C2h, C2v, and C2h point groups respectively. The relative energy of these isomers can be predicted qualitatively based on proximity 111

Figure 3-11: Some possible isomers of HBC NG 3.20. of the aryl substituents in the cove-regions. Isomer 3.20c has all of the cove-substituted aryls above or bottom the plane which brings the aryl groups closer in the space. The relative energy of this product would be highest, hence, is thermodynamically unfavored product. Isomer 3.20d is second highest energy product as it contains three of the cove-substituted aryls on the same side (either above or below the plane of the HBC core). So, the formation of this product is also thermodynamically not favored. Isomer 3.20e also suffers from the steric repulsion between aryls. Because of the far-separated cove-substituents, isomers 3.20a and 3.20b are the lower energy products. The formation of these products also supports our understanding about the relative energies of these isomers. The computational calculations for all possible isomers are underway. 112

The selective formation of chiral isomer 3.20a and meso-isomer 3.20b can be explained by taking an account of order of alkyne benzannulation of the tetrayne precursor 3.47 (Figure 3-12). If first alkyne benzannulation reaction occurs from alkyne 1 to give a triyne intermediate 3.48 having aryl substituent on the newly formed cove-region above the plane, the second alkyne benzannulation will have two choices, based on our observation. synthesis of teropyrene.42 It can occur either on alkyne 2 or on alkyne 3. If we consider the second alkyne benzannulation occurs on the alkyne 2, it can occur in two ways, either from the top giving intermediate 3.44, or from the bottom giving intermediate 3.46. The third alkyne benzannulation can occur on one of the alkyne 3 or 4 which will be directed by the position of cove-aryl group in the newly formed benzene from alkynes 2 and 1 resulting in the formation of product chiral product 3.15a through intermediate 3.47 and meso product 3.15b through intermediate 3.45.

Now, if we consider the second alkyne benzannulation occurs from alkyne 3, it will further have two choices as in previous case. It can occur from the top giving intermediate 3.55 or from the bottom giving intermediate 3.53 which finally leads to the formation of chiral 3.20a and meso-

3.20b product as shown in the figure below. 113

Figure 3-12: Predicted pathways towards chiral 3.20a and meso-3.20b products.

3.3.3.4 Crystal structures and racemization barrier studies of compound 3.20

Both of the isomers obtained were characterized by NMR, IR and mass spectroscopy. Upon the synthesis of the chiral NGs 3.20a, 3.20b, we could grow single crystals of these molecules suitable for the X-ray analysis (Figure 3-13). Crystals of compounds 3.20a and 3.20b were obtained by slow diffusion of methanol into it’s solution in dichloromethane solution. 114

Figure 3-13: a) Crystal strucures of 3.15a b) Crystal structure of 3.15b (hydrogen atoms removed for clarity. All carbons represented with grey spheres, oxygen with red).

With the help of our Italian collaborators, we studied the racemization pathways for compound

3.20a (Figure 3-14). One of the enantiomer of compound 3.20a was heated in decalin at 120 °C.

Assuming the species with two aryl groups on the same side are less stable than the others, isomers

3.20c, 3.20d and 3.20e are not expected to appear during thermal equilibration. If we imagine a stepwise, “single aryl flip” equilibration mechanism, one enantiomer of 3.20a (chiral, stable, detected) gets converted to 3.20b (meso, stable, detected) through 3.20d (unstable, not detected) which in turn can generate ent-3.20d (unstable, not detected) and finally ent-3.20a (stable, detected). Energy barrier for the conversion of chiral compound 3.20a to meso isomer 3.20b is calculated to be 29.82 kcal/mol. The energy barrier for the conversion of meso-3.20b to ent-3.20a is 115

Figure 3-14: Racemization study of chiral HBC NG 3.20a. calculated to be 31.14 kcal/mol. The relative energies of chiral and meso-isomers suggests the greater stability of meso-form which is in agreement with relative yields of two isomers 3.20a and

3.20b which was 41% and 49% respectively.

3.3.4 UV-vis spectroscopy

Upon the synthesis of π-extended HBCs 3.18, 3.19, and 3.20a, we carried out the UV-vis spectroscopic study of these molecules (Figure 3-15). There is no absorption peak observed past 400 nm

43 for an unsubstituted HBC , but the maximum absorption wavelength (λmax) of smallest nanographene 3.18 is found to be 520 nm. Hence, there was significant bathochromic shift of absorption wavelength of compound 3.18 by 120 nm compared to HBC by a π-expansion in pseudo-1-position. The UV-Vis absorption spectra of larger analogues 3.20a and 3.20b is found to be 560 nm 116 which is red shifted by 40 nm compared to the smaller analogue 3.18. Compound 3.19 has maximum absorption at 585 nm. The further red shifted absorption of compound 3.19 compared to 3.20 is because of the aryl groups in the fjord-region in compound 3.19 stacking on the conjugated aromatic core.

compound 3.19 0.8

compound 3.20 0.6

compound 3.18

0.4 normalizedintensity 0.2

0 315 415 515 615 absorption wavelength (nm)

Figure 3-15: Combined UV-vis plots of compounds 3.18, 3.19. 3.20.

3.3.5 Attempted synthesis of pseudo-1,3-extended HBC NG

After successful synthesis of NGs 3.18, 3.19, 3.20, we wanted to investigate effect of π -extension of HBC in pseudo-1,3-positions. The pseudo-1,3-dihalo-functionalized HBC has never been reported. So, we planned to synthesize HBC 3.62 having two bromine substituents in the pseudo-

1,3- positions using an analogous method. Bromoalkyne 3.30 was oxidized to diketone 3.58 with molecular iodine and DMSO. Knoevenagel condensation of 3.58 with 3.28 was carried out with

KOH in ethanol to get compound 3.59 in 55% yield (Scheme 3-9). 117

Scheme 3-9: Synthesis of cyclopentadienone 3.59. Compound 3.59 was then heated with alkyne 3.30 in diphenyl ether to produce compounds 3.60 and 3.61 as a 50:50 mixture of regioisomers (Scheme 3-10). These isomers have a similar affinity to silica gel making it difficult to obtain a pure sample of 3.60. The mixture of isomers were taken through the Scholl reaction. Unfortunately, the resulting HBC isomers 3.62 and 3.63 were also inseparable. Hence, a suitable synthetic method needs to be figured out for the synthesis of HBC

3.62. Due to the difficulties for the synthesis of compound 3.62, we were not successful to synthesize pseudo 1,3-extended HBC product. 118

Scheme 3-10: Attempted synthesis of pseudo-1,3-dibromoHBC 3.62.

3.3.6 Pseudo-1,3,5-extended HBC Propeller-shaped NGs.

3.3.6.1 Propeller-shaped NGs (PNGs)

NGs of distinctive structure have continuously been of interest in materials science owing to their unique conformations, relevant dynamic behaviors electronic and optical properties.44 Highly symmetric PAHs and NGs have gained increasing attention in the material sciences since the discovery of fullerenes.45, 46 When a highly symmetric molecule gets twisted on the same direction with an equal angle along at least three axes of symmetry, that molecule will adopt a propeller-shape (Fig- ure 3-11). Propeller-shaped NGs (PNGs) also known as fan-blade NGs are a special type of helically twisted nanographene. Cloverphene 1.32 is the first PNG reported by Pascal and co-workers

45 in 1999. It adopts a D3 symmetric helical conformation, in which three blades get twisted out of 119 the central benzene ring by 30° per blade, as a result of the steric interaction between the peripheral blades.

Figure 3-16: Mode of twisting in propeller-shaped architecture (A-C).47

Pascal and coworkers have proposed a rule of thumb to explain dichotomy of sterically hindered triphenylene and decacyclene derivatives containing C2/D3 symmetry. According to this rule, if the core benzene is more rigid than the blades, the blades will get twisted into a chair-like form

45, with D3 symmetry that does not disturb the p-orbital overlapping in the peripheral aromatic rings.

48 Conversely, if the blades are more rigid than the core, the core benzene ring will be distorted into a twist boat-like form with C2 symmetry. This is because the resulting conformation will be stabilized via local overlap between the p-orbitals of the peripheral benzene rings.44, 45 This rule is found to be applicable in other larger PNGs as well.

The synthesis of these highly symmetric molecules are at the center of attraction, despite of limited number of reported synthetic methods. Most of the reported fan-blade contain a smaller core (i.e. benzene). Furthermore, all of the reported syntheses have largely relied on a metal-catalyzed

[2+2+2] cyclotrimerization of the corresponding arynes.49-54 For examples, in 2006, Pérez and coworkers reported the synthesis of hexabenzotriphenylene propeller 3.64 using Pd-catalyzed cyclotrimerization reaction.55 Similarly, in 2017, Houk and coworkers reported the synthesis of propeller shaped indolynes-based conjugated trimer 3.65.53 The Haase and Wang groups have 120 reported the synthesis of nitrogen and sulphur doped triphenylene-based propellers 3.66 and 3.67, respectively (Figure 3-17).56-58

Figure 3- 17: PNGs.

In 2011, Sygula and coworkers have reported the synthesis of a beautiful molecular propeller 3.69

(Scheme 3-11), with C1 symmetry, having three corannulene blades fused together on a benzene core.59 They carried out the synthesis utilizing Pd-catalyzed cyclotrimerization of trimethylsilyl corannulenyl triflate 3.68 to get the corannulene trimer 3.69 in 40% yield.

Scheme 3-11: Sygula's synthesis of corannulene PNG 3.69. In the recent years, the utilization of benzene as a propeller core has been replaced by larger molecules like HBC (Figure 3-18), but still relied on the conventional cyclotrimerization followed by

Scholl reaction. In 2018, Wang and coworkers reported the synthesis of propeller- shaped hexapole 121

[7]helicene (Figure 3-18A) through a Co-catalyzed cyclotrimerization of hexaphenylbenzene

(HPB)-based alkyne followed by Scholl reaction.60 In 2019, the same group reported the synthesis of hexapole [9]helicene (Figure 3-18B) by cobalt-catalyzed cyclotrimerization reaction of dinaph- thopyrene functionalized alkyne followed by dehydrocyclization.61 They were able to synthesize nitrogen doped hexapole [7]helicene propeller system (Figure 3-18C).62

Figure 3-18: Propeller-shaped nanographene with HBC core A) Hexapole [7]helicene B) Hexa- pole[9]helicene C) N-doped hexapole [7]helicene [images adapted from ref. 60-62].

Another interesting example of a synthesis of propeller-shaped nanographene is the seven HBC fused fan-blade reported by the Wang group in 2019, which is the largest propeller-shaped nanographene ever reported.32 They started with the hexaphenylbenzene hexayne 3.70. Compound 3.70 was heated with cyclopentadienone to get seven hexaphenylbenzene system 3.71 by a six-fold

Diels-Alder reaction followed by cheletropic extrusion of six CO molecules. Their next step was cyclizing the outer blades on 3.71 with DDQ and MSA-catalyzed Scholl reaction to get compound

3.72 in 92% yield. The second Scholl reaction of 3.72 with DDQ and MSA yielded chiral PNG

3.73 in 65% yield (Scheme 3-12). To the best of our knowledge, synthesis of larger propeller system through alkyne benzannulation has never been reported to date.

122

Scheme 3-12: Wang's synthesis of seven HBC-fused PNG (Figures adapted from ref. 32).

3.3.6.2 Our design of HBC PNG

Our strategy towards the synthesis of HBC PNG is the three-fold Suzuki cross-coupling of pseudo-

1,3,5-triiodoHBC 3.67 with a diyne boronic ester 2.10a followed by a six-fold alkyne benzannulation reactions of the hexayne product 3.66. The resulting product would assume a propeller- shaped geometry because of the sterics, in which three phenalenyl subunits will serve as three blades fused on the central HBC core (Figure 3-19). The aryl groups in the cove-region and t- butyl groups on phenalenyl subunit can be varied to tune the properties like crystallinity and solubility. Hence, this would be a very first molecular propeller synthesized via alkyne benzannulation reaction. 123

Figure 3-19: Retrosynthetic analysis of PNG 3.21.

3.3.6.3 Synthesis of pseudo-1,3,5-triiodoHBC 3.75

We initiated the synthesis of the molecule by synthesizing the triiodoHBC 3.75 following literature procedure (Scheme 3-13).30 TMS-phenylboronic ester 3.78 was synthesized starting from 1,3-di- bromobenzene 3.76 in two steps.63 2’-Bromoacetopheneone 3.79 was obtained commercially, which on refluxing with 10 mol% of the triflic acid under inert atmosphere gave tribromo terphenyl compound 3.80 in 72% yield. Compound 3.80 was undertaken through a three-fold Suzuki cross- coupling reaction with 3-TMS-phenyl boronic ester 3.78 to get compound 3.81 in 90% yield which was converted to triiodo compound 3.82 by treating with ICl solution in 91% yield. Product 3.82 was oxidized using the Scholl reaction to get triiodoHBC 3.75 as a very insoluble yellow powder in 75% yield.30

124

Scheme 3-13: Synthesis of triiodoHBC 3.75.

3.3.6.4 Six-fold alkyne benzannulation reaction towards HBC NGP 3.21 With this insoluble Scholl product 3.75, we carried out three-fold Suzuki cross coupling reaction with boronic ester diyne 2.10a to get hexayne fan-blade precursor 3.74 in 34% yield (Scheme

3.14). The comparatively lower yield is understandable because of the insolubility of triiodo HBC

3.67. Thus, obtained hexayne 3.74 was taken through six-fold alkyne benzannulation reaction catalyzed by InCl3/AgNTf2 to get propeller-shaped molecule 3.21 in the modest yield of 63%. 125

Scheme 3-14: Synthesis of HBC PNG 3.21 via six-fold alkyne benzannulation reaction.

3.3.6.5 Isomers of HBC PNG 3.21

There was a possibility of formation of several stereoisomers based on orientation of the aryl group (being below or above the plane) in the cove-regions (Figure 3-20), such as, compound 3.83 having all aryl groups above and below the plane, five aryls up and one down 3-84, two aryls in the same pyrene blade down and other four up 3.85, two nearest aryls in adjacent pyrene blades down and other four up 3.86, two aryls in alternate positions on two pyrene blades down and other four up 3.87, three alternate aryls up and others down (fan-blade structure) 3.21. The symmetric 126

NMRs (1H and 13C) suggests that we got the highly symmetric propeller-shaped product 3.21 over all other possibilities. Further characterization by X-ray crystallography is underway.

Figure 3-20: Some of the possible isomers of HBC PNG 3.21.

3.3.6.6 Synthesis of soluble pseudo-1,3,5-triiodoHBC To overcome the low yield of the Suzuki cross-coupling step to make hexayne 3.74, we planned to synthesize a soluble version of the triiodoHBC 3.99, which is never reported in the literature.

First, we did Friedel-Crafts acylation of the 3-bromo-t-butylbenzene 3.88 to get acetophenone 3.89 in 44% yield. With compound 3.89, we attempted triflic acid-catalyzed aldol reaction to get tri- bromoterphenyl product 3.90 but the reaction did not work (Scheme 3-15) we ended up getting decomposed black residue. 127

Scheme 3-15: Attempted synthesis of compound 3.90.

Then, we planned a completely new route towards the synthesis of soluble pseudo-1,3,5-triio- doHBC 3.99 (Scheme 3-16). We started with commercially available, cheap starting material, 4- t-butylaniline 3.80. Monobromination of the aniline 3.80 produced 2-bromo-4-t-butylaniline 3.81 in 70% yield, which was cross coupled with TMS-phenyl boronic ester 3.68 under Suzuki cross- coupling condition to afford biphenyl aniline 3.82. The aniline 3.82 was converted to biphenyl bromosilane 3.83 under Sandmeyer reaction conditions in 42% yield over two steps. The resulting bromosilane 3.83 was converted to boronic ester 3.84 by treating with n-BuLi followed by quenching the reaction with isopropoxy boronic acid pinacol ester. The boronic ester 3.85 was subjected to three-fold Suzuki cross-coupling reaction with 1,3,5-tribromobenzene 3.85 to get trisilane compound 3.86. Compound 3.86 was treated with ICl solution to afford compound 3.87. Finally, we did Scholl reaction of 3.87 with FeCl3 to get soluble triiodo HBC 3.88 in 76% yield.

128

Scheme 3-16: Synthesis of soluble triiodoHBC 3.99.

3.3.6.7 Attempted synthesis of HBC PNG starting from soluble triiodoHBC 3.88

We carried out three-fold Suzuki cross-coupling of our soluble triiodoHBC 3.99 with boronic ester

2.10b that gave three-fold cross-coupled product 3.100 in 48% yield (Scheme 3-17). We attempted the six-fold alkyne benzannulation reactions of compound 3.100. To our surprise, highly rearranged product 3.102 was also obtained as a minor product (characterized by X-ray crystallographic analysis). The major fraction obtained after column chromatography is presumed to contain compound 3.101 but purification problems has prevented its characterization. We have tried 129 to grow crystal for X-ray analysis in different solvents using different methods. A suitable crystallization condition is under study.

Scheme 3-17: Serendipitous formation of saddle-shaped NG (SNG) 3.102.

The serendipitous formation of the seven-membered ring containing SNG 3.102 can be explained by taking an account of an intramolecular migration followed by alkyne cyclization (Scheme 3-

18). The structural analysis of the product 3.102 shows that, four out of six alkyne cyclization occurred in a way as expected resulting the formation of two-pyrene blades of the PNG 3.103. 130

However, it’s very unlikely to occur four alkyne benzannulation before the rearrangement. From our previous experiences, after the first cyclization, the system gets planarized to some degree making the second alkyne on each phenyl group much slower to cyclize. so, more likely pathway that causes the formation of rearranged product 3.102 could be two of the three phenyls do a mon- ocyclization first resulting compound 3.103 (there is possibility of formation of more than one isomer of compound 3.102, only one is drawn in Scheme 3.18 for clarity) which is sterically con- gested enough to force remaining diynylbenzene (represented in light red) to migrate from original carbon 1 to carbon 2, forming compound 3.104. However, the mechanism might be more complex than we expect.

Scheme 3-18: Possible pathways towards compound 3.102.

The predicted mechanism for the formation of seven-membered ring is depicted in the scheme 3-

19. We can take a smaller system 3.105 for the ease of drawing mechanism. Indium first activates 131 the triple bond and which undergoes 6-endo-dig-cyclization resulting in the formation of arenium ion 3.107. Arenium ion 3.107 undergoes ring-expansion to result intermediate 3.108 leading to the seven-membered ring (shaded ring in 3.108-110) containing NG 3.110. Derek Chen, one of my colleagues is working in naphthalene system to confirm predicted mechanism of such kind of ring expansion.

Scheme 3-19: a) Possible mechanism for the formation of compound 3.102 b) Part of molecule

(highlighted in blue) 3.104 that resembles with the smaller compound 3.105.

3.4 Conclusion

In summary, we carried out an efficient synthesis of π-extended HBC NGs using a InCl3 and

AgNTf2-catalyzed two-, four-, and six-fold alkyne benzannulation reactions. These electron-rich conjugated molecules were soluble in many common organic solvents that allowed us to characterize them using various spectroscopic methods. The position of extension was varied to study the changes in the photophysical properties such as absorption emission behaviors crystal packing and other CPL properties which are under study and will be reported soon. The racemization barrier of a chiral HBC NGs 3.18 and 3.20a were high enough to separate the two enantiomers using 132 chiral HPLC while other NGs are still under study. The X-ray crystallographic analysis of single crystals of compound 3.18, 3.20a and 3.20b revealed the considerable twisting in the molecule because of the steric repulsion arising due to the overcrowding in the cove-region of the molecules.

3.5 Experimental section

3.5.1 General Methods

Reagents were purchased reagent grade from commercial suppliers and used without further purification unless otherwise noted. Solvents such as THF, DCM, and toluene were purified using a

PureSolv MD 5 solvent purification system. Where appropriate, reactions were performed in standard, flame-dried glassware under an inert atmosphere of N2. Purification of the crude products was carried out by column chromatography using silica gel irregular 60 Å (40-60 micron) from

VWR International. Analytical TLC was performed on glass sheets covered with silica gel 60 F254 from Millipore a Corporation. The TLC plates were visualized under ultraviolet light (UV, 254 nm) light. NMR spectra were recorded on a 400 or 500 MHz NMR spectrometer in CDCl3. Proton chemical shifts are expressed in parts per million (ppm, δ scale) and are referenced to residual

1 protium in the NMR solvent (CDCl3, δ 7.26). Data for H NMR are reported as follows: chemical shift, multiplicity (s=singlet, d=doublet, t=triplet, q=quartet, m= multiplet, bs=broad singlet), coupling constant (J) in Hertz, and integration. 13C NMR chemical shifts are expressed in parts per million (ppm, δ scale) and are referenced to the carbon resonance of the NMR solvent (CDCl3, δ

77.16). Infrared (IR) spectra were recorded on an ATR/FTIR spectrometer as a thin film on a composite of zinc selenide and diamond crystal and only major functional group peaks are reported in cm–1. High-resolution mass spectra (HRMS) were obtained on Matrix-assisted laser desorption/ionization (MALDI TOFMS) spectroscopy. A suitable crystal was mounted on a glass fiber 133 and placed in the low-temperature nitrogen stream. For compounds 3.18, 3.20a, and 3.20b, data were collected on a Bruker Apex CCD area detector diffractometer equipped with a low-temperature device, using graphite-mono-chromated Mo Kα radiation (λ= 0.71073 Å) and a full sphere of data was collected. Integration, data reduction and scaling were carried out with the programs

SAINT and SADABS in the Bruker APEX3 suite of software. The structure was solved using intrinsic phasing methods and refined using full‐matrix least‐squares refinement using SHELXL.

3.5.2 Synthesis and characterizations

Compound 3.33

In a 100 mL round bottom flask fitted with magnetic stirrer was added compound 3.32 (329 mg,

0.285 mmol), boronic ester 2.10c (257 mg, 0.537 mmol) and toluene (50 mL). A solution of

Et4NOH (10 mL, 35 % solution in water) was added and the resulting solution was thoroughly degassed by bubbling with N2 gas for 30 min. Pd(PPh3)4 (56 mg, 0.048 mmol) was then added to the solution and the reaction was heated under a N2 atmosphere at 110 °C for 24 h. The reaction was cooled, diluted with water, extracted with CH2Cl2and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, hexane:DCM = 2:1) afforded 284 mg (yield 75%) of compound 3.33 as a yellow solid. Rf =

-1 1 0.29 (CHCl3:hexane, 1:3). FTIR (neat) 2959, 2205, 1605, 1579 cm . H NMR (500 MHz, CDCl3)

δ 10.09 (s, 2H), 9.63 (s, 2.0 Hz, 8H), 9.58 (s, 2H), 7.91 (s, 2H), 7.29 – 7.20 (m, 4H), 6.59 – 6.48 134

13 (m, 4H), 3.61 (s, 6H), 2.75 (s, 3H), 2.10 (s, 27H), 1.85 (s, 18H) ppm. C NMR (500 MHz, CDCl3)

δ 159.5, 149.4, 149.3, 149.2, 142.5, 137.4, 136.5, 133.4, 133.2, 130.8, 130.7, 130.5, 130.0, 125.5,

124.9, 124.2, 124.1, 121.2, 121.0, 120.9, 120.7, 119.7, 119.2, 119.11, 119.05, 115.1, 113.8, 93.3,

88.5, 55.2, 35.9, 35.7, 32.2, 31.9, 21.1 ppm. MS (MALDI-TOF): calcd for C87H76O2[M]+ 1152.58, found 1152.57.

Synthesis of compound 3.18

a) Bronsted acid catalyzed two-fold alkyne benzannulation

To the solution of compound 3.33 (84 mg, 0.073 mmol) in anhydrous dichloromethane, trifluoroacetic acid (TFA) (400 mg, 3.50 mmol) was added in a 100 mL flame-dried round bottom flask fitted with magnetic stirrer and solution was stirred for 1.3 h under nitrogen environment. The reaction mixture was cooled to 0 oC and solution of triflic acid (16 mg, 0.11 mmol) in anhydrous dichloromethane (5 mL) was added dropwise and the reaction mixture was stirred at 0 oC for 20 minutes. After completion of reaction, it was quenched with 5 mL of saturated sodium bicarbonate, extracted in DCM, dried over sodium sulfate and purified by column chromatography (silica gel, hexane:DCM 2:1) to get 59 mg (yield 70%) of compound 3.18 as orange solid. Rf = 0.27

(DCM:hexane 1:3). b) Lewis acid catalyzed two-fold alkyne benzannulation 135

In a 50 mL flame-dried round bottom flask, compound 3.33 (40 mg, 0.035 mmol) was dissolved in 25 mL of anhydrous toluene. The solution was degassed by bubbling nitrogen gas for 30 minutes. A mixture of InCl3 (1.1 mg, 0.049 mmol) and silver bistriflimide (1.9 mg, 0.049 mmol) were added into the reaction mixture inside the glovebox. The reaction mixture was heated at 90

-C for 14 h. after reaction was complete, it was quenched with 5 mL of a saturated sodium bicar֯ bonate, extracted in DCM, dried over Na2SO4 and was purified by column (silica gel, DCM:hexane

1:2) to get 33 mg (yield 82%) of product 3.18 as orange solid. Rf = 0.27 (DCM:hexane 1:3). FTIR

-1 1 (neat) 2959, 2906, 1606, 1575 cm . H NMR (500 MHz, CDCl3) δ 7.18 (s, 4H), 7.10 (s, 2H), 6.88

(bs, 2H), 6.48 (s, 2H), 6.08 (bs, 4H), 5.26 (s, 4H), 4.29 (s, 4H), 1.38 (s, 6H), 0.73 (bs, 3H), -0.33

13 (d, J = 3.2 Hz, 27H), -0.63 (s, 18H) ppm. C NMR (500 MHz, CDCl3) δ 158.5, 149.24, 149.22,

147.8, 139.4, 136.7, 135.4, 132.2, 130.9, 130.8, 130.7, 129.7, 129.6, 128.8, 128.0, 127.9, 126.4,

124.4, 124.3, 124.1, 123.2, 122.9, 121.3, 120.9, 120.8, 119.9, 119.2, 119.1, 119.0, 118.8, 113.8,

+ 55.3, 36.0, 35.6, 32.2, 32.0, 22.3 ppm. MS (MALDI-TOF): calcd for C87H76O2[M] 1152.58, found

1152.47.

Compound 3.42

In a 100 mL round bottom flask, boronic ester 2.10b (196 mg, 0.377 mmol), 3.41 (136 mg, 0.150 mmol) and Et4NOH (15 mL, 35% w/w solution in water) were dissolved in toluene (50 mL). The solution was degassed by bubbling nitrogen for 30 min. Then, Pd(PPh3)4 (18 mg, 0.015 mmol) 136

was added and the resulting mixture was refluxed under a N2 atmosphere for 24 h. After the reaction was complete, reaction was diluted with water. The mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane = 1:1) to give 280 mg (yield

48%) of compound 3.42 as a light yellow solid. Rf = 0.29 (DCM:hexane, 1:1). FTIR (neat) 2960,

-1 1 2835, 2204, 1605, 1500 cm . H NMR (400 MHz, CDCl3) δ 9.94 (s, 2H), 9.81 (s, 2H), 9.36 (d, J

= 3.5 Hz, 6H), 7.81 (s, 6H), 7.10 – 7.07 (m, 8H), 6.38 – 6.35 (m, 8H), 3.38 (s, 12H), 1.85 (s, 18H),

13 1.57 (s, 18H), 1.51 (s, 18H) ppm. C NMR (400 MHz, CDCl3) δ 159.5, 150.5, 149.4, 149.3, 142.3,

136.7, 133.1, 133.0, 130.9, 130.85, 130.82, 130.5, 130.13, 130.07, 129.9, 125.4, 125.1, 124.9,

124.2, 124.1, 123.6, 121.3, 121.2, 121.0, 119.9, 119.1, 115.1, 115.0, 113.91, 113.86, 113.8, 92.9,

+ 88.9, 55.0, 35.9, 35.7, 34.8, 32.2, 31.9, 31.4. MS (MALDI-TOF): calcd for C114H98O4[M]

1530.75, found 1530.69.

Compound 3.19

Compound 3.42 (65 mg, 0.042 mmol) was dissolved in anhydrous toluene (25 mL) in a 50 mL flame-dried round bottom flask. The solution was degassed by bubbling nitrogen gas through the solution for 30 min. A catalytic mixture of InCl3 (2 mg, 0.01 mmol) and AgNTf2 (3.3 mg, 0.009 mmol) was added inside a glovebox. Color of the reaction mixture immediately started to change 137 to dark red upon addition of the catalyst mixture. Then the reaction mixture was refluxed for 15 h under nitrogen environment. After the reaction was complete (checked by TLC), it was quenched with 5 mL of a saturated solution of sodium bicarbonate, extracted in DCM, dried with sodium sulfate. Solvent was removed by rotatory evaporation and purification by column chromatography

(silica gel, hexane:DCM = 1:1) to get 33 mg (yield 51%) of the compound 3.19 as a deep red solid.

-1 1 FTIR (neat) ) 2954, 2868, 1607 cm . H NMR (400 MHz, CDCl3) δ 9.36 (d, J = 34.6 Hz, 7H),

9.04 (s, 2H), 8.65 (s, 2H), 8.45 (s, 6H), 6.64 (s, 8H), 5.53 (s, 2H), 5.21 (s, 2H), 4.95 (s, 2H), 3.67

13 (s, 6H), 2.79 (s, 6H), 1.89 (s, 18H), 1.80 (s, 18H), 1.53 (s, 18H) ppm. C NMR (400 MHz, CDCl3)

δ 158.5, 156.9, 149.3, 147.7, 135.3, 133.9, 131.0, 130.9, 129.6, 129.4, 128.0, 127.9, 125.5, 124.2,

123.3, 122.7, 122.1, 121.73, 121.70, 120.8, 119.5, 119.1, 118.8, 114.3, 113.9, 113.6, 112.5, 111.5,

+ 110.3, 55.4, 53.8, 36.0, 35.6, 32.33, 32.29, 32.0 ppm. MS (MALDI-TOF): calcd for C114H98O4[M]

1530.75, found 1530.89.

Compound 3.47

In a 100 mL round bottom flask, boronic ester 2.10c (181 mg, 0.378 mmol), 3.46 (136 mg, 0.150 mmol) and Et4NOH (15 mL, 35% w/w solution in water) were dissolved in toluene (50 mL). The solution was degassed by bubbling nitrogen for 30 min and Pd(PPh3)4 (18 mg, 0.016 mmol) was 138

added and the resulting mixture was refluxed under a N2 atmosphere for 24 h. After the reaction was complete, reaction was diluted with water. The mixture was extracted with DCM, washed with H2O and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, DCM:hexane = 1:1) to give 181 mg (yield

82%) of compound 3.38 as a light yellow solid. Rf = 0.22 (DCM:hexane, 1:1). FTIR (neat) 2960,

-1 1 2835, 2205, 1605, 1508 cm . H NMR (400 MHz, CDCl3 δ 9.79 (s, 4H), 9.34 (d, J = 1.6 Hz, 4H),

9.30 (s, 4H), 7.70 (d, J = 0.8 Hz, 5H), 7.07 – 7.03 (m, 8H), 6.42 – 6.39 (m, 8H), 3.54 (s, 12H),

13 2.56 (s, 6H), 1.59 (s, 36H) ppm. C NMR (400 MHz, CDCl3) δ 159.5, 149.4, 142.5, 137.5, 136.6,

133.4, 133.2, 130.8, 130.6, 130.1, 125.5, 124.9, 124.1, 124.0, 121.2, 119.7, 119.0, 115.1, 113.9,

+ 93.3, 88.5, 55.3, 35.8, 31.9, 21.1 ppm. MS (MALDI-TOF): calcd for C108H86O4[M] 1446.653, found 1446.643.

Compounds 3.20

Compound 3.47 (61 mg, 0.042 mmol) was dissolved in dry toluene (25 mL) in a 50 mL flame- dried round bottom flask. The solution was degassed by bubbling nitrogen gas through the solution for 30 min. A catalytic mixture of InCl3 (2.2 mg, 0.0099 mmol) and silver bistriflimide (3.3 mg, 139

0.088 mmol) was added inside a glovebox. Color of the reaction mixture immediately started to change to dark red upon addition of the catalyst mixture. Then the reaction mixture was refluxed for 15 h under nitrogen environment. After the reaction was complete (checked by TLC), it was quenched with 5 mL of a saturated solution of sodium bicarbonate, extracted in DCM, dried with

Na2SO4. Solvent was removed by rotatory evaporation and purification by column chromatography (silica gel, hexane:DCM = 1:1). Compound 3.20a, 25 mg (yield 41%) of chiral isomer 3.20a

-1 as a dark red solid. Rf = 0.30 (hexane:DCM 1:1). FTIR (neat) 2955, 2868, 1681, 1610, 1510 cm .

1 H NMR (400 MHz, CDCl3) δ 8.93 (s, 4H), 8.73 (s, 4H), 8.31 (bs, 8H), 7.41 (bs, 8H), 6.44 (s, 8H),

13 3.52 (s, 12H), 2.98 (s, 6H), 1.58 (s, 36H) ppm. C NMR (400 MHz, CDCl3) δ 158.5, 147.7, 139.3,

136.7, 135.4, 132.2, 129.9, 129.6, 129.5, 128.8, 127.9, 127.5, 126.5, 126.4, 124.5, 123.1, 122.7,

121.4, 120.9, 120.2, 119.2, 113.8, 55.3, 35.7, 32.1, 22.4 ppm. MS (MALDI-TOF): calcd for

+ C108H86O4[M] 1446.653, found 1446.67. Compound 3.20b, 30 mg (yield 49%) of meso-isomer

-1 1 3.20b as dark red solid., Rf = 0.23 (hexane:DCM 1:1). FTIR (neat) 2953, 1607, 1510 cm . H

NMR (400 MHz, CDCl3) δ 8.96 (s, 4H), 8.75 (s, 4H), 8.35 (s, 4H), 8.30 (s, 4H), 7.44 (bs, 8H),

13 6.46 (bs, 8H), 3.53 (s, 12H), 2.99 (s, 6H), 1.60 (s, 36H) ppm. C NMR (400 MHz, CDCl3) δ 158.5,

147.7, 139.3, 136.7, 135.4, 132.2, 129.9, 129.6, 129.5, 128.8, 127.9, 127.5, 126.5, 126.4, 124.5,

123.1, 122.7, 121.3, 120.9, 120.2, 119.2, 113.8, 55.3, 35.7, 32.1, 22.4 ppm. MS (MALDI-TOF):

+ calcd for C108H86O4[M] 1446.65, found 1446.63.

140

Compound 3.74

In a 100 mL round bottom flask fitted with magnetic stirrer, was added triiodoHBC 3.75 (150 mg,

0.167 mmol), boronic ester 2.10a (444 mg, 0.672 mmol), toluene (30 mL) and tetraethylammonium hydroxide (35% w/w in water, 10 mL). The mixture was then degassed by bubbling nitrogen gas for 30 min and then, Pd(PPh3)4 (50 mg, 0.043 mmol) was added. The reaction mixture was then refluxed at 110 °C for 48 h under nitrogen environment. Then, the reaction mixture was diluted with water (20 mL) and organic layer was extracted in DCM. The crude product was concentrated using rotatory evaporator and purified through column chromatography (silica gel,

DCM:hexane, 1:3) to get 119 mg (yield 34%) of the product 3.74. Rf = 0.21 (DCM:hexane, 1:1).

-1 1 FTIR (neat), 2841, 2242, 1607, 1508 cm . H NMR (400 MHz, CDCl3) δ 9.76 (s, 6H), 9.30 (d, J

= 8.1 Hz, 6H), 8.05 (d, J = 7.9 Hz, 3H), 7.83 (s, 6H), 7.05 – 6.99 (m, 12H), 6.38 – 6.32 (m, 12H),

3.54 (t, J = 6.6 Hz, 12H), 1.52 (s, 27H), 1.49 – 1.47 (m, 8H), 1.19 – 1.08 (m, 40H), 0.76 – 0.70

13 (m, 18H) ppm. C NMR (400 MHz, CDCl3) δ 159.2, 150.8, 142.3, 137.4, 133.0, 131.1, 130.0,

129.9, 127.4, 126.0, 125.1, 123.8, 122.5, 122.0, 121.8, 114.7, 114.4, 93.2, 88.6, 67.9, 34.9, 31.6,

+ + 31.4, 29.1, 25.6, 22.6, 14.1 ppm. MS (MALDI-TOF) m/z [M] calcd for [C156H150O6] 2119.14, found 2119.37.

141

Compound 3.21

3.21.

In a flame dried 50 mL round bottom flask fitted with magnetic stirrer was added 30 mL of anhydrous toluene. Compound 3.74 (35 mg, 0.017 mmol) was added to it. The reaction was degassed by bubbling nitrogen gas for 30 min. A mixture of InCl3 (1.1 mg, 0.0049 mmol) and silver bistriflimide (2.1 mg, 0.0054 mmol) was added inside a glovebox. The reaction mixture was refluxed for 15 h. After the reaction was complete, it was quenched with 5 mL of sodium bicarbonate solution. Organic layer was extracted with DCM, dried over Na2SO4, concentrated under reduced pressure. The crude product was purified through column chromatography (silica gel, hexane:DCM,

2:1) to get 22 mg (yield 63%) of product as a red solid product 3.21. Rf = 0.71 (DCM:hexane, 2:1).

1 FTIR (neat). H NMR (400 MHz, CDCl3) δ 8.68 – 8.29 (m, 18H), 7.47 – 7.25 (m, 15H), 6.32 (s,

12H), 3.49 (s, 12H), 1.74 – 1.68 (m, 20H), 1.42 – 1.34 (m, 13H), 1.12 – 0.97 (m, 36H), 0.70 – 0.56

13 (m, 18H) ppm. C NMR (101 MHz, CDCl3) δ 158.0, 149.9, 139.4, 135.7, 131.7, 129.7, 129.6,

127.9, 126.5, 125.4, 124.3, 123.9, 123.1, 122.9, 121.9, 120.8, 120.6, 114.2, 67.7, 32.0, 31.4, 29.9, 142

+ + 29.0, 25.5, 22.4, 13.9 ppm. MS (MALDI-TOF) m/z [M] calcd for [C156H150O6] 2119.14, found

2119.23.

Compound 3.94

In a 250 mL round bottom flask, 4-t-butyl-2-bromoaniline 3.92 (4.00 g, 17.5 mmol), 4,4,5,5-tetra- methyl-2-[3-(trimethylsilyl)phenyl]-1,3,2-dioxaborolane 3.78 (5.8 g, 21 mmol), K2CO3 (9.69 g,

70.1 mmol) was dissolved in 100 mL of THF and 30 mL of distilled water. The resulting mixture was degassed by bubbling nitrogen gas for 30 min. Then, Pd(PPh3)4 (202 mg, 0.175 mmol) was added and the reaction was refluxed for 24 h under nitrogen. After, the reaction was complete, it was diluted with water, extracted in DCM. The solvent was removed under reduced pressure. The obtained crude 3.93 was directly taken into next step. The crude product 3.82 (3.23 g, 10.9 mmol), p-toluene sulfonic acid (7.00 g, 32.6 mmol) was dissolved in 200 mL of acetonitrile. NaNO2 (1.60 g, 21.6 mmol) in 5 mL water was added dropwise into the reaction mixture. The resulting yellow solution was stirred for 90 min at room temperature. After 90 min, CuBr (4.00 g, 27.3 mmol) was added in portions. After 2-3 min, 5 mL of water was added and reaction further stirred for 30 min.

Then, reaction was diluted with 200 mL of distilled water, extracted with DCM, concentrated in rotatory evaporator, and purified through column chromatography (silica gel, hexane) to get 1.85

1 g (yield 42%) of pure product as a viscous colorless oil 3.94. Rf = 0.52 (100% hexane). H NMR

(400 MHz, CDCl3) δ 7.62 – 7.58 (m, 3H), 7.58 (s, 1H), 7.43 – 7.39 (m, 3H), 7.36 (d, J = 2.5 Hz,

13 1H), 7.24 (dd, J = 8.4, 2.5 Hz, 1H), 1.34 (s, 7H), 0.31 (s, 7H) ppm. C NMR (400 MHz, CDCl3) 143

δ 150.8, 142.3, 140.9, 140.2, 134.7, 132.8, 132.5, 129.9, 128.7, 127.5, 126.1, 124.7, 34.8, 31.4, 0.1

+ + ppm. HRMS (ESI-TOF) m/z: [M] calcd for [C19H25BrSi] 360.0908, found 360.0913.

Compound 3.95

In a 200 mL flamed-dried flask fitted with a magnetic stirrer, compound 3.94 (1.85 g, 5.12 mmol), was dissolved in anhydrous THF under nitrogen. The resulting mixture was cooled to -78 °C, and n-BuLi (3.7 mL, 1.8 M in hexane) was added dropwise. The resulting brown solution was stirred at -78 °C for 1 h. The reaction was quenched with isopropoxy boronic acid pinacol ester (1.50 g,

7.70 mmol) and allowed to warm to the room temperature. After that, reaction was extracted with

DCM, concentrated under reduced pressure, and purified through column chromatography (silica gel, DCM:hexane, 1:3) to get 1.03 g (yield 49%) of the product 3.95. Rf = 0.34 (DCM:hexane,

. 1 1:3). H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.7 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 7.52 – 7.47

(m, 1H), 7.39-9.35 (m, 4H), 1.34 (s, 9H), 1.25 (s, 9H), 1.17 (s, 12H) ppm. HRMS (ESI-TOF) m/z:

+ + [M] calcd for [C25H37BO2Si] 408.2656, found 408.2632.

Compound 3.97

144

In a flame dried 100 mL round bottom flask fitted with a magnetic stirrer, 1,3,5-tribromobenzene

3.96 (198 mg, 0.629 mmol), boronic ester 3.95 (1.03 g, 2.52 mmol), K2CO3 (1.50 g, 7.56 mmol) was dissolved in 50 mL of THF and 10 mL of distilled water. Then, the solution was degassed by bubbling nitrogen gas for 30 min. Pd(PPh3)4 (300 mg, 0.260 mmol) was added and the reaction was heated to reflux for 24 h. Then, the reaction was diluted with water, extracted in DCM, concentrated under reduced pressure. The crude product was purified by column chromatography ( silica gel, DCM:hexane 1:3) to get 442 mg (yield 76%) of the product as a fluffy white solid

1 compound 3.97. Rf = 0.76 (DCM:hexane, 1:3). H NMR (400 MHz, CDCl3) δ 7.50 – 7.45 (m, 4H),

7.42 – 7.39 (m, 7H), 7.30 – 7.25 (m, 7H), 6.96 – 6.93 (m, 3H), 6.59 (d, J = 8.1 Hz, 3H), 1.40 (s,

13 27H), 0.20 (s, 27H) ppm. C NMR (400 MHz, CDCl3) δ 150.0, 141.8, 140.4, 140.2, 140.0, 137.8,

135.2, 131.4, 130.9, 130.1, 129.9, 127.3, 127.2, 124.3, 34.7, 31.5, -0.1 ppm. HRMS (ESI-TOF)

+ + m/z: [M] calcd for [C63H78Si] 918.5411, found 918.5329.

Compound 3.98

In a flame-dried 100 mL round bottom flask fitted with a magnetic stirrer, compound 3.97 (441 mg, 0.480 mmol) was dissolved in 30 mL of anhydrous DCM. The reaction was bubbled with nitrogen for 20 min and then ICl (3 mL, 1 M in DCM) was added dropwise at room temperature.

The reaction was stirred for 2 h. Then, excess of ICl was quenched with 5 mL of saturated sodium thiosulfate solution. The reaction was then extracted in DCM, concentrated under reduced 145 pressure, purified through column chromatography (silica gel, DCM:hexane, 1:3) to get 400 mg

1 (yield 77%) of product as spongy white solid compound 3.98. Rf = 0.62 (DCM:hexane, 1:3). H

NMR (400 MHz, CDCl3) δ 7.67-7.58 (m, 7H), 7.39-7.31 (m, 7H), 7.11 – 6.92 (m, 7H), 6.84-6.64

13 (m, 1H), 1.39 (s, 27H) ppm. C NMR (400 MHz, CDCl3) δ 150.6, 144.7, 140.3, 138.7, 138.4,

137.4, 135.5, 130.5, 130.0, 129.9, 129.8, 127.3, 125.1, 94.1, 34.8, 31.5 ppm. MS (MALDI-TOF)

+ + m/z [M] calcd for [C54H51I3] 1080.11, found 1080.25.

Compound 3.99

In a 200 mL flame-dried round bottom flask fitted with magnetic stirrer, compound 3.98 (200 mg,

0.187 mmol) was dissolved in dry DCM and the mixture was degassed by bubbling nitrogen gas for 30 min. Then, the solution of FeCl3 (991 mg, 6.12 mmol) in 10 mL MeNO2 was added dropwise at room temperature. The reaction was stirred under slow stream of nitrogen gas for 1.5 h and quenched with methanol. The resulting yellow precipitate was filtered through sintered glass fun- nel. The residue was washed with water, cold methanol and dried under reduced pressure to get

1 150 mg (yield 76%) of yellow solid as product 3.99. H NMR (400 MHz, CDCl3) δ 8.49 (s, 6H),

13 8.24 (s, 6H), 1.80 (s, 27H) ppm. C NMR (400 MHz, CDCl3) δ 148.2, 130.7, 129.7, 127.3, 122.4,

+ 121.3, 119.1, 117.6, 110.2, 93.2, 35.8, 32.4 ppm. MS (MALDI-TOF) m/z calcd for [C54H39I3]

1068.01, found 1068.36.

Compound 3.100 146

In a 100 mL round bottom flask fitted with a magnetic stirrer, was added compound 3.99 (150 mg,

0.140 mmol), boronic ester 2.10b (329 mg, 0.632 mmol), 20 mL of tetraethyl ammonium hydroxide, and 50 mL of toluene. The resulting mixture was bubbled with nitrogen for 30 min. After that,

Pd(PPh3)4 (50 mg, 0.042 mmol) was added. The resulting mixture was heated to reflux under nitrogen for 48 h. After reaction was complete, it was diluted with water. Organic layer was extracted with DCM, dried with Na2SO4 and concentrated under reduced pressure. The crude product was purified through column chromatography (silica gel, DCM:hexane, 1:1) to get 114 mg (yield 44%)

1 of product as orange solid compound 3.100. Rf = 0.21. H NMR (400 MHz, CDCl3) δ 9.84 (s, 6H),

9.34 (s, 6H), 7.89 (s, 6H), 7.11 – 7.04 (m, 12H), 6.42 – 6.33 (m, 12H), 3.47 (s, 18H), 1.55 (s, 27H),

13 1.37 (s, 27H) ppm. C NMR (400 MHz, CDCl3) δ 159.6, 150.7, 149.8, 142.4, 136.6, 133.1, 130.7,

130.0, 125.5, 125.0, 124.1, 123.8, 122.0, 120.9, 119.7, 115.0, 115.0, 113.8, 93.1, 88.8, 55.2, 35.7,

+ + 34.9, 31.7, 31.5 ppm. MALDI-TOF MS m/z [M] calcd for [C138H114O6] 1866.86, found 1866.37.

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152

4. Synthesis of longer pyrenacenes

4.1 Introduction

Pyrene 4.1 is a flat PAH containing four fused aromatic rings in a non-linear fashion.1 It was first isolated by Laurent in 1937 from the destructive distillation of coal tar.2 It is the smallest peri- fused PAH, first synthesized by Weitzenbock in 1913, starting from o,o′-ditolyl. Because of its commercial availability and chemically modifiability, it has been used as a good starting material for the synthesis of a variety of NGs. Plenty of molecules having pyrene-fused π-systems are known to possess interesting photophysical properties and have been used in the variety of organo- electronic devices like chiral sensors, optical switches and transistors.3-6 Further π-extension of pyrene is reported to enhance optical and electronic properties.7 Peropyrene 4.2, also called dibenzo[cd,lm]perylene, is a peri-condensed, even alternant, benzenoid hydrocarbon; yellow in color and was first reported by Loffe in 1934. In solution, peropyrene exhibits blue fluorescence under natural light. Peropyrene is getting attention for its fascinating photochemical properties and is a potential candidate for singlet fission materials.8-10 The next longer pyrenacene analogue teropyrene 4.3 and the synthesis of teropyrene was first reported in 1975 by Misumi and coworker.11 It is found to exhibit a bathochromic shift in both absorption and emission bands and lower HOMO-LUMO band gap compared to its shorter analogues (i.e. peropyrene and pyrene).7

This trend shows that even longer derivatives would exhibit even enhanced photophysical properties like emission and absorption behaviors. Numerous works have been done to synthesize pyrene or to incorporate pyrene sub-unit within the molecules.3, 7, 12-14 Synthesis of peropyrene is less studied than pyrene but still there are handful of synthetic methods reported.7, 15-18 Synthesis of 153 teropyrene is rarely reported.7, 18, 19 longer analogues, quateropyrene 4.4, quinteropyrene 4.5 have never been reported.

Figure 4-1: Structure of pyrenacenes.

Figure 4-2 displays the Kekulé structures of pyrenacenes showing the canonical Clar structures of the pyrenacenes. Pyrene 4.1, the lowest member of pyrenacene family contains two aromatic sextets. Peropyrene 4.2 has three aromatic sextets and teropyrene 4.3 has four aromatic sextets. Next higher analogues quateropyrene 4.4 and quinteropyrene 4.5 have even longer conjugated system with an extended aromatic sextets.

Figure 4-2: Pyrenacenes structures and their Clar’s aromatic sextet representation. 154

The development of the convenient, efficient and mild methods leading towards the longer functionalized pyrenacenes are still on demand. The Chalifoux group have developed acid-catalyzed alkyne benzannulation reactions which are found efficient to afford a variety of NGs and GNRs starting from an easily accessible high energy alkyne precursor. Recently, our group reported the synthesis of soluble pyrenacenes such as pyrenes 4.7, peropyrenes 4.9, and teropyrenes 4.11 via a

Brønsted acid-catalyzed alkyne benzannulation reaction as the key step (Scheme 4-1) starting from the diyne and tetrayne precursors 4.6, 4.8, and 4.10 respectively.15, 20 Our group was also able to utilize the alkyne benzannulation to synthesize sterically demanding, highly twisted, soluble chiral peropyrene 4.13. The maximum absorbance of soluble and functionalized pyrene, peropyrene and teropyrene were found to be 353 nm, 465 nm and 570 nm respectively. Figure 4-3 is a maximum absorption wavelength (λmax) vs pyrenacene length plot. The extrapolation of the trendline in the curve gives a rough idea about the λmax values for the longer analogues (although it might not grow linearly), which shows that quateropyrene and quinteropyrene will have λmax values of around 670 nm and 800 nm (red points in the graph) respectively.

800

700

600

(nm) max

λ 500

400

300 1 2 3 4 5 6 pyrenacene lengths

Figure 4-3: The λmax vs. pyrenacene length plot for pyrenacenes. The numbers 1, 2, 3, 4, and 5 on the x-axis represents the pyrene, peropyrene, teropyrene, quateropyrene and quinteropyrene, respectively (blue dots are experimental values and red dots are predicted values). 155

Scheme 4-1: The Chalifoux group's synthesis of pyrenacenes. 156

4.2 Our design of the longer pyrenacenes

Following the synthesis of teropyrene, we planned an efficient synthesis of longer pyrenacenes using the similar approach. For the synthesis of teropyrene, the tetrayne precursor was obtained by a two-fold Suzuki cross-coupling of 2,7-dibromopyrene. So, our approach here for the synthesis of quateropyrene 4.13 is by synthesizing a 2,9-dihalofuctionalized peropyrene 4.16 which on a two-fold Suzuki cross-coupling will afford a tetrayne precursor 4.15. The two-fold alkyne benzannulation of tetrayne 4.15 will afford quateropyrene. Similarly, if we replace 2,9-dihaloperopyrene

4.16 with 2,11-dihaloteropyrene 4.19, the resulting tetrayne will afford a quinteropyrene 4.17. Bay-

Scheme 4-2: Our design of quateropyrene and quinteropyrene. 157 substituted alkyloxyphenyl groups and t-butyl groups at two ends will make these molecules highly soluble in common organic solvents. So, the key steps of overall synthesis are making halogen- functionalized peropyrene 4.16 and teropyrene 4.19 coupling partners.

4.3 Attempted synthesis of quateropyrene

4.3.1 Convergent approach toward the synthesis of chiral diiodoperopyrene

4.3.1.1 Synthesis of chiral diiodoperopyrene 4-19

We initiated the synthesis of the diiodoperopyrene core starting with a commercially available starting material 4-bromonitrobenzene 4.20 (Scheme 4-4). Diiodination of 4-bromonitrobenzene was attempted under various conditions (KI, KIO3, H2SO4; H2O2, KI, H2SO4, etc.). We found that diiodination reaction worked well with periodic acid and iodine in concentrated sulfuric acid.21

The diiodinated product was reduced to amine 4.21 by refluxing with iron powder in acetic acid for 1 hour following a literature procedure.22 Amine 4.21 was converted to a diazonium salt with

BF3·OEt2 and t-butyl nitrite and was then treated with diethylamine and potassium carbonate to get triazine 4.22 in 81% yield.23 Compound 4.22 was subjected to a selective two-fold Sonogashira cross-coupling reaction with 4-hexyloxyethynylbenzene to afford triazine bromodiyne 4.23. We attempted a two-fold Suzuki cross-coupling reaction of bromotriazine 4.23 with 1,4-(bis)pinaco- lato benzene 4.24 which did not work and no desired product 4.25 was obtained (Scheme 4.3).

The failure of this reaction is understandable because of the sterically hindered bromine (flanked by two bulky alkynes) in the reactant 4.23. 158

Scheme 4-3: Attempted synthesis of ditriazine tetrayne 4.25.

Our next step was conversion of bromodiyne to boronic ester (Scheme 4-4). We carried out lithium-halogen exchange of compound 4.23 and the reaction was quenched with isopropoxyboronic acid pinacol ester that gave compound 4.26 in 74%. Compound 4.26 was subjected to Suzuki cross-coupling with 1,4-diiodobenzene. We first attempted regular Suzuki conditions [Pd(PPh3)4,

K2CO3, THF/H2O] that gave the desired product 4.25 in 26% yield. When we changed the Suzuki condition to anhydrous THF as solvent and Ag2CO3, the yield improved to 61%.

Scheme 4-4: Synthesis of ditriazine tetrayne. 159

Next, we focused our attention to the alkyne benzannulation reaction of ditriazine tetrayne 4.25

(Scheme 4-5). We tried Brønsted acid (TfOH) condition first where we observed a rapid color change of the reaction mixture from red to black. The NMR analysis showed the decomposition of the starting material 4.25. then, we attempted Lewis acid (InCl3/InCl3+AgNTf2) catalyzed alkyne benzannulation of compound 4.25 but there was no conversion of the starting material observed. Both of the conditions failed to give desired benzannulated product 4.27.

Scheme 4-5: Attempted alkyne benzannulation of ditriazine tetrayne.

Our understanding for the failure of the alkyne benzannulation of ditriazine tetrayne 4.25 is acid catalysts were wasted in coordinating N-N double bonds and/or in protonating to the nitrogen atoms in triazine rather than activating C-C triple bonds. So, we decided to convert acid sensitive triazine group in compound 4.25 to iodo analogue 4.28 prior to four-fold alkyne benzannulation reaction (Scheme 4-6). We heated compound 4.25 with MeI in a sealed tube at 150 °C for 48 h.

The yield of this reaction was very poor initially (approximately 10-20%). When the reaction mixture was purged with nitrogen gas for 20 minutes prior to heating with MeI, reaction yielded quantitative amount of the product 4.28. 160

Scheme 4-6: MeI reaction of ditriazine 4.25 yielding diiodo analogue 4.28. Our next attempt was the alkyne benzannulation of the diiodo tetrayne 4.28 to get diiodo-functionalized chiral peropyrene 4.16. We first tried Bronsted acid (TfOH) conditions with a 0.041 mmol scale ‘test’ reaction of 4.25 in an anhydrous DCM. An aliquot of the reaction was analyzed with mass spectrometry which conformed the formation of diiodinated compounds 4.30 and 4.31 as the products. We tried InCl3-catalyzed alkyne benzannulation conditions, which gave two-fold alkyne benzannulated product 4.29. It appears that the activation barrier for the cyclization of the remaining two alkynes is much higher. So, we tried using a series of high boiling solvents such as xylene, mesitylene, 1,3,5-trichlorobenzene, and diphenyl ether. Even at 250 °C in diphenyl ether, the reaction gave no desired product but rather decomposed. After that, We attempted InCl3 and

AgNTf2-catalyzed alkyne benzannulation in anhydrous toluene at reflux for up to 20 h, we observed a trace amount of product 4.16 with the major product being compound 4.31 (Table 4-1).

A yellow insoluble solid was formed that was presumed to be AgI. This suggests that AgNTf2 used 161

S.N. Catalyst Solvent T (°C) Time(h) Product*

1 TFA/TfOH DCM 0 to -40 1 4.30, 4.31

2 TfOH DCM -40 1 4.31

3 InCl3 toluene 90 to 110 24 4.29

4 InCl3 xylene 140 48 4.29

5 InCl3 mesitylene 170 48 none

6 InCl3 Ph2O 250 24 none

7 In(OTf)3 toluene 90 to 110 24 4.29

8 InCl3/AgNTf2 toluene 90 to 110 24 4.31

(trace 4.16)

9 InCl3/AgSbF6 toluene 90 to 110 24 4.31

10 AuCl toluene 90 to 110 24 NR

11 PtCl2 toluene 90 to 110 60 NR

Table 4-1: Catalyst screening for two-fold alkyne benzannulation of compound 4.25 *(Product identification was done based on NMR/MALDI/IR data of crude products). 162 as a promoter deiodinated the iodo-group(s) in compound 4.25 because of the greater affinity of silver with iodine. We repeated the reaction with AgNTf2 and InCl3 to make more of the product

4.16 to move to the next step but the formation of trace amount of compound 4.16 was not always reproducible and the yield of the reaction was inconsistent. With the trace amount of compound

4.16, we carried out a two-fold Suzuki cross-coupling with diyne boronic ester 2.10a to afford tetrayne quateropyrene precursor 4.15 in 34% yield. Compound 4.15 was then subjected to alkyne benzannulation reaction to yield quateropyrene 4.14. MALDI MS and IR spectroscopic analysis showed the formation of desired product 4.14. Because of the very small amount of product, we were not able to characterize compound 4.14 (Scheme 4-7). Attempts to grow crystals for X-ray analysis is underway.

Scheme 4-7: Synthesis of quateropyrene 4.14.

163

4.3.1.2 Eight-fold alkyne benzannulation towards the synthesis of quateropyrene

We attempted a convergent approach to quateropyrene 4.14 in which a one-pot, eight-fold alkyne benzannulation reaction of octayne 4.31. To synthesize octayne compound 4.31, we first tried a direct two-fold Suzuki cross-coupling reaction of the ditriazine 4.25 with boronic ester 2.10a following the protocol reported by Wei group.24 But, the reaction didn’t work and no conversion of the starting materials was observed (Scheme 4-8).

Scheme 4-8: Attempted synthesis of octayne precursor via direct Suzuki cross-coupling of triazine with boronic ester.

We used a different route towards octayne 4.36, which could be synthesized in a four steps starting from a diyne boronic ester 2.10a (Scheme 4-9). The diyne boronic ester 2.10a was cross-coupled with diyne 4.32 selectively on iodine. The resulting bromotetrayne 4.33 was taken through lithium- halogen exchange followed by quenching with isopropoxy boronic acid pinacol ester to get tetrayne boronic ester 4.34. Compound 4.34 was coupled with iodo tetrayne 4.35 to arrive at octayne 4.31. Octayne 4.31 was then subjected to a eight-fold alkyne benzannulation reaction with

InCl3 and AgNTf2. There was formation of an inseparable mixture of products as detected in TLC plate and we were not able to separate desired product 4.14. The mixture of product as detected in 164

TLC plate might be the mixture of one- to eight-fold alkyne benzannulated product. Furthermore, there might be some unwanted alkyne benzannulated products as well. In the poly-yne systems such as 4.31. After the first cyclization, the molecule gets planarized at benzannulated site, direct- ing the aryl closer in space with alkyne 3 (in compound 4.31a) that can undergo such unwanted alkyne benzannulation (represented by dotted arrows) resulting additional isomers.

Scheme 4-9: Attempted eight-fold alkyne benzannulation reaction towards chiral quateropyrene

4.14. 165

4.3.2 Linear route towards chiral quateropyrene

Convergent synthetic routes are always in organic chemistry because they contain less number of steps, often possesses higher yields, and are more economic. Because of very low and inconsistent yield of the convergent route, we designed a different chiral quateropyrene 4.42 with shifted chirality (from middle to end) and came up with an alternative more linear route towards the synthesis of the iodoperopyrene and finally quateropyrene (Scheme 4-10).

Scheme 4-10: Proposed linear route towards chiral quateropyrene 4.42.

We initiated the synthesis of compound 4.42 starting with triazine diyne boronic ester 4.26

(Scheme 4-11). Compound 4.26 was cross-coupled with compound 4.35 and the resulting triazine 166 bromodiyne 4.36 was coupled with diyne boronic ester 2.10a to get compound 4.37 in 45% yield.

Compound 4.37 was converted to iodotetrayne 4.38 treating with MeI in a sealed tube at 140 °C in quantitative yield. Iodotetrayne 4.38 was subjected to alkyne benzannulation reaction under different conditions as described in Table 4-1. All of the attempts were failed and we were unable to get the desired iodoperopyrene 4.39.

Scheme 4-11: Attempted linear synthesis.

Hence, we tried a series of approaches towards the synthesis of quateropyrenes 4.14 and 4.42 but became unsuccessful to afford desired compounds. The major problem encountered in the synthesis of these compounds was in the synthesis of halogen functionalized peropyrene coupling part- ner. After a series of attempts, we came to know that iodo-functionalized tetrayne precursors 4.25 and 4.38 do not undergo alkyne benzannulation under both Bronsted acid and Lewis acid conditions because of the deiodination side reactions. 167

We can try few other routes in the future to arrive at these highly desirable products (Scheme 4-

12) overcoming the challenges in synthesis of dihaloperopyrene. One way we can try is making dibromo-analogue (4.43) of compound 4.14 followed by a two-fold alkyne benzannulation reaction to get 2,9-dibromoperopyrene 4.44. Another way, we can try is synthesis of less-sterically crowded peropyrenes 4.47. Synthesis of 4.47 is expected to be feasible because of the reduced steric crowding in bay-region (containing two aryls in the bay region) compared to compound 4.16

(containing four aryls in the bay region).

Scheme 4-12: Methods to try in the future towards dihalo-functionalized peropyrene.

4.4 Attempted synthesis of quinteropyrene

4.4.1 Synthesis of diiodoteropyrene

After a series of unsuccessful trials towards the synthesis of quateropyrene 4.14 and 4.42, we moved to the synthesis of next higher analogue, quinteropyrene 4.17 using similar strategy. The failure of the synthesis of chiral diiodoperopyrene is the steric hindrance of four bulky substituents in the bay region close to each other making the four-fold alkyne benzannulation impossible. But, if we replace the benzene core with longer core, pyrene, it will minimize the steric repulsion and 168 hence alkyne benzannulation will be faster than the deiodination reaction. With this hypothesis, we moved towards the synthesis of quinteropyrene (Scheme 4-13). We started with synthesis of

2,7-dibromopyrene 4.47 starting from the pyrene 4.1 following the literature procedure.25 Com- pound 4.47 was taken through the two-fold Suzuki cross-coupling with triazine boronic ester 4.26 to get ditriazine tetrayne 4.50. Compound 4.50 was converted to diidodotetrayne 4.51 by heating with MeI and the product was cyclized down to diiodoteropyrene 4.19 using InCl3 under inert condition. This reaction was carried out in a test scale and yielded a very small amount of the product 4.19 which was not enough for the NMR analysis. However, mass, IR, and UV-vis spectroscopy confirmed the formation of product 4.19. The IR spectrum showed no peak around 2200 cm-1 which confirmed four-fold alkyne benzannulation. The precursor compound 4.51 contains pyrene core that would have UV-vis absorption maxima at around 353 nm. The UV-vis absorption pattern of red-colored compound 4.19 (Figure 4-5) was largely redshifted with λmax value of 578 nm that matched with that of teropyrene reported by Yang et al.7 This preliminarily confirmed the formation of diiodoteropyrene and hence, we are just two steps away from quinteropyrene.

0.8

0.6

0.4

0.2 normalaized normalaized intensity

0 278 378 478 578 678 wavelength (nm)

Figure 4-5: UV-vis spectra of compound 4.19.

169

Scheme 4-13: Progresses towards synthesis of diiodoteropyrene 4.19.

We will scale up the synthesis of compound 4.19 that will be cross-coupled with boronic ester diyne 2.10a to produce tetrayne 4.18. The four-fold alkyne benzannulation reaction of 4.18 will result in the formation of quinteropyrene 4.17

4.5 Conclusion

Pyrenacenes such as pyrene, peropyrene, teropyrene, quateropyrene and quinteropyrene or even longer analogues are very important graphitic materials. We were very close towards the synthesis 170 of quateropyrene and quinteropyrene utilizing alkyne benzannulation reaction. There was difficulties in the synthesis of these quateropyrenes because of the low and inconsistent yields of the diiodoperopyrene synthesis step. We attempted both Brønsted acids as well as Lewis acid-catalyzed alkyne benzannulation conditions for the synthesis of the chiral diiodoperopyrene. In both cases, iodine(s) were lost resulting in the formation of unfunctionalized chiral peropyrene as a major product. The later condition yielded trace amount of the desired diiodo functionalized peropyrene core. We repeated the reaction using similar conditions but formation of that product was not consistent. We also attempted various other routes such as one-pot, eight-fold alkyne benzannulation, linear and stepwise synthetic approach. All of these approaches were unsuccessful to afford target quateropyrene. However, for the synthesis of quinteropyrene, we have screened and found good conditions for the synthesis of diiodoteropyrene, although a very small scale. So, further scale-up of this reaction to get more diiodoperopyrene followed by Suzuki cross-coupling and alkyne benzannulation reaction yielding quinteropyrene is still needed.

4.6. Experimental section

4.6.1 General experimental:

All reactions dealing with air- or moisture-sensitive compounds were carried out in a dry reaction vessel under nitrogen. All reagents, and solvents such as dichloromethane, ethyl acetate (EtOAc), were commercially obtained and used without prior purification, unless otherwise noted. Anhy- drous Toluene and tetrahydrofuran (THF) were obtained by passing the solvent (HPLC grade) through an activated alumina column on a PureSolv MD 5 solvent drying system. 1H and 13C NMR spectra were recorded on Varian 400 MHz or Varian 500 MHz NMR Systems Spectrometers.

Spectra were recorded in deuterated chloroform (CDCl3). Chemical shifts are reported in part per 171 million (ppm) Coupling constants (J) are reported in Hz. The multiplicity of 1H signals are indicated as: s = singlet, d = doublet, t = triplet, m = multiplet, bs = broad singlet. High resolution

ESI/APPI mass spectrometry was recorded using an Agilent 6230 TOF MS. TLC information was recorded on Silica gel 60 F254 glass plates. Purification of reaction products was carried out by flash chromatography using Silica Gel 60 (230-400 mesh).

4.6.2 Synthesis and characterizations

Compound 4.21

In a 40 mL round bottom flask charged with a magnetic stirrer, 100 mL acetic acid was added.

Then, 4-bromo-3,5-diiodonitrobenzene (1.50 g, 3.30 mmol) was added and heated to reflux for about 30 min. The reaction mixture was cooled down to room temperature and iron powder (650 mg, 11.6 mmol) was added in multiple portions. The resulting brown suspension was heated to reflux for additional 30 min. Then reaction mixture was poured into 200 mL ice water and filtered.

The residue was dissolved in ethyl acetate, dried with Na2SO4. Solvent was evaporated under vacuum and the resulting white solid was further purified by recrystallization with 100% ethanol. 1.15 g (yield, 80%) of pure white needles obtained as a pure product 4.21. FTIR (neat) 3464, 3363,

-1 1 13 2955, 2867, 1613 cm . H NMR (400 MHz, CDCl3) δ 7.19 (s, 1H), 3.65 (s, 1H) ppm. C NMR

+ (101 MHz, CDCl3) δ 151.5, 132.3, 130.7, 99.4 ppm. HRMS (ESI-TOF) m/z: [M+Na] for

+ [C6H4BrI2Na] 445.751, found 445.755.

172

Compound 4.22

In a flamed-dried 100 mL round bottom flask charged with a magnetic stirrer, was added 20 mL of dry dichloromethane and BF3·OEt2 (502 mg, 3.54 mmol) was added with a long needle at 0 °C.

Amine 4.21 (1.00 g, 2.36 mmol) was added keeping the environment of the flask inert. t-Butylni- trite (304 mg, 2.95 mmol) was then added and reaction mixture stirred at 0 °C for 40 min. After that, K2CO3 (1.18 g, 8.55 mmol) was added followed by addition of diethylamine (1.00 g, 11.5 mmol). Resulting dark red solution was stirred at room temperature for 2 h. The, reaction diluted with water, extracted in ethyl ether, dried over sodium sulfate and purified through a column (silica gel, ethyl acetate:hexane, 1:10) to get 950 mg (yield, 79%) of compound 4.22 as a red viscous

1 liquid. H NMR (400 MHz, CDCl3) δ 7.90 (s, 2H), 3.76 (s, 4H), 1.34 – 1.21 (m, 6H) ppm. HRMS

+ + (ESI-TOF) m/z: [M+Na] for [C10H12BrI2Na] 529.8201, found 529.8253.

Compound 4.23

In a 250 mL flame-dried round bottom flask fitted with a magnetic stirrer was added 100 mL tetrahydrofuran. Then, was added compound 4.22 (5.21 g, 10.30 mmol), p-hexyloxyethynyl benzene (4.800 g, 23.61 mmol), and triethylamine 15 mL. The resulting mixture was degassed by 173

bubbling with nitrogen gas for 30 min. Pd(PPh3)2Cl2 (115 mg, 0.164 mmol) and CuI (78 mg, 0.41 mmol) was added. The reaction was stirred for 15 h at room temperature. After the reaction was complete, it was filtered through a pad of silica to remove ammonium salts. The filtrate was then concentrated in rotatory evaporator and purified through a column (silica gel, DCM : Hexane, 1:3) to get 5.68 g (yield, 84%) yellow solid product 4.23. FTIR (neat) 2935, 2868, 2211, 1605, 1570

-1 1 cm . H NMR (400 MHz, CDCl3) δ 7.55 (s, 4H), 7.56 – 7.48 (m, 5H), 6.90 – 6.85 (m, 4H), 3.97

(t, J = 6.6 Hz, 4H), 3.77 (q, J = 7.1 Hz, 4H), 1.79 (dt, J = 14.6, 6.7 Hz, 4H), 1.46 (tdd, J = 7.2, 5.1,

13 2.3 Hz, 4H), 1.40 – 1.18 (m, 14H), 0.96 – 0.87 (m, 6H). C NMR (400 MHz, CDCl3) δ 159.6,

149.9, 133.3, 126.7, 124.4, 123.5, 115.0, 114.7, 93.7, 87.5, 68.2, 31.7, 29.3, 25.8, 22.7, 14.2 ppm.

+ + HRMS (ESI-TOF) m/z: [M+Na] for [C38H46BrN3O2Na] 678.267, found 678.249.

Compound 4.26

In a flame-dried round bottom flak charged with a magnetic stirrer, was added anhydrous THF (20 mL). Then, compound 4.23 (500 mg, 0.761 mmol) was added. Then, the flask containing the solution was cooled to -78 °C and n-BuLi (2.4 M, 0.40 mL, 0.91 mmol) was added dropwise over the period of 5 min. The color of the solution turned into dark black. The reaction mixture was then stirred at that temperature for 1 h. Isopropoxyboronic acid pinacol ester (213 mg, 1.15 mmol) was added and the reaction was allowed to warm to room temperature. Reaction was stirred for additional 30 min at room temperature and quenched with water. Organic layer was extracted with 174

water, washed with ammonium chloride and dried with Na2SO4. The crude was concentrated in a rotatory evaporator, and purified by column chromatography (silica gel, DCM : hexane, 1:2) to get a 1.59 g (yield, 74%) of pure product 4.26 as a viscous reddish brown liquid. FTIR (neat) 2931,

-1 1 2869, 2209, 1605 cm . H NMR (400 MHz, CDCl3) δ 7.53 (s, 2H), 7.46 – 7.42 (m, 4H), 6.88 –

6.82 (m, 4H), 3.96 (t, J = 6.6 Hz, 4H), 3.77 (q, J = 7.1 Hz, 4H), 1.83 – 1.74 (m, 4H), 1.50 – 1.43

13 (m, 4H), 1.40 – 1.23 (m, 27H), 0.95 – 0.88 (m, 6H) ppm. C NMR (400 MHz, CDCl3) δ 159.2,

151.7, 133.0, 127.7, 123.7, 115.6, 114.5, 90.0, 88.7, 84.1, 68.1, 31.7, 29.3, 25.8, 25.1, 22.7, 14.1

+ + ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C44H59BO4] 704.459, found 704.452.

Compound 4.25

In a 200 mL round bottom flask, 1,4-diiodobenzene (335 mg, 1.02 mmol) and boronic ester 4.26

(1.79 g, 2.54 mmol) was dissolved in anhydrous THF (15 mL) and silver carbonate (1.40 g, 2.54 mmol) was added. Then, the reaction mixture was degassed by bubbling nitrogen gas for 30 min.

Then, Pd(PPh3)4 (120 mg, 0.104 mmol) was added and reaction was heated to reflux for 48 h. After reaction was complete, it was diluted with water. The organic layer was extracted with DCM and dried with sodium sulfate. The crude product was concentrated in rotatory evaporator and purified by column chromatography (silica gel, DCM : hexane, 1:2) to get 759 mg (yield, 61%) of pure

-1 1 product 4.25. FTIR (neat) 2930, 2857, 2210, 1605, 1579 cm . H NMR (400 MHz, CDCl3) δ 7.80

(s, 4H), 7.76 (s, 3H), 7.13 – 7.07 (m, 7H), 6.61 – 6.56 (m, 7H), 3.83 (dt, J = 21.3, 6.8 Hz, 16H),

13 1.75 – 1.68 (m, 8H), 1.45 – 1.30 (m, 42H), 0.96 – 0.93 (m, 12H) ppm. C NMR (400 MHz, CDCl3) 175

δ 158.9, 150.0, 143.0, 138.8, 132.9, 129.7, 124.2, 123.3, 115.1, 114.2, 93.1, 88.2, 67.9, 31.6, 29.2,

+ + 25.7, 22.74, 22.67, 14.2, 14.1 ppm. HRMS (ESI-TOF) m/z: [M+H] calcd for [C82H97N6O4]

1229.757, found 1229.752.

Compound 4.28

In a flamed-dried 50 mL high pressure reaction tube with teflon screw cap fitted with a magnetic stirrer, was added compound 4.25 (759 mg, 0.617 mmol) and 7 mL of MeI. The solution was bubbled with nitrogen gas for 20 min and then tube was sealed with cap. The reaction set up was heated at 140 °C for 48 h. After reaction was complete, it was cooled to room temperature and excess MeI was evaporated in rotatory evaporator. The crude product was purified by column chromatography (silica gel, hexane:DCM, 2:1) to get 725 mg (yield, 91%) of spongy yellow solid

-1 1 product 4.28. FTIR (neat) 2935, 2867, 2214, 1604, 1557 cm . H NMR (400 MHz, CDCl3) δ 7.92

(s, 4H), 7.66 (s, 4H), 7.00 – 6.93 (m, 8H), 6.54 – 6.46 (m, 8H), 3.76 (t, J = 6.6 Hz, 8H), 1.71 –

13 1.63 (m, 8H), 1.41 – 1.29 (m, 24H), 0.92 – 0.87 (m, 12H) ppm. C NMR (400 MHz, CDCl3) δ

159.3, 145.4, 139.3, 138.4, 133.0, 129.5, 125.8, 114.38, 114.37, 95.1, 91.6, 86.2, 68.0, 31.7, 29.2,

+ + 25.8, 22.7, 14.2 ppm. HRMS (ESI-TOF) m/z: [M+Na] for [C74H76I2O4Na] 1305.3731, found

1305.3752.

176

Compound 4.16

In a flame-dried 100 mL round bottom flask fitted with a magnetic stirrer, compound 4.28 (234 mg, 0.182 mmol) was dissolved in 30 mL of anhydrous toluene. The solution was degassed by bubbling N2 gas for 30 min. InCl3 (4.2 mg, 0.018 mmol) and AgNTf2 (7.1 mg, 0.018 mmol) was added inside a glove box. Then, reaction mixture was heated to reflux for 15 h. After the reaction was complete, solvent was removed under reduced pressure. The inorganic impurities were removed by a short silica plug. Thus obtained red crude solid was extracted with hot hexane to get pure product in hexane fraction to get 21 mg (yield, 9%) of compound 4-16. FTIR (neat) = 2927,

-1 1 2857, 1606, 1506 cm . H NMR (400 MHz, CDCl3) δ 8.48 (s, 2H), 7.69 (s, 2H), 6.69 (s, 16H),

4.07 – 3.93 (m, 8H), 1.87 – 1.81 (m, 6H), 1.56 – 1.49 (m, 8H), 1.40 (d, J = 8.5, 4.1 Hz, 12H), 1.08

13 – 0.84 (m, 18H) ppm. C NMR (400 MHz, CDCl3) δ 158.4, 140.8, 135.7, 133.6, 133.4, 126.6,

126.1, 124.6, 120.9, 113.1, 92.4, 68.3, 31.8, 29.4, 25.9, 22.8, 14.2 ppm. MS (MALDI-TOF) calcd for [C74H76I2O4]+ 1282.38, found 1282.49.

Compound 4.15

In a 50 mL flame-dried round bottom flask fitted with a magnetic stirrer, chiral diiodoperopyrene

4.16 (15 mg, 0.012 mmol), diyne boronic ester 2.10a (23 mg, 0.035 mmol), Ag2CO3 (15 mg, 0.054 177 mmol) was added. Anhydrous THF (10 mL) was added into the flask maintaining an inert environment. The reaction mixture was degassed by bubbling N2 for 25 min. Pd(PPh3)4 (3 mg, 0.002 mmol) was added and reaction was refluxed at 90 °C for 24 hours. After the reaction was complete, it was diluted with DCM. The organic layer was extracted with DCM, concentrated under reduced pressure and purified through column chromatography (silica gel, DCM:hexane, 1:2) to get 5 mg

(yield, 34%) of the product 4.15 as a white spongy solid. Rf = 0.27. FTIR (neat) 2914, 2862, 2213,

-1 1 1609 cm . H NMR (400 MHz, CDCl3) δ 8.56 (s, 4H), 7.91 (s, 4H), 7.74 (s, 4H), 7.11 – 6.96 (m,

8H), 6.69 – 6.56 (m, 8H), 4.04 – 3.89 (m, 7H), 3.84 – 3.69 (m, 8H), 1.88 – 1.77 (m, 7H), 1.67 –

1.58 (m, 8H), 1.53 – 1.43 (m, 24H), 1.43 – 1.20 (m, 52H), 0.96 – 0.80 (m, 24H) ppm. 13C NMR

(400 MHz, CDCl3) δ 159.3, 159.2, 158.1, 150.4, 142.5, 139.8, 137.3, 136.4, 133.2, 133.1, 133.0,

131.0, 129.6, 128.2, 126.4, 124.4, 123.7, 123.6, 121.6, 115.2, 114.7, 114.5, 114.3, 114.1, 92.8,

88.7, 68.3, 68.1, 34.8, 31.91, 31.87, 31.69, 31.4, 31.3, 29.5, 29.3, 29.2, 25.9, 25.8, 22.8, 22.7,

+ 14.23, 14.19, 14.15, 14.10 ppm. MS (MALDI-TOF) calcd for [C148H164O8] 2069.24, found

2069.49.

Compound 4.36

In a 200 mL round bottom flask fitted with magnetic stirrer, compound 4.26 (1.12 g, 1.59 mmol),

1-bromo-4-iodobenzene (450 mg, 1.59 mmol), and K2CO3 (880 mg, 6.40 mmol) was dissolved in

THF (100 mL) and water (20 mL). Then the solution was degassed by bubbling nitrogen gas for 178

30 min and Pd(PPh3)4 (18 mg, 0.016 mmol) was added. The reaction was heated to reflux for 24 h under N2 environment. After the reaction was complete, it was diluted with water, extracted in

DCM, concentrated under reduced pressure. The crude was purified by column chromatography

(silica gel, DCM:hexane, 1:3) to get 660 mg (yield, 56%) of product 4.36 as a spongy brown solid.

-1 1 Rf = 0.24. FTIR (neat) = 2930, 2209, 1604, 1548 cm . H NMR (400 MHz, CDCl3) δ 7.64 (s, 2H),

7.61 – 7.52 (m, 4H), 7.21 – 7.13 (m, 4H), 6.83 – 6.77 (m, 4H), 3.94 (t, J = 6.6 Hz, 4H), 3.81 (q, J

= 7.2 Hz, 4H), 1.81 – 1.74 (m, 4H), 1.48 – 1.43 (m, 4H), 1.33 (q, J = 8.1, 6.8 Hz, 14H), 0.93 – 0.89

13 (m, 6H) ppm. C NMR (101 MHz, CDCl3) δ 159.4, 150.3, 140.6, 138.4, 133.2, 132.93, 132.85,

132.7, 130.4, 124.0, 123.7, 121.5, 115.2, 114.6, 92.8, 87.9, 68.2, 31.7, 29.3, 25.8, 22.7, 14.2 ppm.

+ + HRMS (ESI-TOF) m/z: [M+Na] for [C44H50BrN3O2Na] 754.2984, found 754.2979.

Compound 4.37

In a 200 ml round bottom flask fitted with magnetic stirrer, was added 4.36 (700 mg, 0.589 mmol), boronic ester 2.10a (762 mg, 1.15 mmol) and K2CO3 (553 mg, 4.19 mmol). The resulting mixture was degassed by bubbling with N2 gas for 30 min and Pd(PPh3)4 (11 mg, 0.0095 mmol) was added.

The reaction was heated to 90 °C for 24 hours under nitrogen environment. After the reaction was complete, it was diluted with water, extracted in DCM, concentrated under reduced pressure. The crude was purified by column chromatography (silica gel, DCM:hexane, 1:2) to get 889 mg (yield,

78%) of product 4.37 as a spongy brown solid. Rf = 0.21. FTIR (neat) = 2930, 2869, 2208, 1605, 179

-1 1 1540 cm . H NMR (400 MHz, CDCl3) δ 7.77 – 7.67 (m, 6H), 7.65 (s, 2H), 7.09 – 6.99 (m, 8H),

6.56 – 6.50 (m, 8H), 3.84 (q, J = 7.1 Hz, 6H), 3.77 (m, 9H), 1.73 – 1.63 (m, 10H), 1.46 (s, 10H),

13 1.33 (q, J = 5.7, 3.9 Hz, 28H), 0.91 (t, J = 6.9, 3.0 Hz, 19H) ppm. C NMR (400 MHz, CDCl3) δ

159.0, 158.9, 150.1, 150.0, 143.8, 142.9, 138.9, 138.8, 133.0, 132.9, 129.8, 129.5, 128.5, 124.2,

123.6, 123.4, 115.2, 115.0, 114.32, 114.31, 93.1, 93.0, 88.25, 88.18, 68.0, 34.8, 34.7, 34.73, 31.67,

31.4, 29.2, 25.8, 25.4, 22.8, 22.7, 20.8, 14.3, 14.2 ppm. HRMS (ESI-TOF) m/z: [M+Na]+ for

+ [C82H95N3O4Na] 1208.7220, found 1208.7259.

Compound 4.33

In a 200 mL round bottom flak fitted with a magnetic stirrer was added boronic ester diyne 2.10a

(595 mg, 0.900 mmol), 4.32 (614 mg, 0.898 mmol), and K2CO3 (500 mg, 3.60 mmol). The reaction was degassed by bubbling N2 gas for 30 min. Pd(PPh3)4 (10 mg, 0.0086 mmol) was added and the reaction was heated to reflux under nitrogen for 24 h. After reaction was done, it was diluted with water, extracted in DCM, concentrated under reduced pressure and purified by column chromatography (silica gel, DCM:hexane, 1:2) to get 392 mg (yield, 42%) of the product 4.33 as a white

-1 1 solid. Rf = 0.49 (DCM:hexane, 1:2). FTIR (neat) 2929, 2869, 2207, 1605, 1564 cm . H NMR

(400 MHz, CDCl3) δ 7.95 (s, 2H), 7.62 (s, 2H), 7.53 – 7.47 (m, 4H), 7.42 – 7.37 (m, 4H), 6.88 (d,

J = 8.2 Hz, 4H), 6.76 (d, J = 8.4 Hz, 4H), 3.98 (t, J = 6.6 Hz, 4H), 3.88 (t, J = 6.6 Hz, 4H), 1.85 –

1.70 (m, 9H), 1.41 (s, 16H), 1.35 (td, J = 7.7, 3.6 Hz, 16H), 0.92 (q, J = 6.3 Hz, 12H). 180

Compound 4.34

In a 100 mL flame-dried round bottom flask fitted with a magnetic stirrer was added bromotetrayne 4.33 (382 mg, 0.35 mmol) was dissolved in 30 mL of anhydrous THF under nitrogen environment. The solution was cooled to -78 °C and n-BuLi (0.3 mL, 0.50 mmol, 1.6 M in hexane) was added dropwise over 5 min and stirred for 1 hour. Then, the reaction was quenched with isopropoxyboronic acid pinacol ester and warmed to room temperature over 20 min. After that, organic layer extracted in DCM, concentrated under reduced pressure, and purified by column chromatography (silica gel, DCM:hexane, 1:2) to get 300 mg (yield, 75%) of the product 4.34 as

-1 1 a white solid. Rf = 0.25 (DCM:hexane, 1:2). FTIR (neat) 2931, 2204, 1605, 1547 cm . H NMR

(400 MHz, Chloroform-d) δ 7.91 (s, 1H), 7.58 (s, 1H), 7.45 – 7.32 (m, 8H), 6.88 – 6.81 (m, 4H),

6.76 – 6.70 (m, 4H), 3.96 (q, J = 6.4 Hz, 4H), 3.87 (q, J = 6.6 Hz, 4H), 1.84 – 1.69 (m, 9H), 1.44

– 1.37 (m, 20H), 1.38 – 1.28 (m, 22H), 1.28 – 1.20 (m, 9H), 0.94 – 0.87 (m, 12H).

Compound 4.31

181

In a 100 mL flame-dried round bottom flask fitted with a magnetic stirrer was added 30 mL of anhydrous THF. Tetrayne boronic ester 4.34 (100 mg, 0.088 mmol), 1,4-diiodobenzene (12 mg,

0.35 mmol), and silver carbonate (44 mg, 0.16 mmol) were added under nitrogen. The resulting mixture was degassed by bubbling N2 gas for 30 min followed by addition of Pd(PPh3)4 (8 mg,

0.007 mmol). Then the reaction mixture was heated to reflux for 24 h. After reaction was complete, it was diluted with water. Organic layer was extracted in DCM, concentrated under reduced pressure, and purified by column chromatography (silica gel, DCM:hexane, 1:3) to get 88 mg (yield,

88%) of the product 4.31 as a white solid. Rf = 0.37 (DCM:hexane, 1:3). FTIR (neat) 2954, 2930,

-1 1 2206, 1605, 1564 cm . H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 0.8 Hz, 3H), 7.62 (s, 4H), 7.43

– 7.38 (m, 8H), 7.15 – 7.09 (m, 8H), 6.78 – 6.70 (m, 16H), 3.92 (t, J = 6.6 Hz, 8H), 3.85 (t, J = 6.6

Hz, 9H), 1.76 – 1.56 (m, 20H), 1.46 – 1.39 (m, 32H), 1.35 – 1.28 (m, 30H), 0.92 – 0.87 (m, 24H).

Compound 4.51

In a 200 mL round bottom flask, dibromopyrene 4.49 (360 mg, 1.00 mmol) and boronic ester 4.26

(2.30 g, 3.20 mmol) was dissolved in THF (60 mL) and water (15 mL). Potassium carbonate (691 mg, 5.0 mmol) was added and the reaction mixture was degassed by bubbling nitrogen gas for 30 min. Pd(PPh3)4 (35 mg, 0.03 mmol) was added and reaction heated to reflux for 48 h. After reaction was complete, reaction diluted with water. The organic layer was extracted with DCM and dried with Na2SO4. The crude product was concentrated in rotatory evaporator and purified by column chromatography (silica gel, DCM:hexane, 3:2) to get 763 mg (yield, 56%) of pure product 4.51 as 182 a spongy white solid. FTIR (neat) 3431, 2974, 2852, 2208, 1604, 1579 cm-1. 1H NMR (400 MHz,

CDCl3) δ 8.61 (s, 4H), 8.18 (s, 4H), 7.78 (s, 4H), 7.01 – 6.94 (m, 8H), 6.60 – 6.54 (m, 8H), 3.87

(q, J = 7.2 Hz, 8H), 3.73 (t, J = 6.6 Hz, 8H), 1.67 – 1.60 (m, 8H), 1.39 – 1.22 (m, 36H), 0.88 –

13 0.81 (m, 12H) ppm. C NMR (400 MHz, CDCl3) δ 159.2, 142.0, 136.7, 132.9, 130.7, 127.7, 124.4,

124.3, 124.1, 115.1, 114.5, 92.7, 88.6, 68.0, 31.7, 29.2, 25.7, 22.7, 14.1 ppm. HRMS (ESI-TOF)

+ + m/z: [M+H] calcd for [C92H101N6O4] 1352.7806, found 1352.7930.

4.7 References

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4. Anthony, J. E. Angew. Chem. Int. Ed. 2008, 47 (3), 452.

5. Shirota, Y.; Kageyama, H. Chem. Rev. 2007, 107 (4), 953-.

6. Diring, S.; Camerel, F.; Donnio, B.; Dintzer, T.; Toffanin, S.; Capelli, R.; Muccini, M.;

Ziessel, R. J. Am. Chem. Soc. 2009, 131 (50), 18177.

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8. Nichols, V. M.; Rodriguez, M. T.; Piland, G. B.; Tham, F.; Nesterov, V. N.; Youngblood,

W. J.; Bardeen, C. J. J. Phys. Chem. C 2013, 117 (33), 16802.

9. Wenzel, U.; Löhmannsröben, H. G. J. Photoch. Photobiol. A 1996, 96 (1), 13-18.

10. Jinno, K.; Ibuki, T.; Lamparczyk, H.; Okamoto, M.; Tanaka, N.; Fetzer, J. C.; Biggs, W.

R.. Chromatographia 1988, 25 (6), 483. 183

11. Umemoto, T.; Kawashima, T.; Sakata, Y.; Misumi, S. Tetrahedron Lett. 1975, 16 (12),

1005.

12. Mateo-Alonso, A. Chem. Soc. Rev. 2014, 43 (17), 6311.

13. Kawano, S.-i.; Yang, C.; Ribas, M.; Baluschev, S.; Baumgarten, M.; Müllen, K.

Macromolecules 2008, 41 (21), 7933.

14. González, A. Z.; Benitez, D.; Tkatchouk, E.; Goddard, W. A.; Toste, F. D. J. Am. Chem.

Soc. 2011, 133 (14), 5500.

15. Yang, W.; Longhi, G.; Abbate, S.; Lucotti, A.; Tommasini, M.; Villani, C.; Catalano, V.

J.; Lykhin, A. O.; Varganov, S. A.; Chalifoux, W. A. J. Am. Chem. Soc. 2017, 139 (37),

13102.

16. Pogodin, S.; Agranat, I. J. Am. Chem. Soc. 2003, 125 (42), 12829.

17. Merner, B. L.; Unikela, K. S.; Dawe, L. N.; Thompson, D. W.; Bodwell, G. J. Chem.

Commun. 2013, 49 (53), 5930.

18. Merner, B. L.; Dawe, L. N.; Bodwell, G. J. Angew. Chem. Int. Ed. 2009, 48 (30), 5487.

19. Ghasemabadi, P. G.; Yao, T.; Bodwell, G. J. Chem. Soc. Rev. 2015, 44 (18), 6494.

20. Yang, W.; Chalifoux, W. A. Synlett 2017, 28 (06), 625.

21. Tao, W.; Nesbitt, S.; Heck, R. F. J. Org. Chem. 1990, 55 (1), 63.

22. Agrawal, A.; Tratnyek, P. G. Environ. Sci. Technol. 1996, 30 (1), 153.

23. Devasagayaraj, A.; Tour, J. M. Macromolecules 1999, 32 (20), 6425.

24. Nan, G.; Zhu, F.; Wei, Z. Chin. J. Chem. 2011, 29 (1), 72.

25. Sasaki, S.; Suzuki, S.; Igawa, K.; Morokuma, K.; Konishi, G.-i. J. Org. Chem. 2017, 82

(13), 6865.

184

5. Synthesis of tetrasubstituted alkenes starting from a TMS- protected internal alkynes

5.1 Introduction

Alkenes are the planar, unsaturated organic molecules with the general formula CnH2n. The synthesis and chemistry of alkene have always been of interest because of their easy and interesting chemical reactions and they serve as a common substrate for the synthesis of a complex chemical compounds. There are various methods reported for the synthesis of alkenes. Wittig1, Petersons2,

Tebbe3, and alkene metathesis reactions4 are the most useful textbook reactions that are recognized for their excellence towards the synthesis of alkenes. But, these reactions have some serious problems in the synthesis of tetrasubstituted alkenes.5 Alkenes with all of the hydrogens on the double- bonded carbons replaced with alkyl, aryl or any other groups are called tetrasubstituted alkenes.

The syntheses of these fully-substituted alkenes are very difficult, hence there is a paucity of synthetic routes towards these compounds. Adjacent, fully-substituted sp2 centers experience eclips- ing and steric interactions that can distort the double bonds.5 The crystal structure of tetra-aryl substituted ethene (Figure 5-1A), reported by Daik et al. in 1998 showed a distortion of 12° from the plane. The angle between two vicinal aryl groups in this compound is found to be 180°.6 This shows a significant distortion from the regular sp2 geometry. Even the smaller dimethyl-substituted alkene (Figure 5-1B) shows distortion from the planarity by 3-4°.7

185

A B

Figure 5-1: Distortion from a normal trigonal planar structure observed in tetrasubstituted alkenes.

The synthesis of tetrasubstituted alkenes is extremely relevant for the development of biologically active compounds. Various drugs such as Tamoxifen 5.1 (anti-cancer drug), Vioxx 5.2 (anti-in- flammatory drug), and natural products such as Nileprost analogues 5.3 or epi-illudol derivatives

5.4, exhibit biological activity related to the tetrasubstituted alkene within their backbones (Figure

5-2).

Figure 5-2: Biologically active natural products containing tetra-substituted alkenes.

Recently, compounds containing tetrasubstituted alkenes have been examined for their potential as dipeptide mimetics and as polymerization substrates or catalysts.8 Stereodefined tetrasubstituted olefins are also key starting materials for various asymmetric transformations such as hydrogena- tions, osmylations, epoxidations, and other processes that generate contiguous, stereogenic, sp3- 186 hybridized centers.9,10,11,12 Tetrasubstituted alkenes such as compounds 5.5-5.8 (Figure 5-3) have also been found useful in material chemistry, because of their interesting physical, electronic, and structural properties. A number of studies have reported about the helicenes containing fully substituted alkenes and they have been found to be a potential liquid crystal materials13. Because of the unusual twisting in the tetrasubstituted alkenes, they can induce axial chirality when incorporated into the backbone of the structure. Conformationally-locked, fully-substituted alkenes have also been utilized in electronic devices such as molecular switches, data storage, and chiroptical devices.5, 14-16

Figure 5-3: Examples of tetra-substituted alkenes used in organo-electronic devices.

5.2 Alkynes as a tetrasubstituted alkene precursors

As mentioned in chapter 1, alkynes are high energy substrates than can undergo a variety of chemical transformations that results in the formation of number of different compounds. There are number of classic reactions that can be used for the formation of alkene products starting from alkynes. For instance, partial reduction of alkynes with Lindlar’s catalyst stereoselectively results in the formation of (Z)-alkene with low amount of Z/E isomerization.17 Dissolved metal reduction of alkynes produces exclusively (E)-alkenes. The halogenation of alkynes affords halogen- 187 functionalized alkenes. Alkynes has also been reported as a good precursor for the synthesis of fully substituted alkenes.

Carbometallation of alkynes is one of the most widely used methods for the synthesis of tetrasubstituted alkenes with high degree of regio- and stereocontrol.18 Copper19, boron20, nickel21, mag- nesium22, zinc23, zirconuim24 are common metals used in the carbometallation of alkynes (Scheme

5-1). Palladium-catalyzed stereoselective synthesis of tetrasubstituted alkenes starting from alkynes has been reported by Tsukamoto et al. to afford a library of six-membered allylic alcohols with endo-tri- or tetrasubstituted olefins.25

Scheme 5-1: Carbometallation of alkynes resulting tetrasubstituted alkenes.

Several reports have been published on the synthesis of tetrasubstituted alkenes by direct functionalization of alkynes. Trost and Pinkerton found serendipitous formation of tetrasubstituted alkene 188

5.26 when they were studying Ru-catalyzed stereoselective synthesis of vinyl halides starting from internal alkynes 5.24 (Scheme 5-2).26

Scheme 5-2: Ruthenium-catalysed functionalization of alkyne yielding tetrasubstituted alkene.

In 2002, Raschke et al. reported an efficient synthesis of tetrasubstituted alkenes by palladium- catalyzed domino-Heck double-cyclization in good yields. Alkyne 5.27, when heated with potassium acetate in DMF and tetrapropylammonium bromide in the presence of a catalytic amount of

27 Pd(PPh3)4, yielded cyclic, substituted alkene 5.28 as the product in 73% yield (Scheme 5-3).

Scheme 5-3: Palladium-catalyzed domino-Heck double cyclization yielding tetrasubstituted alkene.

Another interesting economical direct functionalization of alkynes was reported by Hosomi group in 2001, wherein they utilized iron-catalyzed regio- and stereoselective carbolithiation for the synthesis of tetrasubstituted alkenes. They treated 3-pentynyl ether 5.29 with n-BuLi and added iron

(III) salt followed by addition of electrophiles to obtain tetrasubstituted alkene 5.30 (Scheme 5-

4).28 189

Scheme 5-4: Hosomi's iron-catalyzed synthesis of tetrasubstituted alkene.

The Larock group reported the multicomponent one pot synthesis of tetrasubstituted alkene by utilizing palladium-catalyzed direct functionalization of alkynes. They treated aryl iodide 5.32, aryl boronic ester 5.31, and an internal alkyne 5.33 in DMF/water, with palladium catalyst to get tetrasubstituted alkene 5.34 in 72% yield with reasonable regioselectivity (Scheme 5-5).29

Scheme 5-5: Larock's multicomponent one-pot synthesis of tetrasubstituted alkene.

5.3 Our strategy for the synthesis of tetrasubstituted alkenes

Halogenation of alkynes is an introductory organic chemistry textbook reaction in which two halogen atoms are added to the two triple-bonded carbons of an alkyne resulting in the formation of vicinal dihaloalkenes. Typically, these reactions occur stereoselectively giving anti- products. For instance, we can look at the example of addition of Br2 in 2-butyne 5.35. The first step is the electrophilic addition of bromine resulting in the formation of the bromonium intermediate 5.36.

Then, there is nucleophilic attack by bromide ion resulting in the formation of anti-dihalogen substituted alkene 5.37 (Figure 5-4).30 190

Figure 5-4: Classical anti-dibromination of alkyne.

While studying ICl-mediated two-fold alkyne benzannulation reaction of 2,6-dialkynylbiphenyl

5.38 to get 5,9-diiodopyrene 5.39, we observed serendipitous formation of double ICl addition product 5.40 in excellent yield (Scheme 5-6). The ICl addition occurred through syn-facial selectively overriding the classical anti-addition.31 Similar reaction of the desilylated compound 5.41 afforded anti-addition product 5.42.

Scheme 5-6: ICl addition generating bis(Z)-haloalkene and bis(E)-haloalkene.

Based on these observation, we can conclude that TMS-group is playing a pivotal role in the observed regioselectivity. What we think is, the β-silyl effect favors the formation of stabilized 191 cationic intermediate 5.47, disrupting the formation of iodonium intermediate 5.45 leading toward the formation of syn-product 5.48 (Scheme 5-7).31

Scheme 5-7: Mechanism of syn-dihalogenation.

With this highly functionalized vicinal dihalosilyl alkene in hand, we planned to further utilize the newly installed halogens and the trimethylsilyl (TMS) group as synthetic handles to arrive at tetrasubstituted alkenes. With the vinyl iodides, we planned to carry out Sonogashira or Suzuki cross-coupling which will be the first step toward tetrasubstituted alkene. With the chlorine in the molecule, we planned to utilize Kumada coupling or Grignard reactions. The TMS groups remaining in the molecule can be further modified. For instances, we can convert TMS group easily into iodo-group by treating with molecular iodine or can be carbonylated via hydromagnesiation.32, 33

Hence, this method will be an efficient stepwise route toward the tri- and tetrasubstituted alkenes.

5.4 Synthesis of bis(Z)-haloalkene 5.51

The starting material, phenyl-TMS-acetylene 5.50, was synthesized using a literature procedure.34

Phenylacetylene 5.49 was treated with n-BuLi and the resulting lithium acetylide was quenched 192 with TMSCl to get phenyl-TMS-acetylene. Compound 5.50 was then treated with iodine monochloride at -78 °C to get the syn-dihalosilyl alkene 5.51 as product (Scheme 5-8).31

Scheme 5-8: Synthesis of syn-dihalo-TMS-alkene starting 5.51.

We first tried to utilize the vinyl iodide group of compound 5.51 as the very first synthetic handle to synthesize tetrasubstituted alkene. We decided to carry out Sonogashira cross-coupling of the iodo group in compound 5.51 with ethynyl benzene. For that, starting materials 5.51 and 5.52 were dissolved in anhydrous THF and taken through the Sonogashira cross-coupling conditions. After stirring for 20 hours, an the aliquot was taken and NMR study showed that product 5.53 was not formed (Scheme 5-9). Then, the reaction was heated at 80 °C for another 12 hours. Even after heating for 12 hours, and still there was no desired product formed.

Scheme 5-9: Attempted Sonogashira cross-coupling of vinyl iodide with phenyl acetylene.

193

S.N. alkyne Pd catalyst ligand Amine Solvent T Time yield (°C) (h) 1 Pd(PPh3)2Cl2 Et3N THF 90 24 Nd

2 Pd(PPh3)2Cl2 Et3N THF 90 24 Nd

3 Pd(PPh3)2Cl2 PPh3 Et3N THF 90 24 Nd

4 Pd(PPh3)2Cl2 Et3N THF 90 24 Nd

5 Pd(PPh3)Cl2 PPh3 Et3N THF 90 24 Nd

6 Pd(PPh3)2Cl2 dppf i)ipr2NH THF 90 24 Nd ii) Et3N 7 Pd(PPh3)2Cl2 dppp Et3N THF 90 24 Nd

8 Pd(PPh3)2Cl2 xPhos Et3N NMP 90 24 Nd

9 Pd(PPh3)2Cl2 dppe Et3N DMF 120 36 Nd

10 Pd(dba)2 piperidine DMF 120 36 Nd

11 Pd(dba)2 P(t-bu)3 piperidine DMF 120 36 Nd

12 Pd(OAc)2 dppf TBAF NMP r.t. 12 to Nd to 90 24

Table 5-1: Screening of Sonogashira cross-coupling of vinyl halide with ethynyl benzene deriva-

tives.

We screened a series of alkynes, palladium catalysts, ligands, bases, reaction time, temperature,

and solvents (Table 5-1).35 We varied the alkyne to p-methylethynylbenzene and p-methoxy-

ethynylbenzene and repeated the reaction which was unable to afford cross-coupled product. Elec-

tron rich alkynes generally show less reactivity towards Sonogashira cross-coupling reactions.36

So, we also attempted the cross-coupling reactions with electron poor alkynes (Entries 3 to 11) in

the presence of various Pd-catalysts and ligands but that was also unable to afford cross-coupled 194 product. After screening a number of conditions, it appears that the Sonogashira cross-coupling on a vinyl iodide in tetrasubstituted alkene is difficult.

We then moved to utilizing another powerful organometallic reaction, Suzuki cross- coupling, in our system. We first attempted the Suzuki cross- coupling on iodo-group of compound 5.51 with phenyl boronic acid 5.54. The reaction mixture was heated at 90 °C for up to 48 hours. There was no product 5.55 formed and all of the starting materials were recovered.

Scheme 5-10: Attempted Suzuki cross-coupling of vinyl iodide with phenyl boronic acid.

The reaction was repeated under different conditions (Table 5-2) to optimize the reaction conditions. We screened palladium catalysts, ligands, temperature, solvents, and bases. None of the conditions afforded desired cross-coupled product 5.55. based on these observations, it can be concluded that the bulky Pd-catalysts can not get enough space for oxidative addition or reductive elimination.

195

S.N. Catalyst Ligands Base Solvent Temp Time Yield (°C) (h) (%) 1 Pd(PPh3)4 K2CO3 THF:H2O:EtOH 90 24 Nd (10:2:5) 2 Pd(PPh3)4 Et4NOH Toluene 110 24 Nd

3 Pd(OAc)2 PPh3 K2CO3 THF:H2O:EtOH 90 24 Nd (10:2:5) 4 Pd(OAc)2 dppf K2CO3 THF:H2O:EtOH 90 24 Nd (10:2:5) 5 Pd(OAc)2 dppe K2CO3 THF:H2O:EtOH 90 24 Nd (10:2:5) 6 Pd(dba)2 xPhos K3PO4 THF:H2O 100 24 Nd (10:1) 7 Pd(Cl2(PPh3)2 Na2CO3 THF:H2O 90 24 Nd (10:1) 8 Ni(cod)2 PCy3 K2CO3 THF 90 48 Nd 9 Pd(dppf)Cl2·CH2Cl2 tBuNH2 iPrOH:H2O 95 24 Nd (1:1) 10 Pd(acac)2 XantPhos K3PO4 + dioxane 135 24 Nd CsF t 11 Pd2(dba)3 P Bu3 KOH THF 90 24 Nd

Table 5-2: Screening of the conditions for Suzuki cross-coupling of vinyl iodide with phenyl boronic acid.

Our next attempt was Negishi cross-coupling which is cross-coupling reaction of an aryl/vinyl halide with aryl zinc chloride. We synthesized an aryl zinc reagent, 5.57, following the literature procedure starting from the iodobenzene 5.56.37 We carried out lithium-halogen exchange of phenyl iodide 5.56 and the resulting carbanion was treated with zinc chloride to afford phenyl zinc chloride 5.57 in 75% yield. Phenyl zinc chloride 5.57 was taken through Negishi cross-coupling conditions with vinyl iodide 5-51 using Ni(cod)2 catalyst (Scheme 5-11). There was no desired product formed and starting material 5-51 was recovered. 196

Scheme 5-11: Attempted Negishi cross-coupling of phenyl zinc iodide with vinyl iodide.

The reaction was attempted using the procedure reported by Lipshutz and coworkers.38 Compound

5.51 was treated with n-decyl zinc iodide 5.58 (prepared following the literature procedure39) using palladium acetate as a catalyst and xPhos as a ligand at room temperature (Scheme 5-12). There was, again, no product 5.59 formed. Furthermore, heating the reaction to 90 °C for 24 h was also unsuccessful.

Scheme 5-12: Failed Negishi cross-coupling of decyl zinc iodide with vinyl iodide.

We tried to reverse the zinc reagent by synthesizing vinyl zinc chloride 5.60. We treated compound

5.51 with n-BuLi and the resulting intermediate was allowed to react with added zinc chloride. We observed the formation of the phenyl-TMS-acetylene 5.50 and no 5.61 was detected. This shows that the intermediate 5.60 obtained by lithium-halogen exchange readily undergoes syn-elimination before it reacts with zinc chloride (Scheme 5-13). 197

Scheme 5-13: Failed attempt to synthesize vinyl zinc iodide.

Following this failed attempt, we tried to trap the vinyl lithium intermediate 5.60 with benzaldehyde (Scheme 5-14). This time, we did lithium-halogen exchange of compound 5.51 for short time

(10 min) to minimize/prevent syn-elimination. The intermediate 5.60 was treated with benzaldehyde and stirred for another 40 minutes while letting the reaction mixture to warm up to room temperature. This strategy also failed and we, again, obtained only phenyl-TMS-acetylene 5.50.

All of these experiments shows that the intramolecular syn-elimination is faster than the intramolecular reaction of vinyl lithium intermediate 5.60 with external electrophiles.

Scheme 5-14: Attempted trapping of vinyl carbanion with benzaldehyde.

Next, we did a control experiment (Scheme 5-15) to know if we could trap the resulting vinylic carbanion with a proton, we carried out the lithium-halogen exchange of compound 5.51 followed by addition of water. Again, we got phenyl-TMS-acetylene 5.50 as a product. Our understanding of the formation of alkyne 5.50 is that elimination of ICl is faster than trapping of the vinylic carbanion with any other electrophile. 198

Scheme 5-15: Control experiment to trap vinyl carbanion with water.

5.5 Conclusion:

We attempted to broaden the scope of tetrasubstituted syn-dihalosilyl alkenes utilizing various cross-coupling reactions starting from the commercially available, cheap starting materials (phenyl-TMS-acetylene and iodine monochloride). This would be mild, controlled, stepwise route towards the tetra-alkyl substituted alkenes. We tried some of the very powerful organometallic cross- coupling reactions (such as Sonogashira, Suzuki, and Negishi cross-coupling) which were unable to afford desired tetrasubstituted alkenes. We also tried the lithium-halogen exchange of the vinyl iodide followed by trapping of the anion intermediate with some electrophiles that was also unsuccessful. The syn-elimination of the ICl was faster than the intermolecular trapping of those vinyl anions. We believe that further screening of other more reactive palladium catalysts, bases, ligands and reaction conditions are required to make these reactions to happen. There are several other things to try in future on these substrates. We can try the Stille coupling of vinyl iodide with tin reagents to afford divinyl ketones.40 Copper-catalyzed cross coupling of vinyl iodide and thiols are also reported to yield vinyl sulfides.41

199

5.6 References

1. Schlosser, M., Stereochemistry of the Wittig reactions. Topics in Stereochemistry 1970,

5, pp 1-30.

2. van Staden, L. F.; Gravestock, D.; Ager, D. J. Chem. Soc. Rev. 2002, 31 (3), 195.

3. Clift, S. M.; Schwartz, J. J. Am. Chem. Soc. 1984, 106 (26), 8300.

4. Fürstner, A., Alkene metathesis in organic synthesis. Springer: 2003; Vol. 1.

5. Flynn, A. B.; Ogilvie, W. W. Chem. Rev. 2007, 107 (11), 4698.

6. Daik, R.; James Feast, W.; S. Batsanov, A.; A. K. Howard, J. New J. Chem. 1998, 22

(10), 1047.

7. Tietze, L. F.; Kahle, K.; Raschke, T. Chem. Eur. J. 2002, 8 (2), 401.

8. Oishi, S.; Miyamoto, K.; Niida, A.; Yamamoto, M.; Ajito, K.; Tamamura, H.; Otaka,

A.; Kuroda, Y.; Asai, A.; Fujii, N. Tetrahedron 2006, 62 (7), 1416.

9. Tang, W.; Wu, S.; Zhang, X. J. Am. Chem. Soc. 2003, 125 (32), 9570.

10. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94 (8), 2483.

11. Adam, W.; Blancafort, L. J. Am. Chem. Soc. 1996, 118 (20), 4778.

12. Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103 (8), 2829.

13. Harada, N.; Saito, A.; Koumura, N.; Uda, H.; de Lange, B.; Jager, W. F.; Wynberg,

H.; Feringa, B. L. J. Am. Chem. Soc. 1997, 119 (31), 7241.

14. Vicario, J.; Walko, M.; Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2006, 128 (15),

5127.

15. Jager, W. F.; de Jong, J. C.; de Lange, B.; Huck, N. P.; Meetsma, A.; Feringa, B. L.

Angew. Chem. Int. Ed. 1995, 34 (3), 348.

16. Feringa, B. L.; Jager, W. F.; de Lange, B. Tetrahedron 1993, 49 (37), 8267. 200

17. Campos, K. R.; Cai, D.; Journet, M.; Kowal, J. J.; Larsen, R. D.; Reider, P. J. The J.

Org. Chem. 2001, 66 (10), 3634.

18. Normant, J. F.; Alexakis, A. Synth. 1981, 1981 (11), 841.

19. Corey, E. J.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1969, 91 (7), 1851.

20. Chu, K. H.; Wang, K. K. J. Org. Chem. 1986, 51 (5), 767.

21. Shirakawa, E.; Yamasaki, K.; Yoshida, H.; Hiyama, T. J. Am. Chem. Soc. 1999, 121

(43), 10221.

22. Mornet, R.; Gouin, L. Tetrahedron Lett. 1977, 18 (2), 167.

23. Stüdemann, T.; Ibrahim-Ouali, M.; Knochel, P. Tetrahedron 1998, 54 (7), 1299.

24. Negishi, E. Acc. Chem. Res. 1987, 20 (2), 65.

25. Tsukamoto, H.; Ueno, T.; Kondo, Y. J. Am. Chem. Soc. 2006, 128 (5), 1406.

26. Trost, B. M.; Pinkerton, A. B. J. Am. Chem. Soc. 2002, 124 (25), 7376.

27. Tietze, L. F.; Kahle, K.; Raschke, T. Chem. Eur. J. 2002, 8 (2), 401.

28. Hojo, M.; Murakami, Y.; Aihara, H.; Sakuragi, R.; Baba, Y.; Hosomi, A. Angew.

Chem. Int. Ed. 2001, 40 (3), 621.

29. Zhou, C.; Larock, R. C. J. Org. Chem. 2005, 70 (10), 3765.

30. Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H.; Curran, D. P. J. Am. Chem. Soc.

2002, 124 (44), 12946.

31. Sproul, K. C.; Chalifoux, W. A. Org. Lett. 2015, 17 (13), 3334.

32. Katsukiyo, M.; Yoshifumi, I.; Kyoko, N.; Keigo, F.; Koichiro, O.; Kiitiro, U. B. Chem.

Soc. Jpn 1989, 62 (1), 143.

33. Zhao, H.; Cai, M.-Z. Synth. Commun. 2003, 33 (10), 1643. 201

34. Shimbo, D.; Shibata, A.; Yudasaka, M.; Maruyama, T.; Tada, N.; Uno, B.; Itoh, A.

Org. Lett. 2019, 21 (23), 9769.

35. Chinchilla, R.; Nájera, C. Chem. Soc. Rev. 2011, 40 (10), 5084.

36. Sonogashira, K. J. Organomet. Chem. 2002, 653 (1), 46.

37. Hernán-Gómez, A.; Herd, E.; Hevia, E.; Kennedy, A. R.; Knochel, P.; Koszinowski,

K.; Manolikakes, S. M.; Mulvey, R. E.; Schnegelsberg, C. Angew. Chem. Int. Ed. 2014,

53 (10), 2706.

38. Krasovskiy, A.; Lipshutz, B. H. Org. Lett. 2011, 13 (15), 3822.

39. Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem. 1988, 53 (10), 2390.

40. Goure, W. F.; Wright, M. E.; Davis, P. D.; Labadie, S. S.; Stille, J. K. Am. Chem. Soc.

1984, 106 (21), 6417.

41. Kabir, M. S.; Van Linn, M. L.; Monte, A.; Cook, J. M. Org. Lett. 2008, 10 (15), 3363.

202

Appendixes

203

Appendix-1

A-1.1 Synthesis of 1,2-diketo-functionalized skipped cyclohexadiene†

Skipped cyclohexadiene also known as 1,4-cyclohexadienes are important structural motifs and serve as intermediates in the synthesis of a number of biologically active natural products.1-6 They are a cyclic tetrasubstituted alkenes with two double bonds separated by a single sp3-carbon and can undergo a variety of reactions yielding functionalized useful cyclic intermediates/products.7

However, there are a limited number of methods for the synthesis of skipped dienes. The most common method used for the synthesis of skipped dienes is dissolved metal reduction of arenes, also known as the Birch reduction. The product obtained from the birch reduction is highly dependent on the nature of the substituent on the parent arene. Electron donating group substituted benzene 1 lead to the product 2 with the most highly substituted double bond while electron withdrawing group substituted benzene 3 affords least substituted skipped diene 4. (Scheme A-1).8-11

Hence, a mild, easy, and functional group tolerant synthetic method towards skipped dienes is still demanding.

Scheme A-1: Synthesis of skipped cyclo-1,4-hexadiene through Birch reduction.

† This work has been included in a publication (Hamal, K. B.; Sitaula, P.; Chalifoux, W. A. Eur. J. Org.

Chem. 2019 (6), 1225) 204

One of my senior colleagues, Dr. Khagendra Hamal, studied the synthesis of a library of highly functionalized skipped dienes 6 starting from diynones 5. He also studied the applications of these important structural motifs towards the synthesis of bicyclic furan derivatives 7 via copper-catalyzed alkyne cyclization reactions (Scheme A2). He has also showed the further chemical modifications of the skipped diene 7 to arrive at bicyclic compounds of diverse functionalities.7, 12

Scheme A-2: Synthesis of bicyclic furan via copper-catalyzed alkyne cyclization reactions.

When the copper catalyst was switched to silver nitrate, skipped diene 6 afforded dihydroiosben- zofuran carboxaldehyde derivatives 8 through a sequential protodesilylation/oxidation/cyclization reactions.13 Dr. Hamal screened the scoped of reaction with various aryl and heteroaryl groups as

R1, and aryl, heteroaryl, and alkyl groups as R2.The reaction was robust with moderate to excellent yields of 51 to 91%.

Scheme A-3: Synthesis of dihydroisobenzofuran carboxaldehyde via silver catalyzed alkyne cyclization. 205

Building on Hamal's work, I attempted to further expand the scope of the reaction by including various alkyl groups as R1 (Scheme A-4). With R1 as alkyl groups, we serendipitously observed the formation of diketo-functionalized skipped dienes as the products 9a and 9b.

Scheme A-4: Synthesis of vicinal diketone functionalized skipped dienes.

Our understanding for the formation of diketo skipped dienes is shown in the Scheme A-5.13 From the control experiment, we found that the first step is the disilylation of the TMS-protected alkyne

6, resulting in the formation of terminal alkyne 10. Then, it gets converted to an oxocarbenium intermediate 11, which can proceed via either of two pathways. When, R1 group is an aryl or heteroaryl, the intermediate goes through the path I, resulting in the formation of dihydroisobenzofuran carboxaldehydes 8. But, when R1 is an alkyl group, oxocarbenium intermediate 11 follows path II through intermediate 12 resulting in the formation of diketo functionalized skipped dienes

9. 206

Scheme A-5: Mechanism of formation of dihydroisobenzofuran carboxaldehyde (path I) and diketo skipped diene (path II).

A-1.2 References 1. Payette, J. N.; Yamamoto, H. Angew. Chem. Int. Ed. 2009, 48 (43), 8060.

2. Ishihara, K.; Fushimi, M. J. Am. Chem. Soc. 2008, 130 (24), 7532.

3. Liu, L.-Z.; Han, J.-C.; Yue, G.-Z.; Li, C.-C.; Yang, Z. J. Am. Chem. Soc. 2010, 132 (39),

13608.

4. Winkler, J. D.; Holland, J. M.; Peters, D. A. J. Org. Chem. 1996, 61 (26), 9074.

5. Kraus, G. A.; Taschner, M. J. J. Am. Chem. Soc. 1980, 102 (6), 1974.

6. Doherty, S.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Organometallics 2009, 28 (17),

5273.

7. Hamal, K. B.; Bam, R.; Chalifoux, W. A. Synlett 2016, 27 (14), 2161.

8. Zimmerman, H. E. Tetrahedron 1961, 16 (1-4), 169.

9. Birch, A. J. Chem. Soc. 1944, 430, 436.

10. Donohoe, T. J.; House, D. J. Org. Chem. 2002, 67 (14), 5015. 207

11. Lei, P.; Ding, Y.; Zhang, X.; Adijiang, A.; Li, H.; Ling, Y.; An, J. Org. lett. 2018, 20

(12), 3439.

12. Hamal, K. B.; Chalifoux, W. A. J. Org. Chem. 2017, 82 (23), 12920.

13. Hamal, K. B.; Sitaula, P.; Chalifoux, W. A. Eur. J. Org. Chem. 2019, 1225.

208

Appendix-2

1 13 H and C NMR spectra of new compounds

209

2. Synthesis, Characterizations and Photophysical Properties of [5]helicene-like π-Extended Naphtho[1,2-a]pyrenes

1 13 H and C NMR spectra of new compounds

210

1 Figure 1: H NMR spectrum of compound 2.17c in CDCl3 at 298 K.

13 Figure 2: C NMR spectrum of compound 2.17c in CDCl3 at 298 K.

211

1 Figure 3: H NMR spectrum of compound 2.17e in CDCl3 at 298 K.

13 Figure 4: H NMR spectrum of compound 2.17e in CDCl3 at 298 K. 212

1 Figure 5: H NMR spectrum of compound 2.17f in CDCl3 at 298 K.

13 Figure 6: C NMR spectrum of compound 2.17f in CDCl3 at 298 K.

213

1 Figure 7: H NMR spectrum of compound 2.17g in CDCl3 at 298 K.

13 Figure 8: C NMR spectrum of compound 2.17g in CDCl3 at 298 K. 214

1 Figure 9: H NMR spectrum of compound 2.17h in CDCl3 at 298 K.

1 Figure 10: H NMR spectrum of compound 2.17h in CDCl3 at 298 K.

215

1 Figure 11: H NMR spectrum of compound 2.17j in CDCl3 at 298 K.

13 Figure 12: C NMR spectrum of compound 2.17j in CDCl3 at 298 K.

216

1 Figure 13: H NMR spectrum of compound 2.10c in CDCl3 at 298 K.

13 Figure 14: C NMR spectrum of compound 2.10c in CDCl3 at 298 K. 217

1 Figure 15: H NMR spectrum of compound 2.10d in CDCl3 at 298 K.

13 Figure 16: C NMR spectrum of compound 2.10d in CDCl3 at 298 K.

218

1 Figure 17: H NMR spectrum of compound 2.10e in CDCl3 at 298 K.

13 Figure 18: C NMR spectrum of compound 2.10e in CDCl3 at 298 K.

219

1 Figure 19: H NMR spectrum of compound 2.10f in CDCl3 at 298 K.

13 Figure 20: C NMR spectrum of compound 2.10f in CDCl3 at 298 K. 220

1 Figure 21: H NMR spectrum of compound 2.10h in CDCl3 at 298 K.

13 Figure 22: C NMR spectrum of compound 2.10h in CDCl3 at 298 K. 221

1 Figure 23: H NMR spectrum of compound 2.10i in CDCl3 at 298 K.

13 Figure 24: C NMR spectrum of compound. 2.10i in CDCl3 at 298 K.

222

1 Figure 25: H NMR spectrum of compound 2.8a in CDCl3 at 298 K.

13 Figure 26: C NMR spectrum of compound 2.8a in CDCl3 at 298 K.

223

1 Figure 27: H NMR spectrum of compound 2.8b in CDCl3 at 298 K.

13 Figure 28: C NMR spectrum of compound 2.8b in CDCl3 at 298 K.

224

1 Figure 29: H NMR spectrum of compound 2.8c in CDCl3 at 298 K.

13 Figure 30: C NMR spectrum of compound 2.8c in CDCl3 at 298 K.

225

1 Figure 31: H NMR spectrum of compound 2.8d in CDCl3 at 298 K.

13 Figure 32: C NMR spectrum of compound 2.8d in CDCl3 at 298 K.

226

1 Figure 33: H NMR spectrum of compound 2.8e in CDCl3 at 298 K.

13 Figure 34: C NMR spectrum of compound 2.8e in CDCl3 at 298 K. 227

1 Figure 35: H NMR spectrum of compound 2.8f in CDCl3 at 298 K.

13 Figure 36: C NMR spectrum of compound 2.8f in CDCl3 at 298 K.

228

1 Figure 37: H NMR spectrum of compound 2.8g in CDCl3 at 298 K.

229

13 Figure 38: C NMR spectrum of compound 2.8g in CDCl3 at 298 K.

1 Figure 39: H NMR spectrum of compound 2.8h in CDCl3 at 298 K.

230

13 Figure 40: C NMR spectrum of compound 2.8h in CDCl3 at 298 K.

1 Figure 41: H NMR spectrum of compound 2.8i in CDCl3 at 298 K.

231

13 Figure 42: C NMR spectrum of compound 2.8i in CDCl3 at 298 K.

1 Figure 43: H NMR spectrum of compound 2.8j in CDCl3 at 298 K.

232

13 Figure 44: C NMR spectrum of compound 2.8j in CDCl3 at 298 K.

1 Figure 45: H NMR spectrum of compound 2.8k in CDCl3 at 298 K. 233

13 Figure 46: C NMR spectrum of compound 2.8k in CDCl3 at 298 K.

1 Figure 47: H NMR spectrum of compound 2.8l in CDCl3 at 298 K.

234

13 Figure 48: C NMR spectrum of compound 2.8l in CDCl3 at 298 K.

1 Figure 49: H NMR spectrum of compound 2.8m in CDCl3 at 298 K. 235

13 Figure 50: C NMR spectrum of compound 2.8m in CDCl3 at 298 K.

1 Figure 51: H NMR spectrum of compound 2.7a in CDCl3 at 298 K.

236

13 Figure 52: C NMR spectrum of compound 2.7a in CDCl3 at 298 K.

1 Figure 53: H NMR spectrum of compound 2.7b in CDCl3 at 298 K.

237

13 Figure 54: C NMR spectrum of compound 2.7b in CDCl3 at 298 K.

1 Figure 55: H NMR spectrum of compound 2.7c in CDCl3 at 298 K.

238

13 Figure 56: C NMR spectrum of compound 2.7c in CDCl3 at 298 K.

1 Figure 57: H NMR spectrum of compound 2.7d in CDCl3 at 298 K.

239

13 Figure 58: C NMR spectrum of compound 2.7d in CDCl3 at 298 K.

1 Figure 59: H NMR spectrum of compound 2.7e in CDCl3 at 298 K.

240

13 Figure 60: C NMR spectrum of compound 2.7e in CDCl3 at 298 K.

1 Figure 61: H NMR spectrum of compound 2.7f in CDCl3 at 298 K.

241

13 Figure 62: C NMR spectrum of compound 2.7f in CDCl3 at 298 K.

1 Figure 63: H NMR spectrum of compound 2.7g in CDCl3 at 298 K.

242

13 Figure 64: C NMR spectrum of compound 2.7g in CDCl3 at 298 K.

1 Figure 65: H NMR spectrum of compound 2.7h in CDCl3 at 298 K. 243

13 Figure 66: C NMR spectrum of compound 2.7h in CDCl3 at 298 K.

1 Figure 67: H NMR spectrum of compound 2.7i in CDCl3 at 298 K.

244

13 Figure 68: C NMR spectrum of compound 2.7i in CDCl3 at 298 K.

1 Figure 69: H NMR spectrum of compound 2.7j in CDCl3 at 298 K.

245

13 Figure 70: C NMR spectrum of compound 2.7j in CDCl3 at 298 K.

1 Figure 71: H NMR spectrum of compound 2.7k in CDCl3 at 298 K.

246

13 Figure 72: C NMR spectrum of compound 2.7k in CDCl3 at 298 K.

3. Synthesis of HBC-based π-extended nanographenes via alkyne benzannulation reactions

1 13 H and C NMR spectra of new compounds

247

1 Figure 73: HNMR spectrum of compound 3.33 in CDCl3 at 298 K.

248

13 Figure 74: C NMR spectrum of compound 3.33 in CDCl3 at 298 K.

1 Figure 75: H NMR spectrum of compound 3.18 in CDCl3 at 298 K.

249

13 Figure 76: C NMR spectrum of compound 3.18 in CDCl3 at 298 K.

1 Figure 77: H NMR spectrum of compound 3.42 in CDCl3 at 298 K. 250

13 Figure 78: H NMR spectrum of compound 3.42 in CDCl3 at 298 K.

1 Figure 79: H NMR spectrum of compound 3.19 in CDCl3 at 298 K.

251

13 Figure 80: C NMR spectrum of compound 3.19 in CDCl3 at 298 K.

13 Figure 81: H NMR spectrum of compound 3.47 in CDCl3 at 298 K.

252

13 Figure 82: C NMR spectrum of compound 3.47 in CDCl3 at 298 K.

1 Figure 83: H NMR spectrum of compound 3.20a in CDCl3 at 298 K. 253

13 Figure 84: C NMR spectrum of compound 3.20a in CDCl3 at 298 K.

1 Figure 85: H NMR spectrum of compound 3.20b in CDCl3 at 298 K.

254

13 Figure 86: C NMR spectrum of compound 3.20b in CDCl3 at 298 K.

13 Figure 87: C NMR spectrum of compound 3.74a in CDCl3 at 298 K.

255

13 Figure 88: C NMR spectrum of compound 3.74a in CDCl3 at 298 K.

1 Figure 89: H NMR spectrum of compound 3.74b in CDCl3 at 298 K.

256

13 Figure 90: C NMR spectrum of compound 3.74b in CDCl3 at 298 K.

1 Figure 91: H NMR spectrum of compound 3.21a in CDCl3 at 298 K.

257

13 Figure 92: C NMR spectrum of compound 3.21a in CDCl3 at 298 K.

1 Figure 93: H NMR spectrum of compound 3.94 in CDCl3 at 298 K.

258

13 Figure 94: C NMR spectrum of compound 3.94 in CDCl3 at 298 K.

259

1 Figure 95: H NMR spectrum of compound 3.95 in CDCl3 at 298 K.

260

1 Figure 96: H NMR spectrum of compound 3.97 in CDCl3 at 298 K.

1 Figure 97: H NMR spectrum of compound 3.97 in CDCl3 at 298 K.

261

1 Figure 98: H NMR spectrum of compound 3.98 in CDCl3 at 298 K.

13 Figure 99: C NMR spectrum of compound 3.98 in CDCl3 at 298 K.

262

1 Figure 100: H NMR spectrum of compound 3.99 in CDCl3 at 298 K.

13 Figure 101: C NMR spectrum of compound 3.99 in CDCl3 at 298 K. 263

1 Figure 102: H NMR spectrum of compound 3.100 in CDCl3 at 298 K.

13 Figure 103: C NMR spectrum of compound 3.100 in CDCl3 at 298 K.

264

4. Synthesis of longer pyrenacenes

1 13 H and C NMR spectra of new compounds

265

1 Figure 104: H NMR spectrum of compound 4.21 in CDCl3 at 298 K.

13 Figure 105: C NMR spectrum of compound 4.21 in CDCl3 at 298 K. 266

1 Figure 106: H NMR spectrum of compound 4.22 in CDCl3 at 298 K.

267

1 Figure 107: H NMR spectrum of compound 4.23 in CDCl3 at 298 K.

13 Figure 108: C NMR spectrum of compound 4.23 in CDCl3 at 298 K.

268

1 Figure 109: H NMR spectrum of compound 4.26 in CDCl3 at 298 K.

13 Figure 110: C NMR spectrum of compound 4.26 in CDCl3 at 298 K. 269

1 Figure 111: H NMR spectrum of compound 4.25 in CDCl3 at 298 K.

13 Figure 112: C NMR spectrum of compound 4.25 in CDCl3 at 298 K.

270

1 Figure 113: H NMR spectrum of compound 4.28 in CDCl3 at 298 K.

13 Figure 114: C NMR spectrum of compound 4.28 in CDCl3 at 298 K.

271

Figure 115: 1H NMR spectrum of compound 4.16 in CDCl3 at 298 K.

13 Figure 116: C NMR spectrum of compound 4.16 in CDCl3 at 298 K.

272

1 Figure 117: H NMR spectrum of compound 4.15 in CDCl3 at 298 K.

13 Figure 118: C NMR spectrum of compound 4.15 in CDCl3 at 298 K.

273

1 Figure 119: H NMR spectrum of compound 4.36 in CDCl3 at 298 K.

13 Figure 120: c NMR spectrum of compound 4.36 in CDCl3 at 298 K. 274

1 Figure 121: H NMR spectrum of compound 4.33 in CDCl3 at 298 K.

1 Figure 122: H NMR spectrum of compound 4.34 in CDCl3 at 298 K.

275

1 Figure 123: H NMR spectrum of compound 4.37 in CDCl3 at 298 K.

13 Figure 124: C NMR spectrum of compound 4.37 in CDCl3 at 298 K.

276

1 Figure 125: H NMR spectrum of compound 4.31 in CDCl3 at 298 K.

277

1 Figure 126: H NMR spectrum of compound 4.51 in CDCl3 at 298 K.

13 Figure 127: C NMR spectrum of compound 4.51 in CDCl3 at 298 K.