Synthesis, Polymerization and Reactions of Enantiomerically Pure Phosphaalkenes

by

Spencer Christopher Serin

B.Sc. (Hons.) The University of Western Ontario, 2010

A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF

THE REQUIREMENTS FOR THE DEGREE OF

DOCTOR OF PHILOSOPHY

in

THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES

(Chemistry)

THE UNIVERSITY OF BRITISH COLUMBIA

(Vancouver)

August 2016

© Spencer Christopher Serin, 2016 Abstract

This thesis outlines the polymerization and novel reactivity of enantiomerically pure compounds featuring the relatively uncommon phosphaalkene moiety.

Chapter 1 introduces the chemistry of the phosphaalkene (Ar-P=CR2) structural fragment.

This motif is compared and contrasted to the established chemistry of C=N and C=C groups.

Similarities and differences are highlighted by an examination of: (a) phosphaalkene synthesis, (b) phosphaalkene polymerization and (c) phosphaalkene-metal coordination.

Chapter 2 details the addition reactions of MeM (M = MgBr, Li) nucleophiles to enantiomerically pure phosphaalkene-oxazoline 1.10a [PhAk-Ox, MesP=CPh(CMe2Ox)]. Of note, the reaction of MeMgBr and PhAk-Ox is highly diastereoselective and affords a new P-chiral phosphine oxazoline ligand.

Chapters 3 and 4 report the free radical initiated homo- and co-polymerizations (with styrene) of enantiomerically pure phosphaalkene-oxazolines 1.10a (Chapter 3) and 4.1a

[MesP=CPh(3-C6H4Ox), Chapter 4]. The coordination of rhodium(I) to copolymers of 1.10a and styrene permits the isolation of novel macromolecular complexes. Additionally, polymers of 4.1a display unique spectroscopic signatures that permit the direct assignment of styrene- phosphaalkene linkages in the polymer backbone.

Chapters 5 and 6 highlight the coordination chemistry of phosphaalkenes. Chapter 5 discusses the syntheses of κ3(PNN)-copper(I) complexes featuring enantiomerically pure pyridine- bridged phosphaalkene-oxazoline 5.1a [ArP=CPh(2-C5H3N-6-Ox)]. Chapter 6 explores the insertion of the P=C functional group into Pd–R bonds, permitting the synthesis of novel

ii

phosphapalladacyclopropanes (6.1a-b) and palladium(II) complexes featuring 1,2- dihydropyridinato donors (6.3 and 6.4).

Chapter 7 provides perspective for the work contained within this thesis.

iii

Preface

Sections of this work have previously been published. Sections of the introductory Chapter

1 have been published in Chemical Society Reviews, for a review on main group containing polymers which was written in equal collaboration with Andrew M. Priegert and Benjamin W.

Rawe along with our supervisor Prof. Derek P. Gates. Andrew M. Priegert, Benjamin W. Rawe,

Spencer C. Serin and Derek P. Gates. Polymers and the p-block elements. Chem. Soc. Rev. 2016,

45, 922-953.

The information presented in Chapter 2 has been published in Organometallics, for which

I performed all the synthetic work and wrote the manuscript in collaboration with both my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. The X-ray data was collected, integrated, refined, and solved by myself, however one structure was refined and solved by Dr.

Brian O. Patrick. Spencer C. Serin, Brian O. Patrick, Gregory R. Dake and Derek P. Gates.

Reaction of an Enantiomerically Pure Phosphaalkene-Oxazoline with MeM (M = Li and MgBr):

Stereoselectivity and Noninnocence of the P-Mesityl Substituent. Organometallics 2014, 33,

7215-7222.

The information in Chapter 3 has been published in two separate journal articles. The first report of a copolymer obtained from an enantiomerically pure phosphaalkene-oxazoline was published in Chemistry – A European Journal¸ for which I performed all the synthetic work, wrote the experimental, and prepared the figures pertaining to the copolymer. This work also detailed the synthesis of a number of phosphaalkene-oxazolines for which the synthetic work was performed and written by the other authors. Julien Dugal-Tessier, Spencer C. Serin, Emmanuel B.

Castillo-Contreras, Eamonn D. Conrad, Gregory R. Dake and Derek P. Gates. Enantiomerically

Pure Phosphaalkene-Oxazolines (PhAk-Ox): Synthesis, Scope and Copolymerization with iv

Styrene. Chem. Eur. J. 2012, 18, 6349-6359. Additional copolymers, microstructure analysis and rhodium(I) coordination to these copolymers was published in Dalton Transactions, for which I performed all the synthetic work, X-ray analysis, and wrote the manuscript in collaboration with my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. Spencer C. Serin, Gregory R.

Dake and Derek P. Gates. Phosphaalkene-oxazoline Copolymers with Styrene as Chiral Ligands for Rhodium(I). Dalton Trans. 2016, 45, 5659-5666.

The work in Chapter 4 has been published in Macromolecules, for which I performed all the synthetic work, X-ray analysis, and wrote the manuscript in collaboration with my supervisors

Prof. Gregory R. Dake and Prof. Derek P. Gates. Spencer C. Serin, Gregory R. Dake and Derek P.

Gates. Addition-Isomerization Polymerization of Chiral Phosphaalkenes: Observations of

Styrene-Phosphaalkene Linkages in a Random Copolymer. Macromolecules 2016, 49(11), 4067-

4075.

The work in Chapter 5 has been published in Inorganic Chemistry, for which I performed all the synthetic work, X-ray analysis and wrote the manuscript in collaboration with my supervisors Prof. Gregory R. Dake and Prof. Derek P. Gates. Computational data was obtained by

Fraser S. Pick. Spencer C. Serin, Fraser S. Pick, Gregory R. Dake and Derek P. Gates. Copper(I)

Complexes of Pyridine-Bridged Phosphaalkene-Oxazoline Pincer Ligands. Inorg. Chem. 2016,

55(13), 6670-6678.

The work in Chapter 6 will be submitted shortly for publication and I performed all the synthetic work and X-ray analysis. Spencer C. Serin, Gregory R. Dake, Derek P. Gates, to be submitted

v

Table of Contents

Abstract ...... ii

Preface ...... iv

Table of Contents ...... vi

List of Tables ...... xii

List of Figures ...... xiii

List of Schemes ...... xvi

List of Abbreviations and Symbols ...... xix

Acknowledgements ...... xxv

Dedication ...... xxvi

Foreword ...... xxvii

Chapter 1: Introduction: Phosphaalkenes as Monomers and Ligands ...... 1

1.1 Introduction ...... 1

1.1.1 Low-Coordinate Phosphorus ...... 2

1.1.2 Synthetic Approaches to Phosphaalkenes ...... 4

1.1.2.1 Synthesis of Achiral Phosphaalkenes ...... 5

1.1.2.2 Synthesis of Enantiomerically Pure Phosphaalkenes ...... 6

1.2 Phosphaalkenes as Monomers ...... 9

1.3 Phosphaalkenes as Ligands ...... 14

1.3.1 Coordination Properties of Phosphaalkenes ...... 14

1.3.2 Selected Complexes that Feature Phosphaalkenes ...... 16

1.3.3 Phosphaalkenes as Ligands for Catalysis ...... 17 vi

1.4 Goal of the Project ...... 21

1.5 Outline of Thesis ...... 21

Chapter 2: Reaction of an Enantiomerically Pure Phosphaalkene-Oxazoline with MeM

Nucleophiles (M = Li and MgBr) ...... 23

2.1 Introduction ...... 23

2.2 Results and Discussion ...... 24

2.2.1 General Synthetic Strategy ...... 24

2.2.2 Analysis of MeMgBr Addition to Phosphaalkene 1.10a ...... 26

2.2.2.1 Synthesis of Chiral Phosphine-Oxazoline 2.1a,a ...... 26

2.2.2.2 Postulated Mechanism for Formation of Phosphine 2.1a,a ...... 27

2.2.2.3 Palladium Complexes of Phosphine 2.1a,a ...... 29

2.2.3 Analysis of MeLi Addition to Phosphaalkene 1.10a ...... 33

2.2.3.1 Unexpected Synthesis of Palladium Complex 2.5 ...... 33

2.2.3.2 Postulated Mechanism for Formation of Complex 2.5 ...... 37

2.3 Summary ...... 39

2.4 Experimental Section ...... 40

2.4.1 Materials and Methods ...... 40

2.4.2 Synthesis of (R)-MesMeP-(S)-CHPhC(Me)2(CNOCH(i-Pr)CH2) (2.1a,a) ...... 40

2.4.3 Synthesis of d-2.1a,a ...... 42

2.4.4 Synthesis of (2.1a,a)PdCl2 (2.2) ...... 43

2.4.5 Synthesis of (2.1a,a)PdMeCl (2.3) ...... 44

2.4.6 Synthesis of (2.1a,a)Pd(C3H5)∙OTf (2.4) ...... 46

2.4.7 General Procedure for Addition of MeLi to 1.10a ...... 47 vii

2.4.8 Synthesis of Palladium(II) Dimer 2.5 ...... 48

2.4.9 X-ray Crystallographic Studies ...... 50

Chapter 3: Phosphaalkene-Oxazoline Copolymers with Styrene as Chiral Ligands for

Rhodium(I) ...... 53

3.1 Introduction ...... 53

3.2 Results and Discussion ...... 55

3.2.1 Synthesis of Phosphaalkene-Oxazoline/Styrene Copolymers ...... 55

3.2.2 Structural Characterization of Copolymer 3.1 ...... 56

3.2.3 Coordination of Rhodium(I) to Copolymer 3.1 ...... 60

3.2.4 Integrated 31P NMR Spectra of Copolymer-Rhodium(I) Complexes as a Method for

Estimating Phosphorus Incorporation ...... 64

3.3 Summary ...... 67

3.4 Experimental ...... 68

3.4.1 Materials and Methods ...... 68

3.4.2 General Procedure for Synthesis of Copolymers...... 68

3.4.3 Synthesis of [((R)-MesMeP-(S)-CHPhC(Me)2(CNOCH(i-Pr)-CH2)Rh(cod)]BF4

(3.2)…...... 70

3.4.4 Synthesis of [3.1a·Rh(cod)]BF4...... 70

3.4.5 General Procedure for Titration of Copolymer 3.1 with Rh(cod)2BF4 ...... 71

3.4.6 Procedure for the Displacement of Rhodium from Metallated Copolymer 3.1...... 72

3.4.7 X-ray Crystallographic Studies...... 72

Chapter 4: Addition-Isomerization Polymerization of Chiral Phosphaalkenes: Observation of Styrene-Phosphaalkene Linkages in a Random Copolymer ...... 74 viii

4.1 Introduction ...... 74

4.2 Results and Discussion ...... 76

4.2.1 Monomer Synthesis and Characterization ...... 76

4.2.2 Homo and Co-polymerization of Monomer 4.1a ...... 80

4.2.3 Microstructures of Polymers 4.4a and 4.5a ...... 81

4.2.4 Chemical Functionalization of Polymers 4.4a and 4.5a ...... 88

4.3 Summary ...... 89

4.4 Experimental Section ...... 90

4.4.1 Materials and Methods ...... 90

4.4.2 Synthesis of (S)-PhC=OC6H4(CNOCH(i-Pr)-CH2) (4.3)...... 91

4.4.3 Synthesis of (S)-MesP=CPhC6H4(CNOCH(i-Pr)-CH2) (4.1a)...... 92

4.4.4 Synthesis of (S)-Mes*P=CPhC6H4(CNOCH(i-Pr)-CH2) (4.1b)...... 94

4.4.5 Synthesis of Homopolymer 4.4a...... 95

4.4.6 Synthesis of Copolymer 4.5a ...... 96

4.4.7 Standard Procedure for Gold Coordination to PMP (4.4a·AuCl and 4.5a·AuCl). ... 97

4.4.8 X-ray Crystallographic Studies...... 97

Chapter 5: Copper(I) Complexes of Pyridine-Bridged Phosphaalkene-Oxazoline Pincer

Ligands ...... 100

5.1 Introduction ...... 100

5.2 Results and Discussion ...... 102

5.2.1 Phosphaalkene Synthesis and Characterization...... 102

5.2.2 Coordination of Phosphaalkene 5.1a to Copper...... 107

5.2.3 Characterization of Copper Complexes...... 111 ix

5.2.4 Computational Section ...... 114

5.3 Summary ...... 116

5.4 Experimental ...... 116

5.4.1 Materials and Methods ...... 116

5.4.2 Synthesis of 6-Benzoylpicolinic acid (5.2) ...... 117

5.4.3 Synthesis of (S)-PhC=OC5H3N(CNOCH(i-Pr)-CH2) (5.3a) ...... 118

5.4.4 Synthesis of Synthesis of (S)-PhC=OC5H3N(CNOCH(CH2Ph)-CH2) (5.3b) ...... 120

5.4.5 Synthesis of (S)-MesP=CPhC5H3N(CNOCH(i-Pr)-CH2) (5.1a) ...... 121

5.4.6 Synthesis of (S)-Mes*P=CPhC5H3N(CNOCH(i-Pr)-CH2) (5.1b) ...... 122

5.4.7 Synthesis of (S)-MesP=CPhC5H3N(CNOCH(CH2Ph)-CH2) (5.1c)...... 123

5.4.8 Synthesis of [Cu2(6.1a)2(OTf)(MeCN)]OTf (5.7) ...... 124

5.4.9 Synthesis of [Cu(6.1a)(PPh3)]OTf (5.8a) ...... 124

5.4.10 Representative Addition of a Neutral Ligand to Complex 5.7 (5.8b-e) ...... 125

5.4.11 X-ray Crystallographic Studies ...... 125

5.4.12 Computational Details ...... 126

5.5 Supplementary Section ...... 128

Chapter 6: Carbopalladation of Phosphaalkenes as a Route to Palladacycles ...... 132

6.1 Introduction ...... 132

6.2 Results and Discussion ...... 134

6.2.1 Carbopalladation of MesP=CPh2 ...... 134

6.2.2 Carbopalladation of a Phosphaalkene-Oxazoline ...... 139

6.2.3 Carbopalladation of 2-Pyridyl-Substituted Phosphaalkenes ...... 141

6.2.3.1 Carbopalladation of MesP=CPh(2-py) ...... 141 x

6.2.3.2 Carbopalladation of Phosphaalkene Pincer 5.1a ...... 144

6.3 Summary ...... 146

6.4 Experimental ...... 147

6.4.1 Materials and Methods ...... 147

6.4.2 Synthesis of Mes(Me)P–CPh2∙PdCl(PPh3) (6.1a) ...... 147

6.4.3 Synthesis of Mes(Ph)P–CPh2∙PdI(PPh3) (6.1b) ...... 148

6.4.4 Representative Procedure for the Synthesis of Complex 6.2 ...... 149

6.4.5 Synthesis of Mes(Me)P–C(Ph)C5H3N∙PdCl(PPh3) (6.3) ...... 149

6.4.6 Synthesis of Mes(Me)P–C(Ph)C5H3N(CNOCH(CH2Ph)–CH2)∙PdCl (6.4) ...... 150

6.4.7 X-ray Crystallographic Studies ...... 151

Chapter 7: Concluding Remarks ...... 154

Bibliography ...... 155

xi

List of Tables

Table 2.1 COSY Correlation for Compound 2.1a,a...... 42

Table 2.2 COSY Correlation for Compound 2.2...... 44

Table 2.3 COSY Correlation for Compound 2.3...... 46

Table 2.4 COSY Correlation for Compound 2.5...... 49

a Table 2.5 X-ray Data Collection and Refinement Details for Compounds 2.1a,a, 2.2, and 2.3. .. 51

Table 2.6 X-ray Data Collection and Refinement Details for Compounds 2.4, 2.5, and 2.6.a ..... 52

Table 3.1 Selected Data for Copolymers 3.1a-3.1c...... 56

Table 3.2 Estimated Phosphorus Incorporation in Copolymers 3.1a-3.1c...... 66

Table 3.3 X-ray Data Collection and Refinement Details for Compound 3.2.a ...... 73

Table 4.1 X-ray Data Collection and Refinement Details for Compounds 4.1a and 4.1b...... 99

Table 5.1 31P NMR data (ppm) and λmax values (nm) for band I and band II of 5.8a-5.8e...... 114

Table 5.2 X-ray Data Collection and Refinement Details for Compounds 5.3a, 5.1a, 5.7, and

5.8a...... 127

Table 5.3 Computed Low Energy Absorptions for 5.8a ...... 131

Table 5.4 Computed Low Energy Absorptions for 5.8d ...... 131

Table 6.1 Important Metrical Parameters for P–C–Pd Rings...... 138

Table 6.2 X-ray Data Collection and Refinement Details for Compounds 6.1a, 6.1b, 6.2, and 6.3.

...... 153

xii

List of Figures

Figure 1.1 Selected Motifs Incorporating Low-coordinate Phosphorus...... 3

Figure 1.2 Reactivity of P=C Bonds...... 4

Figure 1.3 Synthetic Approaches to Phosphaalkenes...... 5

Figure 1.4 Structural Variations in PhAk-Ox Ligands...... 9

Figure 1.5 Poly(methylenephosphine) as a Flame Retardent for Paper...... 13

Figure 1.6 Coordination Modes of Phosphaalkenes.69...... 15

Figure 1.7 Contributing AOs of the π*-bond in Carbonyl, Phosphaalkene and Imine Ligands.71 16

Figure 1.8 Selected Examples of Phosphaalkene Complexes...... 17

Figure 2.1 31P{1H} NMR Spectra (121 MHz, 298 K, THF) of the Reaction and Quenched

Products of MeMgBr and MeLi with 1.10a...... 25

Figure 2.2 Molecular Structure of 2.1a,a (50% Probability Ellipsoids)...... 27

2 1 Figure 2.3 Analysis of the H{ H} NMR Spectrum for d-2.1a,a...... 29

Figure 2.4 Molecular Structure of 2.2 (50% Probability Ellipsoids)...... 32

Figure 2.5 Molecular Structure of 2.3 (50% Probability Ellipsoids)...... 32

Figure 2.6 Molecular Structure of 2.4 (50% Probability Ellipsoids)...... 33

Figure 2.7 Molecular Structure of 2.5 (50% Probability Ellipsoids)...... 35

Figure 2.8 Molecular Structure of 2.6 (50% Probability Ellipsoids)...... 36

Figure 2.9 Postulated Intermediates after MeLi Addition to Phosphaalkene 1.10a...... 37

Figure 3.1 Selected Examples of Known Optically-active Metal-coordinating Polymers...... 54

31 1 Figure 3.2 P{ H} NMR Spectrum (162 MHz, 298 K) in CDCl3 of poly(methylenephosphine- co-styrene) 3.1a...... 57

Figure 3.3 Representative 13C{1H} NMR Spectra of 1.10a, 3.1a, and Polystyrene...... 58 xiii

Figure 3.4 1H-13C HSQC NMR Spectrum of Copolymer 3.1a...... 60

Figure 3.5 Molecular Structure of Complex 3.2 (50% Probability Ellipsoids)...... 62

Figure 3.6 Representative (i) UV/Vis and (ii) 1H NMR Spectra for the Characterization of

[3.1a·Rh(cod)]BF4...... 63

Figure 3.7 Representative 31P NMR Spectra of the Addition of Rhodium(I) to 3.1a and 3.1b.... 64

Figure 3.8 Addition of Rhodium(I) to 3.1a, 3.1b, and 3.3c to Estimate mol% 1.10a...... 66

Figure 4.1 Molecular Structures of (a) Z-4.1a and (b) Z-4.1b (50% Probability Ellipsoids)...... 79

31 1 Figure 4.2 P{ H} NMR Spectra (162 MHz, 298 K) in CDCl3 of (a) Homopolymer 4.4a, (b)

4.4a·AuCl, (c) Copolymer 4.5a, and (d) 4.5a·AuCl...... 82

Figure 4.3 Representative 13C{1H} and 1H 2D NMR Spectra for Homopolymer 4.4a and

Copolymer 4.5a...... 84

Figure 4.4 The Most Likely Environments for a Central Phosphaalkene Unit (in blue) Within

Copolymer 4.5a...... 85

13 1 Figure 4.5 Inverse-gated C{ H} NMR Spectrum (101 MHz, 298 K) in CDCl3 of Copolymer

4.5a...... 88

Figure 5.1 Selected Examples of Pincer and Mixed PN Phosphaalkene Ligands...... 101

Figure 5.2 Molecular structure of Ketone 5.3a (50% Probability Ellipsoids)...... 105

Figure 5.3 Molecular structure of Phosphaalkene 5.1a (50% Probability Ellipsoids)...... 106

Figure 5.4 Molecular structure of Complex 5.7 (50% Probability Ellipsoids)...... 109

Figure 5.5 Known Dimeric Copper Pyridine-oxazoline Complex...... 109

Figure 5.6 Molecular structure of Complex 5.8a∙(C4H8O)3 (50% Probability Ellipsoids)...... 111

Figure 5.7 Representative UV/Vis Spectra of 5.8a-5.8e in CH2Cl2 Solution (All Concentrations

Were ca. 5 × 10-5 mol L-1)...... 113 xiv

Figure 5.8 Important Molecular Orbitals for the Low Energy Transitions of 5.8a and 5.8d. .... 115

1 1 Figure 5.9 H- H COSY (a) and NOESY (b) NMR Spectra (400 MHz, 298 K) in CDCl3 of E/Z-

5.1a...... 128

1 31 1 Figure 5.10 H- P HMBC NMR Spectrum (400 MHz for H, 298 K) in CDCl3 of E/Z-5.1a... 129

1 1 Figure 5.11 H- H NOESY NMR Spectrum (400 MHz, 298 K) in CDCl3 of Complex 5.7...... 129

Figure 5.12 Optimized structure of 5.8a...... 130

Figure 5.13 Optimized structure of 5.8d...... 130

Figure 6.1 Molecular Structure of Complex 6.1a∙CHCl3 (50% Probabilty Ellipsoids)...... 136

Figure 6.2 Molecular Structure of Complex 6.1b (50% Probabilty Ellipsoids)...... 138

Figure 6.3 Molecular Structure of 6.2∙CH2Cl2 (50% Probability Ellipsoids)...... 140

Figure 6.4 Molecular Structure of 6.3∙C4H8O (50% Probability Ellipsoids)...... 142

xv

List of Schemes

Scheme 1.1 Synthesis of Mes-substituted Phosphaalkenes Using the Base-catalyzed Phospha-

Peterson Reaction...... 5

Scheme 1.2 Synthesis of a P-Menthyl Phosphaalkene...... 7

Scheme 1.3 Synthesis of Planar-chiral Ferrocene-phosphaalkene...... 7

Scheme 1.4 Representative Synthesis of an Enantiomerically Pure Phosphaalkene Oxazoline. ... 8

Scheme 1.5 Addition Homo- and Copolymerization of MesP=CPh2 to Yield

Poly(methylenephosphine) and Poly(methylenephosphine-co-styrene)...... 9

Scheme 1.6 Anionic Polymerization of Substituted Phosphaalkenes...... 10

Scheme 1.7 Preparation of Polystyrene-block-poly(methylenephosphine) by Living Anionic

Polymerization...... 10

Scheme 1.8 Functionalization of Poly(methylenephosphine)s...... 12

Scheme 1.9 Alternative Microstructure of Poly(methylenephosphine) Using a Nitroxide- mediated Radical Polymerization Initiator...... 14

Scheme 1.10 Application of Phosphaalkene-based Catalysts in Hydroamination Reactions...... 18

Scheme 1.11 Synthesis and Application of an Ir(I)-phosphaalkene Catalyst in N-alkylations of

Amines...... 18

Scheme 2.1 Possible Stereoisomeric Products of the Reaction of Methyllithium or

Methylmagnesium Bromide and PhAk-Ox 1.10a...... 23

Scheme 2.2 Synthesis of Enantiomerically Pure Phosphine Oxazoline 2.1a,a...... 26

Scheme 2.3 Postulated Mechanism for the Formation of 2.1a,a...... 28

Scheme 2.4 Synthesis of Palladium Complexes of 2.1a,a...... 30

Scheme 2.5 Unexpected Synthesis of Dimeric Palladium Complex 2.5...... 34 xvi

Scheme 2.6 Postulated Mechanism for the Formation of Complex 2.5...... 38

Scheme 3.1 Synthesis of Poly(methylenephosphine-co-styrene) 3.1...... 55

Scheme 3.2 Synthesis of Phosphine-oxazoline Rhodium(I) Complex 3.2 as a Model for

[3.1·Rh(cod)]BF4...... 61

Scheme 4.1 The Isolobal Analogy Between Olefins and Phosphaalkenes as Applied to Addition

Polymerization (top). Selected Examples of Polymerizable Phosphaalkene Monomers (bottom).

...... 75

Scheme 4.2 Synthesis of Enantiomerically Pure Phenyl-bridged Phosphaalkene-oxazolines. .... 76

Scheme 4.3 Synthesis of poly(methylenephosphine) 4.4a and poly(methylenephosphine-co- styrene) 4.5a...... 80

Scheme 5.1 Synthetic Approach to Pyridine-bridged Phosphaalkene-oxazolines...... 103

Scheme 5.2 Synthesis of Enantiomerically Pure Pyridyl-ketones...... 103

Scheme 5.3 Synthesis of Pyridine-bridged Phosphaalkene-oxazolines...... 106

Scheme 5.4 Synthesis of Copper(I)-phosphaalkene Complexes...... 108

Scheme 6.1 Carbopalladation of E=C Double Bonds (E = N, C, P)...... 132

Scheme 6.2 Synthesis of Phosphapalladacyclopropanes...... 133

Scheme 6.3 Postulated Reactions Involving Phosphapalladacyclopropanes...... 134

Scheme 6.4 Carbopalladation of MesP=CPh2...... 135

Scheme 6.5 Synthesis and Postulated Mechanism for the Formation of Complex 6.2...... 139

Scheme 6.6 Carbopalladation as a Method to Obtain a 1,2-Dihydropyridinato Complex...... 141

Scheme 6.7 Synthesis of a Previously Reported 1,2-Dihydropyridinato Pyridine Palladium(II)

Complex and Comparison to Complex 6.3...... 143

xvii

Scheme 6.8 Carbopalladation of a Phosphaalkene as a Route to a New Palladium(II) Pincer

Complex...... 145

Scheme 6.9 Palladium Complexes Featuring 1,2-Dihydropyridinato Donors as Olefin

Polymerization Catalysts...... 147

xviii

List of Abbreviations and Symbols

t [훼]D specific rotation at temperature t and D line Å angstrom (1 x 10-10 metres) Ac acetyl anal. analysis (combustion analysis) AO atomic orbital APT attached proton test (NMR spectroscopy) Ar aryl AW atomic weight b block (copolymer) BOX bisoxazoline BPEP 2,6-bisphosphaethylenepyridine br broad or broadened (spectra) BSA N,O-bis(trimethylsilyl)acetamide Bu butyl m-CPBA meta-chloroperoxybenzoic acid

χx electronegativity of element x C centi (10-2) c concentration (g/100 mL) in optical roation °C degrees Celsius ca. circa, about calcd calculated cat. catalytic cf. compare co copolymer (random) cod cyclooctadiene (ligand) compd compound COSY correlation spectroscopy Cp cyclopentadienyl

xix

crys crystal δ chemical shift in parts per million (ppm) Δδ difference in chemical shift (spectroscopy) d type of orbital deuterated d1 recycle delay d day(s) deci (10-1) doublet (NMR spectroscopy) dba dibenzylideneacetone DBU 1,8-diazabicyclo[5.4.0]undec-7-ene de diastereomeric excess deg or ° degree (angle or temperature) DFT density functional theory DMAP dimethylaminopyridine DMF N,N-dimethylformamide DMSO dimethylsulfoxide dppe 1,2-bis(diphenylphosphino)ethane dppf 1,2-bis(diphenylphosphino)ferrocene ε molar attenuation coefficient E entgegen (configuration)

Ea activation energy ed., eds. edition, editions Ed., Eds. editor, editors ee enantiomeric excess e.g. example EI electron impact equiv equivalents ESI electron spray ionization

Et ethyl or CH3CH2–

xx

etc. and so forth eV electronvolt Fc ferrocene FMO frontier molecular orbital FW free weight g gram g gas gem geminyl GOF goodness of fit GPC gel permeation chromatography {1H} proton decoupled (NMR spectroscopy) η hapticity h hour HMBC heteronuclear multiple bond correlation HSQC heteronuclear single quantum correlation HOMO highest occupied molecular orbital HRMS high resolution mass spectrometry Hz hertz i iso (as in i-Pr)

Ix relative integration value of x (NMR spectroscopy) in situ in place or in the reaction in vacuo in a vacuum init. initiator int internal (X-ray) J coupling constant (NMR spectroscopy) κ denticity k kilo (103) K kelvin Kα spectral line L absolute configuration

xxi

ligand litre λ wavelength lit. literature LRMS low resolution mass spectrometry LUMO lowest unoccupied molecular orbital μ absorption coefficient (X-ray) micro (10-6)

μn bridging ligand (n = number of metals bridging) m meta m/z mass-to-charge ratio m metre milli (10-3) multiplet (NMR spectroscopy) M mega (106) metal molar (moles per litre) M/I monomer to initiator ratio MALS multi angle light scattering

Me methyl or CH3– Mes 2,4,6-trimethylphenyl Mes* 2,4,6-tri-tert-butylphenyl min minute(s)

Mn number-average molecular weight Mw weight-average molecular weight mol mole(s) mp melting point mult. multiple (NMR spectroscopy) n normal (in n-butyl) total number of units

xxii

n nano (10-9) NMR nuclear magnetic resonance no. number NOESY nuclear overhauser effect (NOE) spectroscopy o ortho ORTEP oak ridge thermal ellipsoid plot OTf trifluoromethanesulfonate Ox oxazoline π type of bonding orbital π* type of anti-bonding orbital % percent (parts per hundred) p type of orbital para param parameter

PDI polydispersity index (Mw/Mn) Ph phenyl PhAk-Ox phosphaalkene-oxazoline (proligand or ligand) PHOX phosphinooxazoline (proligand or ligand) PMP poly(methylenephosphine) ppm parts per million Pr propyl py pyridine (C5H5N) or pyridyl PyBox 2,6-pyridinebisoxazoline R generic substituent residual factor (X-ray) R rectus (configurational) refln reflection

Rh hydrodynamic radius rt room temperature σ background (X-ray)

xxiii

type of bonding orbital s type of orbital sec secondary (as in sec-Bu) S styrene SADABS siemens area detector absorption correction program SCE saturated calomel electrode syst system θ angle t tertiary (as in t-Bu) t triplet (NMR spectroscopy) T temperature TEMPO 2,2,6,6-tetramethylpiperidyl-1-oxyl THF tetrahydrofuran tht tertahydrothiophene TMEDA N,N,N',N'-tetramethylethylenediamine TMS trimethylsilyl tolyl paramethylbenzene

TP temperature of polymerization Ts paratoluenesulfonyl UBC University of British Columbia UV/Vis ultraviolet/visible V volume v:v volume to volume ratio VAZO 88 or VAZO 1,1'-azobis(cyclohexanecarbonitrile) vide infra see below wrt with respect to wt% weight percent Z zusammen (configurational) Z number of units in a cell (X-ray)

xxiv

Acknowledgements

To my professors: Dr. Derek Gates and Dr. Greg Dake… You are my rocks. Thank you for your help, the wisdom you donated over these many years, and the willingness to release me into your labs.

To my labmates in the Dake and Gates groups, past and present, thank you for your contributions, assistance, and understanding through these challenging years. There are too many to name, but certainly the people who have contributed intimately to my work (in no particular order): Andrew, Ben, Han, Julien, Khatera, Eamonn, Alex Enders, Chris, Ivo, Paul, Emmanuel,

Shuai, Kaoru, Tom(s), and Josh. You have been indispensable.

As someone who is constantly breaking things or needing answers, thank you to the amazing analytical and in house shops and services at UBC. In particular, Brian P. (Xray), Brian

D. (glassblowing), K. Love/Raz (mechanical engineering), Milan/Dave (electronic shop), Pat/John

(shipping/receiving), Maria/Paul (NMR), Derek (mass spec), and David (IT).

A special thanks to Prof. Dr. Rainer Streubel, and his group, for hosting me in Germany and teaching me the wonders of serious inorganic chemistry.

To my friends… the ones with whom I did a little bit of sneaky collaborating, idea swapping, coolin’, OVCing, and golfing: Benny, Picks, Chad 85, Wambach, Preggers, thank you for the fun. It’s not always about the science, ya kno’. And of course, the whole F-BALM crew, past and present, I hope you remain strong in my absence. And Dirk, thanks for your tireless effort.

To my family and friends, not directly linked to UBC, of course thank you for the distractions. All my memories at 127 will be cherished.

Elise, thank you for your never-ending support. xxv

Dedication

To the Reader…

If you are reading this not because you have to,

but because you want to,

that’s what makes it all worth it

xxvi

Foreword

This dissertation discusses the polymerization of preexisting and newly developed phosphaalkene-oxazolines, along with some serendipitous discoveries about the curious reactivity of this class of compound. In addition, the development and coordination chemistry of new ligand scaffolds that feature phosphaalkenes are highlighted. The synthetic procedures within this thesis that lead to new compounds expand on preexisting strategies. In addition, new, less conventional, approaches to inorganic compounds utilizing phosphaalkenes are developed that truly reflect the versatility of P=C double bond-containing compounds.

A few comments are required to explain the numbering of compounds in this work. Two numbers are used to name compounds of importance: the first number refers to the chapter where the compound first appears and the second denotes the order where it appears within that Chapter.

For example, compound 3.1 is the first compound discussed or synthesized within Chapter 3 and does not change throughout the manuscript. Within chapters, generic or previously reported compounds are referred to with capital letters such as A, B, C, etc. Mechanistic details or reaction intermediates within a Chapter are numbered using roman numerals i, ii, iii, etc. The use of small letters (a, b, c, etc.) after the number indicates a relation between the compounds in question. Some simple organic and inorganic compounds are referred simply by name or structural formula.

Other than Chapters 1 and 7, the dissertation is written in manuscript style. The stylistic and formatting requirements of this document follow The ACS Style Guide. Chapter 1 contains a more general introduction to provide historical aspects that place this work in perspective, however each Chapter is self-contained and includes an introduction to familiarize the reader with the relevant background.

xxvii

Chapter 1: Introduction: Phosphaalkenes as Monomers and Ligands*

1.1 Introduction

The fundamental philosophy of coordination chemistry can be over simplified as the rational design, synthesis and evaluation of metal-ligand systems. There is no denying that the choice of metal can dictate a complexes’ effectiveness (e.g. the 2010 Nobel prize was awarded for palladium-catalyzed carbon-carbon bond forming reactions), yet the importance of ligand design must not be overlooked. In many ways, the modulation of the inherent reactivity at a metal centre using a particular ligand dictates the metal’s capabilities. For this reason, fundamental research into unique ligand design strategies that influence electronic and steric environments remains a valuable pursuit.

Phosphorus, an element capable of a broad range of oxidation states, geometries, and bonding environments, is ubiquitous in ligand and materials chemistry. In particular, phosphine- based ligands (i.e. PR3) are exceedingly common due to the ease at which diversity may be

1, 2 obtained at the P-centre. Using this PR3 motif, where R can be bulky, small, electron-rich, electron-poor, chiral, or tethering, variable denticity ligands with high levels of complexity can be obtained.3-5 Furthermore, phosphorus can be a centre of point chirality and a number of methodologies exist to obtain P(III) centres in high enantiomeric purity, paving the way to P-chiral phosphine ligands for application in transition metal-based asymmetric catalysis.6-9

* Versions of sections of this chapter have been published. Andrew M. Priegert, Benjamin W. Rawe, Spencer C. Serin and Derek P. Gates. Polymers and the p-block elements. Chem. Soc. Rev. 2016, 45, 922-953 1

It follows that the development of novel methods for the synthesis of selectively substituted phosphine ligands is an area of importance. Additionally, the incorporation of phosphines into macromolecular architectures opens the door to numerous exciting possibilities such as polymer- supported catalysis.10, 11 To that end, compounds containing low-coordinate phosphorus moieties

[i.e. incorporating a P(III)=C multiple bond] are interesting synthetic targets. Certain low- coordinate phosphorus compounds can serve as precursors to both monomeric and polymeric phosphine-containing systems. Furthermore, ligands featuring low-coordinate phosphorus(III) atoms are comparatively less-developed than trivalent phosphorus(III) derivatives and possess unique electronic properties that may be advantageous. Therefore, as the focus of this dissertation is the exploitation of low-coordinate phosphorus containing compounds for polymer and coordination chemistry, a short introduction into their unique chemistry is warranted.

1.1.1 Low-Coordinate Phosphorus

Common low-coordinate organophosphorus(III) compounds, both cyclic and acyclic, are

-1 shown in Figure 1.1. The calculated strength of a P=C π-bond (43 kcal mol in HP=CH2) is much

-1 12, 13 weaker than the related C=C π-bond (65 kcal mol in H2C=CH2) due to the poor orbital overlap between 2nd and 3rd row elements. Therefore, kinetic stabilization of the P=C bond is required to prevent unwanted polymerization, oligomerization, or dimerization. For acyclic phosphaalkenes this is accomplished by incorporating a bulky substituent on phosphorus [e.g.

14 2,4,6-(t-Bu)3C6H2 (Mes*) or 2,4,6-(Me)3C6H2 (Mes)] or having electron rich substituents on the

15 carbon atom of the P=C bond [i.e. HP=C(NMe2)2]. The incorporation of the P=C bond into an aromatic system, such as cyclic phosphinines (P analogs of pyridines),16, 17 phospholides (P analogs of Cp– rings),18, 19 and benzoxaphospholes (P analogs of benzoxazoles)20-22 motifs shown

2

in Figure 1.1, also stabilizes the reactive functionality. The work discussed herein deals exclusively with acyclic phosphaalkenes so only this class of molecule will be examined in detail.

Figure 1.1 Selected Motifs Incorporating Low-coordinate Phosphorus.

Although steric or electronic strategies are required to kinetically synthesize isolable phosphaalkenes, phosphaethylene (HP=CH2) has been obtained by vacuum gas-solid dehydrochlorination of methylchlorophosphine and characterized by directly coupling the reaction manifold to either a NMR or photoelectron spectrometer.23 This approach permitted the experimental measurement of the frontier molecular orbitals (FMOs) energies of phosphaethylene

[i.e. the P=C π-bond (-10.3 eV) and phosphorus lone pair (-10.7 eV)]. Surprisingly, the energy of

MO belonging to the phosphorus lone pair is lower than the MO for the P=C π-bond and differ significantly from the analogous FMOs in nitrogen analogue methanimine (i.e. HN=CH2, N=C π- bond: -12.5 eV, N-lone pair: -10.6 eV). The energy level for the P=C π-bond is strikingly similar to the analogous C=C π-bond (-10.5 eV in ethylene).24 Due to this similarity, the reactivity of phosphaalkenes most closely resembles that of analogous carbon compounds (Figure 1.2).14, 25-27

Cycloadditions, such as the Diels-Alder reaction (A), and 1,2-addition reactions (B), such as the reaction of HX molecules across the double bond to create a mixture of regioisomeric products, have been observed with compounds containing P=C groups. Additionally, if the phosphorus lone pair is protected {i.e. [M] = W(CO)5}, epoxidation with m-CPBA (C) or hydrogenation with molecular hydrogen in the presence of a rhodium catalyst (D) have been demonstrated.

Phosphaalkenes, unlike olefins, possess a lone pair at phosphorus and retain the ability to coordinate metals in a κ1(P) fashion in addition to a more olefin-like η2(P,C) fashion (E). This will 3

be discussed in a later section of this introduction. Overall, the analogous reactivities of P=C and

C=C bonds has led to low-coordinate phosphorus being dubbed a carbon copy, a property highlighted extensively within the 1998 book by Dillon, Mathey, and Nixon: Phosphorus: the

Carbon Copy.27

Figure 1.2 Reactivity of P=C Bonds.

1.1.2 Synthetic Approaches to Phosphaalkenes

Selected synthetic routes to phosphaalkenes are highlighted in Figure 1.3 and demonstrate the diversity of methods one can use to obtain these compounds. The first isolable phosphaalkene,

28 PhP=C(t-Bu)(OSiMe3), was obtained by Becker in 1976 using method F. In this early work, a small library of phosphaalkenes were prepared by treating a bissilylphosphine [RP(SiMe3)2] with pivaloyl chloride. The first stable phosphaalkene bearing solely carbon substituents, MesP=CPh2, was prepared by elimination of HCl from chlorophosphine MesP(Cl)–CHPh2 using DBU as the base (G).29 The thermal-30 or base-catalyzed31 isomerization of secondary vinylphosphines (H) can also be used to obtain phosphaalkenes. Modern syntheses of phosphaalkenes utilize strategies based on established olefin synthetic routes, namely the phospha-Peterson (I),32-36 phospha-Wittig

(J)37 and phospha-Wittig-Horner (K)38-40 reactions.

4

Figure 1.3 Synthetic Approaches to Phosphaalkenes.

1.1.2.1 Synthesis of Achiral Phosphaalkenes

All novel phosphaalkenes presented within this work are obtained using the phospha-

Peterson reaction. Although the reaction can be performed under stoichiometric41 or catalytic32 conditions, both require the synthesis of a silylphosphine precursor [e.g. RP(SiMe3)2 or

RPH(SiMe3)]. Fortunately, bissilylphosphines can be obtained in a straightforward manner as outlined in Scheme 1.1. Commercially available 2-bromomesitylene (Mes–Br) is converted to the corresponding Grignard reagent by treatment with Mg turnings in THF. The Grignard solution is then added dropwise to a cold (-78 °C), rapidly stirred solution of PCl3 (1.4 equiv wrt Mes-Br) in

THF via cannula. Extraction of the reaction mixture followed by reduction of the crude products with LiAlH4 affords a mixture of MesPH2 and Mes2PH that can be separated by distillation.

Overall, this route prevents the use of amino protecting groups on phosphorus and permits the synthesis of MesPH2 on a 200 mmol (30 g) scale.

Scheme 1.1 Synthesis of Mes-substituted Phosphaalkenes Using the Base-catalyzed Phospha-Peterson Reaction.

5

Elaboration of MesPH2 to MesP(SiMe3)2 is accomplished by treating the phosphine with

2.2 equivalents of n-BuLi followed by the addition of excess TMS-Cl. This step usually proceeds with high conversion and the product can be purified by distillation. Other arylphosphines (i.e.

Mes*PH2) can be converted to silylphosphines in analogous fashion, however sterics may prevent disubstitution. With MesP(SiMe3)2 in hand, the base-catalyzed phospha-Peterson reaction is performed as follows: a mixture of ketone and silylphosphine (ca. 1.1:1) in minimal THF is treated with a catalytic amount of dry KOH and the reaction mixture is stirred.32 The reaction is monitored

31 by P NMR spectroscopy and deemed complete once all the MesP(SiMe3)2 (δ = -187) has been converted to phosphaalkene (δ = 200-250). Using this method, a number of P-mesityl phosphaalkenes have been prepared with various carbon substituents (1.1a-f).32, 42, 43

1.1.2.2 Synthesis of Enantiomerically Pure Phosphaalkenes

To date, there are limited examples that incorporate the acyclic phosphaalkene functionality into chiral structural motifs. The first example was reported by Mathey in 1992 with the synthesis of the tungsten complex 1.4.44 This complex was synthesized using the aforementioned phospha-Wittig-Horner reaction, beginning with tungsten-protected P-menthyl phosphine 1.2. Treatment of phosphine 1.2 with n-BuLi, followed by triethylphosphite and in situ oxidation with m-CPBA afforded phosphonate 1.3. Compound 1.3 was deprotonated with n-BuLi and added to isobutyraldehyde to afford phosphaalkene 1.4. A key advantage of having tungsten- protected phosphine (1.3) and phosphaalkene (1.4) derivatives is the bulky metal carbonyl protecting group permits column chromatography purification under ambient conditions.

Interestingly, hydrogenation and cycloaddition reactions using 1.4 proceed with moderate stereoselectivity due to the enantiomerically pure P-menthyl substituent (de > 90 %). Notably, a metal-free phosphaalkene was never reported. 6

Scheme 1.2 Synthesis of a P-Menthyl Phosphaalkene.

A more recent report from Ozawa in 2008 detailed the synthesis of phosphino- phosphaalkenes possessing planar chirality (1.7, Scheme 1.3).45 Chiral acetal 1.5, obtained by the protection of ferrocenecarboxyaldehyde with a chiral diol, can be selectively deprotonated on the

Cp ring using t-BuLi and functionalized with Ph2PCl. Hydrolysis of the acetal functionality using

TsOH affords aldehyde 1.6, a suitable precursor for the phospha-Peterson reaction. Addition of one equivalent of LiMes*PSiMe3 [obtained in situ from Mes*PH(SiMe3)] to aldehyde 1.6 yields phosphaalkene 1.7 as exclusively the E-isomer.

Scheme 1.3 Synthesis of Planar-chiral Ferrocene-phosphaalkene.

The Gates/Dake group foray into the field of enantiomerically pure phosphaalkenes began in 2008 with the synthesis of the first phosphaalkene-oxazoline (1.10a, Scheme 1.4).46 This class of compound is colloquially referred to as the PhAk-Ox ligand, a contraction of the featured functional groups and homage to the well-established PHOX and BOX ligands from which it was inspired.47, 48 The synthesis of phosphaalkene 1.10a begins with (L)-valinol, which is obtained by

49 the reduction of (L)-valine using NaBH4/I2 in THF. Dehydrative cyclization of this amino alcohol and isobutyric acid yields oxazoline 1.8, which can be converted to ketone 1.9 by deprotonation

7

with sec-BuLi followed by Claisen-type condensation of ethyl benzoate. Importantly, these synthetic steps can be performed on a >10g scale without the need for column chromatography.

Ketone 1.9 can be elaborated to phosphaalkene 1.10a by treatment with one equivalent of

LiMesPSiMe3 [formed in situ from MesP(SiMe3)2], followed by TMS-Cl quench and recrystallization using hexanes or n-pentane.

Scheme 1.4 Representative Synthesis of an Enantiomerically Pure Phosphaalkene Oxazoline.

This modular synthetic route permitted the synthesis of a number of PhAk-Ox derivatives

50 with structural variations shown in Figure 1.4. For example, the use of different Li[ArP(SiMe3)]

51 derivatives [Ar = 2,4,6-(i-Pr)3C6H2, 2-(i-Pr)C6H4, 2-(t-Bu)C6H4] in place of Li[MesP(SiMe3)] in

Scheme 1.4 leads to different steric environments around the phosphorus atom. Additionally, the electronics of C-Ar’ group of PhAk-Ox can be modulated (i.e. Ar’ = 4-(MeO)C6H4, 3,5-

(CF3)2C6H3) by substituting other aryl esters or Weinreb amides for ethyl benzoate. The linking aliphatic gem-dimethyl functionality can be replaced with a cyclopentyl group [i.e. R = (CH2)4] by substituting cyclopentanecarboxylic acid for isobutyric acid. An obvious choice to increase the steric influence of the enantiomerically pure oxazoline moiety would be the substitution of the i-

Pr substituent with a bulkier t-Bu group. This derivative was not prepared due to the high cost of the unnatural t-Bu analogue of (L)-valine [(L)-tert-leucine], however a comparable surrogate52

53 was synthesized with a gem-dimethyl group in the 5-position of the oxazoline (i.e. R’ = CH3).

8

Figure 1.4 Structural Variations in PhAk-Ox Ligands.

1.2 Phosphaalkenes as Monomers

The analogous reactivity of phosphaalkenes and olefins has already been highlighted by the reactions shown in Figure 1.2. The most important method of producing commodity polymers is through the addition polymerization of the C=C bond of olefins. The addition polymerization of a P=C bond in a phosphaalkene was accomplished in 2003.54 Specifically, the polymerization of

MesP=CPh2 (1.1a) afforded poly(methylenephosphine) (PMP, 1.11a, Scheme 1.5). Polymer 1.11a was first isolated from the residue that remained after the distillation of the phosphaalkene monomer. In the same report, the radical- and anion-initiated polymerizations afforded samples of

1.11a with near-identical spectroscopic properties. Shortly after, the radical-initiated polymerization was amenable to the random copolymerization of MesP=CPh2 and styrene (1.12a,

Scheme 1.5).55

Scheme 1.5 Addition Homo- and Copolymerization of MesP=CPh2 to Yield Poly(methylenephosphine) and

Poly(methylenephosphine-co-styrene).

9

Mass spectrometric investigations of oligomers prepared by treating MesP=CPh2 with

MeLi as initiator (25 mol%) provided the first evidence for chain growth in solution at ambient temperature.56 Subsequently, the room temperature polymerization of phosphaalkenes using n-

BuLi was shown to follow a living mechanism. PMPs 1.11a-b were prepared with controlled

-1 molecular weights and low PDIs (M/I = 25:1-100:1, Mn = 8 900 – 29 600 g mol , PDI = 1.04 –

1.15).57 In addition, employing living polystyrene as the anionic initiator afforded polystyrene- block-poly(methylenephosphine) copolymers (1.12b, Scheme 1.7). These novel copolymers possess interesting film-forming properties. Detailed studies of the kinetics of the living anionic polymerization of MesP=CPh2 allowed for the determination of the activation energy for

-1 propagation (Ea = 14.0 ± 0.9 kcal mol ), one of the largest recorded for an addition polymerization.58

Scheme 1.6 Anionic Polymerization of Substituted Phosphaalkenes.

Scheme 1.7 Preparation of Polystyrene-block-poly(methylenephosphine) by Living Anionic Polymerization.

As long as the P=C bond is kinetically stabilized with sterically encumbering substituents, phosphaalkenes bearing a variety of functional substituents can be polymerized. To this end, the ferrocene-containing monomer, MesP=CPh(Fc) (1.1c), has been anionically polymerized to afford

-1 42 the novel redox-active PMP 1.11c (Mn = 9 500 g mol , PDI = 1.21, ΔE1/2 = 0.41 V vs. SCE). 10

Phosphaalkenes bearing polyaromatic chromophores (e.g. 1-naphthyl, 9-phenanthryl) have been synthesized and polymerized using anionic initiators to afford the PMPs 1.11d-e (Mn = 15 100 –

27 100 g mol-1, PDI = 1.14 – 1.37).43 These polymers demonstrate turn-on fluorescent emission selectively when oxidized, making them attractive for sensor applications.

A unique feature of PMPs is their chemical functionality through the phosphorus lone pairs.

54 Homopolymer 1.11a can be oxidized with either H2O2 or S8 (1.13a and 1.13b), coordinated to either borane (1.13c)59 or gold(I) (1.13d),60 and alkylated to yield an ionomer (1.13e) (Scheme

1.8).59 In the case of borane and gold(I), uncoordinated phosphorus moieties could not be observed by 31P NMR spectroscopy indicating complete conversion to the phosphine-borane or phosphine- gold adducts. In contrast, the phosphonium ionomer 1.13e could not be obtained in higher than

50% conversion, possibly due to ionic repulsion. In all cases, molecular weight analysis by GPC of the resulting polymers showed no degradation of the polymer chain, but only the expected increase in molecular weight. For example, gold(I) complex 1.13d, synthesized from a sample of

-1 -1 polymer 1.11a (Mn = 38 900 g mol ), was found to have an Mn of 71 600 g mol .

11

Scheme 1.8 Functionalization of Poly(methylenephosphine)s.

When coordinated to gold(I), amphiphilic phosphaalkene-isoprene block copolymers,

[PI]404-b-[PMP]35 formed self-assembled nanostructures in a block-selective solvent [Rh = 5 nm

(THF), 82 nm (n-heptane)].61 Transmission electron microscopy (TEM) analysis of samples obtained from dilute n-heptane revealed spherical nanostructures (28-32 nm) that were attributed to micelles with a PMP·AuCl core and polyisoprene corona. Remarkably, increasing the PMP block length in the copolymer afforded worm-like gold nanostructures with high aspect ratio.

The use of phosphaalkene/styrene random copolymers in polymer-supported palladium

55 catalysis has been demonstrated. Specifically, the copolymer 1.12a (9 mol% P; Mw = 7000 g

-1 mol , PDI = 1.7) has been employed in combination with Pd2(dba)3 as a catalyst for the Suzuki coupling of phenylboronic acid and bromobenzene. The biphenyl product was isolated in high yield (90 %) and purity without the need for chromatography and the polymer was recovered by simple precipitation.

12

The use of poly(methylenephosphine)s as flame retardants has been reported recently

(Figure 1.5).62 Paper samples were treated with homopolymer 1.11a and its oxide 1.13a and subjected to flame testing and both were found to be competent flame retardants (limiting oxygen index = 25.9 %), with the oxidized homopolymer performing slightly better. Importantly, after leaching with water no loss of flame retardancy was observed.

Figure 1.5 Poly(methylenephosphine) as a Flame Retardent for Paper.

Top: Dynamic sheet formed (DSF) paper made from thermomechanical pulp (TMP) was coated with poly(methylenephosphine oxide) 70a (0.8 mmol P / g) and ignited with a lighter in air. This flame retardant paper is self-extinguishing. Bottom: An untreated DSF TMP sheet was ignited in air and burns completely.

Recently, detailed spectroscopic analysis of homopolymer previously formulated as 1.11a synthesized by radical-initiated polymerization revealed the presence of an unexpected microstructure 1.14 resulting from an isomerization polymerization (Scheme 1.9).63 It was speculated that after the addition of the radical species to the P in MesP=CPh2 affording a C-based radical, a hydrogen atom migrates from the o-Me of mesityl to this carbon radical. Thus, a benzylic 13

radical is formed at the o-Me position that functions as the propagating species and accounts for the microstructure 1.14 (x >> y). The same microstructure has since been observed in PMPs synthesized by anionic polymerization (e.g. 1.11d-e).43

Scheme 1.9 Alternative Microstructure of Poly(methylenephosphine) Using a Nitroxide-mediated Radical

Polymerization Initiator.

1.3 Phosphaalkenes as Ligands

1.3.1 Coordination Properties of Phosphaalkenes

Five coordination modes are possible for phosphaalkene ligands due to the presence of both a phosphorus lone pair and a P=C double bond (Figure 1.6). Still, the preference for ligands of this motif is κ1(P)-coordination (L).64 In certain cases, such as in the complex

1 2 (MesP=CPh2)Pt(PPh3)2, the complex will interconvert between κ (P) and η (P,C) (M) coordination modes in solution.65 This is attributed to the similar energetics for the FMOs of the phosphorus lone pair orbital and the πP=C orbital (see Section 1.1.1). Each coordination mode (e.g.

31 L and M) in (MesP=CPh2)Pt(PPh3)2 can be observed by distinct P NMR shifts during variable temperature NMR experiments. In extreme cases, more exotic coordination modes (e.g. N-P,

Figure 1.6) are possible. For example, the reaction of Mes*P=CH2 with excess Fe2(CO)9 affords

1 2 66 κ (P), η (P,C)-(Mes*P=CH2)[Fe(CO)4]2 (coordination mode N). Additionally, the in situ

1 67 formation of phosphaalkenes from bridging P-containing complexes can yield κ (P), (μ2-P) (O)

2 68 and η (P,C), (μ3-P) (P) coordination environments. The work discussed in this thesis is primarily

14

concerned with κ1(P) phosphaalkene coordination and therefore only the electronic properties pertaining to this bonding mode will be examined in detail.

Figure 1.6 Coordination Modes of Phosphaalkenes.69

The phosphaalkene-metal bonding interaction is electronically unique from related imine-

[predominately κ1(N)] and olefin [predominately η2(C,C)] metal interactions. Although phosphaalkenes are schematically represented as containing a formal P3p-C2p π–bond, thus implying idealized 120° angles for substituents around phosphorus, they do not adopt traditional sp2 geometry. In fact, the P atom is reluctant to hybridize its 3s and 3p orbitals to form sp2 orbitals due to a weak overlap of these AOs.70 As a result, the angle formed at P (i.e. ∠CPC) in a phosphaalkene is significantly reduced and found to be around 100°. Furthermore, theoretical calculations on phosphaethylene have revealed the phosphorus lone pair is high in s-orbital character (66% of the 3s and 34% of the 3p) and therefore weakly σ-donating.71 By analogy, the nitrogen lone pair in HN=CH2 is considerably p-orbital based (39% of the 2s and 61% of the 2p) and strongly σ-donating. Finally, the phosphorus atom is electropositive (χP = 2.1, Pauling) with respect to its neighbouring carbon atom (χC = 2.5, Pauling), thus phosphaalkenes contain the opposite dipole of related nitrogen (χN = 3.0, Pauling) compounds. The contributing AOs of the

π*-bonds in phosphaalkenes and imines are shown in Figure 1.7 and in each case this interaction is dominated by the more electropositive atom. Due to the large contribution of phosphorus atom in the π*-bond, phosphaalkenes are viewed as a CO analogue and, due to their relatively low-lying

23 π*P=C orbital, are excellent π-acceptors for the coordination of late transition metals [particularly 15

Pd(II) and Pt(II)].71 Phosphaalkene ligands will most often coordinate κ1(P) upon complexation to transition metals. However, this should be thought of as a donor-acceptor type interaction (i.e. a filled metal d-orbital is donating into the heavily phosphorus based π*P=C orbital) since phosphaalkenes are weak σ-donors. Although imine ligands also preferentially bind to transition metals in a κ(N) fashion, the electronics of this interaction are different from phosphaalkenes since imines are strongly σ-donating and weakly π-accepting.

Figure 1.7 Contributing AOs of the π*-bond in Carbonyl, Phosphaalkene and Imine Ligands.71

1.3.2 Selected Complexes that Feature Phosphaalkenes

Selected complexes that highlight the distinctive electronic stabilization properties of phosphaalkenes are shown in Figure 1.8. For example, the 2,6-bisphosphaethylenepyridine

(BPEP) four-coordinate 15-electron Fe(I) complex (BPEP-Ph)FeBr (1.15) was reported recently.72

This unusual complex was prepared by one-electron reduction of the dibromide precursor, (BPEP-

Ph)FeBr2, and characterized crystallographically to reveal a distorted trigonal monopyramidal geometry at the iron centre. Further studies (DFT calculations and Mössbauer spectroscopy) corroborated the presence of a localized Fe(I) centre. In contrast, the analogous nitrogen- containing (2,6-di(N-isopropylimine)pyridine)FeCl complex was found to possess an Fe(II)-centre coupled with a ligand-centred radical.73

The interesting electronic properties of phosphaalkenes are also highlighted in [(BPEP-

Ph)2Cu2(μ-PF6)]PF6, 1.16, which is prepared by the spontaneous dimerization of [(BPEP-

74 – Ph)Cu]PF6. The [PF6] anion is generally considered non-coordinating, however the strong π-

16

accepting properties of the P=C bonds in BPEP render the Cu(I)-centre highly electron deficient.

Complex 1.16 is stable in solution and will not dissociate in the presence of MeCN or CO.

Figure 1.8 Selected Examples of Phosphaalkene Complexes.

1.3.3 Phosphaalkenes as Ligands for Catalysis

The uncommon electronics of the P=C bond makes complexes featuring phosphaalkenes attractive candidates for transition metal catalysis. While catalytic applications are beyond the project scope, some historical context should be provided to highlight the applications of phosphaalkenes in this field. For a more in depth overview in phosphaalkenes’ role in catalysis the reader is referred to the following reviews. 71, 75-77

The dπ(metal)–pπ(phosphaalkene) conjugative stabilization of the P=C bond helps stabilize low-valent metal species and can have beneficial effects in transition metal catalysis. For example, the cationic Pd(II)-complex 1.17 can catalyze the hydroamination of 1,3-dienes with modest nucleophiles such as aniline (Scheme 1.10).78 The reaction with π-allyl complexes bearing diphosphine (e.g. dppe or dppf) or diimine ligands under analogous conditions show no formation of the desired product. This reaction is thought to involve a nucleophilic attack of the amine on either a π-allyl Pd(II) or diene Pd(0) complex and the ligand enhances the electrophilicity of the metal centre.

17

Scheme 1.10 Application of Phosphaalkene-based Catalysts in Hydroamination Reactions.

Iridium(I) complexes featuring phosphaalkenes (i.e. complex 1.20, Scheme 1.11) also demonstrate fascinating catalysis properties. Complex 1.20 is obtained in two steps from (BPEP-

H)IrCl (1.18). The first step is thermal rearrangement of 1.18 via a C–H addition/cyclization of the phosphaalkene group with a Mes* substituent to give phosphino-pyridyl-phosphaalkene complex

1.19.79 Subsequent treatment of this compound with t-BuOK in the presence of a neutral ligand

(i.e. t-BuNC) dearomatizes the pyridine ring to generate complex 1.20.80 It has been demonstrated that primary amines are effectively coupled with alcohols in the presence of complex 1.20 (1 mol%) in nonbasic media.

Scheme 1.11 Synthesis and Application of an Ir(I)-phosphaalkene Catalyst in N-alkylations of Amines.

The postulated mechanism for the catalytic reaction in Scheme 1.11 is shown in Scheme

1.12. The effectiveness of complex 1.20 is partially attributed the non-innocence of the ligand (i.e. 18

the ability to protonate the ligand and rearomatize the pyridine moeity). For example, the primary alcohol (PhCH2OH) is dehydrogenated at room temperature via intermediate i, which forms by metal-ligand cooperative deprotonation of the alcohol to form an alkoxide donor. The β-hydrogen elimination of the newly formed alkoxide affords an aldehyde, PhCHO, and metal-hydride ii.

Dehydration/condensation of PhCHO with amine (PhCH2NH2) forms an imine, which can insert into the Ir–H bond of ii and give amido complex iii. Finally, coordination of the neutral ligand to intermediate iii followed by elimination of the desired N-alkylated product reforms 1.20. The success of this reaction is also attributed to the presence of the P=C donor. The π-accepting properties of the P=C bond greatly enhances the Lewis acidity of the metal centre, facilitating base-free O–H bond cleavage.79, 81 In addition, the electronics of the ligand help stabilize intermediate iii, allowing for improved elimination of the amine product.

19

Our group has reported two examples of phosphaalkene-based complexes for transition metal catalysis. First, [MesP=CPh(2-py)]PdCl2 was demonstrated as effective catalyst for the

Overman-Claisen reaction.82 In addition, π-allyl complex 1.21, featuring PhAk-Ox (1.10), was suitable for Pd(II)-catalyzed asymmetric allyl alkylations (Scheme 1.12).53 In this example, the isolated yield [70 % (R = H), 83 % (R = Me)] and enantioselectivity [ee = 85 % (R = H), 92 % (R

= Me)] could be improved by increasing the steric bulk of the oxazoline moiety.

Scheme 1.12 Application of a π-allyl Pd(II)-phosphaalkene Catalyst in Asymmetric Allyl Alkylation.

20

1.4 Goal of the Project

This project began with a relatively singular goal: could the known enantiomerically pure

PhAk-Ox ligand (1.10), developed in the Gates/Dake group, be polymerized in a reproducible fashion by either anionic of radical means of initiation? The resulting polymers were expected to have interesting chiral properties that would certainly complement our previous work in the field and potentially provide a novel macromolecular ligand for asymmetric catalysis. Therefore, there was a requirement to evaluate the reaction of PhAk-Ox with various initiators (either anionic or radical) and, if polymer could in fact be obtained, evaluate these macromolecules as potential ligands.

Concurrently, there was also a motivation to develop other enantiomerically pure phosphaalkene-oxazoline architectures for use as monomers. If PhAk-Ox could be polymerized, it would be interesting to synthesize and polymerize other structurally analogous compounds.

Furthermore, if a reliable synthetic strategy to new enantiomerically pure phosphaalkenes could be developed, it would be beneficial to evaluate these compounds as ligands for late transition metals. While catalysis is often the goal with ligand design experiments, there may be other interesting molecular transformations discovered using new compounds that feature the rather underexplored P=C bond.

1.5 Outline of Thesis

Chapter 2 details the unexpected products obtained after the reaction of PhAk-Ox (1.10a) with MeM nucleophiles (M = Li and MgBr). These studies were initially attempted to assess the feasibility of anionic initiation for the polymerization of PhAk-Ox and took a surprising turn when a new route to enantiomerically pure P-chiral phosphine oxazolines was discovered. Chapter 3 details the copolymeriation of PhAk-Ox and styrene using radical initiation. These copolymers 21

were demonstrated to be viable polymeric ligands for Rh(I) metals, thus becoming the first examples of Rh(I)–PMP macromolecular complexes reported for our group. Chapter 4 discusses the synthesis and polymerization of a novel class of phenylene-bridged phosphaalkene-oxazolines.

Homo- and co-polymers (with styrene) synthesized from this type of phosphaalkene revealed distinct spectroscopic signatures that allowed for the first direct evidence of styrene-phosphaalkene linkages within a copolymer backbone. Chapter 5 highlights the synthesis and first coordination complexes of a novel class of pyridine-bridged phosphaalkene-oxazoline pincer ligands. Copper(I) complexes featuring this unique hybrid pincer ligand displayed interesting electronic properties that were probed experimentally and computationally. In Chapter 6, the potential fortuitous products that can be obtained by carbopalladation of phosphaalkenes, which react with Pd–R bonds in analogous fashion to olefins, are reported. Of note, 2-pyridyl substituted phosphaalkenes could be converted into monoanionic PN ligands in a single step using a newly discovered carbopalladation/dearomatization reaction. Future work and perspective for this project is provided in Chapter 7.

22

Chapter 2: Reaction of an Enantiomerically Pure Phosphaalkene-Oxazoline with MeM Nucleophiles (M = Li and MgBr)*

2.1 Introduction

A logical starting point towards the stereoselective polymerization of PhAk-Ox (1.10a,

Scheme 2.1) using anionic initiators involves the systematic investigation of the stoichiometric addition of potential initiators across the P=C bond of PhAk-Ox. This approach provides a convenient method to model the initiation and propagation steps of the putative anionic polymerization for 1.10a.

Scheme 2.1 Possible Stereoisomeric Products of the Reaction of Methyllithium or Methylmagnesium Bromide and

PhAk-Ox 1.10a.

To date, studies of the addition of alkyl nucleophiles across P=C bonds have been limited to simple phosphaalkenes.83-85 For example, reactions of organolithium reagents (RLi) with

MesP=CPh2 are highly regioselective to afford racemic Mes(R)P–CEPh2 after quenching with an

* Versions of sections of this chapter have been published. Spencer C. Serin, Brian O. Patrick, Gregory R. Dake and Derek P. Gates. Reaction of an Enantiomerically Pure Phosphaalkene-Oxazoline with MeM Nucleophiles (M = Li and MgBr): Stereoselectivity and Noninnocence of the P-Mesityl Substituent. Organometallics 2014, 33(24), 7215- 7222. 23

electrophile [E = H, Me, SiMe3, SiHMe2, P(NEt2)2], with nucleophile addition occurring exclusively at the phosphorus atom.86 The analogous reactions of PhAk-Ox are far more interesting due to their complex stereochemistry. For example, there are four expected isomeric products (2.1) when Me– and H+ are successively added across the P=C bond in 1.10a as shown in Scheme 2.1.

For convenience, the stereoisomers have been named according to the syn (s) or anti (a) relationship between the Me and i-Pr moieties and between the Me and H moieties, respectively

(e.g. for 2.1a,s the Me and i-Pr are anti, and the Me and H are syn).

2.2 Results and Discussion

2.2.1 General Synthetic Strategy

It has previously been shown that treating the phosphaalkene MesP=CPh2 with RLi (R=Me

83, 86 or n-Bu) followed by MeOH affords Mes(R)P–CHPh2. For the present study, PhAk-Ox

(1.10a) was used to gain additional insight into the addition of nucleophiles to the P=C bond. The colourless THF solution of 1.10a immediately became deeply colored upon addition of the organometallic reagent (red for MeLi, orange for MeMgBr) which is characteristic of the

31 1 analogous reactions of MesP=CPh2. Analysis of each reaction mixture by P{ H} NMR spectroscopy suggested that in each case starting material 1.10a (δ = 244) had been completely consumed, however it should be noted that the reaction with MeLi was complete within 30 min while MeMgBr required overnight reaction to reach completion. The spectra of the strikingly different MeMgBr and MeLi reaction mixtures are shown in Figures 2.1(a) and 2.1(b),

respectively. For comparison, the reaction of MesP=CPh2 (δ = 233) with MeLi affords

86 MesP(Me)CPh2Li quantitatively (δ = –42 in THF). The present results suggest a much more

24

complex product mixture with PhAk-Ox, especially in the case of MeLi where signals are detected in two distinct regions of the 31P{1H} NMR spectrum.

The 31P{1H} NMR spectrum of the Grignard-derived reaction mixture, after quenching with MeOH, is shown in Figure 2.1(c) and suggests a major product [ = –39.5 (ca. 90% by

31P{1H} NMR)] along with three minor products [ = –40.3 (2%), –44.4 (4%), –45.1 (4%)]. The

MeLi-derived reaction mixture after MeOH quench, shown in Figure 2.1(d), exhibited two of the same signals [ = –39.5 (14%), –40.3 (14%)] and at least three additional signals ( = –25.1 (33%),

–26.0 (28%), –26.4 (11%)].

Figure 2.1 31P{1H} NMR Spectra (121 MHz, 298 K, THF) of the Reaction and Quenched Products of MeMgBr and

MeLi with 1.10a.

(a) Reaction mixture of 1.10a and MeMgBr after 16 h, (b) reaction mixture of 1.10a and MeLi after 30 min, (c) crude mixture of products after MeOH quench of (a), (d) crude mixture of products after MeOH quench of (b). Except in the case of 2.1a,a assignments are speculative and inferred from the isolation of Pd(II) complexes.

25

2.2.2 Analysis of MeMgBr Addition to Phosphaalkene 1.10a

2.2.2.1 Synthesis of Chiral Phosphine-Oxazoline 2.1a,a

Attempts were made to separate and isolate the products of each reaction through recrystallization. For the Grignard addition reaction (Scheme 2.2), single crystals suitable for

X-ray diffraction were obtained of the major product (31P = –39.5). The molecular structure is shown in Figure 2.2 and identifies the major product as a single diastereomer (2.1a,a), one of the expected addition products.

Scheme 2.2 Synthesis of Enantiomerically Pure Phosphine Oxazoline 2.1a,a.

The solid state structural data was consistent with the diastereomeric purity of the compound at both the phosphorus and adjacent carbon center, as well as retention of the (S)- configuration of the isopropyl group on the oxazoline ring. Interestingly, the anti-relationship between the P–Me and C–H moieties in 2.1a,a suggests that addition across the P=C bond occurs at opposite faces and is highly stereoselective (vide infra). Compound 2.1a,a was fully characterized

1 13 31 22 using NMR spectroscopy ( H, C, P), HRMS, elemental analysis and polarimetry ([훼]D = –

3 -1 -1 -1 4.91 °cm g dm (c = 1.6 × 10 , CH2Cl2)).

26

Figure 2.2 Molecular Structure of 2.1a,a (50% Probability Ellipsoids).

All hydrogen atoms, except H(11), were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)−C(1) 1.885(2), P(1)−C(2) 1.846(2), N(1)–C(21) 1.269(2), O(1)–C(21) 1.369(2) and C(1)−P(1)−C(2) 102.30(8).

2.2.2.2 Postulated Mechanism for Formation of Phosphine 2.1a,a

The addition of MeMgBr is highly stereoselective with 2.1a,a being the predominant product. The high degree of stereoselective induction at the new carbon and phosphorus stereocenters during the Grignard addition to PhAk-Ox 1.10a is striking. We speculate that chelation of 1.10a to Mg2+ (e.g. i in Scheme 2.3) prior to Me group addition holds the oxazoline in position to favor nucleophilic addition to the P=C bond from the face opposite the i-Pr group to minimize steric interactions.* The more reactive nucleophile, MeLi, was observed to react with

1.10a instantaneously while MeMgBr reacted with 1.10a over 12 h, by analysis of the 31P{1H}

NMR spectra of the reaction mixtures. Thus, the addition of MeLi is comparatively non-selective.

* Although we have suggested a two-electron process in Scheme 2.3, a single-electron transfer process is also conceivable for the reaction of 1.10a with MeMgBr. We have not obtained experimental evidence to dismiss either possibility. 27

Scheme 2.3 Postulated Mechanism for the Formation of 2.1a,a.

The rationale for the stereoselective protonation of the resultant carbanion to generate a C–

H bond having an anti configuration with respect to the newly formed P–Me bond, is less obvious.

One might expect that the position of the i-Pr group would slightly favor the syn isomer (i.e. 2.1a,s) over the anti isomer (i.e. 2.1a,a), however the latter is by far the major product (ca. 90%). To account for this observation, we hypothesize that the proton addition may occur in an intramolecular manner from the o-Me of Mes rather than from the external reagent (i.e. MeOH).

We have already shown that the o-Me of the Mes group is involved in the anionic and radical

43, 63 polymerization of MesP=CPh2. We note that the initial anti relationship between the Me and i-Pr groups in ii ideally positions the Mes group for proton transfer from the o-Me group anti to the P-Me moiety to afford iii. Subsequently, MeOH would protonate the resultant benzylic anion of the former Mes group. To test this hypothesis, the reaction of 1.10a and MeMgBr was quenched

31 1 with methanol-d4 and the crude product (containing ca. 90% d-2.1a,a) analyzed by P, H and

2 1 2 1 1 H{ H} NMR spectroscopy. The H{ H} NMR spectrum of crude d-2.1a,a along with the H NMR

2 spectrum of a pure sample of undeuterated 2.1a,a are shown in Figure 2.3. Importantly, the H signal ( = 2.6) coincides with the o-Me of Mes (now –CDH2) and no evidence of a P–CDPh–

1 moiety was observed. In the H NMR spectrum of d-2.1a,a, the signal assigned to P–CHPh– ( =

4.2) integrates to 1H. Moreover, the signal assigned to the o-Me of the Mes group ( = 2.6) is split into two broad overlapping signals that integrate to 3H and 2H for a total of 5H. These results are

28

consistent our postulated mechanism involving proton transfer from the o-Me of Mes as outlined in Scheme 2.3.

2 1 Figure 2.3 Analysis of the H{ H} NMR Spectrum for d-2.1a,a.

2 1 (a) H{ H} NMR spectrum (61.4 MHz, 298 K) of the crude product (containing mostly d-2.1a,a) dissolved in a

CHCl3/CDCl3 mixture. The crude product was isolated from the reaction of 1 with MeMgBr (2 equiv) in THF followed 1 by the addition of methanol-d4. (b) H NMR spectrum (400 MHz, 298 K) of undeuterated 2.1a,a in CDCl3. Assignments made with the aid of 1H-1H COSY and 1H{31P} NMR experiments.

2.2.2.3 Palladium Complexes of Phosphine 2.1a,a

The complexation of enantiomerically-enriched phosphine oxazoline 2.1a,a to late transition metals for catalysis application is of particular interest. P-stereogenic phosphine oxazoline ligands have been synthesized previously,87-90 however no examples exist where the carbon adjacent to the phosphorus contains a fixed stereocentre. Palladium complexes of P,N ligands have been used to catalyze allylic alkylation,91, 92 conjugate addition93, 94 and alkene/CO copolymerization,95, 96 amongst other transformations.

We prepared the Pd(II) complexes 2.2 and 2.3 by treating phosphine-oxazoline 2.1a,a with

Pd(MeCN)2Cl2 or PdMeCl(cod), respectively, in CH2Cl2 (Scheme 2.4). Both products could be precipitated out of the reaction mixture by the addition of hexanes. Alternatively, the allyl Pd(II) 29

complex 2.4 was prepared by treating phosphine 2.1a,a with [(C3H5)PdCl]2 in CH2Cl2, followed by chloride abstraction using AgOTf. Filtration of insoluble AgCl gave crude 2.4 which was purified by repeated washing with hexanes.

Scheme 2.4 Synthesis of Palladium Complexes of 2.1a,a.

Crystals suitable for X-ray diffraction of the complexes 2.2, 2.3, and 2.4 were obtained (for

2.2: slow diffusion of hexanes into the reaction mixture; 2.3: slow diffusion of hexanes into a concentrated CH2Cl2 solution; 2.4: slow evaporation of a concentrated CDCl3 solution). The molecular structures are shown in Figures 2.4-2.6 and each product was fully characterized using

NMR spectroscopy (1H, 13C, 31P) and elemental analysis. Each complex showed an optical rotation

22 3 -1 -1 -1 3 -1 -1 -1 {[훼]D = 2.2: –25.2 ° cm g dm (c = 1.9 × 10 , CH2Cl2); 2.3: -76.2 °cm g dm (c = 1.3 × 10 ,

3 -1 -1 -1 CH2Cl2); 2.4: -10.2 °cm g dm (c = 1.2 × 10 , CH2Cl2)}.

Complexes 2.2, 2.3, and 2.4 display bond lengths and angles that are typical for P,N-chelate complexes. For example, the Pd–P and Pd–N bond lengths in 2.2 [Pd(1)–P(1) = 2.229(3) Å, Pd(1)–

N(1) = 2.082(9) Å] are similar to those found in related phosphine-oxazoline complexes [e.g.

97 [R2P–(alkylene)–Nox·PdCl2]: R = 3,5-Me-C6H3, Pd–P = 2.2183(6) Å, Pd–N = 2.041(2) Å; R = t-

98 Bu, Pd–P = 2.2728(6) Å, Pd–N = 2.054(2) Å]. Additionally, the Pd–P and Pd–N bonds in 2.3

[Pd(1)–P(1) = 2.214(1) Å, Pd(1)–N(1) = 2.164(4) Å] are similar to those found in related

30

phosphine-oxazoline complexes [e.g. [R2P–(alkylene)–Nox·PdMeCl]: R = Ph, Pd–P = 2.208(2) Å,

Pd–N = 2. 141(3) Å;99 R = Ph, Pd–P = 2.210(5) Å, Pd–N = 2.034(7) Å].100 Comparable to the previously reported (phosphine oxazoline)PdMeCl complexes, one product, with the Pd–CH3 trans to the nitrogen of the oxazoline, is formed exclusively. Finally, the Pd–P and Pd–N bonds in 2.4

[Pd(1)–P(1) = 2.287(1) Å, Pd(1)–N(1) = 2.107(4) Å] are consistent with those found in related

+ phosphine-oxazoline complexes [e.g. [R2P–(alkylene)–Nox·Pd(C3H5)] : R = Ph, Pd–P = 2.262(1)

Å, Pd–N = 2. 110(4) Å;101 R = Ph, Pd–P = 2.257(1) Å, Pd–N = 2.073(3) Å]102

31

Figure 2.4 Molecular Structure of 2.2 (50% Probability Ellipsoids).

All hydrogen atoms, except H(11), and a solvent CH2Cl2 were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)−C(11) 1.83(2), P(1)−C(1) 1.80(1), P(1)−Pd(1) 2.229(3), N(1)−Pd(1) 2.082(9), C(21)–N(1) 1.31(2), C(21)–O(1) 1.34(2), Pd(1)−Cl(1) 2.304(3), Pd(1)−Cl(2) 2.390(3), C(21)–N(1)–Pd(1) 127.6(9), C(11)–P(1)–Pd(1) 112.3(4), C(1)−P(1)−C(11) 108.1(7), P(1)−Pd(1)−N(1) 93.3(3).

Figure 2.5 Molecular Structure of 2.3 (50% Probability Ellipsoids).

All hydrogen atoms, except H(3), were omitted for clarity. Selected bond lengths (Å) and angles (deg): C(1)–P(1) 1.837(5), C(3)–P(1) 1.871(4), P(1)–Pd(1) 2.214(1), Pd(1)–C(2) 2.050(5), Pd(1)–Cl(1) 2.396(1), N(1)–Pd(1) 2.164(4), C(13)–N(1) 1.277(6), C(13)–O(1) 1.362(5), C(3)–P(1)–Pd(1) 111.1(1), P(1)–Pd(1)–N(1) 92.12(9), C(13)–N(1)–Pd(1) 132.7(3). 32

Figure 2.6 Molecular Structure of 2.4 (50% Probability Ellipsoids).

All hydrogen atoms, except H(1), were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.873(5), P(1)–C(26) 1.827(5), P(1)–Pd(1) 2.287(1), N(1)–Pd(1) 2.107(4), C(11)–N(1) 1.282(6), C(11)–O(1) 1.344(6), Pd(1)–C(28) 2.242(6), Pd(1)–C(29) 2.114(8), Pd(1)–C(30) 2.100(6), C(1)–P(1)–Pd(1) 107.5(2), P(1)– Pd(1)–N(1) 93.2(1), C(11)–N(1)–Pd(1) 133.0(3).

2.2.3 Analysis of MeLi Addition to Phosphaalkene 1.10a

2.2.3.1 Unexpected Synthesis of Palladium Complex 2.5

Despite repeated attempts, it was not possible to obtain single crystals or to separate the products from the methyllithium reaction mixture. Therefore, this mixture was dissolved in CH2Cl2 and treated with Pd(cod)Cl2 (1 equiv based on 1.10a) in an effort to make crystalline Pd(II)- complexes (Scheme 2.5). Remarkably, a yellow solid precipitated from the reaction mixture after stirring overnight (yield = 31% from 1.10a). The solid was separated by filtration and was washed

31 with cold CH2Cl2. The air-stable solid was dissolved in DMSO-d6 and analyzed by P NMR spectroscopy to reveal a singlet resonance at 40.2 ppm. Orange crystals suitable for X-ray crystallography were obtained from a concentrated solution of the solid in methanol. To our

33

surprise, the molecular structure (Figure 2.7) identified the product as the dimeric palladium(II) species 2.5. Particularly noteworthy is the apparent activation of the o-Me groups of the P-Mes substituent and the ring-opening of the oxazoline moiety. Complex 2.5 was fully characterized using NMR spectroscopy (1H, 13C, 31P), and elemental analysis. Complex 2.5 showed an optical

22 3 -1 -1 -1 rotation [훼]D = –214 ° cm g dm (c = 1.4 × 10 , MeOH).

Scheme 2.5 Unexpected Synthesis of Dimeric Palladium Complex 2.5.

Despite the unexpected nature of its formation, complex 2.5 possesses metrical parameters that are consistent with related palladium(II) complexes. Interestingly, the molecular structure reveals the anti-relationship between the P–Me and C–H moieties within the bicyclic P,C-chelate ligand. Complex 2.5 crystallizes in the chiral P3221 space group (No. 154) and the point group of the palladium(II) dimer is C2 with the two-fold axis passing through the µ-chloro ligand and bisecting the Pd(1)-Cl(2)–Pd(1') plane. The Pd–P and Pd–C bond lengths in 2.5 [Pd(1)–P(1) =

2.199(2) Å; Pd(1)–C(18)= 2.100(7) Å] are consistent with those found in the related P,C-chelate

103 complexes [i.e. [1,2-C6H4(PR2)(CH2)PdL2]: R = t-Bu, Pd–P = 2.238(2) Å, Pd–C = 2.078(7) Å;

R = o-tolyl, Pd–P = 2.266(2) Å, Pd–C = 2.079(7) Å;104 R = o-tolyl, Pd–P = 2.2325(9) Å , Pd–C =

2.053(3) Å].105 Importantly, the angle at C(12), is consistent with sp2 hybridization and its formulation as the iminium carbon, (C–C–N = 120.3(6)°), and the carbon-nitrogen bond length

34

[1.29(1) Å] is consistent with other iminium compounds.106, 107 The 1H-1H COSY NMR spectrum shows a weak interaction between the postulated N-H proton (δ = 7.69) and the proton of the adjacent carbon (δ = 3.88). In addition, there is a short distance (2.4 Å) between the calculated location of the alcohol proton and the chloro ligand, consistent with a hydrogen-bond.

Figure 2.7 Molecular Structure of 2.5 (50% Probability Ellipsoids).

All hydrogen atoms, except H(1), H(2), and H(3), and phenyl rings were omitted for clarity. Selected bond lengths (Å) and angles (°): P(1)–C(1) 1.851(8), C(18)–Pd(1) 2.100(7), P(1)–C(2) 1.798(8), P(1)–Pd(1) 2.199(2), Pd(1)–Cl(1) 2.411(2), Pd(1)–Cl(2) 2.444(2), C(12)–C(18) 1.48(1), N(1)–C(12) 1.29(1), P(1)–Pd(1)–C(18) 76.7(2), Pd(1)–Cl(2)– Pd(1’) 83.99(8), C(12)–C(18)–Pd(1) 102.3(4), C(12)–C(18)–C(19) 117.7(6), C(18)-C(12)-N(1) 120.3(6).

As mentioned previously, dinuclear complex 2.5 has very low solubility in CH2Cl2 and precipitates directly from the reaction mixture. After filtration to isolate 2.5, the mother liquor was

35

analyzed by 31P{1H} NMR spectroscopy. The presence of several new signals, none of which were present prior to adding Pd(cod)Cl2, suggests that additional Pd(II) complexes were present.

Compound 1.10a was no longer present however 2.2, which was synthesized independently (vide infra), was observed (31P = 10.5). Fortuitously, a single crystal was obtained from the NMR tube on standing for several weeks. Analysis of the crystal by X-ray crystallography permitted it to be identified as the chelating complex 2.6 (Figure 2.8). Interestingly, the P–Me and C–H moieties have a syn arrangement in Pd-complex suggesting that both addition of Me– (from MeLi) and protonation occurred on the same face of the P=C bond. Unfortunately, we were unable to isolate enough 2.6 to enable complete spectroscopic characterization or to assign its 31P NMR chemical shift.

Figure 2.8 Molecular Structure of 2.6 (50% Probability Ellipsoids).

Hydrogen atoms, except H(1), were omitted for clarity. Selected bond lengths (Å) and angles (°): P(1)–C(1) 1.87(1), P(1)–C(2) 1.84(1), P(1)–Pd(1) 2.251(4), N(1)–Pd(1) 2.061(4), Pd(1)–Cl(1) 2.309(3), Pd(1)–Cl(2) 2.387(4), C(1)– P(1)–C(2) 106.1(6), P(1)–Pd(1)–N(1) 93.5(3).

36

2.2.3.2 Postulated Mechanism for Formation of Complex 2.5

As previously stated, no distinct intermediates could be obtained after the MeOH quench of the addition of MeLi to phosphaalkene 1.10a. However, the isolation (or observation by 31P

NMR or X-ray crystallographic analysis) of the complexes 2.2, 2.5, and 2.6 from the subsequent addition of Pd(cod)Cl2 to the reaction intermediates (i.e. 2.7, Scheme 2.5) suggested the formation of at least three distinct products after MeOH quench (Figure 2.9). There are only two resonances common to both MeLi and MeMgBr reactions (31P = –39.5 and –40.3, Figure 2.2c and 2.2d), the former being unequivocally assigned to isolable 2.1a,a. Thus, we conclude that the signal at –40.3 ppm must be attributed to 2.1a,s. We postulate that complex 2.5 comes from intermediate 2.7.

Interestingly, the signals at –44.4 and –45.1 ppm are only observed in the Grignard reaction. We tentatively assign these resonances to the two remaining isomers (2.1s,a and 2.1s,s).

Figure 2.9 Postulated Intermediates after MeLi Addition to Phosphaalkene 1.10a.

A plausible mechanism to account for the formation of complex 2.5 from 2.7 is proposed in Scheme 2.6. Likely, the addition of Me– across the P=C bond in 1.10a proceeds first to afford intermediate iv. The carbanion in iv is ideally positioned to abstract a proton from the o-Me moiety of the P–Mes substituent giving intermediate v. The resultant benzylic carbanion in v is positioned to ring-open the oxazoline moiety to afford the seven-membered heterocyclic species vi. This transformation is quite unusual since alkyllithium reagents are not generally known to add to the carboximidate carbon of oxazolines. We found only one literature example of an intramolecular

37

addition of an aryllithium to an oxazoline carboximidate carbon atom that is vaguely reminiscent of the present observation.108 The protonation of alkoxide vi affords the putative compound 2.7 which we speculate is the major species in the NMR spectrum shown in Figure 2.1(d) [2.7:  = –

25.1]. Presumably, the other signals near –25 ppm result from other possible isomers of 2.7. We also note that the isolated yield of complex 2.5 (31%) is similar to the integration of the 31P{1H} signal tentatively assigned to 2.7 in the initial reaction mixture (33%).

Scheme 2.6 Postulated Mechanism for the Formation of Complex 2.5.

The binding of phosphine 2.7 to palladium(II) affords vii in which the o-CH2 group

(formerly of Mes) is susceptible to Pd-insertion and formal loss of HCl to afford iminium species viii. Similar proton abstractions from the o-Me substituent have been observed for Pd(II) or Pt(II)

38

complexes of o-tolyl-substituted and related phosphines.103, 109 The final step involves the loss of cod from viii and dimerization to the final product 2.5.

It is important to note that reactions involving the C–H bond of the o-Me group in P-Mes compounds are rare and typically involve insertion into the bond rather than proton or hydrogen atom transfer.110 Therefore, the present results are particularly intriguing and further illustrate that mesityl can be a non-innocent substituent in low-coordinate phosphorus chemistry. Furthermore, a straightforward route to enantiomerically-pure phosphine-oxazoline 2.1a,a has been developed, and this ligand is currently being investigated for application in palladium-catalyzed asymmetric transformations.

2.3 Summary

In closing, we have uncovered a surprisingly complex reaction sequence for the seemingly simple addition of nucleophiles across the P=C bond of a chiral phosphaalkene. The addition of

MeMgBr to PhAk-Ox (1.10a) followed by the addition of MeOH (a proton source) affords a mixture of four products which we attribute to the four stereoisomers 2.1a,a, 2.1a,s, 2.1s,a and 2.1s,s.

The reaction is highly diastereoselective with 2.1a,a comprising ca. 90% of the reaction mixture.

In contrast, the analogous reactions of 1.10a with MeLi afford a roughly equimolar mixture of

2.1a,a and 2.1a,s, while bicyclophosphine 2.7 is the predominant product. Although the ultimate fate of the reaction in each case is quite different, we have shown unequivocally that a proton is transferred from the o-Me group of the P-Mes substituent to the intermediate MesP(Me)–

CPhCMe2–Ox anion in both the MeMgBr and MeLi reactions. These unexpected results reveal that P–Mes phosphaalkenes have a much more complex reaction chemistry than previously observed. In future studies, we intend to exploit this stereoselective chemistry to design of enantiopure phosphine ligands and to achieve stereoselective polymerization of P=C bonds. 39

2.4 Experimental Section

2.4.1 Materials and Methods

All manipulations were performed using standard Schlenk or glovebox techniques under nitrogen atmosphere. CH2Cl2 and hexanes were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. THF was dried over sodium/ benzophenone ketyl and distilled prior to use. Methanol, methanol-d4, CDCl3, and DMSO-d6 were deoxygenated with

46 111 112 nitrogen prior to use. Compounds PhAk-Ox (1.10a), Pd(cod)Cl2, PdMeCl(cod) and

113 Pd(MeCN)2Cl2 were synthesized according to literature procedures. NMR spectra were

1 recorded at 298 K on 300 or 400 MHz spectrometers (operating frequency for H). 85% H3PO4 was used as an external standard (δ 0.0) for 31P NMR spectra. 1H NMR spectra were referenced to residual protonated solvent, and 13C{1H} NMR spectra were referenced to the deuterated solvent.

Elemental analyses were performed in the UBC Chemistry Microanalysis Facility. The optical rotations were measured at a concentration in g per 100 mL and their values (average of 10 measurements) were obtained on a Jasco P-1010 polarimeter

2.4.2 Synthesis of (R)-MesMeP-(S)-CHPhC(Me)2(CNOCH(i-Pr)CH2) (2.1a,a)

To a cooled solution (0 °C) of phosphaalkene 1.10a (2.5 g, 6.4 mmol) in THF (25 mL) was added MeMgBr (3.0 M solution in THF, 4.5 mL, 13.4 mmol). The orange reaction was warmed to room temperature and stirred for 14 h. To this solution was added degassed MeOH (2 mL). From the resultant colorless solution, THF was removed in vacuo, affording a yellow solid. The soluble fraction was extracted into hexanes (3 × 10 mL), and the resultant solution was evaporated to dryness, affording a light brown oil. The light brown oil was dissolved in minimal hexanes (5 mL) and filtered through a bed of dry Celite. The filtrate was cooled to −30 °C in a freezer upon which colorless crystals formed. The crystals were filtered and washed with cold hexanes (2 × 5 mL) to 40

afford phosphine 2.1a,a (1.70 g, 65%). Single crystals suitable for X-ray diffraction were obtained after a concentrated solution of 2.1a,a in hexanes was left in a −30 °C glovebox freezer.

31 1 P NMR (162 MHz, CDCl3): δ −39.5 (s). H NMR (400 MHz, CDCl3): δ 7.59−7.20 (br m, 5H), 6.85 (s, 2H), 4.19 (d, JPH = 5 Hz, 1H), 3.68-3.58 (m, 1H), 3.32-3.21 (m, 2H), 2.62 (s, 6H),

2.24 (s, 3H), 1.30 (s, 3H), 1.28 (m, 1H), 1.22 (s, 3H), 0.92 (d, JPH = 7 Hz, 3H), 0.85 (d, J = 7 Hz),

13 1 0.64 (d, J = 7 Hz); C{ H} NMR (101 MHz, CDCl3): δ 171.7 (d, J = 3 Hz), 144.6, 139.6 (d, J =

8 Hz), 138.6, 132.4 (d, J = 26 Hz), 131.9, 129.7, 128.8, 127.9, 126.4, 71.9, 69.3, 51.0 (d, J = 23

Hz), 40.8 (d, J = 21 Hz), 32.2, 26.4 (d, J = 8 Hz), 23.8 (d, J = 11 Hz), 23.2, 20.8, 19.4, 17.7, 10.2,

22 3 −1 −1 10.1. HRMS calcd for C26H36NOP: 409.2535; found: 409.2538; [훼]D = −4.91° cm g dm (c

−1 = 1.6 × 10 , CH2Cl2). Anal. Calcd for C26H36NOP: C, 76.25; H, 8.86; N, 3.42; found: C, 76.40;

H, 9.05; N, 3.42.

41

Table 2.1 COSY Correlation for Compound 2.1a,a.

1H proton no. COSY correlationd δ (ppm)(mult. J(Hz))a,b,c H1/H2e 6.85 (s) H7/H8/H9 H3/H5e 2.62 (s) H1/H2 H4 2.24 (s) H1/H2 H6 0.92 (d, 7) H7 4.19 (d, 5) H8/H9/H10/H11/H2 7.59−7.20 (br m) H13e 1.28 (s) H14e 1.22 (s) H15 3.68-3.58 (m) H15’/H16; H17 H15’ 3.32-3.21 (m) H15; H16; H17 H16 3.32-3.21 (m) H15; H15’; H17 H17 1.28 (m) H15; H15’/H16; H18; H19 H18 0.85 (d, 7) H17 H19 0.64 (d, 7) H17 a Recorded at 400 MHz. b Assignments made based on HSQC, COSY and 1H{31P} data. c H and H’ are assigned arbitrarily. d Only correlations which could unambiguously assigned are recorded. e Arbitrarily assigned.

2.4.3 Synthesis of d-2.1a,a

To a cooled solution (0 °C) of phosphaalkene 1.10a (0.20 g, 0.51 mmol) in THF (5 mL) was added MeMgBr (3.0 M solution in THF, 0.36 mL, 1.1 mmol). The reaction was warmed to room temperature and stirred overnight. To this solution was added methanol-d4 (1 mL). From the resultant colorless solution, THF was removed in vacuo, affording a yellow solid. The soluble fraction was extracted into hexanes (3 × 3 mL), and the resultant solution was evaporated to dryness to yield crude d-2.1a,a (0.17 g, 81%). 42

31 1 1 Major product d-2.1a,a: P{ H} NMR (162 MHz, CDCl3): δ −39.6 (s). H NMR (400 MHz,

CDCl3): δ 7.59 (m, 1H), 7.35−7.20 (m, 4H), 6.85 (s, 2H), 4.22 (d, JPH = 5 Hz, 1H), 3.64 (m, 1H),

3.26 (m, 2H), 2.64 (s, 3H), 2.62 (s, 2H), 2.24 (s, 3H), 1.34 (s, 3H), 1.33 (m, 1H), 1.24 (s, 3H), 0.93

2 1 (d, JPH = 7 Hz, 3H), 0.86 (d, J = 7 Hz), 0.65 (d, J = 7 Hz); H{ H} [61.4 MHz, CHCl3/CDCl3 (ca.

20:1, v:v)]: δ 2.6 (br s).

2.4.4 Synthesis of (2.1a,a)PdCl2 (2.2)

To a solution of 2.1a,a (50 mg, 0.12 mmol) in CH2Cl2 (1 mL) was added solid

PdCl2(MeCN)2 (32 mg, 0.12 mmol). The reaction mixture was layered with hexanes and cooled at

−30 °C overnight. The resulting yellow crystals were washed with hexanes (2 × 1 mL) to yield 2.2

(45 mg, 63%) as a yellow solid. Crystals, suitable for X-ray diffraction, were obtained after a concentrated solution of 2.2 in CH2Cl2 was layered with hexanes and left in a −30 °C glovebox freezer.

31 1 P NMR (162 MHz, CDCl3): δ 10.5 (s). H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8 Hz,

1H), 7.47 (t, J = 8 Hz, 1H), 7.35 (t, J = 8 Hz, 1H), 7.19 (t, J = 8 Hz, 1H), 6.85 (overlapping s, 2H),

6.64 (d, JHH = 8 Hz, 1H), 5.57 (m, 1H), 4.38 (dd, J = 9, 4 Hz, 1H), 4.25 (dd, J = 10, 9 Hz, 1H),

3.31 (d, JPH = 15 Hz, 1H), 2.89 (m, 1H), 2.90-2.70 (br s, 6H), 2.25 (s, 3H), 2.06 (d, JPH = 12 Hz,

13 1 3H), 1.46 (s, 3H), 1.14 (s, 3H), 0.98 (d, J = 7 Hz, 3H), 0.78 (d, JHH = 7 Hz, 3H). C{ H} NMR

(101 MHz, CDCl3): δ 174.5, 141.9 (d, J = 9 Hz), 134.8, 132.2 (d, J = 5 Hz), 131.8 (d, J = 10 Hz),

129.7, 129.1, 128.6, 127.5, 71.4, 68.6, 53.5, 51.4 (d, J = 20 Hz), 43.0, 29.7, 28.1, 27.3 (d, J = 7

22 3 −1 −1 −1 Hz), 25.8, 20.8, 19.0, 17.6 (d, J = 41 Hz), 13.98; [훼]D = −25.2° cm g dm (c = 1.9 × 10 ,

CH2Cl2). Anal. Calcd for C26H36NOPPdCl2: C, 53.21; H, 6.18; N, 2.39; found: C, 53.17; H, 6.03;

N, 2.33.

43

Table 2.2 COSY Correlation for Compound 2.2.

1H proton no. COSY correlationd δ (ppm)(mult. J(Hz))a,b,c H1/H2e 6.85 (s) H3/H4; H5 H3/H4e 2.90-2.70 (br s) H1/H2 H5 2.25 (s) H1/H2 H6 2.06 (d, 12) H7 3.31 (d, 15) H8e 8.01 (d, 8) H9 H9e 7.47 (t, 8) H8; H10 H10 7.35 (t, 8) H9; H11 H11e 7.19 (t, 8) H10; H12 H12e 6.64 (d, 8) H11 H13e 1.46 (s) H14e 1.14 (s) H15 4.38 (dd, 9, 4) H15’; H16 H15’ 4.25 (dd, 10, 9) H15; H16 H16 5.57 (m) H15; H15’; H17 H17 2.89 (m) H16; H18; H19 H18e 0.98 (d, 7) H17 H19e 0.78 (d, 7) H17 a Recorded at 400 MHz. b Assignments made based on HSQC, COSY and 1H{31P} data. c H and H’ are assigned arbitrarily. d Only correlations which could unambiguously assigned are recorded. e Arbitrarily assigned.

2.4.5 Synthesis of (2.1a,a)PdMeCl (2.3)

To a solution of 2.1a,a (300 mg, 0.73 mmol) in CH2Cl2 (6 mL) was added solid

Pd(cod)MeCl (190 mg, 0.73 mmol). The reaction mixture was stirred overnight and subsequently concentrated to 2 mL in vacuo. Hexanes (20 mL) was added to precipitate the product. Filter the resultant white solid, rinsed with additional hexanes (2 × 10 mL), and dried in vacuo to yield 2.3 44

(360 mg, 92%) as a white solid. Crystals, suitable for X-ray diffraction, were obtained after a concentrated solution of 2.3 in CH2Cl2 was layered with hexanes and left in a −30 °C glovebox freezer.

31 1 P NMR (162 MHz, CDCl3): δ 7.9 (s). H NMR (400 MHz, CDCl3): 8.17 (d, J = 8 Hz,

1H), 7.44 (t, J = 8 Hz, 1H), 7.32 (t, J = 8 Hz, 1H), 7.25 (t, J = 8 Hz, 1H), 6.91 (overlapping s, 3H),

5.18 (m, 1H), 4.24 (dd, J = 9 Hz, 4.0 Hz), 4.07 (t, J = 9 Hz, 1H), 3.67-2.11 (overlapping br s, 6H),

3.54 (d, J = 15 Hz, 1H), 2.82 (m, 1H), 2.27 (s, 3H), 1.52 (d, J = 9 Hz, 1H), 1.18 (s, 3H), 1.13 (s,

3H), 0.95 (d, J = 7 Hz, 3H), 0.72 (d, J = 7 Hz, 3H), 0.58 (d, J = 3 Hz, 3H); 13C{1H} NMR (101

MHz, CDCl3): δ 172.9, 140.9, 137.0, 131.9 (d, J = 8 Hz), 131.8 (d, J = 5 Hz), 129.6, 128.5, 127.9,

127.8 (d, J = 5 Hz), 125.6 (d, J = 41 Hz), 70.3, 67.8, 54.3 (d, J = 20 Hz), 42.4 (d, J = 4 Hz), 29.8,

22 3 -1 -1 28.9, 27.7 (d, J = 7 Hz), 20.8, 19.1, 16.2, 15.9, 13.8, -2.1; [훼]D = -76.2 °cm g dm (c = 1.3 ×

-1 10 , CH2Cl2); Anal. Calcd for C27H39ClNOPPd: C, 57.25; H, 6.94; N, 2.47; found: C, 57.02; H,

7.05; N, 2.37.

45

Table 2.3 COSY Correlation for Compound 2.3.

1H proton no. COSY correlationd δ (ppm)(mult. J(Hz))a,b,c H1/H2e 6.91 (br s) H5 H3/H4e 3.67-2.11 (br s) H5 2.27 (s) H1/H2 H6 1.52 (d, 9) H7 3.54 (d, 15) H8e 8.17 (d, 8) H9 H9e 7.44 (t, 8) H8; H10 H10 7.32 (t, 8) H9; H11 H11e 7.25 (t, 8) H10; H12 H12e 6.91 (br s) H11 H13e 1.18 (s) H14e 1.13 (s) H15 4.24 (dd, 8.8) H15’; H16 H15’ 4.07 (t, 9.4) H15; H16 H16 5.18 (m) H15; H15’; H17 H17 2.82 (m) H16; H18; H19 H18e 0.95 (d, 7) H17 H19e 0.72 (d, 7) H17 H20 0.58 (d, 3) a Recorded at 400 MHz. b Assignments made based on HSQC, COSY and 1H{31P} data. c H and H’ are assigned arbitrarily. d Only correlations which could unambiguously assigned are recorded. e Arbitrarily assigned.

2.4.6 Synthesis of (2.1a,a)Pd(C3H5)∙OTf (2.4)

A solution of [(C3H5)PdCl]2 (70 mg, 0.18 mmol) and 2.1a,a (150 mg, 0.37 mmol) in

CH2Cl2 (2 mL) was stirred for 1 h, then AgOTf (94 mg, 0.37 mmol) was added and the mixture stirred for 1 h. The solution was filtered through a bed of dry Celite, and the solvent evaporated

46

in vacuo. The resulting oil was triturated with hexanes (2 mL) and the solid washed with hexanes

(2 × 2 mL). The solid was dried in vacuo to yield 2.4 (150 mg, 58%) as an off-white solid.

Crystals, suitable for X-ray diffraction, were obtained from slow evaporation of a concentrated solution of 2.4 in CDCl3.

31 1 P NMR (162 MHz, CDCl3): δ -5.26 (major), -7.48 (minor) (ca. 1.0:0.5, respectively); H

13 1 and C NMR assigned only for major isomer: H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8 Hz,

1H), 7.74-7.67 (m, 1H), 7.39-7.33 (m, 2H), 7.13 (br s, 1H), 6.98 (br s, 2H), 5.81-5.68 (m, 1H),

4.90-4.81 (m, 1H), 4.76-4.70 (m, 1H), 4.53 (t, J = 9 Hz, 1H), 4.42 (dd, J = 14, 9 Hz, 1H), 4.35-

4.28 (m, 1H), 3.76 (d, J = 15 Hz, 1H), 3.67 (d, J = 7 Hz, 1H), 2.82 (br s, 3H), 2.69 (br s, 3H), 2.61

(d, J = 12 Hz, 1H), 2.30 (br s, 3H), 2.27-2.20 (m, 1H), 1.52 (d, J = 8 Hz, 3H), 1.14 (br s, 6H), 1.02

13 1 (d, J = 7 Hz, 3H), 0.72 (d, J = 7 Hz, 3H); C{ H} NMR (101 MHz, CDCl3): δ 176.0, 141.9 (d, J

= 2 Hz), 141.6, 141.5, 135.6, 132.0, 131.4 (d, J = 5 Hz), 130.4, 128.9, 128.4 (d, J = 2 Hz), 126.9

(d, J = 6 Hz), 125.6, 125.3, 122.3, 120.8 (d, J = 5 Hz), 119.2, 80.6 (d, J = 28 Hz), 76.6, 68.3, 54.5

(d, J = 18 Hz), 54.2, 43.5 (d, J = 6 Hz), 30.5, 29.3 (d, J = 6 Hz), 27.4 (d, J = 6 Hz), 24.5 (br), 20.6,

22 3 -1 -1 -1 18.6, 16.1 (d, J = 32 Hz), 13.6; [훼]D = -10.2 °cm g dm (c = 1.2 × 10 , CH2Cl2); Anal. Calcd for C30H41F3NO4PPdS: C, 51.03; H, 5.85; N, 1.98; found: C, 50.70; H, 5.64; N, 1.97.

2.4.7 General Procedure for Addition of MeLi to 1.10a

To a cooled (−78 °C) solution of phosphaalkene 1.10a (0.30 g, 0.76 mmol) in THF (5 mL) was slowly added MeLi in Et2O (0.76 mL, 1.5 M, 1.14 mmol). The cooled solution was warmed to room temperature and stirred 30 min. To the resultant red solution was added degassed MeOH

(0.5 mL). THF was removed in vacuo, affording a white foam residue. The soluble fraction was extracted into hexanes (3 × 5 mL), and the resultant solution was evaporated to dryness to afford a pale yellow viscous liquid (0.29 g, 93%). 47

31 1 P{ H} NMR (128 MHz, CDCl3): δ −25.1 (33%), −26.0 (28%), −26.4 (11%), −39.5

(14%), −40.3 (14%).

2.4.8 Synthesis of Palladium(II) Dimer 2.5

A solution of the liquid from the previous section (0.29 g, 0.71 mmol) in CH2Cl2 (2 mL) was added to solid Pd(cod)Cl2 (0.22 g, 0.76 mmol). The reaction was stirred at room temperature overnight, affording a yellow precipitate. Filtration and cold CH2Cl2 (3 × 2 mL) washing of the solid, followed by drying in vacuo gave complex 2.5 as a yellow powder (0.14 g, 31%). Crystals, suitable for Xray diffraction, were obtained after a concentrated solution of 2.5 in ethanol was left in a −30 °C freezer.

31 1 P NMR (128 MHz, DMSO-d6): δ 40.16 (s). H NMR (300 MHz, DMSO-d6): δ 7.82 (s,

2H), 7.69 (s, 2H), 6.40 (s, 8H), 5.91-5.88 (overlapping br s, 4H), 4.50 (s, 2H), 4.22 (s, 2H), 3.88

(s, 2H), 3.14 (d, JPH = 17 Hz, 2H), 2.89 (d, J = 11 Hz, 2H), 1.46 (s, 6H), 1.29 (s, 6H), 1.22 (m,

2H), 0.50 (d, JPH = 14 Hz, 6H), 0.31 (d, J = 6 Hz, 6H), 0.15 (s, 6H), 0.11 (d, J = 6 Hz, 6H), −0.14

13 1 (s, 6H). C{ H} NMR (101 MHz, DMSO-d6): δ 193.4 (d, J = 9 Hz), 150.3 (d, J = 20 Hz), 142.0

(d, J = 3 Hz), 139.2, 133.4, 132.8, 131.8 (d, J = 6 Hz), 130.4 (d, J = 8 Hz), 129.3 (d, J = 9 Hz),

128.4, 128.0, 127.9, 124.5 (d, J = 18 Hz), 63.5, 63.2, 63.1, 61.4, 46.9, 42.5, 29.2, 29.0, 27. 7, 20.9,

22 3 −1 −1 −1 20.5 (d, J = 3 Hz), 19.1 (d, J = 9 Hz), 8.0, 7.6; [훼]D = −214° cm g dm (c = 1.4 × 10 , MeOH).

Anal. Calcd for C52H72N2O2P2Pd2Cl4: C, 53.21; H, 6.18; N, 2.39; found: C, 53.21; H, 6.14; N,

2.41.

48

Table 2.4 COSY Correlation for Compound 2.5.

1H proton no. COSY correlationd δ (ppm)(mult. J(Hz))a,b,c H1/H2e 6.91 (overlapping s) H3/H4 H3e 1.46 (s) H1 H4e 1.29 (s) H2 H6 0.50 (d, 14) H7 2.89 (d, 11) H8/H9/H11/H12e 6.40 (s) H10 H10 7.82 (s) H8/H9/H11/H12 H13e 0.15 (s) H14e -0.14 (s) H15 7.69 (s) H16 H16 3.88 (s) H15; H17’; H19 H17 4.22 (s) H17’ H17’ 2.89 (d, 11) H17; H16 H18 4.50 (s) H19 1.22 (m) H16; H20; H21 H20e 0.31 (d, 6) H19 H21e 0.11 (d, 6) H19 a Recorded at 400 MHz. b Assignments made based on HSQC, COSY and 1H{31P} data. c H and H’ are assigned arbitrarily. d Only correlations which could unambiguously assigned are recorded. e Arbitrarily assigned.

49

2.4.9 X-ray Crystallographic Studies

All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX II diffractometer with graphite-monchromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All nonhydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected for absorption effects (SADABS), Lorentz, and polarization effects. All calculations were performed using SHELXL-2014 crystallographic software package from Bruker AXS.114 Absolute configuration was confirmed on the basis of the

115 refined Flack parameter. Compound 2.2 (single PdCl2) crystallizes with a disordered molecule of dichloromethane in the asymmetric unit. In addition, positional disorder was observed, but only two PdCl2 molecules could be located using the difference map and were refined anisotropically.

Their respective populations were refined to the final occupancy of 0.9 {Pd(1)}, 0.05 {Pd(1a)}, and 0.05 {Pd(1b)}. Compound 2.6 (PdCl2) crystallizes with positional disorder, but only the large atoms {Pd(1a), Cl(1a), Cl(2a), P(1a)} could be located using the difference map and were refined anisotropically. Their respective populations were refined to the final occupancy of 0.960(2)

{Pd(1)} and 0.040(2) {Pd(1a)}. Some crystallographic data has been deposited with the

Cambridge Structural Database: 1027332, 1027333, 1027331, 1027330.

50

a Table 2.5 X-ray Data Collection and Refinement Details for Compounds 2.1a,a, 2.2, and 2.3.

2.1a,a 2.2 2.3

formula C26H36NOP C26H36NOPPdCl2·CH2Cl2 C27H39NOPPdCl fw 409.53 671.75 566.41 cryst syst orthorhombic monoclinic monoclinic space group P212121 P1211 P1211 colour colourless yellow yellow a (Å) 7.1579(6) 9.916(2) 9.5338(9) b (Å) 16.068(1) 12.608(3) 18.382(2) c (Å) 20.646(2) 12.643(3) 16.240(2) α (deg) 90 90 90 β (deg) 90 102.349(4) 106.618(5) γ (deg) 90 90 90 V (Å3) 2374.5(3) 1543.9(6) 2727.2(5) T (K) 90(2) 90(2) 90(2) Z 4 2 4 μ(Mo Kα) (mm-1) 0.132 1.019 0.856 cryst size (mm3) 0.15×0.27×0.30 0.24×0.23×0.13 0.19×0.15×0.13 -3 Dcalcd. (Mg m ) 1.146 1.445 1.380 2θ(max) (°) 60.2 50.8 59.4 no. of reflns 41678 13914 23766 no. of unique data 6967 5533 14600 R(int) 0.0427 0.0376 0.0471 refln/param ratio 25.8 16.0 24.5 b R1 [I > 2σ(I)] 0.0342 0.0632 0.0597 c wR2 [all data] 0.0884 .1624 0.1095 GOF 1.021 1.180 1.007 a Adapted with permission from Organometallics, 2014, 33, 7215-7222. © 2014 American Chemical Society. b c 2 2 2 2 2 2 1/2 R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표|. w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

51

Table 2.6 X-ray Data Collection and Refinement Details for Compounds 2.4, 2.5, and 2.6.a

2.4 2.5 2.6

formula C29H41NOPPd∙SO3CF3 C52H72N2O2P2Pd2Cl4 C26H36NOPPdCl2 fw 706.10 1173.66 586.83 cryst syst orthorhombic trigonal monoclinic space group P212121 P3221 P1211 colour yellow orange yellow a (Å) 10.917(1) 20.139(2) 9.246(3) b (Å) 15.378(2) 20.139(2) 15.111(5) c (Å) 18.761(2) 13.776(1) 9.629(3) α (deg) 90 90 90 β (deg) 90 90 95.114(6) γ (deg) 90 120 90 V (Å3) 3149.7(5) 4839(1) 1340.0(7) T (K) 90(2) 90(2) 90(2) Z 4 3 2 μ(Mo Kα) (mm-1) 0.758 0.806 0.970 cryst size (mm3) 0.18×0.15×0.14 0.74×0.28×0.10 0.15×0.12×0.04 -3 Dcalcd. (Mg m ) 1.476 1.208 1.454 2θ(max) (°) 60.1 55.8 44.7 no. of reflns 36512 50106 11966 no. of unique data 9697 7729 3410 R(int) 0.0522 0.0551 0.0577 refln/param ratio 25.3 25.9 11.0 b R1 [I > 2σ(I)] 0.0442 0.0297 0.0458 c wR2 [all data] 0.1051 0.0833 .1134 GOF 0.856 0.604 1.123 a Adapted with permission from Organometallics, 2014, 33, 7215-7222. © 2014 American Chemical Society. b c 2 2 2 2 2 2 1/2 R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표|. w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

52

Chapter 3: Phosphaalkene-Oxazoline Copolymers with Styrene as Chiral

Ligands for Rhodium(I)*

3.1 Introduction

The development of macromolecules containing transition metals is a growing area of study in polymer science.116 These inorganic-organic hybrid materials can display fascinating redox, catalytic, magnetic, or photophysical properties. For these reasons, the exploration of functional phosphorus-containing polymers as macromolecular ligands has attracted considerable attention.117, 118 Ligands containing phosphorus atoms are ubiquitous in coordination chemistry as excellent soft donors for transition metals. Moreover, the structures of molecular phosphines can be finely tuned to control their donor-acceptor properties, incorporate chelating functions and to feature molecular asymmetry at the P(III) atom or elsewhere. In contrast, examples of macromolecules featuring P-chiral phosphines or pendant enantiomerically-pure moieties are relatively sparse.119-122

Selected examples of optically-active polymeric phosphine-metal-complexes are shown in

Figure 3.1. One synthetic strategy involves the step growth polymerization or copolymerization of a functionalized chiral phosphine ligand to incorporate the motif into the polymer main chain

(A,123-126 B127 and C128-130). Typically, low degrees of polymerization are obtained following this

* Versions of sections of this chapter have been published. Julien Dugal-Tessier, Spencer C. Serin, Emmanuel B. Castillo-Contreras, Eamonn D. Conrad, Gregory R. Dake and Derek P. Gates. Enantiomerically Pure Phosphaalkene-Oxazoline (PhAk-Ox): Synthesis, Scope and Copolymerization with Styrene. Chem Eur. J. 2012, 18(20), 6349-6359. Spencer C. Serin, Gregory R. Dake and Derek P. Gates. Phosphaalkene-oxazoline Copolymers with Styrene as Chiral Ligands for Rhodium(I). Dalton Trans. 2016, 45, 5659-5666.

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methodology. Alternatively, chain growth polymerization of vinyl-substituted monomers can afford higher molecular weight P-functional polyacrylates (D)131 or polystyrenes (E).132 The metal-coordinative capabilities of these polymeric ligands have been documented for a variety of late transition metals (e.g. Pd, Ru, Rh, Pt, and Cu). Despite the demonstrated effectiveness of some of these complexes in polymer-supported asymmetric catalysis, examples remain limited. This primarily results from the synthetic difficulty of incorporating P-atoms into long chains.

Figure 3.1 Selected Examples of Known Optically-active Metal-coordinating Polymers.

As a new chain growth strategy to functional P-containing polymers, we have been investigating the addition polymerization of the P=C bond of phosphaalkenes using radical or anionic methods of initiation.54, 58 This methodology permits access to poly(methylenephosphine)s

(PMPs) bearing a variety of C-substituents and possessing fascinating electronic,43 redox,42 flame- retardant,62 or metal-coordination55, 60, 61 properties. To date, only Au(I)-containing macromolecular PMP complexes have been well characterized. We recently reported the copolymerization of an enantiomerically-pure phosphaalkene-oxazoline (PhAk-Ox,46 1.10a,

Scheme 1) with styrene to give copolymer 3.1.50 Herein, we report additional details of the

54

microstructure of copolymer 3.1 which suggest an addition-isomerization mechanism of polymerization for 1.10a and the first coordination complexes of a PMP to rhodium(I).

3.2 Results and Discussion

3.2.1 Synthesis of Phosphaalkene-Oxazoline/Styrene Copolymers

PhAk-Ox 1.10a is an intriguing monomer for polymerization studies. The chiral polymers obtained from 1.10a are of considerable interest as ligands for polymer-supported asymmetric catalysis and for their potential properties, such as helicity. In our attempts to purify 1.10a by vacuum distillation (ca. 200°C), we occasionally noted the formation of a viscous residue that was soluble in THF and from which a small amount of polymer could be isolated after precipitation with hexanes. Analysis of the polymer was consistent with the formation of

31 -1 poly(methylenephosphine) [δ P = -13; Mw = 21,000 g mol (GPC)]. Despite our efforts, we have thus far been unable to reproducibly obtain a homopolymer from 1.10a either thermally or with radical initiators. Furthermore, the observations noted in Chapter 2 preclude the use of anionic initiators as a viable option for polymerization of 1.10a.

Scheme 3.1 Synthesis of Poly(methylenephosphine-co-styrene) 3.1.

As a consequence of the difficulties in homopolymerizing 1.10a, our attention shifted towards copolymerization of PhAk-Ox with styrene in the presence of radical initiators. The radical-initiated copolymerizations of phosphaalkene 1.10a with neat styrene were conducted at

160 °C in the presence of radical initiator, 1,1′-Azobis(cyclohexanecarbonitrile) (VAZO 88). The 55

results of three trials are shown in Table 3.1, including the phosphorus contents as determined by elemental analysis and by 31P NMR spectroscopy (vide infra). The resultant copolymers, 3.1a-

3.1c, were characterized by 31P, 1H, 13C{1H}, 1H-13C HSQC NMR spectroscopy, GPC-MALS,

UV/Vis spectroscopy, and elemental analysis.

Table 3.1 Selected Data for Copolymers 3.1a-3.1c.

VAZO Yield Elem. Anal. a c d [1.10a]:[S] Mw / PDI b e e [%] [%] wt% P3.1 mol% 1.10a 3.1a 1:2 1.0 7,400/ 1.1 22 3.5 17 3.1b 1:5 0.5 18,000/ 1.2 49 1.8 6 3.1c 1:10 1.0 16,000/ 1.3 55 - - a [S] = styrene concentration. b % VAZO = mol VAZO/ (mol 1+mol styrene) 100. c Molecular weights were estimated by gel-permeation chromatography (GPC) versus polystyrene standards. d PDI = polydispersity index (estimated by GPC). e Estimated from wt% of phosphorus measured by elemental analysis.

3.2.2 Structural Characterization of Copolymer 3.1

A representative 31P{1H} NMR spectrum of 3.1 is shown in Figure 3.2 and displays a broad resonance at -7 ppm that is consistent with polymerization through the P=C bond to afford a phosphine-containing polymer. The additional minor broad signals (about -25 and 5 ppm) are also consistent with phosphine moieties of the polymer. Similar patterns of signals have been observed in random copolymers of MesP=CPh2 with styrene and have been attributed to the complex microstructure and regioirregularities within the copolymer.55

56

31 1 Figure 3.2 P{ H} NMR Spectrum (162 MHz, 298 K) in CDCl3 of poly(methylenephosphine-co-styrene) 3.1a.

Additional verification for the polymerization of 1.10a is provided by the 13C{1H} NMR spectrum of 3.1a, which is shown in Figure 3.3(b). For comparison, the spectra of monomer 1.10a and polystyrene [Figure 3.3(a) and 3.3(c), respectively] are also given. Broad signals are detected that are consistent with the functional groups expected for a copolymer with the proposed formulation. Importantly, the doublet resonance assigned to the P=C bond of 1.10a (δ13C = 203.3) is absent in the copolymer. In addition, the characteristic signals assigned to the carbon atoms of the oxazoline ring are present in the polymer and, as expected, are considerably broader than those observed for 1.10a.

57

Figure 3.3 Representative 13C{1H} NMR Spectra of 1.10a, 3.1a, and Polystyrene.

13 1 C{ H} NMR Spectra (101 MHz, 298 K) in CDCl3 of (a) monomer 1.10a, (b) poly(methylenephosphine-co-styrene) 3.1a, and (c) polystyrene. Assignments for monomer 1.10a were made with the aid of 1H-13C HSQC, 1H-13C HMBC,

1 1 and H- H COSY experiments (* indicates CDCl3).

Given our recent observation of an addition-isomerization mechanism for the radical-

63 initiated homo-polymerization of MesP=CPh2, a detailed investigation of the microstructure of copolymer 3.1 was warranted. Particularly informative are the 1H-13C HSQC and 13C APT NMR

13 spectra of 3.1a (Figure 3.4) which reveal signals attributable to a –CH(Ph)CMe2Ox (–PCH–: C:

58

1 * δ = 50.0/49.5; H: δ = 4.2, 3.0, 2.6). For comparison, 2.1a,a (a suitable model for polymer 3.1,

133 13 1 discussed in Chapter 2) showed similar signals for the P–CH(Ph)CMe2Ox ( C: δ = 51.0; H: δ

= 4.2) with assignments aided by 13C{1H}, 13C-1H HSQC, 13C APT and 1H{31P} NMR spectra. In

13 1 addition, signals assigned to an –ArCH2– moiety were also observed ( C: δ = 36.5; H: δ ≈ 1.6).

For comparison, the homopolymer of MesP=CPh2 shows similar spectral data for both the CHPh2

13 1 13 1 63 ( C: δ = 52.4; H: δ = 4.8) and ArCH2 ( C: δ = 33.0; H: δ = 3.6) moieties. Thus, we speculate that a similar addition-isomerization polymerization mechanism is involved in the copolymerization of 1.10a (i.e. x in 3.1, Scheme 3.1). However, the possibility of some degree of

“normal” P–C–P–C (y in 3.1, Scheme 3.1) enchainment cannot be ruled out nor have styrene- phosphaalkene linkages been unequivocally identified. Copolymers 3.1a-3.1c displayed an

22 increased optical rotation as the mol% 1.10a incorporated into polymer 3.1 was increased {[푎]D

-1 -1 = (3.1a): -16.5° (c = 0.68 × 10 , CH2Cl2); (3.1b): -10.6° (c = 2.8 × 10 , CH2Cl2); (3.1c): -6.37° (c

-1 = 2.8 × 10 , CH2Cl2)}.

1 * It must be noted, that the H NMR spectrum of a mixture of the diastereomers of 2.1a,a exhibits signals for the -CH(Ph)CMe2Ox proton at 4.2 and 2.9 ppm. Thus, it is not unexpected to see a signals at 4.2, 3.0 and 2.6 ppm for copolymer 3.1a.

59

Figure 3.4 1H-13C HSQC NMR Spectrum of Copolymer 3.1a.

1 13 1 13 H- C HSQC NMR spectrum (400 MHz for H, 298 K) in CDCl3. The ordinate shows an overlay of the C NMR (black) and 13C-APT NMR (blue) spectra and the abscissa shows the 1H NMR spectrum. The dashed lines show the cross peaks permitting the assignment of the -P–CHPh(CMe2Ox) and the –ArCH2– (formerly Mes) in copolymer 3.1a.

3.2.3 Coordination of Rhodium(I) to Copolymer 3.1

Even though homo- and block copolymers prepared from MesP=CPh2 coordinate to

Au(I),60, 61 we could not obtain conclusive 31P NMR spectroscopic evidence for the formation of a coordination complex from polymer 3.1 and Au(tht)Cl. Taking a step back, we treated a CH2Cl2 solution of phosphine-oxazoline 2.1a,a, the molecular model for polymer 3.1 (discussed in Chapter

2), with [Rh(cod)2]BF4 (1 equiv) at room temperature (Scheme 3.2). Analysis of an aliquot removed from the reaction mixture by 31P NMR spectroscopy showed that the signal assigned to

103 2.1a,a (δ = –39.5) had been replaced by a doublet resonance at 1.7 ppm with a characteristic Rh-

60

31 1 P coupling constant ( JRhP = 146 Hz). The product was tentatively assigned to 3.2 by comparison to related phosphine-oxazoline Rh(I) complexes (e.g. L = 1,1’-binaphthalene-2-PPh2-2’-Ox: J =

134 135 136 147 Hz; L = 1-PPh2-2-Ox-ferrocene: J = 150 Hz; L = 1-PPh2-2-Ox-benzene: J = 154 Hz ).

Analytically pure 3.2 was precipitated from the reaction mixture by adding Et2O and was characterized by 1H, 13C{1H}, 31P NMR spectroscopy, HRMS, elemental analysis, and optical

22 -1 rotation {[훼]D = 35.0° (c = 1.2 × 10 , CH2Cl2)}.

Scheme 3.2 Synthesis of Phosphine-oxazoline Rhodium(I) Complex 3.2 as a Model for [3.1·Rh(cod)]BF4.

Yellow crystals suitable for X-ray diffraction were obtained from a concentrated solution of the isolated product in Et2O/CH2Cl2 (1:1). Complex 3.2 crystallizes in the chiral P212121 space group (no. 19) (Figure 3.5). The Rh–P and Rh–N lengths in 3.2 [Rh(1)–P(1) = 2.2881(8) Å, Rh(1)–

N(1) = 2.132(3) Å] are similar to those found in the related P,N-chelate complexes [e.g.

+ 134 [LRh(cod)] : L = 1,1’-binaphthalene-2-PPh2-2’-Ox: Rh–P = 2.310(1) Å, Rh–N = 2.170(4) Å; L

137 = 1-PPh2-2-Ox-ferrocene: Rh–P = 2.289(3) Å, Rh–N = 2.11(1) Å ). The P–Rh–N angle

[89.20(7)°] is consistent with square planar geometry around the metal centre. The cod ligand is significantly rotated with respect to the P(1)–Rh(1)–N(1) plane, e.g. the angles P(1)–Rh(1)–C(31)

[170.19(8)°] and P(1)–Rh(1)–C(32) [153.40(9)°] are quite different. This phenomenon has been observed with the Binap complex mentioned above.

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Figure 3.5 Molecular Structure of Complex 3.2 (50% Probability Ellipsoids).

– Hydrogen atoms (except H1) and the [BF4] counteranion were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.857(3), P(1)–C(8) 1.823(3), Rh(1)–P(1) 2.2881(8), Rh(1)–N(1) 2.132(3), Rh(1)–C(27) 2.148(3), Rh(1)–C(28) 2.139(3), Rh(1)–C(31) 2.268(3), Rh(1)–C(32) 2.223(3), P(1)–Rh(1)–N(1) 89.20(7), P(1)– Rh(1)–C(31) 170.19(8), and P(1)–Rh(1)–C(32) 153.40(9).

Following the method by which complex 3.2 was synthesized, copolymer 3.1a was treated with [Rh(cod)2]BF4 in either CH2Cl2 or CD2Cl2 ([Rh]:[P] = 1:1 and 1:2; stoichiometry estimated using elemental analysis data, Table 3.1, to determine wt% P3.1). Analysis of each reaction mixture by 31P NMR spectroscopy revealed a new signal at 21 ppm (ca. 70% by integration for 1:1 and 50

% for 1:2) along with a broad resonance assigned to uncomplexed 3.1a (δ = –8). The downfield

31 shift in the P NMR resonances for [3.1a·Rh(cod)]BF4 compared with uncomplexed copolymer

3.1a (Δδ = 29) is consistent with that observed for the Au(I) complex of homopolymer [P(Mes)-

60 103 31 CPh2]n (Δδ = 32). Due to the breadth of the signal at 21 ppm (w1/2 ca. 1200 Hz) the Rh– P

1 138 coupling was not measurable (expected JRhP  150–200 Hz). Similar broad signals were also observed for the Au(I) complex of homopolymer [P(Mes)-CPh2]n. Further evidence for successful

62

1 formation of complexed polymer [3.1a·Rh(cod)]BF4 ([Rh]:[P] = 1:2) was provided by the H

NMR spectroscopic analysis of the product in CD2Cl2 [Figure 3.6(ii)]. In particular, sharp signals for free cod were observed along with broad signals assigned to 3.1a and [3.1a·Rh(cod)]BF4.

1 Figure 3.6 Representative (i) UV/Vis and (ii) H NMR Spectra for the Characterization of [3.1a·Rh(cod)]BF4.

-6 -1 -7 -1 (i) UV/Vis spectra of copolymer 3.1a (2 × 10 mol L ), [Rh(cod)2]BF4 (1 × 10 mol L ), mixture of copolymer 3.1a -7 -1 -8 -1 1 and [Rh(cod)2]BF4 ([Rh]:[P] = 1:2, 1 × 10 mol L ), and model complex 3.2 (7 × 10 mol L ) in CH2Cl2; (ii) H

NMR spectra (400 MHz, 298 K) in CD2Cl2 of a) copolymer 3.1a, b) [Rh(cod)2]BF4, and c) mixture of copolymer 3.1a and [Rh(cod)2]BF4 ([Rh]:[P] = 1:2).

To gain insight into the binding of 3.1a to Rh(I), the reaction mixture containing

[3.1a·Rh(cod)]BF4 ([Rh]:[P] = 1:2) was analyzed by UV/Vis spectroscopy. A broad absorption band was observed [λmax = 370 nm, Figure 3.6(i)] which was considerably different from that of

[Rh(cod)2]BF4 (λmax = 354 and 478 nm) and polymer 3.1a (no strong absorbance >350 nm). This broad absorption was similar to that of model complex 3.2 (λmax = 409 nm) and, thus, provides support for P,N-chelate binding in [3.1a·Rh(cod)]BF4. This macromolecular complex was isolated and GPC analysis of the isolated polymer in THF solution revealed that the molecular weight of

-1 complexed [3.1a·Rh(cod)]BF4 (Mw = 14,000 g mol , PDI = 1.2) was higher than that for free 3.1a

63

-1 (Mw = 7,400 g mol , PDI = 1.1). Additional support for the hypothesis that 3.1 is bound to Rh(I) comes from the fact that treating [3.1·Rh(cod)]BF4 in CD2Cl2 with NaCN (10 equiv) reforms the metal-free copolymer 3.1 (Figure 3.7).

Figure 3.7 Representative 31P NMR Spectra of the Addition of Rhodium(I) to 3.1a and 3.1b.

31 P NMR spectra (CH2Cl2, 162 MHz, 298 K) of copolymers 3.1a (12 mg) and 3.1b (27 mg) after addition of different quantities of [Rh(cod)2]BF4, followed by Rh displacement with NaCN. Free copolymer (3.1a and 3.1b) and bound polymer ([3.1a·Rh] and [3.1b·Rh]) are denoted.

3.2.4 Integrated 31P NMR Spectra of Copolymer-Rhodium(I) Complexes as a Method for

Estimating Phosphorus Incorporation

Careful integration of the 31P NMR spectra of reaction mixtures containing

[3.1·Rh(cod)]BF4 (δ = 21) and uncomplexed 3.1 (δ = –8) provides an alternate method to estimate the mol% 1.10a in copolymers 3.1a-c (Figure 3.7). This method is complimentary to that

64

determined by elemental analysis. Equations (3.1)* and (3.2)55 have been derived to permit the

31 conversion of the P NMR integrals {i.e. mol% [3.1·Rh(cod)]BF4 = IRh/(IRh+IFree), where IRh is the integral at 21 ppm and IFree is the integral at -8 ppm} to the mol% incorporation of 1.10a in copolymer 3.1. Assuming that all the mol [Rh(cod)2]BF4 added (n ) is converted to [Rh(cod)2]BF4

[3.1·Rh(cod)]BF4, the mol of [3.1·Rh(cod)]BF4 present equals the mol of phosphorus in 3.1 (i.e. the mol% 1.10a in 3.1). This assumption is valid for sub-stoichiometric loadings of

[Rh(cod)2]BF4. The results of the calculations are depicted graphically in Figure 3.8 for each of the three copolymers (3.1a, 3.1b and 3.1c).

n [Rh(cod)2]BF4 ( ) (FW1.10a) m1.10a mol% [3.1·Rh(cod)]BF4 (3.1) wt% P3.1 = × wt% P1.10a = × 7.9% m3.1 m3.1

(FW )(wt% P ) mol% 1.10a in 3.1 = S 3.1 × 100 (3.2) AWP-(FW1.10a-FWS)(wt% P3.1)

* Equation 3.1 assumes 1:1 coordination of phosphorus to rhodium (i.e. all Rh added will add to phosphorus and increase the mol% [3.1·Rh(cod)]BF4). 7.9% is the wt% P of pure monomer 1.10a (i.e. wt% P1.10a). 65

Figure 3.8 Addition of Rhodium(I) to 3.1a, 3.1b, and 3.3c to Estimate mol% 1.10a.

Addition of [Rh(cod)2]BF4 (0.25 M solution in CH2Cl2) to a CH2Cl2 solution of copolymers 3.1a (blue, 12 mg), 3.1b 31 (red, 27 mg), and 3.1c (black, 45 mg). mol% [3.1·Rh(cod)]BF4 was measured using P NMR (162 MHz, 298 K) and mol% 1.10a calculated using equations (3.1) and (3.2).

Table 3.2 Estimated Phosphorus Incorporation in Copolymers 3.1a-3.1c.

Elem. Anal. 31P NMR analysis [1]:[S]a b b c d d wt% P3.1 mol% 1.10a m3.1 (mg) wt% P3.1 mol% 1.10a 3.1a 1:2 3.5 17 12 3.4 ± 0.2 17 3.1b 1:5 1.8 6 27 1.3 ± 0.1 5 3.1c 1:10 - - 45 1.2 ± 0.1 4 a [S] = styrene concentration. b Estimated from wt% of phosphorus measured by elemental analysis. c Mass of

d copolymer 3.1 used for [Rh(cod)2]BF4 titration. Estimated from wt% of phosphorus measured by [Rh(cod)2]BF4 titration (see Experimental section for more information).

In each case, the integral for [3.1·Rh(cod)]BF4 (IRh) increases roughly linearly with increasing amount of [Rh(cod)2]BF4 added before plateauing (solid line, Figure 3.8). In the region of linearity, the mol% incorporation of 1.10a in 3.1 remains relatively constant (dotted line, Figure

3.8). Thus, the mol% 1.10a in 3.1 may be estimated to be 17% for 3.1a, 5% for 3.1b and 4% for

66

3.1c.* These results are shown in Table 3.2 and compare favourably with those determined using elemental analyses (17% and 6% for 3.1a and 3.1b, respectively). In the plateau region, the amount of [3.1·Rh(cod)]BF4 does not increase significantly despite the addition of [Rh(cod)2]BF4. Thus, the incorporation of 1.10a in 3.1 is overestimated in this region since there must be unreacted

[Rh(cod)2]BF4 present. Despite the presence of unreacted [Rh(cod)2]BF4, there still exists some uncomplexed 3.1 with maximum conversions to [3.1·Rh(cod)]BF4 reaching 70% for 3.1a, 90% for 3.1b and 93% for 3.1c based on integration of the 31P NMR spectra. This observation is not surprising since higher loadings of 1.10a in copolymer 3.1 result in a higher density of phosphine and perhaps lead to steric crowding or repulsive forces when coordinated to Rh(I).

3.3 Summary

The copolymerization of styrene with oxazoline-functionalized phosphaalkene (PhAk-Ox)

1.10a generates a macromolecule, a poly(methylenephosphine-co-styrene), that coordinates to rhodium(I) ions. The amount of individual monomer incorporation into the copolymer assessed by

31P NMR spectroscopy was consistent with the amount of metal ion coordination. With this proof of principle established, our attention in the future will focus on the optimization of metal coordination and an evaluation of these macromolecular complexes as catalysts for synthetic transformations.

* An additional resonance was observed in the 31P NMR spectrum for copolymer 3.1c (δ31P = 47), attributed to oxidized PMP. Integration of this signal suggested that the polymer was 29% oxidized. Taking this into account, wt% P3.1c was calculated for the polymer sample using the discussed method, followed by compensation for the observed oxide (i.e., wt% P3.1c = wt% P3.1c (measured)/0.71). 67

3.4 Experimental

3.4.1 Materials and Methods

All manipulations of air- and/or water-sensitive compounds were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Dichloromethane (CH2Cl2), and diethyl ether (Et2O) were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. Tetrahydrofuran (THF) was dried over sodium/benzophenone ketyl and distilled prior to use. Methanol was deoxygenated with nitrogen prior to use. 1,1’-

Azobis(cyclohexanecarbonitrile) (VAZO 88) was purchased from Aldrich and recrystallized from

EtOH prior to use. Styrene was purchased from Aldrich and distilled from CaH2 prior to use.

CDCl3 and CD2Cl2 were purchased from Cambridge Isotope Laboratories Inc. and deoxygenated

46 133 139 with nitrogen prior to use. PhAk-Ox 1.10a, phosphine 2.1a,a, and [Rh(cod)2]BF4 were prepared following literature procedures. 1H, 13C{1H} and 31P NMR spectra were recorded at 298

K on Bruker Avance 300 or Avance 400 spectrometers. H3PO4 (85%) was used as an external standard (δ 0.0) for 31P NMR spectra. 1H NMR spectra were referenced to residual protonated solvent, and 13C{1H} NMR spectra were referenced to the deuterated solvent. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV). Solution absorption spectra were obtained in CH2Cl2 on a Varian Cary 5000 UV-Vis-near-IR spectrophotometer using a 1 cm quartz cuvette. The optical rotations were measured at a concentration in g per 100 mL and their values

(average of 10 measurements) were obtained on a Jasco P-1010 polarimeter.

3.4.2 General Procedure for Synthesis of Copolymers

For copolymer 3.1a: Styrene (3.0 g, 29 mmol), PhAk-Ox 1.10a (5.8 g, 15 mmol) and

VAZO 88 (0.11 g, 0.44 mmol) were added to a PyrexTM tube. The tube was flame-sealed in vacuo and, subsequently, heated at 160 °C in an oven equipped with rocking tray. Over a period of 14h, 68

the polymerization mixture became increasingly viscous. The tube was removed from the oven and cooled to ambient temperature, at which point the sample was solid. The tube was broken open in a nitrogen filled glovebox, the contents were dissolved in THF (ca. 10 mL) and transferred to a

Schlenk flask (100 mL). The solution was concentrated in vacuo and dissolved in a minimal amount of THF (ca. 4 mL). The THF solution was precipitated with degassed MeOH (60 mL) and filtered. This process was repeated three times to give a light-yellow powder that was dried in vacuo for 24 h. (2.0 g, 22%).

31 1 P NMR (162 MHz, CDCl3): δ = -8 (br s); H NMR (400 MHz, CDCl3): δ = 7.6–6.3 (br

13 1 m), 4.4–3.2 (br m), 3.0–0.5 (br m); C{ H} NMR (101 MHz, CDCl3): δ = 172.2, 145.4, 139.9,

138.2, 129.8, 127.9, 125.5, 71.6, 69.2, 49.5, 45.9, 43.7, 40.3, 36.5, 32.2, 25.1, 22.6, 21.0, 18.9,

-1 17.9, 17.4; GPC-LLS (THF): Mw = 7,400 g mol ; PDI = 1.1; dn/dc = 0.16. Anal. Found for 3.1a:

22 -1 P, 3.51; [푎]D = -16.5° (c = 0.68 × 10 , CH2Cl2).

Copolymer 3.1b. Styrene (0.46 g, 4.4 mmol), PhAk-Ox 1.10a (0.35 g, 0.89 mmol) and

VAZO 88 (6.5 mg, 2.7 µmol) were used to give the product as a light-yellow powder. (0.40 g,

49%).

GPC-LLS (THF): Mw = 18,000 g mol-1; PDI = 1.2; dn/dc = 0.14. Anal. Found for 3.1b: P,

22 -1 1.79. Spectroscopic data matches copolymer 3.1a; [푎]D = -10.6° (c = 2.8 × 10 , CH2Cl2).

Copolymer 3.1c. Styrene (5.3 g, 51 mmol), PhAk-Ox 1.10a (2.0, 5.1 mmol), and VAZO

88 (0.14 g, 0.56 mmol) were used to give the product as a light-yellow powder. (4.1 g, 55%).

-1 GPC-LLS (THF): Mw = 16,000 g mol ; PDI = 1.3; dn/dc = 0.17. Spectroscopic data

22 -1 matches copolymer 3.1a; [푎]D = -6.37° (c = 2.8 × 10 , CH2Cl2).

69

3.4.3 Synthesis of [((R)-MesMeP-(S)-CHPhC(Me)2(CNOCH(i-Pr)-CH2)Rh(cod)]BF4 (3.2)

To a solution of 2.1a,a (50 mg, 0.12 mmol) in CH2Cl2 (1 mL) was added solid [Rh(cod)2]BF4

(50 mg, 0.12 mmol). The reaction was stirred at room temperature for 2 h. A large excess of Et2O

(ca. 20 mL) was added to precipitate the product as a yellow solid. The product was isolated by filtration in air and rinsed with additional Et2O (2 × 2 mL) to give 3.2 as a yellow solid. (53 mg,

59%). Single crystals suitable for X-ray diffraction analysis were obtained by slow diffusion of

Et2O into a CH2Cl2 solution (1:1) of 3.2.

31 1 1 P NMR (162 MHz, CDCl3): δ = 1.7 (d, JRhP = 146 Hz); H NMR (400 MHz, CDCl3): δ

= 8.49 (d, JHH = 8 Hz, 1H), 7.61 (t, JHH = 8 Hz, 1H), 7.36 (t, JHH = 8 Hz, 1H), 7.21 (t, JHH = 7 Hz,

1H), 6.91 (br s, 2H), 6.75 (d, JHH = 7 Hz, 1H), 5.66 (t, JHH = 7 Hz, 1H), 5.04 (m, 1H), 4.59 (t, JHH

= 9 Hz, 1H), 4.32 (dd, JHH = 9, 3 Hz, 1H), 3.98 (m, 1H), 3.75 (d, JPH = 14 Hz, 1H), 3.48 (m, 1H),

3.37 (m, 1H), 3.00–2.32 (m, 6H), 2.29 (s, 3H), 2.24-2.01 (m, 3H), 1.87 (m, 1H), 1.76 (m, 1H), 1.51

(s, 3H), 1.40 (d, JPH = 8 Hz, 3H), 1.15 (s, 3H), 0.98 (d, JHH = 7 Hz, 3H), 0.60 (d, JHH = 7 Hz, 3H);

13 1 C{ H} NMR (101 MHz, CDCl3): 177.5, 142.5 (d, J = 9 Hz), 141.7, 141.6 135.2, 132.1 (d, J = 5

Hz), 131.7, 129.6 (d, J = 5 Hz), 129.0, 128.4, 128.4 (d, J = 3 Hz), 124.9 (d, J = 34 Hz), 104.4 (t, J

= 8 Hz), 98.2 (dd, J = 12, 8 Hz), 78.0 (d, J = 14 Hz), 74.2 (d, J = 12 Hz), 69.9, 68.0, 51.1 (d, J =

15), 42.6 (d, J = 5 Hz), 34.9 (d, J = 6 Hz), 31.5, 31.1, 29.3 (d, J = 8 Hz), 29.1 (d, J = 8 Hz), 29.1,

- 26.0, 25.6, 20.8, 19.1, 14.2, 10.2 (d, J = 29); HRMS calcd for C34H48NOPRh (3.2-BF4 ): 620.2529;

Found: 620.2512; Anal. Calcd C34H48NOPRhBF4: C 57.73, H 6.84, N 1.98; Found: C 57.70, H

22 -1 6.89, N 2.21; [푎]D = 35.0° (c = 1.2 × 10 , CH2Cl2).

3.4.4 Synthesis of [3.1a·Rh(cod)]BF4

To a solution of copolymer 3.1a (54 mg, 0.061 mmol P) in CH2Cl2 (3 mL) was added

[Rh(cod)2]BF4 (12 mg, 0.030 mmol). The reaction was stirred at room temperature for 2 h. The 70

solvent was evaporated in vacuo and the resulting orange solid was triturated with hexanes (5 mL).

The solid was filtered, washed with additional hexanes (3 × 5 mL), and dried overnight in vacuo affording [3.1a·Rh(cod)]BF4 as an orange solid. (62 mg, quant.).

31 1 1 13 P{ H} NMR (162 MHz, CDCl3): δ = 23 (br s), -8 (br s); H and C NMR is identical to

-1 free copolymer 3.1a; GPC-LLS (THF): Mw = 14,000 g mol ; PDI = 1.2; dn/dc = 0.12.

3.4.5 General Procedure for Titration of Copolymer 3.1 with Rh(cod)2BF4

31 P NMR analysis was performed utilizing an appropriate relaxation delay (d1 = 1.5 s) and tip angle (30°)* to allow for integration. Copolymer 3.1a (12 mg) was weighed into an NMR tube and placed in a tubular Schlenk flask under a nitrogen atmosphere. A minimal amount of CH2Cl2

(ca. 0.1 mL) was added to dissolve the polymer. 31P NMR analysis of this sample revealed the copolymer as a broad resonance (δ31P = -8). The NMR tube was returned to the tubular Schlenk flask under nitrogen. [Rh(cod)2]BF4 (30 mg, 0.074 mmol) was dissolved in 0.30 mL CH2Cl2 to produce a standard 0.25 M [Rh(cod)2]BF4 solution. 10 µL (1.0 mg, 2.5 µmol) of this Rh solution was added to the NMR tube and the resulting mixture sonicated 15 min. 31P NMR analysis of this

31 sample revealed a new resonance (δ P = 21) attributed to [3.1a·Rh(cod)]BF4 (IRh = 0.20) in addition to Rh-free copolymer 3.1a (IFree = 1.0). The integrated ratio of these two resonances was used to determine mol% [3.1a·Rh(cod)]BF4 = 0.17 [where mol% [3.1a·Rh(cod)]BF4 = IRh/(IFree +

IRh) = 0.20/1.2].

The NMR tube was returned to a tubular Schlenk flask under nitrogen. 10 µL (1.0 mg, 2.5

µmol, 5.0 µmol total) of 0.25 M [Rh(cod)2]BF4 solution was added to the NMR tube and the

* The relaxation time (t1) of the phosphorus atoms in copolymers 3.1a-3.1c (t1 = 1.16 s) and [3.1·Rh(cod)]BF4 (t1 = 0.72 - 0.87 s) were measured prior to conduction of this kinetic analysis to ensure adequate delay time for complete relaxation between data acquisitions. This ensures that integrations are reliable. 71

resulting mixture sonicated 15 min. 31P NMR analysis of this sample showed an increase in the resonance attributed to [3.1a·Rh(cod)]BF4 (IRh = 0.70) relative to Rh-free copolymer 3.1a (IFree =

1.0). The integrated ratio of these two resonances indicates mol% [3.1a·Rh(cod)]BF4 = 0.42. wt%

P3.1 was calculated using equation 3.1, and found to be 3.0%. Further additions of the 0.25 M

[Rh(cod)2]BF4 solution, followed by sonication, were recorded and the corresponding values for wt% P3.1 and mol% 1.10a measured (Table 3.2).

3.4.6 Procedure for the Displacement of Rhodium from Metallated Copolymer 3.1

NaCN (10 equiv.) was measured and added to an NMR tube from the previous titration that contains a mixture of [3.1a·Rh(cod)]BF4, Rh-free copolymer 3.1a and Rh(cod)2BF4. The suspension was sonicated for 20 minutes, whereupon a distinct colour change from deep red/orange to yellow, along with a green precipitate, was observed.

31 P NMR (162 MHz, CDCl3): δ = -8 (br s).

3.4.7 X-ray Crystallographic Studies

The single crystal was immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX II diffractometer with graphite-monchromated Mo Kα radiation. The structure was solved by direct methods and subsequent Fourier difference techniques. All nonhydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected for absorption effects (SADABS), Lorentz, and polarization effects. All calculations were performed using SHELXL-2014 crystallographic software package from Bruker AXS.114 Absolute configuration was confirmed on the basis of the refined Flack parameter.115 All crystallographic data has been deposited with the Cambridge

Structural Database: 1447429

72

Table 3.3 X-ray Data Collection and Refinement Details for Compound 3.2.a

formula C34H48NOPRh·BF4 fw 707.42 cryst syst orthorhombic space group P212121 colour orange a (Å) 10.0034(5) b (Å) 17.8518(9) c (Å) 17.9626(9) α (deg) 90 β (deg) 90 γ (deg) 90 V (Å3) 3207.7(3) T (K) 90(2) Z 4 μ(Mo Kα) (mm-1) 0.634 cryst size (mm3) 0.21×0.17×0.08 -3 Dcalcd. (Mg m ) 1.465 2θ(max) (deg) 54.6 no. of reflns 30320 no. of unique data 7353 R(int) 0.0398 refln/param ratio 18.6 b R1 [I > 2σ(I)] 0.0268 c wR2 [all data] 0.0578 GOF 1.042 a Adapted with permission from Dalton Trans., 2016, 45, 5659-5666. © 2016 Royal Society of Chemistry. b c 2 2 2 2 2 2 1/2 R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표|. w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

73

Chapter 4: Addition-Isomerization Polymerization of Chiral Phosphaalkenes:

Observation of Styrene-Phosphaalkene Linkages in a Random Copolymer*

4.1 Introduction

Functional macromolecules featuring heavier p-block elements in the main chain are of current interest due to their unique chemical, physical and electronic properties when compared to their organic analogues.140 For example, the presence of phosphorus within the backbone introduces new oxidation states, geometries, bonding environments and ligand properties that are not found for carbon. Hence, the prospect of utilizing organophosphorus polymers as ligands for transition metals opens the door to numerous exciting possibilities for preparing materials with interesting catalytic, magnetic or sensing properties. Driven by these opportunities, the past decade has witnessed tremendous growth of organophosphorus polymer chemistry.141 Notwithstanding this growth, methods to incorporate P atoms into long chains remain limited to condensation and ring-opening polymerization and poses considerable synthetic challenges.

Inspired by the striking parallels between P=C and C=C bonds in molecular chemistry,142 we have been exploring the addition polymerization of phosphaalkenes by analogy to olefin polymerization (Scheme 4.1). We have demonstrated that MesP=CPh2 (A in Scheme 4.1) polymerizes in the presence of radical or anionic initiators to afford poly(methylenephosphine)

(PMP in Scheme 1).54 Furthermore, the anionic polymerization of A or B is living and permits access to phosphaalkene-olefin block copolymers with different electronic properties.57, 58 PMPs

* Versions of sections of this chapter have been published. Spencer C. Serin, Gregory R. Dake and Derek P. Gates. Addition-Isomerization Polymerization of Chiral Phosphaalkenes: Observation of Styrene-Phosphaalkene Linkages in a Random Copolymer. Macromolecules 2016, 49(11), 4067-4075. 74

represent a fascinating class of functional polymer as illustrated by the following examples: random copolymers of A with styrene have been employed as macromolecular ligands in Pd- catalysis;55 block copolymers of A with isoprene self-assemble as gold(I) complexes in block selective solvents;61 and polymers of A are effective flame retardants.62 Building on our initial discoveries, we reported a number of isolable Mes-functionalized phosphaalkene monomers which permitted the synthesis of homo and copolymers with interesting properties. For example, polymers derived from chromophore-containing monomers C and D show “turn-on” fluorescence with oxygen43 and polymers from ferrocene-containing monomer E show interesting redox activity.42 Most recently, we have shown that the copolymerization of the enantiomerically-pure phosphaalkene F46 with styrene50 will give a macromolecular P,N ligand for chelation of rhodium(I)-atoms.143

Scheme 4.1 The Isolobal Analogy Between Olefins and Phosphaalkenes as Applied to Addition Polymerization

(top). Selected Examples of Polymerizable Phosphaalkene Monomers (bottom).

Herein, we report the synthesis, characterization and polymerization of a new class of enantiomerically-pure phosphaalkene (4.1). The radical-initiated polymerization of P-Mes- containing monomer 4.1a affords homopolymer 4.4a or copolymer 4.5a with styrene (S).

Importantly, multinuclear NMR spectroscopy permitted the confirmation of an addition- isomerization mechanism for the polymerization of 4.1a and provided the first direct evidence for

4.1a-S linkages in a phosphaalkene copolymer. 75

4.2 Results and Discussion

4.2.1 Monomer Synthesis and Characterization

Given that oxazoline-substituted phosphaalkene F does not form homopolymers whilst phenyl-substituted A does, we hypothesized that a phenylene-oxazoline phosphaalkene such as

4.1a may be more likely to homopolymerize. Using the well-known phospha-Peterson reaction,

32, monomer 4.1a was shown to be accessible from MesPLi(SiMe3) and ketone 4.3 (Scheme 4.2).

50, 72, 144 Oxazoline 3 was prepared from commercially available 3-benzoylbenzoic acid in 55% yield via amide 4.2 following procedures analogous to the preparation of napthyl-imidazolines145 and phenylene-oxazolines.145, 146 Ketone 4.3 was fully characterized using 1H and 13C{1H} NMR spectroscopy, mass spectrometry [HRMS (4.3·H+): m/z 294.1494 (found); 294.1495 (calcd)] and

22 3 -1 -1 elemental analysis. Compound 4.3 showed an optical rotation [훼]D = –35.6 °cm g dm (c =

-1 2.4 × 10 , CH2Cl2).

Scheme 4.2 Synthesis of Enantiomerically Pure Phenyl-bridged Phosphaalkene-oxazolines.

Elaboration of 4.3 to phosphaalkenes 4.1a and 4.1b was accomplished using the aforementioned phospha-Peterson reaction32 as the P=C bond forming step. The general synthetic procedure is as follows: a solution of ketone 4.3 in THF was added dropwise to a cooled (–78 °C)

THF solution of either MesP(Li)SiMe3 or Mes*P(Li)SiMe3 [formed in situ from MesP(SiMe3)2 or 76

Mes*PH(SiMe3), respectively]. The reaction mixture was warmed to room temperature whereupon an aliquot was removed for analysis by 31P{1H} NMR spectroscopy. In all cases, the signal assigned to ArP(Li)SiMe3 [δ = –187 (Mes); –127 (Mes*)] was replaced by two new signals in a range consistent with those expected for the E and Z isomers of a phosphaalkene (δ = 4.1a: 237.6,

237.4; 4.1b: 246.9, 246.5). The desired phosphaalkene 4.1a (yield = 47%) was isolated and characterized as the Z-isomer after precipitation with n-pentane. In contrast, air- and moisture- stable 4.1b (yield 64%) was isolated as an E/Z-mixture (E/Z = 58:42) after silica gel column chromatography.

Monomers 4.1a and 4.1b were subjected to full characterization by 31P, 1H and 13C{1H}

NMR spectroscopy, mass spectrometry and for 4.1b elemental analysis. For 4.1a, while the Z- isomer was obtained exclusively upon precipitation in n-pentane, rapid isomerization in solution at ambient temperature was observed until the system reached equilibrium (E:Z = 0.7:1.0). In this case, signals could be unequivocally assigned to either the Z- or E-isomer by using 1H-1H NOESY and 1H-1H COSY NMR spectroscopy. This stereoisomerization is not uncommon in asymmetric phosphaalkenes, especially when the P-substituent is the less sterically-hindered Mes group.43, 147

Conversely, Mes*-substituted phosphaalkenes do not readily undergo isomerization at room temperature unless treated with UV light.147 The mechanism for isomerization is not clearly understood, however the electronics of the P=C bond are reported to play little role.148 Therefore, the increased kinetic stabilization of the P=C functionality by the Mes* group (wrt the Mes group) must also lead to an increase in the energetic barrier for E/Z-stereoisomerization.

Phosphaalkenes 4.1a and 4.1b were recrystallized from hexanes and n-pentane, respectively, to afford pale green crystals of each molecule suitable for X-ray diffraction. The molecular structures of Z-4.1a and Z-4.1b are shown in Figure 4.1. In each case, support for the 77

retention of the S configuration of the oxazoline moiety and enantiomeric purity was obtained from the Flack parameter [Z-4.1a: 0.08(8); Z-4.1b: 0.03(8)] being close to zero. The P=C bond lengths of each phosphaalkene [Z-4.1a: 1.693(2) Å; Z-4.1b: 1.694(6) Å] are at the long end of the range typically found for C-substituted phosphaalkenes (1.61–1.71 Å)149 but are shorter than the P=C

150 bonds in inversely polarized phosphaalkenes (e.g. RP=C(NR2)2, 1.70–1.76 Å). Overall, the metrical parameters are consistent with those observed previously for triaryl-substituted

32, 46, 151 phosphaalkenes such as ArP=CPh2 (Ar = Mes or Mes*) and related systems.

78

Figure 4.1 Molecular Structures of (a) Z-4.1a and (b) Z-4.1b (50% Probability Ellipsoids).

All Hydrogen atoms omitted for clarity. Selected bond lengths (Å) and angles (deg): Z-1a: P(1)–C(1) 1.693(2), P(1)– C(20) 1.834(2), C(1)–C(2) 1.485(2), C(1)–C(8) 1.481(2), C(1)–P(1)–C(20) 104.31(8), C(2)–C(1)–P(1) 118.5(1), C(8)–C(1)–P(1) 126.3(1), C(2)–C(1)–C(8) 115.2(2). Z-1b: P(1)–C(1) 1.694(6), P(1)–C(20) 1.857(5), C(1)–C(2) 1.483(7), C(1)–C(8) 1.500(8), C(1)–P(1)–C(20) 102.2(2), C(2)–C(1)–P(1) 117.8(4), C(8)–C(1)–P(1) 125.7(4), C(2)– C(1)–C(8) 116.5(5).

79

4.2.2 Homo and Co-polymerization of Monomer 4.1a

The homopolymerization of phosphaalkene 4.1a was performed in the melt (160 °C, 16 h) in the presence of the radical initiator 1,1′-azobis(cyclohexanecarbonitrile) (VAZO 88, 1 mol%)

(Scheme 4.3). A significant increase in viscosity was observed suggestive of polymerization. 31P

NMR spectroscopic analysis of a THF solution of the crude polymer revealed that the signals assigned to phosphaalkene 4.1a had been partially consumed (δ31P = 237.4, 237.6; ca. 40%) and were replaced by several broad signals assigned to 4.4a (range: 20 to –20 ppm; ca. 60%). The latter signals are consistent with those previously reported for PMPs.42, 43, 54 Despite repeated trials involving larger amounts of initiator (5 mol% VAZO 88), longer polymerization times (t > 24 h), and higher melt temperatures (Tp >180 °C), higher monomer-to-polymer conversions were not attainable. Yellow polymer 4.4a was isolated in pure form by precipitation of the crude reaction mixture in THF with MeOH (3). GPC-MALS analysis of polymer 4.4a revealed a monodisperse

-1 distribution with modest molecular weight (Mn = 5,300 g mol ; PDI = 1.2). The Mn value suggests

22 a degree of polymerization of ca. 12. Polymer 4.4a had an optical rotation [훼]D = –19.9

3 -1 -1 -1 °cm g dm (c = 1.4 × 10 , CH2Cl2).

Scheme 4.3 Synthesis of poly(methylenephosphine) 4.4a and poly(methylenephosphine-co-styrene) 4.5a.

80

In addition to the homopolymer of 4.1a, poly(methylenephosphine-co-styrene) 4.5a was prepared in an analogous fashion. Phosphaalkene 4.1a, styrene (1:2 loading ratio, respectively), and VAZO 88 (1 mol%) were flame-sealed in a Pyrex tube in vacuo and heated at 160 °C for 14 h. Again, an increase in viscosity was observed suggestive of polymerization. 31P NMR spectroscopic analysis revealed a larger amount of phosphaalkene had been consumed (ca. 93 % conversion) with respect to homopolymerization (i.e. synthesis of 4.4a). Characteristic PMP signals were again observed in the 31P NMR spectrum between 20 and –20 ppm. Dissolution of the sample in THF and precipitation with MeOH (3) afforded copolymer 4.5a as an off-white

-1 solid. GPC-MALS analysis revealed a lower Mn and narrower PDI than PMP 4.4a (4,000 g mol

22 3 -1 -1 and 1.1, respectively). Copolymer 4.5a had an optical rotation [훼]D = –29.3 °cm g dm (c = 1.1

-1 × 10 , CH2Cl2)

4.2.3 Microstructures of Polymers 4.4a and 4.5a

Given our recent observation of an addition-isomerization mechanism for the radical-

63 initiated homo-polymerization of MesP=CPh2 (A) and copolymerization of phosphaalkene F with styrene,143 a detailed investigation of the microstructure of polymers 4.4a and 4.5a was

31 undertaken. The P NMR spectrum of homopolymer 4.4a in CDCl3 shows broad resonances centered at 4 (minor), –8 (major) and –48 ppm (minor), each potentially having some additional fine structure [see Figure 4.2(a)]. For reference, the homopolymer of A displays a broad resonance at -10 ppm with some fine structure. We previously speculated that the fine structure results from tacticity effects and presume that the additional complexity for 4.4a may arise from the chiral Ox moiety and the stereogenic center adjacent to P. The 31P NMR spectrum of phosphaalkene-styrene copolymer 4.5a displays similar broad signals centered at 6 (major), –8 (major) and –44 ppm

(minor) [see Figure 4.2(c)]. Other than a slight increase in the intensity of the signal at 6 ppm, the 81

incorporation of styrene in 4.5a does not significantly change the 31P NMR spectroscopic features when compared to 4.4a.

31 1 Figure 4.2 P{ H} NMR Spectra (162 MHz, 298 K) in CDCl3 of (a) homopolymer 4.4a, (b) 4.4a·AuCl, (c)

copolymer 4.5a, and (d) 4.5a·AuCl.

The 13C{1H} and 1H NMR spectra of both 4.4a and 4.5a exhibit signals attributed to the

13 1 expected substituents: oxazoline [ C:   160 (N=C), 73 (CH), 70 (CH2), 19, 18 (2  CH3); H: δ

13 = 4.6 – 3.7 (CH and CH2), and 1.0, 0.90 (2  CH3)], mesityl [ C:   145-126 (Ar-C), 23 (o-CH3),

1 21 (p-CH3); H: δ = 8.1-6.1 (Ar-H), 2.3-1.8 (o,p-CH3)] as well as the phenyl and phenylene- 82

oxazoline groups. These assignments were supported by edited 1H-13C{1H} HSQC NMR experiments (edHSQC), where the experiment is collected with multiplicity editing during the

13 1 selection step permitting C{ H} NMR signals to be classified as either CH/CH3 or CH2 groups.

Importantly, these experiments also permitted the assignment of PCH (13C: δ = 52.1; 1H: δ = 4.9)

13 1 and ArCH2 ( C: δ = 33.6; H: δ = 3.5) within homopolymer 4.4a. These signals are denoted by cross correlations in Figure 4.3(i) and are phased positive (blue, CH) and negative (red, CH2), respectively. These values are in close agreement with our previous detailed analysis of the

13 1 13 1 microstructure of poly(A) [PCH ( C: δ = 52.4; H: δ = 4.8) and ArCH2 ( C: δ = 33.0; H: δ =

3.6)].152 Therefore, we conclude that the microstructure of 4.4a results from an addition- isomerization polymerization mechanism where propagation occurs through the o-Me moiety of the former Mes group (i.e. x >> y in 4.4a).

83

Figure 4.3 Representative 13C{1H} and 1H 2D NMR Spectra for Homopolymer 4.4a and Copolymer 4.5a.

1 13 1 1 H- C{ H} edHSQC NMR spectra (400 MHz for H, CDCl3, 298 K) of (i) homopolymer 4.4a and (ii) copolymer 1 1 1 1 4.5a, (iii) H- H NOESY NMR spectrum (400 MHz, CDCl3, 298 K) of copolymer 4.5a, and (iv) H- H COSY NMR 13 1 spectrum (400 MHz, CDCl3, 298 K) of copolymer 4.5a. For (i) and (ii), the ordinate shows the C{ H} NMR spectrum and the abscissa shows the 1H NMR spectrum. The dashed lines show the cross peaks permitting the assignment of the –PCHPh(3-C6H4Ox) and the –ArCH2– (formerly Mes) in polymers 4a and 5a. The edHSQC spectra were collected with multiplicity editing during the selection step permitting assignments of CH/CH3 (blue) vs. CH2 (red) moieties.

84

Our previous studies of phosphaalkene-styrene random copolymers involving monomers

A and F did not reveal NMR spectroscopic evidence for styrene-phosphaalkene linkages.

Therefore, we embarked on additional NMR spectroscopic experiments on copolymer 4.5a to gain additional insight into these fascinating copolymers. Since we did not observe the non-isomerized form of 4.4a (i.e. y in Scheme 4.3), there are four possible environments for a phosphaalkene unit within copolymer 4.5a (Figure 4.4 shows its nearest neighbors). Given that the feed ratio of styrene to phosphaalkene is 2:1 and that phosphaalkene incorporation is typically lower than the feed ratio,55, 143 then microstructure (i: S–1a–S) should statistically be the most prominent. Since styrene is in excess and the phosphaalkene has the most diagnostic NMR signals, the environments for a central styrene unit are not considered here (e.g. S–S–S, 1a–S–S, etc.). Of course, the aforementioned microstructures (i-iii) do not take into account the additional complexity arising from tacticity.

Figure 4.4 The Most Likely Environments for a Central Phosphaalkene Unit (in blue) Within Copolymer 4.5a

(Ar = 3-C6H4Ox).

85

1H-13C{1H} HSQC NMR spectroscopy has been demonstrated to be a valuable tool for detailed backbone analysis of organic polymers.153-155 Analogous to that described above for homopolymer 4.4a, cross correlations were observed that were attributed to PCH and ArCH2 moieties in 4.5a [see Figure 4.3(ii): 13C: δ = 50.9; 1H: δ = 4.7 (PCH) and 13C: δ = 33.6; 1H: δ = 2.2

(ArCH2)]. Strikingly, a new and more intense cross correlation was observed in the region of the

13 1 1 PCH moiety [ C: δ = 48.4; H: δ = 3.6]. Moreover, the H chemical shift attributed to the ArCH2 moiety of copolymer 4.5a is found considerably upfield from that in homopolymer 4.4a ( = 2.2 vs. 3.6). We hypothesize that these striking differences between the spectra of homopolymer 4.4a and copolymer 4.5a are a consequence of the microstructure of copolymer 4.5a. For example, microstructure i where the phosphaalkene is surrounded by two styrenes would be expected to have significant differences in the chemical shifts of the PCH and ArCH2 groups, both being influenced by the adjacent styrene. In contrast, microstructure iia in 4.5a has a similar chemical environment to homopolymer 4.4a for its ArCH2 whilst the PCH group would be quite different.

In microstructure iib, the reverse is expected. Microstructure iii, being the lowest in probability, might be expected to display similar ArCH2 and the PCH chemical shifts to the homopolymer.

Based on the above, a mixture of all three microstructures of 4.5a is expected to show at least two distinct ArCH2 and PCH environments. In the case of the PCH group, two distinct signals are observed in each of the 1H and 13C{1H} NMR spectra [13C: δ = 50.9, 48.4; 1H: δ = 4.7, 3.6] whilst one is observed for 4.4a [13C: δ = 52.1; 1H: δ = 4.9]. We postulate that the more intense upfield signals are attributable to S–4.1a linkages in microstructures i and iia [e.g. –CHPh–

P(CHPhAr)]. ,-Disubstituted polymers of the type [–CHR–CH(CHR'2)–]n show similar upfield shifts in 1H and 13C NMR signals of the CH unit that have been attributed to γ-gauche interactions between R and the CH.156 In 4.5a, similar interactions may be present between the PCH and S (i.e. 86

R = Ph). To probe this linkage further, a 1H-1H NOESY NMR spectrum of 4.5a was recorded

[Figure 4.3(iii)]. Importantly, an NOE correlation was observed between the proton of the PCH and the CHPh of S along with the expected NOE correlations involving the oxazoline. Additional evidence for various types of S-PCH connectivities in copolymer 4.5a was gained from the analysis of the 1H-1H COSY NMR spectrum [Figure 4.3(iv)]. Namely, two cross correlations between the backbone protons of S and the PCH proton are observed [ = 3.6 (PCH) and 2.4

(SCHPh); 3.8 (PCH) and 1.9 (SCHPh)]. The aforementioned data marks the first time we have observed direct spectroscopic evidence for phosphaalkene-styrene linkages in copolymers.

1 13 1 In contrast to the PCH unit, only one signal is observed for the ArCH2 in the H- C{ H} edHSQC NMR spectrum of 4.5a (13C: δ = 33.6; 1H: δ = 2.2). This resonance is shifted upfield with respect to homopolymer 4.4a (δ = 3.5) which presumably arises from the predominance of microstructures i and iib. For comparison, the diastereotopic CH2 of model compound PhCH2–

1 63 P(Mes)(CHPh2) exhibits a similar downfield shift in its H NMR spectrum (δ = 3.4, 2.9) with

157 respect to the analogous polystyrene model compound PhCH2–CH2CH(Ph)CH3 (δ = 2.5). This further demonstrates the effect of the adjacent atom to the ArCH2–E unit of 4.5a (i.e. E = P vs. C).

The absence of the expected second signal for the ArCH2 (i.e. microstructures iia and iii) may reflect the preference for the putative propagating radical from 4.1a (i.e. ArCH2·) to add to styrene

(e.g. r1a = k1a/kS << 1). Moreover, it must be noted that it is very difficult to detect the broad ArCH2 signals in either the 1H or the 13C{1H} NMR spectrum; thus, structure types iia and iii may be present but not observed.

Confident that the 13C{1H} NMR spectrum had been suitably assigned, integration of the styrenic signals relative to those from 4.1a was performed to estimate the phosphaalkene incorporation (mol% 4.1a) within copolymer 4.5a. Inverse-gated 13C{1H} NMR spectroscopy has 87

been employed to estimate monomer incorporation within organic copolymers.158, 159 The inverse gated 13C{1H} NMR spectrum of 4.5a is shown in Figure 4.5 along with assignments and integrals.

13 The aliphatic styrene carbons (δ C: 39-47, –CH2CHPh–) integrate to 8.4 relative to either aliphatic carbon of the oxazoline in 4.1a (δ13C: 70, 73; both integrate to 1.0). Therefore, the styrene to phosphaalkene ratio in 4.5a is 4.2:1 [i.e. z:(x+y)] which corresponds to the formulation of 4.5a

-1 [(x+y) = 0.19n, z = 0.81n where x>>y]. To place this into context, the Mn of 4,000 g mol determined by GPC-MALS for 4.5a corresponds to ca. 5 phosphaalkene units and ca. 20 styrene units.

13 1 Figure 4.5 Inverse-gated C{ H} NMR Spectrum (101 MHz, 298 K) in CDCl3 of Copolymer 4.5a.

13 1 1 13 1 Assignments were made with the aid of C{ H}-APT and H- C{ H} edHSQC NMR experiments.

4.2.4 Chemical Functionalization of Polymers 4.4a and 4.5a

We have previously shown that the phosphine moieties of homo- and co-polymers of

43, 55, 60, 143 phosphaalkene A are effective ligands for transition metals. Thus, CH2Cl2 solutions of either 4.4a or 4.5a were treated with Au(tht)Cl (1 equiv per P, tht = tetrahydrothiophene). In each case, the reaction solutions were precipitated with n-pentane to afford off-white solids that were separated by centrifugation and dried in vacuo. The 31P{1H} NMR spectra of the products are shown in Figure 4.2 and are consistent with that expected for complexes 4.4a·AuCl and

4.5a·AuCl. In particular, the complex features of the broad signals are retained in each case

[4.4a·AuCl:  = 41.0 (minor), 23.5 (major); 4.5a·AuCl:  = 41.9 (major), 24.7 (major)]. These 88

signals are downfield shifted by ca. 35 ppm compared to the chemical shifts for the uncomplexed homo- and co-polymers. By comparison, the gold(I) complex of the homopolymer from monomer

A is shifted downfield by ca. 32 ppm from its uncomplexed form.60 Interestingly, complexed polymers 4.4a·AuCl and 4.5a·AuCl display modest air stability with all work-up procedures being conducted in air atmosphere. GPC-MALS analysis of the isolated polymers in THF solution

-1 revealed the molecular weight of complexed 4.4a·AuCl (Mn = 13,000 g mol , PDI = 1.2) and

-1 4.5a·AuCl (Mn = 7,500 g mol , PDI = 1.1). In each case, a considerable increase in mass is

-1 observed upon coordination to the heavy gold atom (cf. 4.4a: Mn = 5,300 g mol , PDI = 1.2; 4.5a:

-1 Mn = 4,000 g mol , PDI = 1.1).

4.3 Summary

We have described the synthesis and structural characterization of a novel class of phosphaalkene monomer bearing chiral oxazoline substituents (4.1a-b). Unlike the previously reported P-mesityl phosphaalkene-oxazoline (F), the new monomer 4.1a can be homo- polymerized using radical methods of initiation to afford polymers of modest molecular weight.

In both the homo- and co-polymerization of 4.1a an addition-isomerization mechanism of propagation predominates. The presence of chiral centers at both the P- and C-centers of the former

P=C bond, as well as the enantiomerically pure oxazoline moiety, leads to fascinating NMR spectroscopic properties of polymers derived from 4.1a. Of particular interest is the random copolymer of 4.1a and styrene. For the first time, we have provided definitive spectroscopic evidence for styrene-phosphaalkene linkages in a phosphaalkene-styrene copolymer. Specifically,

1H-13C{1H} edHSQC and 1H-1H COSY/NOESY NMR spectroscopy on 4.5a gives evidence for

CHPh–P(CHPhAr) (i.e. S–4.1a) and ArCH2–CH2 (i.e. 4.1a–S) linkages. Finally, we have shown that both new polymers derived from 4.1a are amenable to the formation of coordination 89

complexes with metals. Future investigations will focus on further exploring the fascinating microstructures, properties, and potential applications of these and related functional P-containing polymers.

4.4 Experimental Section

4.4.1 Materials and Methods

Unless stated otherwise, all manipulations of were performed under a nitrogen atmosphere using standard Schlenk or glovebox techniques. Dichloromethane (CH2Cl2), and diethyl ether

(Et2O) were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. Tetrahydrofuran (THF) was dried over sodium/benzophenone ketyl and distilled prior to use. Methanol was deoxygenated with nitrogen prior to use. 1,1’-

Azobis(cyclohexanecarbonitrile) (VAZO 88) was purchased from Aldrich and recrystallized from

EtOH prior to use. Styrene was purchased from Aldrich and freshly distilled from CaH2 prior to use. CDCl3 and CD2Cl2 were purchased from Cambridge Isotope Laboratories Inc. and

49 160 161 deoxygenated with nitrogen prior to use. Compounds (L)-valinol, MesP(SiMe3)2, Mes*PH2, and Au(tht)Cl162 were synthesized according to literature procedures. 3-benzoylbenzoic acid,

SOCl2, Et3N, 4-toluenesulfonyl chloride (Ts-Cl), methyllithium (1.6M solution in Et2O) and trimethylsilylchloride (TMS-Cl) were purchased from Sigma-Aldrich and used as received. 1H,

13C{1H} and 31P NMR spectra were recorded at 298 K on Bruker Avance 300 or Avance 400

31 1 spectrometers. H3PO4 (85%) was used as an external standard (δ = 0) for P NMR spectra. H

NMR spectra were referenced to residual protonated solvent, and 13C{1H} NMR spectra were referenced to the deuterated solvent. edHSQC spectra were collected using the standard pulse sequence (pulprog: HSQCedetdp; 1J coupling constant: 145 Hz) taken from the Bruker software library. Inverse-gated 13C{1H} collected using 90° pulse (pulprog: zgig; 1J coupling constant: 145 90

Hz) and d1 = 3 s. Mass spectra were recorded on a Kratos MS 50 instrument in EI mode (70 eV).

Elemental analyses were performed by Mr. Derek Smith in the UBC Microanalysis Facility. The optical rotations were measured at a concentration in g per 100 mL and their values (average of 10 measurements) were obtained on a Jasco P-1010 polarimeter. Polymer molecular weights were determined by gel permeation chromatography -multi-angle light scattering (GPC-MALS) using an Agilent liquid chromatograph equipped with an Agilent 1200 series isocratic pump, Agilent

1200 series standard autosampler, Phenomenex Phenogel 5 mm narrow bore columns (4.6×300

4 3 mm) 10 Å (5,000–500,000 g mol-1), 500 Å (1000–15,000 g mol-1), and 10 Å (1,000–75,000 g mol-1),

Wyatt Optilab T-rEx differential refractometer (λ = 658nm, 40 °C), Wyatt TriStar miniDAWN

(laser light scattering detector at  = 690 nm) and a Wyatt ViscoStar viscometer. A flow-rate of

0.5 mL min-1 was used and samples were dissolved in THF (ca. 2 mg mL-1). The molecular weights were determined using 100% mass recovery methods from Astra software version 5 with each polymer sample being run at least three times to ensure reproducibility of the calculated refractive index increment (dn/dc).

4.4.2 Synthesis of (S)-PhC=OC6H4(CNOCH(i-Pr)-CH2) (4.3)

[In ambient moisture and atmosphere] To a suspension of 3-benzoylbenzoic acid (5.00 g,

22.1 mmol) in CH2Cl2 (50 mL) was added a few drops of DMF and a septum affixed to the flask with an outlet to an external oil bubbler. (COCl)2 (2.25 mL, 3.36 g, 26.5 mmol) was added dropwise over 30 minutes and the reaction mixture was stirred until the bubbling subsided (ca. 2 h). Volatiles were removed by rotary evaporation to give the crude acid chloride. To a cooled (0

°C) solution of (L)-valinol (2.47 mL, 2.30 g, 22.1 mmol) in Et3N (15.5 mL, 11.2 g, 111 mmol) and dry CH2Cl2 (100 mL) was added a solution of acid chloride in CH2Cl2 (50 mL) in one batch. The reaction mixture was warmed to room temperature and stirred 1 h whereupon it was quenched with 91

sat. aqueous NaHCO3 (100 mL) and the organic layer was separated. The organic layer was washed with 1 M HCl (100 mL), separated, and dried over Na2SO4. Volatiles were removed by rotary evaporation to give crude amide 4.2.

1 H NMR (300 MHz, CDCl3): δ = 8.20 (t, JHH = 2 Hz, 1H), 8.03 (dt, JHH = 8, 1 Hz, 1H),

7.87 (dt, JHH = 9, 1 Hz, 1H), 7.80-7.73 (m, 2H), 7.65-7.45 (m, 4H), 6.62 (d, JHH = 9 Hz, 1H), 4.01-

3.92 (m, 1H), 3.85-3.75 (m, 1H), 2.32 (br s, 1H), 2.08-1.97 (m, 1H), 1.03 (d, JHH = 6 Hz, 3H), 1.01

(d, JHH = 6 Hz, 3H).

To a solution of the previously synthesized amide 4.2 (22.1 mmol) in CH2Cl2 (100 mL) was added Ts-Cl (8.43 g, 44.2 mmol) followed by Et3N (15.4 mL, 11.2 g, 111 mmol). The reaction mixture was heated to reflux overnight. The reaction mixture was successively washed with water

(3 x 100 mL), sat. CuSO4 (2 x 100 mL), and brine (100 mL). The organic layer was separated and dried over Na2SO4. Volatiles were removed by rotary evaporation to give crude ketone 4.3.

Recrystallization in MeOH gave the title compound 4.3 as a white solid (3.54 g, 55%).

1 H NMR (400 MHz, CDCl3): δ = 8.34 (t, JHH = 1 Hz, 1H), 8.20 (dd, JHH = 6, 1 Hz, 1H),

7.91 (m, 1H), 7.81 (dd, JHH = 8, 1 Hz, 2H), 7.64-7.59 (m, 1H), 7.57-7.48 (m, 3H), 4.47-4.39 (m,

1H), 4.19-4.09 (m, 2H), 1.92-1.83 (m, 1H), 1.04 (d, JHH = 7 Hz, 3H), 0.93 (d, JHH = 6 Hz, 3H);

13C{1H} NMR (101 MHz, CDCl3): δ = 195.8, 162.3, 137.7, 137.0, 132.5, 132.2, 131.8, 129.9,

22 3 -1 -1 -3 129.4, 128.2, 128.2, 128.1, 72.6, 70.2, 32.7, 18.8, 18.0; [훼]D = –35.6 °cm g dm (c = 2.4 × 10

-3 + g cm , CH2Cl2); HRMS calcd for C19H20NO2 (M+H ): 294.1494; Found: 294.1495; Anal. Calcd for C19H19NO2: C, 77.79; H, 6.53; N, 4.77; Found: C, 77.51; H, 6.60; N, 4.59.

4.4.3 Synthesis of (S)-MesP=CPhC6H4(CNOCH(i-Pr)-CH2) (4.1a)

To a solution of MesP(SiMe3)2 (1.70 g, 5.73 mmol) in THF (10 mL) was added methyllithium (1.6 M in Et2O, 3.6 mL, 5.73 mmol). The reaction mixture was heated to 55 °C for 92

1-2 h. 31P NMR analysis of an aliquot removed from the reaction mixture suggested quantitative formation of MesP(Li)SiMe3 (δ = –187). The reaction mixture was cooled to –78 °C and treated with a solution of oxazoline 4.3 (1.68 g, 5.73 mmol) in THF (5 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P NMR spectroscopy revealed two singlet resonances which are consistent with phosphaalkene (E/Z-4.1a) (δ = 238.4,

238.2). The reaction mixture was quenched with excess TMS-Cl (ca. 3 mL), the solvent evaporated in vacuo, and the product extracted into hexanes (3 × 10 mL). After filtration, the hexanes was removed in vacuo. The product was dissolved in 5 mL n-pentane and stirred at 0 °C until a precipitate formed. The solid was filtered and dried in vacuo to give the product as a yellow solid

(1.15 g, 47%). Single crystals of Z-4.1a suitable for X-ray diffraction analysis were obtained by slow evaporation of a CDCl3 solution of E/Z-4.1a.

31 1 1 13 P{ H} NMR (121 MHz, CDCl3): δ = 237.6 (Z), 237.4 (E); H and C NMR assigned

1 only for major Z-isomer: H NMR (400 MHz, CDCl3): δ = 7.68 (m, 1H), 7.54 (m, 3H), 7.35 (m,

3H), 7.11 (d, JHH = 7.7 Hz, 1H), 7.00 (d, JHH = 8.0 Hz, 1H), 6.71 (br s, 1H), 6.70 (br s, 1H), 4.32

(m, 1H), 3.99 (m, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.16 (s, 3H), 1.70 (m, 1H), 1.00 (d, JHH = 6.9 Hz,

13 1 3H), 0.93 (d, JHH = 6.9 Hz, 3H); C{ H} NMR (101 MHz, CDCl3): δ = 192.8 (d, JPC = 44.5 Hz),

162.9, 144.1 (d, JPC = 23.0 Hz), 143.1 (d, JPC = 15.3 Hz), 140.4 (d, JPC = 6.1 Hz), 140.0 (d, JPC =

1.0 Hz), 138.3, 136.0 (d, JPC = 43.0 Hz), 131.0 (d, JPC = 6.1 Hz), 128.9 (d, JPC = 4.6 Hz), 128.6 (d,

JPC = 7.7 Hz), 128.2, 128.2, 127.5, 127.5, 127.3 (d, JPC = 3.1 H), 127.1 (d, JPC = 7.7 Hz), 72.4,

69.9, 32.7, 22.2 (d, JPC = 9.2 Hz), 22.1 (d, JPC = 7.7 Hz), 21.0, 18.7, 18.0. MS (EI): m/z 428, 427

+ + [30, 100, M ], 351, 350 [12, 44, M-Ph ]; HRMS (EI): m/z 427.2065 (calcd for C28H30NOP

427.2066).

93

4.4.4 Synthesis of (S)-Mes*P=CPhC6H4(CNOCH(i-Pr)-CH2) (4.1b)

To a cooled solution (–78 °C) of Mes*PH2 (0.898 g, 3.23 mmol) in THF (40 mL) was added n-butyllithium (1.5 M in hexanes, 2.8 mL, 4.2 mmol). The reaction mixture was warmed to room temperature, stirred 1 h, and cooled to –78 °C. TMS-Cl (0.53 mL, 0.46 g, 4.2 mmol) was added, the reaction mixture was warmed to room temperature, and stirred for 1 h. The reaction mixture was cooled to –78 °C and treated with a solution of oxazoline 4.3 (0.759 g, 2.58 mmol) in

THF (15 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P NMR spectroscopy revealed a singlet resonance that is consistent with phosphaalkene (E/Z-4.1b) (δ = 246.9, 246.3). The reaction mixture was quenched with excess

TMS-Cl (ca. 1 mL) and the solvent evaporated in vacuo. At this point the product could be handled under ambient moisture and air. The product was dissolved in hexanes (ca. 3 mL) and filtered through a small plug of Celite. Volatiles were removed using rotary evaporation, the green residue was purified by column chromatography (SiO2, gradient Hex:EtOAc (50:1) to Hex:EtOAc (10:1)), and both stereoisomers of 4.1b isolated as a green solid [0.92 g, 58:42 (E:Z), 64%]. Single crystals of Z-4.1b suitable for X-ray diffraction analysis were obtained from a saturated n-pentane solution of E/Z-4.1b.

31 1 1 Z-4.1b: P{ H} NMR (162 MHz, CDCl3): δ = 246.9; H NMR (400 MHz, CDCl3): δ =

7.60 (d, JHH = 7.6 Hz, 1H), 7.42 (m, 2H), 7.34 (m, 3H), 7.25 (br s, 1H), 7.22 (br s, 2H), 6.88 (t,

JHH = 7.9 Hz, 1H), 6.51 (d, JHH = 7.9 Hz, 1H), 4.32 (t, JHH = 8.2 Hz, 1H), 3.99 (m, 2H), 1.78 (m,

1H), 1.51 (s, 9H), 1.49 (s, 9H), 1.28 (s, 9H), 1.03 (d, JHH = 6.7 Hz, 3H), 0.89 (d, JHH = 6.7 Hz, 3H);

13 1 C{ H} NMR (101 MHz, CDCl3): δ = 180.1 (d, JPC = 45.4 Hz), 163.2, 154.4, 150.2, 145.5 (d, JPC

= 27.8 Hz), 142.7 (d, JPC = 16.1 Hz), 135.7, 135.1, 132.1 (d, JPC = 5.9 Hz), 129.1 (d, JPC = 7.3 Hz),

94

128.6, 128.4, 128.3, 128.0, 126.9, 126.8, 126.5, 121.7 (d, JPC = 14.6 Hz), 72.7, 70.2, 38.2, 34.9.

33.4, 33.4, 33.0, 31.4, 19.2, 18.3.

31 1 1 E-4.1b: P{ H} NMR (162 MHz, CDCl3): δ = 246.5; H NMR (400 MHz, CDCl3): δ =

7.98 (d, JHH = 7.6 Hz, 1H), 7.95 (s, 1H), 7.52 (d, JHH = 7.6 Hz, 1H), 7.39 (t, JHH = 7.6 Hz, 1H),

7.31 (s, 2H), 6.97 (t, JHH = 7.3 Hz, 1H), 6.86 (t, JHH = 8.2 Hz, 2H), 6.37 (d, JHH = 7.6 Hz, 2H), 4.40

(m, 1H), 4.13 (m, 2H), 1.88 (m, 1H), 1.48 (s, 18H), 1.36 (s, 9H), 1.04 (d, JHH = 6.7 Hz, 3H), 0.94

13 1 (d, JHH = 6.7 Hz, 3H); C{ H} NMR (101 MHz, CDCl3): δ = 179.2 (d, JPC = 45.5), 163.2, 154.5,

154.4, 150.7, 145.8 (d, JPC = 29.3 Hz), 142.1 (d, JPC = 16.9 Hz), 135.8, 135.2, 129.1 (d, JPC = 8.8

Hz), 128.1, 127.7 (d, JPC = 3.7 Hz), 127.1 (d, JPC = 2.2 Hz), 126.7, 126.4, 121.9 (d, JPC = 2.2 Hz),

72.6, 70.0, 38.1, 34.9, 33.1 (d, JPC = 7.3 Hz), 32.8, 31.4, 19.0, 18.0; MS (ESI): m/z 578, 577 [30,

+ + 85, M·Na ], 556, 555 [35, 100, M ]; HRMS (ESI): m/z 554.3549 (calcd for C37H48NOP 554.3552);

Anal. Calcd for C37H48NOP: C, 80.25; H, 8.74; N, 2.53; Found: C, 80.60; H, 8.80; N, 2.53.

4.4.5 Synthesis of Homopolymer 4.4a

Phosphaalkene 4.1a (2.0 g, 4.7 mmol) and VAZO 88 (11 mg, 0.047 mmol) were added to a PyrexTM tube. The tube was flame-sealed in vacuo and, subsequently, heated at 160 °C in an oven equipped with rocking tray. Over a period of 14 h, the polymerization mixture became increasingly viscous. The tube was removed from the oven and cooled to ambient temperature, at which point the sample was solid and broken in a nitrogen filled glovebox. The contents were dissolved in THF

(ca. 10 mL) in the glovebox and transferred to a Schlenk flask (250 mL). The solution was concentrated in vacuo and precipitated with MeOH (100 mL) to give a light-yellow solid. This process was repeated two times to give polymer 4.4a as a light-yellow powder that was in vacuo for 24 h (0.12 g, 6%).

95

31 1 1 P{ H} NMR (162 MHz, CDCl3): δ = 4.0 (br s), -7.6 (br s); H NMR (400 MHz, CDCl3):

δ = 8.1-6.1 (br m, aryl H), 4.9 (br s, P-CH), 4.6-3.7 (br m, methane CH from oxazoline), 3.0-0.5

13 1 (br m, alkyl CH3 and isopropyl CH); C{ H} NMR (101 MHz, CDCl3): δ = 163.2, 146.6, 142.6,

138.1, 131.9, 128.4, 127.9, 126.3, 125.8, 72.5, 69.8, 52.1, 32.8, 23.2, 20.9, 19.1, 18.0; GPC-LLS

−1 22 3 -1 -1 -3 (THF): Mn = 5300 g mol ; PDI = 1.2; dn/dc = 0.19; [훼]D = –19.9 °cm g dm (c = 1.4 × 10 g

-3 cm , CH2Cl2).

4.4.6 Synthesis of Copolymer 4.5a

Styrene (1.2 g, 12 mmol), phosphaalkene 4.1a (2.5 g, 5.9 mmol) and VAZO 88 (43 mg,

0.18 mmol) were added to a PyrexTM tube. The tube was flame-sealed in vacuo and, subsequently, heated at 160 °C in an oven equipped with rocking tray. Over a period of 14 h, the polymerization mixture became increasingly viscous. The tube was removed from the oven and cooled to ambient temperature, at which point the sample was solid and broken in a nitrogen filled glovebox. The contents were dissolved in THF (ca. 10 mL) in the glovebox and transferred to a Schlenk flask

(250 mL). The solution was concentrated in vacuo and dissolved in a minimal amount of THF (ca.

5 mL). The THF solution was precipitated with degassed MeOH (50 mL) and collected by centrifugation. After decanting the solvent, the precipitation and centrifugation was repeated two additional times. The resulting solid was dried in vacuo for 24 h to give polymer 4.5a as an off- white powder (0.54 g, 14 %).

31 1 1 P{ H} NMR (162 MHz, CDCl3): δ = 5.9 (br s), -7.6 (br s); H NMR (400 MHz, CDCl3):

δ = 8.1-6.0 (br m, aryl H), 4.5-3.8 (br m, methane CH from oxazoline), 3.6 (br s, P-CH), 2.9-0.5

13 1 (br m, styrene CH2/CH, alkyl CH3 and isopropyl CH); C{ H} NMR (101 MHz, CDCl3): δ

=163.3, 145.2, 142.4, 138.3, 130.3, 127.9, 127.6, 125.6, 72.5, 69.9, 48.4, 43.8, 40.5, 32.8, 23.2,

96

−1 22 20.9, 19.0, 18.0; GPC-LLS (THF): Mn = 4000 g mol ; PDI = 1.1; dn/dc = 0.20; [훼]D = –29.3

3 -1 -1 -3 -3 °cm g dm (c = 1.1 × 10 g cm , CH2Cl2).

4.4.7 Standard Procedure for Gold Coordination to PMP (4.4a·AuCl and 4.5a·AuCl)

To a solution of either polymer 4.4a (20 mg, 0.047 mmol P) or 4.5a (43 mg, 0.047 mmol

P) in CH2Cl2 (2 mL) was added Au(THT)Cl (15 mg, 0.047 mmol) and the reaction was stirred for

1 h. After 1 h the mixture was handled in ambient air and moisture, and was precipitated in n- pentane (20 mL). The product as collected by centrifugation and the solvent decanted. The resulting solid was dissolved in CH2Cl2 (1 mL), precipitated in n-pentane (20 mL), and collected by centrifugation. The solvent was decanted and the residual solid was dried in vacuo for 24 h to give the product as an off-white solid (4.4a·AuCl: 30 mg, 97%; 4.5a·AuCl: 36 mg, 67%).

31 1 1 4.4a·AuCl: P{ H} NMR (162 MHz, CDCl3): δ = 41.0, (br minor), 23.5 (br, major); H

NMR (400 MHz, CDCl3): δ = 8.6-6.3 (br m, aryl H), 5.3 (br s, P-CH), 4.8-3.8 (br m, methane CH from oxazoline), 3.0-0.6 (br m, alkyl CH3 and isopropyl CH); GPC-LLS (THF): Mn = 13000 g mol−1; PDI = 1.2; dn/dc = 0.086.

31 1 1 4.5a·AuCl: P{ H} NMR (162 MHz, CDCl3): δ = 41.9 (br, major), 24.7 (br, major); H

NMR (400 MHz, CDCl3): δ = 8.2-6.1 (br m, aryl H), 4.5-3.8 (br m, methane CH from oxazoline),

3.6 (br s, P-CH), 2.9-0.6 (br m, styrene CH2/CH, alkyl CH3 and isopropyl CH); GPC-LLS (THF):

−1 Mn = 7500 g mol ; PDI = 1.1; dn/dc = 0.13.

4.4.8 X-ray Crystallographic Studies

All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX II diffractometer with graphite-monochromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All nonhydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated 97

positions but not refined. All data sets were corrected for absorption effects (SADABS), Lorentz, and polarization effects. All calculations were performed using SHELXL-2014 crystallographic software package from Bruker AXS.114 Absolute configuration was confirmed on the basis of the refined Flack parameter.115 Compound Z-4.1b crystallized with two inequivalent molecules of Z-

4.1b in the asymmetric unit and three disordered t-Bu groups. Additional crystal data and details of data collection and structure refinement are given in the supporting information. All crystallographic data has been deposited with the Cambridge Structural Database: 1460770,

1460771.

98

Table 4.1 X-ray Data Collection and Refinement Details for Compounds 4.1a and 4.1b.

4.1a 4.1b

formula C28H30NOP C37H48NOP fw 427.50 553.73 cryst syst monoclinic triclinic space group P21 P1 colour green green a (Å) 8.593(2) 10.369(3) b (Å) 6.543(1) 10.511(3) c (Å) 20.975(4) 16.499(4) α (deg) 90 94.563(7) β (deg) 99.002(4) 96.525(6) γ (deg) 90 114.894(6) V (Å3) 1164.7(4) 1604.2(6) T (K) 90(2) 90(2) Z 2 2 μ(Mo Kα) (mm-1) 0.138 0.114 cryst size (mm3) 0.10×0.10×0.05 0.16×0.16×0.12 -3 Dcalcd. (Mg m ) 1.219 1.146 2θ(max) (°) 55.1 53.0 no. of reflns 9603 25215 no. of unique data 4954 20331 R(int) 0.0382 0.0467 refln/param ratio 17.3 13.1 a R1 [I > 2σ(I)] 0.0292 0.0370 b wR2 [all data] 0.0904 0.1161 GOF 1.022 1.019 a R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표|. b 2 2 2 2 2 2 1/2 w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

99

Chapter 5: Copper(I) Complexes of Pyridine-Bridged Phosphaalkene-

Oxazoline Pincer Ligands*

5.1 Introduction

The tridentate pincer motif, a classic ligand framework, is often used to investigate both profound and subtle steric and electronic effects within ligand design.163 2,6-Disubstituted pyridines are well recognized as obvious chemical systems for the creation of tridentate pincer ligand sets. Often these pyridines are difunctionalized with common donor sets based on N, O, S, and P atoms. Although symmetric ligands can be easier to synthesize, non-symmetric 2,6- substituted pyridines offer the possibility of fortuitous binding properties, upon κ3-coordination of a metal ion, by forced orientation of different donors in a trans-geometry within a metal complex

(e.g. A and B in Figure 5.1).164

* Versions of sections of this chapter have been published. Spencer C. Serin, Fraser S. Pick, Gregory R. Dake and Derek P. Gates. Copper(I) Complexes of Pyridine-Bridged Phosphaalkene-Oxazoline Pincer Ligands. Inorg. Chem. 2016, 55(13), 6670-6678. 100

Figure 5.1 Selected Examples of Pincer and Mixed PN Phosphaalkene Ligands.

There is considerable interest in the coordination chemistry of compounds containing low coordinate phosphorus, such as phosphaalkenes or phosphinines, for potential applications in catalysis.165, 166 The P=C double bond features a low-energy π*-orbital that leads to excellent π- accepting properties.167 Examples of phosphaalkene-containing pincer ligands are limited to the symmetric ligand D [i.e. 2,6-bis(phosphaethylene)pyridine or BPEP, R = H168 and R = Ph72]. This class of ligand has attracted attention due to its highly delocalized π-electron backbone that is not found in analogous bisphosphine derivatives. BPEP-Ph offers distinctive metal stabilization properties that permit the isolation of a four-coordinate Fe(I) species [e.g. (BPEP-Ph)FeBr] in an unusual 15-electron configuration.72, 169 Additionally, BPEP-Cu(I) complexes {e.g. Cu(X)(BPEP-

– – Ph), where X = [PF6] and [SbF6] } are extremely electron-deficient, exhibiting strong affinity

– – 74, 170 toward both [PF6] and [SbF6] , due to the strong π-accepting ability of the P=C bonds.

We have previously developed bidentate ligands such as the achiral phosphaalkene- pyridine E32 which is an effective ligand for the Pd(II)-catalyzed Overman-Claisen rearrangement 101

of allyl trichloroacetimidates.82 In addition, we have developed a modular route to the first enantiomerically pure phosphaalkene-oxazoline ligands (F, PhAk-Ox)46, 50 and have demonstrated their utility in the Pd(II)-catalyzed asymmetric allylic alkylation reaction.171 Related work involves the use of the mixed phosphaalkene-imine ligand G for the Pd(II)-catalyzed oligomerization of ethylene.172 Inspired by the ubiquity of bisoxazoline pyridine pincer ligands (C, PyBox) in asymmetric catalysis,173 we envisioned the development of a hybrid phosphaalkene-pyridine- oxazoline PNN ligand (5.1).

In this report, we present the modular synthesis of enantiomerically pure phosphaalkenes

5.1a-c (PhAk-Pyr-Ox) as a new ligand class that effectively coordinates to Cu(I). This hybrid PNN ligand increases the sophistication possible for low-coordinate phosphorus compounds as well provides a new nonsymmetric PNN-pincer motif for application in coordination chemistry.

5.2 Results and Discussion

5.2.1 Phosphaalkene Synthesis and Characterization

The general synthetic strategy towards phosphaalkene 5.1 is outlined in Scheme 5.1. By analogy to PhAk-Ox and PyBox, the strategy takes advantage of well-established literature condensation reactions. Specifically, the condensation of α-silylphosphides with ketones, the phospha-Peterson reaction, generates phosphaalkenes in high yield.32 Similarily, the (multistep) condensation of chiral pool derived α-amino alcohols with carboxylic acids produces oxazolines.

Consequently, ketones of type 5.2 are critical synthetic building blocks. Ketones of type 5.2 could be conveniently prepared from a mono esterified derivative of 2,6-pyridine dicarboxylic acid.

102

Scheme 5.1 Synthetic Approach to Pyridine-bridged Phosphaalkene-oxazolines.

Carboxylic acid 5.4 can be prepared from commercially available 2,6-pyridinedicarboxylic acid.174 Reaction of 5.4 with thionyl chloride generates an acid chloride that undergoes Friedel-

Crafts acylation with benzene in the presence of AlCl3 (Scheme 5.2). The acidic workup of this acylation also hydrolyzed the methyl ester to yield 6-benzoyl-2-pyridinecarboxylic acid (5.2) as an off-white solid in a 68% overall yield. Importantly, only solvent extraction was required to purify large batches (ca. 20 g) of acid 5.2. Analysis of the 13C{1H} NMR spectrum of 5.2 revealed the expected characteristic signals for the C=O carbon of the benzoyl and carboxylic acid (δ13C =

192.1 and 163.7) respectively.

Scheme 5.2 Synthesis of Enantiomerically Pure Pyridyl-ketones.

A multistep procedure to oxazolines 5.3a-b from 5.2 was adopted from a previous report.175

Amides 5.5a-b could be prepared in a straightforward manner by the reaction of the acid chloride

103

derived from 5.2 and either (L)-valinol (a) or (L)-phenylalaninol (b) (Scheme 5.2). The alcohol functions in 5.5a-b could be converted to chlorides 5.6a-b using SOCl2 in hot CHCl3. A traditional cyclization176 of related chlorides to form oxazolines that used alkaline aqueous conditions (NaOH in refluxing MeOH/H2O) was not possible in this instance due to the hydrolytic instability of the oxazoline product. Fortunately, cyclization was successful under anhydrous conditions using NaH in refluxing THF, as no aqueous workup step was required to afford ketones 5.3a-b. Importantly, these steps can be performed without thorough purification of the amides 5.5a-b and chlorides

5.6a-b.

Recrystallization of the oxazolines 5.3a-b in Et2O afforded analytically pure ketones in

45% and 66% yield, respectively. Compounds 5.3a-b were fully characterized using 1H and

13C{1H} NMR spectroscopy and mass spectrometry. Particularly diagnostic are the 13C NMR signals for the C=N of the oxazoline and C=O of the ketone in 5.3 {δ13C [C=N, C=O] = (5.3a):

22 161.9, 192.1; (5.3b): 162.6, 192.2}. Each ketone displayed optical activity {[훼]D = 5.3a: –118

3 -1 -1 -1 3 -1 -1 -1 °cm g dm (c = 2.2 × 10 , CHCl3); 5.3b: –47.6 °cm g dm (c = 2.8 × 10 , CHCl3)}. Crystals of ketone 5.3a were obtained by slow evaporation of a saturated Et2O solution. The resulting solid state molecular structure (Figure 5.2), confirmed the configuration of the (S)-stereocentre of the amino alcohol in the oxazoline.

104

Figure 5.2 Molecular structure of Ketone 5.3a (50% Probability Ellipsoids).

Hydrogen atoms were omitted for clarity. Selected bond lengths (Å) and angles (deg): O(1)–C(7) 1.217(2), N(2)– C(13) 1.268(2), O(2)–C(13) 1.353(2), C(1)–C(7)–C(8) 120.9(2), C(12)–C(13)–O(2) 117.0(1), C(12)–C(13)–N(2) 123.5(2), O(2)–C(13)–N(2) 119.4(2).

The phospha-Peterson reaction32 was performed as the P=C bond forming step (Scheme

5.3). The representative procedure is as follows: a solution of ketone 5.3a in THF was added dropwise to a cooled (-78 °C) solution of MesP(Li)SiMe3 in THF. The reaction was warmed to room temperature whereupon an aliquot was removed for analysis by 31P NMR spectroscopy. The signal assigned to MesP(Li)SiMe3 (δ = -187) was replaced by two new signals of equal intensity at 266.6 and 248.3 ppm, in a range consistent with those expected for phosphaalkenes32 and indicating the product was formed as a mixture of E and Z stereoisomers. The desired phosphaalkene 5.1a (yield = 54 %) was isolated by trituration with hexanes to give the product as a red solid (ca. 1.0:0.64, Z:E) and crystallographically characterized as the Z-isomer after recrystallization from benzene (Figure 5.3). Overall the metrical parameters are consistent with those observed previously for Mes-substituted phosphaalkene such as MesP=CPh2 and related systems.32, 43

105

Scheme 5.3 Synthesis of Pyridine-bridged Phosphaalkene-oxazolines.

Figure 5.3 Molecular structure of Phosphaalkene 5.1a (50% Probability Ellipsoids).

Hydrogen atoms were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.693(2), P(1)–C(19) 1.834(2), C(1)–C(2) 1.488(3), C(1)–C(8) 1.491(3), C(1)–P(1)–C(19) 104.2(1), C(2)–C(1)–P(1) 119.3(2), C(8)–C(1)– P(1) 125.4(2), and C(2)–C(1)–C(8) 115.2(2). Phosphaalkene 5.1a was fully characterized using 1H, 13C{1H} and 31P NMR spectroscopy, and mass spectrometry [HRMS (5.1a+): m/z 428.2018 (found); 428.2016 (calcd)]. Signals could be unequivocally assigned to either the Z- or E-isomer by using 1H-1H NOESY, 1H-1H COSY, and

31P-1H HSQC NMR spectroscopy (Figures 5.9 and 5.10, Section 5.5). Consistent with previous reports of pyridyl-substituted phosphaalkenes, the more upfield 31P NMR signal is indicative of a

106

Z-isomer [e.g. δ31P = MesP=CPh(2-py): 260.1 (E), 242.1 (Z);32 Mes*P=CH(2-py): 285.4 (E), 259.6

(Z)168].

To illustrate the modularity of our synthetic route to chiral phosphaalkenes, two additional phosphaalkenes 5.1b and 5.1c were prepared in 27% and 42% yields respectively. These compounds were prepared following the same procedure as described for 5.1a. The steric bulk of the P-substituent is increased in 5.1b by employing the Mes* moiety. Additionally, by using ketone 5.3b instead of 5.3a, a benzyl moiety (5.1c) was substituted in place of the isopropyl group

(5.1a). Each new phosphaalkene was characterized by 31P NMR spectroscopy [δ31P = 5.1b: 266.0

(E), 257.6 (Z); 5.1c: 264.4 (E), 245.5 (Z)], 1H/13C NMR spectroscopy, spectroscopy and mass spectroscopy [HRMS (5.1b+): m/z 555.3491 (found); 555.3504 (calcd), (5.1c+): m/z 476.2018;

476.2018 (calcd)]

5.2.2 Coordination of Phosphaalkene 5.1a to Copper

The coordination chemistry of PNN-proligand 5.1a is of considerable interest. As a starting point, we investigated binding of 5.1a to copper(I) since related NNN-pincer complexes have been used in a variety of asymmetric transformations, such as hydrosilylations,177, 178 aziridinations,179 alkyne additions to imines,180, and conjugate additions,181, 182 among others. Moreover, copper(I) complexes of phosphaalkene-pyridine ligands have been reported previously.74, 168, 170, 183, 184

A mixture of 5.1a and Cu(MeCN)4OTf in CH2Cl2 was stirred for 2 h over which time a color change from red to deep brown was observed (Scheme 5.4). Analysis of an aliquot using

31 1 P{ H} NMR spectroscopy revealed quantitative conversion of both isomers of phosphaalkene

5.1a to a single new resonance at 186 ppm, a value shifted considerably upfield relative to pincer precursor E-5.1a (Δδ = -62). The appearance of a single resonance in the 31P{1H} NMR spectrum of the reaction mixture suggests isomerization of the ligand prior to coordination. An upfield shift 107

of >60 ppm for 5.1a and Cu(I) is larger than any previously reported copper(I) phosphaalkene-

+ 168 pyridine complexes [Δδ = {E-Mes*P=C(2-Py)(H)}Cu(MeCN)2 : -15 ppm; (BPEP-

74 + 184 Ph)Cu(SbF6): -35 ppm; (BPEP-H)Cu(MeCN) : -16 ppm ]. The product was precipitated by addition of Et2O, and filtered to give complex 5.7 as a brown solid in 79% yield.

Scheme 5.4 Synthesis of Copper(I)-phosphaalkene Complexes.

Single crystals of complex 5.7 were obtained by slow diffusion of Et2O into a CH2Cl2 solution. X-ray crystallographic analysis produced the structure of an unexpected dimeric Cu(I) complex (Figure 5.4). Phosphaalkene 5.1a did not coordinate to copper as a neutral κ3(PNN) ligand as expected, but rather κ(P), κ2(NN). Each Cu(I) is bound to an oxazoline-pyridine moiety in addition to the phosphaalkene of a neighbouring 5.1a molecule.

108

Figure 5.4 Molecular structure of Complex 5.7 (50% Probability Ellipsoids).

Structure truncated and hydrogen atoms were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)– Cu(2) 2.160(1), P(2)–Cu(1) 2.180(1), N(1)–Cu(1) 2.186(3), N(2)–Cu(1) 2.072(3), N(3)–Cu(2) 2.157(3), N(4)–Cu(2) 2.073(4), P(1)–C(1) 1.694(4), P(2)–C(28) 1.690(3), N(5)–Cu(1) 2.016(3), O(3)–Cu(2) 2.156(8), C(1)–P(1)–Cu(2) 119.8(2), C(28)–P(2)–Cu(1) 121.9(1), N(1)–Cu(1)–P(2) 130.84(8), N(1)–Cu(1)–N(2) 79.6(1), P(2)–Cu(1)–N(2) 115.6(1), P(1)–Cu(2)–N(3) 136.35(8), N(3)–Cu(2)–N(4) 80.2(1), P(1)–Cu(2)–N(4) 118.6(1).

This coordination mode has not been observed for related BPEP-Cu(I) complexes. The closest example is the dimeric copper complex H (Figure 5.5) which was isolated from the reaction of (S,S)-i-Pr-PyBox with Cu(MeCN)4PF6. Unlike complex 5.7, the Cu(I) centers in H have different coordination numbers. In each case, the pincer serves as a bridging ligand.

Figure 5.5 Known Dimeric Copper Pyridine-oxazoline Complex. 109

It should be noted that the steric environment around the Mes-substituted phosphorus atom in 5.1a is smaller than that of the Mes*-substituted phosphorus atoms within BPEP. Therefore, ligand 5.1a is more likely to form a bridging dimeric complex such as 5.7 whilst all the previously reported BPEP complexes are monomeric. It was envisioned that substituting the weakly coordinating [OTf]– and MeCN ligands in 5.7 with a larger neutral ligand (L, Scheme 5.4) would facilitate the isolation of a monomeric [(PNN)Cu(L)]+ complex. Fittingly, upon addition of a bulky ligand (2 equiv) to complex 5.7 (1 equiv) the reaction colour drastically changed from deep brown to dark red [L = PPh3 (5.8a) and P(OPh)3 (5.8b)], dark green [L = 2,6-lutidine (5.8c)], or dark blue

[L = 4-DMAP (5.8d) and 1-methylimidazole (5.8e)]. In each case, analysis of the 31P{1H} NMR spectra of the reaction mixture showed complete conversion of complex 5.7 to a new product with a distinct chemical shift (5.8a: 232 ppm; 5.8b: 227 ppm; 5.8c: 215 ppm; 5.8d: 208 ppm; 5.8e: 207 ppm). Additionally, for 5.8a and 5.8b, the free phosphine and phosphite signals (δ31P = -6 and

129, respectively) were replaced with new resonances (δ31P = 9 and 114, respectively), which were tentatively assigned to coordinated phosphine or phosphite. Complex 5.8a was isolated and crystals suitable for X-ray diffraction were obtained by the diffusion of hexanes into a THF solution. Analysis of the solid state molecular structure revealed the monomeric

+ [(PNN)Cu(PPh3)] complex (Figure 5.6).

110

Figure 5.6 Molecular structure of Complex 5.8a∙(C4H8O)3 (50% Probability Ellipsoids).

Hydrogen atoms, THF molecules and [OTf]– counterion were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.710(2), P(1)–Cu(1) 2.3119(6), P(2)–Cu(1) 2.2263(6), N(1)–Cu(1) 2.043(2), N(2)–Cu(1) 2.072(2), C(1)–C(8) 1.464(3), N(1)–C(8) 1.350(3), N(2)–C(13) 1.281(3), C(12)–C(13) 1.469(3), P(1)–Cu(1)–P(2) 106.10(2), P(1)–Cu(1)–N(1) 78.23(5), P(1)–Cu(1)–N(2) 135.94(5), N(1)–Cu(1)–N(2) 80.34(7), P(2)–Cu(1)–N(2) 115.37(5), N(1)–Cu(1)–P(2) 138.62(6), Cu(1)–P(1)–C(1) 102.70(8), P(1)–C(1)–C(2) 127.2(2), P(1)–C(1)–C(8) 112.4(2), C(12)– C(13)–N(2) 121.9(2), Cu(1)–N(2)–C(13) 110.5(5).

5.2.3 Characterization of Copper Complexes

In addition to obtaining the solid state molecular structures for complexes 5.7 and 5.8a, both complexes were characterized by 1H, 13C{1H}, 19F, and 31P NMR analysis, elemental analysis

(for 5.7) and mass spectrometry (for 5.8a). Complexes 5.7 and 5.8a showed an optical rotation

22 3 -1 -1 -1 3 -1 -1 -1 {[훼]D = 5.7: –24.7 °cm g dm (c = 1.8 × 10 , CH2Cl2); 5.8a: 89.2 °cm g dm (c = 0.72 × 10 ,

CH2Cl2)}. Complex 5.7 displayed remarkable air and moisture stability as a solid, and could be stored for weeks on the benchtop with no signs of degradation (by 31P NMR analysis), while 5.8a

111

decomposed in ambient conditions. The NOESY NMR spectrum of complex 5.7 in CDCl3 (Figure

5.11, Section 5.5) suggests the dimer remains stable in solution and does not dissociate into two monomeric copper complexes. In particular, a NOE correlation was observed between one ortho-

CH3 group of the P-Mes substituent and the methyl group of the oxazoline isopropyl moiety, confirming a proximity that could only be present in the dimeric form. The hydrogen atoms of these moieties are ca. 3.5 Å apart in the X-ray structure of 5.7.

Both 5.7 and 5.8a display distorted tetrahedral geometry around the Cu(I) centre, where the dihedral angle of (P-Cu-L)–(N-Cu-N) (L = ancillary ligand) differs significantly from 90° [ca.

78.6° (5.7) and 48.6° (5.8a)]. The large distortion of dihedral angle observed for complex 5.8a rationalizes the requirement of a bulky ancillary ligand, as 5.7 is able to achieve a more ideal tetrahedral geometry when 5.1a binds κ(P), κ2(NN). Particularly diagnostic are the 31P NMR shifts for the phosphaalkene resonances in complexes 5.7 (186 ppm) and 5.8a (232 ppm). 31P NMR chemical shifts for phosphaalkene metal complexes have been shown to be sensitive to P–M distance,185 with shorter P–M bonds having more upfield resonances. Complex 5.7 possesses a largely upfield 31P signal and, accordingly, the P–Cu(I) bond lengths in 5.7 (ca. 2.17 Å) are shorter than 5.8a (ca. 2.31 Å) and other BPEP-Cu(I) complexes [e.g. (BPEP-Ph)Cu(SbF6), P–Cu: 2.26 and δ31P = 213;74 (BPEP-H)Cu(MeCN)+, P–Cu: 2.31 Å and δ31P = 269184].

UV/Vis spectroscopic analysis of CH2Cl2 solutions of complexes 5.8a-5.8e revealed two distinct energy transitions (band I: 450-700 nm and band II: 350-425 nm, Figure 5.7). The absorptions in the visible region of the UV spectrum are consistent with the observed colors of

5.8: 5.8a (λmax = 540 nm, red), 5.8b (λmax = 513 nm, red), 5.8c (λmax = 587 nm, green), 5.8d (λmax

= 609 nm, blue) and 5.8e (λmax = 604 nm, blue). It is intriguing to note that complexes with the highest energy band I transitions (5.8a, 5.8b) also have significantly upfield 31P NMR shifts (Table 112

5.1). Conversely, more downfield 31P NMR shifts are observed for complexes with low energy band I absorbances (5.8d, 5.8e). We hypothesize that an upfield chemical shift is a consequence of a contraction of the =P–Cu(I) bond in complex 5.8. Such a bond contraction would be observed for strongly donating ligands (i.e. pyridine and imidazole-based donors) which push electron density towards the Cu(I) center and onto π-accepting phosphaalkene ligand strengthening the =P–

Cu(I) interaction. In contrast, where π-accepting ligands [i.e. PPh3 and P(OPh)3] compete with the

π-accepting phosphaalkene ligand, weakening the =P–Cu(I) interaction. This is consistent with that discussed earlier where complex 5.7, possessing a shorter =P–Cu bond, was shifted upfield with respect to 5.8a. Clearly, these trends are more complex and additional effects (e.g. sterics)

31 cannot be disregarded. Moreover, more subtle trends in UV/Vis and  PP=C have been reported for bis(phosphaalkene) platinum(0) complexes.186

-5 Figure 5.7 Representative UV/Vis Spectra of 5.8a-5.8e in CH2Cl2 Solution (All Concentrations Were ca. 5 × 10

mol L-1).

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Table 5.1 31P NMR data (ppm) and λmax values (nm) for band I and band II of 5.8a-5.8e.

31 # L δ PP=C band I: λmax (log ε) band II: λmax (log ε)

5.8a PPh3 232 540 (4.24) 373 (4.50)

5.8b P(OPh)3 227 513 (4.04) 341 (4.46) 5.8c 2,6-lutidine 215 487 (4.10) 386 (4.35) 5.8d 4-DMAP 208 609 (4.06) 400 (4.19) 5.8e 1-methylimidazole 207 604 (4.14) 392 (4.31)

5.2.4 Computational Section

To gain further insight into the orbitals involved in the electronic transitions in complex 5.8 and the trends in max (band 1), we modeled 5.8a bearing the accepting PPh3 and 5.8d bearing the strongly donating 4-DMAP. Each structure was geometrically optimized (Figure 5.12 and Figure

5.13, Section 5.5) and, in the case of 5.8a, matched well with the obtained solid state molecular structure. In the previous section, we hypothesized that the more downfield 31P NMR shift for 5.8d is indicative of a shortened P–Cu bond. Accordingly, the computed P–Cu(I) bonds (5.8a: 2.414 Å,

5.8d: 2.387 Å) contract when PPh3 is replaced with 4-DMAP.

Time-dependent DFT (TD-DFT) calculations were performed for 5.8a and 5.8d and the frontier molecular orbitals are shown in Figure 6. It is important to note the LUMO is largely composed of the π*-P=C bond, confirming its π-accepting ability even vs. PPh3, and its composition does not change significantly with different ancillary ligands. In each complex, the

HOMO orbital shows interactions between the pincer ligand and the Cu(I) center. In contrast, the

HOMO(-1) are quite different for each complex. In 5.8a, the HOMO(-1) is primarily phosphaalkene-based whereas it consists primarily of DMAP-based electron density in 5.8d.

114

Figure 5.8 Important Molecular Orbitals for the Low Energy Transitions of 5.8a and 5.8d.

Two absorption bands (I and II) were identified. For 5.8a, band I includes major and minor contributions of the HOMO/LUMO (66%), HOMO(-1)/LUMO (15%), HOMO(-3)/LUMO (12%), and HOMO(-4)/LUMO (11%). In contrast, band I of 5.8d is composed mainly of the

HOMO/LUMO transition (67%). The calculated HOMO-LUMO gap for 5.8a (E = 0.297 eV) is larger than for 5.8d (E = 0.285 eV). Moreover, there is additional mixing of lower energy

HOMOs into the band I transition of 5.8a but not in the case of 5.8d. Both these factors are consistent with the blue shift observed in band I of the UV/Vis spectrum. For 5.8a, band II includes 115

a significant contribution of the HOMO(-1)/LUMO (52%) whilst band II for 5.8d is largely based on the HOMO(-2)/LUMO (64%) transition.

5.3 Summary

The synthesis of new tridentate PhAk-Pyr-Ox ligands increases the scope of ligand motifs by combining a phosphaalkene and a chiral oxazoline. The spectroscopic properties of Cu(I)- complexes of this new class of pincer ligand highlights the excellent π-accepting properties of these phosphaalkene ligands. In particular, the =P–Cu bond length can be altered by manipulating the electron density around the metal center, which can be observed experimentally by changes in the UV/Vis spectra, with different ancillary ligands. A shorter =P–Cu bond length leads to the an

31 upfield δ PP=C NMR chemical shift. In addition, red shifted bands in the UV/Vis spectrum suggest a =P–Cu bond contraction. We further investigate this property computationally and propose that, in complexes bearing more electron rich ancillary ligands (i.e. 4-DMAP), the low-lying π*P=C orbital (the LUMO of these complexes) is able to electronically strengthen the =P–Cu(I) interaction. Future studies will attempt to take advantage of the donor-acceptor properties of these enantiomerically pure pincer ligands in asymmetric catalysis.

5.4 Experimental

5.4.1 Materials and Methods

Unless stated otherwise, all manipulations were performed using standard Schlenk or glovebox techniques under nitrogen atmosphere. CH2Cl2 and hexanes were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. THF was dried over sodium/ benzophenone ketyl and distilled prior to use. CD2Cl2 and CDCl3 were deoxygenated with nitrogen prior to use. SOCl2, Benzene, AlCl3, (COCl)2, Et3N, NaH, 1-methylimidazole, and

P(OPh)3 were purchased from Sigma Aldrich and used as received. PPh3 and 4-DMAP were 116

recrystallized from Et2O prior to use. 2,6-Lutidine was dried over sodium and distilled prior to use.

174 160 187 Compounds 6-(methoxycarbonyl)picolinic acid (5.4), MesP(SiMe3)2, Mes*PH2, (L)-

49 49 188 Valinol, (L)-Phenylanalinol, Cu(MeCN)4OTf, were synthesized according to literature procedures. NMR spectra were recorded at 298 K on 300 or 400 MHz spectrometers (operating

1 31 1 frequency for H). 85% H3PO4 was used as an external standard (δ 0.0) for P NMR spectra. H

NMR spectra were referenced to residual protonated solvent, and 13C{1H} NMR spectra were referenced to the deuterated solvent. Mass spectra were recorded on a Kratos MS 50 instrument in

EI mode (70 eV). Elemental analyses were performed in the UBC Chemistry Microanalysis

Facility. The optical rotations were measured at a concentration in g per 100 mL and their values

(average of 10 measurements) were obtained on a Jasco P-1010 polarimeter.

5.4.2 Synthesis of 6-Benzoylpicolinic Acid (5.2)

In air, a suspension of 6-(methoxycarbonyl)picolinic acid (5.4)(30.4 g, 168 mmol) in SOCl2

(79.2 mL, 130 g, 1.09 mol) was heated to reflux for 2 h. The residual SOCl2 was removed by rotary evaporation, the resulting solid was dissolved in benzene (200 mL) and the benzene was removed by rotary evaporation (to remove additional SOCl2). This was repeated two additional times to give the crude acid chloride. A 1-L roundbottom flask was charged with freshly ground AlCl3

(44.8 g, 336 mmol) followed by benzene (250 mL). The suspension was heated to 50 °C, and a solution of the crude acid chloride in benzene (250 mL) was added in one batch with vigorous stirring. The flask was equipped with a reflux condenser and a septum affixed to the condenser with an outlet to an external oil bubbler. The reaction was heated to reflux until the HCl bubbling subsided (ca. 3 h). The reaction was quenched by pouring into a 2-L Erlenmeyer flask containing

100 mL conc. HCl in 500 g ice. Residual solids in the reaction flask we dissolved in EtOAc and added to the aqueous solution. The organic layer was separated, and the aqueous layer extracted 117

with EtOAc (3 x 200 mL). The organic layers were combined, washed with brine (300 mL), dried over Na2SO4, and volatiles were removed by rotary evaporation. The resulting light brown solid was dissolved in 200 mL CH2Cl2 and extracted with 1 M NaOH (3 x 200 mL). The combined aqueous extracts were acidified with 1 M HCl until cloudy and extracted with CH2Cl2 (3 x 200 mL). The combined organic layers were dried over Na2SO4, and volatiles were removed by rotary evaporation to give the title compound 5.2 as an off-white solid (26.0 g, 68%).

1 H NMR (400 MHz, CDCl3): δ = 9.08 (br s, 1H), 8.42 (d, JHH = 8 Hz, 1H), 8.27 (d, JHH =

7 Hz, 1H), 8.19 (t, JHH = 8 Hz, 1H), 7.96 (d, JHH = 7 Hz, 1H), 7.64 (t, JHH = 8 Hz, 1H), 7.51 (t, JHH

13 1 = 7 Hz, 2H); C{ H} NMR (101 MHz, CDCl3): δ = 192.1, 163.7, 153.5, 144.9, 139.7, 135.3,

133.5, 130.6, 128.5, 128.4, 126.2; HRMS (ESI): m/z 250.0480 (calcd for NaC13H19NO3 250.0480);

Anal. Calcd for C13H19NO3: C, 68.72; H, 3.99; N, 6.16; Found: C, 68.45; H, 4.10; N, 6.15; Mp:

132–134 °C.

5.4.3 Synthesis of (S)-PhC=OC5H3N(CNOCH(i-Pr)-CH2) (5.3a)

In air, picolinic acid 5.2 (7.00 g, 30.9 mmol) was suspended in 100 mL CH2Cl2. A few drops of DMF were added, and a septum affixed to the flask with an outlet to an external oil bubbler. (COCl)2 (3.18 mL, 4.71 g, 37.1 mmol) was added dropwise over 30 minutes and the reaction was stirred until the bubbling subsided. Volatiles were removed by rotary evaporation to give the crude acid chloride. A 250 mL Schlenk flask was dried and charged with ʟ-Valinol (3.43 mL, 3.18 g, 30.9 mmol), Et3N (21.5 mL, 15.6 g, 150 mmol) and dry CH2Cl2 (100 mL). The flask was cooled to 0 °C and a solution of the acid chloride in CH2Cl2 (50 mL) was added in one batch.

The reaction was warmed to rt and stirred 1 h. The reaction was quenched with sat. NaHCO3 (150 mL) and the organic layer was separated. The organic layer was washed with 1 M HCl (150 mL),

118

separated, and dried over Na2SO4. Volatiles were removed by rotary evaporation to give amide

5.5a in suitable purity for further reaction.

1 H NMR (400 MHz, CDCl3): δ = 8.28 (dd, JHH = 8, 1 Hz, 1H), 8.12 (dd, JHH = 8, 1 Hz, 1H),

8.05-7.98 (m, 4H), 7.57 (tt, JHH = 8, 1 Hz, 1H), 7.44 (t, JHH = 8 Hz, 2H), 3.90 (m, 1H), 3.72 (dd,

JHH = 11, 4 Hz, 1H), 3.65 (dd, JHH = 11, 6 Hz, 1H), 3.40 (br s, 1H), 1.95 (m, 1H), 0.93 (d, JHH = 7

Hz, 3H), 0.86 (d, JHH = 7 Hz, 3H).

In a 500 mL round bottom flask, the amide 5.5a synthesized in the previous step was dissolved in 200 mL CHCl3. SOCl2 (13.4 mL, 22.1 g, 185 mmol) was added and the flask was equipped with a reflux condenser. The reaction was heated to reflux for 3 h, cooled to rt and the volatiles removed by rotary evaporation. The residual oil was dissolved in EtOAc (50 mL) filtered through a silica plug (ca. 8”) using EtOAc as the eluent. The EtOAc was removed by rotary evaporation to give chloride 5.6a in suitable purity for further reaction.

1 H NMR (400 MHz, CDCl3): δ = 8.35 (dd, JHH = 8, 1 Hz, 1H), 8.20 (dd, JHH = 8, 1 Hz, 1H),

8.08-7.98 (m, 4H), 7.57 (tt, JHH = 8, 2 Hz, 1H), 7.45 (t, JHH = 8 Hz, 2H), 4.10 (m, 1H), 3.72 (dd,

JHH = 11, 4 Hz, 1H), 3.67 (dd, JHH = 11, 4 Hz, 1H), 1.97 (m, 1H), 0.96 (d, JHH = 7 Hz, 3H), 0.89

(d, JHH = 7 Hz, 3H).

A 250 mL Schlenk flask was dried and charged with chloride 5.6a synthesized in the previous step and NaH (60% dispersion in oil, 1.80 g, 46.4 mmol) (*Note: for reactions involving greater than 100 mmol, dry 95% NaH should be used as an excess of oil can impede purification).

The solids were suspended in dry THF (125 mL) and heated to reflux for 3 h. The reaction was cooled to rt and the sodium salts removed by filtration (*Note: do not use Celite or silica as a filter medium, as accidental hydrolysis can take place). The volatiles were removed by rotary evaporation and the resulting oil was triturated with pentane to give a brown/red solid. The solid 119

was collected by filtration and recrystallized in Et2O to give the title compound 5.3a as a light yellow solid. (4.12 g, 45% over 3 steps). Single crystals suitable for X-ray diffraction analysis were obtained after a concentrated solution of 5.3a in Et2O was left in a −30 °C freezer.

1 H NMR (400 MHz, CDCl3): δ = 8.20 (d, JHH = 8 Hz, 1H), 8.13 (d, JHH = 7 Hz, 2H), 7.99

(d, JHH = 8 Hz, 1H), 7.88 (t, JHH = 8, 1H), 7.49 (t, JHH = 7, 1H), 7.39 (t, JHH = 8, 2H), 4.43 (m, 1H),

13 1 4.11 (m, 2H), 1.80 (m, 1H), 0.98 (d, JHH = 7 Hz, 3H), 0.88 (d, JHH = 7 Hz, 3H); C{ H} NMR

(101 MHz, CDCl3): δ = 192.1, 161.9, 154.7, 145.7, 137.3, 135.4, 132.9, 131.1, 127.9, 126.0, 125.8,

72.6, 70.7, 32.6, 18.7, 18.1; HRMS (ESI): m/z 317.1260 (calcd for C18H18N2O2Na 317.1266);

22 Anal. Calcd for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52; Found: C, 73.30; H, 6.21; N, 9.38; [훼]D

3 -1 -1 -1 = –118 °cm g dm (c = 2.2 × 10 , CHCl3).

5.4.4 Synthesis of Synthesis of (S)-PhC=OC5H3N(CNOCH(CH2Ph)-CH2) (5.3b)

Ketone 5.3b was synthesized in an analogous fashion to 5.3a: Picolinic acid 5.4 (5.60 g,

24.8 mmol), COCl2 (3.77 g, 29.7 mmol), (L)-phenylalaninol (3.75 g, 24.8 mmol), and Et3N (12.5 g, 124 mmol) to make the corresponding pyridyl amide 5.5b.

1 H NMR (400 MHz, CDCl3): δ = 8.23 (dd, JHH = 8, 1 Hz, 1H), 8.15 (d, JHH = 9 Hz, 1H),

8.02 (dd, JHH = 8, 1 Hz, 1H), 7.98-7.88 (m, 3H), 7.56 (tt, JHH = 8, 2 Hz, 1H), 7.43 (t, JHH = 8 Hz,

2H), 7.17-7.07 (m, 5H), 4.35 (m, 1H), 3.82-3.62 (m, 2H), 3.03-2.81 (m, 3H).

SOCl2 (17.7 g, 150 mmol) in CHCl3 (125 mL) was used to produce the crude chloride 5.6b.

1 H NMR (400 MHz, CDCl3): δ = 8.38 (dd, JHH = 8, 1 Hz, 1H), 8.24 (dd, JHH = 8, 1 Hz, 1H),

8.19-8.06 (m, 4H), 7.67 (tt, JHH = 7, 2 Hz, 1H), 7.54 (t, JHH = 8 Hz, 2H), 7.25-7.19 (m, 5H), 4.62

(m, 1H), 3.70 (dd, JHH = 11, 4 Hz, 1H), 3.60 (dd, JHH = 11, 3 Hz, 1H), 3.00 (m, 2H).

120

NaH (0.893 g, 37.2 mmol) in THF (100 mL) was used to produce the crude product, which was recrystallized in Et2O to give the title compound 5.3b as an off-white solid (5.64 g, 66% over

3 steps).

1 H NMR (400 MHz, CDCl3): δ = 8.26 (d, JHH = 8 Hz, 1H), 8.20 (d, JHH = 8 Hz, 2H), 8.07

(d, JHH = 8 Hz, 1H), 7.95 (t, JHH = 8 Hz, 1H), 7.57 (d, JHH = 7 Hz, 1H), 7.47 (t, JHH = 8 Hz, 2H),

7.32-7.21 (m, 5H), 4.65 (m, 1H), 4.44 (t, JHH = 9 Hz, 1H), 4.22 (t, JHH = 8 Hz, 1H), 3.24 (dd, JHH

13 1 = 14, 5 Hz, 1H), 2.80 (dd, JHH = 14, 9 Hz, 1H); C{ H} NMR (101 MHz, CDCl3): δ = 192.2,

162.6, 154.9, 145.6, 137.5, 137.5, 133.0, 131.2, 129.1, 128.4, 128.0, 126.4, 126.1, 126.0, 72.4,

67.9, 41.4; HRMS (ESI): m/z 343.1447 (calcd for C22H19N2O2 343.1451); Anal. Calcd for

22 3 - C22H18N2O2: C, 77.17; H, 5.30; N, 8.18; Found: C, 77.10; H, 5.35; N, 8.17; [훼]D = –47.6 °cm g

1 -1 -1 dm (c = 2.8 × 10 , CHCl3).

5.4.5 Synthesis of (S)-MesP=CPhC5H3N(CNOCH(i-Pr)-CH2) (5.1a)

To a solution of MesP(SiMe3)2 (1.85 g, 6.24 mmol) in THF (10 mL) was added methyllithium (1.6 M, 3.9 mL, 6.24 mmol). The reaction mixture was heated to 55 °C for 1-2 h.

31P NMR analysis of an aliquot removed from the reaction mixture suggested quantitative formation of MesP(Li)SiMe3 (δ = -187). The reaction mixture was cooled to -78 °C and treated with a solution of ketone 5.3a (1.67 g, 5.67 mmol) in THF (5 mL). After warming to room temperature, analysis of an aliquot removed from the reaction mixture by 31P NMR spectroscopy revealed two singlet resonances consistent with phosphaalkene (E/Z-5.1a) (δ = 248/267 ppm). The reaction mixture was quenched with excess SiMe3Cl (ca. 3 mL) and the solvent evaporated in vacuo. The product was extracted into toluene (10 mL and 2 × 5 mL) and filtered. The toluene was evaporated in vacuo and the resultant red paste precipitated with hexanes (10 mL). The solid was filtered and dried in vacuo to give the product as a pink solid (1.3 g, 54%). Single crystals of Z- 121

5.1a suitable for X-ray diffraction analysis were obtained by slow evaporation of a C6H6 solution of E/Z-5.1a.

31 1 1 P{ H} NMR (162 MHz, CDCl3): δ = 248.3 (Z), 266.6 (E); H NMR (400 MHz, CDCl3,

Z-isomer): δ = 7.75 (d, JHH = 8 Hz, 1H), 7.60-7.56 (m, 2H), 7.44 (t, JHH = 8 Hz, 1H), 7.35-7.26

(m, 3H), 6.94 (d, JHH = 8 Hz, 1H), 6.61 (s, 2H), 4.45-4.39 (m, 1H), 4.19-4.07 (m, 2H), 2.32 (s,

1 6H), 2.13 (s, 3H), 1.90-1.83 (m, 1H), 1.04 (d, JHH = 7 Hz, 3H), 0.94 (d, JHH = 7 Hz, 3H); H NMR

(400 MHz, CDCl3, E-isomer): δ = 8.10 (d, JHH = 8 Hz, 1H), 7.62 (t, JHH = 8 Hz, 1H), 7.14 (d, JHH

= 8 Hz, 1H), 7.12-7.06 (m, 3H), 6.92-6.88 (m, 2H), 6.68 (s, 2H), 4.62-4.55 (m, 1H), 4.30-4.22 (m,

1H), 4.14-4.07 (m, 1H), 2.26 (s, 3H), 2.25 (s, 3H), 2.18 (s, 3H), 1.93-1.86 (m, 1H), 1.10 (d, JHH =

13 13 1 7 Hz, 3H), 0.98 (d, JHH = 7 Hz, 3H); C NMR data only provided for the major Z-isomer: C{ H}

NMR (101 MHz, CDCl3): δ = 191.5 (d, JPC = 41 Hz), 162.7, 160.7, 160.1, 146.0, 142.3 (d, JPC =

23 Hz), 140.4 (br s), 138.0, 136.7, 135.6, 128.9 (d, JPC = 5 Hz), 128.2, 127.5, 126.5 (d, JPC = 22

Hz), 124.7 (d, JPC = 6 Hz), 123.2, 121.8, 72.5, 70.4, 32.6, 22.4 (d, JPC = 8 Hz), 20.9, 18.8, 18.0;

+ + MS (EI): m/z [%] 430, 429, 428 [3, 29, 100, M ], 386, 385 [4, 17, M -CHMe2]; HRMS (EI): m/z

428.2016 (calcd for C27H29N2OP 428.2018).

5.4.6 Synthesis of (S)-Mes*P=CPhC5H3N(CNOCH(i-Pr)-CH2) (5.1b)

To a cooled (-78 °C) solution of MesPH2 (1.35 g, 4.85 mmol) in THF (15 mL) was added n-butyllithium (1.6 M in hexanes, 3.6 mL, 5.81 mmol). The reaction was warmed to room temperature and stirred 1 h. The solution was cooled (-78 °C), and TMSCl (0.63 g, 5.81 mmol) was added. The reaction was warmed to room temperature and immediately cooled (-78 °C), and n-butyllithium (1.6 M in hexanes, 3.3 mL, 5.34 mmol) was added. The reaction was stirred 1 h and ketone 5.6a (1.14 g, 3.88 mmol) in THF (5 mL) was added to the cooled solution and the mixture was allowed to warm to room temperature. The reaction was quenched with excess TMS-Cl (ca. 122

1 mL) and the solvent evaporated in vacuo. At this point the product could be handled under ambient moisture and air. The product was dissolved in hexanes (ca. 3 mL) and filtered through a small plug of celite. Volatiles were removed using rotary evaporation, the yellow residue was purified by column chromatography (neutral Al2O3, 1:10 EtOAc:Hexanes as the eluent) to give

E/Z-5.1b as a yellow solid. (0.59 g, 27%).

31 1 1 13 P{ H} NMR (121 MHz, CDCl3): δ = 266.0 (E), 257.6 (Z); H and C NMR assigned only

1 for major Z-isomer: H NMR (400 MHz, CDCl3): δ = 7.71 (d, JHH = 8 Hz, 1H), 7.56-7.53 (m, 2H),

7.37-7.33 (m, 3H), 7.24-7.20 (m, 3H), 6.49 (d, JHH = 8 Hz, 1H), 4.49-4.42 (m, 1H), 4.18-4.06 (m,

2H), 1.90-1.86 (m, 1H), 1.57 (s, 9H), 1.55 (s, 9H), 1.32 (s, 9H), 1.09 (d, JHH = 7 Hz, 3H), 0.97 (d,

13 1 JHH = 7 Hz, 3H); C{ H} NMR (101 MHz, CDCl3): δ = 179.0 (d, JPC = 45 Hz), 163.0, 159.2 (d,

JPC = 14 Hz), 154.6 (d, JPC = 41 Hz), 149.9, 145.8, 143.9, 143.6, 136.2, 134.7, 134.3, 129.1 (d, JPC

= 8 Hz), 128.1, 127.8, 127.6, 125.9 (d, JPC = 6 Hz), 121.9, 121.3, 121.2, 72.5, 70.5, 38.1, 34.8 (d,

JPC = 15 Hz), 33.5, 33.5, 33.3 (d, JPC = 6 Hz), 32.8, 31.3; MS (ESI): m/z 579, 578 [35, 100, M-

+ Na ]; HRMS (ESI): m/z 555.3491 (calcd for C36H48N2OP 555.3504).

5.4.7 Synthesis of (S)-MesP=CPhC5H3N(CNOCH(CH2Ph)-CH2) (5.1c).

5.1c was synthesized in an analogous fashion to 5.1a: MesP(SiMe3)2 (1.05 g, 3.53 mmol), and ketone 5.6b (1.10 g, 3.21 mmol) in THF (10 mL) was used to produce the crude product, which was extracted with toluene and washed with Et2O to give the title compound E/Z-5.1c as a pink solid (0.64 g, 42%).

31 1 1 P{ H} NMR (121 MHz, CDCl3): δ = 264.4 (Z), 245.5 (E); H NMR assigned only for

1 major E-isomer: H NMR (400 MHz, CDCl3): δ = 8.07 (d, JHH = 8 Hz, 1H), 7.65 (t, JHH = 8 Hz,

1H), 7.36-7.22 (m, 5H), 7.16 (d, JHH = 8 Hz, 1H), 7.12-7.08 (m, 3H), 6.91-6.87 (m, 2H), 6.68 (s,

2H), 4.69-4.65 (m, 1H), 4.50 (t, JHH = 9 Hz, 1H), 4.29 (t, JHH = 8 Hz, 1H), 3.31 (dd, JHH = 13, 5 123

Hz, 1H), 2.79 (dd, JHH = 14, 9 Hz, 1H), 2.25 (s, 6H), 2.19 (s, 3H); MS (EI): m/z 477, 476 [37, 100,

+ + + + M ], 386, 385 [20, 76, M -CH2Ph], 240, 239 [15, 74, MesPCPh ], 92, 91 [6, 45, PhCH2 ]; HRMS

(EI): m/z 476.2018 (calcd for C31H29N2OP 476.2018).

5.4.8 Synthesis of [Cu2(6.1a)2(OTf)(MeCN)]OTf (5.7)

A solution of phosphaalkene 5.1a (0.40 g, 0.932 mmol) and Cu(MeCN)4OTf (0.36 g, 0.932 mmol) in CH2Cl2 (10 mL) was stirred for 2 h. The solution was concentrated to 5 mL in vacuo and the product was precipitated with Et2O (ca. 10 mL). The suspension was stirred 30 min and filtered, and dried in vacuo to give 5.7 as a brown solid. (0.49 g, 79%). Single crystals suitable for X-ray diffraction analysis were obtained by slow diffusion of Et2O into a CH2Cl2 solution of 5.7.

31 1 1 P{ H} NMR (162 MHz, CDCl3): δ = 186.0; H NMR (400 MHz, CDCl3): δ = 8.04 (m,

4H), 7.43 (d, JHH = 8 Hz, 2H), 7.22 (br s, 2H), 7.1 (br s, 8H), 6.85 (s, 2H), 6.06 (s, 2H), 4.48 (t,

JHH = 10 Hz, 2H), 4.37 (t, JHH = 9 Hz, 2H), 2.75 (s, 6H), 2.32 (m, 2H), 2.17 (s, 6H), 2.04 (s, 3H),

13 1 1.83 (m, 2H), 1.29 (s, 6H), 1.02 (d, JHH = 6 Hz, 6H), 0.83 (d, JHH = 7 Hz, 6H); C{ H} NMR (101

MHz, CDCl3): δ = 117.4 (m), 166.7, 160.4, 143.5, 142.6, 141.7, 140.7, 139.9, 130.6, 130.0, 129.9,

129.5, 129.4, 129.1, 128.7, 125.0, 74.0, 70.7, 32.3, 23.5, 21.7, 21.5, 18.9, 17.6, 2.6; 19F{1H} NMR

(114 MHz, CDCl3): δ = -78.2; Anal. Calcd for C58H61Cu2F6N5O8P2S2: C, 52.64; H, 4.65; N, 5.29;

22 3 -1 -1 -1 Found: C, 52.44; H, 4.74; N, 4.93; [훼]D = –24.7 °cm g dm (c = 1.8 × 10 , CH2Cl2).

5.4.9 Synthesis of [Cu(6.1a)(PPh3)]OTf (5.8a)

A solution of complex 5.7 (100 mg, 0.075 mmol) and PPh3 (40 mg, 0.150 mmol) in CH2Cl2

(3 mL) was stirred for 30 min. The solution was concentrated and the resultant red residue was triturated with hexanes (2 mL). The solid was filtered and washed with additional hexanes (2 × 2 mL) and dried in vacuo to give 5.8a as a red solid. (90 mg, 67%). Single crystals suitable for X- ray diffraction analysis were obtained by slow diffusion of hexanes into a THF solution of 5.8a. 124

31 1 1 P{ H} NMR (162 MHz, CD2Cl2): δ = 231.7, 8.9; H NMR (400 MHz, CD2Cl2): δ = 8.12

(d, JHH = 8 Hz, 1H), 8.01 (t, JHH = 8 Hz, 1H). 7.79 (d, JHH = 8 Hz, 1H), 7.43-7.21 (m, 21 H), 7.10

(br s, 2H), 6.91 (s, 1H), 6.16 (s, 1H), 4.60 (m, 1H), 4.50 (m, 1H), 2.99 (m, 1H), 2.65 (s, 3H), 2.19

13 1 (s, 3H), 1.62 (m, 1H), 1.01 (s, 3H), 0.83 (d, JHH = 7 Hz, 3H), 0.72 (d, JHH = 7 Hz, 3H); C{ H}

NMR (101 MHz, CD2Cl2): δ = 171.8, 167.0, 156.4 (d, JPC = 9 Hz), 144.1 (d, JPC = 20 Hz), 142.2,

140.9, 139.1, 138.6, 138.0 (d, JPC = 12 Hz), 133.7 (d, JPC = 14 Hz), 131.3, 130.8 (d, JPC = 25 Hz),

129.5, 129.4, 129.3, 129.0, 125.6 (d, JPC = 9 Hz), 123.5, 75.6, 69.9, 33.1, 23.2 (d, JPC = 22 Hz),

19 1 22.2, 21.2, 18.5, 18.3; F{ H} NMR (114 MHz, CDCl3): δ = -78.6; HRMS (EI): m/z 640.0839

63 22 3 -1 -1 -1 (calcd for C28H29O4N2PF3 CuS 640.0834); [훼]D = 89.2 °cm g dm (c = 0.72 × 10 , CH2Cl2).

5.4.10 Representative Addition of a Neutral Ligand to Complex 5.7 (5.8b-e)

A solution of complex 5.7 (3 mg, 5 μmol) and L (5 μmol) in CH2Cl2 (0.7 mL) was sonicated for 30 minutes. The brown colour of complex 5.7 immediately changed to either a deep red (L =

P(OPh)3), deep green (L = 2,6-lutidine) or deep blue (L = 4-DMAP or 1-methylimidazole) colour.

Subsequent 31P{1H} NMR analysis of the mixture revealed quantitative conversion to a new product.

31 1 P{ H} NMR (162 MHz, CH2Cl2): δ = 227.2, 114.3 (L = P(OPh)3), 214.7 (L = 2,6- lutidine), 208.4 (L = 4-DMAP), 207.4 (L = 1-methylimidazole).

5.4.11 X-ray Crystallographic Studies

All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX II diffractometer with graphite-monchromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All nonhydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected for absorption effects (SADABS), Lorentz, 125

and polarization effects. All calculations were performed using SHELXL-2014 crystallographic software package from Bruker AXS.114 Absolute configuration was confirmed on the basis of the refined Flack parameter.115 Compound 5.7 crystallizes with positional disorder for the chelating -

OSO2CF3 ligand. Their respective populations were refined to the final occupancy of 0.564(4)

{S(1), O(3), O(4), O(5), C(57), F(1a), F(2a), F(3a)} and 0.436(4) {S(1a), O(3a), O(4a), O(5a),

C(57a), F(1), F(2), F(3)}. Compound 5.8a recrystallizes with two ordered molecules of THF and a disordered molecule of THF in the asymmetric unit, but only one atom could be located on using the difference map and was refined anisotropically. Their respective populations were refined to the final occupancy of 0.77(1) {C(52)} and 0.23(1) {C(52a)}. Additional information is listed in

Table 5.2. All crystallographic data has been deposited with the Cambridge Structural Database:

1469495, 1469496, 1469497, 1469498.

5.4.12 Computational Details

All Calculations were performed with Gaussian 09189 using the B3LYP density function.

190-193 The full compounds were first optimized using the minimal basis set 6-31G(d,p)194, 195 using an initial geometry obtained from a solid state molecular structure when available. Final optimization and TD-B3LYP calculations were preformed using the TZVP basis set.196

126

Table 5.2 X-ray Data Collection and Refinement Details for Compounds 5.3a, 5.1a, 5.7, and 5.8a.

5.3a 5.1a 5.7 5.8a∙(C4H8O)3 formula C18H18N2O2 C27H29N2OP [C57H61Cu2F3N5O5 [C45H44CuN2OP2]

P2S] [CF3SO3] [CF3SO3]

·3(C4H8O) fw 294.34 428.49 1323.01 1115.65 cryst syst monoclinic monoclinic triclinic orthorhombic space group P21 P21 P1 P212121 colour colourless yellow orange red a (Å) 19.628(1) 8.6564(8) 11.399(1) 12.0076(5) b (Å) 6.5495(4) 6.4176(6) 11.762(1) 15.2895(6) c (Å) 12.9494(9) 21.018(2) 12.253(1) 29.640(1) α (deg) 90 90 92.416(2) 90 β (deg) 111.225(5) 99.396(2) 107.396(2) 90 γ (deg) 90 90 104.977(2) 90 V (Å3) 1551.8(2) 1151.9(2) 1501.8(3) 5441.5(4) T (K) 90(2) 90(2) 90(2) 90(2) Z 4 2 1 4 μ(Mo Kα) (mm-1) 0.083 0.141 0.907 0.563 cryst size (mm) 0.25×0.14×0.13 0.34×0.12×0.10 0.28×0.12×0.10 0.15×0.12×0.04

-3 Dcalcd. (Mg m ) 1.260 1.235 1.463 1.362 2θ(max) (°) 60.1 60.2 60.2 60.2 no. of reflns 16885 13878 17750 15991 no. of unique data 7438 6099 8875 8750 R(int) 0.0396 0.0436 0.0400 0.0504 refln/param ratio 22.5 22.5 25.9 23.4 a R1 [I > 2σ(I)] 0.0269 0.0332 0.0264 0.0328 b wR2 [all data] 0.1035 0.0959 0.0977 0.0735 GOF 1.047 1.014 1.043 0.947 a b 2 2 2 2 2 2 1/2 R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표| w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

127

5.5 Supplementary Section

1 1 Figure 5.9 H- H COSY (a) and NOESY (b) NMR Spectra (400 MHz, 298 K) in CDCl3 of E/Z-5.1a.

128

1 31 1 Figure 5.10 H- P HMBC NMR Spectrum (400 MHz for H, 298 K) in CDCl3 of E/Z-5.1a.

1 1 Figure 5.11 H- H NOESY NMR Spectrum (400 MHz, 298 K) in CDCl3 of Complex 5.7.

129

Figure 5.12 Optimized structure of 5.8a.

Selected bond distances (Å) and angles (°): P(1)–C(1) 1.725, P(1)–Cu(1) 2.414, N(1)–Cu(1) 2.126, N(2)–Cu(1) 2.152, P(2)–Cu(1) 2.319, C(1)–P(1)–Cu(1) 101.47, P(1)–Cu(1)–N(1) 76.70, N(1)–Cu(1)–N(2) 77.66.

Figure 5.13 Optimized structure of 5.8d.

Selected bond distances (Å) and angles (°): P(1)–C(1) 1.730, P(1)–Cu(1) 2.387, N(1)–Cu(1) 2.084, N(2)–Cu(1) 2.183, N(3)–Cu(1) 2.016, C(1)–P(1)–Cu(1) 99.55, P(1)–Cu(1)–N(1) 78.70, N(1)–Cu(1)–N(2) 78.11.

130

Table 5.3 Computed Low Energy Absorptions for 5.8a state no. calculated energy ƒ constitutiona,b /eV 1 2.3412 0.0763 197-198 (66.2%), 196-198 (15%), 194-198 (12.3%), 193-198 (11.3%) 2 2.7614 0.0166 197-199 (65.7%), 193-199 (10.8%) 3 2.9232 0.0707 196-198 (51.8%), 195-198 (24.7%), 194-198 (22.1%) 4 2.9901 0.0318 195-198 (64.1%) 5 3.0106 0.0732 194-198 (55.4%), 193-198 (18.7%), 195-198 (12.9%) 6 3.0530 0.0205 193-198 (59.1%), 189-198 (17.3%), 183-198 (12.3%) a 197 strands for HOMO, 198 strands for LUMO b Greater than 10% contributions

Table 5.4 Computed Low Energy Absorptions for 5.8d state no. calculated energy ƒ constitutiona,b /eV 1 2.2523 0.0680 161-162 (67.1%) 2 2.5263 0.0209 161-163 (68.7%) 3 2.8379 0.0236 160-162 (47.1%), 159-162 (38.8%), 154-162 (18.0%) 157-162 (16.0%) 4 2.9758 0.0774 159-162 (64.1%), 151-162 (14.8%), 161-162 (12.4%) 5 3.1272 0.0024 158-162 (62.0%), 159-162 (14.9%) 6 3.1602 0.02558 157-162 (59.1%), 158-162 (28.1%), 155-162 (22.0%) a 161 strands for HOMO, 162 strands for LUMO b Greater than 10% contributions

131

Chapter 6: Carbopalladation of Phosphaalkenes as a Route to Palladacycles

6.1 Introduction

The analogy of low-coordinate phosphorus compounds to their carbon analogues has been highlighted in the previous chapters (for example, the addition polymerizations of phosphaalkenes discussed in Chapters 3 and 4) and we were interested to see how this process extended to carbopalladation (i.e. addition of Pd–R across a X=Y multiple bond). The carbopalladation of an olefin [which binds η2(C,C)] is extremely rapid (Scheme 6.1),197 a property that has been exploited for both palladium-catalyzed Heck cross coupling198, 199 and olefin polymerization.200, 201

Conversely, while imine functional groups have been observed to insert into acyl-Pd(II) bonds they do not undergo the carbopalladation reaction outlined in Scheme 6.1.202 Insertion reactions are postulated to involve the formation of a π-complex,203, 204 and the reluctance of imines to adopt this mode of coordination to Pd(II) centres may explain their observed chemical inertness.

Although the coordination mode of the P=C bond in metal complexes geometrically mirrors related imine compounds [i.e. κ(P) and κ(N)] as observed in the solid state,41, 53, 71, 82 the electronics of this interaction are quite different.71 Furthermore, rapid conversion between κ(P) and η2(P,C)

65 coordination modes has been observed in (MesP=CPh2)Pt(PPh3)2.

Scheme 6.1 Carbopalladation of E=C Double Bonds (E = N, C, P).

Of particular interest was the singular report that detailed the rapid carbopalladation of phosphaalkene A, which bears a pendant pyridine moiety, with PdMeCl(cod) to give dimeric

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complex B (Scheme 6.2).205 Three membered phosphapalladacyclopropanes of this type are fairly rare and other examples include complexes C and E. Complex C forms by reversible

+ 206 cyclometallation of [(i-Pr3P)2Pd(OAc)] upon treatment with pyridine whilst complex E forms after addition of an alcohol to bisphosphaalkene palladium(II) complex D.207

Scheme 6.2 Synthesis of Phosphapalladacyclopropanes.

The successful formation of complex B suggested that carbopalladation of phosphaalkenes can be achieved, however it is interesting to note that a previously reported 5-membered imine- phosphaalkene PN∙PdMeCl complex,172 a phosphaalkene-containing palladium(II) analogue of

Brookhart’s diimine nickel(II) polymerization catalyst,197, 208 does not undergo carbopalladation.

Our previous experience with additions of organometallic reagents to phosphaalkenes86, 133 prompted us to explore this carbopalladation reaction further using phosphaalkenes previously synthesized within our group.32 Phosphapalladacyclopropanes are interesting compounds that may be capable of further interesting reactions (Scheme 6.3). For example, we envisioned that the

133

strained three-membered palladacycle may undergo ring expansion if a suitable donor atom (e.g.

N, O, S) was appropriately positioned adjacent to the C–Pd linkage. Of particular interest, the carbopalladation/rearrangement of 2-pyridyl substituted phosphaalkenes (i.e. E = N) would afford palladium complexes with a 1,2-dihydropyridinato donor moiety. Metal complexes featuring 1,2- dihydropyridinato ligands have attracted considerable attention for application in metal-ligand cooperative catalysis.209-211 Alternatively, phosphapalladacyclopropanes may insert unsaturated substrates like CO (in analogy to the Heck reaction) or olefins [in analogy to Pd-catalyzed olefin polymerization] into the C–Pd linkage to afford 4- or 5-membered palladacycles. The observation of these cyclic compounds would be valuable in designing catalytic reactions that take advantage of the rather unique phosphapalladacyclopropane functionality.

Scheme 6.3 Postulated Reactions Involving Phosphapalladacyclopropanes.

6.2 Results and Discussion

6.2.1 Carbopalladation of MesP=CPh2

We began by exploring the reaction of the symmetric phosphaalkene MesP=CPh2 with complexes possessing Pd–R bonds (R = alkyl, aryl, Scheme 6.4). In lieu of a pendant donor atom in MesP=CPh2, like that observed in phosphaalkene A, the bidentate cod donor of PdMeCl(cod)

212 was substituted with two monodentate PPh3 donors to ensure the synthesis of a monomeric palladium species. Accordingly, gentle heating of a THF solution of PdMeCl(PPh3)2 and

MesP=CPh2 immediately afforded a deep yellow solution. Analysis of the reaction mixture by

31P{1H} NMR spectroscopy revealed the disappearance of the phosphaalkene (δ = 233)29 and the 134

formation of several new products (δ = 24.8, 21.7, -14.5, -28.8), in addition to free PPh3 (δ = -6).

The 31P{1H} NMR spectrum suggested a new complex had formed, assigned to structure 6.1a, as a near-equal mixture of cis and trans isomers (with respect to the phosphine substituents). These

31 isomers could be identified by their coupling constants [i.e. δ P = cis-6.1a: 24.8 and -14.5 (JPP =

25 Hz); trans-6.1a: 21.7 and -28.8 (JPP = 360 Hz)]. The resulting material was surprisingly stable under ambient air and moisture and could be purified by repeated washings with ether to give a yellow solid in 87% yield.

Scheme 6.4 Carbopalladation of MesP=CPh2.

1 The H NMR spectrum of 6.1a revealed diagnostic P–CH3 signals for both isomers [δ = cis-6.1a: 1.62 (JPH = 13 Hz); trans-6.1a: 1.31 (JPH = 12, 4 Hz)], evidence of a methyl group migration from the Pd(II) precursor to the phosphaalkene. 1H-31P HSQC NMR spectroscopy revealed a correlation between these methyl protons and the more downfield 31P NMR resonances

(δ = 24.8, 21.7), permitting the assignment of the δ31P shifts of both the methylphosphine and triphenylphosphine moieties of 6.1a. Lastly, 13C{1H} NMR spectroscopy confirmed the

29 conversion of the phosphaalkene (δP=C = 193) to a new Pd–CPh2 functionality [δ = cis-6.1a: 61.7

(JPC = 58, 35 Hz); trans-6.1a: 55.6 (JPC = 14, 5 Hz)].

With the successful synthesis of complex 6.1a, we became interested in expanding the reaction scope. In particular, we were intrigued to see if the methyl group on palladium could be exchanged for another carbon-based functionality. Furthermore, PdMeCl(PPh3)2, prepared in

112 multiple steps from PdCl2(cod) and requiring the use of harmful Me4Sn, was a less than desirable 135

starting material. Consequently, we turned our attention to PdPhI(PPh3)2 which can be

213 conveniently prepared in one step from commercially available Pd(PPh3)4 and PhI. The reaction of MesP=CPh2 and PdPhI(PPh3)2 was performed in analogous fashion to 6.1a, and similar diagnostic 31P NMR shifts were immediately observed. These were assigned to cis-6.1b [δ = 25.8 and -2.4 (JPP = 18 Hz)] and trans-6.1b [δ = 21.1 and -9.3 (JPP = 330 Hz)]. The resulting complex could be isolated in air in 88% yield and displayed remarkable benchtop stability. In the case of

6.1b, the cis-isomer was preferred (e.g. ca. 1.0:0.33, cis:trans) by analysis of the 31P NMR

13 1 spectrum. The C{ H} NMR spectrum showed a similar resonance for the newly formed Pd–CPh2 moiety [δ = cis-6.1b: 64.7 (JPC = 63, 28 Hz)].

Figure 6.1 Molecular Structure of Complex 6.1a∙CHCl3 (50% Probabilty Ellipsoids).

Hydrogen atoms and CHCl3 were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(2) 1.808(6); P(1)–Pd(1) 2.203(2); C(2)–Pd(1) 2.204(6); P(2)–Pd(1) 2.360(2); Cl(1)–Pd(1) 2.413(2); P(1)–Pd(1)–C(2) 47.5(2); P(2)–Pd(1)–Cl(1) 92.50(5).

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X-ray analysis of single crystals of 6.1a and 6.1b determined unambiguously that the desired palladacycles had been formed (Figures 6.1 and 6.2). Although both cis and trans isomers were present in solution, 6.1a and 6.1b each crystallize preferentially as the cis-isomer. Table 6.1 contains the important structural features observed for 6.1a and 6.1b and confirms that the metrical parameters of each complex are in close agreement with other previously reported phosphapalladacyclopropanes (i.e. B, C and E, Scheme 6.2). It appears that both the P–C and Pd–

C bonds for 6.1a and 6.1b are slightly elongated with respect to complexes B, C and E. This may be evidence for the increased steric environment around the carbon atom imparted by the gem- phenyl group.

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Figure 6.2 Molecular Structure of Complex 6.1b (50% Probabilty Ellipsoids).

Hydrogen atoms were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.803(6); P(1)–Pd(1) 2.218(2); C(1)–Pd(1) 2.186(6); P(2)–Pd(1) 2.361(2); I(1)–Pd(1) 2.698(2); P(1)–Pd(1)–C(1) 48.3(2); P(2)–Pd(1)–I(1) 94.07(7).

Table 6.1 Important Metrical Parameters for P–C–Pd Rings.

6.1a 6.1b B205 C206 E (R = Et)207 Bond Lengths (Å) P–C 1.808(6) 1.803(6) 1.754(8) 1.748(6) 1.752 Pd–C 2.204(6) 2.186(6) 2.081(8) 2.171(5) 2.101 Pd–P 2.203(2) 2.218(2) 2.222(2) 2.207(2) 2.232 Bond Angles (°) ∠P–Pd–C 47.5(2) 48.3(2) 48.0(2) 47.1(2) 47.6

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6.2.2 Carbopalladation of a Phosphaalkene-Oxazoline

With the successful synthesis of complexes 6.1a and 6.1b, attention was directed towards the carbopalladation of PhAk-Ox (1.10a), an enantiomerically-pure phosphaalkene previously reported by our group.46 It was hypothesized that the presence of a pendant oxazoline donor would lead to a similar palladium dimer as that reported for complex B. Similar to MesP=CPh2, the reaction of PdMeCl(cod) with phosphaalkene 1.10a in CH2Cl2 appeared to proceed rapidly

(Scheme 6.5). For example, analysis of the 31P{1H} NMR spectrum immediately after solvation revealed the phosphaalkene resonance (δ31P = 244 ppm)46 had been replaced by three new broad resonances at -10.6, -11.1, and -16.7 ppm. Interestingly, these observed signals were in a region significantly upfield from palladacycles 6.1a and 6.1b (δ ≈ 20-26). Attempts at isolating a product from the reaction mixture were unsuccessful, however slow evaporation of a concentrated CH2Cl2 solution yielded a single crystal suitable for X-ray diffraction. Fascinatingly, the resultant solid state molecular structure revealed the unexpected connectivity of complex 6.2, with a new bond formed between the Pd(II) centre and an o-methyl group of the P–Mes substituent (Figure 6.3).

Scheme 6.5 Synthesis and Postulated Mechanism for the Formation of Complex 6.2.

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Figure 6.3 Molecular Structure of 6.2∙CH2Cl2 (50% Probability Ellipsoids).

Hydrogen atoms and CH2Cl2 omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(11) 1.878(4); P(1)–Pd(1) 2.1917(9); C(10)–Pd(1) 2.046(4); N(1)–Pd(1) 2.125(3); Cl(1)–Pd(1) 2.3792(8); C(11)–P(1)–Pd(1) 112.2(1); P(1)–Pd(1)–C(10) 82.5(1); N(1)–Pd(1)–Cl(1) 92.51(8).

A postulated mechanism for the formation of complex 6.2 is outlined in Scheme 6.4. It was imagined that carbopalladated intermediate i forms after reaction of the P=C bond in 1.10a and

PdMeCl(cod), similar to what has been observed for complexes 6.1a and 6.1b. However, unlike

6.1a and 6.1b, the Pd–C bond heterolytically cleaves to give anion ii, potentially due to the strain imparted by the donation of the pendant oxazoline to the Pd(II) centre. The carbanion of intermediate ii is positioned to abstract a proton from the o-Mes group to give benzylic anion iii.

Similar proton migrations have been observed during the addition of MeMgBr and MeLi to 1.10a and discussed extensively in Chapter 2.133 Finally, intermediate iii can recombine with the cationic

Pd(II) centre to give the observed complex 6.2. Although the solid state molecular structure of 6.2 is obtained as a single stereoisomer, we can make no comments on the diastereoselectivity of this reaction (new centres of point chirality are generated at both P and C) due to incomplete data.

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6.2.3 Carbopalladation of 2-Pyridyl-Substituted Phosphaalkenes

6.2.3.1 Carbopalladation of MesP=CPh(2-py)

The implied formation of postulated carbanion intermediate ii was an exciting development. It was imagined that the inherent anionic character of the carbon atom in these Pd–

C–P rings could provide an avenue to other interesting palladium phosphine complexes. For

32 example, the carbopalladation of pyridyl phosphaalkene MesP=CPh(2-py) with PdMeCl(PPh3)2 was hypothesized to give the three-membered palladacycle 6.3’ (Scheme 6.6), analogous to 6.1a and 6.1b. In this case, we predicted that 6.3’ would only exist as a transient intermediate since the

Pd–C bond in this compound may heterolytically cleave to give carbanion iv, in a similar process to that postulated for intermediate ii. Carbanion iv is resonance stabilized and can delocalize into the pyridine ring, with negative charge likely localized on the more electronegative nitrogen atom

(i.e. intermediate iv’). Combination of anion iv’ with the cationic Pd(II) centre leads to the formation of a new N–Pd bond, as seen in complex 6.3. Overall, it was hypothesized that the unfavourable loss of aromaticity would occur due to a reduction of the overall ring strain of the palladacycle.

Scheme 6.6 Carbopalladation as a Method to Obtain a 1,2-Dihydropyridinato Complex.

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Gentle heating of a THF solution of MesP=CPh(2-py) and PdMeCl(PPh3)2 resulted in a deep green solution. The volatiles were removed and a green solid was precipitated by addition of

31 Et2O. Analysis of this material using P NMR spectroscopy showed the disappearance of both isomers of phosphaalkene MesP=CPh(2-py) [δ = 260 (E), 242 (Z)]32 and the formation of two new resonances at 38.4 (JPP = 5 Hz) and 21.8 (JPP = 5 Hz), tentatively assigned to complex 6.3 and suggesting a cis orientation of the phosphorus substituents (due to the small JPP coupling constant).

X-ray analysis of crystals obtained from a THF solution confirmed the formation of the desired complex 6.3, with the predicted cis geometry of the two phosphine functionalities (Figure 6.4).

Figure 6.4 Molecular Structure of 6.3∙C4H8O (50% Probability Ellipsoids).

Hydrogen atoms and C4H8O were omitted for clarity. Selected bond lengths (Å) and angles (deg): P(1)–C(1) 1.824(3); P(1)–C(2) 1.757(3); C(2)–C(3) 1.490(4); C(2)–C(9) 1.391(4); P(1)–Pd(1) 2.2653(7); P(2)–Pd(1) 2.2875(8); Cl(1)– Pd(1) 2.3784(7); N(1)–Pd(1) 2.104(2); P(1)–C(2)–C(3) 119.5(2); P(1)–C(2)–C(9) 116.7(2); C(3)–C(2)–C(9) 123.8(3).

Most importantly, analysis of the solid state molecular structure revealed a noticeable contraction of the Cb–Cc bond (1.39 Å), as labelled in Scheme 6.7, compared to the phosphaalkene 142

starting material (1.50 Å).32 The symmetric Pd(II) PNP pincer complex F (Scheme 6.7) showed similar bond contractions upon dearomatization with base.214

Scheme 6.7 Synthesis of a Previously Reported 1,2-Dihydropyridinato Pyridine Palladium(II) Complex and

Comparison to Complex 6.3.

Particularly informative is the 1H and 13C NMR spectra of complex 6.3, which was assigned with the aid of homo- and hetero-nuclear 1D and 2D NMR experiments. For example,

1 13 the characteristic P–CH3 was observed [δ H = 1.73 (JPH = 12, 3 Hz); δ C = 19.8 (JPC = 35, 3 Hz)],

13 analogous to complex 6.1a, along with significantly shielded signals for Cb [δ C = 73.4 (JPC = 72

1 13 1 13 Hz)], CdHd (δ H = 6.23; δ C = 114.6), and CfHf (δ H = 5.73; δ C = 104.1). Similar upfield shifts were observed for analogous 13C and 1H nuclei in the 1,2-dihydropyridinato Pd(II) PNP complex

G. It bears mentioning that the use of a bulkier Mes*-containing phosphaalkene [i.e.

Mes*P=CPh(2-py) is substituted for MesP=CPh(2-py) in Scheme 6.7] would likely not result in an analogous carbopalladation/dearomatization reaction. For example, complex [Mes*P=CH(2- py)]PdMeCl, reported previously, was obtained in 90% isolated yield from PdMeCl(cod) and

Mes*P=CH(2-py) and there was no mention of carbopalladation.215 Therefore, the size of the

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phosphorus substituent plays a role in the carbopalladation of complexes that can form bidentate

PN complexes.*

6.2.3.2 Carbopalladation of Phosphaalkene Pincer 5.1a

With the successful formation of complex 6.3, we wished to determine if other phosphine

Pd(II) complexes could be obtained using this carbopalladation/dearomatization approach, for example enantiomerically pure phosphaalkene-pyridine-oxazoline 5.1a (Chapter 5). A 1:1 mixture of phosphaalkene 5.1a and PdMeCl(cod) turned deep purple immediately upon solvation in

31 1 CH2Cl2 (Scheme 6.8). Analysis of the reaction mixture using P{ H} NMR spectroscopy revealed the conversion of the phosphaalkene [δ = 248 (Z), 267(E)] to two new products at 41.34 and 41.26 ppm, in a similar region to complex 6.3 and suggesting the product, tentatively assigned to complex

6.4, had formed as a mixture of P-stereoisomers. After evaporation of the solvent, the air-stable product could be isolated by repeated extractions with hot n-pentane.

* The reaction of MesP=CPh(2-py) with PdMeCl(cod) in CH2Cl2 was attempted and leads an intractable mixture of products by 31P{1H} NMR spectroscopy (δ = 53.7, 50.26, 47.3, 43.8, 2.1, -19.2). These results suggest carbopalladation has occurred and indicate the potential formation of dimeric species. Based on this, we do not 2 postulate the PPh3 fortuitously aids in the carbopalladation reaction by promoting κ(P) to η (P,C) interconversion. 144

Scheme 6.8 Carbopalladation of a Phosphaalkene as a Route to a New Palladium(II) Pincer Complex.

Although no solid state molecular structure could be obtained for complex 6.4, complementary data was obtained using mass spectrometry [HRMS (6.4∙H+): m/z 583.1063

(found); 583.1059 (calcd)]. Still, the best evidence for the formation of complex 6.4 was obtained

1 13 1 1 from the H and C{ H} NMR spectroscopic data. For example, two P–CH3 signals [CH3’: δ H =

13 1 13 2.11 (JPH = 13 Hz); δ C = 19.4 (JPC = 37 Hz); CH3”: δ H = 2.10 (JPH = 13 Hz); δ C = 19.2 (JPC

= 37 Hz)] were observed in a region similar to the analogous functionalities in complexes 6.1a and

6.3. This is to be expected for complex 6.4 which, due to the presence of the chiral oxazoline

13 moiety, forms as a mixture of P-stereoisomers. Similarly, upfield shifts were observed for Ca [δ C

1 13 1 13 = 82.8 (JPC = 67 Hz)], CbHb (δ H = 6.51; δ C = 120.7), and CcHc (δ H = 6.06; δ C = 106.8), in a similar region to the analogous atoms in complex 6.3, consistent with dearomatization of the pyridine ring. Finally, a two-step synthesis of complex 6.4 was performed by first reacting phosphaalkene 5.1a with 1 equiv MeLi to give the lithium salt Li[Me5.1a]. We have reported reactions of this type proceed with high regioselectivity, with preferential addition to the P- centre.86, 133 Similar to the postulated mechanism for the formation of complex 6.3, the carbanion adjacent to the phosphorus could delocalize into the pyridine ring. Accordingly, salt-metathesis of

145

Me the in situ formed Li[ 5.1a] with PdCl2(MeCN)2 yielded an identical product to the one-step reaction of 5.1a with PdMeCl(cod). Overall, these data are consistent with the structural assignment of complex 6.4 as shown in Scheme 6.7.

6.3 Summary

In summary, we have thoroughly investigated a series of reactions featuring the carbopalladation of phosphaalkenes. This reaction can be used to synthesize air-stable phosphapalladacyclopropanes from MesP=CPh2 or provide sophisticated 1,2-dihydropyridinato palladium complexes from MesP=CR(2-py) derivatives. Whether or not these reactions proceed through the formation of a formal η2(P,C) intermediate remains the topic of future computational and mechanistic investigations. We are currently studying the insertion of olefins and CO into phosphapalladacyclopropanes 6.1a and 6.1b, however these compounds are surprisingly robust and remain stable in the presence of electrophiles such as H2O or MeI.

The 1,2-dihydropyridinato complexes 6.3 and 6.4 are being investigated as potential precursors to novel olefin polymerization catalysts (Scheme 6.9). For example, we envisioned that the cationic Pd(II) complex of 6.3 (v, formed by treatment of 6.3 with AgOTf in MeCN) may be a candidate for a new metal-ligand cooperative polymerization reaction. We postulated that coordination of an olefin to the Pd(II)-centre of complex v may form π-complex vi. Delivery of one of the substituents on phosphorus to the η2(C,C)-olefin, with concomitant aromatization to reform the pyridine moiety, would afford Pd–alkyl complex vii. Complex vii should undergo rapid carbopalladation/dearomatization to reform complex v (R = growing polymer chain) which can further react with an olefin molecule. Work examining the feasibility of this reaction is ongoing.

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Scheme 6.9 Palladium Complexes Featuring 1,2-Dihydropyridinato Donors as Olefin Polymerization Catalysts.

6.4 Experimental

6.4.1 Materials and Methods

Unless stated otherwise, all manipulations were performed using standard Schlenk or glovebox techniques under nitrogen atmosphere. CH2Cl2 and Et2O were deoxygenated with nitrogen and dried by passing through a column containing activated alumina. THF was dried over sodium/ benzophenone ketyl and distilled prior to use. CD2Cl2 and CDCl3 were deoxygenated with

32 46 32 nitrogen prior to use. MesP=CPh2, MesP=C(Ph)(CMe2Ox) (1.10a), MesP=CPh(2-py),

112 212 213 MesP=C(Ph)(C5H3NOx) (5.1a), PdMeCl(cod), PdMeCl(PPh3)2, PdPhI(PPh3)2, were synthesized according to literature procedures. NMR spectra were recorded at 298 K on 300 or

1 400 MHz spectrometers (operating frequency for H). 85% H3PO4 was used as an external standard

(δ 0.0) for 31P NMR spectra. 1H NMR spectra were referenced to residual protonated solvent, and

13C{1H} NMR spectra were referenced to the deuterated solvent. Elemental analyses were performed in the UBC Chemistry Microanalysis Facility.

6.4.2 Synthesis of Mes(Me)P–CPh2∙PdCl(PPh3) (6.1a)

A solution of MesP=CPh2 (0.27 g, 0.85 mmol) and PdMeCl(PPh3)2 (0.48 g, 0.70 mmol) was suspended in THF (30 mL). The mixture was stirred at 40 °C until all the solids dissolved and the reaction turned yellow. At this point the mixture could be handled in ambient atmosphere and

147

the solvent removed using rotary evaporation. The resultant solid was precipitated with Et2O (20 mL) and filtered. The solid was washed with additional Et2O (2 × 10 mL) and dried in vacuo to give 6.1a as a yellow solid. (0.45 mg, 87%). Single crystals suitable for X-ray diffraction analysis were obtained by layering a CH2Cl2 solution of 6.1a with hexanes and cooling to -30 °C.

6.1a was isolated as an inseparable mixture of cis and trans stereoisomers [ca. 1.0:0.75

31 2 2 (cis:trans)]: P NMR (162 MHz, CDCl3): δ = 24.8 ( JPP = 25 Hz, PPh3, cis), 21.7 ( JPP = 360 Hz,

2 2 1 PPh3, trans), -14.5 ( JPP = 25 Hz, Mes-P, cis), -28.8 ( JPP = 360 Hz, Mes-P, trans); H NMR (400

MHz, CDCl3): δ = 8.11-6.54 (m, 27H, aryl-H, cis/trans), 3.22 (s, 3H, o-CH3, trans), 2.40 (s, 3H, o-

CH3, cis), 2.34 (s, 3H, o-CH3, cis), 2.28 (s, 3H, p-CH3, trans), 2.18 (s, 3H, p-CH3, cis), 2.08 (s, 3H, o-CH3, trans), 1.62 (d, JPH = 13 Hz, 3H, P-CH3, cis), 1.31 (dd, JPH = 12, 4 Hz, 3H, P-CH3, trans);

13 1 C{ H} (101 MHz, CDCl3): δ = 146.3-121.4 (aryl C), 61.7 (dd, JPC = 58, 35 Hz, P-CPh2, cis),

55.6 (dd, JPC = 14, 5 Hz, P-CPh2, trans), 25.4 (d, JPC = 14 Hz, o-CH3, trans), 24.0 (dd, JPC = 15, 5

Hz, o-CH3, cis), 22.4, 22.3 (overlapping signals for o-CH3, cis/trans), 21.1 (p-CH3, trans), 21.0 (p-

CH3, cis), 12.0 (dd, JPC = 32, 6 Hz, P-CH3, cis), 10.2 (dd, JPC = 31, 6 Hz, P-CH3, trans); Anal.

Calcd for C41H39P2PdCl: C, 66.95; H, 5.34; Found: C, 66.82; H, 5.51.

6.4.3 Synthesis of Mes(Ph)P–CPh2∙PdI(PPh3) (6.1b)

A solution of MesP=CPh2 (92 mg, 0.29 mmol) and PdPhI(PPh3)2 (200 mg, 0.24 mmol) was suspended in THF (10 mL). The mixture was stirred at 40 °C until all the solids dissolved and the reaction turned orange. At this point the mixture could be handled in ambient atmosphere and the solvent removed using rotary evaporation. The resultant solid was precipitated with Et2O (20 mL) and filtered. The solid was washed with additional Et2O (2 × 10 mL) and dried in vacuo to give

6.1b as a yellow solid. (0.19 mg, 88%). Single crystals suitable for X-ray diffraction analysis were obtained from a room temperature CH2Cl2/Hexanes solution of 6.1b. 148

6.1b was isolated as an inseparable mixture of cis and trans stereoisomers [ca. 1.0:0.33

31 2 2 (cis:trans)]: P NMR (162 MHz, CD2Cl2): δ = 25.8 (d, JPP = 18 Hz, PPh3, cis), 21.1 (d, JPP =

2 2 1 330 Hz, PPh3, trans), -2.4 (d, JPP = 18 Hz, Mes-P, cis), -9.3 (d, JPP = 330 Hz, Mes-P, trans); H

13 1 and C NMR assigned for major cis isomer: H NMR (300 MHz, CD2Cl2): δ = 8.09-6.60 (m, 32H, aryl-H, cis/trans), 3.11 (s, 3H, Mes-CH3, trans), 2.29 (s, 3H, Mes-CH3, trans), 2.28 (s, 3H, Mes-

CH3, cis), 2.24 (s, 3H, Mes-CH3, cis), 2.23 (s, 3H, Mes-CH3, cis), 2.18 (s, 3H, Mes-CH3, trans);

13 1 C{ H} (101 MHz, CD2Cl2): δ = 147.3-117.3 (aryl C), 64.7 (dd, J = 63, 28 Hz, P-CPh2), 24.0 (d,

J = 15 Hz, Mes-CH3), 23.4 (Mes-CH3), 21.4 (Mes-CH3); Anal. Calcd for C46H41P2PdI: C, 62.14;

H, 4.65; Found: C, 62.43; H, 4.68.

6.4.4 Representative Procedure for the Synthesis of Complex 6.2

A solution of phosphaalkene 1.10a (50 mg, 0.13 mmol) and PdMeCl(cod) (34 mg, 0.13 mmol) in CDCl3 (0.8 mL) was sonicated in an NMR tube and for 30 min. Analysis of the reaction mixture using 31P NMR spectroscopy revealed conversion of 1.10a (δ = 244) to three new products

(δ = -10.6, -11.1, and -16.7). Attempts at isolation of a single product were unsuccessful, but single crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of this mixture in CH2Cl2.

6.4.5 Synthesis of Mes(Me)P–C(Ph)C5H3N∙PdCl(PPh3) (6.3)

A solution of MesP=CPh(2-py) (200 mg, 0.63 mmol) and PdMeCl(PPh3)2 (330 mg, 0.49 mmol) was suspended in THF (25 mL). The mixture was stirred at 40 °C until all the solids dissolved and the reaction turned deep green. Solvents were evaporated in vacuo and the resulting material precipitated with Et2O (10 mL). The solid was filtered and washed with Et2O (2 × 5 mL) and dried in vacuo to give 6.3 as a green solid. (0.18 mg, 50%). Single crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of a THF solution of 6.3. 149

31 2 2 P NMR (162 MHz, CDCl3): δ = 38.4 (d, JPP = 5 Hz, Mes-P), 21.8 (d, JPP = 5 Hz, PPh3);

1 H NMR (400 MHz, CDCl3): δ = 8.89 (t, J = 5 Hz, 1H, Hg), 7.46 (dd, J = 11, 8 Hz, 6H, Hr), 7.38

(dd, J = 8, 6 Hz, 3H, Ht), 7.27-7.20 (m, 6H, Hs), 7.03 (t, J = 8 Hz, 2H, Hj), 6.96 (d, J = 8 Hz, 1H,

Hk), 6.78 (d, J = 8 Hz, 2H, Hi), 6.72-6.67 (m, 1H, He), 6.54 (br s, 2H, Hm), 6.23 (d, J = 9 Hz, 1H,

Hd), 5.73 (t, J = 6 Hz, 1H, Hf), 3.5-1.5 (br s, 6H, Hp), 2.18 (s, 3H, Ho), 1.73 (dd, J = 12, 3 Hz, Ha);

13 1 C{ H} (101 MHz, CDCl3): δ = 165.3 (d, J = 23 Hz, Cc), 149.1 (Cg), 139.9 (Cn), 139.7 (d, J = 3

Hz, Cl), 134.7 (d, J = 11 Hz, Cr), 134.6 (d, J = 32 Hz, Cq), 134.4 (Ce), 131.6 (d, J = 9 Hz, Ch),

131.0 (Cm), 130.8 (d, J = 9 Hz, Ct), 130.5 (d, J = 3 Hz, Ci), 128.4 (Cj), 128.1 (d, J = 11 Hz, Cs),

125.4 (d, J = 55 Hz, Ck), 124.5 (Ck), 114.6 (dd, J = 17, 3 Hz, Cd), 104.1 (Cf), 73.4 (d, J = 72 Hz,

+ Cb), 24.1 (Cp), 20.9 (Co), 19.8 (dd, J = 35, 3 Hz, Ca); HRMS (ESI ): m/z 734.1283 (calcd for

104 + C40H39NOP2Cl Pd, [M+H] , 734.1287).

6.4.6 Synthesis of Mes(Me)P–C(Ph)C5H3N(CNOCH(CH2Ph)-CH2)∙PdCl (6.4)

Route A: A solution of phosphaalkene 5.1a (0.30 g, 0.70 mmol) and PdMeCl(cod) (0.19 g,

0.70 mmol) in CH2Cl2 (4 mL) was stirred for 1 h and the reaction turned a deep purple colour.

Solvent was evaporated in vacuo and dissolved in Et2O (5 mL). The solution was filtered and the filtrate concentrated. The resultant purple paste was extracted with hot pentane (5 × 5 mL) and concentrated in vacuo to give 6.4 as a purple solid. (0.18 g, 43 %).

6.4 was isolated as an inseparable 50:50 mixture of P-stereoisomers: 31P NMR (162 MHz,

1 CDCl3): δ = 41.34, 41.26; H NMR (400 MHz, CDCl3): δ = 7.12 (t, JHH = 8 Hz, 2H), 7.05-7.00 150

(m, 1H), 6.89 (d, JHH = 8 Hz, 2H), 6.83 (br s, 2H), 6.63 (m, 1H), 6.51 (overlapping d, JHH = 9 Hz,

1H), 6.06 (d, JHH = 6 Hz, 1H), 4.56-4.45 (m, 2H), 4.29-4.33 (m, 1H), 2.99 (br s, 3H), 2.62-2.54

(m, 1H), 2.38 (s, 3H), 2.24 (s, 3H), 2.10 (overlapping d, JPH = 13 Hz, 3H), 0.95-0.90 (m, 6H);

13 1 C{ H} (101 MHz, CDCl3): δ = 169.8, 161.3 (d, J = 23 Hz), 142.8, 142.0 (d, J = 9 Hz), 140.1 (d,

J = 9 Hz), 138.2, 132.2, 131.2 (br s), 128.7 (br s), 128.4 (d, J = 5 Hz), 126.9 (d, J = 38 Hz), 124.6,

120.7, 106.8, 82.8 (d, J = 67 Hz), 70.7, 67.8, 29.4, 23.9 (br s), 20.9, 19.4 (d, J = 37 Hz), 18.9, 14.9;

+ 104 + HRMS (ESI ): m/z 583.1063 (calcd for C28H33N2OPCl Pd, [M+H] , 583.1059).

Route B: To a cooled (-78 °C) solution of phosphaalkene 5.1a (55 mg, 0.13 mmol) in THF

(5 mL) was added MeLi (80 μL, 0.13 mmol). The resultant solution was warmed to ambient temperature, Pd(MeCN)2Cl2 (33 mg, 0.13 mmol) was added and the reaction stirred for 1 h.

Volatiles were removed in vacuo and the reaction extracted with Et2O (3 × 5 mL). Volatiles were removed in vacuo to give 6.4 as a purple solid. (30 mg, 40 %). Spectral data matched that obtained from route A.

6.4.7 X-ray Crystallographic Studies

All single crystals were immersed in oil and mounted on a glass fiber. Data were collected on a Bruker X8 APEX II diffractometer with graphite-monchromated Mo Kα radiation. All structures were solved by direct methods and subsequent Fourier difference techniques. All nonhydrogen atoms were refined anisotropically with hydrogen atoms being included in calculated positions but not refined. All data sets were corrected for absorption effects (SADABS), Lorentz, and polarization effects. All calculations were performed using SHELXL-2014 crystallographic software package from Bruker AXS.114 Absolute configuration was confirmed on the basis of the refined Flack parameter.115 Compound 6.3 crystallized with one disordered THF molecule in the

151

asymmetric unit. Additional crystal data and details of data collection and structure refinement are listed in Table 6.2.

152

Table 6.2 X-ray Data Collection and Refinement Details for Compounds 6.1a, 6.1b, 6.2, and 6.3.

6.1a∙CHCl3 6.1b 6.2∙CH2Cl2 6.3∙C4H8O

formula C41H39P2PdCl, C46H41P2PdI C26H35ClNOPPd, C40H38NP2PdCl,

CHCl3 CH2Cl2 C4H8O fw 854.88 889.03 635.29 809.11 cryst syst monoclinic triclinic orthorhombic monoclinic

space group P21 P-1 P212121 P21/n colour yellow orange yellow green a (Å) 11.7917(8) 12.116(1) 8.4717(6) 14.765(1) b (Å) 13.9449(9) 19.591(2) 16.708(1) 13.415(1) c (Å) 12.0159(8) 20.645(2) 20.306(1) 19.572(2) α (deg) 90 69.772(2) 90 90 β (deg) 96.799(2) 76.936(2) 90 95.887(2) γ (deg) 90 81.418(2) 90 90 V (Å3) 1961.9(2) 4465.5(8) 2874.3(3) 3856.2(6) T (K) 90(2) 90(2) 90(2) 90(2) Z 2 4 4 4 μ(Mo Kα) (mm-1) 0.856 1.206 1.001 0.669 cryst size (mm) 0.20×0.05×0.05 0.18×0.17×0.16 0.20×0.16×0.10 0.19×0.10×0.10

-3 Dcalcd. (Mg m ) 1.447 1.322 1.468 1.394 2θ(max) (°) 55.0 60.2 58.1 57.4 no. of reflns 16860 92563 37749 39596 no. of unique data 4679 25186 9975 9924 R(int) 0.0405 0.1129 0.0314 0.0768 refln/param ratio 18.5 27.7 24.5 20.2 a R1 [I > 2σ(I)] 0.0363 0.0746 0.0486 0.0412 b wR2 [all data] 0.1154 0.1899 0.0638 0.0939 GOF 0.828 1.090 1.048 1.018

a R1 =Σ‖퐹표| − |퐹푐‖/Σ|퐹표| b 2 2 2 2 2 2 1/2 w푅2(퐹 [all data]) = {Σ[푤(퐹표 − 퐹푐 ) ]/Σ[푤(퐹표 ) ]}

153

Chapter 7: Concluding Remarks

By this point, the reader will certainly appreciate that the phosphaalkene functional group is versatile. Depending on the situation the phosphaalkene moiety can react like an olefin, i.e. undergo addition polymerization (Chapters 3 and 4) or carbopalladation (Chapter 6).

Conversely, the phosphorus atom in a phosphaalkenes is apt to coordinate transition metals in a geometry that mirrors analogous imine-containing ligands (Chapter 5). Still, electronically this new phosphorus–metal bond is unique, altering the behavior of the metal ion. The inherent polarity of the P=C bond results in regioselective nucleophilic additions (Chapter 2) and carbopalladation

(Chapter 6) reactions, providing a route to structurally complex phosphine-containing compounds and complexes. Furthermore, the development and optimization of methods to create sophisticated and functional P-containing polymers could be advantageous in the field of materials chemistry and supported catalysis. In this regard, the extensive investigation of phosphaalkenes as monomers is warranted and certainly the work contained in this thesis contributes to that end. Finally, from the perspective of ligand design, the nonsymmetric hybrid phosphaalkene-oxazoline-pyridine pincer ligands discussed in Chapter 5 are structurally unique. This ligand scaffold could potentially provide some advantageous electronic properties for catalytic transformations. To conclude, compounds featuring P=C bonds, while seemingly esoteric, are fascinating synthetic targets with the potential for contribution to the fields of inorganic, polymer, and organic chemistry.

154

Bibliography

(1) Tolman, C. A. Chem. Rev. 1977, 77, 313-348. (2) Dias, P. B.; de Piedade, M. E. M.; Simões, J. A. M. Coord. Chem. Rev. 1994, 135, 737- 807. (3) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070. (4) Wassenaar, J.; Reek, J. N. H. Org. Biomol. Chem. 2011, 9, 1704-1713. (5) Goudriaan, P. E.; van Leeuwen, P. W. N. M.; Birkholz, M.-N.; Reek, J. N. H. Eur. J. Inorg. Chem. 2008, 2008, 2939-2958. (6) Crepy, K. V. L.; Imamota, T. In New Aspects in Phosphorus Chemistry III; Majoral, J., Eds.; Spring Berlin Heidelberg, 2003; Chapter 1. (7) Bayardon, J.; Jugé, S. In Phosphorus(III) Ligands in Homogenous Catalysis: Design and Synthesis; Kamer, P. C. J., van Leeuwen, P. W. N. M., Eds.; Wiley: Chichester, 2012; Chapter 12. (8) Kolodiazhnyi, O. I. Tetrahedron: Asymmetry 2012, 23, 1-46. (9) Chelucci, G.; Orrù, G.; Pinna, G. A. Tetrahedron 2003, 59, 9471-9515. (10) Lu, J.; Toy, P. H. Chem. Rev. 2009, 109, 815-838. (11) Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102, 3217-3274. (12) Schleyer, P. v. R.; Kost, D. J. Am. Chem. Soc. 1988, 110, 2105-2109. (13) Schmidt, M. W.; Truong, P. N.; Gordon, M. S. J. Am. Chem. Soc. 1987, 109, 5217-5227. (14) Mathey, F. Angew. Chem. Int. Ed. 2003, 42, 1578-1604. (15) Issleib, K.; Leißring, E.; Riemer, M.; Oehme, H. Z. Chem. 1983, 23, 99-100. (16) Müller, C.; Broeckx, L. E. E.; de Krom, I.; Weemers, J. J. M. Eur. J. Inorg. Chem. 2013, 2013, 187-202. (17) Müller, C.; Vogt, D. Dalton Trans. 2007, 5505-5523. (18) Mathey, F. Acc. Chem. Res. 2004, 37, 954-960. (19) Mathey, F. Coord. Chem. Rev. 1994, 137, 1-52. (20) Wu, S.; Rheingold, A. L.; Protasiewicz, J. D. Chem. Commun. 2014, 50, 11036-11038. (21) Simpson, M. C.; Protasiewicz, J. D. Pure Appl. Chem. 2013, 85, 801-815. (22) Washington, M. P.; Gudimetla, V. B.; Laughlin, F. L.; Deligonul, N.; He, S.; Payton, J. L.; Simpson, M. C.; Protasiewicz, J. D. J. Am. Chem. Soc. 2010, 132, 4566-4567. (23) Lacombe, S.; Gonbeau, D.; Cabioch, J. L.; Pellerin, B.; Denis, J. M.; Pfister-Guillouzo, G. J. Am. Chem. Soc. 1988, 110, 6964-6967. (24) Mintz, D. M.; Kuppermann, A. J. Chem. Phys. 1979, 71, 3499-3513. (25) Bates, J. I.; Dugal-Tessier, J.; Gates, D. P. Dalton Trans. 2010, 39, 3151-3159. (26) Regitz, M.; Scherer, O. J. Multiple Bonds and Low Coordination in Phosphorus Chemistry; Thieme: Stuttgart, 1990. (27) Dillon, K. B.; Mathey, F.; Nixon, J. F. Phosphorus: the Carbon Copy; Wiley: Chichester, 1998. (28) Becker, V. G. Z. Anorg. Allg. Chem. 1976, 423, 242-254. (29) Klebach, T. C.; Lourens, R.; Bickelhaupt, F. J. Am. Chem. Soc. 1978, 100, 4886-4888. (30) Veits, Y. A.; Karlstedt, N. B.; Beletskaya, I. P. Tetrahedron Lett. 1995, 36, 4121-4124. (31) Yam, M.; Tsang, C. W.; Gates, D. P. Inorg. Chem. 2004, 43, 3719-3723. (32) Yam, M.; Chong, J. H.; Tsang, C. W.; Patrick, B. O.; Lam, A. E.; Gates, D. P. Inorg. Chem. 2006, 45, 5225-5234. (33) Kawanami, H.; Toyota, K.; Yoshifuji, M. J. Organomet. Chem. 1997, 535, 1-5. 155

(34) Jouaiti, A.; Geoffroy, M.; Terron, G.; Bernardinelli, G. J. Am. Chem. Soc. 1995, 117, 2251- 2258. (35) Jouaiti, A.; Geoffroy, M.; Terron, G.; Bernardinelli, G. J. Chem. Soc., Chem. Commun. 1992, 155-156. (36) Becker, G.; Uhl, W.; Wessely, H. J. Z. Anorg. Allg. Chem. 1981, 479, 41-56. (37) Shah, S.; D. Protasiewicz, J. Chem. Commun. 1998, 1585-1586. (38) Marinetti, A.; Bauer, S.; Ricard, L.; Mathey, F. Organometallics 1990, 9, 793-798. (39) Marinetti, A.; Mathey, F. Angew. Chem. Int. Ed. 1988, 27, 1382-1384. (40) Esfandiarfard, K.; Arkhypchuk, A. I.; Orthaber, A.; Ott, S. Dalton Trans. 2016, 45, 2201- 2207. (41) Kawanami, H.; Toyota, K.; Yoshifuji, M. Chem. Lett. 1996, 25, 533-534. (42) Noonan, K. J. T.; Patrick, B. O.; Gates, D. P. Chem. Commun. 2007, 3658-3660. (43) Rawe, B. W.; Chun, C. P.; Gates, D. P. Chem. Sci. 2014, 5, 4928-4938. (44) De Vaumas, R.; Marinetti, A.; Ricard, L.; Mathey, F. J. Am. Chem. Soc. 1992, 114, 261- 266. (45) Takita, R.; Takada, Y.; Jensen, R. S.; Okazaki, M.; Ozawa, F. Organometallics 2008, 27, 6279-6285. (46) Dugal-Tessier, J.; Dake, G. R.; Gates, D. P. Angew. Chem. Int. Ed. 2008, 47, 8064-8067. (47) Pfaltz, A. Acta Chem. Scand. 1996, 50, 189-194. (48) Pfaltz, A.; Drury, W. J. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5723-5726. (49) McKennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. J. Org. Chem. 1993, 58, 3568- 3571. (50) Dugal-Tessier, J.; Serin, S. C.; Castillo-Contreras, E. B.; Conrad, E. D.; Dake, G. R.; Gates, D. P. Chem. Eur. J. 2012, 18, 6349-6359. (51) Dugal-Tessier, J.; Kuhn, P. S.; Dake, G. R.; Gates, D. P. Heteroatom Chem. 2010, 21, 355- 360. (52) Bélanger, É.; Pouliot, M.-F.; Paquin, J.-F. Org. Lett. 2009, 11, 2201-2204. (53) Dugal-Tessier, J.; Dake, G. R.; Gates, D. P. Organic Letters 2010, 12, 4667-4669. (54) Tsang, C. W.; Yam, M.; Gates, D. P. J. Am. Chem. Soc. 2003, 125, 1480-1481. (55) Tsang, C. W.; Baharloo, B.; Riendl, D.; Yam, M.; Gates, D. P. Angew. Chem. Int. Ed. 2004, 43, 5682-5685. (56) Gillon, B. H.; Gates, D. P. Chem. Commun. 2004, 1868-1869. (57) Noonan, K. J. T.; Gates, D. P. Angew. Chem. Int. Ed. 2006, 45, 7271-7274. (58) Noonan, K. J. T.; Gates, D. P. Macromolecules 2008, 41, 1961-1965. (59) Noonan, K. J. T.; Feldscher, B.; Bates, J. I.; Kingsley, J. J.; Yam, M.; Gates, D. P. Dalton Trans. 2008, 4451-4457. (60) Gillon, B. H.; Patrick, B. O.; Gates, D. P. Chem. Commun. 2008, 2161-2163. (61) Noonan, K. J. T.; Gillon, B. H.; Cappello, V.; Gates, D. P. J. Am. Chem. Soc. 2008, 130, 12876-12877. (62) Priegert, A. M.; Siu, P. W.; Hu, T. Q.; Gates, D. P. Fire Mater. 2015, 39, 647-657. (63) Siu, P. W.; Serin, S. C.; Krummenacher, I.; Hey, T. W.; Gates, D. P. Angew. Chem. Int. Ed. 2013, 52, 6967-6970. (64) Holand, S.; Charrier, C.; Mathey, F.; Fischer, J.; Mitschler, A. J. Am. Chem. Soc. 1984, 106, 826-828.

156

(65) Van der Knaap, T. A.; Bickelhaupt, F.; Kraaykamp, J. G.; Van Koten, G.; Bernards, J. P. C.; Edzes, H. T.; Veeman, W. S.; De Boer, E.; Baerends, E. J. Organometallics 1984, 3, 1804- 1811. (66) Apfel, R.; Casser, C.; Knoch, F. J. Organomet. Chem. 1985, 293, 213-217. (67) Lorenz, I.-P.; Pohl, W.; Nöth, H.; Schmidt, M. J. Organomet. Chem. 1994, 475, 211-221. (68) Knoll, K.; Huttner, G.; Wasiucionek, M.; Zsolnai, L. Angew. Chem. Int. Ed. 1984, 23, 739- 740. (69) Nixon, J. F. Chem. Rev. 1988, 88, 1327-1362. (70) Schoeller, W. In Multiple Bonds and Low Coordination in Phosphorus Chemistry; Regitz, M., Scherer, O. J., Eds.; Thieme: Stuttgart, Germany, 1990. (71) Le Floch, P. Coord. Chem. Rev. 2006, 250, 627-681. (72) Nakajima, Y.; Nakao, Y.; Sakaki, S.; Tamada, Y.; Ono, T.; Ozawa, F. J. Am. Chem. Soc. 2010, 132, 9934-9936. (73) Bart, S. C.; Chłopek, K.; Bill, E.; Bouwkamp, M. W.; Lobkovsky, E.; Neese, F.; Wieghardt, K.; Chirik, P. J. J. Am. Chem. Soc. 2006, 128, 13901-13912. (74) Nakajima, Y.; Shiraishi, Y.; Tsuchimoto, T.; Ozawa, F. Chem. Commun. 2011, 47, 6332- 6334. (75) Dugal-Tessier, J.; Conrad, E.; Dake, G. R.; Gates, D. P. In Phosphorus(III) Ligands in Homogenous Catalysis: Design and Synthesis; Kamer, P. C. J., van Leeuwen, P. W. N. M., Eds.; Wiley: Chichester, 2012; Chapter 10. (76) Ozawa, F.; Yoshifuji, M. Dalton Trans. 2006, 4987-4995. (77) Weber, L. Coord. Chem. Rev. 2005, 249, 741-763. (78) Minami, T.; Okamoto, H.; Ikeda, S.; Tanaka, R.; Ozawa, F.; Yoshifuji, M. Angew. Chem. Int. Ed. 2001, 40, 4501-4503. (79) Chang, Y.-H.; Nakajima, Y.; Tanaka, H.; Yoshizawa, K.; Ozawa, F. J. Am. Chem. Soc. 2013, 135, 11791-11794. (80) Chang, Y.-H.; Tanigawa, I.; Taguchi, H.-o.; Takeuchi, K.; Ozawa, F. Eur. J. Inorg. Chem. 2016, 754-760. (81) Chang, Y.-H.; Nakajima, Y.; Tanaka, H.; Yoshizawa, K.; Ozawa, F. Organometallics 2014, 33, 715-721. (82) Dugal-Tessier, J.; Dake, G. R.; Gates, D. P. Organometallics 2007, 26, 6481-6486. (83) van der Knaap, T. A.; Bickelhaupt, F. Tetrahedron Lett. 1982, 23, 2037-2040. (84) Li, B. L.; Neilson, R. H. Inorg. Chem. 1984, 23, 3665-3666. (85) Xie, Z. M.; Wisian-Neilson, P.; Neilson, R. H. Organometallics 1985, 4, 339-344. (86) Gillon, B. H.; Noonan, K. J. T.; Feldscher, B.; Wissenz, J. M.; Kam, Z. M.; Hsieh, T.; Kingsley, J. J.; Bates, J. I.; Gates, D. P. Can. J. Chem. 2007, 85, 1045-1052. (87) Peer, M.; deJong, J. C.; Kiefer, M.; Langer, T.; Rieck, H.; Schell, H.; Sennhenn, P.; Sprinz, J.; Steinhagen, H.; Wiese, B.; Helmchen, G. Tetrahedron 1996, 52, 7547-7583. (88) Korff, C.; Helmchen, G. Chem. Commun. 2004, 530-531. (89) Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T. J. Org. Chem. 2000, 65, 4776-4778. (90) Katagiri, K.; Danjo, H.; Yamaguchi, K.; Imamoto, T. Tetrahedron 2005, 61, 4701-4707. (91) Trost, B. M. J. Org. Chem. 2004, 69, 5813-5837. (92) Lu, Z.; Ma, S. M. Angew. Chem. Int. Ed. 2008, 47, 258-297. (93) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organometallics 2004, 23, 4317-4324. (94) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Chem. Lett. 2005, 34, 720-721. 157

(95) Aeby, A.; Consiglio, G. Inorg. Chim. Acta 1999, 296, 45-51. (96) Sperrle, M.; Aeby, A.; Consiglio, G.; Pfaltz, A. Helv. Chim. Acta 1996, 79, 1387-1392. (97) Hatano, M.; Horibe, T.; Ishihara, K. Angew. Chem. Int. Ed. 2013, 52, 4549-4553. (98) Rubina, M.; Sherrill, W. M.; Rubin, M. Organometallics 2008, 27, 6393-6395. (99) Doherty, M. D.; Trudeau, S.; White, P. S.; Morken, J. P.; Brookhart, M. Organometallics 2007, 26, 1261-1269. (100) Apfelbacher, A.; Braunstein, P.; Brissieux, L.; Welter, R. Dalton Trans. 2003, 1669-1674. (101) Schaffner, S.; Müller, J. F. K.; Neuburger, M.; Zehnder, M. Helv. Chim. Acta 1998, 81, 1223-1232. (102) Schaffner, S.; Macko, L.; Neuburger, M.; Zehnder, M. Helv. Chim. Acta 1997, 80, 463- 471. (103) Dunina, V. V.; Gorunova, O. N.; Livantsov, M. V.; Grishin, Y. K.; Kochetkov, K. A.; Churakov, A. V.; Kuz'mina, L. G. Polyhedron 2011, 30, 27-32. (104) Rheingold, A. L.; Fultz, W. C. Organometallics 1984, 3, 1414-1417. (105) Canty, A. J.; Hoare, J. L.; Skelton, B. W.; White, A. H.; van Koten, G. J. Organomet. Chem. 1998, 552, 23-29. (106) Vicente, J.; Chicote, M. T.; Martinez-Martinez, A. J.; Bautista, D.; Jones, P. G. Org. Biomol. Chem. 2011, 9, 2279-2285. (107) Albrecht, M.; Wesselt, C.; de Groot, M.; Rissanen, K.; Luchow, A. J. Am. Chem. Soc. 2008, 130, 4600-4601. (108) Cartoon, M. E. K.; Cheeseman, G. W. H. J. Organomet. Chem. 1982, 234, 123-136. (109) (a) Gatineau, D.; Giordano, L.; Buono, G. J. Am. Chem. Soc. 2011, 133, 10728-10731. (b) Ferrer, C.; Raducan, M.; Nevado, C.; Claverie, C. K.; Echavarren, A. M. Tetrahedron 2007, 63, 6306-6316. (c) Dunina, V. V.; Gorunova, O. N.; Kuznetsova, E. D.; Turubanova, E. I.; Livantsov, M. V.; Grishin, Y. K.; Kuz’mina, L. G.; Churakov, A. V. Russ. Chem. Bull. 2006, 55, 2193-2211. (d) Baber, R. A.; Orpen, A. G.; Pringle, P. G.; Wilkinson, M. J.; Wingad, R. L. Dalton Trans. 2005, 659-667.(e) Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger, C. P.; Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int. Ed. Eng. 1995, 34, 1844-1848. (f) Alyea, E. C.; Malito, J. J. Organomet. Chem. 1988, 340, 119-126. (g) Gill, D. F.; Shaw, B. L. J. Chem. Soc., Chem. Comm. 1972, 65-66. (110) (a) Karsch, H. H.; Hanika, G.; Huber, B.; Meindl, K.; König, S.; Krüger, C.; Müller, G. J. Chem. Soc., Chem. Commun. 1989, 373-375. (b) McPartlin, M.; Woods, A. D.; Pask, C. M.; Vogler, T.; Wright, D. S. Chem. Commun. 2003, 1524-1525. (c) Harger, M. J. P.; Shimmin, P. A. J. Chem. Soc., Chem. Commun. 1991, 1187-1188. (d) Bucher, G.; Borst, M. L. G.; Ehlers, A. W.; Lammertsma, K.; Ceola, S.; Huber, M.; Grote, D.; Sander, W. Angew. Chem., Int. Ed. 2005, 44, 3289-3293. (e) Hou, Z. M.; Breen, T. L.; Stephan, D. W. Organometallics 1993, 12, 3158-3167. (f) Schmidbaur, H.; Schnatterer, S. Chem. Ber. 1983, 116, 1947-1954. (g) Canac, Y.; Conejero, S.; Soleilhavoup, M.; Donnadieu, B.; Bertrand, G. J. Am. Chem. Soc. 2006, 128, 459-464. (111) Drew, D.; Doyle, J. R. Inorg. Synth. 1990, 28, 346-349. (112) Salo, E. V.; Guan, Z. Organometallics 2003, 22, 5033-5046. (113) Andrews, M. A.; Chang, T. C. T.; Cheng, C. W. F.; Kapustay, L. V.; Kelly, K. P.; Zweifel, M. J. Organometallics 1984, 3, 1479-1484. (114) Sheldrick, G. M. Acta Crystallogr. Sect. A: Found. Crystallogr. 2008, 64, 112-122. (115) Parsons, S.; Flack, H. D.; Wagner, T. Acta Crystallogr. Sect. B: Struct. Sci. 2013, 69, 249- 259. 158

(116) See, for example: (a) C. Friebe, M. D. Hager, A. Winter, and U. S. Schubert, Adv. Mater., 2012, 24, 332; (b) G. R. Whittell, M. D. Hager, U. S. Schubert, and I. Manners, Nat. Mater., 2011, 10, 176; (c) S. Itsuno, Polymeric chiral catalyst design and chiral polymer synthesis, Wiley, Hoboken, 2011; (d) C. L. Ho and W. Y. Wong, Coord. Chem. Rev., 2011, 255, 2469; (e) X. S. Wang and R. McHale, Macromol. Rapid Commun., 2010, 31, 331; (f) R. J. Puddephatt, Chem. Soc. Rev., 2008, 37, 2012; (g) G. R. Whittell and I. Manners, Adv. Mater., 2007, 19, 3439; (h) I. Manners, Synthetic metal-containing polymers, Wiley-VCH, Weinheim, 2004; (i) R. J. Puddephatt, Coord. Chem. Rev., 2001, 216, 313; (j) I. Manners, Science, 2001, 294, 1664. (117) For reviews see: (a) A. M. Priegert, B. W. Rawe, S. C. Serin, and D. P. Gates, Chem. Soc. Rev., 2016, 45, 922-953; (b) H. R. Allcock, Appl. Organomet. Chem., 2013, 27, 620; (c) J. I. Bates, J. Dugal-Tessier, and D. P. Gates, Dalton Trans., 2010, 39, 3151; (d) T. Baumgartner and R. Reau, Chem. Rev., 2006, 106, 4681; (e) M. Hissler, P. W. Dyer, and R. Reau, Coord. Chem. Rev., 2003, 244, 1; (f) J. P. Majoral and A. M. Caminade, Chem. Rev., 1999, 99, 845. (118) See, for example: (a) B. W. Rawe and D. P. Gates, Angew. Chem. Int. Ed., 2015, 54, 11438; (b) R. Guterman, A. R. Kenaree, J. B. Gilroy, E. R. Gillies, and P. J. Ragogna, Chem. Mater., 2015, 27, 1412; (c) Y. B. Zhou, C. Y. Li, M. Lin, Y. J. Ding, and Z. P. Zhan, Adv. Synth. Catal., 2015, 357, 2503; (d) X. S. Wang, K. Cao, Y. B. Liu, B. Tsang, and S. Liew, J. Am. Chem. Soc., 2013, 135, 3399; (e) S. K. Patra, G. R. Whittell, S. Nagiah, C.-L. Ho, W.-Y. Wong, and I. Manners, Chem. Eur. J., 2010, 16, 3240; (f) S. Greenberg, G. L. Gibson, and D. W. Stephan, Chem. Commun., 2009, 304; (g) V. L. de Talance, M. Hissler, L. Z. Zhang, T. Karpati, L. Nyulaszi, D. Caras-Quintero, P. Bauerle, and R. Reau, Chem. Commun., 2008, 2200; (h) Y. Dienes, S. Durben, T. Karpati, T. Neumann, U. Englert, L. Nyulaszi, and T. Baumgartner, Chem. Eur. J., 2007, 13, 7487; (i) K. Naka, T. Umeyama, A. Nakahashi, and Y. Chujo, Macromolecules, 2007, 40, 4854; (j) L. A. Vanderark, T. J. Clark, E. Rivard, I. Manners, J. C. Slootweg, and K. Lammertsma, Chem. Commun., 2006, 3332; (k) R. C. Smith and J. D. Protasiewicz, J. Am. Chem. Soc., 2004, 126, 2268; (l) K. Toyota, J. Ujita, S. Kawasaki, K. Abe, N. Yamada, and M. Yoshifuji, Tetrahedron Lett., 2004, 45, 7609; (m) T. Baumgartner, T. Neumann, and B. Wirges, Angew. Chem Int. Ed., 2004, 43, 6197. (119) Pandey, S.; Lonnecke, P.; Hey-Hawkins, E. Eur. J. Inorg. Chem. 2014, 2456-2465. (120) Suarez-Suarez, S.; Carriedo, G. A.; Tarazona, M. P.; Soto, A. P. Chem. Eur. J. 2013, 19, 5644-5653. (121) Carriedo, G. A.; Ramajo, B.; Valenzuela, M. L. React. Funct. Polym. 2011, 71, 433-439. (122) Maeda, K.; Miyagawa, T.; Furuko, A.; Onouchi, H.; Yashima, E. Macromolecules 2015, 48, 4281-4293. (123) Imoto, H.; Morisaki, Y.; Chujo, Y. Chem. Commun. 2010, 46, 7542-7544. (124) Morisaki, Y.; Suzuki, K.; Imoto, H.; Chujo, Y. Macromol. Rapid Commun. 2010, 31, 1719- 1724. (125) Morisaki, Y.; Suzuki, K.; Imoto, H.; Chujo, Y. Macromol. Chem. Phys. 2011, 212, 2603- 2611. (126) Ouchi, Y.; Morisaki, Y.; Ogoshi, T.; Chujo, Y. Asian J. Chem. 2007, 2, 397-402. (127) Ralph, C. K.; Akotsi, O. M.; Bergens, S. H. Organometallics 2004, 23, 1484-1486. (128) Yu, H. B.; Hu, Q. S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500-6501. (129) Fan, Q. H.; Ren, C. Y.; Yeung, C. H.; Hu, W. H.; Chan, A. S. C. J. Am. Chem. Soc. 1999, 121, 7407-7408. (130) Pu, L. Chem. Eur. J. 1999, 5, 2227-2232. 159

(131) Reggelin, M.; Doerr, S.; Klussmann, M.; Schultz, M.; Holbach, M. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5461-5466. (132) Deschenaux, R.; Stille, J. K. J. Org. Chem. 1985, 50, 2299-2302. (133) Serin, S. C.; Patrick, B. O.; Dake, G. R.; Gates, D. P. Organometallics 2014, 33, 7215- 7222. (134) Valentini, H.; Selvakumar, K.; Worle, M.; Pregosin, P. S. J. Organomet. Chem. 1999, 587, 244-251. (135) Rouzaud, J.; Jones, M. D.; Raja, R.; Johnson, B. F. G.; Meurig Thomas, J.; Duer, M. J. Helv. Chim. Acta 2003, 86, 1753-1759. (136) Semeniuchenko, V.; Khilya, V.; Groth, U. Z Naturforsch B 2009, 64, 1147-1158. (137) Nishibayashi, Y.; Segawa, K.; Arikawa, Y.; Ohe, K.; Hidai, M.; Uemura, S. J. Organomet. Chem. 1997, 545, 381-398. (138) Brown, T. H.; Green, P. J. J. Am. Chem. Soc. 1970, 92, 2359-2362. (139) Qiu, H. B.; Inoue, Y.; Che, S. N. Angew. Chem. Int. Ed. 2009, 48, 3069-3072. (140) For recent reviews, see: (a) Priegert, A. M.; Rawe, B. W.; Serin, S. C.; Gates, D. P. Chem. Soc. Rev. 2016, 45, 922-953. (b) Allcock, H. R. Dalton Trans. 2016, 45, 1856-1862. (c) Zhou, J. W.; Whittell, G. R.; Manners, I. Macromolecules 2014, 47, 3529-3543. (d) He, X. M.; Baumgartner, T. RSC Adv. 2013, 3, 11334-11350. (e) Jahnke, A. A.; Seferos, D. S. Macromol. Rapid Commun. 2011, 32, 943-951. (f) Jakle, F. Chem. Rev. 2010, 110, 3985-4022. (g) Baumgartner, T.; Reau, R. Chem. Rev. 2006, 106, 4681-4727. (141) (a) Womble, C. T.; Coates, G. W.; Matyjaszewski, K.; Noonan, K. J. T. ACS Macro Lett. 2016, 5, 253. (b) Rawe, B. W.; Gates, D. P. Angew. Chem. Int. Ed. 2015, 54, 11438-11442. (c) Marquardt, C.; Jurca, T.; Schwan, K. C.; Stauber, A.; Virovets, A. V.; Whittell, G. R.; Manners, I.; Scheer, M. Angew. Chem. Int. Edit. 2015, 54, 13782-13786. (d) Schäfer, A.; Jurca, T.; Turner, J.; Vance, J. R.; Lee, K.; Du, V. A.; Haddow, M. F.; Whittell, G. R.; Manners, I. Angew. Chem. Int. Ed. 2015, 54, 4836-4841. (e) Guterman, R.; Kenaree, A. R.; Gilroy, J. B.; Gillies, E. R.; Ragogna, P. J. Chem. Mater. 2015, 27, 1412. (f) Wolf, T.; Steinbach, T.; Wurm, F. R. Macromolecules 2015, 48, 3853. (g) Tian, Z. C.; Chen, C.; Allcock, H. R. Macromolecules 2014, 47, 1065. (h) Matano, Y.; Ohkubo, H.; Honsho, Y.; Saito, A.; Seki, S.; Imahori, H. Org. Lett. 2013, 15, 932-935. (i) Wang, X.; Cao, K.; Liu, Y.; Tsang, B.; Liew, S. J. Am. Chem. Soc. 2013, 135, 3399-3402. (j) He, X.; Woo, A. Y. Y.; Borau-Garcia, J.; Baumgartner, T. Chem. Eur. J. 2013, 19, 7620-7630. (k) Patra, S. K.; Whittell, G. R.; Nagiah, S.; Ho, C.-L.; Wong, W.-Y.; Manners, I. Chem. Eur. J. 2010, 16, 3240-3250. (l) Saito, A.; Matano, Y.; Imahori, H. Org. Lett. 2010, 12, 2675-2677. (m) Greenberg, S.; Gibson, G. L.; Stephan, D. W. Chem. Commun. 2009, 304-306. (n) de Talance, V. L.; Hissler, M.; Zhang, L. Z.; Karpati, T.; Nyulaszi, L.; Caras-Quintero, D.; Bauerle, P.; Reau, R. Chem. Commun. 2008, 2200-2202. (o) Naka, K.; Umeyama, T.; Nakahashi, A.; Chujo, Y. Macromolecules 2007, 40, 4854-4858. (p) Vanderark, L. A.; Clark, T. J.; Rivard, E.; Manners, I.; Slootweg, J. C.; Lammertsma, K. Chem. Commun. 2006, 3332-3333. (q) Wright, V. A.; Patrick, B. O.; Schneider, C.; Gates, D. P. J. Am. Chem. Soc. 2006, 128, 8836-8844. (r) Smith, R. C.; Protasiewicz, J. D. J. Am. Chem. Soc. 2004, 126, 2268-2269. (142) For reviews, see: (a) Dillon, K. B.; Mathey, F.; Nixon, J. F. Phosphorus: The Carbon Copy, Wiley, West Sussex, England, 1998. (b) Cather Simpson, M.; Protasiewicz, J. D. Pure Appl. Chem. 2013, 85, 801-815. (c) Bates, J. I.; Dugal-Tessier, J.; Gates, D. P. Dalton Trans. 2010, 39, 3151-3159. (d) Ozawa, F.; Yoshifuji, M. Dalton Trans. 2006, 4987-4995. (e) Mathey, F. Angew. Chem. Int. Edit. 2003, 42, 1578-1604. 160

(143) Serin, S. C.; Dake, G. R.; Gates, D. P. Dalton Trans. 2016, 45, 5659-5666. (144) Fuchs, E. P. O.; Heydt, H.; Regitz, M.; Schoeller, W. W.; Busch, T. Tetrahedron Lett. 1989, 30, 5111-5114. (145) Cannon, J. S.; Frederich, J. H.; Overman, L. E. J. Org. Chem. 2012, 77, 1939-1951. (146) Franco, D.; Gómez, M.; Jiménez, F.; Muller, G.; Rocamora, M.; Maestro, M. A.; Mahía, J. Organometallics 2004, 23, 3197-3209. (147) Yoshifuji, M.; Toyota, K.; Inamoto, N. Tetrahedron Lett. 1985, 26, 1727-1730. (148) Povolotskii, M. I.; Negrebetskii, V. V.; Romanenko, V. D.; Kachkovskaya, L. S.; Markovsky, L. N. Phosphorus, Sulfur, and Silicon and the Related Elements 1990, 51, 319-319. (149) Appel, R. In Multiple Bonds and Low Coordination in Phosphorus Chemistry; Regitz M., Scherer, O. J., Eds.; Thieme: Stuttgart, Germany, 1990. (150) Weber, L. Eur. J. Inorg. Chem. 2000, 2425-2441. (151) Toyota, K.; Takahashi, H.; Shimura, K.; Yoshifuji, M. Bull. Chem. Soc. Jpn. 1996, 69, 141- 145. (152) Siu, P. W.; Serin, S. C.; Krummenacher, I.; Hey, T. W.; Gates, D. P. Angew. Chem. Int. Ed. 2013, 52, 6967-6970. (153) Tiegs, B. J.; Sarkar, S.; Condo, A. M.; Keresztes, I.; Coates, G. W. ACS Macro Letters 2016, 5, 181-184. (154) Markova, N.; Ivanova, G.; Enchev, V.; Simeonova, M. Struct. Chem. 2012, 23, 815-824. (155) Monroy-Barreto, M.; Esturau-Escofet, N.; Briseño-Terán, M.; del Carmen Pérez-Vázquez, M. Int. J. Polym. Anal. Charact. 2012, 17, 515-523. (156) Thompson, R. D.; Jarrett, W. L.; Mathias, L. J. Macromolecules 1992, 25, 6455-6459. (157) De, P.; Faust, R.; Schimmel, H.; Ofial, A. R.; Mayr, H. Macromolecules 2004, 37, 4422- 4433. (158) Brar, A. S.; Charan, S. J. Appl. Polym. Sci. 1994, 51, 669-674. (159) Gan, L. M.; Lee, K. C.; Chew, C. H.; Ng, S. C.; Gan, L. H. Macromolecules 1994, 27, 6335-6340. (160) Takeda, Y.; Nishida, T.; Minakata, S. Chem. Eur. J. 2014, 20, 10266-10270. (161) Bresien, J.; Faust, K.; Schulz, A.; Villinger, A. Angew. Chem. Int. Ed. 2015, 54, 6926- 6930. (162) Usón, R.; Laguna, A. Organometallic Syntheses 1986, 3, 322-342. (163) (a) van Koten, G. J. Organomet. Chem. 2013, 730, 156-164. (b) Schneider, S.; Meiners, J.; Askevold, B. Eur. J. Inorg. Chem. 2012, 412-429. (c) Benito-Garagorri, D.; Kirchner, K. Acc. Chem. Res. 2008, 41, 201-213. (d) Nishiyama, H. Chem. Soc. Rev. 2007, 36, 1133-1141. (e) Organometallic Pincer Chemistry; G. van Koten, D. Milstein, Eds.; Springer-Verlag: Berlin Heidelberg, 2003. (f) Albrecht, M.; van Koten, G. Angew. Chem. Int. Ed. 2001, 40, 3750-3781. (164) For examples and applications of nonsymmetric PNN pincer ligands, see: (A) Cheisson, T.; Auffrant, A. Dalton Trans. 2016, 45, 2069-2078. Butschke, B.; Fillman, K. L.; Bendikov, T.; Shimon, L. J. W.; Diskin-Posner, Y.; Leitus, G.; Gorelsky, S. I.; Neidig, M. L.; Milstein, D. Inorg. Chem. 2015, 54, 4909-4926. Feller, M.; Diskin-Posner, Y.; Shimon, L. J. W.; Ben-Ari, E.; Milstein, D. Organometallics 2012, 31, 4083-4101. Balaraman, E.; Ben-David, Y.; Milstein, D. Angew. Chem. Int. Ed. 2011, 50, 11702-11705. Balaraman, E.; Fogler, E.; Milstein, D. Chem. Commun. 2012, 48, 1111-1113. Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W.; Milstein, D. J. Am. Chem. Soc. 2010, 132, 16756-16758. Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840-10841. (B) Chen, T.; Li, H.; Qu, S.; Zheng, B.; He, L.; Lai, 161

Z.; Wang, Z.-X.; Huang, K.-W. Organometallics 2014, 33, 4152-4155. He, L.-P.; Chen, T.; Gong, D.; Lai, Z.; Huang, K.-W. Organometallics 2012, 31, 5208-5211. Zeng, G.; Chen, T.; He, L.; Pinnau, I.; Lai, Z.; Huang, K.-W. Chem. Eur. J. 2012, 18, 15940-15943. Chen, T.; He, L.-P.; Gong, D.; Yang, L.; Miao, X.; Eppinger, J.; Huang, K.-W. Tetrahedron Lett. 2012, 53, 4409-4412. (165) For selected reviews highlighting P=C bonds in coordination chemistry, see: (a) Müller, C.; Broeckx, L. E. E.; de Krom, I.; Weemers, J. J. M. Eur. J. Inorg. Chem. 2013, 187-202. (b) Dugal-Tessier, J.; Conrad, E.; Dake, G. R.; Gates, D. P. In Phosphorus(III) Ligands in Homogenous Catalysis: Design and Synthesis; Kamer, P. C. J., van Leeuwen, P. W. N. M., Eds.; Wiley: Chichester, 2012; Chapter 10. (c) Müller, C.; Vogt, D. Dalton Trans. 2007, 5505-5523. (d) Le Floch, P. Coord. Chem. Rev. 2006, 250, 627-681. (e) Ozawa, F.; Yoshifuji, M. Dalton Trans. 2006, 4987-4995. (f) Weber, L. Angew. Chem. Int. Ed. 2002, 41, 563-572. (166) For recent work highlighting P=C bonds in coordination chemistry, see: (a) Chang, Y.; Tanigawa, I.; Taguchi, H.; Takeuchi, K.; Ozawa, F. Eur. J. Inorg. Chem. 2016, 754-760. (b) Klein, M.; Schnakenburg, G.; Espinosa Ferao, A.; Streubel, R. Dalton Trans. 2016, 45, 2085-2094. (c) Rigo, M.; Sklorz, J. A. W.; Hatje, N.; Noack, F.; Weber, M.; Wiecko, J.; Muller, C. Dalton Trans. 2016, 45, 2218-2226. (d) Magnuson, K. W.; Oshiro, S. M.; Gurr, J. R.; Yoshida, W. Y.; Gembicky, M.; Rheingold, A. L.; Hughes, R. P.; Cain, M. F. Organometallics 2016, 35, 855-859. (e) Masuda, J. D.; Boere, R. T. Dalton Trans. 2016, 45, 2102-2115. (f) Ghalib, M.; Jones, P. G.; Schulzke, C.; Sziebert, D.; Nyulászi, L.; Heinicke, J. W. Inorg. Chem. 2015, 54, 2117-2127. (g) Ueta, Y.; Mikami, K.; Ito, S. Inorg. Chem. 2015, 54, 8778-8785. (h) Greenacre, V. K.; Trathen, N.; Crossley, I. R. Organometallics, 2015, 34, 2533-2542. (i) Takeuchi, K.; Minami, A.; Nakajima, Y.; Ozawa, F. Organometallics 2014, 33, 5365-5370. (j) Broeckx, L. E. E.; Lutz, M.; Vogt, D.; Müller, C. Chem. Commun. 2011, 47, 2003-2005. (167) Doux, M.; Moores, A.; Mézailles, N.; Ricard, L.; Jean, Y.; Floch, P. L. J. Organomet. Chem. 2005, 690, 2407-2415. (168) Jouaiti, A.; Geoffroy, M.; Bernardinelli, G. Tetrahedron Lett. 1992, 33, 5071-5074. (169) Lin, Y.-F.; Ichihara, N.; Nakajima, Y.; Ozawa, F. Organometallics 2014, 33, 6700-6703. (170) Nakajima, Y.; Tsuchimoto, T.; Chang, Y.-H.; Takeuchi, K.; Ozawa, F. Dalton Trans. 2016. (171) Dugal-Tessier, J.; Dake, G. R.; Gates, D. P. Org. Lett. 2010, 12, 4667-4669. (172) Daugulis, O.; Brookhart, M.; White, P. S. Organometallics 2002, 21, 5935-5943. (173) (a) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103, 3119-3154. (b) Evans, D. A.; Fandrick, K. R.; Song, H.; Scheidt, K. A.; Xu, R. J. Am. Chem. Soc. 2007, 129, 10029-10041. (c) Wei, C.; Li, C. J. Am. Chem. Soc. 2002, 124, 5638-5639. (d) Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.; Campos, K. R.; Connell, B. T.; Staples, R. J. J. Am. Chem. Soc. 1999, 121, 669-685. (e) Evans, D. A.; Barnes, D. M.; Johnson, J. S.; Lectka, R.; von Matt, P.; Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E. A.; Campos, K. R. J. Am. Chem. Soc. 1999, 121, 7582-7594. (f) Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K. Organometallics 1991, 10, 500- 508. (174) Ong, W. Q.; Zhao, H.; Du, Z.; Yeh, J. Z. Y.; Ren, C.; Tan, L. Z. W.; Zhang, K.; Zeng, H. Chem. Commun. 2011, 47, 6416-6418. (175) Ito, F.; Ando, S.; Iuchi, M.; Ukari, T.; Takasaki, M.; Yamaguchi, K. Tetrahedron 2011, 67, 8009-8013. (176) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103, 3119-3154. (177) Lipshutz, B. H.; Shimizu, H. Angew. Chem. Int. Ed. 2004, 43, 2228-2230. (178) Lipshutz, B. H.; Noson, K.; Chrisman, W. J. Am. Chem. Soc. 2001, 123, 12917-12918. 162

(179) Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889-5890. (180) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638-5639. (181) Degrado, S. J.; Mizutani, H.; Hoveyda, A. H. J. Am. Chem. Soc. 2001, 123, 755-756. (182) d’Augustin, M.; Palais, L.; Alexakis, A. Angew. Chem. Int. Ed. 2005, 44, 1376-1378. (183) Orthaber, A.; Belaj, F.; Pietschnig, R. Inorg. Chim. Acta 2011, 374, 211-215. (184) Hayashi, A.; Okazaki, M.; Ozawa, F.; Tanaka, R. Organometallics 2007, 26, 5246-5249. (185) Nakajima, Y.; Nakatani, M.; Hayashi, K.; Shiraishi, Y.; Takita, R.; Okazaki, M.; Ozawa, F. New J. Chem. 2010, 34, 1713-1722. (186) Hayashi, K.; Nakatani, M.; Hayashi, A.; Takano, M.; Okazaki, M.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Organometallics 2008, 27, 1970-1972. (187) Bresien, J.; Faust, K.; Schulz, A.; Villinger, A. Angew. Chem. Int. Ed. 2015, 54, 6926- 6930. (188) Irangu, J. K.; Jordan, R. B. Inorg. Chem. 2003, 42, 3934-3942. (189) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. GAUSSIAN 09, Gaussian, Inc., Wallingford, CT, USA, 2009. (190) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623-11627. (191) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652. (192) Lee, C.; Yang, W.; Parr, R. G. Physical Review B 1988, 37, 785-789. (193) Vosko, S. H.; Wilk, L.; Nusair, M. Can. J. Phys. 1980, 58, 1200-1211. (194) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654-3665. (195) Dill, J. D.; Pople, J. A. J. Chem. Phys. 1975, 62, 2921-2923. (196) Schäfer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100, 5829-5835. (197) Johnson, L. K.; Killian, C. M.; Brookhart, M. J. Am. Chem. Soc. 1995, 117, 6414-6415. (198) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009-3066. (199) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174-238. (200) Sen, A. Acc. Chem. Res. 1993, 26, 303-310. (201) Drent, E.; Budzelaar, P. H. M. Chem. Rev. 1996, 96, 663-681. (202) Dghaym, R. D.; Yaccato, K. J.; Arndtsen, B. A. Organometallics 1998, 17, 4-6. (203) Fryzuk, M. D.; Piers, W. E. Organometallics 1990, 9, 986-998. (204) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 11703-11714. (205) van der Sluis, M.; Beverwijk, V.; Termaten, A.; Bickelhaupt, F.; Kooijman, H.; Spek, A. L. Organometallics 1999, 18, 1402-1407.

163

(206) Thirupathi, N.; Amoroso, D.; Bell, A.; Protasiewicz, J. D. Organometallics 2005, 24, 4099- 4102. (207) Jouaiti, A.; Geoffroy, M.; Bernardinelli, G. Chem. Commun. 1996, 437-438. (208) Killian, C. M.; Tempel, D. J.; Johnson, L. K.; Brookhart, M. J. Am. Chem. Soc. 1996, 118, 11664-11665. (209) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840- 10841. (210) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317, 790-792. (211) Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W.; Milstein, D. J. Am. Chem. Soc. 2010, 132, 16756-16758. (212) Knight, L. K.; Freixa, Z.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Organometallics 2006, 25, 954-960. (213) Andersen, T. L.; Friis, S. D.; Audrain, H.; Nordeman, P.; Antoni, G.; Skrydstrup, T. J. Am. Chem. Soc. 2015, 137, 1548-1555. (214) Feller, M.; Ben-Ari, E.; Iron, M. A.; Diskin-Posner, Y.; Leitus, G.; Shimon, L. J. W.; Konstantinovski, L.; Milstein, D. Inorg. Chem. 2010, 49, 1615-1625. (215) van der Sluis, M.; Beverwijk, V.; Termaten, A.; Gavrilova, E.; Bickelhaupt, F.; Kooijman, H.; Veldman, N.; Spek, A. L. Organometallics 1997, 16, 1144-1152.

164