an exploration of the structural and

An Exploration of the Structural,

Electronic, and Anion Binding Properties

of 2-Indolylphosphines

by

Joanne Yu

A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy

Graduate Department of Chemistry

University of Toronto

© Copyright by Joanne Yu 2008

An Exploration of the Structural, Electronic, and Anion

Binding Properties of 2-Indolylphosphines

Joanne Yu Doctor of Philosophy Department of Chemistry University of Toronto 2008

Abstract

2-Indolylphosphines are unique ligands which have the capability for further

phosphine modification by introducing substituents on an indolyl nitrogen centre.

Substituents can vary in electronics, sterics, chirality, and can contain amino or

phosphino groups which result in a multidentate (P,N)- or (P,P)-2-indolylphosphine.

X-ray crystallography was used predominantly to examine and analyze the

structural features of 2-indolyphosphines and their metal complexes. While the cone

angles could not be determined crystallographically, the sum of the <CPC bond angles

provided some information on the steric crowding around a phosphorus atom in selected

2-indolylphosphines.

The symmetric tris-2-(3-methylindolyl)phosphine demonstrated anion binding

ability through its three indolyl NH sites. Titrations to a series of selected anions were

carried out; it was determined that tris-2-(3-methylindolyl)phosphine binds to these

selected anions in a 1 : 1 receptor to anion binding ratio. Crystal structures of the fluoride

and acetate complexes confirm the binding stoichiometry, and demonstrate the

cooperative interaction of all three indolyl NH sites with the anion guest. Synthetic

routes to new anion receptors with three or two indolyl NH donors were explored. The

second type yielded a molecular cleft that was used in anion binding studies.

The net basicity of a 2-indolylphosphine was determined through formation of a

Ni(CO)3L complex. Net basicity can be tuned by changing the substituents on

ii

phosphorus or on an indolyl nitrogen centre. The [Cu(tris-2-(3-

methylindolyl)phosphine)(phenanthroline)]BF4 complex is a discrete ion pair complex,

exhibiting coordination chemistry at the phosphorus centre of the phosphine, while

simultaneously hydrogen bonding through the indolyl NH sites to the BF4- anion.

Complexes of the type [Pd(L)Cl(μ-Cl)]2 were analyzed by crystallography and the effect

of net basicity on Pd-P bond length examined.

The solid-state structures of (P,N)- and (P,P)-2-indolylphosphines were evaluated.

In general, the sum of the <CPC bond angles increased from the parent unfunctionalized

2-indolylphosphine. The metal complexes of (P,N)- and (P,P)-2-indolylphosphines were

assessed by crystallography to find possible trends of trans-influence.

Lastly, a tetradentate tripodal ligand was synthesized by furnishing

diphenylphosphino substituents on the indolyl nitrogen centres of tris-2-(3-

methylindolyl)phosphine. The coordination of the tetradentate tripodal ligand to Pt(II) or

Rh(I) resulted in five-coordinate trigonal bipyramidal complexes.

iii

Acknowledgments

I would like to thank my advisor Prof. David H. Farrar, first and foremost, for

presenting me an opportunity to learn in a relatively un-structured, and therefore,

independent environment. Thank you for making the time to provide guidance and

criticism, yet allowing me the freedom to find my own way. Dave your dedication to life

outside the walls of academia and gift of positivity are truly inspiring. I would also like

to thank my co-advisor Dr. C. Scott Browning; I would not have been able to string the

story of my research together so eloquently without his valuable input. Scott you are a

talented instructor and your enthusiasm for teaching has been instrumental for me – not

only observing as a student, but observing as an instructor myself.

A warm thank you to my PhD committee: Professors Anthony J. Poë and Robert

H. Morris; and Professors Stephen J. Loeb and Douglas W. Stephan for serving as my

external examiners. I am grateful to you all for investing the time into assessing my work,

and providing helpful feedback.

I owe a great deal of gratitude to Dr. Alan J. Lough for teaching me the

techniques of X-ray crystallography. Alan your wealth of knowledge and expertise in

this field is above and beyond admirable. I appreciate all the times you would let me cut

the queue to run my own samples and answer all of my questions, no matter how simple

they were. I hope I can take the skills that you have taught me and be successful on my

own. I’d also like to thank Dr. Timothy Burrow for all of his NMR advice.

I would especially like to thank the past members of the Farrar group, first for

being superb friends, and second for providing crystalline compounds for my analysis.

The particulars: Dr. Edmond Lam for taking the time to read my thesis and providing

non-stop encouragement; Trisha Ang for being an excellent labmate and conference

buddy; Mengxin Zhao for her infectious happiness and knowledge of phosphine

synthesis; Amina Mulani and Megan Oh for being great labmates; and Dr. Claudia Babij

Krywiak for her wise words. And to the honorary members of the Farrar group: Brian

Mariampillai for his unwavering friendship and support, and for lending me chemicals;

Dr. Alan Hadzovic for his astounding wealth of knowledge and always providing a

shoulder.

iv

Without my family and friends I would not be where I am today. I am indebted to

Mom, Andy, and Allen for their unconditional love, support, and encouragement. I

would not have the courage to see this through without Hiro, you are my constant.

For Shing Chung Yu

v

Wabi-sabi – imperfect and incomplete.

vi

Table of Contents

Abstract ii

Acknowledgments iv

Table of Contents vii

List of Tables xi

List of Figures xiv

List of Schemes xix

List of Compounds xxii

List of Abbreviations xxxii

Chapter 1 Introduction 1

1.1. Tertiary Phosphine Ligands 1

1.1.1 Determining Steric Profiles of Phosphine Molecules 2

1.1.2. Determining Phosphine Ligand Basicity 3

1.1.3. The Utility of Phosphine Ligands 4

1.2. N-Heterocyclic Phosphine Ligands 6

1.3. Reactivity at Indole Nitrogen 8

1.4. 2-Indolylphosphine Ligands 10

1.5. Synthetic Anion Receptors 12

1.6. Scope of the Thesis 17

1.7 References 19

Chapter 2 Monodentate 2-Indolylphosphines: A Study in Structure by X-ray

Crystallography

24

2.1 Introduction 24

2.1.1. Crystallographic Analysis of Common Phosphines in the CSD 25

2.1.2. Crystallographic Analysis of Indole-Containing Structures in the CSD 29

vii

2.2 Results and Discussion 30

2.2.1. Synthesis of Unsubstituted 2-Indolylphosphines 30

2.2.2. X-ray Crystallographic Analysis of Unsubstituted 2-Indolylphosphines 31

2.2.3. Synthesis of Monodentate N-Alkylated 2-Indolylphosphines 40

2.2.4. Crystallographic Analysis of N-Alkylated 2-Indolylphosphines 41

2.3. Examining the Σ{<CPC} of 2-Indolylphosphines 45

2.3.1. Examining Indolyl Aromaticity in 2-Indolylphosphines 48

2.4. Conclusions 50

2.5. Experimental 51

2.6. References 54

Chapter 3 Tris-2-(3-methylindolyl)phosphine: Synthesis, Reactivity and Anion

Binding 55

3.1. Introduction 55

3.1.1. Hydrogen Bonding in 2-Indolylphosphines 56

3.2 Results and Discussion 57

3.2.1. Synthesis of Tris-2-(3-methylindolyl)phosphine 57

3.2.2. Anion Binding Properties of Tris-2-(3-methylindolyl)phosphine 59

3.3. Design of a New C3-Symmetric Anion Receptor 73

3.3.1. Synthesis of New C3-Symmetric Anion Receptor 75

3.3.2. Design of a New Diindolyl-Based Anion Receptor 81

3.3.3. Synthesis of New Diindolyl-Based Anion Receptor 82

3.3.4. Anion Binding Studies of Molecular Cleft 18 85

3.4. Conclusions 88


3.6. References 101

viii

Chapter 4 Coordination Chemistry of Monodentate 2-Indolylphosphines 104


4.2. Results and Discussion 105

4.2.1. An Evaluation of 2-Indolylphosphine Net-Basicity: Coordination to

Ni(CO)3

105

4.2.2. [5·X]- Complexes: Simultaneous Coordination at Phosphorus with

Ni(II)

108

4.2.3. [5·Anion]- Complexes: Simultaneous Coordination at Phosphorus

with Cu(I)

110

4.3. Pd(II) and Pt(II) Complexes of Monodentate 2-Indolylphosphines 116

4.3.1. X-ray Crystallographic Analysis of Pd(II) and Pt(II) Complexes of

Monodentate 2-Indolylphosphines

118

4.3.2. Examining the Effect of Phosphine Net-Basicity on Pd(II)-P Bond

Lengths

128

4.3.3. The Effect of Metal Coordination on the Σ{<CPC} of Monodentate 2-

Indolylphosphines

129

4.3.4. The Effect of Metal Coordination on Indolyl Aromaticity 131

4.4. Conclusions 132


4.6. References 137

Chapter 5 Multidentate N-Functionalized 2-Indolylphosphines and their Metal

Complexes

138


5.1.1. Bidentate (P,N)- and (P,P)-Ligands 138

5.1.2. Symmetric Tetradentate Ligand PP3 and Its Reactivity 139

5.2. Results and Discussion 140

5.2.1. Synthesis of Multidentate 2-Indolylphosphines 140

ix

5.2.2. X-ray Crystallographic Analysis of (P,N)- and (P,P)-2-

Indolylphosphines

142

5.2.3. The Effect of N-Functionalization on the Σ{<CPC} of (P,N)-and

(P,P)-2-Indolylphosphines

150

5.2.4. The Effect of N-Functionalization on Indolyl Aromaticity of (P,N)-

and (P,P)-2-Indolylphosphines

153

5.3. Pd(II) Complexes of (P,N)-2-Indolylphosphines 153

5.3.1. X-ray Crystallographic Analysis of Pd(II) and Pt(II) Complexes of

(P,N)-2-Indolylphosphines

155

5.3.2. X-ray Crystallographic Analysis of Pd(II) Complexes of (P,P)-2-

Indolylphosphines

162

5.4. Examining Trans-Influence Properties of (P,N)- and (P,P)-2-Indolylphosphines 168

5.5. Synthesis and Characterization of Multidentate N-Functionalized Ligands based

on Phosphine 5

171

5.5.1. X-ray Crystallographic Analysis of Metal Complexes of (N-PPh2)3-5 175

5.5.2. The Reactivity of [PtCl(N-PPh2)3-5]BF4 and [RhCl(N-PPh2)3-5] 180

5.6. Metal Coordination on the Σ{<CPC} of (P,N)- and (P,P)-2-Indolylphosphines 182

5.6.1. The Effect of Metal Coordination on Indolyl Aromaticity of

Multidentate 2-Indolylphosphines

184

5.7. Conclusions 185


5.9. References 191

Chapter 6 - Conclusion 193

x

List of Tables

Chapter 1 Introduction Table 1.1. The variation in geometry of some common anions. 12 Chapter 2 Monodentate 2-Indolylphosphines: A Study in Structure by X-ray

Crystallography Table 2.1. Summary of computed average cone angles of selected common

phosphines. 27

Table 2.2. X-ray diffraction data from the CSD for PPh3, PCy3, and PtBu3. 27 Table 2.3. Selected averaged bond distances (Å) and bond angles (o) of indole-

based structures from the CSD. 29

Table 2.4. X-ray crystallographic experimental data of unsubstituted 2-

indolylphosphines. 32

Table 2.5. Selected bond lengths (Å) and bond angles (o) for unsubstituted 2-


Table 2.6. X-ray crystallographic experimental data of N-alkylated monodentate 2-


Table 2.7. Selected bond lengths (Å) and bond angles (o) for N-alkylated 2-


Table 2.8. Sum of <CPC bond angles (o) and 31P (ppm) resonances for

unfunctionalized and alkylated 2-indolylphosphines 46

Chapter 3 Tris-2-(3-methylindolyl)phosphine: Synthesis, Reactivity and Anion

Binding Table 3.1. Stability constants Ka (M-1) of 5 with a selection of anion guests as

determined by 1H NMR titration techniques performed at 298 K following NH resonances in 5.

62

Table 3.2. X-ray crystallographic experimental data of [5·X]- complexes. 67 Table 3.3. Selected bond lengths (Å) and bond angles (o) for [5.X]- complexes. 71

xi

Table 3.4. Stability constants Ka (M-1) of Pfeffer’s indole-based short receptor and indole-based long receptor with chloride and acetate guests as determined by 1H NMR titration techniques performed at 298 K.

74

Table 3.5. Stability constants Ka (M-1) of Chang’s indole-based macrocycle and

indole-based molecular cleft with a selection of anion guests as determined by spectroscopic titration techniques performed at 298 K.

82

Table 3.6. X-ray crystallographic experimental data of molecular cleft 18. 84 Table 3.7. Selected bond lengths (Å) and angles (o) for molecular cleft 18. 85 Table 3.8. Stability constants Ka (M-1) of 18 and 19 with a selection of anion guests

as determined by 1H NMR titration techniques performed at 298 K , following the indolyl NH resonances.

86

Table 3.9. Stability constants Ka (M-1) of Sessler’s diindolylquinoxaline-based

anion receptors with a selection of anion guests as determined by UV-visible spectroscopic titration techniques performed at 298 K in CH2Cl2.

88

Chapter 4 Coordination Chemistry of Monodentate 2-Indolylphosphines Table 4.1. Infrared CO stretching frequencies of Ni(CO)3L in heptanes. 106 Table 4.2. Infrared CO stretching frequencies of [Ni(CO)3(5·X)]- in heptanes. 109 Table 4.3. X-ray crystallographic experimental data for complexes: 23, 24, and 25. 112 Table 4.4. Selected bond lengths (Å) and bond angles (o) for complex 23. 114 Table 4.5. X-ray crystallographic experimental data for complexes: 26, 27, and 28. 118 Table 4.6. Selected bond lengths (Å) and bond angles (o) for complexes 24 and 25. 120 Table 4.7. Selected bond lengths (Å) and bond angles (o) for complexes 26, 27, and

28. 123


monodentate 2-indolylphosphine metal complexes. 130

xii

Chapter 5 Multidentate N-Functionalized 2-Indolylphosphines and their Metal Complexes

Table 5.1. X-ray crystallographic experimental data for (P,N)- and (P,P)-2-


Table 5.2. Selected bond lengths (Å) and bond angles (o) for (P,N)- and (P,P)-2-



uncomplexed multidentate 2-indolylphosphines. 150

Table 5.4. X-ray crystallographic experimental data for Pd(II) and Pt(II) complexes

of (P,N)-2-indolylphosphines. 155

Table 5.5. Selected bond lengths (Å) and bond angles (o) for Pd(II) and Pt(II)

complexes of (P,N)-2-indolylphosphines. 157

Table 5.6. X-ray crystallographic experimental data for Pd(II) complexes of (P,P)-

2-indolylphosphines. 162

Table 5.7. Selected bond lengths (Å) and bond angles (o) for Pd(II) complexes of

(P,P)-2-indolylphosphines. 163

Table 5.8. Increasing order of Pd(II)-Cl bond length that is trans to the phosphine

in Pd(II) complexes of (P,N)-2-indolylphosphines. 168

Table 5.9. Increasing order of Pd(II)-Cl bond length that is trans to the phosphine

in Pd(II) complexes of (P,P)-2-indolylphosphines. 170

Table 5.10. 31P NMR resonances of phosphine 5 and (N-PPh2)3-5 recorded in

CDCl3. 172

Table 5.11. 31P NMR resonances of metal complexes of (N-PPh2)3-5 recorded in

DMSO-d6. 174

Table 5.12. X-ray crystallographic experimental data for complexes 37 and 38. 176 Table 5.13. Selected bond lengths (Å) and bond angles (o) for complexes 37 and 38. 177 Table 5.14. Sum of <CPC bond angles (o) and 31P (ppm) resonances for metal

complexes of multidentate 2-indolylphosphines. 183

xiii

List of Figures

Chapter 1 Introduction Figure 1.1. A basic schematic illustrating the orbitals involved in PH3 bonding to a

generic transition metal, M. 1

Figure 1.2. Method of measuring cone angles for unsymmetrical ligands. 2 Figure 1.3. Early examples of chelating bisphosphines. (a) DIOP (b) DIPAMP, (c)

and BINAP ligands. 5

Figure 1.4. Chiral bidentate (P,N)-ligands: (a) (S)-PHOX ligand, and (b) (R,R)-

nBu-QUINAPHOS. 5

Figure 1.5. N-Heterocyclic phosphine ligands (a) diphenyl(2-pyridyl)phosphine

and (b) diphenyl(2-pyrrolyl)phosphine. 6

Figure 1.6. The numbering scheme of indole. 7 Figure 1.7. N-Phosphination of indole examples: (a) tri(N-3-

methylindolyl)phosphine, and (b) and phosphatri(3-methylindolyl)methane.

9

Figure 1.8. N-metallation of indole examples: (a) (η5-C5H5)Re(NO)(PPh3)(η1-

C8H6N), and (b) (κ1-N-C10H10)2Sm(THF)4. 10

Figure 1.9. Positively charged anion receptors (a) polyammonium tren-based

receptor, and (b) tetrapyridinium macrocycle. 13

Figure 1.10. Metal complex-based anion receptor that functions with both hydrogen

bond donors on the ligand and electrostatic interactions on the metal. 14

Figure 1.11. Examples of neutral anion receptors: (a) amide-based, (b) pyrrole-

based and (c) urea-based. 15

Figure 1.12. Example of an indole-based anion receptor with additional hydrogen

bond donors at the 2- and 7-positions on indole. 15

Figure 1.13. An example of metal coordinated phosphine-based anion receptor. 16

xiv

Chapter 2 Monodentate 2-Indolylphosphines: A Study in Structure by X-ray Crystallography

Figure 2.1. Description of the van der Waals surface of a phosphine ligand to

determine the Tolman cone angle from crystallographic data. 26

Figure 2.2. Selected monodentate unsubstituted 2-indolylphosphines. 31 Figure 2.3. Unit cell diagram of the four molecules of 1. 33 Figure 2.4. Numbering scheme of 1a in unit cell. 34 Figure 2.5. Numbering scheme of 2 in unit cell. 36 Figure 2.6. Numbering scheme of 3. 38 Figure 2.7. Numbering scheme of 5. 39 Figure 2.8. Selected N-alkylated 2-indolylphosphines for crystallographic

analysis: (N-Bn)-1 and (N-F5Bn)2-4. 40

Figure 2.9. Numbering scheme of (N-Bn)-1. 43 Figure 2.10. Numbering scheme of (N-F5Bn)2-4. 44 Chapter 3 Tris-2-(3-methylindolyl)phosphine: Synthesis, Reactivity and Anion

Binding Figure 3.1. Hydrogen bonding in the [Pd(1)Cl(μ-Cl)]2 and [Pd(4)Cl(μ-Cl)]2

complexes. 56

Figure 3.2. Bowl shaped hydrogen bonding cavity of 5. 59 Figure 3.3. A representative example of partial titration stack plots for the

addition of Cl- anion to 5. 61

Figure 3.4. Fit plot for titration experiment of 5 with tetrabutylammonium

chloride in CD2Cl2. 62

Figure 3.5. Sessler and co-workers’ diindolylquinoxaline-based anion receptors. 63 Figure 3.6. ORTEP diagram of one of the two independent sets of molecules in

the asymmetric unit of complex 6 with concomitant uncomplexed 5. 64

Figure 3.7. ORTEP diagram illustrating the hydrogen bonding in complex 6. 65

xv

Figure 3.8. ORTEP diagram of 7. 68 Figure 3.9. ORTEP diagram of symmetric dimer of 8 in the crystallographic ab-

plane. 72

Figure 3.10. Flexible indole-based anion receptors by Pfeffer and co-workers. 73 Figure 3.11. (a) New C3-symmetric 5-based anion receptor target, P(C9H8N)3, 9.

(b) Model phosphine P(C9H8N)(C6H5)2, 10. 75

Figure 3.12. Indole-based anion receptors by Chang and co-workers. 81 Figure 3.13. ORTEP diagram of 18. 83 Figure 3.14. A representative of partial stack plots of 18 titrations with Cl- in

CD2Cl2 at 298 K. 86


chloride in CD2Cl2. 87


bromide in CD2Cl2. 95

Figure 3.17. Fit plot for titration experiment of 5 with tetrabutylammonium iodide

in CD2Cl2. 96

Figure 3.18. Fit plot for titration experiment of 5 with tetrabutylammonium acetate

in CD2Cl2. 96


hydrogensulfate in CD2Cl2. 97

Figure 3.20. Fit plot for titration experiment of 5 with tetrabutylammonium nitrate

in CD2Cl2. 97


tetrafluoroborate in CD2Cl2. 98


bromide in CD2Cl2. 98


acetate in CD2Cl2. 99


hydrogensulfate in CD2Cl2. 99

xvi

Figure 3.25. Fit plot for titration experiment of 18 with tetrabutylammonium nitrate in CD2Cl2.

100


tetrafluoroborate in CD2Cl2. 100

Chapter 4 Coordination Chemistry of Monodentate 2-Indolylphosphines Figure 4.1. The ORTEP diagram and numbering scheme of [Cu(5)(phen)]BF4, 23. 113 Figure 4.2. The unit cell diagram of [Cu(5)(phen)]+, viewing along the

crystallographic c-face. 115

Figure 4.3. Metal complexes of monodentate 2-indolylphosphines 117 Figure 4.4. The ORTEP diagram and numbering scheme of 24. 119 Figure 4.5. The ORTEP diagram and numbering scheme of 25. 121 Figure 4.6. The ORTEP diagram and numbering scheme of 26. 122 Figure 4.7. The ORTEP diagram and numbering scheme of 27. 124 Figure 4.8. Extended hydrogen bonding network of 27 along the crystallographic

a-axis. 125

Figure 4.9. The ORTEP diagram and numbering scheme of 28. 126 Figure 4.10. The varied intra- and intermolecular hydrogen bonding of 28. 127 Chapter 5 Multidentate N-Functionalized 2-Indolylphosphines and their Metal

Complexes Figure 5.1. (a) Tris(2-(diphenylphosphino)ethyl)phosphine, PP3. (b) A generic

metal complex of PP3 exhibiting trigonal bipyramidal coordination geometry enforced by the PP3 ligand.

139

Figure 5.2. The multidentate 2-indolylphosphines that will be structurally

characterized with X-ray crystallography: (a) (N-CH2NMe2)-20 (b) (N-CH2NMe2)2-4 (c) (N-PCy2)-1 (d) 29.

142

Figure 5.3. ORTEP diagram and numbering scheme of (N-CH2NMe2)2-20. 145 Figure 5.4. ORTEP diagram and numbering scheme of (N-CH2NMe2)2-4. 146

xvii

Figure 5.5. ORTEP diagram and numbering scheme of (N-PCy2)-1. 147 Figure 5.6. ORTEP diagram and numbering scheme of 29. 149 Figure 5.7. The selected metal complexes of (P,N)-2-indolylphosphines to be

assessed by X-ray crystallography: (a) 30 (b) 31 (c) 32 (d) 33. The selected Pd(II) complexes of (P,P)-2-indolylphosphines to be analyzed by X-ray crystallography: (e) 34 (f) 35 (g) 36.

154

Figure 5.8. ORTEP diagram and numbering scheme of 30. 156 Figure 5.9. ORTEP diagram and numbering scheme of 31. 158 Figure 5.10. ORTEP diagram and numbering scheme of 32. 159 Figure 5.11. ORTEP diagram and numbering scheme of 33. 161 Figure 5.12. Brown and co-workers demonstrate absence of axial chirality in 1-

methyl-2-diphenylphosphino-3-(1’-isoquinolyl)indole upon coordination to a chiral Pd(II) complex.

161

Figure 5.13. ORTEP diagram and numbering scheme of 34. 164 Figure 5.14. ORTEP diagram and numbering schemes of the two independent

molecules of 35 in the asymmetric unit. 166

Figure 5.15. ORTEP diagram and numbering scheme of complex 36. 167 Figure 5.16. Ciclosi and co-workers’ example of an indolyl-based C3-symmetric

ligand, CP3, that binds to Pd(II). 172

Figure 5.17. ORTEP diagram and numbering scheme of complex 37. 178 Figure 5.18. ORTEP diagram and numbering scheme of complex 38. 179

xviii

List of Schemes

Chapter 1 Introduction Scheme 1.1. Examples of reactivity at the nitrogen centre of indole: (a) N-

alkylation, (b) N-arylation, (c) N-phosphination, and (d) N-metallation.

8

Scheme 1.2. Reactivity at the 1- and 3-positions of indole to form tris(3-methyl-

1H-indol-1-yl)phosphine. 9

Scheme 1.3. Synthesis of 2,2’-bis-diphenylphosphino[3,3’]biindolyl. 11 Scheme 1.4. General reaction scheme for the synthesis of 2-indolylphosphine

ligands 11

Chapter 2 Monodentate 2-Indolylphosphines: A Study in Structure by X-ray

Crystallography Scheme 2.1. A general scheme demonstrating the aufbau assembly of N-

substituted 2-indolylphosphines. 24

Scheme 2.2. The synthesis of phosphine 1 from the commercially available 3-

methylindole. 30

Scheme 2.3. The synthesis of (N-Bn)-1. 40 Chapter 3 Tris-2-(3-methylindolyl)phosphine: Synthesis, Reactivity and Anion

Binding Scheme 3.1. The synthesis of 5 from the aminal-protected 3-methylindole. 58 Scheme 3.2. The synthesis of 5 from 3-methylindole with CO2 as a protecting

group for the indole nitrogen. 59

Scheme 3.3. General titration scheme of 5 with anions as their

tetrabutylammonium salts in CD2Cl2. 60

Scheme 3.4. Reaction scheme to form 8 from 5 and CH3I. 69 Scheme 3.5. The two unsuccessful methods used to install the N,N’-

dimethylaminomethylene protecting group on the nitrogen centre of 11.

76

xix

Scheme 3.6. Reaction scheme of t-Boc-protected indole-2-carboxylic acid ethyl ester, 12, to the t-Boc-protected indole-2-methyl alcohol, 13.

77

Scheme 3.7. Reaction scheme of Cbz-protected indole-2-carboxylic acid ethyl

ester, 14, to the Cbz-protected indole-2-methyl bromide, 16. 78

Scheme 3.8. Attempted synthesis of Cbz-protected 10 from 16 using n-BuLi and

PPh2Cl. 79

Scheme 3.9. Attempted synthesis of Cbz-protected 10 from 16 through Grignard

reagent and PPh2Cl. 79

Scheme 3.10. Attempted synthesis of Cbz-protected 10 from 16 using a

Ni(dppe)Cl2 catalyst in the presence of Zn and PPh2Cl. 80

Scheme 3.11. Synthesis of 4-tert-butyl-7-(4-(4-tert-butyl-1H-indol-7-yl)phenyl)-

1H-indole, 18, from 1-bromo-4-tert-butylbenzene. 83

Scheme 3.12. General titration scheme of 18 and selected anions as their

tetrabutylammonium salts in CD2Cl2. 85

Scheme 3.13. Proposed mode of acetate interaction with molecular cleft 18. 87 Chapter 4 Coordination Chemistry of Monodentate 2-Indolylphosphines Scheme 4.1. General scheme for the formation of a monodentate

Ni(CO)3(phosphine) complex. 105

Scheme 4.2. General scheme for the formation of a monodentate

[NEt4][Ni(CO)3(5·X)] complex. X = F-, Cl-, Br-. 108

Scheme 4.3. Anticipated four-coordinate tetrahedral Cu(I) complex in the

reaction of 5 (2 eq), phen , and [Cu(MeCN)4]BF4. 110

Scheme 4.4. Three coordinate trigonal planar Cu(I) complex, 23, yielded from

reaction of 5 (2 eq), phen, and [Cu(MeCN)4]BF4. 111

Scheme 4.5. Reaction scheme for the formation of [Pd(1)Cl(μ-Cl)]2, 24. 116 Scheme 4.6. Reaction scheme for the formation of cis-Pt(3)2Cl2, 28. 117

xx

Chapter 5 Multidentate N-Functionalized 2-Indolylphosphines and their Metal Complexes

Scheme 5.1. General reaction sequence to generate CH2NMe2-functionalized 2-


Scheme 5.2. Reaction scheme for the synthesis of pyridyl-functionalized (N-

py)-1. 140

Scheme 5.3. Reaction scheme for the synthesis of isoquinoline-functionalized

(N-isoquin)-1. 141

Scheme 5.4. General reaction scheme to generate phosphorus-functionalized 2-


Scheme 5.5. Reaction scheme for the synthesis of diphosphine, 29. 142 Scheme 5.6. The reaction sequence for the synthesis of complex 30. 154 Scheme 5.7. General reaction scheme for the synthesis of multidentate

phosphine ligand (N-PPh2)3-5. 171

Scheme 5.8. Reaction schemes for the synthesis of metal coordinated (N-

PPh2)3-5 complexes. (a) [PtCl(N-PPh2)3-5]BPh4, 37. (b) [RhCl(N-PPh2)3-5], 38.

173

Scheme 5.9. The attempted synthesis of [PtH(N-PPh2)3-5]BPh4 by reaction of

complex 37 and NaBH4. 180

Scheme 5.10. The attempted SnCl2 insertion into the Pt(II)-Cl bond of complex

37. 181

Scheme 5.11. The attempted metathesis of the chloro ligand in complex 38 for

either a methyl or phenyl ligand. 181

xxi

List of Compounds

Compound Number

HN

P

1 P(C9H8N)(C6H5)2

*

HN

P

2 P(C9H8N)(C6H11)2

*

NH

PHN

3 P(C9H8N)2(C6H5)*

HN

PNH

4 P(C17H12N2)(C6H5)*

HN

PNH

HN

5 P(C9H8N)3

* Refer to Dr. Edmond Lam’s PhD thesis (University of Toronto, 2007) for synthetic protocol.

xxii

NP

(N-Bn)-1 P(C9H8NC7H7)(C6H5)2

*

NP

N

F

FF

FF

F F

F

FF

(N-F5Bn)2-4 P(C17H12N2C14H4F10)(C6H5) *

P

HN

3

O

NEt4

O

6 [NEt4][P(C9H8N)3

.(CH3COO)]

P

HN

3

F

NEt4

7 [NEt4][P(C9H8N)3

.F]

P

HN

3

I

NEt4

8 [CH3P(C9H8N)3]I


xxiii

HN

HN

NHP

9 P(C9H8N)3

HN

P

10 P(C9H8N)(C6H5)2

HN

OEt

O

11 1H-indole-2-carboxylic acid ethyl ester

N

OEt

O

O O

12 tert-butyl ethyl 1H-indole-1,2-dicarboxylate

N

OH

O O

13 tert-butyl 2-(hydroxymethyl)-1H-indole-1-carboxylate

N

OEt

O

OO

14 benzyl ethyl 1H-indole-1,2-dicarboxylate

xxiv

N

OH

OO

15 benzyl 2-(hydroxymethyl)-1H-indole-1-carboxylate

N

Br

OO

16 benzyl 2-(bromomethyl)-1H-indole-1-carboxylate

HN

Br

17 4-tert-butyl-7-bromoindole

NH HN

18 4-tert-butyl-7-(4-(4-tert-butyl-1H-indol-7-yl)phenyl)-1H-indole

NH HN

19 7-(4-(1H-indol-7-yl)phenyl)-1H-indole **

HN

P

20 P(C9H8N)(C4H9)2

*

NP

(N-Me)-1 P(C10H10N)(C6H5)2

*

** Refer to M. Trisha C. Ang’s MSc thesis (University of Toronto, 2007) for synthetic protocol. * Refer to Dr. Edmond Lam’s PhD thesis (University of Toronto, 2007) for synthetic protocol.

xxv

P

HN

3

Cl

NEt4

21 [NEt4][P(C9H8N)3

.Cl]

P

HN

3

Br

NEt4

22 [NEt4][P(C9H8N)3

.Br]

CuN

N

P

HNHN

HN BF4

23 {Cu[P(C9H8N)3](phen)}BF4

NH

PPd

Cl

ClCl

HN

PPd

Cl

24 {Pd[P(C9H8N)(C6H5)2]Cl(μ-Cl)}2

*

NH

PPd

Cl

ClCl

HN

PPd

Cl

25 {Pd[P(C9H8N)(C6H11)2]Cl(μ-Cl)}2

*


xxvi

NH

PPd

Cl

ClCl

HN

PPd

ClHN N

H

26 {Pd[P(C9H8N)2(C6H5)]Cl(μ-Cl)}2

*

NHP

PdCl

ClClPd

ClNH

HNP H

N

27 {Pd[P(C17H12N2)(C6H5)]Cl(μ-Cl)}2

*

HN

PPt

ClCl

HN

NH

P HN

28 cis-Pt[P(C9H8N)2(C6H5)]Cl2

NP

N

(N-CH2NMe2)-20 P(C12H15N2)(C4H9)2

*

NP

N

N N

(N-CH2NMe2)2-4 P(C23H26N4)(C6H5)*


xxvii

NP

N

(N-py)-1 P(C14H11N2)(C6H5)2

*

NP

N

(N-isoquin)-1 P(C18H13N2)(C6H5)2

*

NP

P

(N-PPh2)-1 P(C9H7NP(C6H5)2)(C6H5)2

*

NP

P

(N-PCy2)-1 P(C9H7NP(C6H11)2)(C6H5)2

*

NP

PO O

(N-(R)-BINO)-1 P(C9H7NP(O2C20H12))(C6H5)2

*


xxviii

HN

P

P

HN

NH

NH

29 [P(C18H16N2)(CH2)]2

NP

NPd

Cl

Cl

30 [PdCl2P(C12H15N2)(C6H5)2

]*

NP

NPt

Cl

Cl

31 [PtCl2P(C12H15N2)(C6H5)2]

NP

NPd

Cl

Cl

32 [PdCl2P(C14H11N2)(C6H5)2] *

NP

NPd

Cl

Cl

33 [PdCl2P(C18H13N2)(C6H5)2]*


xxix

NP

PPd Cl

Cl

34 [PdCl2P(C9H7NP(C6H5)2)(C6H5)2]*

NP

PPd Cl

Cl

35 [PdCl2P(C9H7NP(C6H11)2)(C6H5)2]*

NP

Pd Cl

ClOO P

36 [PdCl2P(C9H7NP(O2C20H12))(C6H5)2]*

NP

N

N

PPh2

PPh2

PPh2

(N-PPh2)3-5 P[C9H7NP(C6H5)2]3

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

37 {PtClP[C9H7NP(C6H5)2]3}BF4


xxx

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

38 {RhClP[C9H7NP(C6H5)2]3}

xxxi

List of Abbreviations

Å angstroms

BF4- tetrafluoroborate

BINAP 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl

BnBr benzyl bromide

Boc2O di-tert-butyl dicarbonate

t-Boc tert-butoxycarbonyl

BPh4- tetraphenylborate

br broad tBu tert-butyl

Bu n-butyl

bpy 2,2’-bipyridine

Br- bromide 13C NMR carbon-13 nuclear magnetic resonance spectrometry

Cbz carbobenzyloxy

CbzCl carbobenzyloxy chloride

CDCl3 deuterated chloroform

CD2Cl2 deuterated dichloromethane

CHCl3 chloroform

CH2Cl2 dichloromethane

CH3COO- acetate

Cl- chloride

COD 1,5-cyclooctadiene

CP3 tris(3-methyl-1-(diphenylphosphino)-1H-indol-2-yl)methane

CSD Cambridge Structural Database

Cy cyclohexyl oC degrees Centigrade

δ chemical shift

Δ reflux

d doublet

xxxii

dd doublet of doublets

DIBAL-H diisobutylaluminum hydride

DMAP 4-dimethylaminopyridine

DMSO dimethylsulfoxide

DMSO-d6 deuterated dimethylsulfoxide

dppe 1,2-bis(diphenylphosphino)ethane

e- electron

ee enantiomeric excess

EI-MS electron impact mass spectrometry

Et ethyl

Et2O diethyl ether

EtOAc ethyl acetate

EtOH ethanol

F- fluoride

g gram

h hour 1H NMR proton nuclear magnetic resonance spectrometry

H3PO4 phosphoric acid

HCl hydrochloric acid

HNO3 nitric acid

HRMS high resolution mass spectrometry

HSO3- hydrogen sulfate

Hz hertz

I- iodide

IR infrared spectroscopy

L litre

M molar

m multiplet

m.p. melting point

Me methyl

MeCN acetonitrile

xxxiii

MeI methyl iodide

MeOH methanol

MgSO4 magnesium sulfate

MHz megahertz

μmol micromole

μL microlitre

mL mililitre

mmol milimole

mol mole

NaBH4 sodium borohydride

Na2SO4 sodium sulfate

NaH sodium hydride

NaHCO3 sodium bicarbonate

NBu4 tetrabutylammonium

NEt4 tetraethylammonium

NH4Cl ammonium chloride

NMR nuclear magnetic resonance

NO3- nitrate

O=PCl3 phosphorus oxychloride

O=PCy3 tricyclohexylphosphine oxide

O=PPh3 triphenylphosphine oxide

OAc- acetate

ORTEP Oak Ridge Thermal Ellipsoids Plot 31P NMR phosphorus nuclear magnetic resonance spectrometry

P(tBu)3 tri-tert-butylphosphine

PCl3 trichlorophosphine

PCy3 tricyclohexylphosphine

Ph phenyl

P(o-tol)3 tri-ortho-tolylphosphine

PP3 tris(2-(diphenylphosphino)ethyl)phosphine

PPh2Cl chlorodiphenylphosphine

xxxiv

xxxv

PPh3 triphenylphosphine

ppm parts per million

phen 1,10-phenanthroline

q quartet

QUINAP 1-(2-diphenylphosphino-1-naphthyl)isoquinoline

rms root mean squared

rt room temperature

s singlet

satd. saturated

SiMe4 tetramethylsilane

t triplet

TBSCl tert-butyldimethylsilyl chloride

THF tetrahydrofuran

TLC thin layer chromatography

TMS tetramethylsilane

v/v volume / volume

X- halide

Chapter 1

Introduction

1.1. Tertiary Phosphine Ligands

Tertiary phosphines, PR3, are recognized as a class of important ligands for

coordination chemistry as they are excellent 2-electron neutral donor ligands that have

the potential for steric and electronic adjustments. Phosphine ligands primarily function

as σ-donors via the phosphorus lone pair, but can also behave as π-acceptors through the

P-R σ*-antibonding orbitals.1-3 Because of this dual property, phosphine ligands can

effectively stabilize transition metals of low oxidation states. A fundamental scheme of

the orbitals involved in the bonding of PH3 with a generic metal centre is illustrated in

Figure 1.1.

HH

P

H

HH

P

HM

(a) (b)

M

Figure 1.1. A basic schematic illustrating the orbitals involved in PH3 bonding to a generic transition

metal, M. (a) σ-Donation from the phosphine to an empty d-orbital of a metal. (b) π-Acceptance into the

σ*-antibonding orbitals of the phosphine from the appropriate occupied d-orbitals of the metal.

Changing the R-substituents on PR3, can lead to several results: an

increase / decrease in the σ-donicity or π-acidity of the phosphine molecule, and / or

large variations in the steric profile of the phosphine ligand. Their utility in catalysis has

led to the development of numerous examples of phosphine molecules that have

properties ranging in sterics and basicities.4,5 There is continuing interest to improve

1

2

phosphine-mediated catalysis, which also requires the modification or tailoring of

phosphine ligands to incorporate additional functional groups. The steric bulk and

electron-donating ability of a phosphine ligand are difficult properties to quantify

exclusively since both properties are closely related.6,7

1.1.1. Determining Steric Profiles of Phosphine Molecules

Tolman suggested that a geometrical cone angle could be utilized as a description

of a ligand’s steric size.6 This parameter is estimated from idealized space-filling CPK

models and requires the van der Waals surface of the phosphine to be known, particularly

the surface generated by the tangential hydrogen atoms. The cone angle for PR3 is

defined as the vertex of a cylindrical cone, situated 2.28 Å from the centre of the

phosphorus atom, which diverges outwards toward the R groups and borders the van der

Waals radii of the peripheral atoms (Figure 1.2). This model can be used to estimate

cone angles for unsymmetrical phosphines PR1R2R3 by minimizing the sum of the half-

angles θi of each R substituent (Equation 1.1).

Figure 1.2. Method of measuring cone angles for unsymmetrical ligands.6

3

Θ = 2/3 Σ θi/23

i=1 (1.1)

While Tolman’s method appears to be quite simple and crude, the values obtained by this

technique have been useful in correlating the chemical reactivity of a variety of

coordination compounds on the dependence of ligand steric properties. Attempts to

improve the Tolman cone angle model are also based on the geometrical parameters of a

phosphine compound, either acquired from crystallographic data8 or from quantum

mechanically calculated structures of the ligand-metal complex.9,10

1.1.2. Determining Phosphine Ligand Basicity

Strohmeier first proposed that the CO stretching frequencies of monosubstituted

transition-metal carbonyls could be used to evaluate the electron-donor ability of

phosphine ligands, and Tolman expanded on this concept with Ni(CO)3L complexes,

where L is the monodentate phosphine ligand.7,11 The Ni(CO)3L complexes are formed

quickly upon mixing the phosphine molecule and Ni(CO)4 in a 1 : 1 ratio at room

temperature, even if the ligands are large in size. Ligands with strong electron-donating

ability contribute to a larger degree of back-bonding from the metal centre into the C≡O

π*-antibonding orbitals, which therefore result in decreased C≡O bond order and leads to

lower C≡O stretching frequencies. On the other hand, weakly donating ligands induce

less M-C≡O back-bonding, which leads to higher C≡O stretching frequencies.

As a standard measure, the A1 carbonyl mode of Ni(CO)3L complexes is

referenced against the analogous stretching frequency of Ni(CO)3(PtBu3) to give the

electronic parameter χ (Equation 1.2).

χ χ1χ2χ3 = νCO(A1) - 2056.1 cm-1 = Σ3

i=1χi

P (1.2)

4

Tolman noted a linear additive electronic effect of each substituent on phosphorus

(χi in Equation 1.2) to estimate the net-basicity of phosphines that have not been

quantified.6 Bartik and co-workers have clarified that the additivity rule is not wholly

linear, especially concerning aromatic substituents, and the deviations from Tolman’s χ-

values are dependent on the combined donor and acceptor character of the atoms in the

α-position to the phosphorus.12

The basicity of phosphines towards protons has also been measured by several

groups, where the pKa values obtained give a quantitative measurement of the σ-donicity

of a ligand.13-16 The method of quantitative analysis of ligand effects,17,18 QALE, is a

more generalized approach to measure the combined effects of electron-donor ability and

steric size. This approach considers other electronic parameters such as the so-called

‘aryl effect’ and a size parameter called ‘steric threshold’.

1.1.3. The Utility of Phosphine Ligands

Phosphine ligands are often used in transition metal-mediated catalysis because of

the potential to tune the steric and electronic properties by simply changing the

substituents on phosphorus. Minor adjustments in the electronic and / or steric size of a

phosphine can alter the reactivity of a catalyst by increasing its stability, promoting

reactions, and influencing enantioselectivity in organic transformation reactions.19

The utility of PPh3, PCy3, and PtBu3 as ligands in transition metal catalysis is well

documented in the literature.4,20-23 These common monodentate phosphines are found to

be active species in C-C and C-heteroatom bond formation reactions such as Negishi

coupling,21 Suzuki coupling,23 and Kumada coupling.20 While monodentate phosphines

continue to flourish as co-catalysts, the development of chelating bidentate bisphosphines

has led to superior enantioselectivity compared to monodentate ligands.24 Early

examples such as DIOP,25-27 DIPAMP,28,29 and BINAP30-32 (Figure 1.3) have led to the

optimization of transition metal-catalyzed asymmetric hydrogenation reactions and

inspired the emergence of new chiral bisphosphine ligands. The common thread among

DIOP, DIPAMP, and BINAP is that they are chelating bisphosphines. These ligands

5

differ in the basis of their chirality: DIOP contains a rigid chiral backbone; the

phosphorus atoms of DIPAMP are chiral centres, having different substituents; the C2-

symmetric BINAP is atropisomeric by hindered rotation about the C-C single bond.

PPh2PPh2

P

POO

PPh2

PPh2O

O

(a) (c)(b) Figure 1.3. Early examples of chelating bisphosphines. (a) DIOP25-27 (b) DIPAMP,28,29 (c) and BINAP30-32

ligands.

The combination of (P,N)-donors as chiral bidentate ligands has proven to be

more effective than (P,P)-donors at directing enantioselectivity of a reaction. This is in

part due to the distinct differences in the σ-donor abilities of the soft P-ligand with π-

acceptor properties compared to the hard N-ligand functioning primarily as a σ-donor.

For example the mixed (P,N)-ligands of the PHOX19 series are particularly well-suited

for Ir-catalyzed asymmetric hydrogenation of simple olefins, and (R,R)-n-Bu-

QUINAPHOS33 is a highly efficient ligand in Rh-catalyzed asymmetric hydrogenation of

itaconic acid (Figure 1.4).

P N

O

tBu(o-Tol)2 O

OP N

Ph2P

Bun

(a) (b) Figure 1.4. Chiral bidentate (P,N)-ligands: (a) (S)-PHOX ligand,19 and (b) (R,R)-nBu-QUINAPHOS.33

6

1.2. N-Heterocyclic Phosphine Ligands

Phosphines with aromatic heterocyclic substituents are interesting ligands in

coordination chemistry because they offer several potential modes of coordination to

transition metals. The most frequently studied of these polydentate ligands are the

pyridylphosphines34 in which the pyridyl substituents are bound to phosphorus at the 2-

position (Figure 1.5a).

N

P P

NH

(a) (b) Figure 1.5. N-Heterocyclic phosphine ligands (a) diphenyl(2-pyridyl)phosphine and (b) diphenyl(2-

pyrrolyl)phosphine.

Mono-, bis-, and tris(2-pyridyl)phosphines have been prepared and their coordination

chemistry remains an area of considerable activity in part because of the difference in

character between the two centres of Lewis basicity. As a softer σ-donor and stronger π-

acceptor than the nitrogen atom, the phosphorus centre of diphenylpyridylphosphine

preferentially coordinates to transition metals to obtain mononuclear complexes.34

In principle, diphenyl(2-pyrrolyl)phosphine (Figure 1.5b) should provide a

similarly rich and varied chemistry in reaction with transition metals upon deprotonation

of its pyrrolyl nitrogen centre. However, its low yielding synthesis, coupled with its

propensity for complicated and unpredictable behaviour in metal coordination have

rendered diphenyl(2-pyrrolyl)phosphine a rarely used ligand in reaction with transition

metals.35,36

Electron-rich heteroaromatic indole, like pyrrole, also offers further modes of

coordination through its nitrogen atom in a potentially polydentate ligand (Figure 1.6).

7

NH

12

345

67

Figure 1.6. The numbering scheme of indole.

The required deprotonation of the indolyl nitrogen centre provides the opportunity to

control secondary N-coordination. It is reasoned that relative to pyrrole, indole has lesser

reactivity due to its fused benzene moiety, which permits an easier synthesis of mono-

and di- substituted indolylphenylphosphines and that these ligands provide a rich and

interesting coordination chemistry that is based upon their expected polydenticity rather

than the propensity for P-C bond cleavage and other complications observed upon

coordination of diphenyl(2-pyrrolyl)phosphine.35

Traditionally, the functionalization of a phosphine ligand after P-C bond

formation is an arduous process that can require several time- and atom-consuming steps.

Therefore in many cases, the tailoring of a phosphine ligand requires a “ground-up”

strategy where the substituents must be modified prior to the formation of a phosphine

molecule. Changes to the substituents on a preformed phosphine ligand without extra

protection and deprotection steps would be a valuable commodity with which a large

variety of phosphine ligands having varied electronic and steric properties can be

generated easily and efficiently. An indolyl group would be an ideal candidate as a

phosphine substituent as it will provide the necessary site of reactivity for future

functionalization, but it can also be capable of coordinating to transition metal centres.

An additional attractive feature of indoles is the availability of substituted indoles, either

commercially or via well-documented indole syntheses37 in the literature.

8

1.3. Reactivity at Indole Nitrogen

One of the most reactive sites on indole is at the nitrogen centre; generally

deprotonation of the acidic NH proton occurs prior to the formation of any new bond at

this site. Some common reactions that involve an indole nitrogen centre are shown in

Scheme 1.1. One of the most common reactions at an indolyl nitrogen centre is N-

alkylation (Scheme 1.1a).37 Addition of the appropriate alkyl halide after deprotonation

of the NH proton yields the desired N-alkylated indole. Several bases can be utilized to

perform the same deprotonation and they include: NEt3, n-BuLi, NaOH and NaH. Aryl

groups can be installed on the nitrogen centre of indole with the aid of a Cu(I) catalyst

(Scheme 1.1b). This reaction has shown to be useful for furnishing N-heterocycles on the

indole nitrogen centre.38

HN

NR

NAr

NPR2

NM

(a) (b)

(d)(c)

baseR-X Ar-X

base basePR2Cl

Cu(I)

M

Scheme 1.1. Examples of reactivity at the nitrogen centre of indole: (a) N-alkylation, (b) N-arylation, (c) N-

phosphination, and (d) N-metallation.

N-Phosphination of indole (Scheme 1.1c) is well documented in the literature.

Direct reaction of indole with dichlorophenylphosphine, in the presence of NEt3, forms

phosphine ligands that have a combination of N-bound and C3-bound indolyl substituents

on phosphorus (Scheme 1.2).39

9

HN

HN

P NNEt3

PPhCl2

Scheme 1.2. Reactivity at the 1- and 3-positions of indole to form tris(3-methyl-1H-indol-1-yl)phosphine.39

Similarly, the indolyl substituents are all N-bound to the phosphorus atom in tri(N-3-

methylindolyl)phosphine (Figure 1.7a) and phosphatri(3-methylindolyl)methane (Figure

1.7b).40

NP

NN

N NPN

(a) (b) Figure 1.7. N-Phosphination of indole examples: (a) tri(N-3-methylindolyl)phosphine, and (b) and

phosphatri(3-methylindolyl)methane.40

This reactivity at indole nitrogen with chlorophosphines poses a synthetic challenge in

forming 2-indolylphosphines. Thus an appropriate protecting group for the indole

nitrogen centre, which does not hinder the reactivity at the C2-position in reaction, will

be necessary.

The N-metallation of indole (Scheme 1.1d) involves coordinating deprotonated

indole to a transition metal. The indole ligand acts as an anionic 2-electron N-donor in

(η5-C5H5)Re(NO)(PPh3)(η1-C8H6N)41 and (κ1-N-C10H10)2Sm(THF)442

(Figure 1.8).

10

N

Re PPh3ONSmTHF

THF THFTHF

N

N

(a) (b) Figure 1.8. N-metallation of indole examples: (a) (η5-C5H5)Re(NO)(PPh3)(η1-C8H6N),41 and (b) (κ1-N-

C10H10)2Sm(THF)4.42

1.4. 2-Indolylphosphine Ligands

One of the goals in our research is to be able to modify a phosphine ligand post P-

C bond formation. Indolyl is a suitable substituent on phosphorus for this objective only

if the nitrogen centre is free to react further; this can be accomplished through the

synthesis of 2-indolylphosphine ligands, in which the phosphorus centre is bonded to

indole at its C2-position. This also allows the phosphorus centre to be proximal to the

reactive nitrogen centre, which would allow for communication between the two centres.

Brown and co-workers43 reported the synthesis of 2,2’-bis-

diphenylphosphino[3,3’]biindolyl, the first example of a phosphine ligand with the

phosphorus atom bonded to the 2-position on indole (Scheme 1.3). The indolyl nitrogen

centres in Brown and co-workers’ system is protected with an N,N’-

dimethylaminomethylene protecting group, which has been shown by Katrizky and co-

workers44 to be effective at directing lithiation to the C2-position on indole.

11

N

N

N

N

N

N

N

N

PPh2

PPh2

1. nBuLi2. Ph2PCl

Scheme 1.3. Synthesis of 2,2’-bis-diphenylphosphino[3,3’]biindolyl.43

We required explicit reactivity at the C2-position on indole, however the C3-

position is also susceptible to attack by chlorophosphines45 due to contributing resonance

structures in which there is extra electron density at this position. Therefore, we chose 3-

methylindole as a starting material; by blocking the C3-position on indole with a methyl

group we have removed the reactivity at this site. A general reaction scheme for the

synthesis of 2-indolylphosphine ligands is shown in Scheme 1.4. Modifying Katrizky

and co-workers protocol,44 lithiation of indole is achieved at the C2-position, and the

subsequent addition the appropriate chlorophosphine reagent leads to the desired aminal-

protected phosphine. The N,N’-dimethylaminomethylene aminal protecting group can be

straightforwardly removed upon reaction of the protected phosphine with NaBH4.

N

N

N

N

PR2

HN

PR2

1. n-BuLi2. PR2Cl

THF, -78oC

NaBH4EtOH/THF

Δ

Scheme 1.4. General reaction scheme for the synthesis of 2-indolylphosphine ligands.

12

1.5. Synthetic Anion Receptors

Anions are pervasive in the natural world. They are essential to a broad range of

biological and chemical processes. For example, research is being conducted on using

anion receptors as membrane transport agents for chloride in biological systems.46 The

interest in anion recognition has been quickly gaining momentum, as seen in the large

number of reviews describing the chemistry involved in making and evaluating anion

receptors.47-58

The basic concepts which are considered when designing anion receptors are:

hydrogen bonding and / or electrostatic interactions; metal-anion complex formation; and

size and shape complementarity. In contrast to isoelectronic cations, anions are larger in

size, thus having lower charge-to-radius ratio and weaker electrostatic interactions.

Anions may be susceptible to protonation and only exist above a certain pH level.

Anions come in a wider range of geometries compared to common cations (Table 1.1),

necessitating a higher degree of design and complementarity to generate receptors that

are selective for one anion guest over another.58 Anion binding strength and selectivity

are dependent upon the type of solvent in which the interaction occurs. This is especially

true for neutral anion receptors that function primarily by hydrogen bonding; these

receptors will have difficulty competing with polar protic solvents that form strong

hydrogen bonds with anions.

Table 1.1. The variation in geometry of some common anions.

Geometrical Shape Anion

Spherical F-, Cl-, Br-, I-

Linear N3-, CN-, SCN-, OH-

Trigonal Planar CO32-, NO3

-

Tetrahedral PO43-, SO4

2-, BF4-

Octahedral Fe(CN)64-, Co(CN)6

3-

There are several methods used to determine the strength of interaction between

an anion receptor and an anion guest.58 Generally these techniques require titration of

anion guest into a host solution. The titration may be monitored by NMR, UV-visible or

13

fluorescence-emission spectroscopy, or isothermal titration calorimetry. 1H NMR

spectroscopy can be useful for following the NH proton chemical shifts of receptors

containing these functionalities, and can offer insight into the immediate interaction of an

anion guest with a receptor’s hydrogen bond donors. Both UV-visible and fluorescence-

emission spectroscopy exhibit the changes in the optical properties of the light

absorbing / emitting segments of an anion receptor upon binding. Isothermal calorimetry

affords information about a receptor’s energy changes upon anion interaction. These

titration techniques operate at different sensitivity limits: ~10-3 M for NMR; ~10-4 M for

isothermal calorimetry; ~10-5 M (or lower) for UV-visible and fluorescence-emission

spectroscopy. Titrations are often performed in several different solvents, as solvent

polarity has a direct impact on the strength of anion-to-receptor interaction. Anion

binding strengths tend to be higher in less polar organic solvents (such as CH2Cl2), and

often tetrabutylammonium anion salts are used as they are soluble in these less

competitive solvents.

Anion recognition hosts fall into two categories: positively charged receptors and

neutral receptors. Positively charged anion receptors often contain groups such as

ammonium55,59,60 or pyridinium61 that can interact with an anion guest through a

combination of electrostatic and hydrogen bonds. For example, Bowman-James and co-

workers60 examined the anion binding ability of a polyammonium tren-based tripodal

species (Figure 1.9a) and determined that the receptor has high affinity for dihydrogen

phosphate and hydrogen sulfate (log Ka = 3.25 and 3.20 in CDCl3, respectively). A

tetrapyridinium macrocycle (Figure 1.9b) from Shinoda and co-workers61 exhibits

binding to tricarboxylate anions with high affinities (log Ka = 5.1 in D2O at pH 7-8).

N

N

N

N

(a) (b)

N N N

NH

HH

H H

H

Figure 1.9. Positively charged anion receptors (a) polyammonium tren-based receptor,60 and (b)

tetrapyridinium macrocycle.61

14

Transition metal centres can provide a positive charge to the receptor to increase

the electrostatic interaction between the host and anionic guest, and impart geometrical

constraints by coordination geometry to organize the hydrogen-bonding groups for

optimal guest interaction.48,62-68 For example, Loeb and co-workers63 have demonstrated

the use of Pt(II) to arrange four isoquinolyl ligands with pendant urea functionalities into

close proximity (Figure 1.10). The receptor was found to have high binding affinity for

sulfate and dihydrogen phosphate in 1 : 1 receptor to anion ratio (Ka values in excess of

105 M-1) through a combination of hydrogen bonding and electrostatic interactions

between the anion and the Pt(II).

N

NH

NHO

Bu

Pt2+

4 Figure 1.10. Metal complex-based anion receptor that functions with both hydrogen bond donors on the

ligand and electrostatic interactions on the metal.63

Commonly, electroneutral anion recognition hosts have suitable NH donors and

are frequently based on small molecules with organic structures that can contain

combinations of functional groups such as amides,69-74 pyrroles,46,75-81 and ureas.82-87 For

example, Gale and co-workers58 have demonstrated that two amide pendant arms on a

receptor (Figure 1.11a) has improved anion binding affinity and increased selectivity

towards dihydrogen phosphate anion (Ka = 2.6 x 104 M-1 in MeCN containing 0.5%

DMSO) relative to a receptor only containing one amide pendant arm. In addition,

Gale’s group76 has constructed an anion receptor which incorporates a pyrrolyl moiety

between two amide functionalities (Figure 1.11b). The crystal structure of this pyrrolyl-

based anion receptor with benzoate anion demonstrates the interaction between the anion

and the receptor, and more importantly that all three of the hydrogen bond donors are

engaged in the interaction. Fabbrizzi and co-workers82 reported a urea-based anion

15

receptor that contains two electron withdrawing nitro substituents (Figure 1.11c) which

act to increase the acidity of the hydrogen bond donors. This receptor shows strong

binding to fluoride, acetate and benzoate in a 1 : 1 receptor to anion stoichiometry (log Ka

= 7.38, 6.61, and 6.42, respectively in CH3CN).

O

NH

O

HN

NH HN OO NH

NH

OHN

O

HN

O

NHBu Bu

(a) (b) (c)

NO2O2N

Figure 1.11. Examples of neutral anion receptors: (a) amide-based,58 (b) pyrrole-based76 and (c) urea-

based82.

The limited number of reports of indole-based anion receptors is somewhat

remarkable, considering for example, the indole-containing amino acid tryptophan is a

component of a sulfate binding protein that helps to stabilize sulfate binding in biological

systems.88 Only recently attention has been given to indole-based hosts and they have

demonstrated anion binding capability and high selectivity for various anions.88-104 For

instance, Gale and co-workers90 have synthesized a series of 2,7-functionalized indoles

that have additional amide and / or urea or thiourea moieties. Figure 1.12 shows one of

the indole-based receptors in the series that has urea functionality at the 7-position and an

amide functionality at the 2-position. This particular receptor shows very strong binding

to acetate anions with a stability constant of Ka = 10000 M-1 in DMSO-d6 / 0.5% water.

HN

O

HNNH

NH

O

Figure 1.12. Example of an indole-based anion receptor with additional hydrogen bond donors at the 2-

and 7-positions on indole.90

16

A survey of the literature for phosphine ligand-based anion receptors yields a

small number of reports. Often phosphine ligands are designed such that they contain a

hydrogen bond donor displaced at some distance from the phosphorus centre, and the

phosphorus atom itself is used for metal coordination.84-87 For example, Knight and co-

workers86 have reported a Pd(II) with two urea-functionalized phosphine ligands that

exhibit intramolecular hydrogen bonding (Figure 1.13a). In the presence of a chloride

guest, the self-association is disrupted and the urea functionalities concurrently hydrogen

bond to the anion (Figure 1.13b). The association constant for this Pd(II) system was

found to be 1000 M-1 in CDCl3, and is considered a relatively strong interaction in this

solvent.

PPh2

Pd

P

MeCl

Ph2

NH

NH

HN

HN

O

O

EtOOC

EtOOC

Cl

-

PPh2

Pd

P

MeCl

Ph2

NH

NH

NH

O

EtOOC

NH

EtOOC

OCl-

CDCl3

(a) (b) Figure 1.13. An example of metal coordinated phosphine-based anion receptor. (a) The urea functionalities

are engaged in intramolecular hydrogen bonding in the absence of an anion guest. (b) Upon the addition of

chloride, the intramolecular hydrogen bonding is disrupted to allow the urea functionalities to act as an

anion receptor.86

One of the goals of this thesis is to evaluate 2-indolylphosphine ligands as anion

receptors and to assess how hydrogen bonding can alter their properties. Furthermore,

since indole-based receptors have shown to be as promising as their pyrrole-based

counterparts, and there is a general absence of phosphine ligands acting as anion

receptors, it is thought that 2-indolylphosphines as anion receptors would be a timely

addition to this burgeoning field.

17

1.6. Scope of the Thesis

A series of unfunctionalized and N-functionalized 2-indolylphosphine ligands

have been synthesized in our group, and further coordinated to Pd(II). The main goal of

this research is to structurally analyze these new 2-indolylphosphines and their

subsequent metal complexes, as well as examine the anion binding properties of tris-2-(3-

methylindolyl)phosphine. This thesis is divided into four parts:

Chapter 2 describes the solid-state structures of monodentate 2-indolylphosphine

ligands and their N-alkylated derivatives. A detailed investigation of the structural

features, namely implications to the steric bulk around a phosphorus atom, and indole

aromaticity upon N-functionalization will be addressed.

The anion binding properties of tris-2-(3-methylindolyl)phosphine will be

examined in Chapter 3. Various anions have been examined to determine the utility of

tris-2-(3-methylindolyl)phosphine as an anion receptor. In addition, attempted syntheses

for new indole-based anion receptors will be presented.

In Chapter 4, the metal complexes of monodentate 2-indolylphosphines will be

examined. The net-basicities of these ligands will be determined through coordination to

Ni(CO)3, it will also be demonstrated how N-alkylation affects the net-basicity of the

parent phosphine molecule. Complexation of tris-2-(3-methylindolyl)phosphine to

[Cu(MeCN)4]BF4 generates a discrete ion-pair complex in which the BF4- anion interacts

with the phosphine ligand through hydrogen bonds. The coordination chemistry of

monodentate 2-indolylphosphines will be investigated by X-ray crystallography.

Chapter 5 will present multidentate 2-indolylphosphine ligands, where the indole

nitrogen centres are functionalized with substituents that have the ability to further

coordinate to metal complexes. The structural analyses of these new bidentate (P,N)- and

(P,P)-2-indolylphosphine ligands and their metal complexes will be presented.

Furthermore, a new tetradentate 2-indolylphosphine ligand will be examined along with

its coordination chemistry to both Pt(II) and Rh(I).

All the crystallographic and synthetic work presented in this thesis was performed

by Joanne Yu, with the exception of the syntheses of the unfunctionalized and N-

18

functionalized 2-indolylphosphines and their Pd(II) complexes, which were conducted by

Dr. Edmond Lam.105

19

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23

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Chapter 2

Monodentate 2-Indolylphosphines: A Study in

Structure by X-ray Crystallography*

2.1. Introduction

2-Indolylphosphines are ideal ligands due to their ability to coordinate Lewis

acids via the phosphorus centre, and the indolyl NH moiety can serve as a secondary site

of reactivity. The indolyl substituent provides a basis for aufbau or stepwise assembly of

potentially more complex phosphines. Functionality can be incorporated on the

phosphine at the nitrogen centre upon deprotonation with a variety of substituents that

can possess properties which alter the overall bulkiness, electronics, or chirality of the

phosphine (Scheme 2.1). This modular approach to creating new phosphines via N-

modification following P-substituent bond formation, lies in contrast to the more

customary methods of phosphine synthesis. Therein, the challenging and often

substituent-specific intricacies and sometimes unpredictability of P-C bond formation

must be overcome each time that a different structural element of interest is incorporated

into the phosphine.

HN

HN

PR1

R1

NP

R1

R1

R2

(a) (b) (c) Scheme 2.1. A general scheme demonstrating the Aufbau assembly of N-substituted 2-indolylphosphines.

(a) 3-Methylindole is the starting point (b) A generic unsubstituted 2-indolylphosphine (c) An N-

functionalized 2-indolylphosphine. * Reproduced in part with permission from: J. O. Yu, E. Lam, J. L. Sereda, N. C. Rampersad, A. J. Lough, C. S. Browning, and D. H. Farrar. Organometallics 2005, 24, 37-47. Copyright 2006 American Chemical Society.

24

25

A variety of methods can be utilized to characterize the 2-indolylphosphines that

we have generated, most commonly are spectroscopic methods for routine analysis of

these compounds. Single crystal X-ray diffraction has proven to be a useful method to

analyze the bond lengths and angles of phosphines to provide insight into the steric bulk

associated with the ligands, which is an important aspect in phosphine design particularly

for transition metal catalysis.1,2 Additionally, X-ray crystallography can be used to

examine the effect of substituents on the indolyl moiety to determine how they impact the

aromaticity of the pyrrole ring.

In this Chapter, X-ray crystallography will be used to examine the structural

features of unfunctionalized and N-alkylated 2-indolylphosphines. A correlation between

steric crowding around a phosphorus atom and a phosphine ligand’s size will also be

discussed.

2.1.1. Crystallographic Analysis of Common Phosphines

in the CSD

While the Tolman cone angle is a good estimate of a phosphine’s steric bulk, the

Tolman cone angle does not consider the variation in ligand conformation or the impact

of these conformations on a ligand’s cone angle.1 Mingos and co-workers devised a

method to determine a phosphine’s cone angle based on crystallographic data, and used

statistical information from the Cambridge Crystallographic Structural Database (CSD)

to analyze the method.3 The crystallographic method used the geometric relationship

originally proposed by Tolman where the metal-phosphorus bond in phosphine

complexes was adjusted to 2.28 Å and a van der Waals radius of 1.00 Å was used for

hydrogen atoms (Figure 2.1).

26

Figure 2.1. Description of the van der Waals surface of a phosphine ligand to determine the Tolman cone

angle from crystallographic data.3

Mingos et al. gathered statistical data on the phosphines’ cone angles from the CSD and

determined that the statistics of these data could be characterized well with a normal

distribution.3 Based on the normal distributions, they were able to determine the mean

and median parameters which allowed them to calculate the average values of cone

angles for several common phosphines (Table 2.1). The average calculated cone angles

for the common phosphines correlated reasonably well with Tolman’s cone angles based

on space-filling models, however the statistical spread of crystallographic cone angles

due to varied conformation in the phosphine’s substituents was greater than had been

originally expected. The advantage of this approach is that a ligand’s cone angle can be

easily determined from its crystal structure; the disadvantage is that a crystal structure of

the phosphine must be available. The crystal structure must have the ligand coordinated

to a metal atom and free of secondary interactions, such as hydrogen bonding or ionic

interactions that may affect its cone angle.

27

Table 2.1. Summary of computed average cone angles of selected common phosphines.3

P

P

CH3

PH3CCH3

No. of structures 1507 78 560

No. of phosphines 2388 108 1203

Crystallographic cone angle (o) 148.2 (4.9)a 160.1 (5.1)a 111.1 (2.4)a

Range of cone angles (o) 129.0 – 168.3 146.2 – 171.7 95.8 – 121.2

Tolman cone angle (o)1 145 ± 2 170 ± 2 118 ± 2 aValues in brackets give the standard deviation.

The influence of a substituent on the phosphorus atom of a tertiary phosphine can

be seen in the bond distances and angles of its crystal structure. An examination of the

CSD (version 5.29 January 2008) for the following common phosphines: PPh3, PCy3, and

PtBu3 had provided P-C bond distances and <CPC bond angles, that when averaged, gave

the values listed in Table 2.2. The CSD search on the phosphines listed was restricted to

the criteria that all structures had R-values < 0.05, were not disordered, were not

coordinated via the phosphorus to a Lewis acid, or contained alternative secondary

bonding interactions, such as hydrogen bonding or ionic charges that may distort the

steric profile of the phosphine. The P-C bond distances and the <CPC bond angles for

the phosphines are listed in Table 2.2.

Table 2.2. X-ray diffraction data from the CSD for PPh3, PCy3, and PtBu3. Bond lengths (Å), bond

angles (o), Σ{<CPC} (o), and cone angles(o) are listed.

Entry Phosphine Average P-C (Å)

Average <CPC (o)

Average Σ{<CPC} (o)

Cone Angle (o)1

1 P

1.831

102.39

307.17

145

2

P

1.868a

103.81a

311.43

170

3 P

1.911a

107.42a

322.27

182 aThe sample size was only one for both PCy3 and PtBu3 in the CSD based on the search criteria.

28

The P-C bond distances can provide a measure of carbon atom hybridization of

the substituent on phosphorus, for example an sp3-hybridized carbon will have a longer

P-C bond length compared to a carbon with sp2-hybridization. Additionally, the

phosphines in Table 2.2 can be categorized by their basicity4,5 and the order of least basic

to most basic is PPh3 < PCy3 < PtBu3. The basicity of the phosphine is directly related to

the nature of substituents on the phosphorus atom, and generally the more electron-

withdrawing a substituent is, the less basic the phosphine will be. This example of

basicity approximation is also reflected in the P-C bond lengths of the phosphines listed

in Table 2.2, with PPh3 being the least basic it has the shortest P-C bond lengths, whereas

the PtBu3 being the most basic has the longest P-C bond lengths.

While the traditional gauge of phosphine steric bulk is measured using Tolman’s

cone angle method,1 an alternative simple method to assess steric bulk at the phosphorus

centre can be achieved by comparing the sums of the angles around the phosphorus,

Σ{<CPC}.6 For a three-coordinate molecule possessing absolute trigonal planar

geometry, the Σ{<CPC} would be 360o, whereas a perfect trigonal pyramidal structure

having ideal tetrahedral bond angles will have a Σ{<CPC} of 328o. The average

Σ{<CPC} are calculated for PPh3, PCy3, and PtBu3 and are listed in Table 2.2. The

average Σ{<CPC} for the phosphines in Table 2.2 are consistent with their cone angle

values determined using Tolman’s method: PPh3 has the smallest Σ{<CPC} and PtBu3

has the largest Σ{<CPC}. While bond angles can be affected immensely by

crystallographic packing forces, in silico studies comparing Σ{<CPC} of

triarylphosphines to crystallographically obtained Σ{<CPC} values indicate that the bond

angles are only slightly affected by crystallographic packing forces, and the experimental

and calculated Σ{<CPC} values are comparable.6 Therefore, in the event that suitable

crystal structures of a phosphine-metal complex are not available, and thus Tolman’s

method to determine the phosphine’s cone angle is impossible by analysis of

crystallographic data, then an approximation of the phosphine’s steric bulk can be

estimated from its Σ{<CPC}.

29

2.1.2. Crystallographic Analysis of Indole-Containing

Structures in the CSD

Changes in the aromaticity of the pyrrolyl ring on indole may be seen

crystallographically in the bond distances and bond angles of its crystal structures. In

order to determine the standard of aromaticity in the pyrrole ring of indole, a CSD search

was conducted to find aromatic indole-based structures and examine their bond distances

and angles. The following search restrictions were applied to maintain consistency on the

structures that were returned: R-values < 0.05, no disorder was present, the absence of

coordination to either the nitrogen centre or either of the rings (in η-fashion), alternative

secondary bonding interactions were omitted, such as hydrogen bonding or ionic charges

that may distort the aromaticity of the pyrrolyl moiety, and finally carbazole-based

structures were not permitted. The search criteria produced a sample size of 11

structures.7 Selected bond distances and angles are listed in Table 2.3 along with the

numbering scheme.

Table 2.3. Selected averaged bond distances (Å) and bond angles (o) of indole-based structures from the

CSD.

C4

C9

C3

C2

N1

R3

R2

R1

N1-C2 1.389 C2-C3 1.364 C3-C4 1.439 C4-C9 1.413 C9-N1 1.382

C9-N1-C2 108.251 N1-C2-C3 109.789 C2-C3-C4 107.313 C3-C4-C9 106.44 C4-C9-N1 108.156

30

The average pyrrolyl-moiety bond distances were found to be midway between

true N-C or C-C single bonds and N=C or C=C double bonds, consistent with the

delocalized characteristic of a pyrrole ring, with the exception of the C2-C3 bond

distance which is closer to a true C=C double bond.(note C-C, C-N, C=C, and C=N) The

bond angles were all averaged to be about 108o, the only angle being smaller than the

ideal 108o was the <C3-C4-C9 (106.44o) poses no significant influence on the structural

features of the pyrrolyl moiety. Thus, these bond distances and angles may be used as a

benchmark for aromaticity when analyzing our 2-indolylphosphines.

2.2. Results and Discussion

2.2.1. Synthesis of Unsubstituted 2-Indolylphosphines

Our group has established methods for the preparation of a variety of 2-

indolylphosphines.8,9 A general reaction sequence is shown in Scheme 2.2, the details of

the synthesis will be discussed in Chapter 3.

HN

P

HN

N

N

NP

N1. n-BuLi

2. PCl3-xRxTHF

1. NaBH4EtOH/THF

reflux2. HCl workup

Me2NHH2O

reflux

H H

O

quantitative 89% overall 85% Scheme 2.2. The synthesis of phosphine 1 from the commercially available 3-methylindole. This is a

representative example of the facile method for 2-indolylphosphine synthesis.

These phosphines can be varied in several ways just by adding the desired

chlorophosphine. For example, the number of indolyl substituents can be modified from

one indolyl substituent in 1, to three indolyl substituents in the C3-symmetric 5.

Alternatively, the two other substituents on the phosphorus can also be altered from

phenyl in 1 to cyclohexyl in 2. A library of 2-indolylphosphines has been generated by

this simple method8 and are shown in Figure 2.2.

31

HN

P

NH

P HN

NH

P

HN

HNH

NP

(a) (b) (c) (d)

1 2 3 5

Figure 2.2. Selected monodentate unsubstituted 2-indolylphosphines. (a) P(C9H8N)(C6H5)2, 1

(b) P(C9H8N)(C6H11)2, 2 (c) P(C9H8N)2(C6H5), 3 (d) P(C9H8N)3, 5.

2.2.2. X-ray Crystallographic Analysis of Unsubstituted 2-

Indolylphosphines

Discussion of the crystallographic analysis of the 2-indolylphosphines will be

confined to the structures shown in Figure 2.2. X-ray diffraction data will be used to

interpret how exchanging the substituents can affect the steric crowding of the

phosphorus centre by inspecting the bond lengths and angles associated with the

phosphorus centre (Section 2.3), and the influence of N- or C2-substitution on the

aromaticity of the pyrrole moiety of the indolyl substituent (Section 2.3.1). The X-ray

diffraction experimental data are shown in Table 2.4.

32

Table 2.4. X-ray crystallographic experimental data of unsubstituted 2-indolylphosphines.

1

HN

P

2

HN

P

3

NH

PHN

5

NH

P

HN

HN

Formula C21H18NP C21H30NP C24H21N2P C27H24N3P Formula Weight 315.33 327.43 368.40 421.46 Crystal colour, shape colourless, block colourless, block colourless, block colourless, plate Crystal size, mm 0.35 x 0.30 x 0.30 0.26 x 0.08 x 0.06 0.20 x 0.18 x 0.18 0.16 x 0.12 x 0.08 Crystal system Triclinic Monoclinic Monoclinic Rhombohedral Space group Pī P21/c P21/c R3 a, Å 9.9678(2) 11.1906(9) 10.3563(3) 14.415(3) b, Å 10.3453(2) 14.3772(12) 10.3027(6) 14.415(3) c, Å 17.4704(4) 11.7375(5) 19.0016(8) 9.4877(16) α deg 79.973(8) 90 90 90 β, deg 75.992(7) 98.016(5) 104.383(3) 90 γ deg 74.133(9) 90 90 120 V, Å3 1670.09(6) 1870.0(2) 1963.9(2) 1707.3(6) Z 4 4 4 3 Dcalcd, g cm-3 1.254 1.163 1.246 1.230 F(000) 664 712 776 666 μ, mm-1 0.163 0.148 0.150 0.140 λ (Mo Kα), Å 0.71073 0.71073 0.71073 0.71073 Limiting indices 0<=h<=12 -14<=h<=14 -13<=h<=13 -18<=h<=15 -12<=k<=13 -16<=k<=18 -13<=k<=13 -16<=k<=18 -21<=l<=22 -15<=l<=15 -24<=l<=24 -11<=l<=12 2θ range, deg 2.55 to 27.48 1.84 to 27.55 2.27 to 27.50 2.70 to 27.43 Max. and min. transmission 0.9526 and 0.9450 0.993 and 0.834 0.993 and 0.602 1.003 and 0.937 No. of reflections collected 22759 14623 16135 2314 No. of independent reflections/Rint 7596 / 0.046 4469 / 0.081 4736 / 0.0904 1510 / 0.0571 Absolute structure parameter - - - 0.2(2) Extinction coefficient 0.0014(16) 0.0027(12) 0.0111(16) 0.0033(7) No. of refined parameters 426 210 255 96 Final R1, wR2 0.0449, 0.1140 0.0513, 0.1093 0.0546, 0.1221 0.0548, 0.1002 Final R1, wR2 (all data) 0.0767, 0.1320 0.1023, 0.1268 0.1017, 0.1442 0.1142, 0.1208 Goodness of fit 1.029 1.027 1.020 0.950 Δρmin, Δρmax, eÅ-3 -0.258, 0.257 0.212 and -0.280 -0.318, 0.359 0.193 and -0.187

Colourless block-shaped single crystals of phosphine 1 were grown by slow

evaporation from toluene. Phosphine 1 crystallizes in the triclinic space group Pī, with

two crystallographically independent molecules in the asymmetric unit (Figure 2.3). The

molecular structures and numbering scheme of the independent molecules are shown in

Figure 2.4, and Table 2.5 lists selected bond distances and angles. The independent

molecules are adequately similar in structure such that discussion is confined to one of

them (the most significant difference between the two molecules is the <C2-P1-C17 bond

angle of 99.94(8)o and 101.94(9)o). The geometry about the phosphorus atoms is best

33

described as trigonal pyramidal with the aromatic substituents adopting a twisted,

propeller blade-like orientation presumably to minimize the steric repulsion associated

with each ring. All of the hydrogen atoms on carbon were placed in calculated positions,

while the indolyl NH protons could have been located in the electron density map, they

were included in the refinement in the riding model on nitrogen. The solid-state structure

of 1 does not appear to possess secondary bonding interactions, as the closest non-

bonding distance is 2.70 Å between N1A-H1A and the phenyl ring of a symmetry

equivalent molecule.

Figure 2.3. Unit cell diagram of the four molecules of 1. Crystallographically independent molecules are

labeled. Hydrogen atoms are removed for clarity.

34

Figure 2.4. Numbering scheme of 1a in unit cell. Non-acidic protons removed for clarity. Thermal

ellipsoids are drawn at 35% probability.

It can be seen clearly in Figure 2.3 that both independent molecules of 1 have

their indolyl rings oriented in a fashion where the indolyl NH’s are pointing away from

the lone pair of the phosphorus atoms. This indolyl ring orientation may be a result of the

presence of the methyl group at the C3-position and the lack of substitution on the

nitrogen centre. The smaller proton substituent on nitrogen would assist in the indolyl

ring to be oriented in the lowest energy conformation prior to crystallization. While the

methyl group on the C3-position is directed towards the phosphorus lone pair, it is distant

enough not to induce any chemical changes to the phosphorus centre (average of

3.336(3) Å).

The P1-C2indolyl bond distance of 1.813(2) Å is significantly shorter than the bond

distances from P1-C11phenyl and P1-C21phenyl (average = 1.838(2) Å). No chemical

significance is associated with the bond angle between the indolyl and one of the phenyl

substituents, <C2A-P1A-C17A (99.9(8)°), being significantly smaller than the other bond

angles of <C2A-P1A-C11A (101.6(8)°) and <C11A-P1A-C17A (103.0(8)°).

35

Table 2.5. Selected bond lengths (Å) and bond angles (o) for unsubstituted 2-indolylphosphines.

1a in asymmetric unit

HN

P

1b in asymmetric unit

HN

P

2

HN

P

3

NH

PHN

5

NH

P

HN

HN

P1-C2 1.813(2) 1.811(2) 1.818(2) 1.812(2) 1.812(3) P1-C12 1.837(2) 1.833(2) 1.858(2) 1.809(2) 1.812(3) P1-C22 1.837(2) 1.834(2) 1.858(2) 1.841(2) 1.812(3)

N1-C2 1.399(2) 1.396(2) 1.395(2) 1.398(3) 1.390(5) C2-C3 1.374(3) 1.372(3) 1.375(3) 1.372(3) 1.378(5) C3-C4 1.438(3) 1.438(3) 1.438(3) 1.436(3) 1.427(5) C4-C9 1.409(3) 1.411(3) 1.407(3) 1.410(3) 1.427(5) C9-N1 1.378(2) 1.378(2) 1.373(2) 1.373(3) 1.389(4)

C9-N1-C2 109.2(2) 109.1(2) 110.1(2) 109.2(2) 109.5(3) N1-C2-C3 109.0(2) 109.0(2) 108.1(2) 109.1(2) 108.4(3) C2-C3-C4 106.8(2) 107.0(2) 107.3(2) 106.8(2) 107.6(3) C3-C4-C9 107.8(2) 107.4(2) 107.4(2) 107.6(2) 107.6(3) C4-C9-N1 107.3(2) 107.4(2) 107.1(2) 107.4(2) 106.9(3)

N11-C12 - - - 1.397(3) - C12-C13 - - - 1.379(3) - C13-C14 - - - 1.439(3) - C14-C19 - - - 1.407(3) - C19-N11 - - - 1.381(3) -

C19-N11-C12 - - - 109.2(2) - N11-C12-C13 - - - 108.8(2) - C12-C13-C14 - - - 106.8(2) - C13-C14-C19 - - - 107.6(2) - C14-C19-N11 - - - 107.4(2) -

It is evident from the crystal structure of 1 that the C2-bound methylindolyl group

constitutes a markedly larger phosphorus substituent than the phenyl ring. An average

separation of 2.40(6) Å between the two phenyl carbon atoms positioned ortho to

phosphorus on each ring (C12..C16 and C18..C22) serves as an effective measure of the

width of the phosphine’s two phenyl groups. In comparison, measured from its nitrogen

atom to the methyl carbon atom C10A, the equivalent width of 3.713(4) Å for the

methylindolyl group of 1 suggests that the 2-indolylphosphines possess cone angles

larger than that of PPh3,1 perhaps bearing a closer similarity in size to P(o-tolyl)3.1

Colourless block-shaped single crystals of 2 were obtained from hexane vapour

diffusion into a solution of the phosphine in CH2Cl2. The numbering scheme of 2 is

shown in Figure 2.5 and selected bond distances and angles listed in Table 2.5. The

36

phosphine crystallized in the monoclinic space group P21/c with one molecule in the

asymmetric unit. The hydrogen atoms were placed in calculated positions and included

in the refinement as riding atoms. There are no secondary bonding interactions in the

solid-state structure of 2 as the closest N1-H1A distance is 3.86 Å to the pyrrolyl ring of a

symmetry equivalent molecule. Similar to 1, the geometry about the phosphorus atom of

2 can best be described as trigonal pyramidal.

The P1-C2indolyl distance of 1.818(2) Å is similar to the analogous P-Cindolyl bond

distance of 1. Additionally, the coordination of a phosphorus atom at the C2-position on

indole does not result in any significant changes to its structural features. The P-Ccyclohexyl

bonds (1.858(2) Å) are significantly longer than the analogous P-Cphenyl bonds found in 1

(average 1.835(4) Å) as anticipated for the sp3-hybridized carbons of the cyclohexyl rings

compared to the sp2-hybridized carbons of the phenyl rings.

Figure 2.5. Numbering scheme of 2 in unit cell. Non-acidic protons removed for clarity. Thermal


The indolyl NH moiety of 2 points away from the phosphorus lone pair, which is

similar to the solid-state structure of 1. In this case, the orientation of the indolyl ring is

likely to alleviate any steric crowding that may occur between the methyl group at the

C3-position and the two bulky cyclohexyl substituents on phosphorus. The methyl group

is sufficiently distant from the phosphorus atom (3.390(2) Å) that it should not impart

any significant chemical changes to its lone pair.

A measure of the width of the phosphine’s two cyclohexyl groups was conducted

by determining the average separation between the two cyclohexyl carbon atoms

positioned ortho to phosphorus on each ring (C12..C16 and C18..C22) gave a value of

37

2.506(3) Å. In comparison to the analogously measured average separation for the

phenyl groups on 1 (2.40(6) Å), as it would be expected the cyclohexyl substituents are

slightly larger. However, performing the same measurement with the indolyl substituent

on 2 (from N1...C10) gave a distance of 3.705(3) Å, suggesting that a 3-methylindolyl is a

wider substituent than cyclohexyl.

Phosphine 3 crystals were grown as colourless blocks from a saturated solution in

CH2Cl2 via slow evaporation. Figure 2.6 shows the molecular structure and numbering

scheme of the ligand and Table 2.5 lists selected bond distances and angles. Phosphine 3

crystallizes in the space group P21/c with one molecule in the asymmetric unit. All of the

hydrogen atoms were placed in calculated positions, even though the indolyl protons

could be located in the electron density map, and included in the refinement as riding

atoms. There are no secondary bonding interactions in the solid-state structure of 3, since

the closest N11-H11A distance is to an indolyl moiety of a symmetry equivalent

molecule at 2.64 Å.

The phosphorus atom adopts a trigonal pyramidal geometry with the aromatic

substituents situated in a twisted, propeller blade-like fashion, similar to the solid-state

structures of 1 and 2. Likewise, the indolyl substituents are oriented such that the methyl

moieties at the C3 and C13 positions point away from the pyramid formed by the

substituents around P1. In addition, the P1-C2indolyl and P1-C12indolyl bond distances of

1.812(2) Å and 1.809(2) Å, respectively, are shorter than the P1-C21phenyl bond distance

of 1.841(2) Å.

38

Figure 2.6. Numbering scheme of 3. Non-acidic protons removed for clarity. Thermal ellipsoids are

drawn at 35% probability.

Single crystals of 5 were acquired by slow evaporation of a saturated solution of

the phosphine in CH2Cl2. The numbering scheme of 5 is shown in Figure 2.7 and

selected bond distances and angles listed in Table 2.5. C3-Symmetric 5 crystallized in the

chiral rhombohedral space group R3 indicating resolution of phosphine 5 in the solid-

state. One-third of a molecule exists in the asymmetric unit with a crystallographic C3-

axis that is parallel to the molecular C3-axis running through the phosphorus atom to

generate two symmetry equivalent indolyl rings. The indolyl substituents are oriented in

a propeller-like fashion, not unlike the previously discussed 2-indolylphosphines.

39

Figure 2.7. Numbering scheme of 5. Non-acidic protons removed for clarity. Thermal ellipsoids are


As was determined for phosphines 1, 2, and 3, the indolyl NH functionalities of 5

point inwards toward the pyramid created by its three indolyl substituents and the

phosphorus atom as the apex. The importance of the indolyl rings orientation of

phosphine 5 will become apparent in Chapter 3 when the anion binding ability of this

molecule will be discussed in detail. While the indolyl NH proton could have been

located in the electron density map, it was refined as a riding model on nitrogen, as were

the hydrogen atoms on carbon that were placed in calculated positions. The solid-state

structure of 5 does not appear to possess secondary bonding interactions, since the closest

N1-H1A distance is to a phenyl moiety of a symmetry equivalent molecule at 2.71 Å.

The P1-C2indolyl bond distances for 5 were determined to be 1.812(3) Å, which correlates

well to analogous P-Cindolyl bonding distances of the previously described 2-

indolylphosphines.

40

2.2.3. Synthesis of Monodentate N-Alkylated 2-

Indolylphosphines

More complex 2-indolylphosphines can be synthesized easily by a stepwise

approach that involves making the phosphine scaffold first and introducing modifying

groups on the indolyl nitrogen centre second. Just by adding the desired alkyl group, the

overall physical and chemical characteristics of the phosphine can be transformed to be

electron withdrawing, electron donating, or even have additional stereocentres. In the

presence of NaH, the nitrogen centre is deprotonated, and the addition of the desired alkyl

halide will produce a newly functionalized 2-indolylphosphine (Scheme 2.3), without the

extra steps of protection and deprotection of the phosphorus centre. Selected examples of

N-functionalization post P-C bond formation are shown in Figure 2.8.

HN

P1. NaH2. BnBr

THFN

P

52% Scheme 2.3. The synthesis of (N-Bn)-1. This is a representative scheme for N-substitution of 2-

indolylphosphines.

NP

N

F

FF

FF

F F

F

FFNP

(a) (b)

N-Bn-1 (N-CH2C6F5)2-4

Figure 2.8. Selected N-alkylated 2-indolylphosphines. (a) P(C9H8NC7H7)(C6H5)2, (N-Bn)-1

(b) P(C17H12N2C14H4F10)(C6H5), (N-F5Bn)2-4.

41

2.2.4. Crystallographic Analysis of N-Alkylated 2-

Indolylphosphines

Discussion of the crystallographic analysis of the N-alkylated 2-indolylphosphines

will be confined to the structures shown in Figure 2.8. The X-ray diffraction

experimental data for the N-alkylated 2-indolylphosphines are shown in Table 2.6.

Selected bond distances and angles for the crystal structures of the N-alkylated 2-

indolylphosphines are listed in Table 2.7.

Table 2.6. X-ray crystallographic experimental data of N-alkylated monodentate 2-indolylphosphines.

(N-Bn)-1

NP

(N-F5Bn)2-4

NP

N

F

FF

FF

F F

F

FF

Formula C28H24NP C37H19F10N2P.CHCl3 Formula Weight 405.45 831.88 Crystal colour, shape colourless, block colourless, block Crystal size, mm 0.46 x 0.30 x 0.22 0.32 x 0.30 x 0.22 Crystal system Monoclinic Monoclinic Space group P21/c P21/n a, Å 13.7780(5) 16.5993(5) b, Å 8.7875(4) 12.0034(3) c, Å 18.6350(7) 17.1393(4) α deg 90 90 β, deg 105.301(2) 98.8110(17) γ deg 90 90 V, Å3 2176.24(15) 3374.67(15) Z 4 4 Dcalcd, g cm-3 1.237 1.637 F(000) 856 1672 μ, mm-1 0.141 0.409 λ (Mo Kα), Å 0.71073 0.71073 Limiting indices -17<=h<=17 -21<=h<=21 -10<=k<=11 -15<=k<=15 -23<=l<=24 -22<=l<=22 2θ range, deg 2.38 to 27.50 1.59 to 27.53 Max. and min. transmission 0.971 and 0.909 0.964 and 0.852 No. of reflections collected 19191 32929 No. of independent reflections/Rint 5299 / 0.0466 8134 / 0.0528 Extinction coefficient 0.0073(17) 0.0013(4) No. of refined parameters 273 488 Final R1, wR2 0.0520, 0.1298 0.0438, 0.1071 Final R1, wR2 (all data) 0.0866, 0.1529 0.0721, 0.1221 Goodness of fit 1.029 1.027 Δρmin, Δρmax, eÅ-3 0.346 and -0.391 0.367 and -0.494

42

Table 2.7. Selected bond lengths (Å) and bond angles (o) for N-alkylated 2-indolylphosphines.

(N-Bn)-1

NP

(N-F5Bn)2-4

NP

N

F

FF

FF

F F

F

FF

P1-C2 1.819(2) 1.802(2) P1-Cb 1.831(2) 1.813(2) P1-Cc 1.836(2) 1.844(2)

N1-C2 1.400(3) 1.383(3) C2-C3 1.385(3) 1.378(3) C3-C4 1.425(3) 1.436(3) C4-C9 1.401(4) 1.410(3) C9-N1 1.377(3) 1.399(3)

C9-N1-C2 108.8(2) 108.5(2) N1-C2-C3 108.4(2) 109.3(2) C2-C3-C4 107.2(2) 106.9(2) C3-C4-C9 107.6(2) 107.3(2) C4-C9-N1 108.1(2) 108.0(2)

N11-C12 - 1.396(3) C12-C13 - 1.370(3) C13-C14 - 1.442(3) C14-C19 - 1.412(3) C19-N11 - 1.378(3)

C19-N11-C12 - 108.9(2) N11-C12-C13 - 109.4(2) C12-C13-C14 - 106.9(2) C13-C14-C19 - 107.0(2) C14-C19-N11 - 107.8(2)

Single crystals of (N-Bn)-1 were obtained as colourless blocks from slow

evaporation of a saturated solution of the phosphine in CH2Cl2. Figure 2.9 shows the

molecular structure and numbering scheme of the ligand, and Table 2.7 lists selected

bond distances and angles. The ligand (N-Bn)-1 crystallizes in the monoclinic space

group P21/c with one molecule in the asymmetric unit. The geometry about P1 is trigonal

pyramidal and the aromatic substituents are oriented in a similar propeller-fashion as the

unsubstituted 2-indolylphosphines. There appear to be no secondary bonding interactions

in the crystal structure of (N-Bn)-1.

43

Figure 2.9. Numbering scheme of (N-Bn)-1. Hydrogen atoms removed for clarity. Thermal ellipsoids are


In contrast to the unsubstituted 2-indolylphosphines, the methyl group at the C3-

position of the indolyl substituent of (N-Bn)-1 points away from the phosphorus lone

pair. The much larger benzyl moiety on the nitrogen centre results in the indolyl ring

being oriented such that the bulkier group is not pointing inwards towards the pyramid

created by the three P-substituents. The distance between the methylene C23 and P1 was

found to be 3.138(3) Å, thus the benzyl moiety should not cause significant chemical

changes to the phosphorus lone pair.

The benzyl group adopts an orientation in which it forms a slipped pseudo-

eclipsed π-stacking interaction with one of the phenyl moieties on P1 with a ring-to-ring

distance of 4.413 Å. The benzylated-methylindolyl substituent is a significantly larger

phosphorus substituent than the phenyl moieties. The analogous width of the benzylated-

methylindolyl, measured from indolyl’s methyl carbon atom C10 to the N-substituted

methylene carbon C23 was determined to be 5.061(4) Å; suggesting that the introduction

of any group on the indolyl nitrogen renders that phosphine substituent a cone angle

markedly greater than that of a phenyl group.

44

The P1-C2indolyl bonding distance of 1.819(2) Å is consistent with the

unsubstituted 2-indolylphosphines, as are the P1-C11phenyl and P1-C17phenyl bond

distances comparable to the analogous bond distances found within 1.

The formation of the phosphacycle was evident in the structure determination of

(N-F5Bn)2-4, single crystals of which were obtained by slow solvent evaporation from a

CDCl3 solution of the phosphine. (N-F5Bn)2-4 crystallizes in the monoclinic space group

P21/n with one deuterochloroform solvent molecule present. There was an absence of

intermolecular hydrogen bonding even though there are many hydrogen bond acceptors

located on the pentafluoro moieties. Figure 2.10 shows the molecular structure and

numbering scheme of (N-F5Bn)2-4 and Table 2.7 lists selected bond distances and angles.

Figure 2.10. Numbering scheme of (N-F5Bn)2-4. Hydrogen atoms and solvent molecule removed for

clarity. Thermal ellipsoids are drawn at 35% probability.

The P1-C2indolyl and P1-C12indolyl bond lengths of 1.802(2) Å and 1.813(2) Å

respectively in (N-F5Bn)2-4 are not significantly different from the P1-C2indolyl separation

of 1.813(2) Å observed in 1. The structural data for (N-F5Bn)2-4 suggests that its six-

membered phosphacycle does not experience substantial ring strain. The <C3-C10-C13

bond angle of 112.9(2)° about the methylene carbon of the phosphacycles of (N-F5Bn)2-4

is only slightly smaller than the corresponding bond angle of 115.4(2)° measured in 3,3’-

diindolylmethane.10

45

Interestingly, coupling of the indolyl substituents does produce a compression of

almost 6° upon the <C2-P1-C12 bond angle of 94.36(9)° in (N-F5Bn)2-4 compared with

that of 100.3(1)° measured between the uncoupled indolyl substituents of 3. This is not

considered to result in significant ring strain to the phosphacycle because of the facility

with which phosphorus subtly changes hybridization in order to accommodate

substituents of differing electronic or steric requirements. These changes in <CPC bond

angles are undeniably reflected in the Σ{<CPC} value for (N-F5Bn)2-4, which will be

discussed in greater detail in Section 2.3.

In the solid state, the pentafluorobenzyl groups of (N-F5Bn)2-4 adopt

conformations in which they are oriented in the same direction as the phenyl substituent

on the phosphorus atom. The fluorinated benzyl groups additionally exhibit a slipped

pseudo-eclipsed π-stacking conformation with the lone phenyl substituent of P1.

Distances between ring centroids of 3.547Å and 3.805Å, and an angle of 146° described

by them suggest the near-planar π-stacking of the three rings.

2.3. Examining the Σ{<CPC} of 2-Indolylphosphines

The sums of the <CPC bond angles from crystallographic data will be used to

asses the steric crowding around the phosphorus atoms of each of the 2-

indolylphosphines, and how the alkylation of an indolyl nitrogen centre will affect the

Σ{<CPC} values. A possible correlation with Σ{<CPC} and the 31P signal of a

phosphine will also be investigated. The Σ{<CPC} values are listed in Table 2.8.

46

Table 2.8. Sum of <CPC bond angles (o) and 31P resonances (ppm) for unfunctionalized and alkylated 2-indolylphosphines.

Entry

Complex

<C2-P1-C12

<C12-P1-C22

<C22-P1-C2

avg. Σ{<CPC}

31P δ

1

1

HN

P

99.94(8)b

101.94(9)c

102.97(8)b

101.60(9)c

101.64(9)b

100.43(9)c

304.6(1)b

304.0(2)c

-33.1

2

2 HN

P

103.17(9)

104.13(8)

101.12(9)

308.4(2)

-26.9

3

3

NH

PHN

100.3(1)

101.3(1)

102.2(1)

303.8(2)

-59.3

4

5

NH

P

HN

HN

102.3(1)

102.3(1)

102.3(1)

306.9(2)

-81.7

5

(N-Bn)-1

NP

101.0(1)

103.60(9)

103.24(9)

307.8(2)

-32.0

6

(N-F5Bn)2-4

NP

N

F

FF

FF

F F

F

FF

94.36(9)

101.63(9)

103.20(9)

299.2(2)

-30.8

aSpectra collected in CDCl3. b<C-P-C of 1a in asymmetric unit. c<C-P-C of 1b in asymmetric unit.

The average Σ{<CPC} for 1 was calculated to be 304.3(2)o from both

independent molecules in the asymmetric unit (the contrast between their individual

Σ{<CPC} was less than 3σ indicating no crystallographic distinction in their bond angles

around the phosphorus), which would suggest that the steric crowding around the

phosphorus is less than that of PPh3 (307.17o) and implies that the basicity of the lone

pair on phosphorus in 1 is correspondingly less donating than that of PPh3.

47

The average Σ{<CPC} for 2 was determined to be 308.4(2)o implying less steric

bulk around the phosphorus atom than PCy3 (311.43o), but slightly more steric crowding

than PPh3 (307.17o) and 1 (304.3(2)o). The increase in steric crowding of 2 in

comparison to 1 is most likely due to the change in substituents on phosphorus. The

bulkier cyclohexyl moieties would in principle cause the <CPC in 2 to “spread out” to

relieve steric crowding in contrast to the planar phenyl rings of 1. The basicity of the

phosphorus lone pair should change accordingly to the change in P-substituents, it is

reasonable to expect the donating ability of 2 to be greater than 1.

The average Σ{<CPC} for 3 was determined to be 303.8(2)o and while it appears

to be slightly less than the corresponding Σ{<CPC} for 1 (304.3(2)o), they are

crystallographically the same with a difference less than 2σ. The parity of the Σ{<CPC}

values of 1 and 3 is somewhat surprising since the exchange of one phenyl substituent for

an indolyl substituent appeared to have little to no effect on the sum of the <CPC. In the

case of 3, the lower than expected Σ{<CPC} may be due to the orientation of the three

aryl rings in the solid-state structure and perhaps to a lesser extent, crystallographic

packing forces. The two methyl groups at the C3 and C13 positions on the indolyl rings

are almost perpendicular in space with respect to each other, and this rotation of the

indolyl rings is possibly to avoid steric interactions between the two indolyl rings. Due to

the comparability of the Σ{<CPC} values for 1 and 3, one might predict the donating

ability of the phosphorus lone pair to be alike.

The Σ{<CPC} for 5 was calculated to be 306.87(24)o, a value that is larger than

the Σ{<CPC} of 1 (304.3(2)o) and 3 (303.8(2)o) but slightly less than PPh3 (307.17o).

The increased value of Σ{<CPC} of 5 is plausible due to the replacement of all of the

phenyl rings for indolyl rings and the orientation of the indolyl rings in the solid-state can

cause a “spreading out” of the phosphorus substituents. What is interesting to note, is

that the Σ{<CPC} of 5 is approaching the value of Σ{<CPC} of PPh3, which suggests

that the steric crowding around the phosphorus atoms in both phosphines is relatively

similar, and as such the basicity of the phosphorus lone pair should also reflect this

likeness.

48

The Σ{<CPC} value for (N-Bn)-1 was determined to be 307.8(2)o, and is larger

than the Σ{<CPC} value for 1 presumably due to the introduction of the benzyl group at

the nitrogen centre. The greater steric crowding seen in (N-Bn)-1 from the Σ{<CPC}

determination is complementary to the description of the size of the benzylated-

methylindolyl substituent discussed in Section 2.2.4.

Analysis of the Σ{<CPC} in (N-F5Bn)2-4 shows that the coupled indolyl

substituent causes a consequential decrease of this value to 299.2(2)o. Interestingly the

average Σ{<HPH} for PH3 is 280.8o, the geometry about the phosphorus atom is

generally regarded as highly pyramidal and the molecule as having almost perfect

tetrahedral bond angles.11 The Σ{<CPC} for (N-F5Bn)2-4 might suggest that the

coupling of the indolyl moieties to create one bidentate substituent on phosphorus has

caused the phosphorus atom in the N-alkylated derivative of 4 to become more

pyramidal.

Upon closer inspection, it seems there is little correlation with the Σ{<CPC} and

the 31P chemical shifts of the 2-indolylphosphines. While the Σ{<CPC} values do show

some relationship with phosphine basicity (as will be discussed in Chapter 4), the 31P

chemical shifts appear to be more sensitive to the type of substituent on the phosphorus

atom.

2.3.1. Examining Indolyl Aromaticity in 2-

Indolylphosphines

Two methods were employed to determine if the introduction of a phosphino

substituent to the C2-position on indole would affect the aromaticity of the indole,

particularly the five-membered pyrrolyl moiety. The first method examined the bond

distances that make up the pyrrolyl moiety of the indolyl ring of 2-indolylphosphines and

compared to those listed in Table 2.3. The second method to examine pyrrolyl

aromaticity was to define a least-squares mean plane by the five atoms making up the

pyrrolyl ring: N1-C2-C3-C4-C9, then compute the root mean squared (rms) deviation of

49

the five atoms in that plane. If any of the atoms of the pyrrolyl ring diverged appreciably

from the plane of the pyrrolyl ring, this deviation would suggest a loss of aromaticity in

the five-membered ring.

It was found that the distances in 1 were comparable to the analogous bond

distances in indoles from the CSD search. The likeness in bond distances would suggest

no loss of aromaticity in the pyrrolyl ring of indole upon phosphorus bonding at the C2-

position. The pyrrolyl ring in one of the crystallographically independent molecules of 1

has an rms deviation of 0.0044 Å, while the other independent molecule has an analogous

rms deviation of 0.0092 Å. The minor rms deviations of each of the pyrrolyl rings imply

planarity of the five atoms that make up the rings, and as such aromaticity is retained.

Comparing the bond distances of the pyrrolyl ring in 2 and the analogous bond

distances listed in Table 2.3 shows that the five-membered ring appears to be structurally

unaffected by the incorporation of a phosphorus at the C2-position. The rms deviation of

the five atoms in the pyrrolyl ring was calculated based on the plane described by the

same ring and found to be 0.0035 Å, suggestive of ideal planarity.

As with 1, the bonding of the phosphorus atom at the C2-positions on indolyl of 3

do not impose chemically significant changes in the structural features of the pyrrolyl

rings in its 3-methylindolyl substituents. The rms deviation of the five atoms in each of

pyrrolyl rings were found to be 0.0047 Å and 0.0108 Å with respect to the planes

described by the pyrrolyl rings, however the difference in the rms deviation values bear

no chemical significance, and the indolyl substituents of 3 are entirely aromatic.

The bond distances of the pyrrolyl moiety in the indolyl substituent of 5 were

comparable to the corresponding distances listed in Table 2.3, also an rms deviation of

0.0037 Å was calculated for the five atoms in the pyrrolyl ring with regard to the plane

described by the same ring. These properties are consistent with the aforementioned 2-

indolylphosphines as aromatic substituents. As demonstrated in these other 2-

indolylphosphines, the installation of a phosphorus atom at the C2-position on indole

does not perturb the aromaticity of the pyrrole moiety of the indolyl substituents.

For phosphine (N-Bn)-1, neither the bonding of the phosphorus atom at the C2-

position of the indolyl substituent, nor the installation of an alkyl group on the indolyl

nitrogen, display any structural changes that would suggest a departure from aromaticity.

50

Furthermore, the rms deviation of the atoms in the pyrrolyl ring with respect to the plane

described by the pyrrolyl ring was computed to be 0.0043 Å, consistent with the indolyl

substituent remaining aromatic with substituents at N1- and C2-positions.

The solid-state structure of (N-F5Bn)2-4 reveals that the introduction of the

electron withdrawing pentafluorobenzyl substituents imparts little structural change upon

the rest of the molecule. For example, the bond distances of the pyrrolyl moieties in the

coupled indolyl substituent are comparable to the bond distances listed in Table 2.3.

Additionally, the rms deviation of the atoms in the pyrrolyl rings with respect to the plane

described by the pyrrolyl rings were determined to be 0.0035 Å and 0.0046 Å, consistent

with the indolyl substituent remaining aromatic with substituents at N1- and C2-positions

as seen in phosphine (N-Bn)-1.

2.4. Conclusions

In the multiple derivatives of 2-indolylphosphines, the presence of the phosphorus

and the introduction of an alkyl group on the indolyl nitrogen do not seem to impart any

structural changes in pyrrolyl ring that would alter the aromaticity of this ring. The rings

remain planar and the five bond distances that make up the pyrrolyl moiety are consistent

with the CSD search on aromatic indolyl compounds. For the unsubstituted 2-

indolylphosphines, it was found that the methyl group on the indolyl substituents

preferentially crystallized pointing towards the phosphorus lone pair and away from the

pyramid created by the three substituents on phosphorus. In contrast, the methyl group

would point towards the pyramid in the crystal structures of the N-alkylated 2-

indolylphosphines, possibly to reduce the strain within the pyramid created by the

presence of the alkyl group on the indolyl nitrogen.

While the cone angles of these 2-indolylphosphines could not be determined

through the crystal structure data available, the steric crowding of the phosphorus atom

and therefore the relative size of the phosphine may be discussed using Σ{<CPC} values.

The Σ{<CPC} values for the unsubstituted 2-indolylphosphines exhibited a small

relationship where replacing the number of phenyl substituents with indolyl ones resulted

51

in a slight increase in Σ{<CPC}. The Σ{<CPC} did not change appreciably from DPIP

to PDIP, and it may have been due to crystal packing effects. However, as expected, the

exchange of phenyl substituents for bulkier cyclohexyl ones did increase the Σ{<CPC}

drastically from 1 to 2. The Σ{<CPC} calculated for (N-Bn)-1 was considerably larger

than 1, which follows that the introduction of a substituent on the indolyl nitrogen results

in greater steric crowding of the phosphorus lone pair. Contrary to (N-F5Bn)2-4, the

coupled indolyl rings are effectively one substituent on phosphorus that occupies two

coordination sites, and as such the Σ{<CPC} will be smaller for the coupled indolyl

substituent than the analogous uncoupled 2.

In (N-F5Bn)2-4, Additionally, the atoms of the pyrrolyl rings were found to have

rms deviations from the plane described by the pyrrolyl rings of 0.0035 Å and 0.0046 Å,

in agreement with pyrrolyl aromaticity.

2.5. Experimental

Unless otherwise stated, the synthetic protocol for 2-indolylphosphines are reported in

Dr. Edmond Lam’s thesis.8

General Considerations. All reactions and manipulations were carried out under an

atmosphere of dinitrogen using standard Schlenk techniques unless otherwise stated.

PCl3, 1.6 M n-BuLi, NaBH4 were purchased from Aldrich and used as received. 1-[(N,N-

Dimethylamino)methyl]-3-methylindole12 was synthesized according to literature

procedures. THF was distilled from sodium benzophenone ketyl under a dinitrogen

atmosphere. 1H, 13C, and 31P NMR spectra were recorded on Varian 400 MHz or 300

MHz NMR systems, and referenced to SiMe4 (TMS) and 85% H3PO4, respectively.

Splitting patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;

br, broad peak.

52

PNH NH

HN

Tris-2-(3-methylindolyl)phosphine, P(C9H8N)3, 5. 1-[(N,N-Dimethylamino)methyl]-3-

methylindole (4.25 g, 22.6 mmol) was dissolved in THF (60 mL) and cooled to -78oC. n-

BuLi (17.0 mL, 27.2 mmol) was added dropwise over 10 minutes. The reaction was

stirred at -78oC for 10 minutes, warmed to ambient temperature and stirred for 3 hours.

The resulting orange mixture was cooled to -78oC, and PCl3 (0.66 mL, 7.56 mmol) was

added dropwise over 5 minutes. The mixture was allowed to warm to ambient

temperature over 5 hours and then quenched with MeOH. Solvents were removed in

vacuo to yield a yellow solid. Water (100 mL) was added to the solid, and the suspension

extracted with DCM (3 x 100 mL). The organic layers were combined, dried over

anhydrous MgSO4, filtered, and concentrated in vacuo to afford dark orange oil. MeOH

was added to triturate pure aminal-protected product as a white solid, which was isolated

by filtration and dried in vacuo (2.09 g, 47%). Mp: 122oC; 31P NMR (CD2Cl2,

121 MHz): δ -71.3 (s); 1H NMR (CD2Cl2, 300 MHz): δ 7.48 (d, J = 8.1 Hz, 6H, Ar-H),

7.20 (t, J = 7.4 Hz, 3H, Ar-H), 7.07 (t, J = 7.4 Hz, 3H, Ar-H), 4.78 (d, J = 12 Hz, 3H,

amine NCH2), 4.62 (d, J = 12 Hz, 3H, anime NCH2), 2.15 (s, 18H, amine N(CH3)2), 1.84

(s, 9H, indole CH3); 13C NMR (CD2Cl2, 75 MHz):.139.54, 130.14, 126.86, 123.08,

121.39, 119.64, 119.08, 111.06, 67.92, 42.86, 9.11; HRMS EI for C36H45N6P: calcd m/z

592.344334, found m/z 592.344809; Microanalysis for C36H45N6P: calcd (%) C = 72.94,

H = 7.65, N = 14.18, found (%) C = 72.56, H = 7.57, N = 13.78. A solution of

THF/EtOH (120 mL, 1:1 v/v) was added to a solid mixture of the aminal-protected

product (3.75 g, 6.33 mmol) and NaBH4 (1.50 g, 39.7 mmol). The mixture was refluxed

for 5 hours. The solution was reduced to dryness in vacuo and acidified water was added

to the resultant white solid, which was extracted with DCM (3 x 100 mL). The organic

phases were combined and dried over anhydrous MgSO4, filtered and taken to dryness to

afford a dark yellow coloured oil. MeOH was added to triturate pure product as a white

solid, which was isolated by filtration and dried in vacuo (1.84 g, 69 %). Mp: 166oC; 31P

53

NMR (CD2Cl2, 121 MHz): δ -81.7 (s); 1H NMR (CD2Cl2, 300 MHz): δ 7.90 (br s, 3H,

indole NH), 7.60 (d, J = 7.2 Hz, 3H, Ar-H), 7.27 (d, J = 7.5 Hz, 3H, Ar-H), 7.21 – 7.12

(m, 6H, Ar-H), 2.41 (s, 9H, indole CH3); 13C NMR (CD2Cl2, 75 MHz): 138.94, 130.29,

125.53, 123.69, 121.34, 120.17, 119.54, 111.80, 9.90; HRMS EI for C27H24N3P: calcd

m/z 421.170357, found m/z 421.170786; Microanalysis for C27H24N3P: calcd (%)

C = 76.94, H = 5.74, N = 9.97, found (%)C = 76.70, H = 5.78, N = 9.79.

X-ray Crystallography. X-ray data were collected on a Nonius Kappa CCD

diffractometer using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). A

combination of 1º φ and ω (with κ offsets) scans were used to collect sufficient data. The

data frames were integrated and scaled using the Denzo-SMN package.13 The structures

were solved and refined with the SHELXTL-PC v6.12 software package.14 Refinement

was by full-matrix least squares on F2 using data (including negative intensities) with

hydrogen atoms bonded to carbon and nitrogen atoms included in calculated positions

and treated as riding atoms. Absorption corrections were made for every structure. All

the heavy atoms were refined anisotropically.

54

2.6. References



(3) Muller, T. E.; Mingos, D. M. P. Transition Met. Chem. 1995, 20, 533 - 539.

(4) Bartik, T.; Himmler, H.-G.; Seevogel, K. J. Organomet. Chem. 1984, 272, 29 -

41.


(6) Boere, R. T.; Zhang, Y. J. Organomet. Chem. 2005, 690, 2651 - 2657.

(7) CSD Database (version 5.29, January 2008).



1720-1722.

(10) Rampersad, N. C., MSc Thesis, University of Toronto, 2001.

(11) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements; 2nd ed.;

Butterworth-Heinemann: Oxford, 1997.


(13) Otwinowski, Z.; Minor, W. Methods Enzymol. 1997, 276, 307-326.

(14) Sheldrick, G. M. In SHELXTL-Windows NT. V6.12, Bruker Analytical X-Ray

Systems Inc. Madison, WI, 2001.

54

Chapter 3

Tris-2-(3-methylindolyl)phosphine:

Synthesis, Reactivity and Anion Binding

3.1. Introduction

Electroneutral anion recognition hosts have suitable NH donors to bind anion

guests, and are commonly based on small molecules with organic scaffolds that usually

incorporate a combination of amides,1-4 pyrroles,5-8 and / or ureas.9-12 The acidity of the

hydrogen bond donors can be increased in order to improve anion binding, often through

the incorporation of electron-withdrawing substituents on the receptor.13,14 Another

method to increase the acidity of a hydrogen bond donor is to fuse a pyrrole ring to a

benzene ring, which creates an indole moiety; this changes the pKa of the NH from 23.0

in pyrrole to 20.9 in indole (in DMSO).15 Interestingly, indole-based hosts have only

recently been investigated, and they have demonstrated anion binding capability and high

selectivity for various anions (refer to Chapter 1 for a detailed review).

Only several reports of phosphines acting as anion receptors have been reported,

where the phosphorus centres are situated more than two bonds away from the hydrogen

bond donor sites.10-12,16 In these examples the phosphorus centre appears to provide a

metal coordination site, and provide precedence for simultaneous coordination at the

phosphorus site while the receptor is engaged in hydrogen bonding to anion guests.

55

56

3.1.1. Hydrogen Bonding in 2-Indolylphosphines

The palladium chloride dimer complexes of the mono- and di-indolylphosphines

have demonstrated the propensity to form intramolecular (Figure 3.1a) as well as

intermolecular hydrogen bonds (Figure 3.1b) in their solid-state structures, which will be

discussed in greater detail in Chapter 4.3 The C3-symmetric phosphine 5, was

synthesized to investigate whether the three indolyl NH sites are suitably positioned to act

collectively to form strong hydrogen bonding interactions with anions. Its phosphorus

centre serves as an additional site of reactivity through which the receptor may, in

principle, simultaneously coordinate to transition metals or other Lewis acids. The close

spatial proximity of the phosphorus centre to the NH moieties in 5 lies in contrast to

phosphines which have previously been reported to act as anion receptors in which the

phosphorus centres are well-displaced from the sites of hydrogen-bonding.10-12,16

(a) (b)

Figure 3.1. (a) Intramolecular hydrogen bonding in the [Pd(1)Cl(μ-Cl)]2 between N1 and Cl2 [3.109(3) Å].

(b) Hydrogen bonding in the [Pd(4)Cl(μ-Cl)]2·H2O complex: intramolecular hydrogen bonding between

N11 and Cl2 [3.243(3) Å], and intermolecular hydrogen bonding between N1 and O1 [2.941(4) Å].

57

In this Chapter, symmetric phosphine 5 will be examined for anion binding

capability through a series of anion titrations. Based on the utility of 5 to bind anions, a

new indolylphosphine-based anion receptor is designed, and the attempted synthesis of

this new phosphine molecule will be presented. Furthermore, a molecular cleft based on

two indole rings separated by a rigid phenyl linker, will be investigated for its anion

binding ability.


3.2.1. Synthesis of Tris-2-(3-methylindolyl)phosphine

Lithiation of indole preferentially occurs at the nitrogen or at the C3-position; by

controlling the reactivity at these more vulnerable centres with protecting groups the

desired lithiation at the C2-position is achieved. The C3-position is easily blocked from

reactivity by the introduction of a methyl group, and this convenient 3-methylindole

starting material is commercially available. Several protecting groups commonly used

for amine protection have been investigated and it was determined that the N,N’-

dimethylaminomethylene protecting group is the most suitable for our purpose as it

directs lithiation to the C2-position on indole. Following the work of Katrizky and co-

workers, the N,N’-dimethylaminomethylene moiety can be introduced easily by refluxing

3-methylindole with formaldehyde and dimethylamine in water to afford the protected 3-

methylindole in quantitative yield following aqueous work-up.17 Lithiation of indole is

achieved at the C2-position with n-BuLi at -78oC, and the subsequent addition of

trichlorophosphine leads to chloride substitution by the indolyl groups to provide the

desired aminal-protected phosphine in 47% yield after reacting for 24h. The 31P NMR

spectrum of aminal-protected 5 exhibited one signal indicating a single phosphorus

environment at δ = -71.3 ppm in CD2Cl2, and in the 1H NMR the presence of the NMe2

resonances for the protecting group attached to the indole nitrogen.

58

The N,N’-dimethylaminomethylene aminal protecting group can be

straightforwardly removed upon reaction of the protected phosphine with NaBH4 in a

THF / EtOH reflux. After successive aqueous work-up, phosphine 5 is afforded in 32%

yield from trituration with MeOH (Scheme 3.1). The 31P NMR spectrum of 5 exhibited

only one phosphorus environment at δ = -81.7 ppm in CD2Cl2; the 1H NMR spectrum

showed the absence of the aminal protecting group and the emergence of an indole NH

proton resonance at δ = 7.87 ppm in CD2Cl2.

N

N

N

P

N

1. n-BuLi2. PCl3

THF-78oC

1. NaBH4EtOH/THF

reflux2. HCl workup

47% overall 32%

N NN

N

HN

P

HN NH

Scheme 3.1. The synthesis of 5 from the aminal-protected 3-methylindole.

An alternative one-pot synthesis of ligand 5 can be carried out by using CO2 as a

protecting agent for the indolyl nitrogen18 that is also capable of directing lithiation to the

C2-position on indole. The indolyl NH proton of 3-methylindole is deprotonated with n-

BuLi; subsequent bubbling of the reaction with a stream of CO2 gas furnishes the

protecting group onto the nitrogen centre. The C2-position on the CO2-protected indole

is deprotonated with t-BuLi, and addition of trichlorophosphine generates the CO2-

protected derivative of phosphine 5. The CO2 protecting group is conveniently cleaved

upon aqueous workup of 5 (Scheme 3.2). Phosphine 5 is easily recovered by trituration

from MeOH in yields that are comparable to the aforementioned synthetic procedure.

59

1. n-BuLi2. CO2

THF, -78oC

HN

N

OOLi 1. t-BuLi

2. PCl3THF, -78oC3. Aqueous

workup

NH

P

HN

HN

39% Scheme 3.2. The synthesis of 5 from 3-methylindole with CO2 as a protecting group for the indole

nitrogen.

3.2.2. Anion Binding Properties of Tris-2-(3-

methylindolyl)phosphine

It is evident from the crystal structure of 5 that the indolyl substituents are

arranged such that the indolyl NH functionalities are in proximity to form the necessary

hydrogen bond donor cavity (Figure 3.2). Refer to Chapter 2 for a detailed discussion on

the solid-state structure of 5. 1H NMR titration techniques with anions will provide

information on the extent to which 5 can function as an anion receptor.

Figure 3.2. Bowl shaped hydrogen bonding cavity of 5. Selected bond angle: <C2-P1-C2 102.3(1)o,

Σ{<CPC} = 306.9(2)o.

1H NMR titration techniques in CD2Cl2 were employed to assess the anion binding

capability of 5 with selected anions as their tetrabutylammonium salts (Scheme 3.3).

60

PNH NH

HNCD2Cl2

+ NBu4X P

HN

3

X

NBu4

Scheme 3.3. General titration scheme of 5 with anions as their tetrabutylammonium salts in CD2Cl2.

Selected anions: X- = Cl-, Br-, CH3COO-, HSO4-, NO3

-, and BF4-.

The interaction of 5 with anions was monitored by the increasing downfield shift of the

indolyl NH resonances (δ = 7.87 ppm for the uncomplexed 5) with increasing anion

concentration until saturation was obtained. Figure 3.3 shows a general compilation of 1H NMR spectra from a typical titration experiment using the Cl- anion. The ambient

temperature 1H NMR titrations reveal that the hydrogen bonding interactions between 5

and the anion are fast on the NMR time scale, suggested by only one resonance being

observed for the indolyl NH sites. In general, the larger the downfield chemical shift of

the protons being monitored at any point during the titration, the stronger the binding to

that particular anion.

61

NH

0 eq

0.5 eq

1 eq

2 eq

4 eq

ppm (t1)7.08.09.010.011.012.013.0

6 eq

Figure 3.3. A representative example of partial titration stack plots for the addition of Cl- anion to 5 in

CD2Cl2 at 298K.

In all cases the data could be fitted to a 1 : 1 receptor : anion binding model by means

of the EQNMR software19 to obtain the stability constants listed in Table 3.1.

Figure 3.4 is a fit plot illustration for the titration of 5 with Cl-, it is a representative

example of the saturation curve for the titration experiment. A minor amount of 2 : 1

receptor : anion binding was observed at low concentrations of strongly coordinating

anions (Cl-, Br-, CH3COO-). The fit plots for the remainder of the titration

experiments are deposited in the Experimental section of this chapter. The errors

associated with the stability constants were determined by the fit of the experimental

curve to the calculated curve, and the overall errors computed as the quotient between

the error in Ka and the value of Ka. The fit of the acetate anion titration curve

(Figure 3.18) is imperfect even though the error on the stability constant is

approxiamtely 4%. The poorer fit is most likely due to the interaction of additional

hydrogen atoms on the indolyl moiety with the acetate anion (Figure 3.7). The errors

62

associated with the iodide, hydrogensulfate, and tetrafluoroborate are expected to be

higher since these titration experiments do not appear to reach a saturation point.

Thus, the stability constants for these experiments may not be entirely accurate.

Figure 3.4. Fit plot for titration experiment of 5 with tetrabutylammonium chloride in CD2Cl2.

Table 3.1. Stability constants Ka (M-1) of 5 with a selection of anion guests as determined by 1H NMR

titration techniques performed at 298 K following NH resonances in 5.a

Anion Ka Error in Ka Overall error (%)

Cl- 3920 +/- 86 2.2

Br- 320 +/- 0.5 0.2

I- 20 +/- 0.3 1.5

CH3COO- 2730 +/- 120 4.4

HSO4- 35 +/- 0.6 1.7

NO3- 100 +/- 0.4 0.4

BF4- 150 +/- 14 9.3

The symmetry and position of the NH groups of the receptor provide a well-

defined hydrogen bonding cavity of geometry and size suitable for binding well to

spherical anions such as halides, in particular to Cl- as it has the largest stability constant.

The high charge densities on the oxygen atoms of CH3COO- are likely responsible for the

strong interaction that it exhibits with 5. While the NO3-, HSO4

-, and BF4- anions provide

an improved complement in symmetry to the hydrogen bond cavity of receptor 5, the

63

reduced ability of 5 to bind these anions may be due to their diffuse singly negative

charges being delocalized over several terminal atoms.

The stability constants of 5 are relatively modest (considering the anion

binding studies are carried out in dichloromethane), in comparison to most indole-based

receptors reported in the literature, which are predominantly studied in more polar

solvents such as DMSO or acetonitrile.20-27 Phosphine 5 does show better binding to

chloride anion (Ka = 3920 M-1) than the two diindolylquinoxaline-based anion receptors

reported by Sessler and co-workers (Ka = 170 M-1 for the unfunctionalized receptor, and

250 M-1 for the nitro functionalized receptor) (Figure 3.5 and Table 3.9).28 It is suspected

that the better binding to chloride seen in 5 is most likely due to the additional hydrogen

bond donor that is not present in Sessler’s two diindolylquinoxaline-based receptors.

N N

NH

NH

NO2

N N

NH

NH

(a) (b) Figure 3.5. Sessler and co-workers’ diindolylquinoxaline-based anion receptors. (a) Unfunctionalized

bisindole. (b) Nitro functionalized bisindole.28

Single crystals of the [NEt4][5·CH3COO] complex, 6, were grown from slow

evaporation from a MeOH/CH2Cl2 solution of the complex, and X-ray diffraction

experimental data are listed in Table 3.2. Complex 6 crystallizes in the monoclinic space

group P21/n, with two independent sets of molecules in the asymmetric unit (Figure 3.6).

Selected bond distances and angles are listed in Table 3.3. One molecule of

uncomplexed 5 concomitantly crystallizes with one complex of 6; the NEt4+ cation is

disordered over two sites with the major component modeled at 60% occupancy and the

minor component at 40% occupancy; two methanol solvent molecules are hydrogen

bonded to the acetate anion.

64

Figure 3.6. ORTEP diagram of one of the two independent sets of molecules in the asymmetric unit of

complex 6 with concomitant uncomplexed 5. Non-acidic protons removed for clarity. Disordered NEt4+

cation removed for clarity. Thermal ellipsoids drawn at 35%.

The crystal structure of 6 confirms the 1 : 1 receptor to anion binding ratio

determined through 1H NMR titration techniques. The acetate anion hydrogen bonds to 5

through one of its oxygen atoms, O1A, with typical hydrogen bonding distances in the

range N…O- of 2.817(2) Å to 2.927(2) Å; coupled with the hydrogen bond angles

<NH…O- (range from 155.8o to 172.7o) these can be considered of moderate interaction

strength.29 An additional interaction from C18B to O2A can be seen in Figure 3.7, and is

thought to give rise to the poorer fitting of the titration plot of acetate with phosphine 5

(Figure 3.18). While the interaction between C18B and O2A is not considered a

hydrogen bond (the 3.488(3) Å distance is longer than accepted hydrogen bond lengths),

presumably it contributes to the binding strength of phosphine 5 to the acetate anion.

65

Figure 3.7. ORTEP diagram illustrating the hydrogen bonding in complex 6. Only selected protons are

shown for clarity. Disordered NEt4+ cation, and concomitantly crystallized phosphine 5 removed for

clarity. Thermal ellipsoids drawn at 35%.

Two methanol solvates are seen to hydrogen bond to the other oxygen atom, O2A,

of the acetate anion. The C-O bond lengths of the acetate anion are indistinguishable

from each other (C1AA-O1A 1.264(3) Å and C1AA-O2A 1.257(3) Å), indicating

delocalization of the C-O double bond even in the presence of hydrogen bonding to 5. It

is interesting to note that while the possibility exists for the acetate anion to hydrogen

bond to 5 in two modes (such as both oxygen atoms hydrogen bonding to the cavity), the

acetate anion preferentially coordinates to 5 via one oxygen atom; a result of all three

indolyl NH sites collectively engaged in hydrogen bonding and possibly a small

hydrogen bond donor cavity size.

While the acetate anion does not appear to impart important structural changes in

the bond lengths and angles of 5, the Σ{<CPC} value for 6 was determined to be

313.2(2)o, and is larger than the corresponding Σ{<CPC} value for 5. The concomitantly

crystallized uncomplexed 5 moiety has a Σ{<CPC} value of 305.0(2)o, and is comparable

to the crystal structure of 5 (306.9(2)o) as discussed in Chapter 2. The increase in the

Σ{<CPC} value in 6 may be due to the necessary expansion of the <CPC bond angles to

accommodate a hydrogen bonded guest; it suggests that hydrogen bonding to acetate does

not pull the indolyl substituents together but rather forces them apart. The uncomplexed

5 in the 6 structure additionally hydrogen bonds to the two methanol solvent molecules

66

that are hydrogen bonding to an acetate anion of an adjacent asymmetric unit with

ordinary hydrogen bond donor-to-acceptor distances (2.856(3) Å to 3.106(2) Å), and

hydrogen bond angles <NH…O- (141o to 145o). While there is considerable hydrogen

bonding among the components of the unit cell, it does not extend beyond the unit cell.

While the absence of a clean fit to a 1 : 1 receptor : anion binding model

precluded an accurate determination of its stability constant, the 1H NMR of 5 in the

presence of F- anion exhibited the largest downfield change in chemical shift of the

indolyl NH signals (ca. 6.7 ppm), suggesting a very strong interaction with them.30 This

is consistent with the well-known propensity of F- to serve as a strong hydrogen bond

acceptor. To confirm the interaction between F- and 5, single crystals of the [5·F]-

complex, as its tetraethylammonium salt, 7, were obtained from a solution of the complex

in a MeCN / MeOH mixture layered with Et2O. The X-ray diffraction experimental data

are shown in Table 3.2, whereas Table 3.3 lists selected bond distances and angles. The

numbering scheme of complex 7 is shown in Figure 3.8.

67

Table 3.2. X-ray crystallographic experimental data of [5·X]- complexes.

6

P

HN

3

O

NEt4

O

7

P

HN

3

F

NEt4

8

P

HN

3

I

CH3+

Formula C66H79N7O4P2 C73H100F2N8O3P2 C32H37IN3OP Formula Weight 548.15 1237.55 637.52 Crystal colour, shape colourless, block colourless, block colourless, plates Crystal size, mm 0.38 x 0.14 x 0.10 0.58 x 0.30 x 0.20 0.24 x 0.14 x 0.08 Crystal system Monoclinic Orthorhombic Monoclinic Space group P21/n P212121 P21/c a, Å 15.2163(2) 11.3758(1) 10.4385(5) b, Å 20.6034(3) 24.2008(2) 22.9652(14) c, Å 20.4701(3) 24.9237(2) 12.8667(7) α deg 90 90 90 β, deg 111.1640(10) 90 91.542(4) γ deg 90 90 90 V, Å3 5984.67(15) 6861.6(1) 3083.3(3) Z 4 4 4 Dcalcd, g cm-3 1.217 1.198 1.373 F(000) 2344 2664 1304 μ, mm-1 0.127 0.121 1.119 λ (Mo Kα), Å 0.71073 0.71073 0.71073 Limiting indices -19<=h<=19 -11<=h<=14 -13<=h<=13 -24<=k<=26 -31<=k<=31 -29<=k<=29 -26<=l<=26 -31<=l<=32 -13<=l<=16 2θ range, deg 2.85 to 27.48 2.57 to 27.55 1.77 to 27.50 Max. and min. transmission 1.008 and 0.479 0.998 and 0.591 0.899 and 0.490 No. of reflections collected 55668 46395 21801 No. of independent reflections/Rint 13676 /0.0971 15463 / 0.0807 7160 / 0.1133 Absolute structure parameter - 0.01(7) - Extinction coefficient 0.0028(3) 0.0014(5) 0.0029(5) No. of refined parameters 763 811 350 Final R1, wR2 0.0558, 0.1231 0.0532, 0.1278 0.0713, 0.1497 Final R1, wR2 (all data) 0.1072, 0.1470 0.0707, 0.1389 0.1775, 0.2038 Goodness of fit 1.022 1.056 1.057 Δρmin, Δρmax, eÅ-3 -0.411, 0.372 -0.345, 0.572 1.490, -0.921

68

Complex 7 crystallizes in the orthorhombic space group P212121 with two

independent complexes, 7a and 7b, and three methanol solvate molecules in the

asymmetric unit (Figure 3.8). The solid-state structure confirms the interaction between

fluoride and 5 to be a 1 : 1 anion to receptor stoichiometry. Phosphine 5 exhibits

hydrogen bonding to the fluoride with all three of the indolyl NH sites in both complexes,

with typical hydrogen bond donor-to-acceptor distances that range from N…F- 2.632(3) Å

to 2.790(2) Å;31 along with the hydrogen bond angles <NH…F- (159.1o to 176.2o) these

interactions can be considered hydrogen bonds of moderate strength.29 The fluoride

anion does not appear to impart significant structural changes to the phosphine, and bond

lengths and angles are comparable to the uncomplexed 5. Correspondingly, the

aromaticity of the pyrrolyl ring is not affected by the hydrogen bonded fluoride anion.

Figure 3.8. ORTEP diagram of 7. Non-acidic protons removed for clarity. NEt4

+ cations removed for

clarity. Thermal ellipsoids drawn at 35% probability.

The fluoride anion of complex 7a hydrogen bonds to one MeOH solvate, and has a

distorted four-coordinate tetrahedral coordination geometry, with hydrogen bond donor-

to-acceptor distance and angle of 2.597(3) Å and 171.4o, respectively. The fluoride anion

of 7b hydrogen bonds to two MeOH solvent molecules, and has a distorted five-

coordinate geometry, bearing average hydrogen bond donor-to-acceptor distance and

angle of 2.669(4) Å and 178.3o, respectively. Despite the fact that there is extensive

hydrogen bonding between the components in the unit cell, the hydrogen bonding is

considered zero-dimensional and does not form an extended array.

69

Even though F- and CH3COO- strongly bind to 5, the hydrogen bonding distance

of the CH3COO- is slightly longer than the analogous interaction of 7 (N…F- 2.722(1) Å),

presumably due to the more compatible fit of the spherical halide to that of the bulkier

acetate. Compared to uncomplexed 5 (Σ{<CPC) = 306.9(2)o), the hydrogen bonding of

the fluoride anion results in an increase in the C-P-C bond angles of the phosphine as

seen in the Σ{<CPC} bond angles in 7, which are determined to be 311.6(2)o and

312.2(2)o for 7a and 7b, respectively. This suggests the necessity for 5’s <CPC bond

angles to “open up” in order to accommodate hydrogen bonding to a guest. Presumably,

the larger the guest, the greater is the increase in the Σ{<CPC} value. Therefore 6 with

its larger acetate guest has a larger Σ{<CPC} value than 7.

The titration of NBu4I with 5 indicated a 1 : 1 receptor : anion interaction, albeit a

weak one with a stability constant of 20 M-1. However, the reaction with

tetraethylammonium iodide with 5 did not yield crystals as the analogous reactions

between 5 and F- or CH3COO- did. However it was thought that the formation of a

phosphonium cation would increase indolyl NH acidity. The generation of the

phosphonium cation of 5 was carried out by reaction with a stoichiometric amount of

methyl iodide in THF (Scheme 3.4).

P

NH

HN

NH + CH3I THF

P

HN

CH3

3

I

Scheme 3.4. Reaction scheme to form [CH3-5]I, 8, from 5 and CH3I.

The 31P NMR spectrum of the [CH3-5]I species, 8, contains the presence of one signal

occurring at -12.1 ppm, indicating a single phosphorus environment that is shifted

downfield from 5 (δ -81.7 ppm) and is consistent with methylation at the phosphorus

centre.32 Similarly, the downfield chemical shift of the indolyl NH resonances in the 1H

NMR spectrum is also consistent with some degree of NH-iodide interaction. Single

crystals of 8 were obtained from Et2O vapour diffusion into a solution of CH2Cl2

70

containing the complex; the X-ray diffraction experimental data are listed in Table 3.2,

while selected bond angles and distances are listed in Table 3.3. Complex 8 crystallizes

in the monoclinic space group P21/c, with one [CH3-5]+ complex, one iodide anion, and a

hydrogen bonded Et2O solvate in the asymmetric unit. The complex forms a hydrogen

bonded dimer in the solid state, one half of which is related to the other by a

crystallographic 21 screw axis along the b-axis. Two iodide anions interact with two

[CH3-5]+ cations via symmetry equivalent indolyl NH sites (Figure 3.9).

71

Table 3.3. Selected bond lengths (Å) and bond angles (o) for [5.X]- complexes. 6

P

HN

3

O

NEt4

O

5 in crystal of 6

PNH NH

HN

7a

P

HN

3

F

NEt4

7b

P

HN

3

F

NEt4

8

P

HN

3

I

CH3+

P1-C2 1.817(2) 1.815(2) 1.814(3) 1.817(2) 1.767(7)

P1-C12 1.823(2) 1.805(2) 1.812(3) 1.819(2) 1.773(6) P1-C22 1.805(2) 1.821(2) 1.813(2) 1.808(2) 1.780(7)

<C2-P1-C12 103.2(1) 103.2(1) 101.9(1) 102.7(1) 110.2(3) <C12-P1-C22 105.6(1) 102.1(1) 106.2(1) 105.5(1) 108.2(3) <C22-P1-C2 104.5(1) 99.7(1) 103.5(1) 104.0(1) 111.1(3)

avg. Σ{<CPC} 313.2(2) 305.0(2) 311.6(2) 312.2(2) 329.5(5)

N1-C2 1.393(3) 1.387(3) 1.391(3) 1.389(3) 1.394(8) C2-C3 1.382(3) 1.378(3) 1.388(4) 1.382(3) 1.362(9) C3-C4 1.431(3) 1.435(3) 1.431(4) 1.437(4) 1.426(10) C4-C9 1.406(3) 1.412(3) 1.415(4) 1.416(4) 1.421(9) C9-N1 1.371(3) 1.375(3) 1.367(3) 1.368(3) 1.373(8)

<C9-N1-C2 109.3(2) 109.5(2) 109.6(2) 109.6(2) 108.6(5) <N1-C2-C3 108.4(2) 109.1(2) 108.5(2) 108.9(2) 109.6(6) <C2-C3-C4 107.2(2) 106.7(2) 106.9(2) 106.8(2) 107.3(6) <C3-C4-C9 107.2(2) 107.5(2) 107.2(2) 107.1(2) 107.0(6) <C4-C9-N1 107.9(2) 107.3(2) 107.8(2) 107.7(2) 107.5(6)

N11-C12 1.389(3) 1.392(3) 1.392(3) 1.400(3) 1.385(8) C12-C13 1.372(3) 1.382(3) 1.380(4) 1.376(4) 1.385(9) C13-C14 1.437(3) 1.436(3) 1.438(4) 1.431(4) 1.429(9) C14-C19 1.410(3) 1.410(3) 1.419(4) 1.407(4) 1.407(9) C19-N11 1.370(3) 1.368(3) 1.371(3) 1.367(3) 1.363(8)

<C19-N11-C12 109.3(2) 109.3(2) 109.2(2) 109.0(2) 108.8(5) <N11-C12-C13 108.8 (2) 109.0(2) 109.1(2) 108.7(2) 109.8(6) <C12-C13-C14 107.3(2) 106.5(2) 107.2(2) 107.1(2) 105.7(6) <C13-C14-C19 106.7(2) 107.4(2) 106.6(2) 107.2(2) 107.8(6) <C14-C19-N11 107.9(2) 107.8(2) 108.0(2) 108.1(2) 108.0(6)

N21-C22 1.394(3) 1.392(3) 1.404(3) 1.401(3) 1.388(9) C22-C23 1.382(3) 1.376(3) 1.373(3) 1.374(3) 1.370(9) C23-C24 1.435(3) 1.435(3) 1.442(3) 1.432(3) 1.432(9) C24-C29 1.410(3) 1.409(3) 1.407(3) 1.414(3) 1.396(9) C29-N21 1.369(3) 1.377(3) 1.362(3) 1.369(3) 1.381(8)


N1 .. X 2.870(2) - 2.727(3) 2.726(3) - N11 .. X 2.817(2) - 2.716(3) 2.790(2) 3.427(5) N21 .. X 2.927(2) - 2.632(3) 2.711(2) 3.490(5)

<N1-H1-X 155.8 - 172.5 175.7 -

<N11-H11-X 163.8 - 159.1 168.6 167.6 <N21-H21-X 172.7 - 175.1 176.2 156.0

72

Figure 3.9. ORTEP diagram of symmetric dimer of 8 in the crystallographic ab-plane. Non-acidic protons

removed for clarity. Thermal ellipsoids are drawn at 35% probability.

The unsymmetrical intermolecular iodide to indolyl NH interaction distances

(3.427(5) Å and 3.490(5) Å) are in agreement with previously reported hydrogen bonds

to iodide.31 The indolyl NH interaction with iodide has <NH…I- bond angles (156.0o and

167.6o) suggesting near linear interactions. The Et2O solvent molecule hydrogen bonds

to one of the indolyl NH sites not already interacting with the iodide anion, with a typical

hydrogen bond distance of 2.950(7) Å. Three C-H…I- interactions contribute to the three-

dimensional arrangement of the molecules in the unit cell. The C…I- interaction distances

[3.978(7),33 3.970(7), and 3.794(8) Å34] are comparable to those found in the solid-state

structure of (benzoylmethyl)triphenylphosphonium iodide (C…I- range 3.696(2) to

3.983(2) Å).35 The Σ{<CPC} bond angle was found to be 329.5(5)o and the increase in

this value from 5 is most likely due to the methylation of the phosphorus centre which

has altered its hybridization,35 as opposed to the indolyl NH interaction with iodide.

73

3.3. Design of a New Symmetric Anion Receptor

While compound 5 has shown capacity for binding anions, greater anion

selectivity cannot be achieved in phosphine 5 without further structural modifications to

it. One design strategy is to build an anion receptor that has greater flexibility in its

structure that may allow for discriminatory binding to larger and more complex anions.

Pfeffer and co-workers have shown how changing the size of an anion receptor,

through the addition of an elongated flexible linker, results in its subsequent selectivity

for acetate over other anions.36 The authors present two indole-based receptors that are

structurally similar in that both receptors contain indolyl and amido NH functionalities;

the short receptor contains a urea functionality which is separated from the indolyl and

amido hydrogen bond donors through an ethyl linker; the long receptor instead contains a

nitro-functionalized thiourea substituent, and is separated from the indolyl and amido

groups by a hexyl linker (Figure 3.10). Although the presence of the thiourea and the

electron withdrawing nitro substituent in the longer receptor should increase the acidity

of the hydrogen bond donors, thus leading to stronger anion interaction, the authors’ main

concern was whether the flexibility and the length of the linker would have an influence

on the anion binding ability of the receptors.36 The stability constants from titrations of

selected anions with these varied length receptors are listed in Table 3.4.

NH

N

O

H NH

O

NH

NH

N

O

H NH

S

NH NO2

(b)(a) Figure 3.10. Flexible indole-based anion receptors by Pfeffer and co-workers:36 (a) short indole-based

anion receptor, (b) long indole-based anion receptor.

In the case of the short receptor, the lack of chloride binding suggested that the

ethyl linker was not long enough to allow for cooperative interaction of all four of the

hydrogen bond donors. Similarly, the binding to acetate was predominantly through the

urea NH donor site. The long receptor has preference for binding acetate, and it has been

74

suggested that the length of the linker is responsible for allowing the four hydrogen bond

donors to function collectively, which consequently leads to a strong interaction with

acetate.

Table 3.4. Stability constants Ka (M-1) of indole-based short receptor and indole-based long receptor with

chloride and acetate guests as determined by 1H NMR titration techniques performed at 298 K.36

Anion

Ka

NH

N

O

H NH

O

NH

Ka

NH

N

O

H NH

S

NH NO2

Cl- 125 no binding detected

CH3COO- 1260 7940

A new anion receptor based on C3-symmetric 5 would incorporate an additional

methylene-bridge between the indolyl substituent and the phosphorus atom. The added

methylene functionality should provide an extra degree of freedom that may allow for

greater anion selectivity, and greater conformational flexibility to accommodate a larger

number of anions.

75

3.3.1. Synthesis of New C3-Symmetric Anion Receptor

A retrosynthetic methodology was used in determining the best route to take to

generate the target C3-symmetric 5-based anion receptor, (CH2)3-5, 9 (Figure 3.11a).

However, prior to embarking on the synthesis of the target anion receptor, a model

phosphine, (CH2indolyl)PPh2, 10 (Figure 3.11b), would be synthesized first to establish

the viability of the reaction routes. The commercially available 1H-indole-2-carboxylic

acid ethyl ester, 11, was chosen as a suitable starting material, as there has been literature

precedence for the formation of the desired methylene-bridged indolyl substituent using

this material.37

HN

HN

NHP

HN

P

9 1

(a) (b)

0

Figure 3.11. (a) New C3-symmetric 5-based anion receptor target, P(C9H8N)3, 9. (b) Model phosphine

P(C9H8N)(C6H5)2, 10.

Initially the familiar N,N’-dimethylaminomethylene protecting group, normally

utilized for the protection of 3-methylindole to generate the aminal-protected starting

material to 2-indolylphosphines, could not be installed on the nitrogen centre. Two

known methods (reacting 11 with NEt3 followed by addition of N,N’-

dimethylmethyleneammonium chloride,3 or alternatively reacting 11 with formaldehyde

and dimethylamine17) were unsuccessful in the protection of the indole nitrogen

(Scheme 3.5).

76

HN O

OEt

N O

OEt

N

Me2NHH2O

reflux

H H

O

NEt3THFr.t.

no reactionMe2N CH2Cl11

Scheme 3.5. The two unsuccessful methods used to install the N,N’-dimethylaminomethylene protecting

group on the nitrogen centre of 11. (a) Reaction conditions: formaldehyde, dimethylamine, and 11 refluxed

in water. (b) Reaction conditions: Dimethylmethyleneammonium chloride, triethylamine, and 11 stirred in

THF at room temperature.

The t-Boc-protecting group is a versatile protecting group that can be used to

protect a variety of nitrogen centres and is resistant to diverse reaction conditions.38 The

t-Boc group is easily furnished on the indole nitrogen in near quantitative yield by

reaction of 11 with di-tert-butyl dicarbonate in the presence of DMAP at ambient

temperature. The reaction was completed in 1.5 h as monitored by TLC. Aqueous

workup, extraction, and subsequent removal of volatile solvents gave t-Boc-protected

indole-2-carboxylic acid ethyl ester, 12 (Scheme 3.6). The 1H NMR spectrum of 12

lacked the indole NH proton resonance, and exhibited a large singlet at δ = 1.63 ppm (in

CDCl3) that is associated with the t-Boc protecting group.

Compound 12 was reduced to the alcohol with DIBAL-H in toluene at -40oC

according to literature procedures.37 The reaction was allowed to stir at -40oC for 50

minutes, allowed to warm to -10oC and then quenched with MeOH and water. Following

an extraction and removal of volatile solvents, a dark-orange oil was recovered. Column

chromatography was required to purify the t-Boc-protected indole-2-methyl alcohol, 13,

which was recovered in 78 % yield. The characterization of 13 is identical to the one

reported for the same compound by Belanger and co-workers.37 The 1H NMR of 13

clearly exhibits the appearance of the methylene functionality at the C2-position on

indole as a singlet at δ = 1.68 ppm (in CDCl3), and the EI-HRMS is consistent with the

formation of the alcohol.

77

Alcohol 13 can be transformed into the useful bromide reagent through several

means: the classic method of alcohol conversion to bromide uses PBr3,39 or by reaction of

the alcohol with PPh3Br2, a milder reaction that proceeds at room temperature under 30

minutes.40,41 A solution of 13 in CH2Cl2 is added dropwise to a suspension of PPh3Br2 in

CH2Cl2. After stirring for 10 minutes the reaction is quenched with water. Upon workup

and subsequent chromatography, it was discovered that the acid sensitive t-Boc-

protecting group was cleaved from the indole due to minute, but sufficient amounts of

HBr generated as a side product in the reaction. Thus re-evaluation of the protecting

group was necessary in order to make the useful indole-2-methyl bromide.

HN

OEt

ON

OEt

O

O ON

OH

O ON

Br

O ODMAPBoc2O

THFr.t.

DIBAL-HCH2Cl2-40oC

PPh3Br2CH2Cl2

r.t.

quantitative 78% no reaction

12 1311 Scheme 3.6. Reaction scheme of t-Boc-protected indole-2-carboxylic acid ethyl ester, 12, to the t-Boc-

protected indole-2-methyl alcohol, 13.

The Cbz-group can be utilized to protect amines and has been found to resist

cleavage in a variety of reaction conditions.38 The installation of the Cbz-protecting

group on the indole nitrogen is a facile process (Scheme 3.7); deprotonation with NaH,

and subsequent addition of carbobenzyloxy chloride affords the Cbz-protected indole-2-

carboxylic acid ethyl ester, 14, in 96 % yield. The 1H NMR spectrum of 14 exhibited the

loss of the indole NH proton and the presence of the benzyl moiety of the Cbz-protecting

group.

Similar reaction conditions for 12 were carried out for 14. The Cbz-protected

indole-2-methyl alcohol, 15, was acquired in 65 % yield after reaction of 14 with

DIBAL-H in CH2Cl2 at -40oC. The characterization of 15 by 1H NMR was consistent

with the reduction of the carboxylate moiety of 14 to form the methyl alcohol moiety of

15; the appearance of the methylene protons at δ = 4.81 ppm (CDCl3) as a doublet from

78

coupling to the alcohol proton, and the alcohol proton resonates at δ = 2.73 ppm (CDCl3)

as a broad singlet.

A solution of alcohol 15 in CH2Cl2 was added dropwise to a suspension of

PPh3Br2 in CH2Cl2. After 10 minutes of stirring, the reaction was quenched with water

and extracted. Removal of volatile solvents, and subsequent column chromatography

revealed that Cbz-protected indole-2-methyl bromide, 16, was successfully synthesized

and purified in 40 % yield. The 1H NMR spectrum of 16 shows the methylene protons as

a singlet at δ = 4.94 ppm (CDCl3), and the EI-HRMS confirms the presence of the bromo

moiety.

N

OEt

O

OO

N

OH

OO

N

Br

OO

HN

OEt

O NaHCbzClTHFr.t.

DIBAL-HCH2Cl2-40oC

PPh3Br2CH2Cl2

r.t.

96% 65% 40%

11 14 15 16 Scheme 3.7. Reaction scheme of Cbz-protected indole-2-carboxylic acid ethyl ester, 14, to the Cbz-

protected indole-2-methyl bromide, 16.

Several methods are proposed to synthesize the model phosphine, 10, from Cbz-

protected indole-2-methyl bromide 16. The first method is to follow the protocol for 2-

indolylphosphines synthesis,3 through the generation of a lithiated indole moiety (Scheme

3.8). A solution of bromide 16 in THF was cooled to -78oC, n-BuLi was added dropwise.

The reaction was allowed to stir at -78oC for several hours prior to the addition of PPh2Cl.

Aqueous workup followed after 12 h of reaction with PPh2Cl. The 31P NMR of the crude

reaction indicated mostly hydrolyzed PPh2Cl, suggesting the phosphine chloride did not

react with the proposed lithiated 16. Further inspection of the 1H NMR spectrum of the

crude material showed that the Cbz-group had been cleaved off since an indole NH peak

was present. Generally hydrogenolysis is required to remove the Cbz-protecting group,38

however Shieh and co-workers42 have reported that selective deprotection of Cbz-

protected heterocycles can be achieved with bases such as sodium methoxide or DBU

79

(diaza(1,3)bicyclo[5.4.0]undecane) in methanol, while aliphatic amines remained

unaffected.

N

P

OO

N

Br

OO 1. n-BuLi

2. PPh2ClTHF, -78oC3. Aqueous

workup

no reaction

16

Scheme 3.8. Attempted synthesis of Cbz-protected 10 from 16 using n-BuLi and PPh2Cl.

The second method proposed to synthesize target phosphine 10 is based on the

reactivity of a Grignard reagent generated in situ through the treatment of 16 with

activated Mg dust in THF.43 Addition of PPh2Cl followed after the Mg was consumed,

and the resultant reaction mixture was refluxed overnight. Following an aqueous

workup, the 31P NMR spectrum of the crude reaction mixture was disappointingly mostly

hydrolyzed PPh2Cl. Interestingly, the major product formed in this reaction is Cbz-

protected 2-ethylindole, which suggests the formation of the Grignard reagent. While

Landaeta and co-workers43 were successful in the formation of tribenzylphosphine using

this protocol, the synthesis of the Cbz-protected model phosphine 10 could not be

realized by this method.

N

P

OO

N

Br

OO 1. Mg(s), r.t. to reflux, THF

2. PPh2Cl, -10oC to reflux3. Aqueous workup

no reaction

16

Scheme 3.9. Attempted synthesis of Cbz-protected 10 from 16 through Grignard reagent and PPh2Cl.

80

The third method proposed to generate the target model phosphine 10 involves a

nickel catalyst in the presence of zinc for P-C bond formation, and has shown to be

widely applicable for the synthesis of tertiary phosphines.44 The reaction conditions

involve the addition of Ni(PPh3)2Cl2 to 16 in DMF at 0oC, followed by the addition of

activated Zn dust and PPh2Cl at 10oC (Scheme 3.10). The Zn dust serves two roles: to

reduce the Ni(II) catalyst to the reactive Ni(0) species, and to generate the Ph2PZnCl for

transmetallation. The resultant mixture is heated to 100oC and maintained at this

temperature for 18 hours. The mixture is then cooled to 80oC, filtered, and rinsed with a

minimal amount of DMF. The combined filtrate and rinses were further cooled to 5oC, at

which point the pure product should crystallize from the solution. When no solids were

present, the mixture was concentrated in vacuo to afford a dark-orange coloured oil that

appeared to be a mixture containing three different species by TLC. The oil was

subjected to column chromatography and the three compounds separated. Surprisingly,

the major product was found to be Cbz-protected 2-ethylindole, and the other two

compounds did not have any 31P NMR resonances.

N

P

OO

N

Br

OO 1. Ni(dppe)Cl2

PPh2Cl, ZnDMF

15oC to 85oC2. Aqueous

workup

no reaction

16

Scheme 3.10. Attempted synthesis of Cbz-protected 10 from 16 using a Ni(dppe)Cl2 catalyst in the

presence of Zn and PPh2Cl.

81

3.3.2. Design of a New Diindolyl-Based Anion Receptor

While the synthesis of a new C3-symmetric 5-based anion receptor was

unsuccessful, alternative designs for indole-based anion receptors are limitless. It has

been demonstrated that anion receptors with deliberately placed hydrogen bond donors

can have greater selectivity for anion guests. For example, indole-based anion receptors

reported by Chang and co-workers are methodically designed to consist of indolyl NH

donors confined in macrocyles24 or molecular clefts22 (Figure 3.12).

HN

HN

NH

NH

NN

N

O

N

O

H HH H

H H

(a) (b) Figure 3.12. Indole-based anion receptors by Chang and co-workers. (a) Indole-based macrocycle.24

(b) Indole-based molecular cleft.22

The anion binding capabilities of the two indole-based receptors were determined using

spectroscopic titration techniques and the stability constants determined are listed in

Table 3.5. The macrocycle clearly binds anions with higher anion binding affinities,

presumably due to the rigidity of the hydrogen bond donors. However, the molecular

cleft demonstrates better anion selectivity toward the acetate anion over others. This

selectivity is most likely due to the flexibility of the molecular cleft by free rotation to

arrange its amide donors around the acetate anion to provide a better binding pocket.

82

Table 3.5. Stability constants Ka (M-1) of indole-based macrocyclea and indole-based molecular cleftb with

a selection of anion guests as determined by spectroscopic titration techniques performed at 298 K.22,24

Anion Ka

HN

HN

NH

NH

Ka

NN

N

O

N

O

H HH H

H H

Cl- 1.5 x 106 5.1 x 103

Br- K1 = 1.9 x 103, K2 = 10 2.1 x 102

CH3COO- 5.9 x 106 1.4 x 105

HSO4- 6.5 x 105 77

aTitrations performed in CD3CN and monitored with 1H NMR. bTitrations performed in CH3CN and monitored with

UV-visible spectroscopy.

3.3.3. Synthesis of New Diindolyl-Based Anion Receptor

Based on the work of Chang and co-workers, the design of a new molecular cleft-

based anion receptor bearing two indolyl moieties separated by a rigid phenyl linker

should allow for more selective binding of anions compared to 5. The molecular cleft, 4-

tert-butyl-7-(4-(4-tert-butyl-1H-indol-7-yl)phenyl)-1H-indole, 18, is based on a similar

one previously synthesized and investigated for its anion binding properties;45 the

difference in the new molecular cleft features two tert-butyl substituents at the C4-

position on indole to increase solubility of the receptor in less polar organic solvents.

The synthesis of 17 is shown in Scheme 3.11 and began with the nitration ortho to

the bromo substituent of 1-bromo-4-tert-butylbenzene with nitric acid and sulfuric acid at

ambient temperature. The nitrated species was then treated with vinyl magnesium

bromide in a Bartoli indole synthesis to form 4-tert-butyl-7-bromoindole, 17. Subsequent

Suzuki coupling with benzene-1,4-diboronic acid in the presence of Pd(PPh3)4 catalyst

gave the desired molecular cleft, 18, in moderate yields.

83

HN

BrBr Br

HN

NH

HNO3H2SO4

3oC to r.t.

H2C CHMgBrTHF

-40oC

Pd(PPh3)41,4-(BOH)2benzene

toluene / EtOHNa2CO3, H2O

reflux

NO2

89% 40%

34%17

18 Scheme 3.11. Synthesis of 4-tert-butyl-7-(4-(4-tert-butyl-1H-indol-7-yl)phenyl)-1H-indole, 18, from 1-

bromo-4-tert-butylbenzene.

Single crystals of the molecular cleft were acquired from slow evaporation of a

concentrated solution of 18 in CH2Cl2; the experimental X-ray diffraction data are listed

in Table 3.6. The numbering scheme for the molecular cleft are shown in Figure 3.13,

while Table 3.7 lists selected bond distances and angles.

Figure 3.13. ORTEP diagram of 18. Non-acidic hydrogen atoms removed for clarity. Thermal ellipsoids

are drawn at 35% probability.

The molecular cleft crystallizes in the monoclinic space group P21/c, where half of the

molecule lies on a crystallographic inversion centre that generates the other half through

symmetry. The phenyl linker is nearly perpendicular from the plane of the indoles, with a

dihedral angle <C16-C14-C8-C9 of -94.5(3)o that suggests this orientation to minimize

repulsion from the protons on the phenyl linker and the indolyl NH sites. Additionally,

the indolyl NH functionalities are oriented in opposite directions with respect to each

84

other, with a distance of 6.96 Å separating the two indolyl NH across the phenyl linker.

There are no significant structural changes with the addition of either the tert-butyl or the

phenyl moieties on the aromaticity of the indole, as the bond distances and angles are

comparable to indole (refer to Chapter 2).

Table 3.6. X-ray crystallographic experimental data of molecular cleft 18.

NH HN

Formula C30H32N2 Formula Weight 420.58 Crystal colour, shape colourless, plate Crystal size, mm 0.30 x 0.06 x 0.04 Crystal system Monoclinic Space group P21/c a, Å 11.9000(15) b, Å 6.6563(5) c, Å 16.244(2) α deg 90 β, deg 110.922(4) γ deg 90 V, Å3 1201.9(2) Z 2 Dcalcd, g cm-3 1.162 F(000) 452 μ, mm-1 0.067 λ (Mo Kα), Å 0.71073 Limiting indices -15<=h<=15 -8<=k<=8 -20<=l<=21 2θ range, deg 2.66 to 27.63 Max. and min. transmission 1.054 and 0.834 No. of reflections collected 9294 No. of independent reflections/Rint 2966 / 0.0947 Extinction coefficient 0.004(2) No. of refined parameters 149 Final R1, wR2 0.0575, 0.1162 Final R1, wR2 (all data) 0.1670, 0.1509 Goodness of fit 0.958 Δρmin, Δρmax, eÅ-3 -0.181, 0.176

85

Table 3.7. Selected bond lengths (Å) and angles (o) for molecular cleft 18.

NH HN

N1-C2 1.370(3) C2-C3 1.357(3) C3-C4 1.439(3) C4-C9 1.416(3) C9-N1 1.376(3)

<C9-N1-C2 108.7(2) <N1-C2-C3 109.8(2) <C2-C3-C4 107.7(2) <C3-C4-C9 105.5(2) <C4-C9-N1 108.2(2)

3.3.4. Anion Binding Studies of Molecular Cleft 18

Similar to 5, the anion binding capability of 18 was examined by 1H NMR

titration techniques in CD2Cl2 with selected anions (Scheme 3.12); the chemical shifts of

the indolyl NH protons were monitored via 1H NMR with increasing anion concentration

(Figure 3.14); the stability constants were determined by investigation of the titration data

by non-linear regression analysis and which were best fit a 1 : 1 receptor to anion binding

model (Figure 3.15 and Table 3.8). The stability constants of the unsubstituted

derivative, 7-(4-(1H-indol-7-yl)phenyl)-1H-indole, 19, are included in Table 3.8 for

comparison.45

HN

NH

+ NBu4XCD2Cl2

HN

NH

X- NBu4+

18 Scheme 3.12. General titration scheme of 18 and selected anions as their tetrabutylammonium salts in

CD2Cl2. Selected anions: X- = Cl-, Br-, CH3COO-, HSO4-, NO3

-, and BF4-.

86

0 eq

NH

0.5 eq

1.2 eq

2 eq

ppm (t1)7.08.09.010.011.0

4 eq

Figure 3.14. A representative of partial stack plots of 18 titrations with Cl- in CD2Cl2 at 298 K.

Table 3.8. Stability constants Ka (M-1) of 18 and 19 with a selection of anion guests as determined by 1H

NMR titration techniques performed at 298 K , following the indolyl NH resonances.

Anion

Ka

NH HN

+/- Error in Ka

(overall error %)

Ka

NH HN

+/- Error in Ka

(overall error %)

Cl- 20 0.1 (0.7) 65 3 (4)

Br- 10 0.3 (3) 45 1 (3)

CH3COO- 190 1 (0.5) 480 48 (10)

HSO4- 35 1 (3) 60 1 (2)

NO3- 15 0.6 (4) 30 0.1 (0.3)

BF4- <1 - <1 -

87

Figure 3.15. . Fit plot for titration experiment of 18 with tetrabutylammonium chloride in CD2Cl2.

The stability constants indicate a strong selectivity for acetate anion over the other

anions titrated for both molecular clefts 18 and 19. This affinity for acetate by both

molecular clefts suggests a better complementary fit of the anion in the hydrogen bonding

pocket of the receptor because the indole NH hydrogen bond donors are spatially

predisposed to bind acetate. In contrast to the [5·CH3COO]- complex, it is speculated

that both oxygen atoms of acetate are binding to both indolyl NH donors in molecular

clefts 18 and 19 (Scheme 3.13). However, the stability constant determined for complex

6 (Ka = 2730 M-1) is greater than that for both molecular clefts, which is most likely due

to the additional hydrogen bond donor in receptor 5.

N NH HO O

CH3

Scheme 3.13. Proposed mode of acetate interaction with molecular cleft 18.

As can be seen from the stability constants listed in Table 3.8, the tert-butyl

functionalized molecular cleft does not have as strong anion binding affinities as that of

the unfunctionalized molecular cleft. The decrease in anion binding is most likely due to

the electron donating power of the tert-butyl substituents at the C4- and C4’-positions on

88

indole. While the tert-butyl moieties are situated four bonds away from the indolyl NH

centres, they do appear to have an effect on the acidity of these protons. Similarly,

Sessler and co-workers have demonstrated that the installation of an electron withdrawing

nitro substituent on their indole-based anion receptor has profoundly increased the acidity

of indolyl NH sites that are reflected in the stability constants (Table 3.9).28 Even though

the nitro group is seven bonds away from the hydrogen bond donors, it not only increases

the anion binding affinities for all anions, but it also enhances selectivity for phosphate

anion.

Table 3.9. Stability constants Ka (M-1) of diindolylquinoxaline-based anion receptors with a selection of

anion guests as determined by UV-visible spectroscopic titration techniques performed at 298 K in

CH2Cl2.28

Anion

Ka

N N

NH

NH Ka

N N

NH

NH

NO2

Cl- 170 470

HSO4- 80 250

C6H5COO- 600 2700

H2PO4- 6800 20 000

3.4. Conclusions

It was found that the C3-symmetric 2-indolylphosphine, 5, has demonstrated anion

binding ability. The solid-state structure of 5 exhibits how the three indolyl NH hydrogen

bond donors are oriented in the same direction, thus are available to capture anion guests.

Through 1H NMR titration techniques in CD2Cl2, it was determined that 5 has the

strongest affinity for chloride and acetate in a 1 : 1 receptor : anion ratio, and that the

interactions are confirmed by the solid-state structure involving the acetate anion.

Although an accurate stability constant could not be determined for the fluoride titration

89

with 5, its titration series did have the largest overall shift in the indolyl NH resonances,

implying a strong interaction. This interaction between 5 and F- was demonstrated in the

solid-state structure of its [NEt4][5·F] complex, 7, as a 1 : 1 receptor to anion binding

stoichiometry.

The solid-state structure of the phosphonium complex, 8, shows iodide

interactions with indolyl NH functionalities. It was thought that the methylation of the

phosphorus centre would encourage iodide interaction, which is seen with only one of the

indolyl NH sites. The remaining two indolyl NH sites of 5 are either hydrogen bonding

to Et2O solvate, or are not engaged in secondary bonding interactions.

Attempts to design and synthesize a new C3-symmetric anion receptor based on 5

were unsuccessful; complications arose from the reactivity of the nitrogen protecting

groups, and P-C bond formation procedures that were unpredictable. However, a

diindolyl-based molecular cleft, 18, was synthesized and found to have anion binding

capability.45 While the unfunctionalized molecular cleft is capable of anion binding, its

relative insolubility in most organic solvents makes it difficult to examine. The

installation of tert-butyl substituents on the molecular cleft has improved its solubility,

but has decreased the acidity of the indolyl NH donors, thus resulting in lower stability

constants compared to the unfunctionalized analogue.

3.5. Experimental



PCl3, 1.6 M n-BuLi, NaBH4, MeI, 1H-indole-2-carboxylic acid ethyl ester, DMAP,

Boc2O, CbzCl, 1.0 M DIBAL-H, NaH, PPh2Cl, benzene 1,4-diboronic acid, 1-bromo-4-

tert-butylbenzene, tetraethylammonium and tetrabutylammonium salts (fluoride, chloride,

bromide, iodide, acetate, sulfate, nitrate, tetrafluoroborate) were purchased from Aldrich

and used as received. Pd(PPh3)4 was purchased from Strem and used without further

90

purification. 1-[(N,N-Dimethylamino)methyl]-3-methylindole,17 and 1-bromo-4-tert-

butyl-2-nitrobenzene46 were synthesized according to literature procedures. THF was

distilled from sodium benzophenone ketyl under a dinitrogen atmosphere. CH2Cl2 was

distilled from calcium hydride under a dinitrogen atmosphere. 1H, 13C, and 31P NMR

spectra were recorded on Varian 400 MHz or 300 MHz NMR systems, and referenced to

SiMe4 (TMS) and 85% H3PO4, respectively. Splitting patterns are indicated as s, singlet;

d, doublet; t, triplet; q, quartet; m, multiplet; br, broad peak. High resolution mass spectra

were obtained from a Micromass 70S-250 spectrometer (EI).

P

HN

CH3

3

I

Methyltris-2-(3-methylindolyl)phosphonium iodide, 8. To a clear colourless solution

of tris-2-(3-methylindolyl)phosphine (0.307 g, 0.73 mmol) in THF (15 mL) was added

dropwise methyl iodide (0.25 mL, 4.0 mmol). The resultant reaction was left to stir at

ambient temperature for 18 h during which a white precipitate formed. The product was

isolated by filtration, washed with Et2O (2 x 5 mL), and air dried (0.254 g, 62 %). 31P

NMR (CDCl3, 161 MHz): δ -12.7 (s); 1H NMR (CDCl3, 400 MHz): δ 10.29 (br s, 3H,

indole NH), 7.72 (d, J = 8.3 Hz, 3H, Ar-H), 7.58 (d, J = 8.1 Hz, 3H, Ar-H), 7.30 (t,

J = 7.2, 15.2 Hz, 3H, Ar-H) 7.18 (t, J = 7.9, 15.8 Hz, 3H, Ar-H), 3.39 (d, J = 13.8 Hz, 3H,

P+-CH3), 2.01 (d, J = 1.8 Hz, 9H, indole CH3); 13C NMR (CDCl3, 75 MHz): 140.0, 128.5,

126.8, 121.1, 120.0, 113.2, 107.9, 106.2, 15.9, 9.1.

N

OEt

O

O O

Indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester, 12. THF (50 mL) was

added to 1H-Indole-2-carboxylic acid ethyl ester (2.45 g, 13.0 mmol), DMAP (1.74 g,

14.3 mmol), and Boc2O (3.57 g, 16.4 mmol) to afford a clear pale yellow-coloured

solution. The reaction was stirred at rt for 1.5 h and monitored by TLC. Solvents were

91

removed in vacuo to yield a pale orange-yellow oil. Added CH2Cl2 (50 mL) and

extracted with 2N HCl (2 x 50 mL). Dried organic layer over anhydrous MgSO4, filtered,

and concentrated in vacuo to afford the pure product as an orange-coloured oil (3.73 g,

99%). 1H NMR (CDCl3, 300 MHz): δ 8.08 (d, J = 8.4 Hz, 1H, Ar-H), 7.60 (d, J =

7.8 Hz, 1H, Ar-H), 7.41 (t, J = 7.8 Hz, 1H, Ar-H), 7.26 (t, J = 7.5 Hz, 1H, Ar-H), 7.10 (s,

1H, Ar-H), 4.38 (q, J = 7.2, 14.1 Hz, 2H, CH2CH3), 1.63 (s, 9H, C(CH3)3), 1.40 (t,

J = 6.8 Hz, 3H, CH2CH3); 13C NMR (CDCl3, 75 MHz): 162.1, 152.4, 149.5, 138.0, 131.0,

127.8, 126.9, 123.5, 122.3, 115.0, 84.8, 61.6, 28.1, 14.5; HRMS EI for C16H19NO4Na:

calcd m/z 312.1206, found m/z 312.1215.

N

OH

O O

2-Hydroxymethyl-indole-1-carboxylic acid tert-butyl ester, 13. Added toluene

(14 mL) to indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (1.99 g,

6.88 mmol) and cooled to -40oC. Added DIBAL-H (1 M in CH2Cl2, 16.5 mL,

16.5 mmol) dropwise over 10 minutes. The resultant mixture was allowed to stir for 50

minutes at -40oC. The reaction vessel was vented and MeOH (8 mL) was added

dropwise, followed by the dropwise addition of water (4 mL), which formed a precipitate.

The reaction was warmed to rt and filtered. The filtrate was extracted with CH2Cl2 (3 x

50 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and

reduced to afford a dark orange coloured oil. The crude material was purified by column

chromatography (silica gel, 4 : 1 hexanes-EtOAc) to yield the pure product (1.39 g, 78 %)

as a colourless oil. 1H NMR (CDCl3, 400 MHz): δ 8.14 (d, J = 8.4 Hz, 1H, Ar-H), 7.51

(d, J = 8 Hz, 1H, Ar-H), 7.29 (t, J = 7.8 Hz, 1H, Ar-H), 7.21 (t, J = 7.6 Hz, 1H, Ar-H),

6.66 (s, 1H, Ar-H), 5.43 (s, 2H, CH2OH), 1.68 (s, 9H, C(CH3)3); 13C NMR (CDCl3,

75 MHz): 153.5, 140.0, 137.1, 134.9, 128.9, 124.7, 123.1, 120.8, 115.8, 110.0, 84.6, 63.5,

28.3; HRMS EI for C14H17NO3: calcd m/z 247.120844, found m/z 247.121422.

92

N

OEt

O

OO

Indole-1,2-dicarboxylic acid 1-benzyl ester 2-ethyl ester, 14. THF (50 mL) was added

slowly to 1H-indole-2-carboxylic acid ethyl ester (7.09 g, 37.5 mmol) and NaH (60 %wt,

2.53 g, 63.3 mmol) to afford a bright pink solution. Allowed the reaction mixture to stir

for 3 h before adding benzyl chloroformate (12 mL, 85.3 mmol) dropwise, and allowed

the reaction to stir at rt overnight. The orange-coloured reaction mixture was poured into

satd. NH4Cl and extracted with EtOAc (2 x 200 mL). The combined organic layers were

washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to

give a golden-orange-coloured oil. The crude material was purified by flash

chromatography (silica gel, 10 : 5 : 1 hexanes-CH2Cl2-Et2O) to afford the pure product

(11.5 g, 96 %) as a golden-orange oil. 1H NMR (CD2Cl2, 400 MHz): δ 8.13 (d, J =

8.4 Hz, 1H, Ar-H), 7.66 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 – 7.39 (m, 6H, Ar-H), 7.32 (t,

J = 7.5 Hz, 1H, Ar-H), 7.17 (s, 1H, Ar-H), 5.46 (s, 2H, CH2Ph), 4.27 (q, J = 7.2, 14 Hz,

2H, CH2CH3), 1.32 (t, J = 7.2 Hz, 3H, CH2CH3); 13C NMR (CD2Cl2, 75 MHz): 162.1,

156.2, 151.3, 138.2, 136.2, 135.3, 131.5, 129.2, 128.3, 127.5, 124.1, 122.8, 115.6, 115.4,

70.2, 62.1, 14.5; HRMS EI for C19H17NO4: calcd m/z 323.115758, found m/z 323.115143.

N

OH

OO

2-Hydroxymethyl-indole-1-carboxylic acid benzyl ester, 15. CH2Cl2 (50 mL) was

added to indole-1,2-dicarboxylic acid 1-benzyl ester 2-ethyl ester (6.41 g, 19.8 mmol)

and cooled to -40oC. DIBAL-H (47 mL, 47 mmol, 1.0 M in CH2Cl2) was added dropwise

to afford an orange-coloured solution and the mixture allowed to stir at -40oC overnight.

The reaction was warmed to 0oC and MeOH (50 mL) was added dropwise to give a

bright yellow mixture, followed by the dropwise addition of H2O (40 mL), which formed

93

a white precipitate. The bright yellow suspension was warmed to rt over 3 h. The

mixture was filtered, the filtrate was extracted with CH2Cl2 (3 x 100 mL), the organic

layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give a

cream-coloured oil. The crude material was purified by flash chromatography (silica gel,

4 : 1 hexanes-EtOAc) to afford the pure product as a white solid (3.6 g, 65 %). 1H NMR

(CD2Cl2, 400 MHz): δ 8.05 (d, J = 8 Hz, 1H, Ar-H), 7.56 - 7.24 (m, 8H, Ar-H), 6.63 (s,

1H, Ar-H), 5.51 (s, 2H, CH2Ph), 4.81 (d, J = 7 Hz, 2H, CH2OH), 2.73 (bs, 1H, OH); 13C

NMR (CD2Cl2, 75 MHz): 152.9, 142.0, 141.2, 135.4, 129.8, 129.3, 127.9, 127.4, 125.1,

123.9, 121.4, 116.3, 110.2, 69.6, 59.4; HRMS EI for C17H15NO3: calcd m/z 281.105194,

found m/z 281.105106.

N

Br

OO

2-Bromomethyl-indole-1-carboxylic acid benzyl ester, 16. To a suspension of PPh3Br2

(0.65 g, 1.54 mmol) in CH2Cl2 (0.8 mL), was added dropwise a solution of 2-

hydroxymethyl-indole-1-carboxylic acid benzyl ester (1.0 g, 3.6 mmol) in CH2Cl2

(1.5 mL). The mixture becomes clear and dark pink coloured after 5 minutes of stirring.

The reaction was quenched with water (1.5 mL), and the layers separated. The organic

layer was washed with water (3 x 10 mL), dried over anhydrous MgSO4, filtered and

concentrated in vacuo. The residue was fused to silica and purified by flash

chromatography (silica gel, 9 : 1 hexanes-EtOAc) to afford the pure product as a white

solid (2.2 g, 40 %). 1H NMR (CD2Cl2, 400 MHz): δ 8.13 (d, J = 8.4 Hz, 1H, Ar-H), 7.56

(dd, J = 1.6, 8 Hz, 1H, Ar-H), 7.53 (d, J = 7.6 Hz, 2H, Ar-H), 7.44 - 7.38 (m, 3H, Ar-H),

7.32 (td, J = 1.2, 7.8 Hz, 1H, Ar-H), 7.24 (td, J = 0.8, 7.6 Hz, 1H, Ar-H) 6.77 (s, 1H, Ar-

H), 5.52 (s, 2H, CH2Ph), 4.94 (s, 2H, CH2Br); 13C NMR (CD2Cl2, 75 MHz): 151.7, 137.8,

136.9, 135.5, 129.4, 129.0, 126.0, 124.0, 121.5, 116.4, 112.9, 69.8, 27.7; HRMS EI for

C17H14NO2Br: calcd m/z 343.020790, found m/z 343.020130.

94

HN

Br

7-Bromo-4-tert-butylindole, 17. A solution of 1-bromo-4-tert-butyl-2-nitrobenzene

(2.82 g, 10.9 mmol) in THF (20 mL) was cooled to -40oC. Vinylmagnesium bromide

(33 mL, 1.0 M in THF, 33 mmol) was added dropwise via an addition funnel over 10

minutes. The resultant dark brown solution was allowed to warm to ambient temperature

overnight. The reaction was quenched with the addition of saturated aqueous NH4Cl, the

organic layer was separated, and the aqueous layer was extracted with CH2Cl2

(2 x 50 mL). The organic layers were combined, dried over anhydrous MgSO4, filtered,

and concentrated in vacuo to afford a dark brown oil. The product was obtained pure

after flash chromatography (silica gel, 5% EtOAc in hexanes) as a pale brown coloured

oil (0.9 g, 30%). 1H NMR (CDCl3, 400 MHz): δ 8.52 (s, 1H, indole NH), 7.33 (d, J =

8 Hz, 1H, Ar-H), 7.24 (t, J = 3.2, 5.8 Hz, 1H, Ar-H), 6.99 (d, J = 8 Hz, 1H, Ar-H), 6.87

(dd, J = 2.2, 3.3 Hz, 1H, Ar-H), 1.56 (s, 9H, C(CH3)3); 13C NMR (CDCl3, 100 MHz):

143.0, 135.1, 126.7, 124.1, 123.5, 117.4, 105.3, 103.0, 35.8, 30.8; HRMS EI for

C12H14NBr: calcd m/z 251.030961, found m/z 251.031127.

NH HN

4-tert-butyl-7-(4-(4-tert-butyl-1H-indol-7-yl)phenyl)-1H-indole, 18. A mixture of

toluene / EtOH (65 mL, 1 : 1, v / v) was added to a solid mixture of 7-bromo-4-tert-

butylindole (2.054 g, 8.2 mmol), benzene 1,4-diboronic acid (0.682 g, 4.1 mmol), and

Pd(PPh3)4 (0.475 g, 0.4 mmol) to give a dark yellow coloured suspension. The mixture

was stirred at r.t. for 15 minutes until all of the boronic acid was in solution. A clear

colourless solution of Na2CO3 (2.52 g, 20.4 mmol) in H2O (19.5 mL) was added quickly

via syringe to the reaction mixture. The biphasic mixture was refluxed for 1 h. A

suspension of Pd(PPh3)4 (0.50 g, 0.4 mmol) in toluene / EtOH (33 mL, 1 : 1, v / v) was

added via addition funnel. The reaction continued to reflux overnight. Subsequent

cooling to r.t., followed by removal of solvent in vacuo afforded a dark brown residue,

95

which was extracted with CH2Cl2 (2 x 100 mL). The organic layers were combined,

washed with brine, dried over anhydrous MgSO4, filtered and reduced in vacuo. The

residue was fused to silica gel and purified by flash chromatography (silica gel, 10%

EtOAc in hexanes) to produce the pure product as a pale yellow solid (0.58 g, 34%). 1H

NMR (CDCl3, 400 MHz): δ 8.51 (s, 2H, indole NH), 7.75 (s, 4H, Ph-H), 7.22 (m, 2H, Ar-

H), 7.20 (q, J = 7.6 Hz, 4H, Ar-H), 6.88 (dd, J = 2.1, 3.3 Hz, 2H, Ar-H), 1.56 (s, 18H,

C(CH3)3); 13C NMR (CDCl3, 100 MHz): 143.1, 138.5, 134.6, 129.2, 125.9, 123.7, 123.2,

122.0, 116.8, 104.7, 36.0, 31.0; HRMS EI for C30H32N2: calcd m/z 420.256549, found m/z

420.256767.

Titration Methods. 1H NMR titration experiments were carried out by dissolving 5 or

18 (15.4 μmol) in CD2Cl2 (0.65 mL) and adding sequential 10 μL aliquots of a solution

of the selected anions as their tetrabutylammonium salts (154 μmol) in CD2Cl2 (1 mL)

(which corresponds to 0.1eq of anion) to 5 or 18 until saturation. Association constants,

Ka, were determined by non-linear least-squares fit of the data using the program

EQNMR.19

Figure 3.16. Fit plot for titration experiment of 5 with tetrabutylammonium bromide in CD2Cl2.

96

Figure 3.17. Fit plot for titration experiment of 5 with tetrabutylammonium iodide in CD2Cl2.

Figure 3.18. Fit plot for titration experiment of 5 with tetrabutylammonium acetate in CD2Cl2.

97

Figure 3.19. Fit plot for titration experiment of 5 with tetrabutylammonium hydrogensulfate in CD2Cl2.


98

Figure 3.21. Fit plot for titration experiment of 5 with tetrabutylammonium tetrafluoroborate in CD2Cl2.

Figure 3.22. Fit plot for titration experiment of 18 with tetrabutylammonium bromide in CD2Cl2.

99

Figure 3.23. Fit plot for titration experiment of 18 with tetrabutylammonium acetate in CD2Cl2.

Figure 3.24. Fit plot for titration experiment of 18 with tetrabutylammonium hydrogensulfate in CD2Cl2.

100


Figure 3.26. Fit plot for titration experiment of 18 with tetrabutylammonium tetrafluoroborate in CD2Cl2.










101

3.6. References

(1) Brooks, S. J.; Evans, L. S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E. Chem.

Commun. 2005, 734-736.

(2) Coles, S. J.; Frey, J. G.; Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Navakhun,

K.; Thomas, G. L. Chem. Commun. 2003, 568-569.


1720-1722.

(4) Lakshminarayanan, P. S.; Ravikumar, I.; Suresh, E.; Ghosh, P. Inorg. Chem.

2007, 46, 4769-4771.

(5) Evans, L. S.; Gale, P. A.; Light, M. E.; Quesada, R. Chem. Commun. 2006, 965-

967.

(6) Gale, P. A. Chem. Commun. 2005, 3761-3772.

(7) Gale, P. A.; Camiolo, S.; Chapman, C. P.; Light, M. E.; Hursthouse, M. B.

Tetrahedron Lett. 2001, 5095 - 5097.

(8) Gale, P. A.; Camiolo, S.; Tizzard, G. J.; Chapman, C. P.; Light, M. E.; Coles, S.

J.; Hursthouse, M. B. J. Org. Chem. 2001, 66, 7849-7853.

(9) Brooks, S. J.; Gale, P. A.; Light, M. E. Chem. Commun. 2006, 4344-4346.

(10) Duckmanton, P. A.; Blake, A. J.; Love, J. B. Inorg. Chem. 2005, 44, 7708-7710.

(11) Knight, L. K.; Freixa, Z.; vanLeeuwen, P. W. N. M.; Reek, J. N. H.

Organometallics 2006, 25, 954-960.

(12) Tovilla, J. A.; Vilar, R.; White, A. J. P. Chem. Commun. 2005, 4839 - 4841.

(13) Ayling, A. J.; Perez-Payan, M. N.; Davis, A. P. J. Am. Chem. Soc. 2001, 123,

12716-12717.

(14) Kwon, J. Y.; Jang, Y. J.; Kim, S. K.; Lee, K. H.; Kim, J. S.; Yoon, J. J. Org.

Chem. 2004, 69, 5155-5157.

(15) Bordwell, F. G.; Zhang, X.; Cheng, J.-P. J. Org. Chem. 1991, 56, 3216-3219.

(16) Eisler, D. J.; Puddephatt, R. J. Inorg. Chem. 2003, 42, 8192-8202.


(18) Katritzky, A. R.; Akutagawa, K. Tetrahedron Lett. 1985, 26, 5935-5938.

(19) Hynes, M. J. J. Chem. Soc. Dalton Trans. 1993, 311-312.

101

102

(20) Bates, G. W.; Gale, P. A.; Light, M. E. Chem. Commun. 2007, 2121-2123.

(21) Bates, G. W.; Triyanti; Light, M. E.; Albrecht, M.; Gale, P. A. J. Org. Chem.

2007, 72, 8921-8927.

(22) Chang, K. J.; Chae, M. K.; Lee, C.; Lee, J. Y.; Jeong, K. S. Tetrahedron Lett.

2006, 47, 6385-6388.

(23) Kwon, T. H.; Jeong, K. S. Tetrahedron Lett. 2006, 47, 8539-8541.

(24) Chang, D. -J.; Moon, D.; Lah, M. S.; Jeong, K. -S. Angew. Chem. Int. Ed. 2005,

44, 7926-7929.

(25) Lee, J.-Y.; Lee, M.-H.; Jeong, K.-S. Supramol. Chem. 2007, 19, 257 - 263.

(26) Wang, Y.; Lin, H.; Shao, J.; Cai, Z. S.; Lin, H. K. Talanta 2008, 74, 1122-1125.

(27) Zielinski, T.; Dydio, P.; Jurczak, J. Tetrahedron 2008, 64, 568-574.

(28) Sessler, J. L.; Cho, D.-G.; Lynch, V. J. Am. Chem. Soc. 2006, 128, 16518-16519.

(29) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John Wiley & Sons, Ltd.:

New York, NY, 2001.

(30) Deprotonation of the indolyl NH sites was not observed, even though it is a well

documented phenomenon: Boiocchi, M.; DelBoca, L.; Gomez, D. E.; Fabbrizz, L.;

Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507-16514.

(31) Steiner, T. Acta Cryst. 1998, B54, 456-463.

(32) Bugner, D. E. J. Org. Chem. 1989, 54, 2580-2586.

(33) Symmetry code: -x,-y+1,-z+1

(34) Symmetry code: x,-y+1/2,z-1/2

(35) Baby Mariyatra, M.; Kayanasundari, B.; Panchanatheswaran, K.; Goeta, A. E.

Acta Cryst. 2003, E59, o255-o257.

(36) Pfeffer, F. M.; Lim, K. F.; Sedgwick, K. J. Org. & Biomol. Chem. 2007, 5, 1795-

1799.

(37) Belanger, G.; Larouche-Gauthier, R.; Menard, F.; Nantel, M.; Barabe, F. J. Org.

Chem. 2006, 71, 704-712.

(38) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Third

Edition ed.; John Wiley & Sons, Ltd.: New York, NY, 1999.

(39) March, J. Advanced Organic Chemistry; 4th ed.; John Wiley & Sons, Ltd.: New

York, NY, 1992.

103

(40) Bressy, C.; Alberico, D.; Lautens, M. J. Am. Chem. Soc. 2005, 127, 13148-13149.

(41) Vizitiu, D.; Walkinshaw, C. S.; Gorin, B. I.; Thatcher, G. R. J. J. Org. Chem.

1997, 62, 8760-8766.

(42) Shieh, W. C.; Xue, S.; McKenna, J.; Prasad, K.; Repic, O.; Blacklock, T.

Tetrahedron Lett. 2006, 47, 5645-5648.

(43) Landaeta, V. R.; Peruzzini, M.; Herrera, V.; Bianchini, C.; Sanchez-Delgado, R.

A.; Goeta, A. E.; Zanobini, F. J. Organomet. Chem. 2006, 691, 1039-1050.

(44) Ager, D. J.; East, M. B.; Eisenstadt, A.; Laneman, S. A. Chem. Commun. 1997,

2359-2360.

(45) Ang, M. T. C., MSc Thesis, University of Toronto, 2007.

(46) Wegner, H. A.; Reisch, H.; Rauch, K.; Demeter, A.; Zachariasse, K. A.; de

Meijere, A.; Scott, L. T. J. Org. Chem. 2006, 71, 9080-9087.




Chapter 4

Coordination Chemistry of Monodentate

2-Indolylphosphines*

4.1. Introduction

One method to study a phosphine molecule is to examine its coordination

chemistry to transition metal centres. It is well documented that the coordination of a

phosphine ligand to Ni(CO)3 can provide information on the net-basicity of the ligand

through the complex’s infrared CO stretches.1,2 Likewise, studies have shown that the

trans-influence of ligands can be seen in the bond lengths of their metal complexes, and

can be correlated to the basicity of that ligand.3 The trans-influence of a ligand

influences the ground state properties of transition metal coordination complexes, such as

metal-ligand bond distances and NMR chemical shifts. Often the experimental measure

of a ligand’s trans-influence is to examine the M-X bond trans to the ligand in square

planar Pd(II) or Pt(II) complexes.4

In this Chapter, the coordination of monodentate 2-indolylphosphines to Ni(CO)3

will be examined, and the net-basicities of several 2-indolylphosphines deduced by this

technique. The reaction of phosphine 5 to Cu(I) in the presence of phenanthroline yields

a complex that exhibits simultaneous coordination at the phosphorus centre and anion

binding through the indolyl NH hydrogen bond donors 5. The solid-state structures of

Pd(II) and Pt(II) 2-indolylphosphine complexes will be discussed, with focus on the

trans-influence of different 2-indolylphosphine ligands.

* Reproduced in part with permission from: J. O. Yu, E. Lam, J. L. Sereda, N. C. Rampersad, A. J. Lough, C. S. Browning, and D. H. Farrar. Organometallics 2005, 24, 37-47. Copyright 2006 American Chemical Society.

104

105


4.2.1. An Evaluation of 2-Indolylphosphine Net-Basicity:

Coordination to Ni(CO)3

The net-basicities of several 2-indolylphosphines were determined by reacting

them with Ni(CO)4 in THF as shown in Scheme 4.1. The reaction proceeds under inert

dinitrogen atmosphere where Ni(CO)4 is added dropwise from its lecture bottle via static

vacuum into a Schlenk flask containing a THF solution of the phosphine. After several

hours of stirring the unreacted Ni(CO)4, CO, and THF are removed in vacuo into a

secondary trap containing bleach, which renders the Ni(CO)4 unreactive. The remaining

solid is the desired Ni(CO)3L complex, which has an unambiguous IR pattern consistent

with monosubstitution of Ni(CO)4.

R3R1

R2P + Ni(CO)4

THF R2R1

R3P Ni(CO)3

Scheme 4.1. General scheme for the formation of a monodentate Ni(CO)3(phosphine) complex.

In accordance with Tolman’s method of determining phosphine basicity, the A1

carbonyl stretching frequency of each of the monosubstituted Ni(CO)3L complexes

(where L = 2-indolylphosphine) were measured by IR spectroscopy in heptanes.

Hydrocarbon solvents tend to produce sharper peaks for the Ni(CO)3L complexes,

whereas halogenated solvents result in broadening of the CO stretching bands.5 These A1

CO stretching frequencies are subsequently compared to the analogous carbonyl stretch

of Ni(CO)3(PtBu3) (νCO = 2056.1 cm-1), the most basic phosphine in Tolman’s series, to

give the net-basicity value denoted χ.2 The χ-values determined for the selected 2-

indolylphosphines are listed in Table 4.1 along with some common phosphines from the

literature to provide frames of references for comparison.

106

Table 4.1. Infrared CO stretching frequencies of Ni(CO)3L in heptanes.

Entry

L = Phosphine

νCO (A1) (cm-1)

χ (cm-1)

1

P(tBu)3

2056.1a

0

2 PMe3 2064.1 a 8.0

3

HN

P (20)

2065.7

9.6

4

P(o-tolyl)3

2066.6 a

10.5

5 PPh3 2068.9 a 12.8

6

NP (N-Me)-1

2070.9

14.8

7

HN

PNH (4)

2071.7

15.6

8

HN

P (1)

2072.8

16.7

9

NH

PHN (3)

2074.9

18.8

10

NP

N

F

FF

FF

F F

F

FF (N-F5Bn)2-4

2076.2

20.1

11

NH

P

HN

HN

(5)

2076.5

20.4

12 P(2-CH2CH2CN)3 2077.9 a 21.8 aValues determined in CH2Cl2.2

107

Ligand 20 is found to be the most basic of the 2-indolylphosphines, with a χ-

value of 9.6 cm-1, and is most likely due to the electron donating power of the tert-butyl

substituents on phosphorus. The χ-value of 20 makes it less basic than PMe3, but more

basic than P(o-tolyl)3. By exchanging the tert-butyl substituents for less electron rich

phenyl moieties, the net-basicity of 1 has decreased substantially (χ-value = 16.7 cm-1)

and renders it less basic than PPh3. As the phenyl substituents are replaced with

increasing number of 3-methylindolyl groups, the χ-values increase as well, suggesting a

weaker donating ability for 3-methylindolyl compared to phenyl. The exception to this is

the coupled indolyl phosphine, 4, which has a χ-value greater than 1. A possible reason

for the increase in net-basicity of 4 may be a change in the hybridization of the

phosphorus from the coupling of the indolyl substituents, resulting in greater p-character

of the lone pair.

As it was discussed in Section 2.3.1, 2-indolylphosphines can be modified at the

nitrogen centre to produce functionalized ligands. The utility of the indolyl NH site is

demonstrated with the N-alkylated 2-indolylphosphines, whereby the net-basicity of the

parent phosphine can be altered depending on the substituent on nitrogen. For example,

the electron donating methyl group of (N-Me)-1 (χ = 14.8 cm-1) increases the net-

basicity of 1 (χ = 16.7 cm-1); similarly as expected, the electron withdrawing

pentafluorobenzyl moieties of (N-F5Bn)2-4 appear to decrease the net-basicity of 4 from

χ = 15.6 cm-1 to χ = 20.1 cm-1. Consequently, the net-basicity of 2-indolylphosphines

can be tuned easily by two methods: changing the substituents on phosphorus, or

furnishing different substituents on nitrogen. The symmetric phosphine 5 possesses the

largest χ-value (20.4 cm-1) of the 2-indolylphosphines investigated, with a net-basicity

that approaches P(2-CH2CH2CN)3 (χ = 21.8 cm-1). The three indolyl NH sites of 5 have

demonstrated collective hydrogen bonding to bind anion guests, as discussed in

Section 3.2.2. Alternatively, the nitrogen centres can be modified with a variety of

different substituents, analogous to (N-Me)-1 and (N-F5Bn)2-4, which would increase the

range of net-basicities that can be achieved with 2-indolylphosphines.

108

4.2.2. [5·X]- Complexes: Simultaneous Coordination at

Phosphorus with Ni(II)

As it was detailed in Section 3.2.2, phosphine 5 has the ability to act as an anion

receptor through its three indolyl NH functionalities. It was anticipated that simultaneous

coordination at the phosphorus centre may be feasible, while the NH sites were engaged

in hydrogen bonding. To explore the possibility of concurrent P-coordination and

hydrogen bonding, three [5·X]- complexes were isolated by mixing 5 with F-, Cl-, or Br-

(as their tetraethylammonium salts), which were subsequently reacted with Ni(CO)4 in

THF (Scheme 4.2).

P

HN

3

X

NEt4THF+ Ni(CO)4 P

HN

3

X

NEt4 Ni(CO)3

Scheme 4.2. General scheme for the formation of a monodentate [NEt4][Ni(CO)3(5·X)] complex. X = F-,

Cl-, Br-.

The reaction produced a product which exhibited an unambiguous IR spectrum consistent

with a monosubstituted Ni(CO)3L complex. The χ-values for the three [5·X]- complexes

were determined, and are listed in Table 4.2.

109

Table 4.2. Infrared CO stretching frequencies of [Ni(CO)3(5·X)]- in heptanes.

Entry

[5.X]-

νCO (A1) (cm-1)

χ (cm-1)

1

P

HN

3

F

(7)

2069.6

13.5

2

P

HN

3

Cl

(21)

2074.2

18.1

3

P

HN

3

Br

(22)

2074.2

18.1

The χ-values determined for the [5·X]- complexes show an increase in the net-

basicity compared to uncomplexed 5 (χ = 20.4 cm-1). This increase in χ-value suggests

that the presence of the hydrogen bonded anion not only influences the net-basicity of the

phosphine, but provides evidence that simultaneous coordination chemistry can occur at

the phosphorus centre while the phosphine is acting as an anion receptor. Although the

Cl- and Br- complexes of 5 do not appear to have a significant impact on its net-basicity,

complex [5·F]- has a χ-value (13.5 cm-1) that approaches PPh3 (χ = 12.8cm-1). The

hydrogen bonds are strong enough (as seen in the hydrogen bond distances and stability

constants, Section 3.2.2) that they can survive solvation and simultaneous coordination at

the phosphorus centre. Thus the anion binding ability of 5 provides a supplementary

means to alter the net-basicities of 2-indolylphosphines.

110

It is unlikely that the χ-values determined for the [5·X]- complexes are due to the

coordination of the halide to Ni(CO)3. According to Cassar and co-workers,6 the

treatment of a [Ni(CO)3X]- complex with PPh3 irreversibly yields Ni(CO)3PPh3 and free

halide. Additionally, the A1 carbonyl stretching frequencies for the [Ni(CO)3X]-

complexes are substantially lower than those of the [Ni(CO)3(5·X)]- complexes: Br-

νCO = 2051.0 cm-1 and Cl- νCO = 2049.0 cm-1.

4.2.3. [5·Anion]- Complexes: Simultaneous Coordination

at Phosphorus with Cu(I)

In continuing to explore the simultaneous coordination at phosphorus while

hydrogen bonding at nitrogen, the initial intent was to develop a four-coordinate

tetrahedral [Cu(5)2(phen)]+ complex as a building block for supramolecular assemblies

(Scheme 4.3). One can envisage the addition of an appropriately shaped dianion that can

result in the self-assembly of higher architectures through hydrogen bonding to the two

hydrogen bond donating cavities of the [Cu(5)2(phen)]+ complex.

N

NHN

P

HN NH

N

N Cu PP

HNHN

3

3

BF4

NCMe

CuMeCN NCMe

NCMe

BF4

MeCN

2 +

no reaction

Scheme 4.3. Anticipated four-coordinate tetrahedral Cu(I) complex in the reaction of 5 (2 eq), phen , and

[Cu(MeCN)4]BF4.

111

The reaction of 5 and phen with [Cu(MeCN)4]BF4 in CH2Cl2 in a 2 : 1 : 1 stoichiometry

resulted in the formation of a [Cu(5)(phen)]BF4 complex (Scheme 4.4).

N

NHN

P

HN NH

NCMe

CuMeCN NCMe

NCMe

BF4

MeCN

2 +

34%

CuN

N

P

HNHN

HN BF4

23 Scheme 4.4. Three coordinate trigonal planar Cu(I) complex, 23, yielded from reaction of 5 (2 eq), phen,

and [Cu(MeCN)4]BF4.

The stoichiometry of the [Cu(5)(phen)]BF4 complex, 23, was confirmed by single crystal

X-ray diffraction, and experimental details are listed in Table 4.3. Crystals of 23 were

grown from Et2O vapour diffusion into a CH2Cl2 solution of the complex. Tables 4.4 and

4.8 lists selected bond angles and distances and the numbering scheme is shown in Figure

4.1.

Complex 23 crystallizes in the space group Pī with two molecules in the unit cell.

The Cu(I) adopts a three-coordinate essentially trigonal planar geometry where P1 of 5

deviates from the plane defined by the chelated phen ligand and Cu(I) by 0.654(3) Å.

The Cu(I)-P1 distance is 2.1729(8) Å and is short for Cu(I)-P bond lengths. A survey of

the literature does not produce three-coordinate copper(I)-phosphine complexes; however,

several examples of four-coordinate copper(I)-phosphine complexes were found to have

Cu(I)-P bond lengths that ranged from 2.24 to 2.37 Å.7-9 The shorter Cu(I)-P bond length

of 23 is most likely due to the smaller coordination number around the Cu(I) centre,

which eliminates some of the steric crowding from the ligands observed in the four-

coordinate copper(I) complexes.

112

Table 4.3. X-ray crystallographic experimental data for complexes: 23, 24, and 25.

23

CuN

N

P

HNHN

HN BF4

24

NH

PPd

Cl

ClCl

HN

PPd

Cl

25

NH

PPd

Cl

ClCl

HN

PPd

Cl

Formula C39H32CuN5PBF4 C42H36Cl4N2P2Pd2 C44H64Cl8N2P2Pd2 Formula Weight 752.02 985.27 1179.31 Crystal colour, shape yellow, cubes dark orange, plates orange, block Crystal size, mm 0.26 x 0.20 x 0.10 0.56 x 0.30 x 0.02 0.14 x 0.12 x 0.06 Crystal system Triclinic Monoclinic Rhombohedral Space group P -1 P21/c R -3 a, Å 12.1112(4) 15.6092(5) 26.5804(11 b, Å 12.1741(4) 8.0167(2) 26.5804(11) c, Å 13.4482(6) 15.9823(4) 21.1789(7) α deg 68.866(2) 90 90 β, deg 70.427(2) 96.823(1) 90 γ deg 72.803(2) 90 120 V, Å3 1707.76(11) 1985.77(9) 12958.6(9) Z 2 2 9 Dcalcd, g cm-3 1.462 1.648 1.360 F(000) 772 984 5400 μ, mm-1 0.746 1.289 1.080 λ (Mo Kα), Å 0.71073 0.71073 0.71073 Limiting indices -15<=h<=15 -20<=h<=20 -34<=h<=26 -15<=k<=15 -8<=k<=10 -30<=k<=34 -15<=l<=17 -19<=l<=20 -27<=l<=27 2θ range, deg 2.78 to 27.52 2.85 to 27.54 2.61 to 27.50 Max. and min. transmission 0.950 and 0.564 0.978 and 0.763 0.9380 and 0.8635 No. of reflections collected 18062 14479 15629 No. of independent reflections/Rint 7758 / 0.1151 4839 / 0.0501 6527 / 0.0579 Extinction coefficient - 0.0021(5) 0.00006(5) No. of refined parameters 463 237 285 Final R1, wR2 0.0549, 0.1299 0.0321, /0.0827 0.0627, 0.1593 Final R1, wR2 (all data) 0.1176, 0.1534 0.0408, 0.0880 0.1206, 0.1852 Goodness of fit 1.042 1.032 0.988 Δρmin, Δρmax, eÅ-3 -0.731, 0.575 -1.065, 0.675 -0.841, 1.795

113

Figure 4.1. The ORTEP diagram and numbering scheme of [Cu(5)(phen)]BF4, 23. The broken lines show

the hydrogen bonding between the indolyl NH sites and the BF4- anion. Selected hydrogen atoms shown,

others removed for clarity. Thermal ellipsoids shown at 35% probability.

It appears from Figure 4.1 that the methyl groups of 5 are in relatively close

proximity to the Cu(I) centre in complex 23, suggesting a possible Cu(I)…H-C agostic

interaction. Agostic interactions are typically characterized by interaction distances and

angles ranging from M…H ≈ 1.8 – 2.3 Å, and M…H-C ≈ 90 – 140o, respectively.10

Additionally, an agostic interaction would be indicated by proton signals in the hydride

region in its 1H NMR spectrum. The Cu(I)…H non-bonding distances range from 2.477

to 3.016 Å, and the <Cu(I)…H-C angles range from 134.2 to 146.8o. Even the shortest

Cu(I)…H10A interaction (2.477 Å) with a Cu(I)…H10A-C10 interaction angle at 134.2o

would be considered too large to be an agostic interaction. Furthermore, all the methyl

resonances of 23 appear as a singlet at 2.49 ppm. Thus, the Cu(I)…H interactions of 23

may be classified as electrostatic interactions: the methyl resonances of 23 appear

downfield compared to the uncomplexed ligand; the Cu(I)…H distances and the Cu(I)…H-

C angles are larger than typical agostic interactions.

114

Table 4.4. Selected bond lengths (Å) and bond angles (o) for complex 23.

CuN

N

P

HNHN

HN BF4

(23) Cu1-P1 2.1729(8) N1-C2 1.392(4)

Cu1-N31 2.021(3) C2-C3 1.378(4) Cu1-N34 2.063(3) C3-C4 1.427(5)

C4-C9 1.408(4) N(31)-Cu(1)-P(1) 140.38(8) C9-N1 1.376(4) N(34)-Cu(1)-P(1) 135.01(8)

N(31)-Cu(1)-N(34) 82.24(10) <C9-N1-C2 108.8(2) <N1-C2-C3 109.2(3)

P1-C2 1.806(3) <C2-C3-C4 106.6(3) P1-C12 1.801(3) <C3-C4-C9 107.7(3) P1-C22 1.808(3) <C4-C9-N1 107.6(3)

N21-C22 1.389(4) N11-C12 1.394(3) C22-C23 1.381(4) C12-C13 1.363(4) C23-C24 1.428(4) C13-C14 1.435(4) C24-C29 1.420(4) C14-C19 1.406(4) C29-N21 1.371(4) C19-N11 1.366(4)

<C29-N21-C22 109.4(3) <C19-N11-C12 109.3(2) <N21-C22-C23 109.1(3) <N11-C12-C13 109.3(3) <C22-C23-C24 106.8(3) <C12-C13-C14 106.5(3) <C23-C24-C29 107.5(3) <C13-C14-C19 107.7(3) <C24-C29-N21 107.3(3) <C14-C19-N11 107.2(3)

N1…F4 2.879(3) <N1-H1…F4 151.8

N11…F3 2.994(3) <N11-H11…F3 140.4 N21...F1 2.983(3) <N21-H21…F1 129.9

In contrast to the weak BF4- binding ability of 5 in solution (Ka = 150 M-1) the

solid-state structure of 23 clearly shows the indolylphosphine ligand binding the

tetrafluoroborate counteranion. The anion does not interact with 5 through one of its

fluoride atoms only, as might be anticipated from the crystal structure of [NEt4][5·F].

Rather, the hydrogen bonding between 5 and BF4- demonstrates the C3-symmetric

complementarity between the tetrahedral geometry of the anion and the three hydrogen

bond donors of 5. It appears that the BF4- anion is too large in size to fit well inside the

receptor cavity of 5 as the hydrogen bonding distances are longer than typical N...F-

distances11 and the NH…F- bond angles (130 to 152o) are much less than ideally linear

hydrogen bonding interactions.

115

The complex stacks in alternating head-to-head and tail-to-tail fashion (Figure

4.2). The head-to-head stacking appears to consist of intermolecular π-cation interactions

at a distance of 3.84 Å between the central fused benzene ring of the phen ligand of one

complex and the Cu(I) ion of another complex.

Figure 4.2. The unit cell diagram of [Cu(5)(phen)]+, viewing along the crystallographic c-face. Cation-π

interactions are likely between symmetry equivalent complexes about the crystallographic inversion centre.

Hydrogen atoms have been removed for clarity.

Three-coordinate trigonal planar Cu(I) complexes can result from the dissociation

of ligands as a result of steric interactions between bulky groups, as is seen in

[Cu(dmp)(PPh3)2]+, which has unfavourable contacts between the phenyl substituents of

PPh3 and the methyl groups of 2,9-dimethyl-1,10-phenanthroline (dmp).12 It is likely that

the bulkiness of 5, by virtue of the three methyl groups on the indolyl substituents,

prevented the coordination of a second phosphine to Cu(I) and resulted in the metal

centre to be three-coordinate. Alternatively, the larger steric crowding of the three

methyl moieties of 5 may have caused the dissociation of a second phosphine on the

Cu(I) centre. The ligand stoichiometry of [Cu(5)(phen)]+ suggests that 5 is larger than

PPh3 (cone angle 145o)13 which can readily form four-coordinate tetrahedral

[Cu(PPh3)2(phen)]+ complexes.12 It had been previously suggested that phosphines 1 and

3 are likely to possess cone angles larger than PPh3, and may be similar in size to P(o-

116

tolyl)3.13 Therefore, it is in agreement that 5 should also be similar in size to P(o-tolyl)3,

as is suggested by the ligand stoichiometry of [Cu(5)(phen)]+.

4.3. Pd(II) and Pt(II) Complexes of Monodentate 2-

Indolylphosphines

2-Indolylphosphines can serve as neutral 2e- monodentate phosphorus ligands,

and their coordination chemistry with Pd(II) has been well documented elsewhere.14 A

general reaction scheme for the synthesis of dimeric [Pd(2-indolylphosphine)Cl(μ-Cl)]2

complexes is illustrated in Scheme 4.5. Generally, the reaction involves adding a

stoichiometric amount of phosphine to a stirring solution of Pd(COD)Cl2 in MeCN, the

complex is precipitated from the reaction solution with Et2O. With the ligand to Pd(II)

ratio restricted to 1 : 1, the dimeric species is always formed.

NH

PPd

Cl

ClCl

HN

PPd

ClHN

PPd(COD)Cl2MeCN, r.t.

15 min

24 Scheme 4.5. Reaction scheme for the formation of [Pd(1)Cl(μ-Cl)]2, 24. This is a representative example

of the general reaction sequence for the synthesis of [Pd(2-indolylphosphine)Cl(μ-Cl)]2 complexes.

The addition of 2 : 1 ligand to metal stoichiometry results in the formation of

monomeric species. The cis-Pt(3)2Cl2 complex, 28, was formed by reaction of Zeise’s

salt and two equivalents of phosphine 3 in acetone (Scheme 4.6). Complex 28

precipitated from the reaction solution and was acquired in moderate yield. The 31P

NMR spectrum of 28 exhibited one phosphorus environment at δ = -17.5 ppm (JPt-P =

117

3579 Hz), which is consistent with the 31P chemical shift of cis-Pt(PPh3)2Cl2 (δ =

11.7 ppm, JPt-P = 3679 Hz).15 Attempts to isomerize complex 28 into the trans-isomer by

refluxing 28 in CH2Cl2 led to intractable species. It is thought that the complicated

reactivity of complex 28 may be a result of the indolyl NH hydrogen bond donors

interacting with the chloro ligands on Pt(II), either inter- or intramolecularly.

HN

PPt

ClCl

HN

NH

P HNNH

P HN

K[PtCl3(C2H4)]acetone, r.t.

15 min

66%

28 Scheme 4.6. Reaction scheme for the formation of cis-Pt(3)2Cl2, 28.

Crystallographic analyses of the metal complexes of various monodentate 2-

indolylphosphines are shown in Figure 4.3.

NH

PPd

Cl

ClCl

HN

PPd

Cl

NH

PPd

Cl

ClCl

HN

PPd

ClHN N

H

NHP

PdCl

ClClPd

ClNH

HNP H

N

NH

PPd

Cl

ClCl

HN

PPd

Cl

HN

PPt

ClCl

HN

NH

P HN

(a) (b)

(c) (d) (e)

24 25

26 27 28

Figure 4.3. Metal complexes of monodentate 2-indolylphosphines. (a) [Pd(1)Cl(μ-Cl)]2 (24).

(b) [Pd(2)Cl(μ-Cl)]2 (25). (c) [Pd(3)Cl(μ-Cl)]2 (26). (d) [Pd(4)Cl(μ-Cl)]2 (27). (e) cis-Pt(3)2Cl2 (28).

118

4.3.1. X-ray Crystallographic Analysis of Pd(II) and Pt(II)

Complexes of Monodentate 2-Indolylphosphines

The X-ray crystallographic experimental data for [Pd(1)Cl(μ-Cl)]2, 24, and

[Pd(3)Cl(μ-Cl)]2, 25, are listed in Table 4.3, while the remaining metal complexes are

listed in Table 4.5.

Table 4.5. X-ray crystallographic experimental data for complexes: 26, 27, and 28.

26

NH

PPd

Cl

ClCl

HN

PPd

ClHN N

H

27

NHP

PdCl

ClClPd

ClNH

HNP H

N

28

HN

PPt

ClCl

HN

NH

P HN

Formula C48H42Cl4N4P2Pd2 C48H42Cl8N4O2P2Pd2 C50H48Cl2N4OP2Pt Formula Weight 1091.40 1265.20 1048.85 Crystal colour, shape dark orange, needles dark orange, block colourless, block Crystal size, mm 0.08 x 0.05 x 0.04 0.32 x 0.18 x 0.02 0.40 x 0.36 x 0.26 Crystal system Monoclinic Triclinic Monoclinic Space group P21/c P -1 P21/c a, Å 8.2002(4) 8.7188(2) 11.0184(3) b, Å 19.3095(10) 11.8646(4) 34.3286(5) c, Å 14.4641(9) 12.2122(3) 11.8324(3) α deg 90 79.429(14) 90 β, deg 100.594(2) 79.387(13) 92.221(9) γ deg 90 87.593(13) 90 V, Å3 2251.2(2) 1220.56(6) 4472.2(2) Z 2 1 4 Dcalcd, g cm-3 1.610 1.721 1.558 F(000) 1096 632 2104 μ, mm-1 1.147 1.285 3.371 λ (Mo Kα), Å 0.71073 0.71073 0.71073 Limiting indices -10<=h<=10 -11<=h<=11 -14<=h<=14 -25<=k<=25 -15<=k<=15 -44<=k<=44 -19<=l<=18 -15<=l<=15 -14<=l<=15 2θ range, deg 1.78 to 27.59 1.72 to 27.58 1.19 to 27.50 Max. and min. transmission 0.9556 and 0.9138 0.981 and 0.814 0.430 and 0.336 No. of reflections collected 18674 19119 31469 No. of independent reflections/Rint 5154 / 0.1572 5618 / 0.0635 10223 / 0.0544 Extinction coefficient 0.0138(9) 0.0042(9) 0.00035(10) No. of refined parameters 274 307 547 Final R1, wR2 0.0625, 0.1260 0.0387, 0.0943 0.0421, 0.0925 Final R1, wR2 (all data) 0.1546, 0.1721 0.0510, 0.1018 0.0590, 0.0995 Goodness of fit 0.985 1.050 1.053 Δρmin, Δρmax, eÅ-3 -1.056, 1.167 -1.367, 0.887 -1.455, 1.836

119

Single crystals of 24 were grown from solvent vapour diffusion of hexanes into a

solution of the complex in CH2Cl2. The numbering scheme of the complex is shown in

Figure 4.4 and Tables 4.6 and 4.8 lists selected bond angles and distances. The solid-

state structure of 24 consists of discrete molecules of the dimer sitting about

crystallographic inversion centres in the monoclinic space group P21/c, with one

molecule of the dimer in the asymmetric unit. The Pd(II) exhibits the expected square

planar coordination geometry and share a number of structural similarities with

previously reported [Pd(L)Cl(μ-Cl)]2 dimers. Most notably, the Pd-P bond lengths of

2.2331(7) Å is consistent with Pd-P bond lengths reported for other palladium-phosphine

complexes.16,17 Intramolecular hydrogen-bonding contacts are evident between N1-H1A

and the terminally bound Cl2 at a distance of 3.109(3) Å and a bond angle of 134.0o.

There appear to be no intermolecular hydrogen bonding interactions in the extended

solid-state.

Compared to the crystal structure of 1, the most significant differences in 24 can

be found in the P-C bond lengths. The P-C bond distances in 1 ranged from 1.811(2) to

1.837(4) Å, whereas the corresponding bond distances in 24 are shorter and range from

1.798(3) to 1.810(3) Å. The shortening of P-C bond lengths are consistent with

phosphine coordination to Pd(II).

Figure 4.4. The ORTEP diagram and numbering scheme of 24. The broken lines show the intramolecular

hydrogen bonding between the indolyl NH and the terminal chloro ligand. Non-acidic protons removed for


120

Table 4.6. Selected bond lengths (Å) and bond angles (o) for complexes 24 and 25.

24

NH

PPd

Cl

ClCl

HN

PPd

Cl

25

NH

PPd

Cl

ClCl

HN

PPd

Cl

Pd1-P1 2.2331(7) 2.260(2) Pd1-Cl1 2.3208(6) 2.324(2) Pd1-Cl2 2.2794(7) 2.276(2)

Pd1-Cl1#1 2.4312(6) 2.446(1)

<P1-Pd1-Cl2 89.45(3) 90.24(5) <P1-Pd1-Cl1 94.51(2) 95.60(5)

<Cl2-Pd1-Cl1#1 91.27(2) 89.53(5) <Cl1-Pd1-Cl1#1 84.66(2) 84.68(5)

P1-C2 1.798(3) 1.803(6)

P1-C12 1.810(3) 1.825(6) P1-C22 1.808(3) 1.841(6)

N1-C2 1.380(4) 1.399(7) C2-C3 1.388(4) 1.350(8) C3-C4 1.424(4) 1.433(7) C4-C9 1.408(4) 1.395(8) C9-N1 1.366(4) 1.361(7)

<C9-N1-C2 108.9(2) 108.6(5) <N1-C2-C3 109.6(3) 108.8(5) <C2-C3-C4 105.9(3) 107.6(5) <C3-C4-C9 107.8(3) 106.7(5) <C4-C9-N1 107.8(3) 108.3(5)

N1...Cl2 3.109(3) 3.284(5)a

<N1-H1…Cl2 134.0 163.4a

a -x+y+4/3, -x+2/3, z-1/3, intermolecular hydrogen bonding.

The solid-state structure of 25 was acquired by vapour diffusion of hexanes into a

solution of the complex CH2Cl2. A molecular diagram and numbering scheme for 25 is

illustrated in Figure 4.5, selected bond distances and angles are listed in Tables 4.6 and

4.8. Complex 25 crystallizes in the rhombohedral space group R-3. Within the

asymmetric unit are contained: one dimer molecule; two CH2Cl2 solvate molecules, one

molecule which is disordered about a crystallographic 3-fold rotational axis and modeled

at 33% occupancy, while the other molecule is modeled at 66% occupancy.

121

Figure 4.5. The ORTEP diagram and numbering scheme of 25 Non-acidic protons and CH2Cl2 solvent

molecules removed for clarity. Thermal ellipsoids are drawn at 35% probability.

Similar to the solid-state structure of 24, the Pd(II) centre in complex 25 has

expected square planar coordination geometry. The Pd(II)-P1 bond length of 25

(2.260(2) Å) is comparable to that belonging to 24. While there are no intramolecular

hydrogen bond interactions there is evidence for intermolecular interactions. The

secondary interactions occur between symmetry related dimmers from the terminal Cl2 to

an indolyl NH with a hydrogen bond donor-to-acceptor distance of 3.284(5) Å and an

angle of 163.4o. In comparing the phosphine of complex 25 to the solid-state structure of

the free phosphine, 2, the largest differentiation is the shortening of the P-C bond

distances upon coordination of Pd(II). The P-C bond lengths range from 1.818(2) to

1.858(2) Å in 2, whereas the same bond lengths in 25 ranges from 1.803(6) to 1.841(6) Å.

Single crystals of 26 were obtained from solvent vapour diffusion of Et2O into a

solution of the complex in CH2Cl2. Figure 4.6 shows the molecular structure and

numbering scheme for the complex, while Tables 4.7 and 4.8 lists selected bond distances

and angles. Complex 26 is isostructural to the solid-state structure of 24, also

crystallizing in the monoclinic space group P21/c with one dimer molecule in the

asymmetric unit that sits about a crystallographic inversion centre. The Pd(II) centre is

square planar with a Pd(II)-P1 bond length of 2.220(2) Å, and is comparable to the

analogous bond length found in 24. Similar intramolecular hydrogen-bonding

122

interactions exist between the terminal Cl2 in 26 and the N11-H11A group of the suitably

orientated indolyl substituent. However, intermolecular hydrogen bonding is not seen in

the extended structure between dimers. Consistent with the P-C bond lengths shortening

upon coordination seen in complexes 24 and 25, the phosphine in 26 also exhibits shorter

P-C bond lengths (1.790(8) to 1.805(7) Å) in contrast to the free ligand 3 (1.809(2) to

1.841(2) Å).


hydrogen bonding of an indolyl NH and the terminal chloro ligand. Non-acidic protons removed for clarity.

Thermal ellipsoids are drawn at 35% probability.

123

Table 4.7. Selected bond lengths (Å) and bond angles (o) for complexes 26, 27, and 28.

26

NH

PPd

Cl

ClCl

HN

PPd

ClHN N

H

27

NHP

PdCl

ClClPd

ClNH

HNP H

N

28

HN

PPt

ClCl

HN

NH

P HN

28

HN

PPt

ClCl

HN

NH

P HN

Pd1-P1 2.220(2) 2.2162(8) 2.246(1)c 2.246(1)c Pd1-Cl1 2.319(2) 2.3163(7) 2.334(1)c 2.334(1)c Pd1-Cl2 2.269(2) 2.2901(8) 2.356(1)c 2.356(1)c

Pd1-Cl1#1 2.421(2) 2.4385(8) 2.267(1)d 2.267(1)d

<P1-Pd1-Cl2 86.90(8) 87.42(3) 96.31(4)e 96.31(4)e <P1-Pd1-Cl1 95.43(7) 94.68(3) 90.85(4)f 90.85(4)f

<Cl2-Pd1-Cl1#1 91.72(7) 91.39(3) 86.93(4)f 86.93(4)f <Cl1-Pd1-Cl1#1 86.04(7) 86.75(3) 85.89(4)g 85.89(4)g

P1-C2 1.795(8) 1.772(3) 1.803(5) 1.814(5)i P1-C12 1.790(8) 1.778(3) 1.797(5) 1.809(5)i P1-C22 1.805(7) 1.807(3) 1.820(5) 1.816(5)i

N1-C2 1.388(9) 1.385(4) 1.388(6) 1.395(6)i C2-C3 1.385(10) 1.377(4) 1.379(6) 1.388(7)i C3-C4 1.416(10) 1.426(4) 1.443(7) 1.436(6)i C4-C9 1.438(10) 1.422(4) 1.403(7) 1.394(7)i C9-N1 1.370(10) 1.366(4) 1.385(6) 1.368(6)i

<C9-N1-C2 108.8(6) 108.5(2) 108.0(4) 109.0(4)i <N1-C2-C3 109.7(6) 109.9(3) 110.5(4) 109.1(4)i <C2-C3-C4 106.8(6) 106.6(3) 105.6(4) 105.7(4)i <C3-C4-C9 107.1(7) 106.9(3) 107.9(4) 108.4(4)i <C4-C9-N1 107.5(6) 108.1(3) 108.0(4) 107.9(4)i

N11-C12 1.403(9) 1.390(4) 1.402(6) 1.402(6)i C12-C13 1.365(10) 1.375(4) 1.381(6) 1.384(6)i C13-C14 1.426(10) 1.429(4) 1.427(7) 1.432(7)i C14-C19 1.409(11) 1.408(4) 1.407(7) 1.416(6)i C19-N11 1.380(9) 1.378(4) 1.374(6) 1.376(6)i

<C19-N11-C12 107.2(6) 108.0(2) 109.0(4) 109.5(4)i <N11-C12-C13 110.0(6) 110.2(2) 108.6(4) 108.9(4)i <C12-C13-C14 107.2(6) 106.1(3) 106.9(4) 106.3(4)i <C13-C14-C19 106.9(6) 107.7(2) 107.8(4) 108.4(4)i <C14-C19-N11 108.7(6) 107.9(3) 107.6(4) 106.8(4)i

N1...Cl 3.096(7) 3.243(3)a - 2.994(6)j

N11...Cl - 2.941(4)b 3.195(5)h 3.414(4)k N21...Cl - - - 2.982(6)m

<N1-H1…Cl 130.6 129.2 - 138.4j

<N11-H11…Cl - 160.3 155.6h 123.6k <N21-H21…Cl - - - 152.8m

a-x+2,-y+2,-z+1, intramolecular hydrogen bonding. b-x+1,-y+2,-z+1, intermolecular hydrogen bonding. cPt1-atom bond distance. dPt1-P2 bond distance. e<P1-Pt1-P2 bond angle. f<atom-Pt1-atom bond angle. g<P2-Pt1-Cl2 bond angle. hN11…N41 intramolecular hydrogen bonding. iAngles associated with indolyl substituents on P2. jN31…N11 intramolecular hydrogen bonding. kN41…O1S intermolecular hydrogen bonding. mN41…O1S intermolecular bonding.

124

Single crystals of 27 were obtained from solvent vapour diffusion of hexanes into

a solution of the complex in CH2Cl2. Figure 4.7 shows the molecular structure and

numbering scheme of the complex and Tables 4.7 and 4.8 lists selected bond distances

and angles. The dimeric complex crystallizes in Pī with each half of the dimer sitting

about a crystallographic inversion centre. Per asymmetric unit, there is one molecule of

water and one molecule of CH2Cl2 also present in the lattice.


hydrogen bonding from one of the indolyl NH to the terminal chloro ligand. Non-acidic protons, CH2Cl2,

and water solvate removed for clarity. Thermal ellipsoids are drawn at 35% probability.

As exhibited in complexes 24-26, the Pd(II) centre in 27 adopts the expected

square-planar coordination geometry and monodentate P-coordination of the ligand is

obtained. Structural consequences derived from coordination of 4 in 27 can be acquired

from a comparison of its solid-state structure with those of the uncomplexed N-

substituted derivatives of 4. This reveals that the <C3-C10-C13 bond angle of 113.9(2)°

in the phosphacycle of 27 remains essentially unchanged from the values observed in (N-

CH2NMe2)2-4 and (N-F5Bz)2-4 (which are 113.0(2) and 112.9(2)o, respectively).

Nevertheless, the 4-5° increase in bond angle between indolyl substituents observed upon

P-coordination to Pd(II) in 26 is still seen in 27 and implies that coupling of the indolyl

substituents does not inhibit their “opening up” upon P-coordination (Table 4.8). A

deviation from coplanarity of 5.6(1)° between the two indolyl groups indicates that the

coupled indole remains effectively planar upon P-coordination.

125

Symmetry-related dimers of 27 pack in a laddered head-to-tail fashion that

extends up the a-axis of the unit cell. Both crystallographically independent indolyl NH

groups of each dimer are involved in hydrogen-bonding either within or between the

dimeric units of the ladder as shown in Figure 4.8. One NH group intramolecularly

hydrogen-bonds to its neighbouring terminal chloride as observed in 24 and 26. The

other NH group hydrogen-bonds to the oxygen atom of solvate water which completes a

cyclic network by hydrogen-bonding in turn to the terminal chloride of a symmetry-

related dimer. The CH2Cl2 solvate has no significant intermolecular contacts.

Figure 4.8. Extended hydrogen bonding network of 27 along the crystallographic a-axis. The broken lines

show the intramolecular hydrogen bonding from one of the indolyl NH to the terminal chloro ligand, and

intermolecular hydrogen bonding from the opposite indolyl NH to adventitious water in the lattice. Non-

acidic protons and CH2Cl2 solvent molecules have been omitted for clarity. Thermal ellipsoids are drawn

at 35% probability.

126

Complex 28 has a 31P NMR signal (δ -17.5 ppm, JPt-P = 3579 Hz) consistent with

cis-coordination of the ligands about a Pt(II) centre. The solid-state structure of 28

confirms the isomeric arrangement. Selected bond distances and angles are listed in

Tables 4.7 and 4.8, the molecular structure and numbering scheme is shown in Figure 4.9.

Figure 4.9. The ORTEP diagram and numbering scheme of 28. Non-acidic protons and EtOH solvent

molecule removed for clarity. Thermal ellipsoids are drawn at 35% probability.

Complex 28 crystallizes in the monoclinic space group P21/c with one molecule

of the complex and one additional molecule of EtOH solvate in the asymmetric unit. The

Pt(II) has the expected square planar coordination geometry and the Pt(II)-P1 bond

distances are ordinary (average Pt(II)-P bond length 2.257(2) Å) compared to an

assessment of similar cis-Pt(II)(phosphine)2Cl2 structures in the CSD (average Pt(II)-P

bond length 2.246(3) Å).18 In accord with the Pd(II) complexes, the P-C bond lengths of

ligand 3 shorten upon coordination of the phosphine to Pt(II) (from 1.809(2) -1.841(2) Å

for the free ligand to 1.797(5)-1.820(5) Å for the complexed ligand).

Secondary hydrogen bonding interactions are evident in the solid-state structure

of 28 (Figure 4.10). Interestingly, more intramolecular hydrogen bonding interactions

occur between adjacent NH sites, rather than the conventional intramolecular NH…Cl-

interactions. The close proximity of the indolyl NH sites probably result in the formation

of secondary interactions seen between N11-H11a…N41 (3.195(5) Å, 155.6o), and N31-

H31A…N11 (2.994(6) Å, and 138.4o). Conventional intramolecular hydrogen bonding

127

between N41-H41A…Cl2 is also found in 28 (H41A…Cl2 2.85 Å); however, the

interaction is weaker than the alternate NH…N contacts, as it is approaching the limit of

the sum of van der Waals radii. Intermolecular hydrogen bonding is exhibited between

the OH moiety of the EtOH solvate and one of the indolyl NH sites, N41-H41. An

interaction is formed from N41-H41A to O1S, and the proton of O1S forms an

interaction with N41 in a cyclic fashion. Despite the fact that widespread hydrogen

bonding is apparent in the solid-state structure of 28, these secondary interactions are

restricted to the discrete complex and do not continue into the extended lattice.

Figure 4.10. The varied intra- and intermolecular hydrogen bonding of 28. Broken lines indicate

intramolecular hydrogen bonds from N11…N41, N31…N11, and N41…Cl2. Cyclic intermolecular hydrogen

bonding is exhibited between N41…O1S. Non-acidic hydrogen atoms removed for clarity. Thermal


128

4.3.2. Examining the Effect of Phosphine Net-Basicity on

Pd(II)-P Bond Lengths

The correlation between phosphine net-basicity and Pd(II)-P bond lengths in

complexes 24-27 are examined. While the net-basicity of ligand 2 was not measured, its

net-basicity can be approximated using Tolman’s substituent additivity rule.2 The

individual electronic parameter, χi for a cyclohexyl substituent is 0.1 cm-1 and the

individual electronic parameter of the indolyl substituent of C3-symmetric phosphine 5 is

6.8 cm-1, as determined by Equation 4.1.

χ χ1χ2χ3 = νCO(A1) - 2056.1 cm-1 = Σ3

i=1χi

P (4.1)

By Tolman’s additivity rule, the net-basicity of 2 is estimated to be 2063.1 cm-1, which

makes it the more net-basic than ligands 1, 3, and 4. Therefore, the order of increasing

net-basicity of the 2-indolylphosphines for which there are dimeric [Pd(2-

indolylphosphine)Cl(μ-Cl)]2 complexes is: the diindolylphenylphosphine 3 is the least

net-basic, followed by the indolyldiphenylphosphine 1, then the coupled

indolylphenylphosphine 4, and finally the most net-basic dicyclohexylindolylphosphine 2.

One would expect the Pd(II)-P bond lengths to decrease with increasing

phosphine basicity. On inspection of the Pd(II)-P bond lengths of complexes 24, 25, 26,

and 27, the shortest Pd(II)-P bond length occurs in complex 25 and does indeed belong to

the most net-basic phosphine 2. The trend is consistent with complexes 24 and 26 which

have increasing Pd(II)-P bond lengths, suggesting a decrease in phosphine basicity.

However, the Pd(II)-P bond distance of complex 27 is inconsistent with this argument, it

is the shortest of the four complexes, and can be a result of the difference in hybridization

of the phosphorus atom of 4.

It is anticipated that the more basic the phosphine is, the stronger its trans

influence, which can be seen in a lengthening of the Pd(II)-Cl bond situated trans to the

phosphine. Thus the trans Pd(II)-Cl1#1 bond distances were examined. The order of

129

increasing Pd(II)-Cl1#1 bond lengths is consistent with increasing net-basicity of the 2-

indolylphosphines. The shortest Pd(II)-Cl1#1 bond length is found in complex 26, where

ligand 3 is the least net-basic. The longest Pd(II)-Cl1#1 bond length belongs to complex

25, with ligand 2 being the most net-basic and suggests it has the strongest trans influence.

4.3.3. The Effect of Metal Coordination on the Σ{<CPC}

of Monodentate 2-Indolylphosphines

In general, the average Σ{<CPC} for all of the monodentate 2-indolylphosphines

have shown an increase from the uncoordinated free ligands, and is consistent with the

subtle change of the coordination geometry of the phosphorus atom upon metal

complexation (Table 4.8). This trend however, appears to be irregular and does not seem

to be due to systematic changes in the ligands. The coordination of ligands 1 and 3 with

Pd(II) show an increase in the average Σ{<CPC} to the same value (320.0(2) and

320.1(6)o, respectively) which is expected since both phosphines have similar average

Σ{<CPC} (304.3(2) and 303.8(2)o, respectively). Complex 28 is structurally different

from complex 26, however they both share the same phosphine ligand. Assessment of

the average Σ{<CPC} for 28 reveals that these values (315.6(4) and 312.0(4)o) are

considerably smaller than 26; this appears to be attributable to the cis-conformation of the

two ligands which experience increased steric crowding from the neighbouring ligand’s

substituents, and are thus forced to have a decreased Σ{<CPC}. In addition, the

increased intramolecular hydrogen bonding seen in complex 28 may be a contributing

factor for the smaller Σ{<CPC}, as these secondary interactions function to hold the

substituents together.

130

Table 4.8. Sum of <CPC bond angles (o) and 31P resonances for monodentate 2-indolylphosphine metal

complexes.

Entry

Complex

<C2-P1-C12

<C12-P1-C22

<C22-P1-C2

avg. Σ{<CPC}

31P δ (ppm)a

1

23 Cu

N

N

P

HNHN

HN BF4

102.2(1)

103.7(1)

102.5(1)

308.3(2)

-63.2b

2

24 NH

PPd

Cl

ClCl

HN

PPd

Cl

102.9(1)

107.2(1)

109.9(1)

320.0(2)

14.6

3

25 NH

PPd

Cl

ClCl

HN

PPd

Cl

105.5(3)

106.2(3)

105.4(3)

317.1(5)

20.5

4

26 NH

PPd

Cl

ClCl

HN

PPd

ClHN N

H

104.6(3)

106.2(3)

109.3(4)

320.1(6)

-5.7

5

27 NH

PPd

Cl

ClClPd

ClNH

HNP H

N

99.1(1)

110.4(1)

107.9(1)

317.4(2)

-14.9

6

28 HN

PPt

ClCl

HN

NH

P HN

107.6(2)

101.8(2)b

102.6(2)

107.5(2)b

105.4(2)

102.7(2)b

315.6(4)

312.0(4)b

-17.5

aSpectra collected in CDCl3. bSpectra collected in CD2Cl2. bAngles associated with indolyl substituents on P2.

It was determined that ligand 2 has greater steric crowding in comparison to

ligand 1 (Section 2.2.2), and it was anticipated that the Σ{<CPC} would increase more

for the complexation of a bulkier phosphine, yet this is not the case for 25. The smaller

Σ{<CPC} exhibited in 25 may be a result of the lack of intramolecular hydrogen bonding

which is demonstrated in complexes 24 and 26. Presumably, intramolecular hydrogen

bonding between an indolyl NH and a terminal chloro ligand of the dimeric [Pd(L)Cl(μ-

Cl)]2 complex will encourage the <CPC bond angles to open up to allow for these

secondary interactions.

131

Although a solid-state structure of ligand 4 was not obtained, the average

Σ{<CPC} from the crystal structure of (N-F5Bn)2-4 can be extrapolated to estimate an

average Σ{<CPC} for unsubstituted 4. The average Σ{<CPC} for 4 can be approximated

by the differences in (N-Bn)-1 and ligand 1. The average Σ{<CPC} for 1 is 304.3(2)o

and (N-Bn)-1 is 307.8(2)o. By this extension, the average Σ{<CPC} for (N-F5Bn)-4

(299.2(2)o) should be slightly larger than unfunctionalized 4. Using the approximated

average Σ{<CPC}, the coordination of 4 to Pd(II) has resulted in the largest increase in

the average Σ{<CPC} (317.4(2)o) for all the monodentate 2-indolylphosphines. It is

speculated that the considerable increase in <CPC bond angles may be due to a change in

the hybridization of the phosphorus atom when it coordinates to Pd(II).

Notably, the average Σ{<CPC} for complex 23 did not vary significantly from the

free phosphine, 5. Although the Σ{<CPC} did increase from 306.9(2)o to 308.3(2)o, the

increase is not very substantial in comparison to the other monodentate 2-

indolylphosphines. One explanation may be the collective hydrogen bonding of the

indolyl NH sites to the BF4- anion, which does not allow the <CPC bond angles to open

up as demonstrated with the other ligands.

As it was observed in Section 2.3.1., there is little correlation between the

Σ{<CPC} and the 31P chemical shift of a particular 2-indolylphosphine. Especially when

a 2-indolylphosphine is acting as a monodentate ligand through phosphorus coordination,

the 31P resonance is more greatly influenced by the substituents bonded to it, as well as

the type of transition metal it is coordinating to, rather than the Σ{<CPC} bond angles.

4.3.4. The Effect of Metal Coordination on Indolyl

Aromaticity

The five bond angles within the pyrrolyl ring of the indolyl substituents of each

metal complex were compared to the equivalent bond angles of the free ligands. It was

found that coordination to a metal centre does little to the aromaticity of the indolyl

substituent. Perhaps because the nitrogen centre is not participating in metal coordination,

132

the bond angles of the indolyl ring remain virtually the same as the uncomplexed ligand.

Predictably, the most significant changes to the ligands were to the P-C bond distances

and the <CPC bond angles.

4.4. Conclusions

The coordination of 2-indolylphosphines as monodentate ligands has been

realized with complexes consisting of Ni(0), Cu(I), Pd(II), and Pt(II) species. The

Ni(CO)3(2-indolylphosphine) complexes have allowed for the determination of

phosphine net-basicity based on Tolman’s method. The various 2-indolylphosphines

exhibit a diverse range of net-basicity values: from the most basic ligand 20 with two

electron-donating tert-butyl substituents on phosphorus, to the least basic ligand 5, which

is C3-symmetric with three indolyl substituents on phosphorus. Additionally, the

nitrogen centre can be functionalized with groups of altering electronics that influence the

net-basicity of the parent 2-indolylphosphine.

It was initially introduced in Chapter 3 the ability of phosphine 5 to behave as an

anion receptor through its three indolyl NH functionalities. The coordination of [5·X]-

(where X- = F-, Cl-, Br-) to Ni(CO)3 demonstrates the facility for simultaneous

coordination chemistry at the phosphorus atom while the anion remained hydrogen

bonded to 5. Infrared measurements of the CO stretching frequencies of each

[Ni(CO)3(5·X)]- show that the presence of the hydrogen bonded anions have an impact

on the net-basicity of parent phosphine 5 by increasing it. The fluoride anion imparts the

most significant change, where the [Ni(CO)3(5·X)]- complex has a net-basicity that

approaches PPh3. Consequently, the net-basicity of 2-indolylphosphines can be tuned

relatively easily: by altering the substituents on phosphorus; by adding substituents on

nitrogen; by introducing anions for hydrogen bonding to 5.

Complex 23 also substantiates the ability for simultaneous coordination at

phosphorus while hydrogen bonding to anions at nitrogen for phosphine 5. Most notably,

the three indolyl NH sites collectively hydrogen bond to the BF4- anion in a C3-symmetric

fashion to create a discrete ion pair complex. The stoichiometry of 23 suggests

133

phosphine 5 is quite bulky, which resulted in the formation of the monophosphinated

complex, as opposed to the diphosphinated as originally proposed with the reaction

conditions.

The reaction of one equivalence of 2-indolylphosphine to one equivalence of

Pd(II) produces dimeric [Pd(2-indolylphosphine)Cl(μ-Cl)]2 complexes. Whereas the

addition of an extra equivalent of phosphine ligand, yields a monomeric species, such as

complex 28. It was observed that in all the crystal structures of the monodentate 2-

indolylphosphines that P-C bond distances decreased upon metal coordination from the

uncomplexed ligands.

The net-basicity of a phosphine can be correlated to its trans-influence strength.

Generally, the more basic a phosphine, the shorter the metal-phosphorus bond, and the

longer the metal-atom bond trans to the phosphine. The Pd(II)-P bond distances in

complexes 24-27 demonstrate this trend, with the exception of 26 which can be a result of

the difference in hybridization of the phosphorus atom of ligand 4. Alternatively, the

trans Pd(II)-Cl1#1 bond length is consistent with the expected observation that the more

basic phosphine results in a longer trans Pd(II)-Cl1#1 bonding distance as seen in

complex 25.

Additionally, the Σ{<CPC} of the metal complexes increased from the free

ligands. These changes are most likely from the subtle alteration in the hybridization of

the phosphorus atom when coordinating a metal centre. Since the 2-indolylphosphines

were acting as monodentate ligands through the phosphorus centre, the aromaticity of the

indolyl ring is not affected. Therefore, in the metal complexes, the bond angles within

the pyrrolyl moiety of the indolyl substituents are comparable to the analogous bond

angles of the free ligands.

134

4.5. Experimental

Unless otherwise stated, the synthetic protocol for 2-indolylphosphines and their metal

complexes are reported in Dr. Edmond Lam’s thesis.14



Ni(CO)4 was purchased from Strem Chemicals and used as received. [Cu(MeCN)4]BF419

and K[PtCl3(C2H4)]20 were synthesized according to literature procedures.

Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl still under a

dinitrogen atmosphere. 1H, 13C, and 31P NMR spectra were recorded on Varian 400 MHz

or 300 MHz NMR systems, and referenced to SiMe4 (TMS) and 85% H3PO4, respectively.

Splitting patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet;, m, multiplet;

br, broad peak. IR spectra were obtained using a Perkin-Elmer 1000FT-IR spectrometer

as solutions between NaCl plates. High resolution mass spectra were obtained on an

ABI/Sciex Qstar mass spectrometer (ESI).

General preparation of Ni(CO)3(2-indolylphosphines). To a solution of a 2-

indolylphosphine ligand (~0.12 mmol) in THF (5 mL) is added Ni(CO)4 (~1 mL,

7.6 mmol) dropwise. The resultant mixture is left to stir at room temperature for 30

minutes. Unreacted Ni(CO)4, CO and THF are removed into a secondary trap containing

bleach under vacuum. The remaining residues are washed with minimal hexanes.

Ni(CO)3(1) IR (heptane) ν 2072.8 cm-1 (νCO A1), 2006 (νCO A1). Ni(CO)3(3) IR (heptane)

ν 2074.9 cm-1 (νCO A1), 2005 (νCO A1). Ni(CO)3(4) IR (heptane) ν 2071.7 cm-1 (νCO A1),

2008 (νCO A1). Ni(CO)3(5) IR (heptane) ν 2076.5 cm-1 (νCO A1), 2008 (νCO A1).

Ni(CO)3(20) IR (heptane) ν 2065.9 cm-1 (νCO A1), 1996 (νCO A1). Ni(CO)3(N-Me)-1 IR

(heptane) ν 2076.2 cm-1 (νCO A1), 2004 (νCO A1). Ni(CO)3(N-F5Bn)2-4 IR (heptane) ν

2072.8 cm-1 (νCO A1), 2006 (νCO A1).

135

General preparation of NEt4[Ni(CO)3(5·X)]. To a solution of complex NEt4[5·X]

(~0.12 mmol) in THF (5 mL) is added Ni(CO)4 (~1 mL, 7.6 mmol) dropwise. The

resultant mixture is left to stir at room temperature for 30 minutes. Unreacted Ni(CO)4,

CO and THF are removed into a secondary trap containing bleach under vacuum. The

remaining residues are washed with minimal hexanes. NEt4[Ni(CO)3(5·F)] IR (heptane)

ν 2069.6 cm-1 (νCO A1), 1999 (νCO A1). NEt4[Ni(CO)3(5·Cl)] IR (heptane) ν 2074.2 cm-1

(νCO A1), 1997 (νCO A1). NEt4[Ni(CO)3(5·Br)] IR (heptane) ν 2074.1 cm-1 (νCO A1), 1997

(νCO A1).

CuN

N

P

HNHN

HN BF4

[Cu(5)(1,10-phenanthroline)]BF4, 23. Dissolved [Cu(MeCN)4]BF4 (0.168 g,

0.242 mmol), 1 (0.229 g, 0.543 mmol) and 1,10-phenanthroline (0.049 g, 0.272 mmol) in

DCM (20 mL) to give a clear yellow solution. The resultant yellow solution was placed

into a vial containing Et2O. X-ray quality single crystals were formed within one week

(0.061 g, 34 %). 31P NMR (CD2Cl2, 161 MHz): δ -63.2 (br s); 1H NMR (CD2Cl2,

400 MHz): δ 8.92 (br s, JNHF = 3.6 Hz, 3H, indole NH), 8.65 (d, J = 8.4 Hz, 2H, Ar-H),

8.57 (s, 2H, Ar-H), 8.10 (s, 2H, Ar-H), 7.93 (dd, J = 4.4, 8.0 Hz, 2H, Ar-H), 7.64 (d,

J = 8.0 Hz, 3H, Ar-H), 7.44 (d, J = 8.0 Hz, 3H, Ar-H), 7.29 (t, J = 7.6 Hz, 3H, Ar-H),

7.18 (t, J = 7.6 Hz, 3H, Ar-H), 2.49 (s, 9H, indole CH3); 13C NMR (CD2Cl2, 100 MHz):

150.9, 143.9, 139.6, 138.8, 129.6, 127.5, 126.0, 125.6, 124.5, 121.6, 120.3, 119.4, 112.3,

10.4; HRMS ESI+ for [M+] ion C39N32N5PCu+: calcd m/z 664.1657, found m/z 664.1685.

HN

PPt

ClCl

HN

NH

P HN

136

cis-Pt(3)2Cl2, 28. A solution of ligand 3 (0.88 g, 2.4 mmol) in acetone (5 mL) was added

dropwise to a suspension of K[PtCl3(C2H4)] (0.44 g, 1.2 g) in acetone (5 mL) with

stirring. A pale yellow solid precipitated out of solution within 10 minutes. The solid

was isolated by filtration, washed with minimal acetone, and dried in air. The solid was

determined to be the cis-isomer of the product (0.88 g, 66%). cis-28: 31P NMR (CDCl3,

161 MHz): δ -17.5 (JPt-P = 3579 Hz); 1H NMR (CDCl3, 300 MHz): δ 8.50 (br s, 4H,

indole NH), 7.66 – 7.10 (m, 22H, Ar-H), 6.52 (d, J = 7.5 Hz, 4H, Ar-H), 2.17 (s, 18H,

indole CH3); 13C NMR (CDCl3, 100 MHz): 138.8, 135.3, 132.1, 129.6, 129.1, 128.9,

126.2, 123.3, 122.0, 119.7, 119.5, 113.2, 111.8, 9.9.










137

4.6. References

(1) Bartik, T.; Himmler, H.-G.; Seevogel, K. J. Organomet. Chem. 1984, 272, 29 - 41.


(3) Kapoor, P. N.; Kakkar, R. Theochem 2004, 679, 149-156.

(4) Oksarsson, Å. Acta Cryst. 1990, B46, 748-752.

(5) Bor, G. Spectrochim. Acta 1962, 18, 817-822.

(6) Cassar, L.; Foá, M. Inorg. Nucl. Chem. Letters 1970, 6, 291-294.

(7) Dori, Z.; Ziolo, R. F.; Gaughan, A. P.; Pierpont, C. G.; Eisenberg, R. Inorg. Chem.

1971, 10, 1289-1296.

(8) Darensbourg, D. J.; Longridge, E. M.; Atnip, E. V.; Reibenspies, J. H. Inorg.

Chem. 1991, 30, 357-358.

(9) Saturnino, D. J.; Arif, A. M. Inorg. Chem. 1993, 32, 4157-4160.

(10) Brookhart, M.; Green, M. L. H.; Parkin, G. Proc. Nat. Acad. Sci. 2007, 104, 6908-

6914.

(11) Steiner, T. Acta. Cryst. 1998, B54, 456-463.

(12) Palmer, C. E. A.; McMillin, D. R. Inorg. Chem. 1987, 26, 3837-3840.



(15) de Jong, F.; Bour, J. J.; Schlebos, P. P. J. Inorg. Chim. Acta 1988, 154, 89-93.

(16) Coles, S. J.; Faulds, P.; Hursthouse, M. B.; Kelly, D. G.; Ranger, D. C.; Toner, A.

J.; Walker, N. M. J. Organomet. Chem. 1999, 586, 234.

(17) Slawin, A. M. Z.; Woollins, J. D.; Zhang, Q. Inorg. Chem. Commun. 1999, 2, 386.


(19) Kubas, G. J. Inorg. Synth. 1979, 19, 90.

(20) Chock, P. B.; Halpern, J.; Paulik, F. E. Inorg. Synth. 1973, 14, 90-92.




137

Chapter 5

Multidentate N-Functionalized 2-Indolylphosphines

and their Metal Complexes

5.1. Introduction

5.1.1. Bidentate (P,N)- and (P,P)-Ligands

Bidentate phosphines with hetero-donors such as QUINAP,1 and diphosphines,

such as BINAP,2 are common ligands used in catalysis. Their catalytic success is in part

due to the ability to tune the steric and electronic properties at the various donor sites. It

was revealed in Chapter 2 the ease with which alkyl groups can be furnished at the

indolyl nitrogen; furthermore in Chapter 4 the Ni(CO)3 complexes of the N-alkylated 2-

indolylphosphines demonstrated diverse net-basicities. By this extension, it is possible to

functionalize the nitrogen centre of 2-indolylphopshines to form unsymmetrical bidentate

phosphines with phosphino or amino substituents.

Parent phosphine 1 will serve as the platform for new (P,N)- and (P,P)-2-

indolylphosphines. These new bidentate ligands are coordinated to Pd(II) and Pt(II)

species and their structural features examined by X-ray crystallography. Generally,

phosphines are stronger trans-influence ligands due to their stronger σ-donicity than

amines.3 In this Chapter, the metal complexes of chelating (P,N)- and (P,P)-2-

indolylphosphines will be examined via crystallography to assess the trans-influence of

amino donors versus phosphino donors.

138

139

5.1.2. Symmetric Tetradentate Ligand PP3 and Its

Reactivity

There is continuing interest in the symmetric tripodal tris(2-

diphenylphosphino)ethyl)phosphine, PP3 (Figure 5.1a).4-7 The PP3 ligand has shown to

induce five-coordinate trigonal bipyramidal geometry when it binds to metal centres

(Figure 5.1b). Generally the PP3 ligand binds in a tetradentate fashion to the metal centre

resulting in a trigonal bipyramidal coordination geometry; the remaining fifth

coordination site on the metal is occupied by either an anionic ligand (such as Cl-, Br-, or

I-) or a neutral ligand such as a monophosphine.5,8

P

P

P

P

PP3

(a)

Ph2P MPPh2

PPh2

P

L

ML(PP3)

(b) Figure 5.1. (a) Tris(2-(diphenylphosphino)ethyl)phosphine, PP3. (b) A generic metal complex of PP3

exhibiting trigonal bipyramidal coordination geometry enforced by the PP3 ligand. M denotes a metal

cation, and L is a coordinating ligand.

Ligand 5 has the capacity to be converted to a potential tetradentate phosphine by

functionalizing the nitrogen centres with diphenylphosphino substituents. The utility of

the diphenylphosphino-functionalized 5, (N-PPh2)3-5, will be discussed in this Chapter.

Its coordination chemistry to Pt(II) and Rh(I) and subsequent reactivity will be presented.

140


5.2.1. Synthesis of Multidentate 2-Indolylphosphines

It was introduced in Section 2.2.3. the ease with which a nitrogen centre of 2-

indolylphosphines could be functionalized. Multidentate ligands can be generated by

installing groups that have the capacity to coordinate to metal centres, such groups will

contain for example nitrogen or phosphorus donors. One simple method of obtaining an

N-functionalized 2-indolylphosphine is during its general synthesis (Scheme 5.1); the

aminal-protecting group remains on the nitrogen centre following phosphine molecule

formation, which will produce a (P,N)-ligand where N refers to the donor of the newly

added functional group, and P refers to the phosphorus centre of the 2-indolylphosphine.

The variety in substituents on phosphorus will increase the diversity in (P,N)-ligands.

N

N

NP

R

R

N1. n-BuLi

2. PCl3-xRxTHF

Scheme 5.1. General reaction sequence to generate CH2NMe2-functionalized 2-indolylphosphines.

It has been demonstrated that rigid heteroaromatic rings, such as 2-pyridyl and 2-

isoquinolyl, can be furnished on the indolyl nitrogen centre with a variety of methods.

The pyridyl derivative, (N-py)-1, is synthesized using a method similar for the generation

of N-alkylated 2-indolylphosphines, with the exception of the base used to deprotonate

the nitrogen centre.9

NN

NP

N1. n-BuLi, THF, -78oC

2. Ph2PCl, -78oC3. Workup

(N-py)-1 Scheme 5.2. Reaction scheme for the synthesis of pyridyl-functionalized (N-py)-1.

141

The isoquinolyl derivative, (N-isoquin)-1, is synthesized by initially installing an

isoquinolyl substituent on the indolyl nitrogen by Cu(I) catalyzed cross-coupling between

3-methylindole and 2-bromoisoquinoline.9 Subsequent reaction of the N-functionalized

3-methylindole with n-BuLi, and chlorodiphenylphosphine oxide generates the oxide of

the desired ligand. Reduction with trichlorosilane affords (N-isoquin)-1 in moderate

yields.

NN

NN

PPh2

O NN

PPh2

1. n-BuLiTHF, -78oC

2. Ph2P(O)Cl-78oC

3. Workup

HSiCl3, NEt3dioxane, Δ

(N-isoquin)-1 Scheme 5.3. Reaction scheme for the synthesis of isoquinoline-functionalized (N-isoquin)-1.

Similarly, new (P,P)-ligands can be formed by reacting a 2-indolylphosphine with

a base to deprotonate the nitrogen centre and the ensuing reaction with the desired

phosphino substituent.9 Scheme 5.4 outlines several phosphine functionalized derivatives

of ligand 1. The additional phosphine moieties can range in bulkiness, such as (N-PCy2)-

1, or introduce a second centre of chirality, as in the (N-(R)-BINO)-1 ligand.

HN

PN

P

PR2

1. NaH, THF2. PR2Cl

R = Ph, (N-PPh2)-1R = Cy, (N-PCy2)-1

R = BINAP, (N-(R)-BINO)-1 Scheme 5.4. General reaction scheme to generate phosphorus-functionalized 2-indolylphosphines.

An indolyl-based diphosphine that is related to 2-bis(diphenylphosphino)ethane,

dppe, can be created in the same fashion as other 2-indolylphosphines. Simply reacting

two equivalents of the lithiated aminal-protected 3-methylindole with one equivalent of

142

1,2-bis(dichlorophosphino)ethane, followed by reaction with NaBH4 to cleave the

protecting group affords diphosphine 29 in good yields (Scheme 5.5).

NH

PPHN

HN

NH

N

PPN

N

NN

N

N

NNN 1. n-BuLi, -78oC

2. Cl2P(CH2)2PCl2THF

1. NaBH4EtOH/THF

reflux2. HCl workup

29 Scheme 5.5. Reaction scheme for the synthesis of diphosphine, 29.

Figure 5.2 shows the multidentate 2-indolylphosphines which will be analyzed by X-ray

crystallography.

HN

P

P

HN

NH

NH

NP

P

NP

N

N NN N

P

(N-CH2NMe2)-20

(a)

(N-CH2NMe2)2-4

(b)

(N-PCy2)-1

(c)

29

(d) Figure 5.2. The multidentate 2-indolylphosphines that will be structurally characterized with X-ray

crystallography: (a) P(C12H15N2)(C4H9)2, (N-CH2NMe2)-20 (b) P(C23H26N4)(C6H5), (N-CH2NMe2)2-4

(c) P(C9H7NP(C6H11)2)(C6H5)2, (N-PCy2)-1 (d) [P(C18H16N2)(CH2)]2, 29.

5.2.2. X-ray Crystallographic Analysis of (P,N)- and (P,P)-

2-Indolylphosphines

As it was discussed in Sections 2.2.2. and 2.3., X-ray crystallography will be

employed to determine the impact of altering the substituents on phosphorus and the

introduction of non-alkyl groups on nitrogen on the Σ{<CPC} of 2-indolylphosphines. It

143

was demonstrated in Section 2.3.1. that exchanging substituents on phosphorus or the

incorporation of alkyl groups on nitrogen had very little effect on indolyl aromaticity.

The (P,N)- and (P,P)-ligands will be crystallographically examined to determine if the

presence of non-alkyl moieties on nitrogen will affect indolyl aromaticity. The X-ray

diffraction experimental data for the phosphines in question are listed in Table 5.1.

Table 5.1. X-ray crystallographic experimental data for (P,N)- and (P,P)-2-indolylphosphines.

(N-CH2NMe2)-20

NP

N

(N-CH2NMe2)2-4

NP

N

N

N

(N-PCy2)-1

NP

P

29

HN

P

P

HN

NH

NH

Formula C20H33N2P C29H31N4P C33H39NP2 C38H36N4P2 Formula Weight 332.45 466.55 511.59 610.65 Crystal colour, shape colourless, block colourless, plate colourless, plate colourless, plate Crystal size, mm 0.70 x 0.40 x 0.36 0.30 x 0.25 x 0.12 0.70 x 0.66 x 0.32 0.28 x 0.24 x 0.20 Crystal system Triclinic Monoclinic Monoclinic Monoclinic Space group Pī P21/c P21/c C2/c a, Å 8.2258(2) 12.8780(3) 19.8367(5) 22.6480(7) b, Å 8.8026(2) 18.6590(6) 8.9714(3) 10.8290(2) c, Å 14.4148(4) 11.6680(3) 17.3784(6) 25.8980(8) α deg 83.331(2) 90 90 90 β, deg 74.118(2) 116.2791(18) 115.480(2) 91.9580(12) γ deg 87.283(2) 90 90 90 V, Å3 996.98(4) 2513.94(12) 2791.90(15) 6347.9(3) Z 2 4 4 8 Dcalcd, g cm-3 1.107 1.233 1.217 1.278 F(000) 364 992 1096 2576 μ, mm-1 0.140 0.134 0.178 0.171 λ (Mo Kα), Å 0.71073 0.71073 0.71073 0.71073 Limiting indices -10<=h<=10 -15<=h<=13 -21<=h<=25 -28<=h<=29 -11<=k<=11 -22<=k<=22 -11<=k<=10 -12<=k<=14 -16<=l<=18 -13<=l<=13 -22<=l<=21 -25<=l<=33 2θ range, deg 1.48 to 27.52 2.93 to 25.04 1.14 to 27.49 2.59 to 27.51 Max. and min. transmission 0.959 and 0.450 0.9841 and 0.9609 0.951 and 0.495 0.9666 and 0.9536 No. of reflections collected 9193 17602 17475 21969 No. of independent reflections/Rint 4489 / 0.0778 4431 / 0.065 6795 / 0.0480 7268 / 0.0491 Extinction coefficient 0.38(3) 0.0064(12) 0.0078(17) 0.00044(16) No. of refined parameters 218 312 327 398 Final R1, wR2 0.0626, 0.1586 0.0473, 0.1095 0.0450, 0.1126 0.0522, 0.1208 Final R1, wR2 (all data) 0.0811, 0.1898 0.0725, 0.1237 0.0621, 0.1217 0.0845, 0.1362 Goodness of fit 1.120 1.019 1.022 1.039 Δρmin, Δρmax, eÅ-3 0.516 and -0.973 0.580, -0.229 -0.481, 0.377 -0.329, 0.662

144

Colourless block-shaped crystals of phosphine (N-CH2NMe2)-20 were harvested

from MeOH at -30oC. The molecular structure and numbering scheme of (N-

CH2NMe2)-20 is shown in Figure 5.3, and selected bond distances and angles are listed

in Table 5.2. The solid-state structure of phosphine (N-CH2NMe2)-20 is ordinary; it

crystallizes in the triclinic space group Pī, with one molecule in the asymmetric unit.

There do not appear to be any secondary bonding interactions within the solid-state

structure of the phosphine.

Table 5.2. Selected bond lengths (Å) and bond angles (o) for (P,N)- and (P,P)-2-indolylphosphines.

(N-CH2NMe2)-20

NP

N

(N-CH2NMe2)2-4

NP

N

N

N

(N-PCy2)-1

NP

P

29a

HN

P

P

HN

NH

NH

29b

HN

P

P

HN

NH

NH

P1-C2 1.834(2) 1.811(2) 1.823(2) 1.817(2) 1.807(2)

P1-C12 1.884(2) 1.814(2) 1.830(2) 1.804(2) 1.816(2) P1-C22 1.898(2) 1.845(2) 1.845(2) 1.856(2) 1.851(2)

P2-N1 - - 1.757(1) - - P2-C11 - - 1.858(2) - - P2-C17 - - 1.853(2) - -

N1-C2 1.420(2) 1.404(3) 1.429(2) 1.395(3) 1.400(3) C2-C3 1.385(2) 1.373(3) 1.376(2) 1.376(3) 1.378(3) C3-C4 1.436(2) 1.434(3) 1.432(2) 1.446(4) 1.434(3) C4-C9 1.407(2) 1.408(3) 1.407(2) 1.404(4) 1.406(3) C9-N1 1.375(2) 1.383(3) 1.394(2) 1.363(3) 1.382(3)


N11-C12 - 1.397(3) - 1.396(3) 1.386(3) C12-C13 - 1.368(3) - 1.377(3) 1.381(3) C13-C14 - 1.432(3) - 1.430(3) 1.436(3) C14-C19 - 1.410(3) - 1.407(3) 1.408(3) C19-N11 - 1.379(3) - 1.382(3) 1.382(3)

<C19-N11-C12 - 108.6(2) - 109.4(2) 109.4(2) <N11-C12-C13 - 109.2(2) - 108.4(2) 108.7(2) <C12-C13-C14 - 107.3(2) - 107.4(2) 107.2(2) <C13-C14-C19 - 107.1(2) - 107.6(2) 107.1(2) <C14-C19-N11 - 107.8(2) - 107.2(2) 107.6(2)

aIndolyl rings on P1. bIndolyl rings on P2.

145

The P1-C2indolyl bond distance of 1.834(2) Å in (N-CH2NMe2)-20 is considerably

longer than the analogous bond length found in both the unfunctionalized and N-alkylated

2-indolylphosphines described in Chapter 2 (which averages to 1.813(5) Å for the

unfunctionalized phosphines, and 1.811(5) Å for the N-alkylated derivatives). Several

reasons may be considered for the lengthening of the P1-C2indolyl bond but the most

evident is the steric bulk associated with the tert-butyl groups that cause a lengthening of

all the P-C bonds. In order to relieve the steric crowding around the phosphorus atom, all

of the P-C bonds lengthen and the Σ{<CPC} increases. These effects are observed in the

increase of the Σ{<CPC} to 322.9(1)o for (N-CH2NMe2)-20 compared to the less bulky

dicyclohexyl derivative, 2, which has a Σ{<CPC} of 308.4o.

Figure 5.3. ORTEP diagram and numbering scheme of (N-CH2NMe2)2-20. Hydrogen atoms removed for


As exhibited in the crystal structure of (N-Bn)-1, the methyl group on C3 in (N-

CH2NMe2)-20 is oriented away from the phosphorus lone pair and points towards the

pyramid created by the three substituents of phosphorus. The argument for this methyl

group orientation is likely to be similar to the one described for (N-Bn)-1, a relief of

steric crowding near the lone pair results in the methyl group be oriented into the pyramid.

The width of the indolyl substituent determined by measuring the distance from the

methyl carbon, C10, to the methylene carbon on nitrogen, C11, indicates a length of

5.113(3) Å, which is in agreement with the analogous width measurement in (N-Bn)-1

(5.061(4) Å). The average width of the tert-butyl substituents was found to be

146

2.492(7) Å, determined by calculating the distance from each methyl group to its adjacent

methyl group on the same tert-butyl moiety. As expected, the (N-CH2NMe2)-3-

methylindolyl substituent is larger than the tert-butyl moieties, and a larger cone angle

would be expected for this phosphine in comparison with an unsubstituted derivative.

Crystals of aminal-protected 4, (N-CH2NMe2)2-4, were grown as colourless

plates by solvent vapour diffusion of pentane into a solution of the phosphine in CH2Cl2

Phosphine (N-CH2NMe2)2-4 crystallizes in the monoclinic space group P21/c with one

molecule in the asymmetric unit. Figure 5.4 shows the molecular structure and

numbering scheme of the phosphine, and Table 5.2 lists selected bond distances and

angles. The X-ray structure determination of (N-CH2NMe2)2-4 confirmed the

incorporation of the phosphorus atom P1 into the six-membered ring through bonding to

the coupled indolyl substituent at its two C2-positions: C2 and C12. Secondary bonding

interactions were absent in the solid-state structure of (N-CH2NMe2)2-4.

Figure 5.4. ORTEP diagram and numbering scheme of (N-CH2NMe2)2-4. Hydrogen atoms removed for


A comparison of the solid-state structures of (N-CH2NMe2)2-4 and (N-F5Bn)2-4

reveals that the replacement of the electron-rich aminal-protecting groups with the

electron withdrawing pentafluorobenzyl substituents imparts little structural change upon

the rest of the molecule. For example, the P1-C2indolyl and P1-C12indolyl bond lengths of

1.802(2) Å and 1.813(2) Å respectively in (N-F5Bn)2-4 are effectively the same as the

147

analogous bond lengths of 1.811(2) Å and 1.814(2) Å in (N-CH2NMe2)2-4 and are not

significantly different from the P1-C2indolyl separation of 1.813(2) Å observed in 1.

The structural data for both N-alkylated derivatives of 4 suggest that their six-

membered rings do not experience substantial ring strain. The respective <C3-C10-C13

bond angles of 113.0(2)° and 112.9(2)° about the methylene carbon of the phosphacycles

of (N-CH2NMe2)2-4 and (N-F5Bn)2-4, respectively, are only slightly smaller than the

corresponding bond angle of 115.4(2)° measured in 3,3’-diindolylmethane.10

Interestingly, coupling of the indolyl substituents does produce a compression of

almost 6° upon the <C2-P1-C12 bond angle from comparison of the values of 94.7 (1)°

and 94.36(9)° in (N-CH2NMe2)2-4 and (N-F5Bn)2-4 respectively, with that of 100.3(1)°

measured between the uncoupled indolyl substituents of 3. This is not considered to

result in significant ring strain to the phosphacycle because of the facility with which

phosphorus subtly changes hybridization in order to accommodate substituents of

differing electronic or steric requirements.

Single crystals of (N-PCy2)-1 were acquired by slow evaporation of the

phosphine in a 1 : 1 mixture of hexane-CH2Cl2 as colourless plates. An ORTEP

representation and numbering scheme of (N-PCy2)-1 is illustrated in Figure 5.5, selected

bond lengths and angles are listed in Table 5.2. (N-PCy2)-1 crystallizes in the

monoclinic space group P21/c with one molecule in the asymmetric unit. The solid-state

structure of (N-PCy2)-1 is ordinary and there are no significant secondary interactions.

Figure 5.5. ORTEP diagram and numbering scheme of (N-PCy2)-1. Hydrogen atoms removed for clarity.


148

Both phosphorus atoms, P1 and P2, adopt trigonal pyramidal geometry. The P-C

bond lengths differ according to the type of substituent on phosphorus. The P1-Cphenyl

bond distances are significantly shorter (average 1.838(3) Å) than the P2-Ccyclohexyl bond

lengths (average 1.856(3) Å). The disparity is most likely due to the bulkiness of the

cyclohexyl groups that require longer P-C bond lengths to be accommodated around the

phosphorus centre. The P1-Cindolyl bond length of 1.823(2) Å is appreciably longer than

the P2-N1 bond distance (1.757(1) Å). The lone pair of electrons on P1 is approximately

orthogonal with respect to the lone pair on P2, this causes the phenyl groups on P1 to be

oriented away from the cyclohexyl moieties on P2. Similar to the solid-state structure of

(N-CH2NMe2)-20, the methyl group on C3 of (N-PCy2)-1 is directed into the pyramid

formed by the three substituents on P1.

The P-Cphenyl bond distances are in (N-PCy2)-1 are equivalent to the same bonds

in unfunctionalized 1 (average 1.812(2) Å); while the P-Cindolyl bond length is longer in

(N-PCy2)-1 considering the dicyclohexylphosphino substituent on nitrogen likely makes

the indolyl moiety larger than the unfunctionalized derivative. The width of the

dicyclohexylphosphino substituted 3-methylindole was determined by measuring the

distance from C10 of the methyl substituent to P2 bonded to nitrogen, and a value of

5.441(2) Å was obtained. In comparison to unfunctionalized 1, which has an analogous

width of 3.713(4) Å, the dicyclohexylphosphino substituted 3-methylindole is a much

larger substituent, thus resulting in the longer P-Cindolyl bond lengths observed in (N-

PCy2)-1.

Crystals of diphosphine 29 were acquired as colourless plates from hexane vapour

diffusion into a solution of 29 in CH2Cl2. Figure 5.6 shows the molecular structure and

the numbering scheme of 29, while Table 5.2 lists selected bond distances and angles.

Diphosphine 29 crystallizes in the monoclinic space group C2/c with one molecule in the

asymmetric unit. The diphosphine packs in a herringbone fashion along the

crystallographic c-axis. There are no apparent secondary interactions in the solid-state

structure of 29.

The P1-Cindolyl bond distances are statistically different (~4σ) from the P2-Cindolyl

bond distances, however, the discrepancies are chemically insignificant. The indolyl

rings on each phosphorus atoms are located near perpendicular to each other. The P1-

149

Csp3 (1.856(2) Å) and P2-Csp3 (1.851(2) Å) distances are equivalent, although they are

longer than the analogous P-Csp3 bond lengths in the solid-state structure of dppe

(average 1.829(3) Å). The ethyl bridge between the two phosphorus atoms has a bond

length of 1.526(3) Å, which is consistent with the Csp3-Csp3 bond distance of 1.521(7) Å

in dppe. The P-C-C-P backbone is constrained to the trans-configuration with a dihedral

angle of 159.1(1)o. In contrast to the N-functionalized 2-indolylphosphine derivatives,

the methyl groups of 29 point away from the pyramid created by the three substituents on

phosphorus.

Figure 5.6. ORTEP diagram and numbering scheme of 29. Hydrogen atoms removed for clarity. Thermal


150

5.2.3. The Effect of N-Functionalization on the Σ{<CPC}

of (P,N)- and (P,P)-2-Indolylphosphines

The influence on the sum of the <CPC bond angles with changing phosphine

substituents and N-alkylation was introduced in Section 2.3. The effect of N-

modification with additional amino or phosphino functionalities on the Σ{<CPC} will be

examined for the (P,N)- and (P,P)-2-indolylphosphines. The Σ{<CPC} values are listed

in Table 5.3.

Table 5.3. Sum of <CPC bond angles (o) and 31P (ppm) chemical shifts for uncomplexed multidentate 2-

indolylphosphines.

Entry

Complex

<C2-P1-C12

<C12-P1-C22

<C22-P1-C2

avg. Σ{<CPC}

31P δ (ppm)i

1

(N-CH2NMe2)-1

NP

N

102.84(8)

111.61(9)

108.46(8)

322.9(1)

11.2

2

(N-CH2NMe2)-4

NP

N

N

N

94.7(1)

101.7(1)

101.3(1)

297.7(2)

-61.9

3

(N-PCy2)-1

NP

P

102.94(8)

100.47(7)a

102.70(8)

104.34(7)b

104.69(8)

104.76(7)c

310.3(1)

309.5(1)d

-28.5

53.9

4

29

HN

P

P

HN

NH

NH

100.5(1)e

103.2(1)f

102.3(1)e

98.1(1)f

97.9(1)e

102.1(1)f

300.7(2)g

303.4(2)h

-47.7j

-47.7j

a<N1-P2-C11. b<C11-P2-C17. c<C17-P2-N1. dΣ{<C-P2-C}. e<C-P1-C. f<C-P2-C. gΣ{<C-P1-C}. hΣ{<C-P2-C}. iSpectra collected in CDCl3. jSpectra collected in CD2Cl2.

151

It was observed in the solid-state structure of (N-CH2NMe2)-20 that the P1-

C2indolyl bond distances are longer than the corresponding distances in other 2-

indolylphosphines; the difference is attributed to the steric bulk associated with the tert-

butyl groups that cause a lengthening of all the P-C bonds, and simultaneous increase in

the Σ{<CPC} to 322.9(2)o. Phosphine (N-CH2NMe2)-20 appears to have the largest

Σ{<CPC} value for all 2-indolylphosphines regardless of functionalization at nitrogen,

which is expected for the large bulky tert-butyl groups on phosphorus and the presence of

an aminal-protecting group on the nitrogen centre.

The value of Σ{<CPC} of (N-CH2NMe2)-20 is essentially the same as that of

PtBu3 at 322.27o.11 While this likeness in the sum of the <CPC bond angles suggests that

(N-CH2NMe2)-20 will have a basicity that correlates with PtBu3, the large Σ{<CPC} for

(N-CH2NMe2)-20 is likely due to the orientation of the indolyl substituent around

phosphorus in the solid-state as opposed to a likeness to a tert-butyl group in electron

donating power.

Analysis of the Σ{<CPC} for (N-CH2NMe2)2-4 show that the coupled indolyl

substituent causes a consequential decrease of this value to 297.7(2)o from the uncoupled

diindolyl phosphine 3 (303.8(2)o). Not surprisingly, the Σ{<CPC} for (N-CH2NMe2)2-4

is slightly smaller than that of (N-F5Bn)2-4 since the pentafluorophenyl groups are quite

wide. However, the significance in the difference of these two Σ{<CPC} values for the

N-functionalized derivatives of 4 is debatable. Interestingly the average Σ{<HPH} for

PH3 is 280.8o, the geometry about the phosphorus atom is generally regarded as highly

pyramidal and the molecule as having almost perfect tetrahedral bond angles.12 The

Σ{<CPC} for (N-CH2NMe2)2-4 and (N-F5Bn)2-4 might suggest that the coupling of the

indolyl moieties to create one bidentate substituent on phosphorus has caused the

phosphorus atom in the N-functionalized derivatives of 4 to become more pyramidal.

Phosphine (N-PCy2)-1 contains two Σ{<CPC} values, one for P1 (310.3(1)o) and

the other for P2 (309.5(1)o). In essence, the Σ{<CPC} values are statistically equivalent

even though the substituents on phosphorus are quite different. The increase in Σ{<CPC}

of P1 from 304.3(2)o in the parent phosphine 1 is most likely due to the presence of the

dicyclohexylphosphino substituent on nitrogen, as seen with the N-functionalized

152

derivatives of 1. While the substituents on P2 are identical to the ones on the phosphorus

atom of ligand 2, with the only difference being the site of connectivity of the indolyl

moiety, the Σ{<CPC} of P2 has not increased considerably from that of phosphine 2

(Σ{<CPC} = 308.4(2)o). It would be expected that since the Σ{<CPC} increases for N-

functionalized 1 compared to parent phosphine 1, the Σ{<CPC} of P2 should also

increase correspondingly as there is additional substitution at C2 with the

diphenylphosphino group.

It was anticipated that the averaged Σ{<CPC} for phosphine 29 (302.1(3)o) would

be less than that of diindolylphenylphosphine 3 (303.8(2)o) as the methylene group is a

smaller substituent than the phenyl moiety of 3. Interestingly, the average Σ{<CPC} for

dppe is 304.2(7)o. It was determined in Section 2.2.2. that the 3-methylindolyl

substituent was wider than a phenyl substituent, thus one would expect phosphine 29 to

have a larger average Σ{<CPC} value. The smaller Σ{<CPC} in 29 may be due to

packing forces in the solid-state, and not a direct consequence of the size of the indolyl

substituents.

While there may be a Σ{<CPC} contribution to the 31P chemical shift of a 2-

indolylphosphine, the 31P resonance appears to be dominated by the type of substituents

that are on the phosphorus centre. The prime example would be phosphine (N-PCy2)-1

in which the Σ{<CPC} values for P1 (310.3(1)o) and P2 (309.5(1)o) are nearly equivalent,

yet are quite chemically different. The chemical environment of P1 causes it to resonate

at -28.5 ppm, while P2 resonates at 53.9 ppm. Clearly the substituents around each

phosphorus atom have a greater impact on their respective chemical shifts as opposed to

their Σ{<CPC} values.

153

5.2.4. The Effect of N-Functionalization on Indolyl

Aromaticity of (P,N)- and (P,P)-2-Indolylphosphines

The bond distances that make up the pyrrolyl moiety of the indolyl ring of (P,N)-

and (P,P)-2-indolylphosphines were examined to determine if the installation of an amino

or phosphino substituent would affect the indolyl aromaticity. It was found that the bond

distances of amino-functionalized phosphines: (N-CH2NMe2)-20, (N-CH2NMe2)2-4, and

(N-PCy2)-1 are consistent with those found in the solid-state structure of phosphine 1.

The largest difference from 1 is the N1-C2 bond distance of phosphine (N-PCy2)-1

(1.429(2) Å), however the nitrogen atom appears to stay sp2-hybridized as the remaining

bond lengths in the pyrrolyl ring are consistent with those in 1. Additionally,

diphosphine 29 has pyrrolyl bond distances that are statistically equivalent to those of 1,

as it would be expected for an unfunctionalized indolyl substituent. The uniformity of

the bond distances of unfunctionalized and functionalized indolyl rings do not seem to

change, thus suggesting that the aromaticity of the pyrrolyl ring remains intact.

5.3. Pd(II) Complexes of (P,N)-2-Indolylphosphines

Bidentate (P,N)- and the (P,P)-ligands tend to bind metal centres in a chelating

fashion to form 1 : 1 ligand-to-metal complexes. A general reaction sequence for the

formation of (P,N)- or (P,P)-chelated metal complexes is shown in Scheme 5.6. Usually

an (P,N)- or (P,P)-2-indolylphosphine is reacted in a 1 : 1 stoichiometry with a metal

species such as Pd(COD)Cl2 in acetonitrile and precipitated from solution with Et2O.

154

NP

Pd(COD)Cl2MeCN, r.t.

15 minN

P

NPd

Cl

ClN

30 Scheme 5.6. The reaction sequence for the synthesis of complex 30. This is a representative example for

the synthesis of metal coordinated (P,N)-2-indolylphosphines.

While the synthetic and spectroscopic characterization of selected metal complexes of

(P,N)- or (P,P)-2-indolylphosphines are discussed elsewhere,9 their structural

characterization by X-ray crystallography will be detailed in the following section. The

selected metal complexes for crystallographic analyses are shown in Figure 5.7.

NP

NPd

Cl

Cl

NP

NPd

Cl

Cl

NP

NPt

Cl

Cl

NP

NPd

Cl

Cl

NP

PPd Cl

Cl

NP

PPd Cl

Cl

NP

Pd Cl

ClOO P

30

(a)

31

(b)

32

(c)

33

(d)

34

(e)

35

(f)

36

(g) Figure 5.7. The selected metal complexes of (P,N)-2-indolylphosphines to be assessed by X-ray

crystallography: (a) [PdCl2(N-CH2NMe2)-1], 30 (b) [PtCl2(N-CH2NMe2)-1], 31 (c) [PdCl2(N-py)-1], 32

(d) [PdCl2(N-isoquin)-1], 33. The selected Pd(II) complexes of (P,P)-2-indolylphosphines to be analyzed

by X-ray crystallography: (e) [PdCl2(N-PPh2)-1], 34 (f) [PdCl2(N-PCy2)-1], 35 (g) [PdCl2(N-BINO)-1], 36.

155

5.3.1. X-ray Crystallographic Analysis of Pd(II) and Pt(II)

Complexes of (P,N)-2-Indolylphosphines

The experimental X-ray crystallographic data for the Pd(II) and Pt(II) complexes

of selected (P,N)-2-indolylphosphines are listed in Table 5.4.

Table 5.4. X-ray crystallographic experimental data for Pd(II) and Pt(II) complexes of (P,N)-2-

indolylphosphines.

30

NP

NPd

Cl

Cl

31

NP

NPt

Cl

Cl

32

NP

NPd

Cl

Cl

33

NP

NPd

Cl

Cl

Formula C24H25Cl2N2PPd C24H25Cl2N2PPt C27H23Cl4N2PPd C30H23Cl2N2PPd Formula Weight 549.73 638.42 654.64 619.77 Crystal colour, shape orange, plate yellow, plate dark orange, plate orange, block Crystal size, mm 0.64 x 0.34 x 0.16 0.40 x 0.32 x 0.12 0.50 x 0.28 x 0.06 0.20 x 0.08 x 0.04 Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Space group P21/c P21/c P21/c P21/n a, Å 7.38770(10) 7.4109(1) 13.416(3) 9.0904(3) b, Å 17.2844(4) 17.3060(6) 15.114(3) 20.658(1) c, Å 18.4832(4) 18.4665(5) 14.307(3) 14.0685(7) α deg 90 90 90 90 β, deg 97.9730(12) 98.225(2) 109.21(3) 100.073(3) γ deg 90 90 90 90 V, Å3 2337.34(8) 2344.02(11) 2739.4(10) 2601.2(2) Z 4 4 4 4 Dcalcd, g cm-3 1.562 1.809 1.587 1.583 F(000) 1112 1240 1312 1248 μ, mm-1 1.105 6.296 1.146 1.003 λ (Mo Kα), Å 0.71073 0.71073 0.71073 0.71073 Limiting indices -9<=h<=9 -9<=h<=9 -17<=h<=16 -11<=h<=11 -22<=k<=22 -22<=k<=22 -19<=k<=19 -24<=k<=26 -20<=l<=23 -23<=l<=23 -15<=l<=18 -17<=l<=18 2θ range, deg 1.62 to 27.54 2.35 to 27.59 1.61 to 27.50 1.77 to 27.44 Max. and min. transmission 0.840 and 0.516 0.535 and 0.190 0.951 and 0.743 0.972 and 0.732 No. of reflections collected 18928 18829 20981 26117 No. of independent reflections/Rint 5530 / 0.0577 5569 / 0.0710 6499 / 0.0494 5930 / 0.1272 Extinction coefficient 0.0086(7) 0.0029(5) 0.0068(6) 0.0042(5) No. of refined parameters 275 275 318 327 Final R1, wR2 0.0354, 0.0967 0.0548, 0.1450 0.0500, 0.1303 0.0520, 0.1075 Final R1, wR2 (all data) 0.0423, 0.1059 0.0619, 0.1514 0.0689, 0.1458 0.1296, 0.1435 Goodness of fit 1.065 1.039 1.091 0.999 Δρmin, Δρmax, eÅ-3 -1.082, 1.330 -3.344, 4.282 -1.206, 1.498 -0.906, 1.388

156

Single crystals of complex 30 were acquired as orange coloured plates from Et2O

vapour diffusion into a CH2Cl2 solution containing the complex. The molecular structure

and numbering scheme for 30 is shown in Figure 5.8 and Table 5.5 lists selected bond

lengths and angles. Complex 30 crystallizes in the monoclinic space group P21/c with

one molecule in the asymmetric unit. The Pd(II) centre adopts square planar coordination

geometry with the (N-CH2NMe2)-1 ligand cis-chelated. The Pd(II)-P bond length of

2.2373(6) Å is consistent with those determined for the [Pd(2-indolylphosphine)Cl(μ-

Cl)]2 dimers (which range from 2.2162(8) to 2.260(2) Å) discussed in Chapter 2. The

six-membered metallocycle is non-planar due to the methylene carbon linking the two

nitrogen centres of the aminal protecting group; as such, the metallocycle takes on a boat

conformation. All three of the aromatic rings are virtually perpendicular to one another.

The P-Cindolyl and P-Cphenyl bond lengths in 30 are consistent with those found in the

dimeric [Pd(1)Cl(μ-Cl)]2 complex, 24. However the average <CPC bond angles differ by

an overall 3.8(3)o between complex 30 and complex 24; complex 30 possesses the

smaller Σ{<CPC} angles probably as a result of the added strain from the formation of

the metallocycle. Secondary interactions are absent in the solid-state structure of 30.



157

Table 5.5. Selected bond lengths (Å) and bond angles (o) for Pd(II) and Pt(II) complexes of (P,N)-2-

indolylphosphines.

30

NP

NPd

Cl

Cl

31

NP

NPt

Cl

Cl

32

NP

NPd

Cl

Cl

33

NP

NPd

Cl

Cl

Pd1-P1 2.2373(6) 2.222(2)a 2.218(1) 2.228(1) Pd1-N2 2.125(2) 2.120(6)a 2.063(3) 2.084(4) Pd1-Cl1 2.3791(6) 2.294(2)a 2.274(1) 2.374(1) Pd1-Cl2 2.2860(7) 2.372(2)a 2.370(1) 2.276(1)

<N2-Pd1-P1 94.04(6) 94.3(2) 88.9(1) 88.8(1) <P1-Pd1-Cl2 86.73(2) 88.30(6)b 90.05(4)d 87.73(5) <N2-Pd1-Cl1 90.06(6) 89.36(16)c 91.9(1)e 90.9(1) <Cl2-Pd1-Cl1 90.77(2) 89.12(6) 89.77(4) 93.20(5)

P1-C2 1.800(3) 1.795(6) 1.796(4) 1.807(5) P1-C12 1.812(3) 1.825(6) 1.807(4) 1.809(5) P1-C22 1.809(3) 1.810(6) 1.815(4) 1.798(5)

N1-C2 1.399(3) 1.409(7) 1.426(5) 1.416(6) C2-C3 1.380(3) 1.373(8) 1.363(6) 1.369(7) C3-C4 1.436(4) 1.446(10) 1.449(6) 1.440(7) C4-C9 1.405(4) 1.402(10) 1.396(5) 1.405(8) C9-N1 1.382(3) 1.368(8) 1.410(5) 1.401(6)

<C9-N1-C2 108.6(2) 108.7(5) 107.5(3) 107.7(4) <N1-C2-C3 109.6(2) 109.1(5) 109.4(3) 109.0(4) <C2-C3-C4 105.9(2) 106.3(5) 107.2(4) 107.8(5) <C3-C4-C9 108.4(2) 107.6(5) 108.2(3) 107.1(5) <C4-C9-N1 107.3(2) 108.1(6) 107.6(3) 108.3(5)

aBond distances to Pt1. b<P1-Pt1-Cl1. c<N2-Pt1-Cl2. d<P1-Pd1-Cl1. e<N2-Pd1-Cl2.

Yellow plate-like crystals of the Pt(II) complex of (N-CH2NMe2)-1 were formed

by Et2O vapour diffusion into a CH2Cl2 solution containing the complex. The molecular

structure and numbering scheme are shown in Figure 5.9, while selected bond angles and

distances are listed in Table 5.5. Complex 31 is isostructural to complex 30, so it

crystallizes in the monoclinic space group P21/c with one molecule in the asymmetric

unit. The Pt(II) exhibits square planar coordination geometry, the ligand is coordinated

in a cis-conformation, and the six-membered metallocycle adopts a boat conformation in

the same manner as complex 30. The Pt(II)-P1 distance is 2.222(2) Å is shorter than the

Pd(II)-P1 distance in 30, and the Pt(II)-N1 distance is 2.120(6) Å which is consistent with

the Pd(II)-N1 distance in 30. The P-C bond distances in 31 are crystallographically

158

equivalent to the ones in 30. The three aromatic rings are near orthogonal with respect to

each other, and no secondary interactions are present in the solid-state.



X-ray quality single crystals of complex 32 were obtained as dark-orange plates

from Et2O vapour diffusion into a solution of CH2Cl2 containing the complex. Figure

5.10 shows the molecular structure and the numbering scheme of the complex, and Table

5.5 lists selected bond angles and distances. Complex 32 crystallizes in the monoclinic

space group P21/c with one molecule and one CH2Cl2 solvate in the asymmetric unit.

The Pd(II) centre has square planar coordination geometry, with a Pd(II)-P bond length of

2.218(1) Å and a Pd(II)-N1 bond distance of 2.063(3) Å. The Pd(II)-P1 bond distance is

equivalent to the one found in complex 30. While the Pd(II)-N1 bond length in 32 is

consistent with those reported in the literature,13,14 it is considerably shorter than the

Pd(II)-N bond distance found in 30; this may be a result of the inherent rigidity of the

pyridyl ring to coordinate to Pd(II), whereas the methylene carbon has a degree of

freedom to conformationally adjust when the amino group coordinates to Pd(II).

159

Figure 5.10. ORTEP diagram and numbering scheme of 32. Hydrogen atoms and CH2Cl2 solvent

molecule removed for clarity. Thermal ellipsoids are drawn at 35% probability.

The P-C bond lengths in 32 are also crystallographically equivalent to those in

complexes 30 and 31. The indolyl and the two phenyl rings are oriented near orthogonal

to each other. The indolyl and pyridyl rings deviate from co-planarity by 43.0(1)o. The

biaryl twist angle between the pyridyl and indolyl rings is 50.0(5)o as determined by the

dihedral angle ascribed by the atoms N2-C11-N1-C2. This twist angle is smaller than the

corresponding twist angle found for QUINAP (60o)14 which is necessarily larger to

accommodate steric repulsion between the two biaryl rings. The pyridyl ring is situated

approximately parallel to one of the phenyl rings (ascribed by atoms C16 through C21)

(Figure 5.10); the distance between the two rings was determined to be 5.281 Å (by two

centrally placed points within the pyridyl ring and the phenyl ring in question), much

further than expected solid-state π-π interactions.15 Similar to complexes 30 and 31, the

six-membered metallocycle of 32 adopts a boat conformation.

Multiple weak intermolecular hydrogen bonding interactions are exhibited in the

solid-state structure of 32 between the pyridyl and indolyl rings to the chloro ligands of

symmetry equivalent complexes; the weak C…Cl bond distances range from 3.465(4) to

3.698(4) Å and are within the sum of the van der Waals’ radii. Additional weak

intermolecular hydrogen bonds occur between the CH2Cl2 molecule to the chloro ligands

of symmetry equivalent complexes.

160

Orange coloured block-like crystals of complex 33 were obtained from Et2O

vapour diffusion into a CH2Cl2 solution containing the complex. The molecular structure

and numbering scheme is shown in Figure 5.11, selected bond distances and angles are

listed in Table 5.5. Complex 33 crystallizes in the monoclinic space group P21/n with

one molecule in the asymmetric unit. The solid-state structure of 33 shares very similar

features with complex 32: the Pd(II) takes on a square planar coordination geometry with

the ligand binding in a cis-chelating fashion; the metallocycle adopts a boat

conformation; the Pd(II)-P and Pd(II)-N bond distances, 2.228(1) Å and 2.084(2) Å,

respectively, are crystallographically identical to the ones found in complex 32;

additionally, the P-C bonds lengths of 33 are the same as those in 32. Multiple weak

intermolecular hydrogen bonding interactions are demonstrated in the crystal structure of

33: atoms C16 on the isoquinolyl ring and C28 on a phenyl ring interact with chloro

ligands of symmetry equivalent molecules; weak intramolecular hydrogen bonding

between C19 and a chloro ligand is also evident.

The indolyl and phenyl substituents on phosphorus are nearly orthogonal with one

another. However, the isoquinolyl and indolyl rings deviate from co-planarity by

56.6(8)o, which is larger than the deviation of the pyridyl and indolyl rings in 32. The

dihedral angle ascribed by atoms N2-C11-N1-C2 was determined to be 61.3(6)o. The

deviation from co-planarity coupled with the larger dihedral angle of 33 confirms that the

isoquinolyl functionality on nitrogen is much larger than the pyridyl moiety of 32, the

larger angles also suggest steric repulsion exists between the hydrogen atoms on C8 and

C13 of the indolyl ring and isoquinolyl rings, respectively.

161

Figure 5.11. ORTEP diagram and numbering scheme of 33. Hydrogen atoms removed for clarity.


The (N-isoquin)-1 ligand of 33 may appear to exhibit axial chirality through

hindered rotation about the N1-C11 bond. However, coordination to a chiral metal

species would be necessary to assess whether (N-isoquin)-1 does indeed possess an axis

of chirality. A structurally related ligand by Brown and co-workers13 (Figure 5.12)

demonstrates racemisation of either the ligand or its chiral Pd(II) complex, or both, to

form one enantiopure product upon coordination.

NP

N NPd

Cl

2Pd

PPh2

Me2N

N

N+ KPF6

MeOH

PF6

Figure 5.12. Brown and co-workers demonstrate absence of axial chirality in 1-methyl-2-

diphenylphosphino-3-(1’-isoquinolyl)indole upon coordination to a chiral Pd(II) complex.13

Additionally, the solid-state structure of the chiral Pd(II) complex possessed a biaryl twist

of 46.6o, which was smaller than the QUINAP derivative. Based on the observations by

Brown and co-workers, it is suspected that (N-isoquin)-1 would not possess an axis of

chirality either.

162

5.3.2. X-ray Crystallographic Analysis of Pd(II)

Complexes of (P,P)-2-Indolylphosphines

The experimental X-ray crystallographic data for the Pd(II) complexes of selected

(P,P)-2-indolylphosphines are listed in Table 5.6. Selected bond distances and angles for

complexes 34 – 36 are listed in Table 5.7.

Table 5.6. X-ray crystallographic experimental data for Pd(II) complexes of (P,P)-2-indolylphosphines.

34

NP

PPd Cl

Cl

35

NP

PPd Cl

Cl

36

NP

Pd Cl

ClOO P

Formula C33H27Cl2NP2Pd C33H39Cl2NP2Pd C41H29Cl2 2P2Pd NOFormula Weight

ape ss, needle edle ss, needle 6

4(5) 58(4) 038(11)

76(3) .6730(12)

4.8(3) 1.3(2)

cd, g cm-3 1.521 79 88

0.941 ), Å 3 3 3

s 13 14 26

θ range, deg transmission 5 2 2

s/Rint .0765 0.1059 .1002

0081(14) 0011(3) rs

4, 0.0863 3, 0.1339 3, 0.1425 all data)

-3 0.543 0.880 1.241

676.80 688.89 806.89 Crystal colour, sh colourle yellow, ne colourleCrystal size, mm 0.30 x 0.08 x 0.07 0.24 x 0.10 x 0.0 0.57 x 0.12 x 0.06 Crystal system Monoclinic Triclinic Monoclinic Space group P21/n P-1 C2 a, Å 10.288 11.46 25.3b, Å 14.6103(8) 14.2463(4) 9.8766(2) c, Å 19.9589(9) 19.9934(6) 18.4572(8)α deg 90 97.138(2) 90 β, deg 99.9 91.627(2) 128γ deg 90 106.855(2) 90 V, Å3 295 3094.16(17) 360Z 4 4 4 Dcal 1.4 1.4F(000) 1368 1416 1632 μ, mm-1 0.900 0.790 λ (Mo Kα 0.7107 0.7107 0.7107Limiting indice -13<=h<= -14<=h<= -32<=h<= -18<=k<=18 -18<=k<=18 -12<=k<=12 -22<=l<=25 -24<=l<=25 -21<=l<=23 2 2.79 to 27.49 2.68 to 27.54 1.41 to 27.52 Max. and min. 0.939 and 0.85 0.961 and 0.47 0.963 and 0.45No. of reflections collected 18123 40112 14561 No. of independent reflection 6730 / 0 14125 / 4368 / 0Absolute structure parameter - - -0.01(4) Extinction coefficient 0.0 0. 0.0038(4)No. of refined paramete 386 752 444 Final R1, wR2 0.050 0.055 0.060Final R1, wR2 ( 0.1370, 0.1097 0.1031, 0.1621 0.0861, 0.1638 Goodness of fit 0.962 1.041 1.066 Δρmin, Δρmax, eÅ -0.889, -1.224, -1.827,

163

Table 5.7. Selected bond lengths (Å) and bond angles (o) for Pd(II) complexes of (P,P)-2-

indolylphosphines.

NP

PPd Cl

Cl

34

Major component

(70%)

N P

PPd Cl

Cl

34

Minor component

(30%)

NP

PPd Cl

Cl

35 Independent molecule A

NP

PPd Cl

Cl

35 Independent molecule B

NP

Pd Cl

ClOO P

36

Pd1-P1 2.219(1) 2.219(1) 2.216(1) 2.225(1) 2.235(2) Pd1-P2 2.219(1) 2.219(2) 2.244(1) 2.239(1) 2.189(2) Pd1-Cl1 2.352(1) 2.352(2) 2.341(1) 2.354(1) 2.326(2) Pd1-Cl2 2.358(1) 2.358(2) 2.340(1) 2.347(1) 2.329(2)

<P2-Pd1-P1 88.27(4) 88.27(4) 89.08(4) 88.70(4) 85.22(6) <P1-Pd1-Cl1 88.71(4) 88.71(4) 86.52(4) 89.56(4) 90.33(6) <P2-Pd1-Cl2 87.48(4) 87.48(4) 90.95(4) 88.69(4) 90.87(7) <Cl2-Pd1-Cl1 95.68(4) 95.68(4) 93.46(5) 93.03(4) 93.80(7

P1-C2 1.77(1) 1.69(2) 1.789(5) 1.796(4) 1.795(7)

P1-C11 1.810(5) 1.803(5) 1.826(5) 1.808(5) 1.818(7) P1-C17 1.811(5) 1.800(5) 1.812(5) 1.822(5) 1.795(7)

P2-N1 1.69(2)a 1.69(2) 1.739(4) 1.731(4) 1.679(5) P2-C23 1.803(5) 1.803(5) 1.836(5) 1.827(4) 1.598(5)d P2-C29 1.800(5) 1.800(5) 1.844(5) 1.825(4) 1.589(5)e

N1-C2 1.408(7) 1.408(8) 1.417(5) 1.422(6) 1.428(8) C2-C3 1.36(1) 1.36(1) 1.367(6) 1.363(6) 1.369(9) C3-C4 1.44(1) 1.44(1) 1.422(7) 1.429(7) 1.44(1) C4-C9 1.41(1) 1.41(1) 1.411(6) 1.407(7) 1.402(9) C9-N1 1.41(1) 1.41(1) 1.403(6) 1.410(5) 1.410(8)


aP2-C2A bond distance. b<C2a-P2-C23. c<C29-P2-C2a. dP2-O1 bond distance. eP2-O2 bond distance.

Colourless needle-shaped crystals of complex 34 were produced by Et2O vapour

diffusion into a CH2Cl2 solution containing the complex. Figure 5.13 shows the

molecular structure and the numbering scheme of 34, which crystallizes in the

monoclinic space group P21/c with one molecule in the asymmetric unit. The indolyl

ring in the complex is disordered over the same site. The major component of the indolyl

disorder is modeled at 70% (Figure 5.13a) and the minor component modeled at 30%

(Figure 5.13b). One can envisage that in the absence of the methyl group on the indolyl

164

ring, complex 34 can have pseudo C2-symmetry. The rotational axis would bisect the

Pd(II) and the indolyl ring with the chloro ligands and the diphenylphosphino substituents

on either side of it. Only N1 and C2 would prevent the complex from having true C2-

symmetry. By rotating the complex about this pseudo-C2-rotational axis, N1 and C2 can

switch positions while the remainder of the atoms stay in the same positions. Thus, in the

solid-state structure of 34, the complex has crystallized about 30% of the time with the

indolyl ring flipped “upside down” in other unit cells to give rise to its positional disorder.

(a) (b)

Figure 5.13. ORTEP diagram and numbering scheme of 34. Hydrogen atoms removed for clarity.

Thermal ellipsoids are drawn at 35% probability. (a) Major component of indolyl disorder modeled at 70%

occupancy. (b) Minor component of indolyl disorder modeled at 30% occupancy.

The Pd(II) adopts square planar coordination geometry where the ligand binds in

a cis-chelating conformation. The Pd(II)-P1 and Pd(II)-P2 bond lengths in 34 are

identical at 2.219(1) Å, most likely due to the disorder of the indolyl ring in the solid-

state. These Pd(II)-P bond distances are consistent with those of the Pd(II) complexes of

(P,N)-2-indolylphosphine ligands. The P-Cindolyl bond length of 1.77(1) Å is statistically

equivalent to the analogous bond length found in complexes 30 – 32, as are the P-Cphenyl

bond lengths (average 1.811(7) Å). Weak intermolecular hydrogen bonding between C5

and Cl2 of a symmetry related complex is exhibited at a donor-to-acceptor distance of

165

3.483(6) Å. Alternate classic hydrogen bonding interactions are not demonstrated in the

crystal structure of 34.

Each set of phenyl substituents are near orthogonal to the indolyl ring. The five-

membered metallocycle is approaching planarity with a rms deviation of 0.0697 Å for the

metallocycle ascribed by atoms: Pd1-P1-C2-N1-P2, and a rms deviation of 0.0791 Å for

the minor disordered component ascribed by atoms: Pd1-P1-N1A-C2A-P2. The dihedral

angle of the chelating (N-PPh2)-1 ligand, created by atoms P2-N1-C2-P1 is -20(2)o,

while the minor disordered component has a dihedral angle of -22(7)o. It is evident that

the dihedral angle of 34 is much smaller than those of the (P,N)-2-indolylphosphine

complexes because the coordinating moiety is bonded directly to nitrogen, as opposed to

the (P,N)-ligands with have a carbon spacer between the nitrogen and the coordinating

centre.

Single crystals of complex 35 were produced by Et2O vapour diffusion into a

CH2Cl2 solution containing the complex as yellow needles. Figure 5.14 shows the

molecular structure and the numbering scheme of 35, which crystallizes in the triclinic

space group Pī with two independent molecules in the asymmetric unit. Independent

molecule A possesses a cyclohexyl ring disordered over two positions (Figure 5.14a), the

major component is modeled at 64% occupancy and the minor component is modeled at

36% occupancy.

The (N-PCy2)-1 ligand coordinates to Pd(II) in a cis-chelating manner. The

Pd(II)-P1 and Pd(II)-P2 bond distances in both independent molecules are statistically

different by approximately 9σ and 5σ, respectively. However, the P-C bond distances

are statistically equivalent between the two independent molecules. Thus, the deviation

in Pd(II)-P bond lengths may be a result of crystal packing forces. In comparison the

solid-state structure of the free ligand (N-PCy2)-1, all the P-C and P-N bond distances

shorten upon coordination to Pd(II). In evaluation against the structure of 35, the Pd(II)-

PPh2 bond lengths are equivalent; however, as anticipated the Pd(II)-PCy2 bond lengths

are considerably longer (average 2.242(1) Å) as a result of the bulkier cyclohexyl

substituents on P2 that would prohibit closer Pd(II)-P contacts.

166

The phenyl rings are almost perpendicular to the indolyl ring in both independent

molecules. The five-membered metallocycles are near planar with rms deviations of

0.0387 Å for independent molecule A, and 0.0548 Å for independent molecule B. The

dihedral angle P1-C2-N1-P2 found in independent molecule A is -15.5(5)o, whereas in

molecule B it is 8.1(5)o. While these two dihedral angles are statistically dissimilar, the

disparity may be an artifact of crystal packing, and it is unlikely that the differences

contribute to any chemical distinction between the two molecules.

(a) (b)

Figure 5.14. ORTEP diagram and numbering schemes of the two independent molecules of 35 in the

asymmetric unit. Hydrogen atoms removed for clarity. Thermal ellipsoids are drawn at 35% probability.

(a) Independent molecule A: the major component of the disordered cyclohexyl is modeled at 64%

occupancy, and the minor component (shown with transparent bonds) modeled at 36% occupancy.

(b) Independent molecule B.

Colourless needle-shaped crystals of complex 36 were produced by Et2O vapour

diffusion into a CH2Cl2 solution containing the complex. Figure 5.15 shows the

molecular structure and the numbering scheme of 36, which crystallizes in the chiral

monoclinic space group C2 with one molecule in the asymmetric unit. The chiral Flack

parameter was found to be -0.01(4) which indicates the correct stereochemistry for

complex 36. Additionally, the (N-(R)-BINO)-1 ligand was synthesized using (R)-

BINOL, the solid-state structure of 36 confirms that the chirality of the ligand remained

intact upon chelating to Pd(II). The Pd(II) centre has square planar coordination

geometry with a Pd(II)-P1 bond distance of 2.235(2) Å, which is longer than the

167

analogous distances in the (P,N)-2-indolylphosphine complexes, as well as complexes 34

and 35. The Pd(II)-P2 bond distance is considerably shorter than the corresponding bond

lengths in complexes 34 and 35, this is owing to the two oxygen moieties on P2 which

alter the donating ability of the lone pair on phosphorus. While the phosphine P1-C bond

distances in 36 remain equivalent to those of 34 and 35, the phosphite P2-N1 bond

distance is appreciably shorter at 1.679(5) Å.

Figure 5.15. ORTEP diagram and numbering scheme of complex 36. Hydrogen atoms omitted for clarity.


The phenyl and indolyl rings are near perpendicular with each other. The five-

membered palladacycle is near planarity with a rms deviation of 0.1617 Å. A dihedral

angle ascribed by the atoms P1-C2-N1-P2 was determined to be -4.1(7)o, and is

significantly smaller than the same dihedral angle in complexes 34 and 35. The dihedral

angle of the phosphite’s atoms C33-C34-C24-C23 was found to be -53.1(9)o, and is

consistent with other complexes featuring BINAP.16

Reek and co-workers17 recently introduced a phosphine-phosphoramidite that is

the opposite enantiomer of (N-(R)-BINO)-1 and have evaluated its catalytic performance

in Rh-catalyzed hydrogenation and hydroformylation reactions. Their ligand was found

to have good activity, with moderate enantioselectivity. They had found that by

introducing sterically bulky substituents to the BINOL at the positions ortho to the

oxygen atoms that catalytic activity was greatly enhanced with higher ee’s.

168

5.4. Examining Trans-Influence Properties of (P,N)- and

(P,P)-2-Indolylphosphines

The trans-influence of the phosphino and amino ligands on PdCl2 or PtCl2 are

examined for complexes 30 – 33, while the variation in phosphine and phosphite

substituents are investigated for their trans-influence in complexes 34 – 36. In general,

the stronger the ligand’s σ-donicity, the more trans-influence that particular ligand has.

This correlates into a decreased bond strength of the bond trans to that particular ligand.

In other words, the bond trans to the ligand exerting the trans-influence, experiences

bond lengthening. Relative ligand trans-influence can be assessed by examining the

bond lengths of the ligand trans to the phosphine.12 Table 5.8 lists, in increasing order,

the Pd(II)-Cl bond distances that are trans to the diphenylphosphino substituent on indole

for the Pd(II) complexes of (P,N)-2-indolylphosphines.

Table 5.8. Increasing order of Pd(II)-Cl bond length that is trans to the phosphine in Pd(II) complexes of

(P,N)-2-indolylphosphines.

Complex Pd-Cltrans to phosphine (Å)

32

NP

NPd

Cl

Cl

2.370(1)

33

NP

NPd

Cl

Cl

2.374(1)

30

NP

NPd

Cl

Cl

2.3791(6)

In all cases, the Pd(II)-Cl bond trans to the amino group is shorter than the Pd(II)-

Cl bonds trans to the diphenylphosphino moiety. It is reasonable to say that the amino

group (regardless of whether the nitrogen is sp3- or sp2-hybridized) is a weaker trans-

influence ligand than the diphenylphosphino moiety. In examining the Pd(II)-Cl bond

lengths trans to the diphenylphosphino ligand, the Pd(II) complexes have comparable

169

Pd(II)-Cl bond distances, however they differ by more than 4σ. This suggests that the

nature of the amino substituent on the indolyl nitrogen does have a slight impact on the

σ-donicity of the diphenylphosphino group. According to Table 5.8, the order of

increasing Pd(II)-Cl bond distances, and therefore increasing trans-influence, is 32 < 33

< 30. The shortest Pd(II)-Cl bond distance in complex 32 suggests that the pyridyl

moiety on the indolyl nitrogen does not impart very significant σ-donating power to the

diphenylphosphino substituent. The isoquinolyl group improves the σ-donicity of the

diphenylphosphino substituent in 33. By changing the amino donor from sp2-

hybridization in complexes 32 and 33, to an sp3-donor in complex 30, the σ-donicity of

the amino substituent is enhanced to the diphenylphosphino group, and thus the trans

Pd(II)-Cl bond is the longest of the three Pd(II) complexes.

Interestingly, the trans Pt(II)-Cl bond of complex 31 (2.372(2) Å) would place it

between complexes 32 and 33 on the scale of increasing Pd(II)-Cl bond lengths. This is

in contrast to the analogous Pd(II) complex with the longest Pd(II)-Cl bond. The only

apparent modification between 30 and 31 are the metal centres involved; thus the

variance in trans M-Cl bond distances can be attributed to the subtleties of the chloro

ligand binding to either Pt(II) or Pd(II) as opposed to the trans-influence of the phosphine

ligand.

The order of increasing Pd(II)-Cl bond lengths for the Pd(II) complexes of (P,P)-

2-indolylphosphines are listed in Table 5.9. Since the indolyl is functionalized with

phosphino or phosphito substituents, the trans-influence of each P-donor, as well as the

overall (P,P)-2-indolylphosphine ligand can be assessed.

170

Table 5.9. Increasing order of Pd(II)-Cl bond length that is trans to the phosphine in Pd(II) complexes of

(P,P)-2-indolylphosphines.

Complex

Pd-Cltrans to P1 (Å) Pd-Cltrans to P2 (Å)

36 N

P

Pd Cl

ClOO P

2.329(2)

2.326(2)

35 N

P

PPd Cl

Cl

2.344(1)a

2.348(1)a

34 N

P

PPd Cl

Cl

2.358(1)

2.352(2)

aThe Pd(II)-Cl bond lengths are averaged between independent molecules A and B.

Complexes 34 – 36 can be categorized according to increasing Pd(II)-Cl bond

lengths that are trans to P1 and P2: 36 < 35 < 34. It is interesting to note that the order of

increasing Pd(II)-Cl bond length, which implies increase in trans-influence of the P-

donor, is the same for P1 and P2. This observation suggests that the phosphito or

phosphino substituent on the indolyl nitrogen affects the σ-donicity of the

diphenylphosphino substituent at the C2 position on indole. Not surprisingly, complex

36 has the shortest Pd(II)-Cl bond lengths as it contains a phosphite moiety which is a

better π-acid ligand than a σ-donor ligand.18 Surprisingly, the dicyclohexylphosphine

group does not impart a greater affect on the σ-donicity of the overall (P,P)-ligand. This

may be in part due to the significant deviations in bond lengths among independent

molecules A and B in the solid-state structure of 35, as the Pd(II)-Cl bond distances

shown in Table 5.9 are the averaged values of these independent molecules. Complex 34

has the longest Pd(II)-Cl bonds, suggesting (N-PPh2)-1 has the strongest trans-influence

of the three (P,P)-2-indolylphosphines investigated.

171

In comparing the trans-influence of the (P,N)- and (P,P)-2-indolylphosphines, the

phosphito and phosphino functionalities are weaker at inducing an increase in σ-donating

power of the diphenylphosphino substituent at C2. The amino functionalities increase the

trans-influence of the diphenylphosphino moiety more effectively. The order of

increasing Pd(II)-Cl bond distances, and thus increase in ligand trans-influence: 36 < 35

< 34 <32 < 33 < 30.

5.5. Synthesis and Characterization of Multidentate N-

Functionalized Ligands based on Phosphine 5

Phosphine 5 can be easily transformed into a multidentate ligand by furnishing

diphenylphosphino groups on the nitrogen centre. The multidentate trisubstituted ligand,

(N-PPh2)3-5, is formed by the reaction of 5 with NaH in THF, followed by the addition

of three equivalents of PPh2Cl (Scheme 5.7). The product is isolated by column

chromatography in 35% yield as a white microcrystalline solid.

1. 10 eq NaH2. 3eq PPh2Cl

THF24h

NP

N

N

PPh2

PPh2

PPh2

(N-PPh2)3-5

35%

HN

P

NH

NH

Scheme 5.7. General reaction scheme for the synthesis of multidentate phosphine ligand (N-PPh2)3-5.

The 31P NMR spectrum of (N-PPh2)3-5 is consistent with an AX3 spin system that

confirms trisubstitution of all three indolyl nitrogen centres in phosphine ligand 5 (Table

5.10). The signal pertaining to the bridgehead phosphorus atom is split into a quartet by

coupling to the three equivalent diphenylphosphino substituents, while the resonances of

172

the diphenylphosphino substituents are split into a doublet through coupling to the

bridgehead phosphorus atom.

Table 5.10. 31P NMR resonances of phosphine 5 and (N-PPh2)3-5 recorded in CDCl3.

Phosphine 31P NMR Resonances (ppm) JP-P (Hz)

5

-82.3 (s)

-

(N-PPh2)3-5

36.2 (d) -76.2 (q)

159 159

(s) = singlet, (d) = doublet, (q) = quartet

Recently, Ciclosi and co-workers19 have introduced an indolyl-based C3-

symmetric tripodal ligand, CP3 (Figure 5.16), that is reminiscent of (N-PPh2)3-5. The

bridgehead atom is an sp3-hybridized carbon instead of a phosphorus as in the case of (N-

PPh2)3-5. Ciclosi’s CP3 ligand is capable of binding Pd(II) to induce five-coordinate

trigonal bipyramidal coordination geometry about the metal centre. They have examined

the utility of this [PdCl(CP3)] complex in various Suzuki cross-coupling reactions and

found that it is efficient and reusable for the formation of a variety of biaryls. It was

found that the inherent axial chirality of the complex in solution is retained when the

chloro ligand is replaced with a chiral (2S,5S)-2,5-dimethyl-1-phenylphospholane. The

efficacy of an enantiopure complex was tested in the asymmetric cross-coupling of 1-

iodo-2-methoxynaphthalene and 1-naphthylboronic acid, which led to the formation of

(S)-1-(2-methoxynaphthalen-1-yl)naphthalene, but only in 7% ee. Nevertheless,

Ciclosi’s intrinsically chiral complex can be further explored to increase its potential as a

chiral catalyst.

NCH

N

N

PPh2

PPh2

PPh2

Ph2P PdPPh2

PPh2

Cl

N NN

PdCl2, THFAgBF4, r.t.

Figure 5.16. Ciclosi and co-workers’ example of an indolyl-based C3-symmetric ligand, CP3, that binds to

Pd(II).19

173

The coordination chemistry of trisubstituted 5, (N-PPh2)3-5, is demonstrated with

Pt(II) and Rh(I) (Scheme 5.8). The synthesis of the Pt(II) complex, 37, involves mixing

equimolar (N-PPh2)3-5 with Pt(COD)Cl2 and NaBPh4 in acetone. The orange complex

precipitates from solution in 51% yield. The analogous dark red Rh(I) complex, 38, is

generated in 94% yield by reacting half an equivalence of [Rh(COD)Cl] with (N-PPh2)3-

5 in THF.

NP

N

N

PPh2

PPh2

PPh2

(a) 1eq Pt(COD)Cl21eq NaBPh4

acetone

(b) 0.5eq [Rh(COD)Cl]2THF

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

51%

37

94%

38 Scheme 5.8. Reaction schemes for the synthesis of metal coordinated (N-PPh2)3-5 complexes. (a) [PtCl(N-

PPh2)3-5]BPh4, 37. (b) [RhCl(N-PPh2)3-5], 38.

The 31P NMR spectra of both complexes are simple and confirm coordination of all four

phosphorus donors of (N-PPh2)3-5 in a trigonal bipyramidal geometry to a metal centre

by their downfield chemical shifts and splitting patterns, respectively (Table 5.11).

Complex 37 should be expected to exhibit the anticipated splitting pattern for an AMX3

spin system which consists of two resonances where the axial phosphorus signal is split

into a quartet by coupling to the three equivalent equatorial phosphorus donors, and the

equatorial phosphorus signal is split into a doublet from coupling to the axial phosphorus.

However, both the axial and equatorial phosphorus signals appears as singlets with small

splitting associated with Pax-Peq coupling (JP-P = 10 Hz). Each of the 31P resonances are

flanked by 195Pt satellites (natural abundance 33.8%). The 195Pt-Peq coupling constant of

174

2826 Hz is larger compared to the analogous coupling constant of the [PtCl(PP3)]+

complex (JPt-Peq = 2516 Hz); whereas the 195Pt-Pax coupling constant in 37 is smaller than

the one found in [PtCl(PP3)]+ complex (JPt-Pax = 2585 Hz).20 Interestingly, the δPeq is

shifted more downfield than δPax, which is inconsistent with all of the metal complexes

of PP3; further examination of complex 37 is necessary to reveal the reasons for this

unpredictability.

Table 5.11. 31P NMR resonances of metal complexes of (N-PPh2)3-5 recorded in DMSO-d6.

Complex

31P NMR Resonances (ppm) and J (Hz)

Coordinated Chemical Shifts Δ (ppm)

δPax δPeq ΔPax ΔPeq

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

37

3.3 (d) JPt-Pax = 2225 JPax-Peq = 10

49.4 (d) JPt-Peq = 2826

79.5

13.2

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

38

42.4 (dq) JRh-Pax = 84 JPax-Peq = 24

72.8 (dd) JRh-Peq = 159

118.6

36.6

(s) = singlet, (d) = doublet, (dd) = doublet of doublets, (dq) = doublet of quartets; Pax = axial or bridgehead phosphorus atom, Peq = equatorial phosphorus atom.

The 31P NMR spectrum of complex 38 is consistent with an AMX3 spin system, with

additional coupling to 103Rh (natural abundance 100%); the signal of the axial phosphorus

donor is split into a quartet from coupling to the three equivalent equatorial

diphenylphosphino groups, which is then further split into a doublet by coupling to the 103Rh. Similarly, the signal of the equatorial phosphorus donors is split into a doublet

from coupling to the axial phosphorus atom, and split further into another doublet from

coupling to 103Rh. The Pax-Peq coupling constant is observed in the 31P NMR spectrum of

complex 38 at 24 Hz, and is slightly larger than the analogous coupling observed for

[Rh(PP3)Cl] (JPax-Peq = 17 Hz).21 Similar to complex 37, the JRh-Peq coupling constant is

larger in 38 (JRh-Peq = 159 Hz) than the analogous [Rh(PP3)Cl] complex (JRh-Peq = 126 Hz),

while the JRh-Pax coupling is smaller in 38 (JRh-Pax = 84 Hz) than that observed in the

175

[Rh(PP3)Cl] example (JRh-Pax = 148 Hz).21 Comparable to 37, the δPeq is shifted more

downfield than δPax, which is contradictory to other metal complexes of PP3.

In general, the 31P NMR resonance of a phosphine ligand shifts downfield upon

metal coordination in comparison to the free ligand. The downfield shift is treated

quantitatively as the coordination chemical shift denoted Δ, and is defined as the

difference between the δ(Pcoordinated) and δ(Pfree ligand).7 Additionally, if a phosphorus atom

is incorporated into a 5-membered ring, the δ(Pcoordinated) is shifted even more downfield

due to an additional deshielding contribution denoted ΔR. It has been observed with PP3

metal complexes that if the phosphorus atom is located at the bridgehead of two or three

five-membered chelate rings, then the Δ values for each chelate ring are nearly additive.

This also appears to be the case for complex 38, where the ΔPax is three times larger than

ΔPeq; for complex 37, the difference between ΔPax and ΔPeq is almost six times larger. It

has been observed that the chemical shifts of Pax are sensitive to the variation of the fifth

ligand in the trigonal bipyramidal metal complex.5,7,8,21 Since both complexes 37 and 38

have Cl- as the fifth ligand, the deviation in δPax cannot be commented on.

5.5.1. X-ray Crystallographic Analysis of Metal

Complexes of (N-PPh2)3-5

Single crystals of complex 37 were acquired from Et2O vapour diffusion into a

solution of CH2Cl2 containing the complex. The experimental X-ray data for 37 is listed

in Table 5.12, selected bond distances and angles are listed in Tables 5.13 and 5.14. The

molecular structure and numbering scheme of complex 37 is shown in Figure 5.17.

Complex 37 crystallizes in the triclinic space group Pī with one molecule, consisting of

[PtCl(N-PPh2)3-5]BPh4, and one disordered CH2Cl2 solvate in the asymmetric unit.

Repeated attempts to model the disordered CH2Cl2 were unsuccessful; the SQUEEZE

option in PLATON22 was used and indicated a solvent accessible void of volume 265 Å3

containing approximately 86 e-. In the final cycles of refinement, this contribution to the

electron density was removed from the observed data. The density, the F(000) value, the

176

molecular weight and the formula are given without taking into account the results

obtained with the SQUEEZE option in PLATON.

Table 5.12. X-ray crystallographic experimental data for complexes 37 and 38.

37

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

38

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

Formula C87H71BClN3P4Pt C63H51ClN3P4Rh Formula Weight 1523.70 1112.31 Crystal colour, shape dark orange, block dark red, block Crystal size, mm 0.16 x 0.10 x 0.08 0.34 x 0.24 x 0.20 Crystal system Triclinic Triclinic Space group Pī Pī a, Å 13.481(3) 11.7691(3) b, Å 16.857(3) 15.0323(3) c, Å 17.476(4) 16.9382(5) α deg 67.71(3)°. 83.9670(14) β, deg 85.77(3)°. 86.4380(11) γ deg 87.25(3)°. 69.9640(13) V, Å3 3663.7(13) 2798.60(12) Z 2 2 Dcalcd, g cm-3 1.381 1.320 F(000) 1548 1144 μ, mm-1 2.087 0.509 λ (Mo Kα), Å 0.71073 0.71073 Limiting indices -17<=h<=17 -15<=h<=15 -20<=k<=21 -19<=k<=19 -21<=l<=22 -19<=l<=22 2θ range, deg 1.26 to 27.48 1.21 to 27.53 Max. and min. transmission 0.866 and 0.528 0.910 and 0.776 No. of reflections collected 41593 27186 No. of independent reflections/Rint 16610 / 0.1019 12670 / 0.0508 Extinction coefficient 0.00032(13) 0.0030(5) No. of refined parameters 878 653 Final R1, wR2 0.0543, 0.1010 0.0436, 0.1123 Final R1, wR2 (all data) 0.0924, 0.1107 0.0568, 0.1187 Goodness of fit 0.965 1.057 Δρmin, Δρmax, eÅ-3 -1.786, 1.947 -1.054, 0.707

177

Table 5.13. Selected bond lengths (Å) and bond angles (o) for complexes 37 and 38. 37

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

38

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

M-P1 2.206(2)a 2.1614(7) M-P2 2.348(1)a 2.3001(7) M-P3 2.368(1)a 2.2996(7) M-P4 2.335(1)a 2.3007(7) M-Cl1 2.400(2)a 2.4428(7)

P4-M-P2 123.57(5)a 121.64(2) P4-M-P3 117.76(5)a 116.89(2) P2-M-P3 117.56(5)a 119.87(3)

P1-C2 1.784(5) 1.803(3) P1-C12 1.788(5) 1.806(3) P1-C22 1.796(4) 1.803(3) P2-N1 1.731(4) 1.743(2) P3-N11 1.729(4) 1.745(2) P4-N21 1.716(4) 1.749(2)

N1-C2 1.423(6) 1.417(3) C2-C3 1.372(6) 1.368(4) C3-C4 1.437(7) 1.443(4) C4-C9 1.392(6) 1.394(4) C9-N1 1.407(6) 1.405(3)


N11-C12 1.448(6) 1.424(3) C12-C13 1.351(6) 1.371(4) C13-C14 1.439(7) 1.440(4) C14-C19 1.405(7) 1.403(4) C19-N11 1.404(6) 1.399(3)


N21-C22 1.432(6) 1.415(3) C22-C23 1.363(7) 1.370(4) C23-C24 1.443(7) 1.431(4) C24-C29 1.389(7) 1.405(4) C29-N21 1.415(6) 1.395(3)


aM = Pt1. bM = Rh1.

178

(a) (b)

Figure 5.17. ORTEP diagram and numbering scheme of complex 37. Hydrogen atoms and BPh4+

countercation removed for clarity, thermal ellipsoids drawn at 35% probability. (a) ORTEP diagram

showing coordination sphere about the Pt(II) centre. (b) View along the virtual threefold axis with the

phenyl substituents removed for clarity.

The solid-state structure of 37 confirms the trigonal bipyramidal coordination

geometry of the Pt(II) centre. Although the ligand is C3-symmetric, the three equivalent

phosphorus atoms of the diphenylphosphino groups are crystallographically inequivalent.

The Pt(II) centre deviates from the plane defined by the three equatorial phosphorus

donors by 0.1440(7) Å towards the Cl- ligand. The Pt-Pax bond length is significantly

shorter at 2.206(2) Å than the Pt-Peq bond distances (range from 2.335(1) to 2.368(1) Å),

which is consistent with what is observed in the solid-state structures of [M(PP3)X]+ and

Ciclosi’s [PdCl(CP3)].19 The disparity in the Pt-Pax and Pt-Peq bond lengths may be

attributed to the strong σ-interaction of the axial bond in the trigonal bipyramidal

geometry leading to a shorter Pt-Pax bond, while the participation of the three equatorial

phosphorus donors in three five-membered chelate rings to the Pt(II) facilitate the

lengthening the Pt-Peq interaction. The BPh4- counteranion is ordinary and the [PtCl(N-

PPh2)3-5]+ cation does not possess additional secondary interactions.

Similar to the solid-state structure of 37, complex 38 also crystallizes in the

triclinic space group Pī with one molecule of [RhCl(N-PPh2)3-5], and one disordered

CH2Cl2 solvate in the asymmetric unit. Table 5.12 lists the experimental X-ray

diffraction data, whereas selected bond distances and angles are listed in Tables 5.13 and

5.14. The molecular structure and numbering scheme for 38 is shown in Figure 5.18.

179

The disordered CH2Cl2 could not be successfully modeled, thus the SQUEEZE option in

PLATON22 was used to remove the disorder. A solvent accessible cavity of volume

322 Å3 containing approximately 50 e- was suggested. The density, the F(000) value, the

molecular weight and the formula are given without taking into account the results

obtained with the SQUEEZE option in PLATON.

(a) (b)

Figure 5.18. ORTEP diagram and numbering scheme of complex 38. Hydrogen atoms removed for clarity,

thermal ellipsoids drawn at 35% probability. (a) ORTEP diagram showing coordination sphere about the

Rh(I) centre. (b) View along the virtual threefold axis with the phenyl substituents removed for clarity.

The solid-state structure of 38 confirms the trigonal bipyramidal coordination

geometry of the Rh(I) centre. There are many common similarities between the solid-

state structures of 37 and 38: the three equivalent phosphorus atoms of the

diphenylphosphino groups are crystallographically inequivalent in 38; the Rh(I) centre

deviates from the plane defined by the three equatorial phosphorus donors by

0.1686(4) Å towards the Cl- ligand; the Rh-Pax bond length is significantly shorter at

2.1614(7) Å than the Rh-Peq bond distances (range from 2.2996(7) to 2.3007(7) Å).

Complex 38 does not possess additional secondary interactions.

180

5.5.2. The Reactivity of [PtCl(N-PPh2)3-5]BF4 and

[RhCl(N-PPh2)3-5]

The reactivity of [M(PP3)X]0/+ has been well documented in the literature.4-8,21 In

particular, the metathesis of the fifth ligand appears to be quite facile, and the stability of

these complexes have been investigated thoroughly. In most cases, the ligand remains

coordinated to the metal, which retains trigonal bipyramidal coordination geometry. It

has been noted that small ligands, such as halides and small phosphine ligands (for

instance PMe3 or P(OMe)3) can be easily accommodated in the fifth position of the

metal’s coordination sphere.

Following the work by Brüggeller and co-workers,6 the metathesis of the chloro

ligand in [PtCl(PP3)]Cl was achieved on reaction with NaBH4 at room temperature for

30 minutes to give [PtH(PP3)]BPh4. Repeated attempts to generate the analogous

[PtH(N-PPh2)3-5]BPh4 from complex 37 with Brüggeller’s reaction conditions (Scheme

5.9) were unsuccessful. Complex 37 remained intact despite varying the time and the

temperature of the reaction. Refluxing conditions however, resulted in the cleavage of

the diphenylphosphino substituents from the indolyl nitrogen centre as seen in the 31P

NMR with the absence of the AMX3 spin system. In hindsight, the reaction of 37 with

NaBH4 would not have been successful in the first place, since the deprotection of

aminal-protected 2-indolylphosphines is accomplished by reacting it with NaBH4.

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

37

NaBH4, EtOHr.t., 12 hours Ph2P PtII

PPh2

PPh2

P

H

N NN

BPh4

not formed Scheme 5.9. The attempted synthesis of [PtH(N-PPh2)3-5]BPh4 by reaction of complex 37 and NaBH4.

Fernández and co-workers20 have demonstrated the insertion of SnCl2 into the Pt-

Cl bond of [PtCl(PP3)]+, and shown that the Pt-SnCl3 systems have catalytic activity

181

towards hydroformylation. The clean reaction of [PtCl(PP3)]Cl in CHCl3 with solid

SnCl2 in the presence of PPh3 to form [Pt(SnCl3)(PP3)]SnCl3 requires stirring at room

temperature for 12 hours. Similar reaction conditions were investigated on complex 37

(Scheme 5.10), and the reaction was monitored using 31P NMR. The reaction was

disappointingly unclean compared to the formation of [Pt(SnCl3)(PP3)]SnCl3, it was

found that multiple species were formed and that P-N cleavage was rampant leading to a

loss of the trigonal bipyramidal coordination geometry of the Pt(II) centre.

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

37

SnCl2, PPh3 CH2Cl2

r.t., 24 hours Ph2P PtII

PPh2

PPh2

P

SnCl3

N NN

SnCl3

not formed Scheme 5.10. The attempted SnCl2 insertion into the Pt(II)-Cl bond of complex 37.

The capacity for complex 38 to undergo metathesis of the fifth ligand was

examined by adhering to the reaction conditions set forth by Bianchini and co-workers

for [RhCl(PP3)].5 Bianchini and co-workers were able to replace the chloro ligand in

[RhCl(PP3)] for either methyl or phenyl groups by simply reacting the complex with the

appropriate alkyllithium reagent in THF. Repeated attempts of reacting complex 38 with

either methyllithium or phenyllithium resulted in no reaction (Scheme 5.11). The starting

complex was recovered almost quantitatively.

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

38

RLi, THF-78oC to r.t., 24 hours Ph2P RhI

PPh2

PPh2

P

R

N NN

R = Me or Ph

no reaction Scheme 5.11. The attempted metathesis of the chloro ligand in complex 38 for either a methyl or phenyl

ligand.

182

The lack of reactivity of complex 38 to alkyllithium reagents for the metathesis of

the chloro ligand may be due to the congested environment created by the three

equatorial diphenylphosphino groups on the nitrogen. The inability for even the small

methyllithium reagent to approach the small cavity remaining for the fifth ligand suggests

that the steric crowding of the three equatorial diphenylphosphino groups is greater in

comparison to the analogous [RhCl(PP3)] complex. Presumably, the bite angles <Pax-C-

N-Peq in 38 increase the proximity of the diphenylphosphino substituents; the five-

membered pyrrolyl ring establishes the maximum limit that the diphenylphosphino

groups can be oriented to avoid steric congestion with each other and with the phenyl

backbone of the indolyl moiety. Therefore the closeness of the diphenylphosphino

groups create a smaller cavity for the fifth ligand, and prevents reactivity of incoming

metathesis reagents, and rather reactivity occurs at the more accessible P-N bond sites.

5.6. Metal Coordination on the Σ{<CPC} of (P,N)- and (P,P)-

2-Indolylphosphines

The average Σ{<CPC} angles for metal complexes of (P,N)- and (P,P)-2-

indolylphosphines are listed in Table 5.14. The largest average Σ{<CPC} value for P1

is exhibited in complex 36 at 324.0(5)o. This Σ{<CPC} suggests much steric crowding

around P1, which is not particularly apparent from the solid-state structure (Figure 5.15).

It is speculated that the (R)-BINO substituent on nitrogen plays a dual role in affecting

the average Σ{<CPC} values, firstly it is inherently large, and like complexes 34 and 35,

the phosphite is also coordinating to Pd(II), so it enforces a rigid ligand conformation

about the metal centre which necessitates the opening up of the <C-P1-C angles.

Secondly, the (R)-BINO substituent is a phosphite, the oxygen atoms that link the

biphenyl to the phosphorus donor are not rigid, and therefore can be arranged such that

the <O-P2-O bond angles are much more compact than those around P1. The oxygen

atoms about P2 result in a modest average Σ{<CPC} of 311.5(5)o for the phosphite

moiety.

183

Table 5.14. Sum of <CPC bond angles (o) and 31P (ppm) resonances for metal complexes of multidentate 2-

indolylphosphines.

Entry

Complex

<C2-P1-C12

<C12-P1-C22

<C22-P1-C2

avg. Σ{<CPC}

31P δ (ppm)

1

30 N

P

NPd

Cl

Cl

105.5(1)

105.3(1)

105.4(1)

316.2(2)

4.9v

2

31 N

P

NPt

Cl

Cl

105.6(3)

104.8(3)

105.1(3)

315.5(5)

-2.1v

3

32

NP

NPd

Cl

Cl

109.4(2)

106.3(2)

105.0(2)

320.5(3)

12.5w

4

33

NP

NPd

Cl

Cl

109.7(2)

107.8(2)

105.0(2)

322.5(3)

13.9w

5

34

NP

PPd Cl

Cl

104.5(7)a

104(3)b

108.9(2)a

109.9(2)b

106.8(7)a

102(3)b

320.2(11)a

316(4)b

28.1w

85.7w

6

35

NP

PPd Cl

Cl

108.8(2)c 107.0(2)d 107.7(2)e 103.4(2)f

107.0(2)c 105.6(2)d 106.2(2)e 110.2(2)f

104.1(2)c 105.3(2)d 106.1(2)e 109.4(2)f

319.9(4)c 317.9(4)d 320.0(4)e 323.0(4)f

27.5w 127.4w 27.5w 127.4w

7

36

NP

Pd Cl

ClOO P

106.9(3)g

99.0(3)h

110.2(3)g

103.6(2)i

106.9(3)g

108.9(3)j

324.0(5)g

311.5(5)

24.6w

122.6w

8

37

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

109.3(2) 101.6(2)k 105.2(2)p 105.1(2)s

113.8(2)

105.5(2)m

100.4(2)q 102.9(2)t

109.5(2) 106.4(2)n 104.4(2)r

106.1(2)u

332.6(3) 313.5(3) 310.0(3) 314.1(3)

3.3v

49.4v 49.4v 49.4v

9

38

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

109.2(1) 104.2(1)k 104.5(1)p 103.1(1)s

109.4(1) 99.9(1)m 100.0(1)q 101.5(1)t

107.9(1) 101.9(1)n 102.4(1)r 102.4(1)u

326.6(2) 306.0(2) 306.9(2) 307.0(2)

42.4v 72.8v 72.8v 72.8v

a<C-P1-C of major component (70%). b<C-P2-C of major component (70%). c<C-P1-C of molecule A. d<N-P1-C of molecule A. e<C-P2-C of molecule B. f<N1-P2-C of molecule B. g<C-P1-C. h< N1-P2-O1. i<O1-P2-O2. j<O2-P2-N1. k< N1-P2-C31. m<N1-P2-C37. n<C31-P2-C37. p< N11-P3-C43. q<N11-P3-C49. r<C43-P3-C49. s<N21-P4-C55. t<N21-P4-C61. u<C55-P4-C61. vSpectra collected in DMSO-d6. wSpectra collected in CDCl3.

184

The functionalization of phosphine 5 with diphenylphosphino substituents on

nitrogen and subsequent coordination of the (N-PPh2)3-5 ligand to Pt(II) and Rh(I) have

undoubtedly increased the average Σ{<CPC} of P1 from 306.9(2)o in the free ligand to

332.6(3)o and 326.6(2)o, respectively. The discrepancy between the average Σ{<CPC}

values for complexes 37 and 38 is a result of the larger van der Waals radius of Pt(II)

(1.72 Å) compared to Rh(I) (1.63 Å). The larger Pt(II) causes greater spreading out of

the <C-Pax-C bond angles. Likewise, the equatorial diphenylphosphino substituents on

nitrogen experience greater spreading out of the <C-Peq-C bond angles due to the larger

Pt(II) centre.

The multidentate (P,N)- and (P,P)-2-indolylphosphines in general undergo an

increase in average Σ{<CPC} values upon metal coordination. The increase of Σ{<CPC}

may not necessarily reflect an increase in steric crowding, and care must be taken when

using this estimation to determine a ligand’s steric bulk.

As it was observed in Section 5.2.3., there is little correlation between the

Σ{<CPC} and the 31P chemical shift of a particular 2-indolylphosphine. Especially when

a 2-indolylphosphine is acting as a monodentate ligand through phosphorus coordination,

the 31P resonance is more greatly influenced by the substituents bonded to it, as well as

the type of transition metal it is coordinating to, rather than the Σ{<CPC} bond angles.

5.6.1. The Effect of Metal Coordination on Indolyl

Aromaticity of Multidentate 2-Indolylphosphines

It was realized in Section 5.2.4. the introduction of amino or phosphino

substituents on the indolyl nitrogen does not affect the aromaticity of the pyrrolyl moiety

to an appreciable amount that can be determined by X-ray crystallography. The pyrrolyl

bond distances in the metal complexes of (P,N)- and (P,P)-2-indolylphosphines were

examined (Table 5.5). The overall trend with the metal complexes shows the N1-C2

bonds lengthening, especially in the cases with the phosphino substituents on nitrogen.

Also, the C2-C3 bonds tend to shorten to lengths that range from 1.36(1) Å to 1.380(3) Å

185

from the analogous bonds in 1 (average 1.373(4) Å). Generally, the pyrrolyl bond

lengths do not vary significantly from those found in 1; therefore, even when the (P,N)-

and (P,P)-2-indolylphosphines are acting as cis-chelating ligands, the pyrrolyl ring

remains aromatic.

The pyrrolyl bond distances in complexes 37 and 38 exhibit similar trends seen in

complexes 30 – 36. The N1-C2 and N1-C9 bond lengths have a propensity to lengthen,

while the C2-C3 bond distances shorten, upon coordination to either Pt(II) or Rh(I).

However, the pyrrolyl bond lengths are consistent with aromaticity seen in phosphine 5.

Therefore, functionalization of the indolyl nitrogens with diphenylphosphino substituents

and their subsequent coordination to metal complexes does not impart changes in

aromaticity of the indolyl ring.

5.7. Conclusions

New multidentate (P,N)- and (P,P)-2-indolylphosphine ligands have been

synthesized and subsequently coordinated to Pd(II) or Pt(II). Reacting the multidentate

ligands in a 1 : 1 ligand to metal complex ratio produces cis-chelated complexes. Using

X-ray crystallography, the structural details of the (P,N)- and (P,P)-2-indolylphosphines

show that the aromaticity of the pyrrolyl rings do not change upon N-functionalization or

metal binding.

The Pd(II)-Cl bonds trans to the phosphino substituents of the cis-chelated Pd(II)

complexes, 30 and 32 - 36, were examined for possible trans-influence trends. It was

found that the (P,P)-2-indolylphosphines have the weakest trans-influence, while the

amino functionalized (P,N)-2-indolylphosphines have stronger trans-influence on the

Pd(II)-Cl bond. The weakest trans-influence ligand was determined to be (N-(R)-

BINO)-1, whereas the strongest trans-influence ligand was (N-CH2NMe2)-1.

The average Σ{<CPC} angles of the free (P,N)- and (P,P)-2-indolylphosphines

were assessed. In general the average Σ{<CPC} values increased for the parent

phosphine 1 when substituents were furnished on the nitrogen centre. As anticipated,

variation of the substituents on phosphorus is a has greater influence on the Σ{<CPC}

186

than the addition of functionality at the indolyl nitrogen. The average Σ{<CPC} angles

typically increase from 1 by 15o - 20o.

Installing diphenylphosphino substituents on all three of the indolyl nitrogen

centres of C3-symmetric phosphine 5 resulted in the formation of a tetradentate ligand,

(N-PPh2)3-5. Coordination of the (N-PPh2)3-5 ligand to Pt(II) or Rh(I) enforces five-

coordinate trigonal bipyramidal geometry of the metal centres. Crystallographic analyses

shows the pyrrolyl rings remain aromatic in the indolyl substituents upon coordination.

Furthermore, the average Σ{<CPC} angles increase with N-functionalization and metal

binding. Complexes 37 and 38 were subjected to a variety of reaction conditions that

included attempted metathesis of the fifth ligand. However, these reactions were

unsuccessful, largely resulting in P-N bond cleavage. The reactivity at the P-N bonds

could be a result of the steric crowding of the fifth ligand by the three equatorial

diphenylphosphino substituents.

5.8. Experimental

Unless otherwise stated, the synthetic protocol for the functionalized 2-indolylphosphines

and their metal complexes are reported in Dr. Edmond Lam’s thesis.9


atmosphere of dinitrogen using standard Schlenk techniques unless otherwise stated. 1,2-

Bis(dichlorophosphino)ethane (Cl2P(CH2)2PCl2), 1.6 M n-BuLi, NaBH4, were purchased

from Aldrich and used as received. 1-[(N,N-Dimethylamino)methyl]-3-methylindole23

and Pt(COD)Cl224 were synthesized according to literature procedures. Tetrahydrofuran

(THF) was distilled from sodium benzophenone ketyl still under a dinitrogen atmosphere. 1H, 13C, and 31P NMR spectra were recorded on Varian 400 MHz or 300 MHz NMR

systems, and referenced to SiMe4 (TMS) and 85% H3PO4, respectively. Splitting patterns

are indicated as s, singlet; d, doublet; t, triplet; q, quartet;, m, multiplet; br, broad peak.

187

HN

P

P

HN

NH

NH

1,2-Bis(diindolylphosphino)ethane, (C9H8N)2P(CH2)2P(C9H8N)2, 29. 1-[(N,N-

Dimethylamino)methyl]-3-methylindole (5.0 g, 26.6 mmol) was dissolved in THF

(50 mL) and cooled to -78oC. n-BuLi (20.0 mL, 32.0 mmol) was added dropwise over 10

minutes. The reaction was stirred at -78oC for 10 minutes, warmed to ambient

temperature and stirred for 3 hours. The resulting orange mixture was cooled to -78oC,

and Cl2P(CH2)2Cl2 (0.65 mL, 4.3 mmol) was added dropwise over 5 minutes. The

mixture was allowed to warm to ambient temperature overnight and then quenched with

MeOH. Solvents were removed in vacuo to yield a dark yellow residue. Water (100 mL)

was added to the residue, and the suspension extracted with DCM (3 x 100 mL). The

organic layers were combined, washed with brine, dried over anhydrous MgSO4, filtered,

and concentrated in vacuo to afford dark orange oil. MeOH was added to triturate pure

aminal-protected product as a white solid, which was isolated by filtration and dried in

vacuo (0.84 g, 23%). 31P NMR (CDCl3, 161 MHz): δ -47.7 (s); 1H NMR (CDCl3,

400 MHz): δ 7.47 (d, J = 8 Hz, 4H, Ar-H), 7.30 (d, J = 8.4 Hz, 4H, Ar-H), 7.14 (t,

J = 7.6 Hz, 4H, Ar-H), 7.05 (t, J = 7.6 Hz, 4H, Ar-H), 4.40 (d, J = 12 Hz, 4H, amine

NCH2), 4.19 (d, J = 12 Hz, 4H, anime NCH2), 2.54 (t, J = 4.8 Hz, 10 Hz, 4H, CH2CH2),

2.29 (s, 12H, indole CH3), 1.84 (s, 24H, amine N(CH3)2); 13C NMR (CDCl3,

101 MHz):.139.5, 129.7, 129.3, 122.7, 119.8, 119.4, 118.7, 110.6, 67.0, 42.4, 21.7, 10.7;

HRMS EI for C50H64N8P2: calcd m/z 838.4729, found m/z 838.4719. A solution of

THF/EtOH (13 mL, 1:1 v/v) was added to a solid mixture of the aminal-protected product

(0.812 g, 0.97 mmol) and NaBH4 (0.18 g, 4.8 mmol). The mixture was refluxed for 5

hours. The solution was reduced to dryness in vacuo and acidified water was added to

the resultant white solid, which was extracted with DCM (3 x 50 mL). The organic

phases were combined and dried over anhydrous MgSO4, filtered and taken to dryness to

afford a dark yellow coloured oil. MeOH was added to triturate pure product as a white

188

solid, which was isolated by filtration and dried in vacuo (0.48 g, 81 %). 31P NMR

(CDCl3, 161 MHz): δ -66.9 (s); 1H NMR (CD2Cl2, 300 MHz): δ 7.90 (br s, 3H, indole

NH), 7.60 (d, J = 7.2 Hz, 3H, Ar-H), 7.27 (d, J = 7.5 Hz, 3H, Ar-H), 7.21 – 7.12 (m, 6H,

Ar-H), 2.41 (s, 9H, indole CH3); 13C NMR (CD2Cl2, 75 MHz): 138.9, 130.3, 125.5, 123.7,

121.3, 120.2, 119.5, 111.8, 9.9; HRMS EI for C27H24N3P: calcd m/z 421.170357, found

m/z 421.170786; Microanalysis for C27H24N3P: calcd (%) C = 76.94, H = 5.74, N = 9.97,

found (%)C = 76.70, H = 5.78, N = 9.79.

NP

N

N

PPh2

PPh2

PPh2

2-(Bis(3-methyl-1-(diphenylphosphino)-1H-indol-2-yl)phosphino)-3-methyl-1-

(diphenylphosphino)-1H-indole, P[C9H7NP(C6H5)2]3, (N-PPh2)3-5. Phosphine 5

(0.2211 g, 0.70 mmol) was dissolved in THF (10 mL) to yield a clear colourless solution.

NaH (0.179 g, 4.5 mmol) was added to the solution, immediate effervescence was

observed. The mixture gradually changed colour from yellow to orange to bright orange

over 24 h. The resultant solution was cooled to -78oC, and PPh2Cl (0.38 mL, 2.1 mmol)

was added dropwise via syringe over 10 minutes. The temperature was maintained at -

78oC for 30 minutes while the reaction stirred. The reaction was allowed to warm to

ambient temperature overnight. Volatile solvents were removed in vacuo to give an oily

residue which was fused to silica gel and subjected to column chromatography (silica gel,

2 : 1 hexanes-CH2Cl2). The product (N-PPh2)3-5 is a microcrystalline white solid (0.18 g,

35%). 31P NMR (CD2Cl2, 161 MHz): δ 36.2 (d, J = 159 Hz, 3P, Peq), -76.2 (q, J = 159,

318 Hz, 1P, Pax); 1H NMR (CD2Cl2, 300 MHz): δ 7.44 (d, 3H, J = 7.8 Hz, Ar-H), 7.32-

7.12 (m, 30H, Ar-H), 7.01 (t, J = 7.9, 14.8 Hz, 3H, Ar-H), 6.81 (t, J = 8.2, 15.3 Hz, 3H,

Ar-H), 6.71 (d, J = 8.3 Hz, 3H, Ar-H), 2.07 (s, 9H, indole CH3); 13C NMR (CD2Cl2,

75 MHz): 140.8, 136.2, 136.0, 135.9, 129.2, 128.6, 128.3, 122.7, 120.4, 119.2, 114.6,

189

66.0. Microanalysis for C63H51N3P4: calcd (%) C = 77.69, H = 5.28, N = 4.31, found (%)

C = 76.88, H = 5.40, N = 4.41.

Ph2P PtII

PPh2

PPh2

P

Cl

N NN

BPh4

[PtCl(N-PPh2)3-5]BPh4, 37. Phosphine ligand (N-PPh2)3-5 (0.061 g, 0.063 mmol) was

dissolved in CH2Cl2 (2 mL) and added dropwise to a stirring solution of Pt(COD)Cl2

(0.024 g, 0.063 g) and NaBPh4 (0.022 g, 0.063 mmol) in acetone (2 mL). Gradually the

solution turns bright orange in colour. The solution was left to stir overnight upon which

an orange solid precipitated from solution. The solid was isolated by filtration and

washed with minimal acetone and dried in air (0.049 g, 51%). 31P NMR (DMSO-d6,

161 MHz): δ 49.4 (s, JPt-Peq = 2826 Hz, 3P, Peq), 3.3 (s, JPt-Pax = 2225 Hz, JPax-Peq = 10 Hz,

1P, Pax); 1H NMR (DMSO-d6, 300 MHz): δ 7.85 (d, 3H, J = 8.2 Hz, Ar-H), 7.38-7.05 (m,

30H, Ar-H), 6.92 (t, J = 7.3, 14.8 Hz, 3H, Ar-H), 6.81 – 6.76 (m, 3H, Ar-H), 6.38 (d, J =

8.4 Hz, 3H, Ar-H), 3.34 (s, 9H, indole CH3); 13C NMR (DMSO-d6, 75 MHz): 142.5,

137.2, 136.3, 135.1, 130.2, 128.6, 127.3, 122.2, 121.4, 118.8, 113.2, 68.5.

Ph2P RhI

PPh2

PPh2

P

Cl

N NN

[RhCl(N-PPh2)3-5], 38. Phosphine ligand (N-PPh2)3-5 (0.22 g, 0.23 mmol) was

dissolved in THF (5 mL) and added dropwise to a stirring solution of [Rh(COD)Cl]2

(0.056 g, 0.11 g) in THF (3 mL). Immediately the solution turned dark red in colour, and

allowed to stir for 30 minutes. The solution was concentrated to dryness to afford a dark

red solid. The solid was re-dissolved in minimal CH2Cl2, and added to a copious amount

of Et2O which precipitated out a fine dark red coloured solid. The solid was isolated by

filtration and washed with minimal Et2O and dried in air (0.24 g, 94%). 31P NMR

190

(DMSO-d6, 161 MHz): δ 72.8 (dd, JPt-Peq = 159 Hz, 3P, Peq), 42.4 (dq, JRh-Pax = 84 Hz,

JPax-Peq = 24 Hz, 1P, Pax); 1H NMR (DMSO-d6, 300 MHz): δ 7.88 (d, 3H, J = 7.8 Hz, Ar-

H), 7.36-7.04 (m, 30H, Ar-H), 6.95 (t, J = 7.9, 14.8 Hz, 3H, Ar-H), 6.81 (t, J = 7.9,

14.8 Hz, 3H, Ar-H), 6.36 (d, J = 8.3 Hz, 3H, Ar-H), 3.34 (s, 9H, indole CH3); 13C NMR

(DMSO-d6, 75 MHz): 141.2, 137.8, 136.1, 135.2, 133.2, 128.9, 126.0, 123.1, 120.9,

119.2, 111.6, 68.6.










191

5.9. References

(1) Alcock, N. W.; Brown, J. M.; Hulmes, D. I. Tetrahedron: Asymmetry 1993, 4,

743-756.


(3) Bridgeman, A. J.; Gerloch, M. J. Chem. Soc. Dalton Trans. 1995, 197-204.

(4) Aizawa, S.-I.; Funahashi, S. Anal. Sci. 1996, 12, 27-30.

(5) Bianchini, C.; Masi, D.; Meli, A.; Peruzzini, M.; Zanobini, F. J. Am. Chem. Soc.

1988, 110, 6411-6423.

(6) Brüggeller, P. Inorg. Chem. 1987, 26, 4125-4127.

(7) Hohman, W. H.; Kountz, D. J.; Meek, D. W. Inorg. Chem. 1986, 25, 612-623.

(8) Fernández, D.; García-Seijo, M. I.; Kégl, R.; Peťócz, G.; László, K.; García-

Fernádez, M. E. Inorg. Chem. 2002, 41, 4435-4443.


(10) Rampersad, N. C., MSc Thesis, University of Toronto, 2001.


(12) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements; 2nd ed.;

Butterworth-Heinemann: Oxford, 1997.

(13) Claridge, T. D. W.; Long, J. M.; Brown, J. M.; Hibbs, D.; Hursthouse, M. B.

Tetrahedron 1997, 53, 4035-4050.

(14) Alcock, N. W.; Hulmes, D. I.; Brown, J. M. J. Chem. Soc., Chem. Commun. 1995,

395-397.

(15) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John Wiley & Sons, Ltd.:

New York, NY, 2001.

(16) Filipuzzi, S.; Pregosin, P. S.; Albinati, A.; Rizzato, S. Organometallics 2006, 25,

5955-5964.

(17) Wassenaar, J.; Reek, J. N. H. Dalton Trans. 2007, 3750-3753.


(19) Ciclosi, M.; Lloret, J.; Estevan, F.; Lahuerta, P.; Sanaú; Pérez-Prieto, J. Angew.

Chem. Int. Ed. 2006, 45, 6741-6744.

191

192

(20) Wilson, M. R.; Prock, A.; Giering, W. P.; Fernandez, A. L.; Haar, C. M.; Nolan, S.

P.; Foxman, B. M. Organometallics 2002, 21, 2758-2763.

(21) Gambaro, J. J.; Hohman, W. H.; Meek, D. W. Inorg. Chem. 1989, 28.

(22) Spek, A. L. J. Appl. Cryst. 2003, 36, 7-13.


(24) Drew, D.; Doyle, A. R. Inorg. Synth. 1972, 13, 47-55.




Chapter 6

Conclusion

2-Indolylphosphines represent an interesting class of compounds that can be

systematically modified at an indolyl nitrogen centre with relative ease. It has been

shown that the a variety of functional groups can be incorporated on an indolyl nitrogen

centre that can alter the overall bulkiness, electronics, or chirality of the resultant

phosphine molecule.

The solid-state structures of selected 2-indolylphosphines were analyzed using X-

ray crystallography. Several general trends emerged from this analysis: the orientation of

the methyl substituent on indole in the solid-state appears to have a degree of correlation

with substitution at the nitrogen centre; the aromaticity of the pyrrole ring of each indolyl

substituent is unaffected by the introduction of a phosphorus atom at the C2-position or in

the presence of a substituent on the indolyl nitrogen. A value called the sum of the <CPC

bond angles, Σ{<CPC}, can provide information on the steric crowding around a

phosphorus atom based on the crystallographic bond angles of a phosphine ligand. This

technique is a good estimate for the steric bulk of a phosphine ligand in the absence of

cone angle data. It was determined that the Σ{<CPC} values for N-functionalized 2-

indolylphosphines are in general larger than the unfunctionalized compounds.

The crystal structures of PdCl2 complexes of 2-indolylphosphines exhibit both

inter- and intramolecular hydrogen bonding from an indolyl NH hydrogen bond donor to

a chloro ligand. Thus the utility of the inherent hydrogen bonding ability of tris-2-(3-

methylindolyl)phosphine was examined through a series of anion titrations. The titration

data indicated strong binding of fluoride, chloride, and acetate to tris-2-(3-

methylindolyl)phosphine in a 1 : 1 anion to phosphine receptor ratio. Crystal structures

of the fluoride and acetate complexes to tris-2-(3-methylindolyl)phosphine confirm the

binding stoichiometry. Based on these results, a new indolylphosphine-based anion

receptor was designed to increase anion selectivity. A series of attempts to generate the

193

194

new anion receptor were met with synthetic challenges that prevented the formation of

the desired phosphine compound. However, a molecular cleft that is based on two

indolyl rings linked via a phenyl moiety was synthesized and shown to have anion

binding capability. The molecular cleft exhibited high selectivity for acetate over other

anions.

The coordination of 2-indolylphosphine ligands to transition metal complexes

provides additional ways to investigate their properties. Reaction of a phosphine ligand

with Ni(CO)4, and subsequent examination of the resultant complex’s CO stretching

frequencies gives information about the phosphine’s net-basicity. It was found that 2-

indolylphosphines can have a range of net-basicities, and by introducing substituents at

nitrogen, more subtle changes to the net-basicity of the parent ligand can be made. The

[Cu(tris-2-(3-methylindolyl)phosphine)(phenanthroline)]BF4 complex exhibits

simultaneous P-coordination while the indolyl NH groups are engaging in intermolecular

hydrogen bonding to the BF4- to create a discrete ion pair complex. The trans-influence

of selected 2-indolylphosphines was speculated by examining the Pd-Cl bond lengths

trans to the 2-indolylphosphine in [Pd(L)Cl(μ-Cl)]2 complexes.

Amino and phosphino substituents can be used to functionalize an indolyl

nitrogen centre of 2-indolylphosphines to give (P,N)- and (P,P)-ligands. These

substituents are particularly useful as they provide an additional site for metal

coordination. Metal complexes of (P,N)- and (P,P)-2-indolylphosphines can be used to

examine the trans-influence of amino versus phosphino donors, and correlate σ-donating

strength to trans-influence.

Finally, a tetradentate tripodal ligand can be generated from tris-2-(3-

methylindolyl)phosphine by introducing diphenylphosphino substituents on each indolyl

nitrogen centre. This trisubstituted tripod induces five-coordinate trigonal bipyramidal

coordination geometry on Pt(II) and Rh(I). A variety of attempts were made to exchange

the fifth ligand in both the Pt(II) and Rh(I) complexes, but were unsuccessful due to

complex decomposition.

an exploration of the structural and

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