Ligand Development Directed Towards Applications in Late Metal Catalysis

Christopher Charles Brown

A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Chemistry University of Toronto

Ligand Development Towards Applications in Late Metal Catalysis

Christopher Charles Brown

Doctor of Philosophy

Department of Chemistry University of Toronto

2013 Abstract

Olefin metathesis is a powerful tool in organic chemistry and in the last 20 years has seen prolific expansion. Olefin metathesis has allowed the expedient and concise preparation of otherwise extremely difficult or impossible molecules. The vast majority of research has recently focused on the use of ruthenium olefin metathesis catalysts and relatively simple variations of Grubbs style catalysts.

This research was focused on the preparation and investigation of new ruthenium chemistry and its potential application towards olefin metathesis catalysis. The research hub was the development of new ligand sets and their application. Furthermore, established ligand sets were applied to new applications of ruthenium chemistry and interesting reactivity investigated.

Hitherto, the N-heterocyclic carbenes and phosphines have formed the basis of auxiliary ligands for ruthenium catalysts which most significantly promote catalytic olefin metathesis. The first strategy employed herein was the development of a new class of monodentate ligands. A new class of monodentate heterocyclic phosphinimines is prepared, characterized, and applied.

Subsequently, the successful coordination to silver and gold is described. An interesting reaction is also noted with palladium. ii

In the development of heterocyclic phosphinimines, phosphino-imines were prepared and applied to ruthenium chemistry. Coordination analogues of second generation Grubbs catalyst were prepared. Additionally, investigation into the coordination chemistry to general ruthenium starting materials was investigated and a unique template reaction was observed. The reaction involved the scission of a P-N bond and subsequent formation of a new P,N bidentate ligand.

The final main focus of research was the application of tridentate ligands towards catalytic olefin metathesis. First, bis(imino)pyridine ligands were applied to Grubbs style catalysts and unique reactivity was observed. Second, tridentate phosphinimine ruthenium complexes were prepared and screened for activity in catalytic olefin metathesis.

iii

Acknowledgments

I would like to thank Professor Doug Stephan who gave me the opportunity to complete my degree in an environment which encouraged the development and realization of one's own ideas. Furthermore, I would like to thank him for insightful discussions, support, and tremendous opportunities.

I would like to thank the current and former Stephan lab members for advice, friendship, and assistance throughout my time in Toronto. Dr. Ian Blackmore was especially helpful in my early days in the Stephan lab who shared a great deal of knowledge and patience. Dr. Renan Cariou and Dr. Clinton Lund were directly involved in the Lanxess project and provided perceptive advice.

Last but not least I would like to thank my family for years of support. I would especially like to thank my mother, Shelley Creighton, for never-ending assistance, guidance, and friendship. Without this none of this would have been possible.

Table of Contents

Acknowledgments ...... iv

Table of Contents ...... v

List of Tables ...... x

List of Schemes ...... xi

List of Figures ...... xiv

List of Abbreviations ...... xviii

Chapter 1 Introduction ...... 1

1.1 Catalysts ...... 1

1.1.1 Classification of Catalysts ...... 1

1.1.2 Heterogeneous Catalysis ...... 1

1.1.3 Homogeneous Catalysis ...... 1

1.1.4 Industrial Catalysis ...... 2

1.2 Olefin Metathesis ...... 3

1.2.1 Early Efforts ...... 3

1.2.2 Well Defined Catalysts ...... 5

1.2.3 Mechanism of Olefin Metathesis ...... 7

1.2.4 Olefin Metathesis Catalyst Screening ...... 8

1.2.5 Bidentate Olefin Metathesis Catalysts ...... 11

1.2.6 Tridentate Transition Metal Catalysts ...... 12

1.2.7 Tridentate Ruthenium Catalysts ...... 14

1.3 Lanxess Project ...... 15

1.4 Scope of Thesis ...... 16

Chapter 2 Cyclopropanation of Di-iminopyridine Ligand ...... 17

2.1 Introduction ...... 17

2.1.1 Bis-iminopyridine catalyst development ...... 17

2.1.2 Ruthenium Bis-iminopyridine Chemistry ...... 18

2.2 Results and Discussion ...... 20

2.2.1 Direct Catalyst Synthesis ...... 20

2.2.2 Indirect Synthesis ...... 23

2.2.3 Consideration of Mechanism ...... 26

2.3 Conclusions ...... 27

2.4 Experimental Section ...... 29

2.4.1 General Considerations ...... 29

2.4.2 Synthetic Procedures ...... 29

2.4.3 X-Ray Crystallography ...... 32

Chapter 3 Metal-Free Hydrogenation of Di-Imines ...... 34

3.1 Introduction ...... 34

3.1.1 Hydrogenation ...... 34

3.1.2 Di-Imine Chemistry ...... 35

3.1.3 Bis(imino)pyridine Chemistry ...... 36

3.2 Results and Discussion ...... 39

3.2.1 Di-imine Reduction ...... 39

3.2.2 Bis(imino)pyridine Reduction ...... 41

3.2.3 Bis(amino)pyridine Coordination ...... 43

3.3 Conclusions ...... 44

3.4 EXPERIMENTAL SECTION ...... 45

3.4.1 General Considerations ...... 45

3.4.2 High Pressure Hydrogenations ...... 45

3.4.3 Low Pressure Hydrogenations ...... 46

3.4.4 Table of Conversion ...... 46 vi

3.4.5 Analysis ...... 47

3.4.6 X-Ray Crystallography ...... 49

Chapter 4 Development of Phosphorus-Nitrogen Heterocyclic Ligands ...... 51

4.1 Introduction ...... 51

4.2 Results and Discussion ...... 53

4.2.1 Phosphino-imine synthesis ...... 53

4.2.2 Phosphino-imine cyclization ...... 54

4.2.3 Decomposition ...... 58

4.3 Conclusions ...... 60

4.4 Experimental ...... 61

4.4.1 General Considerations ...... 61

4.4.2 Experimental ...... 61

4.4.3 X-ray Crystallography ...... 66

Chapter 5 P,N Heterocycle Coordination ...... 70

5.1 Introduction ...... 70

5.1.1 N-Heterocyclic Coordination ...... 70

5.1.2 Group 10 Coordination Chemistry ...... 70

5.1.3 Ruthenium Coordination Chemistry ...... 71

5.2 Results and Discussion ...... 72

5.2.1 Silver ...... 72

5.2.2 Gold ...... 74

5.2.3 Ruthenium ...... 79

5.3 Conclusions ...... 80

5.4 Experimental ...... 81

5.4.1 General Considerations ...... 81

5.4.2 Synthesis ...... 82 vii

5.4.3 X-ray Crystallography ...... 84

Chapter 6 P,N Template Synthesis ...... 87

6.1 Introduction ...... 87

6.1.1 P-N Ligands ...... 87

6.1.2 Template Synthesis ...... 89

6.2 Results and Discussion ...... 91

6.2.1 Ruthenium Phosphino-imine Coordination ...... 91

6.2.2 Dimer Synthesis ...... 93

6.2.3 Monomer Synthesis ...... 97

6.2.4 Extended Reactivity ...... 102

6.2.5 Mechanistic Considerations ...... 106

6.3 Conclusion ...... 109

6.4 Experimental ...... 110

6.4.1 General Considerations ...... 110

6.4.2 Additional Information ...... 110

6.4.3 Synthesis ...... 111

6.4.4 X-ray Crystallography ...... 116

6.4.5 Supplementary NMR Data ...... 121

Chapter 7 P,N Catalytic Hydrogenation ...... 125

7.1 Introduction ...... 125

7.1.1 Hydrogenation ...... 125

7.1.2 Transfer Hydrogenation ...... 126

7.2 Results and Discussion ...... 129

7.2.1 Hydrogenation ...... 129

7.2.2 Transfer Hydrogenation ...... 129

7.3 Experimental ...... 136 viii

7.3.1 General Considerations ...... 136

7.3.2 Typical Reduction Protocol ...... 136

7.4 Conclusion ...... 137

Chapter 8 Tridentate phosphinimine ruthenium complexes ...... 138

8.1 Introduction ...... 138

8.2 Results and Discussion ...... 140

8.2.1 Complex Synthesis ...... 140

8.2.2 Preliminary Catalytic Screening ...... 143

8.3 Conclusions ...... 145

8.4 Experimental ...... 146

8.4.1 General Considerations ...... 146

8.4.2 Synthesis ...... 147

8.4.3 X-ray Crystallography ...... 149

Chapter 9 Summary and Future Work ...... 151

9.1 Summary ...... 151

9.2 Future Work ...... 154

References ...... 156

Curriculum Vitae ...... 177

List of Tables

Table 2.4.1 - Select Crystallographic Data for 2-1 and 2-2 ...... 33

Table 3.4.1 - FLP reduction conversions of compounds with 2 imines ...... 46

Table 3.4.2 - Select Crystallographic Data for 3-1 ...... 50

Table 4.4.1 - Select Crystallographic Data for 4-1, 4-2, and 4-4 ...... 67

Table 4.4.2 - Select Crystallographic Data for 4-7, 4-8, and 4-9 ...... 68

Table 4.4.3 - Select Crystallographic Data for 4-10 ...... 69

Table 5.4.1 - Select Crystallographic Data for 5-1, 5-2, and 5-3 ...... 85

Table 5.4.2 - Select Crystallographic Data for 5-4 ...... 86

Table 6.4.1 - Select Crystallographic Data for 6-1, 6-2, and 6-4 ...... 117

Table 6.4.2 - Select Crystallographic Data for 6-5, 6-6, and 6-7 ...... 118

Table 6.4.3 - Select Crystallographic Data for 6-9, 6-10, and 6-11 ...... 119

Table 6.4.4 - Select Crystallographic Data for 6-12 ...... 120

Table 8.4.1 - Select Crystallographic Data for 8-2 ...... 150

List of Schemes

Scheme 1.2.1 - Chauvin mechanism of olefin metathesis...... 7

Scheme 1.2.2 - Standard Screening Reaction for ROMP ...... 8

Scheme 1.2.3 - Standard Screening Reaction for RCM ...... 9

Scheme 1.2.4 - Standard Screening Reaction for CM ...... 9

Scheme 1.2.5 - The decomposition of Grubbs catalyst in the presence of methanol ...... 10

Scheme 1.2.6 - Decomposition pathway of second generation Grubbs catalyst...... 10

Scheme 1.2.7 - Decomposition pathway of second generation Grubbs catalyst from excess ethylene...... 11

Scheme 1.2.8 - Catalytic synthesis of amides using a ruthenium catalyst...... 14

Scheme 2.1.1-Ligand Development...... 17

Scheme 2.1.2-Polymerizaton Catalysts...... 18

Scheme 2.2.1 - Synthesis of 2-1 complexes ...... 21

Scheme 2.2.2-Synthesis of 2-2 olefin metathesis precatalyst ...... 21

Scheme 2.2.3-Examples of Ruthenium olefin metathesis catalyst of 1,5-cyclooctadiene...... 22

Scheme 2.2.4-Failed preparations of new Ru[N3] olefin metathesis catalysts...... 23

Scheme 2.2.5-Synthesis of 2-3 and 2-4...... 24

Scheme 2.2.6 - Proposed mechanism of a bis(imino)pyridine ruthenium complex cyclopropanation ...... 27

Scheme 3.1.1- Initial FLP hydrogenation catalyst, (2,4,6-Me3C6H2)2P(C6F4)B(C6F5)2, and general scheme of "base free" FLP hydrogenation, respectively...... 35

Scheme 3.1.2-Typical synthesis of an Dihydroimidazolium salt...... 36

Scheme 3.1.3-Bis(imino)pyridine Ligand Development...... 36

Scheme 3.1.5 – Synthesis of aromatic bis(amino)pyridines...... 38

Scheme 3.1.6-Concurrent alkylation and reduction of bis(imino)pyridines...... 38

Scheme 3.2.2 Reduction of Di-Imines with B(C6F5)3 ...... 40

Scheme 3.2.3 - Reduction of di-imines with B(C6F5)3 ...... 42

Scheme 3.2.4 - Coordination of reduced BIP to Zr ...... 43

Scheme 4.1.1 - Two possible Lewis diagrams of phosphinimine heterocycles...... 52

Scheme 4.1.2- Synthesis of heterocyclic phosphinimines proposed by Schmidpeter et al...... 53

Scheme 4.2.1 - Methyl acrylate cyclization reactions...... 54

Scheme 4.2.2 - Dimethyl acetylenedicarboxylate cyclization reactions...... 56

Scheme 4.2.3 - Acrylonitrile cyclization reactions...... 57

Scheme 4.2.4 - Proposed mechanism for the decomposition of heterocyclic phosphinimines ... 59

Scheme 5.1.1 - First reported example of a NHC metal coordination complex...... 70

Scheme 5.1.2 - Typical NHC silver coordination complex...... 71

Scheme 5.1.3 - Gold-NHC complex synthesis...... 71

Scheme 5.1.4 - Second generation Grubbs type catalysts...... 72

Scheme 5.2.1 - Coordination of 4-4 with Ag(NO3)...... 72

Scheme 5.2.2 - Synthesis of heterocyclic phosphinimine gold (I) complexes...... 75

Scheme 6.1.1 - Variety of reported P,N bonded ligands...... 87

xii

Scheme 6.1.2 - Precedence of Ruthenium phosphino-imine ligands displaying importance of amine fragment...... 88

Scheme 6.1.3 - Conventional synthesis of phosphine imine bidentate ligands...... 88

Scheme 6.1.4 - Tetradentate ligands obtained through template synthesis...... 89

Scheme 6.1.5 - Group 8 bidentate ligands obtained through template synthesis...... 90

Scheme 6.2.1 - Synthesis of phosphino-imine analogues of second generation Grubbs catalysts 91

Scheme 6.2.2 -- Synthesis of Ruthenium Dimers 6-2, 6-3, 6-4...... 94

Scheme 6.2.3 - Synthesis of ruthenium monomers 6-5, 6-6, 6-7, 6-8...... 99

Scheme 6.2.4 - Synthesis of 6-9...... 102

Scheme 6.2.5 - Synthesis of 6-10 and 6-11...... 102

Scheme 6.2.6 - Proposed intermediates towards the P-N rearrangement...... 107

Scheme 6.2.7 - Synthesis of 6-12 using two methods...... 107

Scheme 7.1.1 - Wilkinson's catalyst transition metal hydrogenation catalytic cycle...... 126

Scheme 7.1.2 -- General transfer hydrogenation of acetophenone to 1-phenylethanol...... 127

Scheme 7.1.3 - Selection of ligands which promote catalytic transfer hydrogenation...... 127

Scheme 7.1.4 - Mechanism of base-mediated transfer hydrogenation...... 128

Scheme 8.2.1 - Phosphorane synthesis of phosphinimine pincer ligand 8-1...... 140

Scheme 8.2.2 - Synthesis of a ruthenium phosphinimine pincer complex with an alkylidene. .. 141

Scheme 8.2.3 - Azide synthesis of phosphinimine pincer ligand...... 141

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List of Figures

Figure 1.1.1 - Depiction of nitrile butadiene rubber, highlighting functionalities...... 2

Figure 1.2.1 - Generalized scheme of olefin metathesis...... 4

Figure 1.2.2 - Early Ta alkylidene catalysts...... 5

Figure 1.2.3 - Schrock type olefin metathesis catalysts...... 5

Figure 1.2.4 - Grubbs type olefin catalysts...... 6

Figure 1.2.5 - Hoveyda-Grubbs catalyst ...... 12

Figure 1.2.6 - The development of olefin metathesis catalysts with pseudohalide bidentate auxiliary ligands ...... 12

Figure 2.2.1-POV-Ray Depiction of cyclopropanated Ru[N3] complexes 2-3 and 2-4 respectively. C: black, Ru: orange, Cl: green, P: orange, N: aquamarine, H: grey...... 26

Figure 3.1.1- Desired bis(amino)pyridine which was not possible to synthesize...... 37

Figure 3.1.2 - Reduced alkyl bis(imino)pyridines...... 38

Figure 3.2.1 - Diimines for the preparation of saturated NHCs...... 39

Figure 3.2.2- 1H NMR spectrum of one pot synthesis of N heterocyclic carbene SIMes...... 41

Figure 3.2.3- POV Ray Depiction of 3-1. C: black, N aquamarine, H grey...... 42

Figure 4.1.1 - Left: N-heterocyclic carbene Middle: Carbene variations Right: Heterocyclic phosphinimine ...... 51

Figure 4.1.2- Idealized orbital configuration, left NHC, right heterocyclic phosphinimine...... 52

Figure 4.2.1 - POV Ray Depiction of phosphino-imines 4-1 and 4-2 respectively. C: black, P: orange, N aquamarine...... 54

xiv

Figure 4.2.2 - POV Ray Depiction of P N heterocycle 4 4. C: black, P: orange, N aquamarine, O red...... 55

Figure 4.2.3 - POV Ray Depiction of P N heterocycle 4 7 and 4 8 respectively. C: black, P: orange, N aquamarine, O red...... 57

Figure 4.2.4 - POV Ray Depiction of P N heterocycle 4 9. C: black, P: orange, N aquamarine. 58

Figure 4.2.5 - POV Ray Depiction of P,N heterocycle 4-10. C: black, P: orange, N aquamarine, O red...... 59

Figure 5.2.1 - POV Ray Depiction of P-N heterocycle 5-1. Ag: dark red, C: black, P: orange, N aquamarine, O light red. Counter anion omitted for clarity...... 73

Figure 5.2.2 - POV Ray Depiction of P N heterocycle 5-2. Au: light yellow, C: black, P: orange, N aquamarine, O light red...... 76

Figure 5.2.3 - POV Ray Depiction of P N heterocycle 5-3. Au: light yellow, C: black, P: orange, N aquamarine, O light red...... 77

Figure 5.2.4 - Optimized structure space filling model demonstrates differences in sterics. 4-4 left, SIMes right ...... 78

Figure 5.2.5 - POV Ray Depiction of P-N heterocycle 5-4. Au: light yellow, C: black, P: orange, N aquamarine, O light red. Triflate ion removed for clarity...... 79

Figure 6.2.1 - POV Ray Depiction of 6-1. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 92

Figure 6.2.2 - POV Ray Depiction of 6-2. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 95

Figure 6.2.3 - POV Ray Depiction of 6-4. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 96

Figure 6.2.4 - POV Ray Depiction of 6-5. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 98

Figure 6.2.5 - POV Ray Depiction of 6-6 and 6-7. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 100

Figure 6.2.6 - POV Ray Depiction of 6-9. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 101

Figure 6.2.7 - POV Ray Depiction of 6-10. C: black, Pd: yellow/green, I: pink, P: orange, N aquamarine. H atoms omitted for clarity...... 103

Figure 6.2.8 - POV Ray Depiction of 6-11. C: black, Fe: yellow, Cl: green, P: orange, O red, N aquamarine, H grey. Most H atoms omitted for clarity except H100 bound to imine...... 105

Figure 6.2.9 - POV-Ray Depiction of 6-12. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity...... 108

Figure 6.4.1 - Clean NMR spectras in lieu of EA of 6-8. Top 1H NMR, middle 31P NMR, and bottom 13C NMR ...... 122

Figure 6.4.2 - Clean NMR spectras of 6-5 in lieu of EA. Top 1H NMR, middle 31P NMR, and bottom 13C NMR ...... 123

Figure 6.4.3 - Overlaid NMR spectra of RuiPrpy dimer. Top 1H NMR mixture of cis and trans isomers. Bottom 1H NMR of cis pyridine ...... 124

Figure 7.2.1 - Transfer hydrogenation of acetophenone employing pre catalyst 6-2 at both room temperature and 50°C...... 131

Figure 7.2.2 - Transfer hydrogenation of acetophenone employing pre catalyst 6-2 at both room temperature and 50°C...... 132

Figure 7.2.3 - Transfer hydrogenation of acetophenone employing pre catalyst 6-5 at both room temperature and 50°C...... 134

Figure 7.2.4 - Transfer hydrogenation of acetophenone employing pre catalyst 6-8 at both room temperature and 50°C...... 135

xvi

Figure 8.1.1 - Examples of coordination complexes based on phosphinimine pincer complexes...... 139

Figure 8.1.2 - Unique reactivity observed with group 10 phosphinimine pincer complexes. .... 139

Figure 8.1.3 - Two additional examples of tridentate phosphinimine pincer complexes...... 140

Figure 8.2.1 - POV-Ray Depiction of 8-2. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. HN and CHPh hydrogen atoms refined and included...... 142

Figure 8.2.2 - The RCM of diethyldiallylmalonate by 8-2...... 143

xvii

List of Abbreviations

Å Angstrom abs absorption

Ar aryl atm atmospheres (pressure) br broad

C Celsius

CAAC cyclic alkylaminocarbenes calc calculated cat. catalyst

CCD charge coupled device

CDP carbodiphosphoranes

CM cross metathesis cm3 cubic centimeter coeff coefficient

Cy cyclohexane d doublet

DCM dichloromethane deg degree

Et ethyl

xviii

Et2O diethyl ether equiv equivalents

FLP frustrated Lewis pair g gram

GOF goodness of fit

Hz hertz hr hour

H2 dihydrogen iPr iso-propyl

J scalar coupling constant

K Kelvin m multiplet

Me methyl

Mes mesityl min minute mL milliliter mm millimeter mmol millimole

N2 dinitrogen

[N3] bis(imino)pyridine ligand

xix

NHC N-heterocyclic carbene

NMR Nuclear Magnetic Resonance

O2 oxygen p para

PCy3 tricyclohexylphosphine

Ph phenyl

PPh3 triphenylphosphine ppm parts per million

POV-Ray Persistence of Vision Raytracer py pyridine q quartet

R residual

RCM ring closing metathesis

ROMP ring opening metathesis polymerization r.t. room temperature

Rw weighted residual

SICy 1,3-dicyclohexylimidazolinium chloride

SIDipp 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride

SIiPr 1,3-diisopropylimidazolinium chloride

SIMes 1,3-bis(2,4,6-trimethylphenyl)imidazolinium chloride

xx temp. temperature

THF tetrahydrofuran

TMS trimethylsilyl

TON Turnover number

xxi 1

Chapter 1 Introduction 1.1 Catalysts

1.1.1 Classification of Catalysts

Catalysts may be divided into several different classes. The two most common classifications are heterogeneous vs. homogenous catalysts. The basis of this classification is solubility. Another classification of catalysts is based on the utility. Examples of such catalysts are transition metal catalysts, organocatalysts, acid-base catalysts, redox catalysts, and enzymes among many others.

1.1.2 Heterogeneous Catalysis

Heterogeneous catalysts are completely insoluble in the reaction medium. This may be because the catalyst itself is completely insoluble, for example palladium on charcoal, or that the catalyst is somehow prevented from entering the medium in which the reactants are found, for example the biphasic hydroformylation of propene.

Heterogeneous catalysts possess several properties which are advantageous. Heterogeneous catalysts tend to offer greatly enhanced thermal stability. Furthermore, catalyst separation from the reaction vessel is unproblematic. Separation may be performed by simple filtration resulting in products which display very low trace metal contamination. This ease of separation allows many subsequent reuses of the catalyst. While heterogeneous catalysts offer many advantages, several disadvantages exist such as detailed control over the reaction site. This lack of control inhibits the formation of many desired products such as chiral products. This may, in certain instances, not be true in cases visa the use of chiral promoters with heterogeneous catalysts. 1 A notable recent exception was recently published by Morris et al.2

1.1.3 Homogeneous Catalysis

Homogeneous catalysts, as opposed to heterogeneous catalysts, reside in the same phase as the reactants. Homogeneous catalysts may offer many advantages over heterogeneous catalysts such as selectivity, rational design, and ease of investigation. The greater selectivity, for example, allows for the production of specific enantiomers which is of great importance in the

2 pharmaceutical industry. The catalyst solubility allows for the in-depth examination of the mechanism of product formation with the greater use of spectroscopy.

In the specific case of homogeneous transition metal catalysis, the solubility and resulting ability to study the catalysis in detail allows for the careful tailoring of catalyst properties. Such catalyst systems offer many avenues for the detailed control of reactivity. Ancillary ligand modification is one such strategy to control the chemistry at a transition metal center.

1.1.4 Industrial Catalysis

Industry makes significant use of catalysis in the production of fine chemicals, pharmaceuticals, polymers among many other substances. One of the most prolific examples of industrial catalysis is the Haber–Bosch process wherein N2 and H2 are mixed at high pressure in the presence of group eight transition metal catalysts to produce NH3. While the Haber-Bosch process is an example of heterogeneous catalysis, homogeneous catalysis also plays an important role in industrial catalysis. A relevant example to this thesis is the application of olefin metathesis in the production of commercial nitrile-butadiene rubber, NBR (Figure 1.1.1).

Figure 1.1.1 - Depiction of nitrile butadiene rubber, highlighting functionalities.

NBR rubber is produced commercially via the anionic emulsion polymerization of 1,3-butadiene and acrylonitrile. This technique, while the only commercially viable route, only provides a polymer with a relatively high molecular weight of 300,000 g/mol which limits the further ability to process the polymer. Transition metal based polymerization is not applicable to the production of NBR. However, transition metal based homogeneous catalysts facilitate additional processing in the production of commercial grade NBR with a wide variety of molecular weights and, therefore, applications.

The anionic polymerization technique leads to residual double bonds within the polymer. Beginning in the early 2000s olefin metathesis chemistry, which is described subsequently in the introduction, became sufficiently advanced in both activity and functional group tolerance to explore the application towards NBR modification.

The cross metathesis, described in thesis section 1.2.4.3, of 1-hexene and NBR allows for the alteration of the structure of NBR. Varying the loading of 1-hexene in the presence of NBR is one strategy in the reduction of the molecular weight from 300,000 Da to a range of 5,000 - 100,000 g/mol. The range of molecular weights allows the application to a variety of purposes. An additional strategy to obtain a desired NBR molecular weight is the variation of catalyst loading. Increasing the catalyst loading leads to lower observed molecular weights, likely due to the fact that catalyst lifetime is limited in the reaction environment and additional equivalents of catalyst are required. The nitrile functionalities and contamination from NBR production necessitate the use of a ruthenium based olefin metathesis catalyst as other catalyst systems either lack appropriate activity or stability in the reaction medium.

1.2 Olefin Metathesis

1.2.1 Early Efforts

Olefin metathesis is defined as a bimolecular process formally involving the exchange of bonds between two chemical species so that the bonding affiliations in the products are identical to those in the reactants.3 A generalized example of olefin metathesis is shown in Figure 1.2.1. While much of the current fundamental research and application development are based on homogeneous catalysts and catalysis much is also known about heterogeneous applications. However, the largest scale industrial processes are based on heterogeneous catalysts.

Olefin metathesis was first discovered in the 1960s. Catalysts were ill-defined and the majority 4 heterogeneous. The catalyst was composed of a Co/MoOn supported on alumina. The catalyst performed the disproportionation of propene to ethylene and butene. Following this work, in

1967 Calderon et al. discovered a reaction wherein the mixing of WCl5/EtOH/Et3Al in the presence of propene yielded ethylene and 2-butene exclusively.5 The Calderon et al. publication in 1967 was the first to use the name olefin metathesis in the literature to describe such a reaction.

Figure 1.2.1 - Generalized scheme of olefin metathesis.

During the intermediate 20 years, work continued with the discovery of the first isolable transition metal alkylidene in 1974 by Schrock with the isolation of 6 Ta[CH2C(CH3)3]3[CHC(CH3)3]. Further research was completed by Schrock and others into the applicability of tantalum towards catalytic olefin metathesis, however, the group 5 catalysts suffered from extreme sensitivity to oxygen and substrates which contain oxygen functional groups.7-12 An early example of an isolable Ta olefin metathesis catalyst is given in Figure 1.2.2. This lack of stability as well as sensitivity to oxygen dramatically limited the scope of potential applications with the exception of purely alkyl substrates.

Due to the fact that Schrock pioneered the synthesis and characterization of alkylidenes such functionalities have been classified as "Schrock carbenes". Schrock carbenes are classified with several unique characteristics such as the metal center typically found to have a high oxidation state, the metal center is generally an early transition metal, and the carbene is comprised either alkyl or hydrogen substituents. Conversely, a Fisher carbene is found on an late transition metal, the metals are in low oxidation states, and donor functionalities such as alkoxy or alkyl amino fragments.

Figure 1.2.2 - Early Ta alkylidene catalysts.

1.2.2 Well Defined Catalysts

In an effort to generate pre-catalysts of greater stability, activity, and tolerance of oxygen containing substrates, research efforts moved to the group 6 transition metals. A great deal of research was completed by Schrock et al. in an effort to obtain group 6 catalysts.13-20 The group 6 catalysts were primarily based on both Mo and W with Mo providing the best mixture of stability and activity. The most noteworthy catalysts are Mo catalysts with imido and alkoxide ancillary ligands and an alkylidene functionality. The group 6 Schrock type catalysts are still, to date, among the most active olefin metathesis catalysts. However, they must be prepared and utilized in inert conditions. The functional group tolerance was greatly improved with respect to esters, amides, ethers, trifluoromethyls and primary halogens among others. The prototypical example of a Schrock type catalyst is shown in Figure 1.2.3.

Figure 1.2.3 - Schrock type olefin metathesis catalysts.

Schrock type catalysts still contained significant drawbacks which were an unresolved problem. The group 6 catalysts still displayed an intolerance to a significant proportion of functional groups such as alcohols, acids, and water. Research efforts moving further to the right in the periodic table were initiated in an attempt to circumvent the problems associated with Group 6 catalysts. The potential of developing Group 7 olefin metathesis catalysts has received a limited amount of research due to a variety of problems. The group 7 analogue of Mo is Tc which, being radioactive, has not elicited any research interest. Rhenium, the group 7 analogue of Tungsten, has been investigated. However, little progress has been made in the development of

Re homogeneous catalysts. The majority of research was focused on efforts to mimic W catalysts and such efforts did not produce highly active catalysts.15,17,21-23 Therefore, a vast amount of research centered around the potential of group 8 metals as potential pre-catalysts for catalytic olefin metathesis.

Grubbs catalysts, developed in the 1990s, provided a solution to many of these deficiencies. Such catalysts are generally air stable, tolerant to the majority of organic functional groups, highly stable, and promote minimal side reactions. The first Grubbs type olefin metathesis 24 catalyst, RuCl2(PPh3)2(=CH-CH=CPh2), was discovered in 1992. While the catalyst showed improved characteristics, the catalyst lifetime was poor and it showed slow initiation. First generation Grubbs catalyst, Ru(PCy3)2Cl2CHPh, was an exceptional catalyst which gave moderate air stability and high activity.25,26 A significant improvement was published in 1999 by three research groups in near unison. The catalyst published by Grubbs and others was the 27-30 second generation Grubbs catalysts, Ru(SIMes)(PCy3)Cl2CHPh. The incorporation of an N-heterocyclic carbene ligand proved to greatly improve catalyst longevity, faster catalyst initiation, and applications towards olefins otherwise only reactive with Schrock type catalysts. First and second generation Grubbs catalysts are shown in Figure 1.2.4.

Figure 1.2.4 - Grubbs type olefin catalysts.

The discovery of highly active group 8 olefin metathesis catalysts inspired work to continue towards group 9 and group 10 metals. However, it was determined that such catalysts offered no advantages and gave evidence of numerous disadvantages. Group 9 catalysts gave predominantly cyclopropanation products, reduced activity and increased costs. Nevertheless, olefin metathesis may be possible but isomerization of the olefin is also facile leading to unexpected and/or undesired product mixtures. Therefore, after initial investigations into this area, efforts were again refocused with group 8 and more specifically ruthenium.

1.2.3 Mechanism of Olefin Metathesis

The mechanism of olefin metathesis was of great debate for more than 30 years during which time there were several mechanisms proposed. Calderon proposed a mechanism wherein the supposed intermediate was a cyclobutane intermediate bound to the transition metal catalyst in an Ƞ4 fashion.5,31-33 Grubbs et al. proposed the formation of a metallocyclopentane intermediate. Such a metallocyclopentane intermediate was proposed to result from the pre-formation of a diolefin complex which may subsequently rearrange about the metal center.34,35 Yves Chauvin and J.L. Herisson of the French Petroleum Institute correctly postulated in 1971 in an obscure German chemistry journal the currently accepted mechanism which went unnoticed for several years.36 Their suggestion was the interaction of a metal carbene with a coordinated olefin to perform a 2 + 2 cycloaddition to form a metallacyclobutane intermediate. The Chauvin mechanism was then first supported by Katz et al. determining the initial ratio of products.37 This was further supported by Grubbs et al. in 1975 with a series of isotopic labeling studies.6,38,39 The studies by both Katz and Grubbs employed variations of the same experiments via the analysis of the isotopic ratios of the ring closing metathesis products of 1,7-dioctene. The mechanism proposed by Chauvin and supported by Katz et al. is shown in Scheme 1.2.1.

Scheme 1.2.1 - Chauvin mechanism of olefin metathesis.

The conclusion that a metal carbene complex was necessary to catalyze olefin metathesis allowed for a rational design strategy for olefin metathesis catalysts. Until this time it was not understood that the metal carbene bond was integral in the catalytic cycle and the majority of catalysts were ill-defined.

1.2.4 Olefin Metathesis Catalyst Screening

The process of screening new olefin metathesis catalysts was highly inconsistent until 2006 as no standard conditions and/or substrates existed. In 2006 Grubbs et al. published a paper outlining several convenient screening protocols which became the defacto standard.40 The protocols involve the use of commercially available materials as well as detailed conditions and benchmarks. Previous to this report the majority of catalytic data was not directly comparable and/or applied to exotic substrates. The screening protocols described by Grubbs et al. surround the three applications of olefin metathesis which are most prevalent. The three applications are ring opening metathesis polymerization, ROMP; ring closing metathesis, RCM; and cross metathesis, CM.

1.2.4.1 Ring Opening Metathesis Polymerization

The first application is ring opening metathesis polymerization, ROMP, which is generally applied to target novel polymers. The driving force of such a reaction is relief of ring strain. The ROMP of cyclic olefins is facilitated by a wide range of catalytic systems. While norbornene is among the most widely used substrates, the ring strain alone causes polymerization to occur at such an elevated rate to preclude the accurate monitoring of conversion over a convenient time period. Therefore, the standard substrate for ROMP is 1,5-cyclooctadiene (Scheme 1.2.2). A 0.5 M solution of 1,5-cyclooctadiene may be fully converted to poly-1,5-cycloctadiene within 5 minutes by an efficient catalyst.40

Scheme 1.2.2 - Standard Screening Reaction for ROMP

1.2.4.2 Ring Closing Metathesis

The second application is ring closing metathesis, RCM, which was the first widely used olefin metathesis reaction in organic synthesis and is a powerful tool in the preparation of complex cyclic organic molecules. RCM allows the circumvention of otherwise multi-step organic synthesis. The RCM reaction is driven by the loss of ethylene, however, it is highly concentration dependent. The concentration of a RCM reaction allows a degree of control of the

9 formation of a ring system over a linear chain. The RCM screening standard for olefin metathesis is diethyldiallyl malonate (Scheme 1.2.3). Reaction conditions employed are room temperature and a concentration of 0.1 M with 1 % ruthenium catalyst. Under such conditions second generation Grubbs catalyst completes the cyclization within 30 minutes.40

Scheme 1.2.3 - Standard Screening Reaction for RCM

1.2.4.3 Cross Metathesis

The third and final application is cross metathesis, CM, which is likely the least prolific synthetic use of catalytic olefin metathesis. The CM of heteroolefins is a challenging reaction with many unsolved problems in catalyst development and application. Two specific challenges are the control of homocoupling vs. heterocoupling, as well as control over the formation of geometric or E/Z isomers. Recent advances have gained some control over the geometric selectivity of catalysis, but examples are few. The ability to control the formation of homocoupled vs. heterocoupled product is generally controlled through a judicious choice in substrates. Of the two standard olefin metathesis test reactions, the one chosen in this work is the cross metathesis of methyl acrylate and 5-hexenyl acetate (Scheme 1.2.4). The reaction is completed with a concentration of 0.4 M and 2.5 mol % catalyst. This reaction is unique in the fact that the homocoupled product of methyl acrylate is not obtained in any significant yield employing ruthenium catalysts. First generation Grubbs catalysts cannot effectively catalyze the cross metathesis of methyl acrylate and 5-hexenyl acetate as observed conversions under the conditions described in scheme 1.2.4 are no greater than 10 %. Second generation Grubbs catalysts facilitate the catalysis effectively with conversions near 80 % within 1 to 2 hours.40

Scheme 1.2.4 - Standard Screening Reaction for CM

1.2.4.4 Decomposition of Olefin Metathesis Catalysts

In an effort to further the understanding of olefin metathesis catalysis and develop superior catalysts, extensive studies have been undertaken on the pathways of decomposition. In the presence of functional groups, a variety of decomposition pathways are viable. In the presence of protic species, a sufficiently acidic proton may be delivered thus inducing decomposition. Furthermore, specifically in the presence of methanol, a recent report by Fogg et al. observed the formation of ruthenium carbonyl species which are devoid of an alkylidene and any observable catalytic activity (Scheme 1.2.5).41

Scheme 1.2.5 - The decomposition of Grubbs catalyst in the presence of methanol

Further decomposition is observed without the presence of a specific substrate but due to involvement of an ancillary ligand or the result of the production of ethylene which is the byproduct in many olefin metathesis reactions.42-44 The formation of a methylidene in the course of the catalytic cycle is the root cause of several such decomposition pathways and their associated products. The formation of a methylidene in the presence of tricyclohexylphosphine allows the tricyclohexylphosphine to attack the methylidene which subsequently results in the formation of a phosphorus ylid and the concurrent formation of a unique ruthenium dimer.43 Both the NHC and the remnants of the methylidene form this bridge. The reaction is outlined in Scheme 1.2.6.

Scheme 1.2.6 - Decomposition pathway of second generation Grubbs catalyst.

In the presence of excess ethylene, which is the byproduct of some olefin metathesis reactions, an alternate decomposition pathway is viable.42 Such a pathway operates by a similar route to the previous decomposition pathway and indeed may form the previously mentioned decomposition species but ultimately proceeds to a separate product. The formally observed phosphorus ylid further decomposes to a phosphonium chloride and a ruthenium dimer containing a C-H activated NHC ligand with ethylene coordination (Scheme 1.2.7).

Scheme 1.2.7 - Decomposition pathway of second generation Grubbs catalyst from excess ethylene.

1.2.5 Bidentate Olefin Metathesis Catalysts

The first and second generation catalysts are based solely on the incorporation of monodentate auxiliary ligands. The introduction of the third generation of Grubbs catalysts, known commonly as the Hoveyda-Grubbs catalyst and shown in Figure 1.2.5, gave new reactivity and selectivity.45 The Hoveyda-Grubbs catalysts, of which there are many variations, contain no auxiliary phosphine ligand. The benzylidene fragment forms a pseudo-bidentate ligand via the ortho substitution of an ethereal group that replaces the phosphine ligand found in the first and second generation Grubbs catalysts. The Hoveyda-Grubbs Catalyst gave drastically diminished yields in yne-ene cross-metathesis, however, it gave dramatically improved yields in the cross-metathesis of electron deficient olefins when compared to the catalytic activity of second generation Grubbs catalysts.45

Figure 1.2.5 - Hoveyda-Grubbs catalyst

While the Hoveyda-Grubbs catalysts may be considered bidentate ligands, the ligand is necessarily removed in the first step of the catalyst turnover and so may not be considered a bidentate auxiliary ligand. Fogg et al. began an extensive study into the preparation and study of catalytic activity of ruthenium based catalysts with bidentate auxiliary ligands.46-51 The application of aryloxides to ruthenium olefin metathesis catalysts illustrated the first highly active group 8 catalyst without incorporating a halide. The complexes, shown in Figure 1.2.6, display comparable catalytic activity to both the first and second generation Grubbs catalysts.

Figure 1.2.6 - The development of olefin metathesis catalysts with pseudohalide bidentate auxiliary ligands

1.2.6 Tridentate Transition Metal Catalysts

Tridentate ligands may adopt either a fac or mer coordination mode about a transition metal center. Meridionally coordinated ligands have recently found greater dominance in transition metal chemistry. Such ligands, which are coordinated to three co-planar adjacent coordination

13 sites, may be called pincer ligands. Tridentate ligands in transition metal chemistry have had a tremendous impact on the isolation of highly reactive species, otherwise unattainable catalysis, and activation of inert substrates. A significant percentage of pincer ligands are supported by phosphorus donors as the outer donors, while the central donor is likely to be an anionic carbon donor of a C-H activated aromatic ring or a nitrogen donor. However, pincer ligands have been prepared which include mixing of boron, carbon, nitrogen, oxygen, silicon, phosphorus, and sulfur among others. The central nitrogen donor is generally a secondary amine or a pyridine ring.52-62

1.2.6.1 Tridentate Ligands in Olefin Metathesis

The vast majority of ruthenium olefin metathesis research and catalysts are based on monodentate ligands. The most obvious examples are the first and second generation Grubbs catalysts and the Schrock catalysts. Furthermore, bidentate ligands have been investigated as described in section 1.3, however, significantly fewer examples exist. Investigations of the application of tridentate ligand towards catalytic olefin metathesis have been extremely sparse. 6 6 The use of Ƞ coordinated arene rings is a unique exception as Ƞ arene rings have seen prolific 6 use as auxiliary ligands for olefin metathesis catalysts. However, the vast majority of Ƞ arene catalysts give poor catalytic activity and selectivity.

The use of true tridentate ligands in the development of olefin metathesis catalysts is rare. Extensive searching of the literature results in only two notable examples of the successful application of tridentate ligands for catalytic olefin metathesis. The first pertains to trispyrazolylborate ligands, a form of scorpionate ligand, as an example of a tridentate ligand which has seen interest towards catalytic olefin metathesis. Trispyrazolylborate ligands are mono-anionic and facially coordinated. The original report of the use of trispyrazolylborate ruthenium coordination complexes for catalytic olefin metathesis was published in 1998 by Grubbs et al.63 The second, published by Erker et al. in 2005, employed O,N,O tridentate dianion ligands.64

Of note is that while the catalytic activity of tridentate based olefin metathesis complexes was observed and lifetime was good, the rate of turnover was slow. Therefore, a strategy for activation of these complexes may need to be considered.

1.2.7 Tridentate Ruthenium Catalysts

Tridenate ruthenium complexes have allowed access to unique and important chemical processes which have not been observed in other transition metal systems. Such processes include material science applications, isolation of unique chemical species, and important catalytic applications. As for material science applications, ruthenium aromatic systems have been proven to be adept in light harvesting for solar cell sensitization.

Significant processes have recently reported made by the group of Milstein et al. through the development and application of new pincer ligand set in ruthenium catalyzed atom economical catalytic transformations. A recent example is the catalytic formation of amides from alcohols and amines with the simultaneous release of dihydrogen. 65 This both produces valuable amides for a variety of applications and dihydrogen which in itself is valuable.

Scheme 1.2.8 - Catalytic synthesis of amides using a ruthenium catalyst.

The catalyst system displayed in Scheme 1.2.8 has also found a number of other uses. These include the activation of ammonia, catalytic hydrogenation of ketones, and peptide synthesis. 66- 70

1.3 Lanxess Project

The work presented herein was sponsored by Lanxess. Lanxess is a leading multinational specialty chemical company. As of the date of this thesis they are the world's leading producer of nitrile-butadiene rubber. Currently, the catalyst utilized for the cross-metathesis modification of nitrile-butadiene rubber is second generation Grubbs catalyst. While second generation Grubbs catalyst has been engineered to perform the cross-metathesis modification of nitrile-butadiene rubber efficiently, the cost associated with the catalyst is significant. This cost is primarily due to intellectual property licensing fees.

The goal of this work was the development of novel olefin metathesis catalysts for the manipulation of nitrile-butadiene rubber. Unlike projects performed in the vast majority of academic laboratories the Lanxess project demanded the development and protection of intellectual property rights. Due to intellectual property considerations all catalysts developed for implementation in the nitrile-butadiene process must be unique and not covered under existing patent literature.

Beginning my Ph.D. I was the first graduate student involved in the search for new olefin metathesis catalysts and sought to develop an approach to solve this problem. A significant volume of patent literature exists involving the use of monodentate and bidentate ligands in catalytic olefin metathesis. However, tridentate ligands have little patent literature. Therefore, we determined a two-pronged approach would be beneficial to tackle the Lanxess project.

First, we sought to develop completely unique monodentate ligands for use in ruthenium based olefin metathesis. Second, we sought to explore the possibility of employing tridentate ligands. The results presented herein evolved from the initial approaches at ligand design and fundamental investigation of ruthenium coordination chemistry. This thesis does not contain industrially significant results but the observations from these fundamental ligand design and ruthenium coordination chemistry projects were used to gain insight into the design on olefin metathesis catalysts.

1.4 Scope of Thesis

The goal of this thesis was the development of novel olefin metathesis catalysts without accompanying patent literature. The project was funded and the overall goal given by Lanxess technical rubber division. The catalysts must be applicable in the cross-metathesis of nitrile-butadiene rubber.

In an effort to develop new olefin metathesis catalysts a two pronged strategy was undertaken and subsequently described in this thesis. First, Chapters 2 and 8 describe the preparation and application of alkylidene-containing ruthenium complexes. In Chapter 2 catalysis was not observed as a unique decomposition reaction was observed.71 In Chapter 8 a successful catalyst was isolated and characterized. It demonstrated activity in catalytic olefin metathesis. Subsequently, in Chapter 3 the ligands applied in Chapter 2 were used as substrates to expand the scope of FLP reductions.72 Since this time FLP reductions were not known to reduce substrates with more than one imine functionality.

Chapters 4 and 5 detail the preparation, characterization, and coordination of a new class of heterocyclic phosphinimine ligands. Chapter 4 describes a modular approach to the synthesis and the preparation of a library of ligands. Furthermore, the stability of the ligands was considered in Chapter 4. Chapter 5 describes the coordination of the heterocyclic phosphinimines to gold and silver.73

Chapter 6 describes a template synthesis of new P,N bidentate ligands using phosphino-imines. The reaction was considered and in Chapter 7 the new complexes were tested for transfer hydrogenation.74

Chapter 8 is a preliminary investigation into the application of phosphinimine pincer ligands towards ruthenium olefin metathesis catalysts. An example of an active catalyst is described and preliminary catalytic results are presented.

The work described herein was completed solely by the author with the exception of the beginning of the work in chapter four which was completed together with a exchange student, Christoph Glotzbach. The remaining exception is the elemental analysis which was completed in house by department staff.

Chapter 2 Cyclopropanation of Di-iminopyridine Ligand

2 2.1 Introduction

2.1.1 Bis-iminopyridine catalyst development

In the early 1990s efforts began to further the development of polymerization chemistry based on late metal polymerization catalysis and the advances made with alpha-diimine catalysts. Concurrent studies by both Brookhart and Gibson developed 2,6-bis(imino)pyridyl ligands, [N3], for late metal catalysis.75,76 The synthesis of 2,6-bis(imino)pyridyl ligands, as shown in Scheme 2.1.1, is straightforward, however, and gives varying yields, sometimes extremely low.

Scheme 2.1.1-Ligand Development.

The bulk of the studies based on 2,6-bis(imino)pyridyl ligands, completed in the 1990s, focused on applications towards olefin polymerization catalysis. Initial studies concentrated primarily on Co and Fe chemistry (Scheme 2.1.2).75,77-79 The catalysts synthesized gave exceptional polymerization activity of alpha-olefins. Since this time, a significant amount of work has been completed in this field. One such study was to determine if the imine fragment was a requirement for the catalytic activity or if steric effects were more influential.

Scheme 2.1.2-Polymerizaton Catalysts.

While the original work focused primarily on Co and Fe polymerization chemistry, more recently a significant amount of interest has been shown in small molecule Fe activation chemistry. Chirik et al. have employed [N3]Fe complexes for catalytic olefin hydrogenation, hydrosilylation, and cycloaddition reactions.80-83 While these ligands have induced remarkable catalytic reactivity, they display substantial non-innocent behavior. The non-innocence may be observed with respect to deprotonation reactions, alkylation, and participation in redox reactions.84-87 For instance, Blackmore et al. demonstrated that in the presence of MeLi, methyl addition to the pyridine nitrogen was facile along with the coordination of a solvated lithium cation.88 Furthermore, it has been shown that both imine fragments are not necessarily coordinated in the presence of additional donors.89

2.1.2 Ruthenium Bis-iminopyridine Chemistry

In 1999, the first report appeared of the coordination chemistry of 2,6-bis(imino)pyridine ligands with ruthenium.90 The report explored catalytic epoxidation employing Ru(II) complexes. Specifically, the report explored the epoxidation of cyclohexene in the presence of iodosobenzene. The conversions were modest with a greatest turn over number of 32, however, the catalysts were noted to be robust. This piqued our interest toward further exploration of ruthenium [N3] complexes and their potential catalytic applications.

In 2000, an additional report appeared of catalysis using 2,6-bis(imino)pyridine ligands with ruthenium.91 This report focused on the use of [N3]Ru complexes in the catalytic cyclopropanation of styrene with ethyl diazoacetate. In these cases, six-coordinate Ru(II) 2,6- bis(imino)pyridine carbene complexes are thought to effect carbene transfer to the olefin via an intermolecular process. However, the authors cautioned that this may not be true in the presence

19 of halide scavengers as this is known to promote olefin metathesis. Our interest in Ru[N3] complexes focused on the reactivity of Ru[N3] alkylidenes. We believed that since the above mentioned complexes could be synthesized and isolated, our synthetic target should be accessible as well.

2.2 Results and Discussion

As stated in the introduction, the scope of known chemistry relating to tridentate ligands and olefin metathesis is extremely limited. In an effort to develop the chemistry of tridentate olefin metathesis catalysts, we decided to explore the chemistry of 2,6-bis(imino)pyridyl ligands on alkylidene bearing ruthenium complexes. In this work, the reactions of [N3] ligands with Ru sources are undertaken in an effort to develop olefin metathesis pre-catalysts. Furthermore, the

Grubbs alkylidene species, (Cy3P)2RuCl2(CHPh), was reacted with [N3] ligands and the results are described and the observations of unexpected reactions are considered. It is demonstrated that [N3] is not an innocent ancillary ligand in these reactions but rather is cyclopropanated to give a dissymmetric amino-imino-pyridyl ligand.

2.2.1 Direct Catalyst Synthesis

To assess the ability of installing both a 2,6-bis(imino)pyridyl ligands and an alkylidene fragment on a ruthenium center the first synthetic target was 2-1. This complex was first targeted due to the ease of preparation and vacant coordination site. Following Cetinkaya et. al., the ruthenium 2,6-bis(imino)pyridyl ligands complex was first prepared via the reaction of

Ru(PPh3)3Cl2 with 2,6-bis(imino)pyridyl ligands in bromobenzene at room temperature.90(Scheme 2.2.1) This reaction resulted in the isolation of 2-1. The spectroscopic data were consistent with published data. Spectroscopic data showed no remaining coordinated

PPh3 while there was only coordinated [N3]. While this complex was not characterized crystallographically, similar data is available in the Cambridge Structural Database.92 The 1 characteristic H NMR signal of the N=C-CH3 protons was observed at 2.28 ppm. The species is thought to be a monomeric five coordinate species in solution. While the presence of a dimeric structure could not be ruled out, the complex was extremely soluble and the 31P NMR is silent, ruling out the coordination of triphenylphosphine.

Scheme 2.2.1 - Synthesis of 2-1 complexes

While the overall synthetic target was Ru[N3]Cl2=CPh, it was determined that a proof of principle target such as 2-2 was a more expedient goal. N2CHSi(CH3)3, a commercially available reagent for the formation of alkylidenes, was chosen as the first candidate to prepare the desired type of alkylidene (Scheme 2.2.2). Following the addition of two equivalents of

N2CHSi(CH3)3 to a dichloromethane solution of 2-1, the deep red/purple colour of 2-1 slowly turned blue/purple over the course of several hours. Furthermore, the bright yellow colour of the

N2CHSi(CH3)3 was no longer apparent. As with the previously prepared 2-1, the complex

Ru[N3]Cl2[CHSi(CH3)3], 2-2, was not sufficiently crystalline to obtain a single crystal X-ray diffraction analysis. Spectroscopic examination of 2-2 showed a new 1H NMR resonance at 25.7 ppm, characteristic of an alkylidene fragment. Furthermore, the spectroscopic evidence implied C2 symmetry of 2-2 as a single resonance in 1H NMR at 2.65 ppm could be assigned to both of the N=C-CH3 groups.

Scheme 2.2.2-Synthesis of 2-2 olefin metathesis precatalyst

Following the isolation of Ru[N3]Cl2[CHSi(CH3)3], 2-2, the complex was tested for catalytic activity towards olefin metathesis. As previously described in the introduction, the complexes are screened against the three standard substrates, the RCM of diethyldiallylmalonate, the ROMP of 1,5-cyclooctadiene, and the CM of methyl acrylate along with 5-hexenyl acetate. Following

22 standard screening protocols there was limited evidence of catalytic activity. Only marginal activity was noted for the ROMP of 1,5-cyclooctadience. Conversion was low, at typically less than 5%. In an effort to boost catalytic activity the reaction was examined again at 50 °C. This too produced limited catalytic activity. The only observable catalytic activity was again noted to be ROMP of 1,5-cyclooctadiene. The observation of catalytic activity for ROMP of 1,5-cyclooctadiene was not unexpected. ROMP of 1,5-cyclooctadiene is one of the more facile applications of catalytic olefin metathesis which is catalyzed by a vast number of complexes. As opposed to more complicated olefin metathesis applications, ROMP of 1,5-cyclooctadiene is promoted by both advanced and simple catalytic systems.93-95 A sample of such complexes is shown in Scheme 2.2.3.

Scheme 2.2.3-Examples of Ruthenium olefin metathesis catalyst of 1,5-cyclooctadiene.

Following the preparation of complexes of the general formula Ru[N3]Cl2CHSi(CH3)3, it was an open question as to the origin of the lack of catalytic activity. Two obvious sources may be envisioned. First, as indicated in the introduction, the most active olefin metathesis catalysts are five coordinate, 16e- Ru(II) complexes. Complex 2-2 does not fit this criteria as it is a six coordinate, 18e- Ru(II) complex. Secondly, the alkylidene functional group installed on the aforementioned set of complexes is known to be a poor promoter of catalytic olefin metathesis. This is thought to be a mix of both electronic and steric properties. The alkylidene which is typically used to promote catalytic activity is derived from styrene. Unlike the previously used alkylidene N2CSi(CH3)3, the benzyl form is not commercially available and must be installed from N2CH(C6H5) which is known to be thermally unstable. In an effort to circumvent this potentially explosive compound, two different approaches were adopted. The first approach was to synthesize alkylidene bearing Ru species by other known methods and the second was to produce a pre-catalyst directly from first generation Grubbs catalyst.

First, as shown in Scheme 2.2.4, two known synthetic steps were employed in an attempt to produce the desired catalyst system. The first attempt used a methodology developed by Milstein et al. involving a sulfur ylide.96 The second attempt used a propargyl alcohol synthon which has been used to prepare catalysts with similar activity to Grubbs catalysts.97 In both cases, the reactions failed to yield appreciable amounts of the desired products and either yielded an intractable mixture or starting material could be isolated.

Scheme 2.2.4-Failed preparations of new Ru[N3] olefin metathesis catalysts.

2.2.2 Indirect Synthesis

The next attempt to synthesize the desired complex used Grubbs first generation catalyst. The reaction of Grubbs first generation catalyst with various [N3] ligands at room temperature in dichloromethane resulted in an incomplete reaction. The 31P NMR spectrum revealed approximately a 10% yield of an unknown product over the course of 18 hours. Free tricyclohexyl phosphine was observed which accounted for ~10% in addition to one new signal at 13.2 ppm. Additionally, the 1H NMR spectrum showed no additional peak in the range of 15- 25 ppm which discounted the synthesis of the desired product. Furthermore, three peaks between 5.60 and 6.10 ppm in the 1H NMR spectrum were unidentifiable and in a region of the spectra which was not expected for the desired product. It was also noted that any ortho substituted [N3] ligands resulted in reactions with intractable products. It is likely that this is primarily a steric effect as bis(2-methyl)-[N3] is likely to have similar electronic properties as bis(4-isopropyl) [N3].

In an effort to produce a more complete reaction and identify the reaction product, the reaction was completed again at 80°C in benzene (Scheme 2.2.5). The initial purple colour of the reaction mixture changed to a deep blue/purple over the course of 2 hours. The reaction mixture was dried in vacuo and isolated as microcrystalline green crystals. Spectroscopic investigation of the solid revealed NMR signals similar to those observed from the previously incomplete reaction mixture. The 1H NMR spectrum implied dissymmetry as the signal integration for the

N=C-CH3 protons was insufficient. Furthermore, greater than five NMR signals could be assigned to aromatic protons. Finally, a signal at 13.50 ppm could not be assigned to the expected structure and would be more characteristic of a signal corresponding to NH or an aldehyde. The precise nature of the products could only be confirmed via single crystal crystallography studies. Crystallographic data was able to unambiguously determine connectivity as C6H3N(CMeNC6H4R)(CCH2CHPh)(NHC6H5)RuCl2(PCy3).(Figure 2.2.1)

Scheme 2.2.5-Synthesis of 2-3 and 2-4.

For 2-3 the Ru center adopts a pseudo-octahedral geometry. The two chlorides are disposed in a trans arrangement with a Cl-Ru-Cl bond angle of 169.97(6)°. The Ru-Cl bond distances were found to be 2.4099(18) Å and 2.4145(17) Å. The [N3] ligand is disposed in a tridentate fashion meridionally on the Ru center in a plane perpendicular to the ruthenium chloride bonds. Finally, the remaining tricyclohexyl phosphine is disposed trans to the pyridine of the [N3] ligand. The corresponding Ru-N and Ru-P distances are 2.001(5) Å and 2.4480(17) Å, respectively. The spectroscopically observed dissymmetry was resolved by the observation that one imino-fragment is reduced to amine with concurrent formation of a cyclopropane ring. It is probable that this would be derived from the alkylidene fragment and the carbons alpha- and beta- to the imine nitrogen. The resulting Ru-N distances for the imino and amino-N atoms are 2.056(5) Å and 2.239(5) Å, respectively. This difference reflects the lower basicity of the amino-N in comparison to the imine-N. The C-C bond distances within the cyclopropane ring

25 are 1.515(9) Å, 1.539(9) Å, and 1.485(9) Å, with C-C-C bond angles of 58.2(4)°, 60.1(4)°, and 61.7(4)°, reflecting the ring strain.

Analogously, the structure was confirmed by crystallographic study for 2-4. The structures of 2-3 and 2-4 share similar general connectivity, therefore, only selected differences are relevant. The Ru center adopts a pseudo-octahedral geometry. The two chlorides are disposed in a trans arrangement with a Cl-Ru-Cl bond angle of 169.484(15)°. The Ru-Cl bond distances were found to be 2.4134(5) Å and 2.4198(5) Å. The spectroscopically observed dissymmetry was once again accounted for by the observation that one imino-fragment was reduced to an amine with concurrent formation of a cyclopropane ring. The resulting Ru-N distances for the imino and amino-N atoms are 2.0583(16) Å and 2.2512(16) Å, respectively. This difference reflects the lower basicity of the amino-N in comparison to the imine-N. Also, of note is that there is no statistical difference in the Ru-N bond differences between 2-3 and 2-4 even with a slightly more basic ligand on complex 2-4. The C-C bond distances within the cyclopropane ring are 1.509(3) Å, 1.542(3) Å and 1.494(3) Å, with C-C-C bond angles of 58.63(13)°, 59.57(13)° and 61.80(13)°, reflecting the ring strain.

Figure 2.2.1-POV-Ray Depiction of cyclopropanated Ru[N3] complexes 2-3 and 2-4 respectively. C: black, Ru: orange, Cl: green, P: orange, N: aquamarine, H: grey.

2.2.3 Consideration of Mechanism

The mechanism of formation of 2-3 and 2-4 is the subject of speculation. Of note is the

Ru[N3]Cl2CSi(CH3)3 species, 2-2, we were able to prepare. As well, Bianchini et al. prepared 91 2,6-bis(imino)pyridyl ligand Ru complexes of the form [N3]RuCl2(CHCO2Et). Thus it is reasonable to suggest that an analogous species could be formed initially upon reaction of the [N3] ligand with the Grubbs first generation Ru-alkylidene precursor. However, it is also noteworthy that tautomerization of such ligands to an exocyclic enamine has been previously observed in several systems.88 It can be hypothesized that transient generation of an enamine combined with the more reactive alkylidene fragment results in cyclopropanation accounting for the formation of 2-3 and 2-4.

The first of two envisioned possibilities was an intramolecular process. This may be facilitated via the transient formation of an enamine tautomer and a further dative interaction with the Ru center. The cyclopropanation would then follow the known route for a ruthenium center. This postulate is illustrated in Scheme 2.2.6. Another possibility is a bimolecular route. This possibility does not require transient binding of an enamine. While possibility of an enamine has been shown previously, the possibility of transient binding has not. It is noteworthy that the reaction is completed under thermal duress so loss of metal alkylidene and subsequent attack on coordinated ligand may be possible.

Scheme 2.2.6 - Proposed mechanism of a bis(imino)pyridine ruthenium complex cyclopropanation

It is reasonable to suggest that the lesser steric congestion favours cyclopropanation of the enamine over olefin metathesis. This is supported via the general observation, as noted in several publications, that a six coordinate Ru(II) complex, in the presence of substrate and stoichiometric alkylidene source, is, in general, an exceptional cyclopropanation catalyst.98-101

These mechanistic postulates could not be unambiguously confirmed. One notable problem is the inherent instability of the first generation Grubbs catalysts in solution, especially at elevated temperatures. While the reaction tends to be relatively high yielding, several prominent side products could be observed via NMR spectroscopy but not identified.

2.3 Conclusions

The ruthenium 2-1 and 2-2 complexes based on 2,6-bis(imino)pyridyl ligands have been investigated. Ruthenium [N3] complexes incorporating alkylidene fragments have been synthesized and were determined to not catalyze olefin metathesis at ambient conditions. In an effort to ease the synthesis of such complexes the direct reaction of [N3] ligands with Grubbs first generation catalyst was explored. It was observed that an unexpected reaction occurred to generate a coordinated, cyclopropanated 2,6-bis(imino)pyridyl ligand. The general implications towards cyclopropanation of imines were considered and found to be not easily attainable.

Further investigation towards catalytic cyclopropanation of imine-enamines should be screened with known cyclopropanation catalysts and optimized conditions.

To put this finding in context, we note that cyclopropanation of olefins using ethyl diazoacetate has been previously described using a variety of Ru precursors.102-104 In addition, Dixneuf and coworkers105 demonstrated catalytic formation of alkenylbicyclo[3.1.0]-hexanes from enynes and

N2CHCO2Et or N2CHPh using Cp*RuCl(COD) as the catalyst precursor. Suitably modified ligand set variants have been employed to effect catalytic asymmetric cyclopropanation.106-115 Despite these previous developments cyclopropanation has not been reported using Grubbs-type alkylidene complexes and thus compounds 2-3 and 2-4 are the first examples that result from transfer of Ru-bound alkylidene to transient enamines. The stoichiometric nature of the present reactions may result from the “non-innocent” nature of the [N3]Ru complexes. The participation of the enamine tautomer in chemistry has been previously reported by Blackmore et al.88 More recently, Berry and coworkers showed that low-valent [N3]Ru complexes delocalize electron density from the metal center further demonstrating the “non-innocent” electronic nature of these ligands.116

2.4 Experimental Section

2.4.1 General Considerations

All manipulations were carried out under an atmosphere of dry, O2-free N2 employing a MBraun glove box and a Schlenk vacuum-line. Solvents were purified with a Grubbs-type column system manufactured by Innovative Technology and dispensed into thick-walled Schlenk glass flasks equipped with Teflon-valve stopcocks (pentane and CH2Cl2), or were dried over the appropriate agents and distilled into the same kind of storage flasks (C6H5Br). All solvents were thoroughly degassed after purification (repeated freeze-pump-thaw cycles). The deuterated solvent was dried over the appropriate agent, vacuum-transferred into storage flasks with Teflon stopcocks and degassed accordingly (CD2Cl2). Pentane was stored over a potassium mirror, while bromobenzene and dichloromethane were stored over 4Å molecular sieves. 1H, 13C, and 31P NMR spectra were recorded at 25 °C on Varian 300 and 400 MHz and Bruker 400 MHz spectrometers. Chemical shifts are given relative to SiMe4 and referenced to the residual solvent 1 13 31 signal ( H, C) or relative to an external standard ( P: 85% H3PO4). Chemical shifts are reported in ppm and coupling constants as scalar values in Hz. Combustion analyses were performed in house employing a Perkin-Elmer CHN Analyzer. 2,6-bis(imino)pyridyl ligands and phenyldiazomethane were synthesized according to literature procedures; all other reagents were purchased from Aldrich.75,117 Liquids were stored over 4Å molecular sieves, gases and solutions were used as received.

2.4.2 Synthetic Procedures

Synthesis of 2-1: [RuCl2(p-cymene)]2 (306 mg, 0.50 mmol) and [N3]Mes (210 mg, 0.55 mmol) were dissolved in bromobenzene (5 ml) and the solution heated to 140 °C for 1 hour. The reaction changed colour to deep purple, was cooled to room temperature and the solvent removed in vacuo. The resulting solid was washed with pentane (15 ml) and dried.

1 3 Yield: (85 %, 0.43 mmol, 242 mg) H NMR (CD2Cl2):7.89 (d, JHH = 7.9 Hz, 2H, py), 7.64(t, 3 JHH = 7.9 Hz, 1H, py), 6.92(s, 4H, Ph), 2.63(s, CH3CN, 6H), 2.28(s, 6H, CH3Ph), 2.18(s, 12H, o-CH3Ph)

Synthesis of 2-2: 2-1 (1 eq, 20 mg, 0.03 mmol) and N2CHSi(CH3)3 (2 eq, 8 mg, 0.06 mmol) were mixed in d2-DCM (2 ml) in an NMR tube and allowed to stand for 1 hour while being shaken every 10 minutes. The reaction turned darker purple. The NMR tube was vented and resealed. The NMR was acquired.

1 Yield determined by NMR ( 60 %) H NMR (CD2Cl2): 25.10 (s, 1H, CHSi(CH3)3), 7.81

(d, 2H, py), 7.59(t, 1H, py), 7.07(s, 4H, Ph), 2.86 (s, 6 H, CH3CN), 2.28(s, 6H, CH3Ph), 2.18(s,

12H, o-CH3Ph), 0.82 (s, 9H, CHSi(CH3)3)

Synthesis of 2-2: (Cy3P)2RuCl2(CHPh) (164 mg, 0.20 mmol) was dissolved in benzene (5 mL) before a benzene solution (5mL) of 2,6-bis(1-phenyliminoethyl)pyridine (65 mg, 0.20 mmol) was added. The reaction was sealed in a Teflon capped reaction tube and heated at 80°C for 36 h. The reaction colour changes from purple to deep green. The reaction was cooled to 25oC and the benzene was removed in vacuo. The solid was dissolved in a minimum amount of dichloromethane (2-3 mL) to which pentane (15 mL) was added. The solution was cooled to -35oC overnight after which large green crystals formed. Subsequent removal of the supernatant, and recrystallization of the remaining crude product yielded a further batch of green crystals.

1 3 Yield: (71 %, 0.14 mmol, 121 mg) 1: H NMR (CD2Cl2): 8.12 (d, JHH = 6.9 Hz, 1H, Ph), 3 3 7.75(d, JHH = 7.4 Hz, 1H, Ph), 7.53 (d, JHH = 6.5 Hz, 2H, Ph), 7.12-6.7 (m, 11H, Ph), 6.07 (d, 3 3 JHH = 7.9 Hz, 1H, Ph), 5.88 (d, JHH = 7.3 Hz, 1H, Ph), 5.67 (s, 1H, Ph), 3.16-2.86 (m, 3H, Cy), 3 2.50 (t, JHH = 9.1 Hz, 1H, Ph(CH)py), 1.89 (s, 3H, CH3), 1.8-1.5 (m, 14H, Cy), 1.41 (d, 1H, 31 1 CHCH2), 1.40 (d, 1H, CHCH2), 1.4-1.0 (m, 13H, Cy ), 0.8-0.7 (m, 3H, Cy) P{ H NMR 13 (CD2Cl2) : 12.81 C NMR (CD2Cl2) (partial): 131.7 (Ph), 131.4 (Ph), 125 (Ph), 124.3 (Ph), 123

(Ph), 122.6 (Ph), 115.3 (Ph), 41.7 Ph(CH)py), 22.8 (CHCH2). C,H,N analysis calc. for

C46H58Cl2N3PRu C, 64.55; H, 6.83; N, 4.91. Found: C, 64.54; H, 7.04; N, 4.76.

Synthesis of 2-3: (Cy3P)2RuCl2(CHPh) (164 mg, 0.20 mmol) was dissolved in benzene (5 mL) before a benzene solution (5mL) of 2,6-Bis(1-(4-iPr-phenyl)iminoethyl)pyridine (65 mg, 0.20 mmol) was added. The reaction was sealed in a Teflon capped reaction tube and heated at 80°C for 36 h. The reaction colour changes from purple to deep green. The reaction was cooled to 25oC and the benzene was removed in vacuo. The solid was dissolved in a minimum amount of dichloromethane (2-3 mL) to which pentane (15 mL) was added. The solution was cooled to -35oC overnight after which large green crystals formed. Subsequent removal of the supernatant, and recrystallization of the remaining crude product yielded more green crystals.

1 3 Yield: (62 %, 0.12 mmol, 116 mg) H NMR (CD2Cl2) : 8.13 (d, JHH = 6.7 Hz, 1H, Ph), 7.74 (d, 3 3 3 JHH = 6.4 Hz, 1H, Ph), 7.60 (d, JHH = 5.7 Hz, 2H, Ph), 7.25-6.86 (m, 8H, Ph), 6.73 (d, JHH = 3 3 7.1 Hz, 1H, Ph), 6.08 (d, JHH = 7.2 Hz, 1H, Ph), 5.85 (d, JHH = 7.3 Hz, 1H, Ph), 5.69(s, 1H, Ph), 3 3.25-2.9 (m, 3H, Cy), 2.66 (m, 2H, CH(CH3)2), 2.51(t, JHH = 9.2 Hz, 1H, Ph(CH)py), 2.4-2.1

(m, 3H, Cy), 1.96 (s, 3H, CH3), 1.9-1.5 (m, 18H, Cy), 1.3-1.2 (m, 6H, Cy), 0.9-0.8 (m, 3H, Cy), 31 1 13 1.13 (m, 12H, CH(CH3)2), 1.43 (m, 2H, CHCH2), P{ H} NMR (CD2Cl2) : 13.22 C NMR

(CD2Cl2) (partial) : 131.8 (Ph), 131.2 (Ph), 123 (m, Ph), 115.6 (Ph), 41.9 Ph(CH)py), 22.4

(CHCH2), 18.6 (CH3). C,H,N analysis calc. for C52H69Cl2N3PRu C, 66.44; H, 7.51; N, 4.47. Found: C, 66.54; H, 7.79; N, 4.60.

2.4.3 X-Ray Crystallography

2.4.3.1 X-Ray Data Collection and Reduction

Crystals were coated in Paratone-N oil in the glovebox, mounted on a MiTegen Micromount and placed under an N2 stream, thus maintaining a dry, O2-free environment for each crystal. The data were collected on a Bruker Apex II diffractometer. Data collection strategies were determined using Bruker Apex software and optimized to provide >99.5% complete data to a 2θ value of at least 55°. The data were collected at 150(±2) K for all. The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. Data were corrected for absorption effects using the empirical multi-scan method (SADABS).

2.4.3.2 X-Ray Data Solution and Refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations. 118 The heavy atom positions were determined using direct methods employing the SHELXTL direct methods routine. The remaining non-hydrogen atoms were located from successive difference Fourier map calculations. The refinements were carried out by using full-matrix least squares techniques 2 2 2 on F, minimizing the function  (Fo-Fc) where the weight  is defined as 4Fo /2 (Fo ) and Fo and Fc are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C-H bond length of 0.95 Å. H-atom temperature factors were fixed at 1.20 times the isotropic temperature factor of the C-atom to which they are bonded. The H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance.

2.4.3.3 Table of Crystallographic Data

Table 2.4.1 - Select Crystallographic Data for 2-1 and 2-2 2-1 2-2

Formula C46H57Cl2N3PRu(2 CH2Cl2)(0.5 H20) C52H69Cl2N3PRu(2 C6H6) Formula weight 1034.75 1173.51 Crystal System triclinic triclinic Space group P-1 P-1 a(Å) 12.5917(8) 12.8962(7) b(Å) 12.8624(7) 13.6877(8) c(Å) 15.5806(10) 15.3752(9) α(deg) 91.817(3) 95.924(4) β(deg) 103.746(4) 92.651(3) γ(deg) 93.184(3) 106.606(3) V(Å3) 2444.7(3) 2578.8(3) Z 2 2 Temp. (K) 150 150 d(calc)gcm-1 1.406 1.511 Abs coeff,μ,mm-1 0.719 0.847 Data collected 29008 83108 2 2 DataFO >3(FO ) 4584 14451 Variables 551 603 R 0.0552 0.0482

Rw 0.1445 0.1076 GOF 1.012 1.016

Chapter 3 Metal-Free Hydrogenation of Di-Imines

3 3.1 Introduction

3.1.1 Hydrogenation

The addition of molecular hydrogen to an unsaturated organic molecule defines a process known as hydrogenation. This seemingly facile transformation is used in a very diverse range of applications. Indeed, the breadth of the application of this chemical process is unparalleled in chemical industry. Large scale commercial use of hydrogenation is required for the upgrading of crude oil, production of bulk commodity materials, as well as fine chemicals used in the food, agricultural and pharmaceutical industries.119 The atom economy and cleanliness of the transformation makes hydrogenation “arguably the most important catalytic method in synthetic organic chemistry both on the laboratory and the production scale".120

Catalytic hydrogenation of unsaturated compounds began with the discovery by Sabatier in 1897 that traces of nickel could mediate the catalytic addition of hydrogen to olefins. 121 This discovery of the use of Ni as a heterogeneous catalyst culminated in a share of the 1912 Nobel Prize with Grignard. The onset of organometallic chemistry and the discoveries of Ru and Rh based hydrogenation catalysts by Wilkinson and others in the 1960s prompted the evolution of homogeneous transition metal based hydrogenation catalysts for a variety of substrates. 122,123 These catalysts may operated by the interaction of hydrogen with the metal to effect oxidative addition affording intermediate dihydride complexes.124 In the 1990s Noyori discovered that transition metal complexes incorporating amido-ligands effect heterolytic cleavage of hydrogen. 125-130 This results in a metal hydride and the protonation of the amide ligand to give an amine. Outer-sphere transfer of the proton and hydride to a substrate affords a distinct strategy to hydrogenation.128,131 A third divergent strategy for the hydrogenation of polar unsaturated molecules is the use of a stoichiometric reducing agent.

Scheme 3.1.1- Initial FLP hydrogenation catalyst, (2,4,6-Me3C6H2)2P(C6F4)B(C6F5)2, and general scheme of "base free" FLP hydrogenation, respectively.

Subsequently in 2006, Stephan et al. reported the first reversible activation of H2 by a non-metal system with the phosphine-borane species (2,4,6-Me3C6H2)2P(C6F4)B(C6F5)2 (Scheme 3.1).132Such reactivity is now widely known as frustrated Lewis pair (FLP) chemistry. Frustrated Lewis pair chemistry is the result of the unquenched reactivity sterically encumbered Lewis acids and bases which are prohibited from forming classic Lewis acid/base adducts. The unquenched reactivity allows for the activation and/or functionalization of small molecules. Subsequently, in 2007, the catalytic hydrogenation of imines with frustrated Lewis pairs was discovered. The discovery of metal-free hydrogenation by FLPs prompted the suggestion that when using a sterically encumbered basic substrate, it should be possible to effect hydrogenation using only a catalytic amount of Lewis acid. Indeed, the combination of a catalytic amount of

B(C6F5)3 (Scheme 3.1.1) with an imine substrate under H2 with mild heating was shown to afford the corresponding amines, which were isolable in high yields.133

3.1.2 Di-Imine Chemistry

While the usefulness of di-imine ligands is beyond question and has been the subject of numerous publications, it is not in the scope of this work.134-138 However, another use of di-imine ligands is as a synthon in the preparation of N-Heterocyclic carbenes.134,139 N-Heterocyclic carbenes are now ubiquitous in transition metal chemistry. Of particular interest are the 1,3-bis(2,4,6-trimethylphenyl)imidazolinium chloride (SIMes), 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride (SIDipp) ligands. The synthesis of these ligands involves the stoichiometric reduction of the di-imine fragment. Typically this reductant is a stoichiometric amount of sodium borohydride. This reduction then facilitates the closure of a diamine to form a heterocyclic framework (Scheme 3.1.2).139,140

Scheme 3.1.2-Typical synthesis of an Dihydroimidazolium salt.

3.1.3 Bis(imino)pyridine Chemistry

In the early 1990s efforts to further the development of polymerization chemistry based on late metal polymerization catalysis and the advances made with alpha-diimine catalysts began. Concurrent studies by both Brookhart and Gibson developed bis(imino)pyridine ligands for late metal catalysis.75,76 The syntheses of bis(imino)pyridine ligands, as shown in Scheme 3.1.3, is straight forward. However, yields vary and are sometimes extremely low.

Scheme 3.1.3-Bis(imino)pyridine Ligand Development.

The bulk of the studies based on bis(imino)pyridine ligands completed in the 1990s focused on applications towards olefin polymerization catalysis. Initial studies concentrated primarily on Co and Fe olefin polymerization chemistry.75 The catalysts synthesized gave exceptional catalytic polymerization activity of alpha-olefins. Since this time, a significant amount of work has been completed in this field. One such study was to determine if the imine fragment was a requirement for the catalytic activity or if steric effects were more influential.

While the original work focused primarily on Co and Fe olefin polymerization chemistry, more recently a significant amount of interest has been shown in Fe chemistry for small molecule activation and organic transformations. Chirik et al. have employed [N3]Fe complexes for catalytic olefin hydrogenation, hydrosilylation, and cycloaddition reactions.80 While these ligands have induced remarkable catalytic reactivity, they are intrinsically non-innocent. The non-innocence may be observed with a variety of transformations such as deprotonation reactions, alkylation, and redox chemistry. For instance, Blackmore et al. demonstrated that in the presence of MeLi [N3] ligands yielded a mixture containing two products. The products were identified as the methylation of a [N3] ligand to produce a N-methylated pyridine ring and a deprotonation reaction to capture an enamine along with the coordination of solvated lithium cations.88 Furthermore, it has been shown that both imine fragments are not necessarily coordinated in the presence of additional donors.89

While the imine system, described immediately previous, has been subjected to extensive research, the corresponding bis(amino)pyridine, shown in figure 3.1.1, has not been explored as attempts to prepare the ligand have been unsuccessful. This is noted in several publications.141 With this in mind, analogues have been prepared to assess the potential properties of this bis(amino)pyridine and are described below.

Figure 3.1.1- Desired bis(amino)pyridine which was not possible to synthesize.

In 1985, it was shown that the corresponding N-alkyl molecules could be prepared.142 The Schiff base condensation of 2,6-diacetylpyridine with primary amines was possible. An example is shown in Scheme 3.1.4. In this study, the bis(imino)pyridines were reduced to the corresponding bis(amino)pyridines with sodium borohydride.142

Figure 3.1.2 - Reduced alkyl bis(imino)pyridines.

Following this, in 1996, it was shown that bis(amino)pyridines could be directly synthesized from the substitution of 2,6-bis(bromomethyl)-pyridine by primary amines (Scheme 3.1.5).143 However, this is not a viable synthetic strategy for the desired product. While, 2,6-bis(bromomethyl)-pyridine is a commercially available compound and has a well known, high yielding synthesis, neither of these are available for 2,6-bis(1-bromoethyl)pyridine.

Scheme 3.1.4 – Synthesis of aromatic bis(amino)pyridines.

In 2011, Tay et al. renewed the effort to synthesize bis(amino)pyridines.141 Noting the 1985 report by Lavery et al., the reduction of bis(imino)pyridines was attempted. The reaction was unsuccessful and a quantitative recovery of starting material was reported. In an effort to synthesize an additional analogue, they observed that for bulky bis(imino)pyridines the reaction with AlMe3 produced the bis-methylated bis(amino)pyridine species.(Scheme 3.1.6)

Scheme 3.1.5-Concurrent alkylation and reduction of bis(imino)pyridines.

With these results in mind and the recent advent of FLP chemistry the potential reduction of bis-imines was investigated.

3.2 Results and Discussion

3.2.1 Di-imine Reduction

As B(C6F5)3 has been shown to catalytically reduce imines, it was envisioned that a similar procedure could promote the reduction of di-imines. If this transformation proved possible, then the investigation into synthesizing N-heterocyclic carbenes with the removal of stoichiometric reduction would be studied.

Among the most common precursors to N-heterocyclic carbenes are 1,3-bis(2,4,6- trimethylphenyl)imidazolinium chloride (SIMes), 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride (SIDipp), 1,3-diisopropylimidazolinium chloride (SIiPr), and 1,3-dicyclohexylimidazolinium chloride (SICy), therefore, these were our initial targets.

Figure 3.2.1 - Diimines for the preparation of saturated NHCs.

The di-imines shown in Scheme 3.2.1 were prepared according to literature procedures.144 The crystals obtained from the reaction of the corresponding amine with glyoxal were filtered and dried in vacuo. The crystals were then dissolved in a toluene solution containing 5 mol % of

B(C6F5)3. After the addition of B(C6F5)3, the imine substrates containing aryl substituents did not change in appearance while the substrates containing alkyl substituents formed a deep red solution. The reduction may be carried out using two protocols, first, using mild pressures in a Schlenk tube, second, using high pressures in a Parr reactor.

In the first protocol, pressures of approximately 4 atm of hydrogen and a temperature of 120°C were employed and required a reaction time of 12 hours. Following the reaction the Schlenk tube was cooled, vented, and the toluene removed slowly. Slow removal of the solvent produced X-Ray quality crystals which were determined to be analytically pure after a wash with cold pentane. D was the exception as no reduction was observed. (Scheme 3.2.2)

Similar results were observed using a high pressure Parr reactor. The Parr reactor was pressurized to approximately 100 atm of hydrogen and heated to a temperature of 120°C. The loading of catalyst B(C6F5)3 of 5% remained while identical amounts of substrates were tested. The reduction was determined to be complete for all substrates, except SIiPr, in 2 hours.

Scheme 3.2.1 Reduction of Di-Imines with B(C6F5)3

In an effort to synthesize N-heterocyclic carbenes two approaches were attempted. First, isolated samples of pure diamines purified from the reduction reaction were used. Secondly, samples directly from the catalytic reduction without purification were employed. Following known reaction protocols for the cyclization of diamines to form SIMes, SIDipp, and SICy, high yielding pure products could be isolated.144 Cumulative yields from both reduction and cyclization were typically in excess of 95% over the course of several trials. Boron or fluorine contamination of the N-heterocyclic carbenes could not be detected by NMR spectroscopic examination and acceptable elemental analysis could be obtained. Figure 3.2.1 shows an 1H NMR spectrum of a sample of SIMes obtained from a one-pot synthesis with subsequent diethyl ether washing. This result demonstrates that catalytic reduction may be used in place of a stoichiometric reductant, such as sodium borohydride, in the synthesis of N-heterocyclic carbenes.

Figure 3.2.2- 1H NMR spectrum of one pot synthesis of N heterocyclic carbene SIMes.

3.2.2 Bis(imino)pyridine Reduction

As B(C6F5)3 has been shown to catalytically reduce imines and di-imines, it was envisioned that a similar procedure could promote the reduction of bis(imino)pyridines. Following a similar reaction protocol a recrystallized sample of (2,6-diisopropylphenyl)bis(imino)pyridine was dissolved in 5 ml of toluene. To this mixture was added a sufficient amount of B(C6F5)3 for a 5 mol% solution and the reaction vessel charged with 4 atm of H2 pressure. As opposed to the samples of di-imines there was no immediate colour change. Following the reaction over the course of 12 hours the NMR spectrum showed marked difference indicating the formation of 3-2. A new peak in the 1H NMR spectrum appeared at 4.39 ppm corresponding to an amine NH. Furthermore the 1H NMR spectrum showed a newly formed quartet at 4.29 ppm. The NMR spectrum was symmetrical in nature confirming that a reaction occurred at both imine centres. The former results indicate the hydrogenation of both imine fragments and this observation was further confirmed with a single crystal X-Ray structure (Figure 3.2.2).

Scheme 3.2.2 - Reduction of di-imines with B(C6F5)3

The structure was unexceptional except to note the N-C bonds lengths. The literature value for the imine N-C bonds are 1.284 Å and 1.272 Å while it was determined to be 1.4820(11) Å and 1.4731(12) Å for 3-1.77 The average lengthening of 0.20 Å may be attributed to the reduction of the imine to an amine.

Figure 3.2.3- POV Ray Depiction of 3-1. C: black, N aquamarine, H grey.

3.2.3 Bis(amino)pyridine Coordination

The above results demonstrated the successful synthesis of reduced bis(imino)pyridine ligands. The reduced bis(imino)pyridine was dissolved in 5mL of toluene and added to a toluene solution 1 of Zr(CH2Ph)4. The clean formation of 3-7 was observed by H NMR spectroscopy. The resulting product was not sufficiently crystalline to enable the collection of single crystal X-ray data. However, the spectroscopic results were similar to those observed by Tay et al. as to conclude the successful coordination of 3-7 to zirconium.141

Scheme 3.2.3 - Coordination of reduced BIP to Zr

In order to prepare a selective polymerization catalyst an enantiopure bis(amino)pyridine ligand must be obtained. However, the resulting bis(amino)pyridines are not reduced selectively in an enantioselective process. Progress in FLP chemistry, at this time, did not enable the enantioselective reduction. Current enantioselective FLPs could not be applied to this goal. Enantioselective isolation of bis(amino)pyridine ligands would allow access to a wide variety of polymerization applications beyond the current basic application towards ethylene polymerization chemistry.

3.3 Conclusions

The reduction of compounds having more than one imine functional group has been investigated and found to be high yielding and allows for the generation of quantitative yields provided sufficient steric bulk is present. The reduction protocol has been found to produce the first catalytic reduction of di-imines and avoids the use of stoichiometric reductants such as NaBH4 or

LiAlH4. Furthermore, the crude reduction products were found to be useful for the "one-pot" synthesis of NHCs.

Bis(imino)pyridines have found prolific use in transition metal chemistry, however, the reduction of such ligands was found to be impossible. It was determined herein that FLP reduction protocols may be applied to their reduction giving way to near quantitative yields and the first report of successful reduction. A single example was applied to the coordination chemistry of Zr. This proof of principle is an entryway into the potential applications of novel Zr coordination complexes.

While the reduction of the above mentioned compounds produces synthetically useful species the application of asymmetric catalysis would be extremely beneficial. While this is desirable the current FLP catalysts were unable to perform an enantioselective reduction at the time this work was completed. It seems likely this will be possible in the near future and this would allow for the synthesis of enantio-pure NHCs and reduced BIPs. The use of chiral NHCs is well known and the use of chiral bis(amino)pyridines may be applicable in early metal polymerization chemistry.

3.4 EXPERIMENTAL SECTION

3.4.1 General Considerations

All manipulations were carried out under an atmosphere of dry, O2-free N2 employing a MBraun glove box and a Schlenk vacuum-line. Solvents were purified with a Grubbs-type column system manufactured by Innovative Technology and dispensed into thick-walled Schlenk glass flasks equipped with Teflon-valve stopcocks (toluene, pentane and CH2Cl2), or were dried over the appropriate agents and distilled into the same kind of storage flasks (C6H5Br). All solvents were thoroughly degassed after purification (repeated freeze-pump-thaw cycles). The deuterated solvent was dried over the appropriate agent, vacuum-transferred into storage flasks with Teflon stopcocks and degassed accordingly (CD2Cl2). Pentane and toluene were stored over a potassium mirror, while bromobenzene and dichloromethane were stored over 4Å molecular sieves. NMR spectra were obtained on a Bruker Avance 400 MHz spectrometer and spectra 1 13 11 19 were referenced to residual solvent ( H, C) or externally ( B; BF3·OEt2, F; CFCl3). Chemical shifts are reported in ppm and coupling constants as scalar values in Hz. Combustion analyses were performed in house employing a Perkin-Elmer CHN Analyzer. 2,6-bis(imino)pyridines and diimine ligands were synthesized according to literature procedures; B(C6F5)3 was purchased from Boulder Scientific Company; all other reagents were purchased from Aldrich. Liquids were stored over 4Å molecular sieves, gases and solutions were used as received

3.4.2 High Pressure Hydrogenations

In a N2 filled glove box, imine substrate (0.7 mmol) was weighed in a vial and dissolved in toluene (2 mL). To this was added catalyst (5 mol%, 0.0035 mmol) and the imine/catalyst solution was thoroughly mixed then transferred to a Parr pressurized reactor equipped with a magnetic stir bar. The reactor was assembled and sealed inside the glovebox. Once removed, it was further tightened. The reactor and its contents were purged 3x with H2 which was first passed through a gas purifier (Matheson Model 8010). The reactor was then heated to the appropriate temperature, pressurized with H2 and stirred for the listed reaction time. Conversions are determined through 1H NMR spectroscopy.

3.4.3 Low Pressure Hydrogenations

In a N2 filled glove box, imine substrate (0.7 mmol) was weighed in a vial and dissolved in toluene (5 mL). To this was added catalyst (5 mol%, 0.0035 mmol) and the imine/catalyst solution was thoroughly mixed then transferred to a 100 ml thick walled Schlenk tube with a teflon tap and a magnetic stir bar. The vessel was assembled and sealed inside a glovebox. Once removed the solvent was thoroughly degassed (repeated freeze-pump-thaw cycles). The vessel was filled with H2 which was first passed through a gas purifier (Matheson Model 8010). The reactor was then heated to the appropriate temperature and stirred for the listed reaction time. Conversions are determined through 1H NMR spectroscopy.

3.4.4 Table of Conversion

Table 3.4.1 - FLP reduction conversions of compounds with 2 imines

Substrate Catalyst T (°C) P (atm) Time Yield (mol %) (h) (%)

(CH2=NC6H2Me3)2 5 120 4 12 99

(CH2=NC6H2Me3)2 5 120 100 2 99

i (CH2=NC6H4 Pr)2 5 120 4 12 99

i (CH2=NC6H4 Pr)2 5 120 100 2 99

(CH2=NC6H11)2 5 120 4 12 99

(CH2=NC6H11)2 5 120 100 2 99

(C5H3N)(MeCHNH(C6H3-2,6-iPr2)2 5 120 4 12 99

(C5H3N)(MeCHNH(C6H2-2,4,6-Me)2 5 120 4 12 99

(C5H3N)(MeCHNH(C6H4-4-iPr)2 5 120 4 12 99

3.4.5 Analysis

1 Synthesis of 3-1 (C5H3N)(MeCHNH(C6H3-2,6-iPr2)2: H NMR

(C6D5CD3): 7.04-7.17 (Ar, 10H), 6.81 (py, 1H), 6.46 (py, 2H), 4.39 3 (br, 2H, NH), 4.29 (br, 2H, CH(CH3)), 3.42 (sept, JHH = 3.8 Hz, 3 2H, CH(CH3)2), 2.15 (br, 2H), 1.65 (d, JHH = 6.9 Hz, 6H, 3 3 CH3(CH)), 1.31 (d, JHH = 6.9 Hz, 12H, (CH3)2(CH)), 1.15 (d, JHH = 6.9 Hz, 12H, (CH3)2(CH)). X-ray crystals were obtained by slow evaporation from toluene solution.

1 Synthesis of 3-2 (C5H3N)(MeCHNH(C6H4-4-iPr)2: H

NMR (C6D5CD3): 8.32 (Ar), 8.09 (Ar), 7.81(Ar), 7.66

(Ar), 7.50 (Ar), 7.70-7.25 (Ar), 4.60 (CH(CH3)), 4.42 (br,

NH), 2.90 (CH(CH3)2), 2.73 (CH(CH3)2), 3 3 2.39(d, JHH = 8.5 Hz, CH3(CH)), 1.47-1.55 (m, CH3(CH)), 1.27 (d, JHH = 6.7 Hz, CH3(CH)), 3 1.15 (d, JHH = 7.1 Hz, CH3(CH)).

1 Synthesis of 3-3 (C5H3N)(MeCHNH(C6H2-2,4,6-Me3)2: H 3 3 NMR (C6D5CD3): 8.45 (d, JHH = 7.9 Hz, Ar), 8.20 (d, JHH = 3 3 7.6 Hz, Ar), 7.87 (t, JHH = 7.9 Hz, Ar), 7.65 (t, JHH = 7.6 Hz, 3 Ar), 7.46 (t, JHH = 7.6 Hz, Ar), 6.70-7.23 (m, Ar), 4.41

(m, CH(CH3)), 4.15 (br, NH), 2.14-2.28 (m, CH3), 1.98 (m, CH3), 1.35-1.45 (m, CH3), 1.47-1.55

(m, CH3(CH)), 1.35 - 1.46 (m, CH3(CH)).

1 Synthesis of 3-4 (CH2-NHC6H2Me3)2: H NMR (C6D5CD3): Agreed with published literature

i 1 Synthesis of 3-5 (CH2-NHC6H3 Pr2)2: H NMR (C6D5CD3): Agreed with published literature

1 Synthesis of 3-6 (CH2-NHC6H11)2: H NMR (C6D5CD3): Agreed with published literature.

Synthesis of 3-7: Tetrabenzylzirconium (46 mg, 0.1 mmol) and 3-1 (49 mg, 0.1 mmol) were dissolved in toluene (3 mL). The solution was heated to 60°C for 1 hour. The solvent was removed in vacuo. The residual white solid was washed with pentane (3 mL) and dried in vacuo.

1 H NMR (C6D5CD3): 7.61-7.23 (m, 16H, Ph), 7.16 (t, 1H, py), 6.95 (d, 2H, py), 3.66 (m, 4H,

CHMe2), 1.58 (d, 12H, CH(CH3)2), 1.32 (s, 12H, NC(CH3)2), 0.93 (s, 4H, CH2Ph).

3.4.6 X-Ray Crystallography

3.4.6.1 X-Ray Data Collection and Reduction

3.4.6.2 X-Ray Data Solution and Refinement

3.4.6.3 Table of Crystallographic Data

Table 3.4.2 - Select Crystallographic Data for 3-1 3-1

Formula (C5H3N)(MeCHNH(C6H3-2,6-iPr2)2 Formula weight 488.76 Crystal System monoclinic

Space group P21/n a(Å) 10.7926(8) b(Å) 21.6647(15) c(Å) 12.7760(9) α(deg) 90.00 β(deg) 95.411(4) γ(deg) 90.00 V(Å3) 2974.0(4) Z 4 Temp. (K) 150 d(calc)gcm-1 1.092 Abs coeff,μ,cm-1 0.063 Data collected 12397 2 2 DataFO >3(FO ) 2394 Variables 343 R 0.0473

Rw 0.1065 GOF 0.957

Chapter 4 Development of Phosphorus-Nitrogen Heterocyclic Ligands

4 « 4.1 Introduction

The advent of N-heterocyclic carbene (NHC) ligands (Figure 4.1.1) has had a dramatic impact on inorganic and organometallic chemistry.145-152 The first isolable persistent carbene was isolated by Bertrand et al. in 1988.153 However, this first example had limited practical use. The most common NHC, a diamino N-heterocyclic carbene, was first reported by Arduengo et al. in 1991.154 Since this time NHCs have supplemented more traditional phosphines as ligands in transition metal chemistry. These ligands have allowed access to unique coordination geometries and, in some cases, the generation of remarkably reactive catalysts.155,156 The steric and electronic features of NHCs are unique. For example, the strong sigma bonding nature of carbenes is well understood to play a role in stabilizing reactive metal species. In addition, judicious choice of substituents permits the tuning of the steric and stereochemical environment proximal to the metal.

Variants of N-heterocyclic carbene ligands have been described. For example, Bertrand et al. have described complexes of cyclic alkylaminocarbenes (CAACs) (Figure 4.1.1).157,158 In addition, carbodiphosphoranes (CDPs), (Figure 4.1.1) which are formally dianionic at the carbon atom, have been extensively investigated as ligands in transition metal chemistry.159-162 More recently, complexes of cyclic carbodiphosphoranes have also been described.160,163,164

Figure 4.1.1 - Left: N-heterocyclic carbene Middle: Carbene variations Right: Heterocyclic phosphinimine

With these precedents in mind, we sought to explore other ligand systems that might offer similar features. Phosphinimines are a class of donors which are known to be strongly basic

(Figure 4.1.1).165 However, these systems are electronically distinct from N-heterocyclic carbenes in that the donor N atom of heterocyclic phosphinimines formally has a filled p-orbital orthogonal to the donor pair whereas in N-heterocyclic carbenes the orthogonal p-orbital is vacant (Figure 4.1.2). The vacant p-orbital is well understood to have a great impact on the chemistry of free carbenes, as well as the coordination chemistry.

Figure 4.1.2- Idealized orbital configuration, left NHC, right heterocyclic phosphinimine.

While phosphinimines, specifically in this case cyclic phosphinimines, are formally neutral molecules electronegativity considerations are noteworthy. The Pauling electronegativity of phosphorus is 2.19 while the electronegativity of nitrogen is 3.04.166 This difference of 0.85 causes polarization within the heterocycle. Scheme 4.1.1 displays the two extremes of phosphinimine donor ability, therefore, implying that phosphinimines may range between 2 e- and 4 e- donors. This is another factor which has the ability to give phosphinimines unique properties towards metal coordination stabilization.

Scheme 4.1.1 - Two possible Lewis diagrams of phosphinimine heterocycles.

While anionic phosphinimide ligands have been exploited extensively as ancillary ligands, phosphinimine ligand systems have drawn much less attention, although some recent work has incorporated such donors into chelating ligand systems.167-172 The structural similarity of cyclic phosphinimines to NHCs suggests that such ligands may also combine the features of a strong donor with the additional flexibility of controlling the steric environment via alteration of the substituents on C and P. While cyclic phosphinimines were first prepared some 40 years ago, to our knowledge, the ability of these systems to act as ligands has not been explored.173-175 In this

53 work, we explore synthetic routes to a series of saturated and unsaturated cyclic phosphinimines with the intent to probe their viability as ligands.

In the 1970s Schmidpeter et al. published a unique reaction wherein they were the first research group able to develop cyclic phosphinimines.174 Since this time no further reactions, applications, or coordination chemistry were published. Convenient synthesis of cyclic phosphinimines was established by Schmidpeter et al. in the 1970s (Scheme 4.1.2). While these researchers examined the cycloaddition chemistry of these systems, the utility of such compounds in metal complex chemistry has not been explored.

Scheme 4.1.2- Synthesis of heterocyclic phosphinimines proposed by Schmidpeter et al.

4.2 Results and Discussion

4.2.1 Phosphino-imine synthesis

Thus, a series of heterocyclic phosphinimine ligands were synthesized. To this end, the compounds R2PNCPh2 (R = Ph 4-1, i-Pr 4-2, Me 4-3) were prepared first by the reaction of benzophenone imine with the corresponding chlorophosphine in the presence of excess base, triethylamine. While 4-1 was prepared from inspiration from the Schmidpeter et al. report, detailed synthetic details were omitted. It was determined that the addition of one equivalent of the corresponding chlorophosphine to one equivalent of benzophenone imine in a diethyl ether solution at -78°C over the course of an hour gave way to the maximum yields. The resulting solution with a voluminous precipitate of triethylammonium hydrochloride was filtered and diethyl ether removed in vacuo. The yields for 4-1 and 4-2 were near quantitative, while the yield of 4-3 was consistently near 70% which was contaminated with small amounts of unidentified impurities. Efforts to gain analytically pure samples of 4-3 were unsuccessful due to the fact that the compound was extremely air sensitive as well as thermally unstable, thus, 4-3 was used in the following steps without detrimental effect. The 1H and 31P NMR data was consistent with the formulations and crystallographic data was obtained for 4-1 and 4-2 which confirmed the formulations (Figure 4.2.1). The metric parameters within the two molecules were unexceptional

54 with P–N bond distances of 1.7203(14) Å and 1.7419(17) Å, respectively, and N=C bond lengths of 1.282(2) Å.

Figure 4.2.1 - POV Ray Depiction of phosphino-imines 4-1 and 4-2 respectively. C: black, P: orange, N aquamarine.

4.2.2 Phosphino-imine cyclization

Following the preparation of 4-1, 4-2, and 4-3, the cycloaddition of these phosphino-imines was attempted. Mixing a 1:1 diethyl ether solution of 4-1 and methyl acrylate yielded a clear and colourless solution with a small amount of white precipitate at room temperature. The solution was filtered through a fritted filter and the diethyl ether removed in vacuo to yield white microcrystalline solid. This observation was in stark contrast to those observations reported by Schmidpeter et al. who reported a white solid completely insoluble in diethyl ether. Cycloaddition of 4-1 with methyl acrylate afforded the phosphinimine

Ph2PNCPh2(CH2CH(CO2Me) 4-4 in a 86% yield. Following this observation the cycloaddition of 4-2 and 4-3 with methyl acrylate afforded the phosphinimines R2PNCPh2(CH2CH(CO2Me)) (R = i-Pr 4-5 and Me 4-6) in 63% and 85% yields, respectively (Scheme 4.2.1).

Scheme 4.2.1 - Methyl acrylate cyclization reactions.

The NMR data were as expected with 31P{1H} chemical shifts of 48.6, 73.8 and 52.7 ppm, respectively. The molecular structure of 4-4 (Figure 4.2.2) confirmed the formation of a puckered five-membered PNC3 ring. The ester substituent adopts an axial position with respect to the ring, presumably minimizing steric conflict with the phenyl substituents on the adjacent carbon. The P–N and P–C bond distances within the ring are found to be 1.573(3) Å and 1.823(3) Å, respectively; while the N–C distance and the C–C distance within the ring were 1.471(4) Å and 1.536(4) Å, respectively. The corresponding P–N–C angle in 4-4 was found to be 109.0(2)°.

Figure 4.2.2 - POV Ray Depiction of P N heterocycle 4 4. C: black, P: orange, N aquamarine, O red.

Attempts to effect similar cyclizations with more electron-rich alkynes such as PhCCPh, tBuCCH, Me3SiCCH, PhCCH were unsuccessful. The preceding alkynes are not exceptionally good Michael acceptors, lack significant polarization of the unsaturated C-C bond, and therefore reasons that cyclization reactions are unlikely. In an effort to install a less reactive backbone in the P-N heterocycle an intermediate unsaturated C-C bond was sought. (C6F5)HCCH2 was mixed with 4-1 and the solution analyzed via NMR spectroscopy. As opposed to cyclizations with methyl acrylate the reaction was not immediate. While a small amount of productive cyclization over the course of days may be observed in 31P NMR, conversion was never greater than 15% and the suspected product could not be isolated.

However, the corresponding reactions of 4-1 and 4-2 with dimethyl acetylenedicarboxylate affords the related cyclized products R2PNCPh2(CCOMe)2 (R = Ph 4-7, i-Pr 4-8) in approximately 80% yields.(Scheme 4.2.2)

Scheme 4.2.2 - Dimethyl acetylenedicarboxylate cyclization reactions.

These five-membered phosphinimine species retain a C=C double bond in the ring and are essentially planar. The 1H and 13C {1H} NMR data were as expected while the 31P{1H} chemical shifts of 4-7 and 4-8 were 49.0 ppm and 73.8 ppm, respectively. X-ray crystallographic data for 4-7 confirmed the cyclic nature and revealed P–N, P–C, N–C and C-C bond lengths of 1.5749(15) Å, 1.7998(17) Å, 1.457(2) Å and 1.331(2) Å in the heterocyclic ring (Figure 4.2.3). The C–N–P angle was found to be 111.98(11)°. The increase in the C–N–P angle in comparison to that in 4-4 is consistent with the rigidity resulting from the planarity of the five-membered ring. In a similar fashion, the crystallography study of 4-8 (Figure 4.2.3) revealed a planar structure where P–N and N-C bond distances were found to be 1.5801(13) Å and 1.4618(19) Å, respectively, while the corresponding C–N–P angle was 112.21(9)°. These structural perturbations are consistent with the presence of a more electron rich P centre in 4-8.

Figure 4.2.3 - POV Ray Depiction of P N heterocycle 4 7 and 4 8 respectively. C: black, P: orange, N aquamarine, O red.

Reaction of 4-1 with acrylonitrile results in the isolation of the white solid in 77% yield. This product 4-9 was formulated as Ph2PNCPh2(CH2CH(CN) (Scheme 4.2.3). The spectroscopic data are similar to the cyclic phosphinimines described above, with a 31P{1H} NMR resonance at 46.0 ppm. The infrared spectrum was also consistent with the presence of the nitrile fragment exhibiting a C≡N stretch of 2240 cm-1.

Scheme 4.2.3 - Acrylonitrile cyclization reactions.

Once again, crystallographic data confirmed the formulation unambiguously (Figure 4.2.4). Similar to 4-4, the ring conformation is puckered with the nitrile substituent adopting an axial position. The P–N and N–C bond distances were found to be 1.5892(13) Å and 1.4802(19) Å, respectively, while the C–N–P angle was determined to be 107.81(9)°. The comparatively long P–N and N–C bonds, together with the small angle at N are consistent with the electron- withdrawing nature of the nitrile substituent.

Figure 4.2.4 - POV Ray Depiction of P N heterocycle 4 9. C: black, P: orange, N aquamarine.

4.2.3 Decomposition

These phosphinimines proved to be moisture sensitive. In the case of 4-4, exposure to H2O resulted in the hydrolytic ring opening of the phosphinimine. While this result could be brought about with the addition of water, the stirring of 4-4 in a flask in air for 5 minutes led to an identical result. This results in the cleavage of the P–N bond and formation of the corresponding amine-phosphine-oxide species Ph2C(NH2)CH(CO2Me)CH2P(O)Ph2 4-10 (Figure 4.2.5). This species is isolated as a white solid. The 1H NMR spectrum reveals a resonance at 1.70–2.30 ppm 31 1 attributable to the NH2 fragment, while the P{ H} NMR spectrum shows a resonance at 29.9 ppm, typical of phosphine oxides. The formulation of this hydrolysis product was confirmed by single crystal X-ray study (Figure 4.2.5). The structure reveals the open chain nature of this species with a P–O bond distance of 1.490(3) Å.

This observation accounts for the initial observation of a white precipitate during the initial synthesis of 4-4 in diethyl ether. This would suggest that trace amounts of H2O in the dried diethyl ether caused the heterocyclic ring opening. Furthermore, this observation, as well as the observed NMR spectroscopic data, agrees with the observations of the 1971 Schmidpeter communication.

Figure 4.2.5 - POV Ray Depiction of P,N heterocycle 4-10. C: black, P: orange, N aquamarine, O red.

Bearing in mind the observation of the acyclic decomposition product, 4-10, with the presence of water the mechanism was considered (Scheme 4.2.4). A likely first step is the deprotonation of water via the highly basic phosphinimine and the formation of a hydroxide ion. Following this nucleophilic attack of a hydroxide anion, the phosphorus center is oxidized and the P-N heterocycle is opened via cleavage of the P-N bond. The resulting molecule consists of a primary amine and a phosphine oxide.

Scheme 4.2.4 - Proposed mechanism for the decomposition of heterocyclic phosphinimines

4.3 Conclusions

The synthesis, characterization and behaviour of P-N cyclic phosphinimines have been described. Following literature precedence a library of such phosphinimines has been obtained. The synthesis was determined to be exceptionally moisture sensitive leading to an acyclic phosphine oxide species 4-10. The reports in the literature were found to be misleading as to the exact characteristics of cyclic phosphinimines, in all likelihood such compounds were in fact prepared by Schmitpeter et al.only briefly and then decomposed. The previously published experimentally data more accurately describes compound 4-10.

4.4 Experimental

4.4.1 General Considerations

All preparations were performed under an atmosphere of dry, O2- free N2 employing both

Schlenk line techniques and a MBraun Labmaster inert atmosphere glove box. Solvents (CH2Cl2,

Et2O and pentane) were purified employing a Grubbs’ type column system manufactured by

Innovative Technology. 1,2-Dichloroethane was dried over CaH2 and distilled under a nitrogen atmosphere. Solvents were stored in the glove box over 4 Å molecular sieves. Molecular sieves (4 Å) were purchased from Aldrich Chemical Company and dried at 150 °C under vacuum for 48 h prior to use. All glassware was dried overnight at 120 °C and evacuated for 1 h prior to use. The chlorophosphines were purchased from Strem Chemicals. All other chemicals were purchased from Aldrich Chemical Co. and used without further purification. 1H, 13C{1H}and 31P{1H} NMR spectroscopy spectra were recorded on Varian 400 MHz and Bruker 400 MHz spectrometers. 1H and 13C{1H} NMR spectra are referenced to SiMe4 using the residual solvent 31 1 peak impurity of the given solvent. P{ H} NMR spectra were referenced to 85% H3PO4.

Chemical shifts are reported in ppm and coupling constants in Hz. C6D6 and CD2Cl2 were used as the NMR solvents after being dried over Na/benzophenone (C6D6) or CaH2 (CD2Cl2), vacuum-transferred into Young bombs and freeze–pump–thaw degassed (three cycles). Combustion analyses were performed in-house employing a Perkin Elmer 2400 Series II CHN Analyzer.

4.4.2 Experimental

Synthesis of R2PNCPh2 (R = Ph 4-1, i-Pr 4-2, Me 4-3) These compounds were prepared in a similar fashion and thus only one preparation is detailed. A solution of benzophenone imine

(9.69 g, 53.5 mmol) and Et3N (6.77 mL, 48.6 mmol) in diethyl ether (400 mL) was cooled to 0°C before adding Ph2PCl (8.72 mL, 48.6 mmol) dropwise. The reaction mixture turned yellow and was stirred overnight. The suspension was filtered and the solvent removed in vacuo. Purification via recrystallization from acetonitrile afforded 4-1 as yellow crystals.

Spectroscopic data for 4-1: Yellow crystals (12.4 g, 34.0 mmol, 70%) 1H 13 1 NMR (CD2Cl2) : 7.35–7.47 (m, 20H, Ph). C{ H} NMR (CD2Cl2): 175.70 (d, 2 2 1 (Ph)2CN, JCP = 13.7 Hz), 142.65 ( JCP =13.7 Hz, o-PPh2), 140.56 (d, o-PPh2, JCP = 7.5 Hz), 132.48 Ph), 132.27 (Ph), 130.16 (Ph), 129.04 (Ph), 128.62–128.73 (m, Ph). 31 1 P{ H} NMR (CD2Cl2) : 36.8. C,H,N analysis calc. for C25H20NP (365.42): C, 82.17; H, 5.52; N, 3.83. Found: C, 82.02; H, 5.69; N, 3.88.

Spectroscopic data for 4-2: Orange crystals (8.52 g, 28.7 mmol, 87.5%), 1H

NMR (CD2Cl2) : 7.38–7.47 (m, 10H, Ph), 1.89 (m, 2H, CH(CH3)2), 1.09 (dd, 3 3 3 3 6H, CH(CH3)2, JHH = 7.4 Hz, JPH = 14.8 Hz), 1.00 (dd, 6H, CH(CH3)3, JHH = 7.4 Hz, JPH = 13 1 2 1 14.8 Hz). C{ H} NMR (CD2Cl2) : 177.27 (d, (Ph)2CN, JCP = 13.7 Hz), 141.04 (d, Ph, JCP =

7.5 Hz), 129.90 (s, Ph), 129.16 (s, Ph), 129.14 (s, Ph), 128.49 (s, Ph), 27.55 (m, CH(CH3)2), 31 1 19.09 (s, CH(CH3)2), 18.90 (s, CH(CH3)2), 18.61 (s, CH(CH3)2), 18.51 (s, CH(CH3)2). P{ H}

NMR(CD2Cl2): 68.6. C,H,N analysis calc. for C19H24NP (297.38): C, 76.74; H, 8.13;N, 4.91. Found:C, 76.75; H, 8.10;N, 5.04. X-Ray quality crystals were grown from cooling a saturated diethyl ether solution to -35 °C.

1 Spectroscopic data for 4-3: Orange oil (Crude yield = 78%) H NMR (C6D6):

7.49–7.51 (m, 4H, Ph), 7.06–7.09 (m, 6H, Ph), 1.07 (d, 6H, CH3, 2JPH = 4.7 31 1 31 1 Hz) P{ H} NMR (C6D6): 27.81 ( P{ H} NMR shows 93% purity). Attempts to purify were unsuccessful, thus the crude product was used as prepared in subsequent reactions.

Synthesis of R2PNCPh2(CH2CH(CO2Me)) (R = Ph 4-4, i-Pr 4-5, Me 4-6) These compounds were prepared in a similar fashion and thus only one preparation is detailed. 1 (731 mg, 2.0 mmol) was completely dissolved in diethyl ether (5 mL) before the addition of methyl acrylate (181 mg, 2.10 mmol). The yellow colour of the solution faded to a clear solution and a white precipitate formed. The solution was stirred overnight. The solution was filtered and washed with cold pentane (15 mL) to afford 4 as a white solid

Spectroscopic data for 4-4: White crystals (772 mg, 1.71 mmol, 85.5%). 1 H NMR (CD2Cl2) : 7.02–7.38, 7.46–7.61, 7.88-7.97 (m, 20H, Ph), 4.25–

4.37 (m, 1H, CHCO2CH3), 2.93–3.03 (m, 4H, CH3 and CH2 trans to 13 1 CO2Me), 2.70-2.85 (m, 1H, CH2 cis to CO2CH3). C{ H} NMR (CD2Cl2) : 173.5 (d, J = 6 Hz), 150.95, 148.63, 148.43, 132.26, 132.17, 131.57, 131.55, 131.11, 131.01, 130.74, 130.71, 128.22, 128.10, 128.02, 127.97, 127.91, 127.42, 127.14, 126.80, 125.92, 125.58, 82,89, 50.90, 31.85, 31 1 31.40. P{ H} NMR (CD2Cl2): 48.61. C,H,N analysis calc. for C29H26NO2P (451.51): C, 77.15; H, 5.80; N, 3.10. Found: C, 76.62; H, 5.89; N, 3.19. X-Ray quality crystals were grown by slow diffusion of pentane into a saturated dichloromethane solution.

Spectroscopic data for 4-5: (800 mg, 2.02 mmol, 63%) white solid, 1H

NMR (CD2Cl2): 7.62–7.63 (m, 2H, Ph), 7.42–7.45 (m, 2H, Ph), 7.25 (tt, 2H, J =8 Hz, Ph), 7.12–7.16 (m, 3H, Ph), 7.06 (tt, 1H, J = 7 Hz, Ph),

4.05-4.13 (m, 1H, CHCO2CH3), 3.08 (s, 3H, CH3), 2.45–2.54 (m, 2H, CH2), 2.08–2.18 (m, 3 3 1H, CH(CH3)2), 1.63–1.68 (m, 1H, CH(CH3)2), 1.38 (dd, 3H, CH(CH3)2, JPH = 10.2 Hz, JHH = 3 3 3 7.3 Hz), 1.34 (dd, 3H, CH(CH3)2, JPH = 10.2 Hz, JHH = 7.3 Hz), 0.98 (dd, 3H, CH(CH3)2, JPH = 3 3 3 31 1 14.7 Hz, JHH = 7.2 Hz), 0.79 (dd, 3H, CH(CH3)2, JPH = 15.5 Hz, JHH = 7.1 Hz). P{ H} NMR 13 1 (CD2Cl2): 73.80. C{ H} NMR (CD2Cl2): 173.97, 173.91, 152.85, 152.82, 149.56, 149.38, 127.94, 127.52, 127.28, 126.57, 125.53, 82.78, 54.58, 54.47, 53.96, 53.69, 53.42, 53.15, 52.88, 50.92, 27.53, 26.99, 26.14, 25.49, 24.41, 24.03, 17.60, 17.58, 17.14, 17.11, 16.41, 16.38, 16.34,

16.31. C,H,N analysis calc. for C23H30NO2P (383.47): C, 72.04; H, 7.89; N, 3.65. Found: C, 71.83; H, 8.05; N, 3.72.

Spectroscopic data for 4-6: (642 mg, 1.96 mmol, 85%). Purification via recrystallization from dichloromethane yields colourless needles. 1H NMR

(CD2Cl2): 7.48–7.54 (m, 4H, Ph), 7.22–7.26 (m, 2H, Ph), 7.12–7.18 (m, 3H,

Ph), 7.06–7.10 (tt, 1H, Ph), 4.17 (m, 1H, CHCO2CH3), 3.00 (s, 3H, CH3), 2.44 (m, 1H, CH2), 2 2 2.02–2.10 (m, 1H, CH2), 1.78 (d, 3H, JPH = 14.0 Hz, P(CH3)2), 1.09 (d, 3H, JPH = 14.0 Hz, 31 1 13 1 P(CH3)2). P{ H} NMR (CD2Cl2): 52.7. C{ H} NMR (CD2Cl2): 174.59, 151.56, 149.03, 148.78, 128.18, 128.08, 128.06, 127.50, 127.40, 126.32, 126.28, 82.97, 66.22, 51.45, 31.00,

30.57, 19.20, 18.62, 17.02, 16.28, 15.67. C,H,N analysis calc. for C19H22NO2P (327.36): C, 69.71; H, 6.77; N, 4.28. Found: C, 71.09; H, 7.05; N, 4.52.

Synthesis of R2PNCPh2(CCO2Me)2 (R = Ph 4-7, i-Pr 4-8) These compounds were prepared in a similar fashion and thus only one preparation is detailed. Compound 1 (365 mg, 1.0 mmol) was dissolved in diethyl ether (5 mL) to which dimethyl acetylenedicarboxylate (150 mg, 1.05 mmol) dissolved in diethyl ether (5 mL) was added dropwise. The reaction turned from light yellow to light orange with a precipitate forming in 10 min. The reaction was stirred overnight. The reaction was filtered and washed with cold pentane (15 mL) to give a pure yellow powder 4-7

Spectroscopic data for 4-7: (380 mg, 0.75 mmol, 75%). 1H NMR

(CD2Cl2): 7.56–7.61 (m, 6H, Ph), 7.42– 7.46 (m, 4H, Ph), 7.29–7.32 (m,

4H, Ph), 7.22–7.25 (m, 6H, Ph), 3.68 (s, 3H, CH3), 3.59 (s, 3H, CH3). 31 1 13 1 P{ H} NMR (CD2Cl2): 49.04. C{ H} NMR (CD2Cl2): 176.71, 176.33, 166.57, 166.33, 162.48, 162.36, 146.58, 146.51, 132.60, 132.50, 132.18, 132.16, 128.40, 128.30, 128.16, 127.36,

126.62, 88.08, 52.49, 52.28, 43.92. C,H,N analysis calc. for C31H26NO4P (507.52): C, 73.36; H, 5.16; N, 2.76. Found: C, 72.91; H, 5.59; N, 2.71.

Spectroscopic data for 4-8: orange powder (1.20 g, 2.73 mmol, 75%). 1 Orange crystals (8.52 g, 28.7 mmol, 88%), H NMR (CD2Cl2): 7.84–7.87 (m, 2H, Ph), 7.65–7.68 (m, 2H, Ph), 7.27–7.49 (m, 6H, Ph), 4.32 (m, 1H,

CHCOOCH3), 3.30 (s, 3H, CH3), 2.66–2.77 (m, 2H, CH(CH3)2), 2.37 (m, 1H, CH2), 1.83–1.93 3 3 (m, 1H, CH2), 1.55–1.63 (m, 6H, CH(CH3)2), 1.20 (dd, 3H, CH(CH3)2, JPH = 15.9 Hz, JHH = 3 3 13 1 7.3 Hz), 1.01 (dd, 3H, CH(CH3)2 , JPH = 16.9 Hz, JHH = 7.2 Hz). C{ H} NMR (CD2Cl2) : 173.95, 152.85, 149.48, 127.94, 127.52, 127.28, 126.57, 125.53, 82.77, 54.54, 50.92, 27.27, 31 1 25.79, 24.22, 17.61, 17.34, 16.37. P{ H} NMR (CD2Cl2): 73.79 C,H,N analysis calc. for

C25H30NO4P (439.48): C, 68.32; H, 6.88; N, 3.19. Found: C, 68.43; H, 6.66;N, 3.65. X-Ray quality crystals were grown by slow cooling of a saturated diethyl ether solution.

Synthesis of R2PNCPh2(CH2CH(CN)) 4-9 Compound 1 (1.096 g, 3.00 mmol) was dissolved in diethyl ether (10 mL) to which acrylonitrile (160 mg, 3.03 mmol) dissolved in diethyl ether (5 mL) was added in addition. The reaction turned from light yellow to colourless with a white precipitate upon stirring for 12 h. The reaction volume was reduced by half in vacuo, filtered, and washed with cold pentane (20 mL) to 1 give a white powder (961 mg, 2.20 mmol, 77%). H NMR (CD2Cl2): 7.75–7.91 (m, 4H, Ph), 31 1 7.11–7.68 (m, 16H, Ph), 4.34 (m, 1H, CH), 3.03 (m, 2H, CH2). P{ H} NMR (CD2Cl2) 46.0.

13 1 C{ H} NMR (CD2Cl2): 149.00, 148.95, 148.74, 148.56, 132.82, 132.71, 132.22, 131.88, 131.78, 131.63, 130.59, 129.25, 129.12, 129.01, 128.89, 128.42, 128.29, 127.84, 127.11, 127.03, 126.85, 121.32, 81.56, 42.40, 42.27, 33.86, 33.42.

Synthesis of Ph2C(NH2)CH(CO2Me)CH2P(O)Ph2 4-10 Compound 4-4 (45mg, 0.1 mmol) was dissolved in dichloromethane (5 mL) and exposed to air for 5 min. The initially clear solution immediately formed a fine white precipitate. After 5 min. the reaction was complete, the volume reduced to 1 mL and filtered. Washing the solid with cold dichloromethane (2 mL) yields a pure white solid. 1 H NMR (CDCl3): 7.62–7.74 (m, 4H, Ph), 7.41–7.51 (m, 8H, Ph), 7.28 (t, 4H, Ph), 7.13–7.20 (m,

3H, Ph), 7.06 (m, 1H, Ph), 4.10 (m, 1H, CH2), 2.82–2.90 (m, 1H, CHCO2CH3), 2.80 (s, 3H, 31 1 CHCO2CH3), 2.48 (m, 1H, CH2), 1.70–2.30 (br, 2H, NH2). P{ H} NMR (CDCl3): 29.9. 13 1 C{ H} NMR (CDCl3): 174.63 (s, CO2CH3), 146.00, 144.78, 133.97, 132.98, 132.15, 132.12, 132.03, 132.00, 131.53 (d, J = 10 Hz), 130.90 (d, J = 10 Hz), 128.97, 128.92, 128.85, 128.65,

128.53, 128.03, 128.20, 126.95, 126.68, 126.34, 63.90 (d, J = 13 Hz, C(Ph)2(NH2)), 51.47 (s,

CO2CH3), 46.66 (CHCO2CH3), 29.44 (d, J = 70 Hz, CH2P(O)Ph2). C,H,N analysis calc. for

C29H28NO3P (469.51): C, 74.19; H, 6.01; N, 2.98. Found: C, 73.32; H, 6.62; N, 2.97.

4.4.3 X-ray Crystallography

4.4.3.1 X-Ray Data Collection and Reduction

Crystals were coated in Paratone-N oil in the glove-box, mounted on a MiTegen Micromount and placed under an N2 stream, thus maintaining a dry, O2-free environment for each crystal. The data were collected on a Bruker Apex II diffractometer employing Mo Kα radiation (λ = 0.71073 Å). Data collection strategies were determined using Bruker Apex software and optimized to provide >99.5% complete data to a 2θ value of at least 55°. The data were collected at 150(±2) K for all crystals. The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. Data were corrected for absorption effects using the empirical multi- scan method (SADABS).

4.4.3.2 X-Ray Data Solution and Refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations. 118 The heavy atom positions were determined using direct methods employing the SHELXTL direct methods routine. The remaining non-hydrogen atoms were located from successive difference Fourier map calculations. The refinements were carried out by using full-matrix least squares techniques 2 2 2 on F, minimizing the function  (Fo–Fc) where the weight  is defined as 4Fo /2 (Fo ) and Fo and Fc are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C-H bond length of 0.95 Å. H-atom temperature factors were fixed at 1.20 times the isotropic temperature factor of the C-atom to which they are bonded. The H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance.

Table 4.4.1 - Select Crystallographic Data for 4-1, 4-2, and 4-4 (4-1) (4-2) (4-4)

Formula C25H20NP C19H24NP C29H26NO2P Formula weight 365.39 297.36 451.48 Crystal System monoclinic triclinic triclinic

Space group P21/c P-1 P-1 a(Å) 14.9681(5) 10.0312(11) 6.1469(12) b(Å) 18.5680(6) 16.5830(19) 12.962(3) c(Å) 6.9944(2) 10.7114(11) 15.073(3) α(deg) 90.00 85.977(3) 90.32(3) β(deg) 90.314(2) 77.378(3) 93.83(3) γ(deg) 90.00 88.752(5) 98.83(3) V(Å3) 1943.91(11) 1734.4(3) 1183.9(4) Z 4 4 2 d(calc)gcm-3 1.248 1.139 1.226 R(int) 0.0470 0.0565 0.0344 Abs coeff,μ,mm-1 0.150 0.153 0.143 Data collected 19952 28715 20194 2 >2(FO ) 5334 7894 5301 Variables 244 379 298 R(>2) 0.0470 0.0515 0.0662

Rw 0.1231 0.1142 0.1712 GOF 1.051 0.993 0.997

Table 4.4.2 - Select Crystallographic Data for 4-7, 4-8, and 4-9 (4-7) (4-8) (4-9)

Formula C34H32NO4P C25H30NO4P C28H23N2P Formula weight 655.93 439.47 418.45 Crystal System monoclinic monoclinic monoclinic

Space group P21/c P21/c P21/c a(Å) 8.6024(6) 15.8375(8) 18.1088(15) b(Å) 18.0080(11) 8.0078(3) 5.9338(4) c(Å) 21.0067(14) 19.2830(9) 20.6934(14) α(deg) 90.00 90.00 90.00 β(deg) 96.638(4) 110.237(3) 96.973(5) γ(deg) 90.00 90.00 90.00 V(Å3) 3232.4(4) 2294.58(19) 2207.1(3) Z 4 4 4 d(calc)gcm-3 1.348 1.272 1.259 R(int) 0.0582 0.1036 0.1262 Abs coeff,μ,mm-1 0.372 0.151 0.142 Data collected 29348 40834 47239 2 >2(FO ) 7927 5264 7699 Variables 388 280 280 R(>2) 0.0410 0.0399 0.0509

Rw 0.0906 0.1022 0.1484 GOF 0.865 1.043 0.996

Table 4.4.3 - Select Crystallographic Data for 4-10 (4-10)

Formula C29H28NO3P Formula weight 469.49 Crystal System monoclinic

Space group P21 a(Å) 5.8622(12) b(Å) 17.456(4) c(Å) 11.936(2) α(deg) 90.00 β(deg) 103.83(3) γ(deg) 90.00 V(Å3) 1186.0(4) Z 2 d(calc)gcm-3 1.315 R(int) 0.0299 Abs coeff,μ,mm-1 0.148 Data collected 1.144 2 >2(FO ) 4825 Variables 306 R(>2) 0.0641

Rw 0.1446 GOF 1.027

Chapter 5 P,N Heterocycle Coordination

5 « 5.1 Introduction

5.1.1 N-Heterocyclic Coordination

We have demonstrated a novel phosphinimine heterocycle which has geometric similarities to N-heterocyclic, (NHC), carbenes while possessing unique electronic features. N-heterocyclic carbenes were developed in 1991 and its the coordination chemistry is now ubiquitous in transition metal chemistry. NHCs have allowed access to unique coordination geometries and, in some cases, the generation of remarkably reactive catalysts.155,156 While the specifics of NHC geometric and electronic considerations were previously discussed in chapter 4 a discussion of the coordination chemistry is relevant in this chapter.

The first example of the coordination of NHCs to a metal was reported in 1968. Wanzlick et al. reported a coordination complex with mercury.176(Scheme 5.1.1) The communication did not include further reactivity.

Scheme 5.1.1 - First reported example of a NHC metal coordination complex.

5.1.2 Group 10 Coordination Chemistry

Silver-NHC chemistry is generally considered an entry point into NHC coordination (Scheme 5.1.2). Primary, this is due to the convenient reaction of silver(I) oxide with an imidazolium salt. The silver(I) oxide acts as both a base and a foundation of a coordination complex. Furthermore, silver coordination complexes are useful transmetallation reagents to further prepare additional transition metal coordination complexes.145,177,178

Scheme 5.1.2 - Typical NHC silver coordination complex.

Recently NHC-gold coordination chemistry has seen increased interest (Scheme 5.1.3). This is the result of unique catalysis and complexes which have been recently discovered. Nolan et al. have recently published a significant portfolio of novel chemistry.156,179-181

Scheme 5.1.3 - Gold-NHC complex synthesis.

5.1.3 Ruthenium Coordination Chemistry

Without doubt the most noteworthy example of NHC metal coordination chemistry and subsequent catalysis to date is the advent of the second generation Grubbs catalysts. (Scheme 5.1.4). The discovery of the second generation Grubbs catalyst, 27,29,30 Ru(SIMes)(PCy3)Cl2(CHPh), had a profound impact on olefin metathesis catalysis. Second generation Grubbs catalyst improved both overall catalyst stability and activity. Soon after, a series of fast-initiating second generation Grubbs catalysts, such as 182,183 Ru(SIMes)(py)Cl2(CHPh), were discovered. The pyridine ligands of the fast initiating catalysts allowed the full complement of catalyst to enter the catalytic cycle immediately to improve the performance towards ring opening metathesis polymerization. Furthermore, the arrival of the Grubbs-Hoveyda catalyst, Ru(SIMes)Cl2(CHPh-OiPr2), enabled further selectivity and stability.184

Scheme 5.1.4 - Second generation Grubbs type catalysts.

5.2 Results and Discussion

5.2.1 Silver

In examining the potential of cyclic phosphinimines as ligands, the starting point was silver(I) coordination chemistry. The reaction of 4-4 with Ag(NO3) was first performed. NHC-silver coordination chemistry is generally not selective with respect to the silver : ligand stoichiometry. Therefore the reaction of 4-4 with silver nitrate was examined with both a 1 : 1 and a 2 : 1 ligand to silver ratio. Silver nitrate was chosen as the silver(I) source due to solubility and counter-ion inertness considerations. Mixing a 1 : 1 ligand : silver dichloromethane in the dark for 4 hours resulted in a clear solution. Crystals of a new species, 5-1, were isolated in 73% yield. The NMR data were consistent with the complexation of the ligand. The 31P NMR spectrum showed two resonances at 52.8 and 52.5 ppm consistent with the two NMR active isotopes of silver, 107Ag and 109Ag.

Scheme 5.2.1 - Coordination of 4-4 with Ag(NO3).

The nature of the product, 5-1, was only unambiguously confirmed via single crystal X-ray diffraction. These experiments revealed the formulation of 5-1 to be a salt with the formulation

[{Ph2PNCPh2(CH2CH(CO2Me)}2Ag][(NO3)2Ag] (Fig. 5.2.1, Scheme 5.2.1). The anion is a linear Ag ion, in which two nitrate groups bind via one oxygen atom to the Ag centre with a Ag-O bond distance of 2.223(3) Å. The cation of this salt is a two-coordinate pseudo-linear Ag

73 ion coordinated to the N of two phosphinimine ligands. The Ag–N bond distance was determined to be 2.0675(17) Å, while the linearity of the N–Ag–N vector was crystallographically imposed. The Ag-N bond distance was determined to be similar to the distances reported for a series of Ag-carbene complexes of the form LAgCl. In these cases the Ag–C bond distances range from 2.094(6) to 2.060(19) Å. The geometry of the cation of 5-1 is similar to that seen in the bis-carbene complex [(C6H4(NEt)2C)2Ag][AgBr2] although the Ag–N distance in 5-1 is slightly shorter than that reported for this carbene species 2.073(26) Å. Furthermore, the P-N bond distance in 5-1 was determined to be 1.5993(19) Å. This may be compared to the P-N bond distance of 4-4 which was determined to be 1.573(3) Å. The coordination to silver results in a small but significant lengthening of the P-N bond by 0.026 Å.

Figure 5.2.1 - POV Ray Depiction of P-N heterocycle 5-1. Ag: dark red, C: black, P: orange, N aquamarine, O light red. Counter anion omitted for clarity.

In an attempt to obtain a mono ligand:silver species, different ratios of silver to ligand were examined. However, the complex 5-1 is always obtained from the reaction mixtures.

Furthermore, the use of other silver(I) starting materials such as AgBF4, AgPF6, and AgOTf

74 yielded similar results. All of the silver complexes obtained were noted to be light sensitive in solution while being stable for greater than one week in the solid state.

5.2.2 Gold

With the results of the silver coordination complexes in mind, the synthesis of gold(I) coordination complexes was attempted.

First, a transmetallation synthetic strategy was attempted. As described in the introduction, there is significant precedence for gold-NHC complex synthesis using silver transmetallation reagents. The previous preparation of silver-cyclic phosphinimine complexes provided an entry. Mixing a

1 : 1 solution of (Me2S)AuCl and 5-1 in dichloromethane did not yield a new product. Observing the mixture by NMR spectroscopy displayed the characteristic pattern from 107Ag and 109Ag without the evolution of new peaks. Heating the reaction mixture produced silver metal and an intractable mixture.

Second, the direct synthesis in reactions conducted in a similar fashion to the formation of 5-1, the cyclic phosphinimines 4-4 and 4-7 were reacted with (Me2S)AuCl. A 1 : 1 mixture of 4-4 and (Me2S)AuCl were stirred together for 30 min in dichloromethane. Removal of the solvent in vacuo yielded a white microcrystalline product in an isolated yield of 89 %. The 1H NMR spectrum, similar to the 1H spectra of 5-1, displayed little difference. However, the 31P NMR spectrum showed a new resonance at 51.3 ppm. The connectivity was unambiguously confirmed via single crystal X-ray diffraction to provide the molecular structure as

Ph2PNCPh2(CH2CH(CO2Me)AuCl, 5-2 (Figure 5.2.2). The molecule, 5-2, was a pseudo-linear Au(I) complex with the cyclic phosphinimine coordinated to a Au-Cl fragment. The pseudo-linear bond consists of a N-Au-Cl bond angle of 177.07(4)°. The Au–N bond distance in 5-2 was determined to be 2.0253(13) Å, with a corresponding Au–Cl distance of 2.2612(4) Å. Furthermore, the P-N bond length was determined to be 1.6122(14) Å which is a significant lengthening compared to the P-N bond distance of 1.573(3) Å found in the parent molecule 4-4.

Scheme 5.2.2 - Synthesis of heterocyclic phosphinimine gold (I) complexes.

Similarly mixing a 1 : 1 solution of 4-7 and (Me2S)AuCl yielded a new species in an isolated yield of 82 %. Of note is that the formerly deep orange colour of 4-7 disappears within 5 1 1 minutes of mixing with (Me2S)AuCl. The H NMR spectrum, similar to the H spectra of 5-1 and 5-2, displayed little difference. However, the 31P NMR spectrum showed a new resonance at 50.0 ppm which is only slightly different to that of 5-2. The connectivity was unambiguously confirmed via single crystal X-ray diffraction to provide the molecular structure as

(Ph2PNCPh2(C(CO2Me)2)AuCl, 5-3 (Figure 5.2.3). The molecule, 5-3, was a pseudo-linear Au(I) complex with the cyclic phosphinimine coordinated to a Au-Cl fragment very similar to that observed in 5-2. The pseudo-linear bond consists of a N-Au-Cl bond angle of 179.7(2)°. The Au–N bond distance in 5-2 was determined to be 2.010(7) Å, with a corresponding Au–Cl distance of 2.257(2) Å. Furthermore, the P-N bond length was determined to be 1.613(7) Å.

Figure 5.2.2 - POV Ray Depiction of P N heterocycle 5-2. Au: light yellow, C: black, P: orange, N aquamarine, O light red.

Figure 5.2.3 - POV Ray Depiction of P N heterocycle 5-3. Au: light yellow, C: black, P: orange, N aquamarine, O light red.

The Au–N distances in 5-2 and 5-3 are slightly longer than those observed for Au–C bond lengths in related NHC-carbene-AuCl complexes,185 which range from 1.965(5) Å to 2.018(3) Å, and slightly shorter than those seen in the CAAC complex cations of the form [L2Au]+ (2.0321(11) 2.033(4) Å). Consequently the Au–Cl distances in 5-2 and 5-3 are slightly shorter as the Au–Cl bond distances in the related carbene complexes range from 2.2698(11) to 2.3061(11) Å. While the structural features of these cyclic phosphinimine ligands are reminiscent of that of carbene ligands the data presented herein is consistent with the anticipated strong donor ability of these ligands. The preceding metric data of Au-Cl bond distances suggest that these ligands exhibit similar sigma donor abilities to N-heterocyclic carbenes, however the geminal substitution at the P and C adjacent to N generates a donor environment that is even more sterically encumbered than that in bulky N-heterocyclic carbenes. This is best demonstrated using space filling models of both a representative cyclic phosphinimine and a NHC. The steric constraints surrounding the donor atom are significantly increased within a cyclic phosphinimine (Figure 5.2.4).

Figure 5.2.4 - Optimized structure space filling model demonstrates differences in sterics. 4-4 left, SIMes right

Efforts to expand the coordination chemistry of gold(I) cyclic phosphinimine complexes led to the preparation of a cationic gold(I) complex. Treatment of 5-3 with one equivalent of AgOTf in tetrahydrofuran yielded the formation of a significant white precipitate. Filtering the resulting solution yielded a clear and colourless solution from which the solvent was removed in vacuo. NMR spectroscopy was not conclusive in the determination of the formation of a new product as the signals were not significantly changed from 5-3. The connectivity was unambiguously confirmed via single crystal X-ray diffraction to provide the molecular structure as + - [(Ph2PNCPh2(C(CO2Me)2)]2Au ·SO3CF3 , 5-4 (Figure 5.2.5). As with the observations in the silver(I) coordination chemistry, it was not possible to isolate a mono-ligand gold(I) species.

Figure 5.2.5 - POV Ray Depiction of P-N heterocycle 5-4. Au: light yellow, C: black, P: orange, N aquamarine, O light red. Triflate ion removed for clarity.

5.2.3 Ruthenium

As stated in the introduction one of the overarching goals was the development of a new class of olefin metathesis catalysts. To this end, the phosphinimine heterocycles developed in chapter 4 were used in the attempted coordination chemistry with ruthenium centers. The full library of heterocycles described herein were tested with a large variety of ruthenium starting materials. A sample of the ruthenium species tested is as follows; chlorohydridotris(triphenylphosphine) ruthenium(II), di-μ-chlorobis[(p-cymene)chloro ruthenium(II)], dichloro(p-cymene)acetonitrile ruthenium(II), and dichlorotris(triphenylphosphine) ruthenium(II). Test reaction with any of the above mentioned combinations did not produce new compounds when completed in either dichloromethane, toluene, or THF. Following these negative results the heterocyclic phosphinimines were tested with first generation Grubbs catalyst. The screening reaction with first generation Grubbs catalyst did, in some instances, yield detectable amounts of new products via NMR spectroscopy but generally less than 10 %. It was not possible to identify or isolate the compounds observed.

5.3 Conclusions

The library of heterocyclic phosphinimines developed and described in chapter 4 has been investigated towards their potential application as ligands for late transition metals. An example of a silver (I) coordination complex has been described herein. The silver complex formed only a 2:1 ligand : metal coordination complex and efforts to obtain a 1:1 ligand : metal coordination complex were unsuccessful. While the report silver(I) complex contained a nitrate counter anion other non-coordinating anions produced an identical result. Silver (I) complexes containing a simple halide could not be isolated.

Following these results efforts then focused on gold (I) coordination chemistry. The reaction of the gold (I) chloride dimethylsulfide adduct with a heterocyclic phosphinimine resulted in the clean formation of a 1 : 1 adduct. Two examples were described within this chapter. The complexes displayed similar solid state structure characteristics to that observed for gold (I) chloride N-heterocyclic carbene structures. In an effort to mimic the results observed in silver (I) chemistry the salt metathesis of halide to a triflate counteranion resulted in the clean formation of a 2 : 1 ligand : gold coordination complex.

Subsequently, further coordination chemistry was investigated. Due to the fact that the development of new olefin metathesis catalysts was a primary goal of this thesis, ruthenium coordination chemistry was investigated. Substantial efforts were carried out to effect the coordination of heterocyclic phosphinimines to a ruthenium center but were unsuccessful. No isolable ruthenium phosphinimine complexes could be found. Either no reaction could be observed or decomposition was detectable via NMR spectroscopy.

5.4 Experimental

5.4.1 General Considerations

All preparations were performed under an atmosphere of dry, O2- free N2 employing both

Schlenk line techniques and a MBraun Labmaster inert atmosphere glove box. Solvents (CH2Cl2,

Et2O and pentane) were purified employing a Grubbs’ type column system manufactured by

Innovative Technology. 1,2-Dichloroethane was dried over CaH2 and distilled under a nitrogen atmosphere. Solvents were stored in the glove box over 4 Å molecular sieves. Molecular sieves (4 Å) were purchased from Aldrich Chemical Company and dried at 150 °C under vacuum for 48 h prior to use. All glassware was dried overnight at 120 °C and evacuated for 1 h prior to use. The metal precursors were purchased from Strem Chemicals. All other chemicals were purchased from Aldrich Chemical Co. and used without further purification. 1H, 13C{1H}, and 31P{1H} NMR spectroscopy spectra were recorded on Varian 400 MHz and Bruker 400 MHz 1 13 1 spectrometers. H and C{ H} NMR spectra are referenced to SiMe4 using the residual solvent 31 1 peak impurity of the given solvent. P{ H} NMR spectra were referenced to 85% H3PO4.

5.4.2 Synthesis

Synthesis of 5-1: Compound 4-4 (226 mg, 0.50 mmol.) was dissolved in dichloromethane (5 mL) and added to a slurry of silver nitrate (85 mg, 0.50 mmol, 1 eq.) in dichloromethane (3 mL). The solution was stirred for 24 h in the dark. The solution colour slowly changed from colourless to a light yellow. The solution was filtered through Celite and the solvent removed in vacuo to yield an off-white solid.

Spectroscopic data for 5-1: (227 mg, 73%) 1H NMR

(CD2Cl2):6.73–7.70 (br. m, 40H, Ph), 4.23–4.34 (br. m, 2H,

CH), 3.31–3.41 (m, 2H, CH2), 3.08 (s, 6H, CH3), 2.93– 31 1 3.04 (m, 2H, CH2). P{ H} NMR (CD2Cl2): 52.83 (d, 2JAg–P = 18 Hz), 52.58 (d, 2JAg–P = 18 Hz) 13C{1H}

NMR (CD2Cl2): 172.18 (d, C=O, J = 6 Hz), 148.30, 145.41, 133.60, 132.3–132.8 (m, Ph), 129.21, 129.08, 128.9, 128.8, 128.4, 127.9, 127.6, 127.17, 126.75, 80.74

(d, CHCOOCH3, J = 8 Hz), 65.7, 51.84 (s, CH3), 30.10. C,H,N analysis calc. for C23H30NO2P (383.47): C, 72.04; H, 7.89; N, 3.65. Found: C, 71.83; H, 8.05; N, 3.72.

Synthesis of 5-2 and 5-3: These compounds were prepared in a similar fashion and thus only one preparation is detailed. (Me2S)AuCl (215 mg, 0.74 mmol) was dissolved in 1,2-dichloroethane (5 mL) before a 1,2-dichloroethane (5 mL) solution of 4-4 (345 mg, 0.75 mmol) was added dropwise. The reaction was stirred for 20 min. at which time the solvent was removed in vacuo. The resulting white solid was washed with pentane (10 mL) to give a white solid.

Spectroscopic data for 5-2 Yield: 450 mg, 0.65 mmol, 89%. 1H

NMR (CD2Cl2): 7.70–7.75 (m, 6H, Ph), 7.56–7.60 (m, 4H, Ph), 7.32– 31 1 7.44 (m, 10H, Ph), 3.70 (s, 3H, OCH3), 3.58 (s, 3H, OCH3). P{ H} 13 1 NMR (CD2Cl2): 51.28. C{ H} NMR (CD2Cl2): 164.6, 161.35, 143.2, 134.89, 134.01, 133.90, 129.82, 129.78, 129.29, 129.02, 128.64, 86.38, 68.1, 28.1, 20.1.C,H,N analysis calc. for

C29H26AuNO2P (683.92): C, 50.93; H, 3.83; N, 2.05. Found: C, 50.52; H, 3.85;N, 2.31. X-Ray quality crystals were grown by slow diffusion of pentane into a saturated dichloromethane solution.

Spectroscopic data for 5-3: Yield: 324 mg, 0.44 mmol, 82%. 1H NMR

(CD2Cl2): 8.03–8.09 (m, 2H, Ph), 7.48–7.77 (m, 10H, Ph), 7.35-7.41

(m, 2H, Ph), 7.26–7.30 (m, 6H, Ph), 4.32 (m, 1H, CHCO2CH3), 3.30

(m, 1H, CH2 trans to CO2CH3), 3.17 (s, 3H, CH3), 2.97–3.05 (m, 1H, CH2 cis to CO2CH3). 31 1 13 1 P{ H} NMR (CD2Cl2): 49.89. C{ H} NMR (CD2Cl2) :171.84 (d, COOCH3), 146.5, 146.7, 144.58, 144.47, 133.69, 132.96, 132.86, 131.82, 131.72, 129.0, 128.95, 128.83, 128.28, 128.05,

128.01, 127.57, 127.51, 127.41, 80.00, 51.9, 29.5 (d, CH2). C,H,N analysis calc. for

C31H26AuClNO4P (739.94): C, 50.32; H, 3.54; N, 1.89. Found: C, 50.82; H, 3.93; N, 1.92.

Synthesis of 5-4: Compound 5-3 (27 mg, 20 µmol) was

dissolved in d2-dichloromethane (1.0 mL) to which silver triflate (5 mg, 20 µmol) was added. The solution was stirred for 5 min after which a white precipitate formed. The mixture was filtered into an NMR tube and NMR acquired. The NMR was nearly indistinguishable from that observed in 5-3. Single crystal X-ray crystals were grown from the slow evaporation of the d2-dichloromethane solution.

5.4.3 X-ray Crystallography

5.4.3.1 X-Ray Data Collection and Reduction

5.4.3.2 X-Ray Data Solution and Refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations. 118 The heavy atom positions were determined using direct methods employing the SHELXTL direct methods routine. The remaining non-hydrogen atoms were located from successive difference Fourier map calculations. The refinements were carried out by using full-matrix least squares techniques 2 2 2 on F, minimizing the function  (Fo–Fc) where the weight  is defined as 4Fo /2 (Fo ) and Fo and Fc are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C-H bond length of 0.95 Å. H-atom temperature factors were fixed at 1.20 times the isotropic temperature factor of the C-atom to which they are bonded. The H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance.

Table 5.4.1 - Select Crystallographic Data for 5-1, 5-2, and 5-3 (5-1) (5-2) (5-3)

Formula C60H56Ag2Cl4N4 C29H26AuCl3N C33H30AuCl5N O10P2 O2P O4P Formula weight 1412.57 766.81 909.77 Crystal System triclinic triclinic monoclinic

Space group P-1 P-1 P21/c a(Å) 11.2357(9) 9.8098(3) 8.9595(7) b(Å) 11.5055(9) 12.3568(3) 14.3413(11) c(Å) 13.2632(11) 12.9623(3) 27.391(2) α(deg) 112.819(4) 107.066(1) 90.00 β(deg) 109.495(4) 102.188(2) 98.231(5) γ(deg) 91.874(4) 94.728(1) 90.00 V(Å3) 1463.6(2) 1450.58(7) 3483.2(5) Z 1 2 4 d(calc)gcm-3 1.603 1.756 1.735 R(int) 0.0331 0.0352 0.0705 Abs coeff,μ,mm-1 0.969 5.431 4.691 Data collected 12144 11621 17636 2 >2(FO ) 10212 34679 4915 Variables 373 352 403 R(>2) 0.0412 0.0356 0.0439

Rw 0.1232 0.0618 0.0866 GOF 1.002 0.958 1.052

Table 5.4.2 - Select Crystallographic Data for 5-4 (5-4)

Formula C63H52AuF3N2 O11P2S Formula weight 1482.72 Crystal System triclinic Space group P-1 a(Å) 12.9074(5) b(Å) 14.1618(5) c(Å) 19.5093(7) α(deg) 98.245(2) β(deg) 105.553(2) γ(deg) 101.709(2) V(Å3) 3289.3(2) Z 2 d(calc)gcm-3 1.497 R(int) 0.0599 Abs coeff,μ,mm-1 2.429 Data collected 12144 2 >2(FO ) 10212 Variables 842 R(>2) 0.0599

Rw 0.1318 GOF 1.069

Chapter 6 P,N Template Synthesis

6 « 6.1 Introduction

6.1.1 P-N Ligands

Ligands containing P-N bonds as well as those containing phosphorus and nitrogen donor functionalities have found wide spread use in coordination chemistry and catalysis. For example, - P-N bonded ligands such as phosphinimines (R3PNR’)[A], and phosphinimides (R3PN )[B] (Scheme 6.1.1) have been used to prepare a large range of main group and transition metal based derivatives as well as in early transition metal based catalysts for olefin polymerization.167,186-188

In a similar fashion, aminophosphine ligands (R’2NPR2) are readily prepared and have been employed in a variety of metal mediated transformations.189-206 While these ligands are most commonly monodentate via P-metal binding[C], ligands of the form (R’HNPR2) have also been shown to be readily deprotonated forming PNM three membered rings[D].

Scheme 6.1.1 - Variety of reported P,N bonded ligands.

Another class of P-N bonded ligands are based on phosphinoimines (R2PN=CR’2)[E]. While, in general, these ligands have received less attention, Igau and coworkers have recently reported interesting Ru-complexes containing the phosphorus bound ligands Ph2PN=CPhR (R = H, Ph)

(Scheme 6.1.2). As well, Igau reported that the ligands R2PN=CPh(NiPr2) (R = Ph, iPr) are

88 shown to bind either in a monodentate fashion through P or in a tethered fashion involving binding through P as well as π-arene interaction involving the imino-phenyl ring[F].207

Scheme 6.1.2 - Precedence of Ruthenium phosphino-imine ligands displaying importance of amine fragment.

Bidentate ligands containing both phosphine and amine or imine donors have also been well developed.208-216 Rauchfuss reported an early synthesis of a phosphine-imine chelate in 1978, although it was not until the 1990s that these ligands found important applications in late transition metal polymerization catalysts and in catalysts for asymmetric transformations. Typical syntheses of bidentate phosphine-imine ligands involve the formation of the phosphine donor with a pendant aldehyde functionality. This is followed by a condensation with an amine (Scheme 6.1.3). Herein, the preparation of Ru-phosphine-imine complexes via the thermal rearrangement of phosphino-imine precursors is described. The nature of the resulting complexes is reported and the mechanism of the rearrangement is considered.

Scheme 6.1.3 - Conventional synthesis of phosphine imine bidentate ligands.

6.1.2 Template Synthesis

Template synthesis is a powerful tool to enable the access of otherwise either synthetically difficult or virtually inaccessible products. The template effect acts via a metal which facilitates the pre-orientation of a molecule to form an otherwise hard to achieve new molecule. While an in-depth discussion of template synthesis is beyond the scope of this work, a selection of directly related previous studies will be briefly reviewed.

The majority of synthetic template strategies involve the formation of multidentate ligands which surround the coordination sphere of the metal.217-219 Notable examples are tetradentate ligands such as those shown in Scheme 6.1.4. The metals chosen to facilitate this transformation, especially when the metal will be removed to utilize the free ligand, are typically base metals. These metals are chosen due to the fact that they are orders of magnitude less expensive than platinum group metals.

Scheme 6.1.4 - Tetradentate ligands obtained through template synthesis.

A smaller application of ligand templating is the synthesis of bidentate ligands. This strategy has been employed recently in several publications.220,221 While the bidentate ligands are more likely to be synthesized without a template, the template approach tends to employ fewer steps and give significantly higher yields. Two examples of bidentate ligands which are uniquely available via a templating synthetic strategy are shown in Scheme 6.1.5.

Scheme 6.1.5 - Group 8 bidentate ligands obtained through template synthesis.

6.2 Results and Discussion

6.2.1 Ruthenium Phosphino-imine Coordination

With several phosphino-imines in hand from the synthesis of heterocyclic phosphinimines and noting little literature precedent of group 8 coordination chemistry of phosphino-imines, we sought to explore the associated reactivity. The overarching goal of the research is group 8 olefin metathesis chemistry and therefore the primary goal was to investigate ruthenium chemistry.

Scheme 6.2.1 - Synthesis of phosphino-imine analogues of second generation Grubbs catalysts

i Mixing a 1:1 combination of first generation Grubbs catalyst and Pr2PN=CPh2 produced a new product identifiable by NMR spectroscopy. However, efforts to isolate this compound were unsuccessful as it was only observable initially in solution followed by decomposition to unidentifiable products. It is known that analogues of first generation Grubbs catalyst are unstable in solution with a variety of decomposition pathways.222 Therefore, coordination analogues of second generation Grubbs catalyst were considered. Mixing a 1:1 combination of second generation Grubbs catalyst and Ph2PN=CPh2 produced a new product identifiable by NMR spectroscopy. Free tricyclohexylphosphine was observed in the 31P NMR spectrum as well as a new peak at 89.8 ppm. A peak at 19.13 ppm in the 1H NMR spectra corresponded to a new alkylidene. This would suggest a similar geometric configuration for complex 6-1 as what is seen for second generation Grubbs catalyst. While the reaction was first completed with second generation Grubbs catalyst, the removal of the tricyclohexylphosphine from the reaction mixture was problematic and resulted in low reaction yields, approximately 50 %. Starting with an analogue of the fast initiating Grubbs catalyst, RuCl2SIMes(CHPh)py, resulted in the

92 displacement of pyridine which could be removed in vacuo thus simplifying the subsequent purification (Scheme 6.2.1). The resulting yield was greater than 95%. The structure was unambiguously confirmed by single crystal X-ray crystallography (Figure 6.2.1). The most defining spectroscopic features of 6-1 are the 1H NMR signal at 19.13 ppm and 13C resonance centered at 302.0 ppm attributable to the alkylidene moiety. X-ray crystallographic data for 6-1 confirmed the five coordinate Ru centre with a similar geometry as that found in

RuCl2SIMes(CHPh)py. The Ru-Cl distances were found to be 2.3719(7) Å and 2.4043(7) Å. The carbene Ru-C bond distance is 2.087(2) Å while the Ru-alkylidene fragment gives rise to a Ru-C distance of 1.830(3) Å. This may be compared to the known structural study of RuCl2[SI(2,6- diMe)](CHPh)py wherein the Ru-C carbene bond distance is 2.025(3) Å and the Ru-C bond of the alkylidene was determined to be 1.829(3) Å. The phosphino-imine binds to Ru via P and occupies the position trans to the N-heterocyclic carbene ligand with a Ru-P distance of 2.3826(7) Å and a P-N distance of 1.680(2) Å. This compares to a bond distance of 1.7203(14) Å found for free phenyl phosphino-imine.

Figure 6.2.1 - POV Ray Depiction of 6-1. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

6.2.2 Dimer Synthesis

In an effort to synthesize compounds such as RuCl2(R2PN=CPh2)n (R = Ph, iPr, Me),

RuCl2(PPh3)3 and R2PN=CPh2 (R = Ph, iPr, Me) were mixed at room temperature in a variety of solvents (DCM, toluene, and THF). This did not result in the isolation of the desired products. Mixed substitution chemistry was observed by NMR spectroscopy with complex spectra. Free

R2PN=CPh2, PPh3, and unreacted RuCl2(PPh3)3 were identifiable. Heating a 1:1 mixture of

RuCl2(PPh3)3 and Ph2PN=CPh2 at 100°C in bromobenzene for 12 hours resulted in the production of a new compound. The reaction turned from deep brown to bright red. 31 Examination of the reaction by P NMR spectroscopy again showed free R2PN=CPh2, PPh3, and 31 unreacted RuCl2(PPh3)3, however, new P signals were observed at 24.5 and 27.5 ppm. Based on 31P NMR spectrum the yield was approximately 25%.

Heating a 1:1 mixture of the RuCl2(PPh3)3 and Ph2PN=CPh2 at 140°C in bromobenzene resulted in the isolation of new compounds (Scheme 6.2.2). Short reaction times, less than 1 hour, produced two new products. One of the products was the species identified previously during the reaction at 100°C along with a red precipitate which was insoluble in all non-coordinating solvents. When the reaction was carried out for 12 hours, predominately the insoluble red solid was obtained. The insoluble compound was washed with dichloromethane and pentane to give a solid which was insoluble and thus could not be characterized by NMR spectroscopy. Elemental analysis of this product was consistent with the formulation RuCl2(PPh3)(C6H4(PPh2)C(Ph)NH) 6-2. This empirical formula infers the presence of insufficient ligand for Ru, implying aggregation, most likely dimerization via bridging chlorides. The same results were obtained for iPr2PN=CPh2 and Me2PN=CPh2 (Scheme 6.2.2).

Scheme 6.2.2 -- Synthesis of Ruthenium Dimers 6-2, 6-3, 6-4.

X-ray quality crystals of 6-2 were obtained by slow cooling of the reaction mixture from 140°C over the course of several hours. The single crystals obtained were of sufficient quality for single crystal X-ray studies, however, the data was of mediocre quality. High quality single crystal could not be obtained due to the extreme low solubility of 6-2. The crystallographic study of 6-2 confirmed its dimeric nature as [RuCl(µ-Cl)(PPh3)(C6H4(PPh2)C(Ph)NH)]2 (Scheme 6.2.2, Fig. 6.2.2). The crystal structure of 6-2 revealed that the species is a symmetric dimer with the two Ru centres bridged by two chloride atoms. The bridging Ru-Cl distances are 2.4761(10) Å and 2.4720(10) Å with a Cl-Ru-Cl angle of 91.03(4)°. The terminal Ru-Cl bond distance was found to be 2.4409(11) Å. Trans to the bridging Cl atoms are the P atoms of the phosphine-imine ligand and Ph3P. The Ru-P bond distances were determined to be 2.2489(11) Å and

2.3078(12) Å, respectively. Perpendicular to the bridging Ru2Cl2 plane is the N of the imine- phosphine ligand and an additional chloride. The Ru-N distance was found to be 2.013(4) Å. The bite angle for the phosphine-imine chelate is 86.49(10)°. It was possible to observe the imine-H in the crystallographic difference map.

Figure 6.2.2 - POV Ray Depiction of 6-2. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

In a similar fashion, X-ray characterization of 6-4 revealed a similar structure (Fig. 6.2.3). While the metric parameters were similar to those in 6-2, the Ru-P distance in the phosphine-imine chelate was found to be 2.2192(4) Å, reflecting the stronger donor character of the PMe2 fragment in comparison to the PPh2 unit in 6-2. This feature also has an impact on the Ru-Cl distances in 6-4 which were found to be slightly longer with the terminal Ru-Cl bond distance in 6-4 at 2.4462(4) Å and the bridging Ru-Cl distances of 2.4642(3) Å and 2.4991(3) Å. Furthermore, the Ru-N bond distance is elongated from 2.013(4) Å in 6-2 to 2.0236(12) Å in 6-4.

Figure 6.2.3 - POV Ray Depiction of 6-4. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

6.2.3 Monomer Synthesis

Due to the insolubility of the dimers, investigating the associated chemistry was problematic. In an effort to isolate a monomeric species, which one would assume would have increased solubility, reactions to attempt to cleave the monomer were attempted.

First, the dimer was treated with acetonitrile and with a 50:50 mixture of dichloromethane:acetonitrile. In pure acetonitrile, there was no significant change over the course of several hours with a similar result in the solvent mixture. However, subsequent reaction of 6-2 with a 50:50 dichloromethane:pyridine solvent mixture at room temperature gave rise to a new and soluble species 6-5 in nearly quantitative yield. The new species displays 31P{1H} NMR coupled resonances at 44.5 and 43.3 ppm with a P-P coupling constant of 33 Hz. 1 This together with the expected H NMR signals, including a signal at 9.65 ppm which arises from the presence of the NH fragment, are consistent with cleavage of the dimer and the formation of the species formulated as RuCl2(PPh3)(py)(C6H4(PPh2)C(Ph)NH) 6-5 (Scheme 6.2.3). X-ray crystallographic characterization of 6-5 confirmed the pseudo-octahedral geometry about ruthenium, with the phosphine-imine chelate and chlorine atoms in one plane, while the PPh3 and pyridine ligands adopting axial positions (Fig. 6.2.4). The Ru-N and Ru-P distances in the phosphine-imine ligand were found to be 2.0011(15) Å and 2.2860(5) Å while the Ru-Cl bonds trans-to these donors were 2.4492(5) Å and 2.4776(4) Å, respectively. The bite- angle of the chelate in 6-5 is 82.08(4)°. The Ru-P and Ru-N distances of the axial PPh3 and pyridine ligands in 6-5 are 2.3179(5) Å and 2.173(2) Å, respectively.

Figure 6.2.4 - POV Ray Depiction of 6-5. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

In a similar fashion, treatment of 6-4 with a 50:50 dichloromethane:pyridine mixture afforded the species RuCl2(PPh3)(py)(C6H4(PMe2)C(Ph)NH) 6-8 in 89% isolated yield (Scheme 6.2.3). Species 6-8 exhibited 1H NMR signals at 9.51 ppm, corresponding to the imine NH, and 31P{1H} NMR signals at 48.6 and 31.2 ppm with a coupling of 34 Hz, indicating a cis arrangement of the phosphorus ligands in solution. While a single crystal structure was not obtained, the NMR spectra suggested a similar geometric configuration to that of 6-5.

The analogous treatment of 6-3 with pyridine, initially analyzed by NMR spectroscopy, gave, at first impression, a significantly more complex product. Elemental analysis of the mixture indicated the general formation of RuCl2(PPh3)(py)(C6H4(PiPr2)C(Ph)NH), as that seen for compound 6-5, while the NMR spectrum, shown in Figure 6.4.3, clearly displays a surplus of signals. These species exhibited singlets in the 31P{1H} NMR spectrum at 59.6 and 57.5 ppm in a 2:1 ratio. In addition 1H NMR resonances at 12.33 and 11.04 ppm attributable to the NH fragment of the phosphine-imine ligand. These data suggest the formation of two new species,

6-6 and 6-7, as isomers of RuCl2(py)2(C6H4(PiPr2)C(Ph)NH) in which the pyridine ligands are

99 cis and trans respectively. The combined yield of the two new species, 6-6 and 6-7, was determined to be 92%.

Scheme 6.2.3 - Synthesis of ruthenium monomers 6-5, 6-6, 6-7, 6-8.

The postulate of the formation of two isomers was unambiguously confirmed via X-ray crystallography. These compounds crystallized as blocks and needles respectively allowing the manual separation of the two species and thus the acquisition of X-ray crystallographic data for both 6-6 and 6-7 (Scheme 6.2.3, Fig. 6.2.5). These data confirmed the geometries of these pseudo-octahedral complexes. In the case of 6-7, the trans-Ru-Cl distances were found to range from 2.414(2) Å to 2.436(2) Å in the two molecules in the asymmetric unit. The cis pyridine ligands result in Ru-N distances average 2.165(5) Å. The Ru-N and Ru-P distances for the iminophosphine chelate average 1.990(5) Å and 2.267(2) Å, while the N-Ru-P angle was found to be 86.1(2)°. In the other isomer 6-7 (figure 6.2.5), the cis-Ru-Cl distances were found to be 2.447(1) Å and 2.511(1) Å. This marked difference may be attributed to the corresponding trans N and P atoms, respectively. The trans-pyridine ligands give rise to Ru-N distances of 2.123(4) Å and 2.120(3) Å. Interestingly the metric parameters for the phosphine-imine chelate in 6-7 did not differ significantly from that in 6-6 as the Ru-N distance in the chelate ligand in 6-7 is

1.991(3) Å while the Ru-P distance is 2.261(1) Å with a N-Ru-P bite angle of 87.7(1)°.

100

Figure 6.2.5 - POV Ray Depiction of 6-6 and 6-7. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

In an endeavour to extend the coordination chemistry of the newly synthesized ligands and to improve stability in air, pyridine free coordination complexes were sought. Treatment of 6-5,

6-6, 6-7, and 6-8 with excess PPh3 only afforded a new species in the case of the reaction with 6-8. This is attributed to a steric effect, as the methyl substituents of 6-8 causes the least

101 sterically crowded center. A new species 6-9 was synthesized in 85% yield. This species exhibited a doublet and a triplet in the 31P{1H} NMR spectrum at 27.5 and 24.5 ppm with a P-P coupling of 27.5 Hz. These data suggest the formulation of 6-9 as

RuCl2(PPh3)2(C6H4(PMe2)C(Ph)NH) in which the two PPh3 ligands are in an identical environment and thus are cis to the P of the phosphine-imine chelate (Scheme 6.2.4). X-ray crystallographic data for 6-9 unambiguously confirmed this formulation with a geometry (Figure 6.2.6) that was analogous to that of 6-8. The two phosphine ligands adopt trans position axial to the NPRuCl2 plane. The Ru-P distances for the axial phosphines are 2.396(1) Å and 2.400(1) Å. The Ru-Cl distances in 6-9 were found to be 2.4658(11) Å and 2.4963(11) Å, while the Ru-P and Ru-N distances associated with the imino-phosphine ligand are found to be 2.015(4) Å and 2.2493(13) Å, respectively. The corresponding bite angle of the N-P chelate of 84.4(1)° is smaller than in 6-8, presumably a result of the increased steric demands of the axial ligands.

Figure 6.2.6 - POV Ray Depiction of 6-9. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

102

Scheme 6.2.4 - Synthesis of 6-9.

6.2.4 Extended Reactivity

6.2.4.1 Palladium

The discovery of the new rearrangement chemistry wherein phosphino-imines, under thermal duress, afforded a new P,N-bidentate ligand has been described. The synthesis of such a ligand, in the absence of a metal mediated process, does not have an obvious route. The reactions to synthesize ruthenium species have been optimized to produce a high yielding, one step synthesis, however, the extent of such reactivity across the d-block was in question.

Scheme 6.2.5 - Synthesis of 6-10 and 6-11.

Looking to extend the reactivity of phosphino-imines, the chemistry of palladium was explored. Dichlorobis(benzonitrile)palladium(II) and palladium(II) iodide were selected and gave way to a similar result. The results of the palladium(II) iodide reactivity were more consistent and therefore were more extensively explored. Mixing a 1:1 or 2:1 mixture of Ph2PN=CPh2 and PdI2 in bromobenzene at room temperature gave near quantitative yields of [PdI2(Ph2PN=CPh2)]2 6-10 with respect to the palladium source (Scheme 6.2.5). The NMR spectrum displayed a single peak in the 31P NMR spectrum at 53.1 ppm. The 1H NMR spectrum displayed only the peaks expected for an extended aromatic system within the range of 7.2 ppm and 9.0 ppm. Primarily of note is the lack of a 1H peak corresponding to the formation of an imine-H. In an effort to induce

103 the thermal rearrangement observed about a ruthenium center, a 1:1 and a 2:1 mixture of

Ph2PN=CPh2 and PdI2 were subjected to varying levels of heating. Samples were allowed to mix at 80°C, 120°C, and 160°C in bromobenzene without observing differing results as those seen at room temperature. Furthermore, isolated crystals of 6-10 were dissolved in bromobenzene and heated to 160°C without observing any reactivity.

The structure of 6-10 was unambiguously confirmed with a single crystal X-ray study (Figure 6.2.7). The molecular structure displayed a dimeric molecular structure bridging via iodides. The dimer has crystallographic imposed symmetry across the bridging iodides. The bridging Pd-I bonds were found to be 2.6140(2) Å and 2.6710(2) Å while the terminal Pd-I bond length was found to be 2.6076(2) Å. The Pd-P bond length was determined to be 2.2516(5) Å which 223 compares to 2.340(2) Å of that found in PdI2(PPh3)2. Finally, of note is the shortening of the P-N bond distance from 1.7203(14) Å found in the free phosphino-imine to the P-N bond distance of 1.6789(16) Å found in 6-10.

Figure 6.2.7 - POV Ray Depiction of 6-10. C: black, Pd: yellow/green, I: pink, P: orange, N aquamarine. H atoms omitted for clarity.

6.2.4.2 Iron

As described in the introduction, the template strategy is a viable strategy to produce a novel ligand which is otherwise unattainable. While ruthenium is a member of the platinum group metals, and therefore of significant relative expense, iron, a member of the base metals, is of less relative expense. The market price of iron is significantly inconsequential thus its use

104 sacrificially in a ligand synthesis may be considered. Therefore, the transfer to iron of the newly developed ruthenium template chemistry was investigated.

Using reaction protocols similar to those employed in ruthenium and palladium chemistry the reactivity towards iron was investigated. Reactions with a range of iron dihalides were investigated, FeX2 (X = Cl, Br, I), similar reactivity was observed in all cases, therefore, only the reactivity of FeCl2 is described. Mixing a 1:1 solution of Ph2PN=CPh2 and FeCl2(THF)2 resulted in the clean formation of FeCl2(Ph2PN=CPh2)2. While X-ray quality crystal could not be obtained, elemental analysis suggested the formation of FeCl2(Ph2PN=CPh2)2. Heating both a mixture of Ph2PN=CPh2 and FeCl2(THF)2 and isolated FeCl2(Ph2PN=CPh2)2 predominantly resulted in the formation of FeCl2(Ph2P(O)N=CPh2)(HN=C(Ph2)) 6-11 (Scheme 6.2.5). An NMR spectrum, obviously paramagnetic, was not possible to assign. X-ray quality crystals were obtained of 6-11 and the connectivity determined (Figure 6.2.8). The reaction forming 6-11 was complex and the route to the product is not obvious. Once again, as observed with ruthenium chemistry, the P-N bond of 6-11 was non-innocent and the resulting complex contained one equivalent of benzophenone imine as well as one equivalent of oxidized phosphino-imine. The iron center of 6-11 is a distorted pseudo-tetrahedral complex. Iron chloride bonds were found to be 2.3114(13) Å and 2.3470(13) Å. The Fe-N bond distance was found to be 2.088(4) Å while the Fe-O distance was 1.926(6) Å. The benzophenone imine hydrogen could be detected in the X-ray difference map and the N-H bond distance determined to be 1.00(6) Å. Finally the P-N bond distance was 1.651(5) Å compared to 1.7203(14) Å found in Ph2PN=CPh2.

105

Figure 6.2.8 - POV Ray Depiction of 6-11. C: black, Fe: yellow, Cl: green, P: orange, O red, N aquamarine, H grey. Most H atoms omitted for clarity except H100 bound to imine.

106

6.2.5 Mechanistic Considerations

In considering the mechanism of the rearrangement of the phosphinoimine ligands leading to 6-2 to 6-9, it is reasonable to speculate that the initial binding of the phosphinoimine to form a ruthenium complex is monodentate via phosphorus. In fact, new 31P NMR signals are immediately observable after the mixing of any combination of Ph2PNCPh2 and Ru(PPh3)3Cl2.

While no monodentate species is isolable from the mixture of Ph2PNCPh2 and Ru(PPh3)3Cl2, as the mixture is intractable, the ability of phosphino-imines to bind in a monodentate fashion was proven via the formation of 6-1 (Figure 6.2.1). In an effort to further study the thermal rearrangement of phosphino-imines, the thermolysis of 6-1 under the conditions used to give 6-2 to 6-9 was carried out. The thermolysis of 6-1 did not led to isolable phosphine-imine chelate complexes. This may suggest that the strong trans influence of the alkylidene ligand in 6-1 precludes interaction of the imino-arene rings with the metal.

Concerning the template synthesis of phosphino-imine ligands, one may presume this begins with initial coordination of the phosphorus of the phosphino-imine to ruthenium. Such coordination would form a species such as Ru(PPh3)2(Ph2PNCPh2)Cl2 (Scheme 6.2.6). This species would be very analogous to the Ru-phosphino-imine complexes of the form 207 RuCl2(iPrC6H4Me)(R2PNCR2) prepared by Igau. Subsequently, the reaction could proceed via transient oxidative addition of an aryl C-H bond to Ru. This reaction has significant precedence with respect to the formation of imine-aryl ligands.224-227 Proton transfer from the metal to N would result in the intermediate A (Scheme 6.2.6). Subsequently, a reductive elimination via P-C bond formation would give rise to the phosphine-imine ligand complexes seen in 6-2 to 6-9. In addition, the demonstrated ability of the complexes reported by Igau to form Ƞ6-arene complexes, Scheme 6.2.6, supports the notion that under thermal duress the proposed transient C-H oxidative addition may be possible (Scheme 6.2.6). Finally the proposition of the intermediate A is notionally supported by the known metallated aryl-imines complexes of the + form [(Arene)Ru(PMe3)(C6H4C(R)=NH)] prepared and fully characterized by Boncella and coworkers.228,229 Analogous metallated-imine Rh complexes have also been described by James and coworkers.220

107

Scheme 6.2.6 - Proposed intermediates towards the P-N rearrangement.

Further support for this proposed intermediate, A, was derived from prolonged heating of the reaction of Me2PN=CPh2 with RuCl2(PPh3)3 in an open reaction vessel. The subsequent species 6-12 could be observed. The new species, 6-12, was isolated, albeit in rather low yield likely less than 10%. This provided a preliminary molecular structure suggesting a formulation of

RuCl2(PPh3)2(HN=C(Ph)C6H4). The complex, 6-12, was subsequently rationally prepared using two different syntheses (Scheme 6.2.7).

Scheme 6.2.7 - Synthesis of 6-12 using two methods.

First, preparation of 6-12 was attempted via combining a 1:1 mixture of benzophenone imine and

RuCl2(PPh3)3. Under such conditions benzophenone imine and RuCl2(PPh3)3 could not be observed to react. The addition of five equivalents of potassium carbonate to a 1:1 mixture of benzophenone imine and RuCl2(PPh3)3 in dichloromethane at room temperature produced a 43% yield of 6-12. Secondly, 6-12 could be prepared in 71% yield via the thermal reaction of

RuH(PPh3)3Cl and benzophenone imine in 1,2-dichloroethane. While the spectroscopic characterization of 6-12 was problematic due to its paramagnetic nature, the magnetic

108 susceptibility was determined to be approximately 1.20 BM. This would suggest the formal oxidation of the formally Ru(II) species to a new Ru(III) species. Furthermore, the crystallographic characterization of 6-12 unambiguously confirmed its formulation to be

RuCl2(PPh3)2(HN=C(Ph)C6H4) (Figure 6.2.9). The crystallographic data of 6-12 showed the two triphenylphosphines adopt a trans configuration, while the two chlorides are cis to each other and trans to an aryl-imine chelate. The Ru-P bond distances were found to be 2.4115(4) Å and 2.3828(4) Å and the Ru-Cl bond distances were found to be 2.4283(4) Å and 2.3573(4) Å. The chelating aryl-imine gave rise to Ru-C and Ru-N bond distances of 2.0384(16) Å and 2.0470(13) Å while the bite angle of this chelate was found to be 76.15(6)°. This Ru-bound metallated aryl-imine fragment is structurally similar to those described by Boncella et al.

Figure 6.2.9 - POV-Ray Depiction of 6-12. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. H atoms omitted for clarity.

Presumably, in the case of thermolytic reaction of Me2PN=CPh2 and the Ru precursor, loss of

•PMe2 generates P2Me4 and the aryl-imine Ru(III) complex 6-12 (Scheme 6.2.6). However, it is noteworthy that the low yield of 6-12 meant that efforts to observe the purported byproduct

P2Me4 by NMR spectroscopy were unsuccessful. Nonetheless, the formation of 6-12 from the

109 phosphino-imine supports the notion of an intermediate incorporating a metallated aryl-imine fragment.

6.3 Conclusion

Herein, we have prepared and characterized Ru-phosphine-imine chelate complexes which are readily derived from the thermolysis of phosphinoimines with suitable Ru precursors. A mechanism involving transient oxidative C-H addition is proposed and supported to some extent by further observations. Further study of the applications of the resulting complexes is described in the on-going chapter. In addition, we attempted to exploit this facile rearrangement to develop phosphine-imine complex chemistry for other transition metal systems.

110

6.4 Experimental

6.4.1 General Considerations

All manipulations were carried out under an atmosphere of dry, O2-free N2 employing a MBraun glove box and a Schlenk vacuum-line. Solvents were purified with a Grubbs-type column system manufactured by Innovative Technology and dispensed into thick-walled Schlenk glass flasks equipped with Teflon-valve stopcocks (pentane and CH2Cl2), or were dried over the appropriate agents and distilled into the same kind of storage flasks (C6H5Br). All solvents were thoroughly degassed after purification (repeated freeze-pump-thaw cycles). The deuterated solvent was dried over the appropriate agent, vacuum-transferred into storage flasks with Teflon stopcocks and degassed accordingly (CD2Cl2). Pentane was stored over a potassium mirror, while bromobenzene and dichloromethane were stored over 4 Å molecular sieves. 1H, 13C, and 31P NMR spectra were recorded at 25 °C on Varian 300 and 400 MHz and Bruker 400 MHz spectrometers. Chemical shifts are given relative to SiMe4 and referenced to the residue solvent 1 13 31 signal ( H, C) or relative to an external standard ( P: 85% H3PO4). Chemical shifts are reported in ppm and coupling constants as scalar values in Hz. Combustion analyses were performed in house employing a Perkin-Elmer CHN Analyzer.

All common organic reagents were purified by conventional methods unless otherwise noted. 73 The compounds R2PN=CPh2 (R = Ph, iPr, Me) were prepared by literature methods. All other reagents were purchased from Aldrich and were used as received. RuCl2(py)(SIMes)(CHPh) was purchased from the Aldrich Chemical Co. and RuCl2(PPh3)3 was prepared according to a literature procedure.230

6.4.2 Additional Information

On occasion repeated attempts to obtain satisfactory EA for Ru complexes resulted in good N and H analyses but consistently low C analysis. This was attributed to the formation metal- carbides during combustion. In these cases, NMR data for the pure samples have been deposited in the experimental section of this thesis.

111

6.4.3 Synthesis

Synthesis of [RuCl(µ-Cl)(PPh3)(C6H4(PPh2)C(Ph)NH)]2 6-2:

To a 5 mL solution of Ru(PPh3)3Cl2 (480 mg, 0.50 mmol) was

added a 5 mL solution of Ph2PN=CPh2 (183 mg, 0.50 mmol). The solution was heated for one hour at 140°C in a Schlenk bomb sealed with a Teflon tap. The solutions initial brown colour changed to a red solution with a red precipitate. The reaction was filtered hot onto a glass fritted filter and washed with bromobenzene (3 x 10 mL) and pentane (3 x 10 mL). The product was insoluble, precluding characterization by NMR spectroscopy. X- ray quality crystals were grown from the slow cooling of a saturated bromobenzene solution at 140°C. Alternatively, if the reaction is carried out in a NMR tube X-ray quality crystals form throughout the course of the reaction.

6-2: Yield: 86 %. EA: Calc for C48H40NP2Cl2Ru: C, 61.52; H, 4.21; N, 1.46. Found: C, 61.60; H, 4.30; N, 1.48

Synthesis of [RuCl(µ-Cl)(PPh3)(C6H4(PR2)C(Ph)NH)]2 (R = iPr 6-3, Me 6-4) These compounds were prepared in a similar fashion and thus only one preparation is detailed. To a 5 mL

solution of Ru(PPh3)3Cl2 (480 mg, 0.50 mmol) was added a

5 mL solution of Ph2PN=CPh2 (183 mg, 0.50 mmol). The solution was heated overnight at 140°C in a Schlenk bomb sealed with a teflon tap. The solution's initial brown colour changed to a red solution with a red precipitate. The reaction was filtered hot onto a glass fritted filter and washed with bromobenzene (3 x 10 mL) and pentane (3 x 10 mL). These products were insoluble, precluding characterization by NMR spectroscopy. X-ray quality crystals of 2 and 3 were grown from the slow cooling of a saturated bromobenzene solution at 140°C.

6-3: Yield: 48 %. EA: Calc for C34H32NP2Cl2Ru: C, 60.67; H, 4.79; N, 2.08. Found: C, 59.30; H, 5.10; N, 2.09.

6-4: Yield: 85 %. EA: Calc for C28H31NP2Cl2Ru: C, 58.67; H, 4.63; N, 2.07. Found: C, 58.13; H, 5.13; N, 2.32.

112

Synthesis of RuCl2(PPh3)(py)(C6H4(PR2)C(Ph)NH) (R = Ph 6-5, Me 6-8) These compounds were prepared in a similar fashion and thus

only one preparation is detailed. To a suspension of the 1 in CH2Cl2 (2.5 mL) was added (2.5 mL) pyridine. The solution was stirred at room temperature for 2 h and filtered through Celite. Pentane (15 mL) was added to precipitate the product which was collected by filtration and dried in vacuo. X-ray quality crystals were grown from the slow evaporate of a pyridine solution.

1 6-5: Yield: 93 %. H NMR (CD2Cl2): 9.93 (br), 9.65 (br, NH), 8.50-8.86 (br), 7.01-7.70 (m); 31 1 2 2 13 1 P{ H} NMR (CD2Cl2): 44.5 (d, , JP-P = 33 Hz), 43.3 (d, JP-P = 33 Hz); C{ H} NMR

(CD2Cl2):149.7, 138.4, 136.6, 135.7, 134.6, 134.0, 130.8, 130.3, 129.3, 128.7, 127.6, 127.4,

127.1, 123.7; EA: Calc. for C53H45N2P2Cl2Ru: C, 65.60; H, 4.59; N,3.19; found: C, 65.16; H, 4.63; N, 3.27.

1 6-8: Yield: 89 %. H NMR (CD2Cl2): 9.51 (br, 1H, NH), 9.05, 8.86, 8.63, 8.09, 6.88-7.52, 1.97 2 2 31 1 (d, JH-H = 8.8 Hz, 3H, CH3), 0.78(d, JH-H = 9.5 Hz, 3H, CH3); P{ H} NMR (CD2Cl2): 48.6 (d, 2 2 13 1 JP-P = 34 Hz,) , 31.2(d, JP-P = 34 Hz); C{ H} NMR (CD2Cl2): 175.40, 175.3, 153.8, 150.2, 140.2, 137.2, 136.8, 136.6, 136.5, 136.1, 134.4, 134.3, 133.4, 133.3, 132.5, 132.1 131.4 131.3 130.4 129.5, 129.5, 129.0, 128.0, 126.8, 126.0, 125.9, 124.0, 123.6, 123.6, 18.3 (d), 9.79 (d). EA:

Calc. for C33H36N2P2Cl2Ru: C, 60.48; H, 4.81; N,3.71; found: C, 60.12; H, 4.92; N, 3.65.

113

Synthesis of cis-RuCl2(py)2(C6H4(PiPr2)C(Ph)NH) 6-6 and

trans-RuCl2(py)2(C6H4(PiPr2)C(Ph)NH) 6-7: To a suspension of

the dimer in CH2Cl2 (2.5 mL) was added (2.5 mL) pyridine. The solution was stirred at room temperature for 2 h and subsequently filtered through Celite. Pentane (15 mL) was added to precipitate the product which was collect by filtration and dried in vacuo. Yield of 6-6 and 6-7: 92 %. Ratio 6-6 : 6-7 = 73:27.

1 6-6: H NMR (CD2Cl2): 12.33 (br, 1H, NH), 7.44-7.74 (8) 2.62-2.76 2 2 (m, 2H, CH(CH3)2), 0.97 (dd, JP-H = 13.6, JH-H = 7.2 Hz, 6H, 2 2 CH(CH3)2), 0.85 (dd, , JP-H = 14.4, JH-H = 7.2 Hz, 6H, CH(CH3)2); 31 1 13 1 P{ H} NMR (CD2Cl2): 59.6; C{ H} NMR (CD2Cl2): 141.5, 134.0, 133.9, 131.0, 130.9, 129.9, 129.7, 129.1, 126.7, 26.2, 26.0, 16.8, 16.5.

1 6-7: H NMR (CD2Cl2): 11.04 (br, 1H, NH), 7.44-7.74 (8) 2.78-2.89 (m, 2H, CH(CH3)2), 1.00- 31 1 1.10 (m, 12H, CH(CH3)2); P{ H} NMR (CD2Cl2): 57.5.

EA(for 6-6/6-7): Calc. for C29H34N3Cl2Ru · ½CH2Cl2 from crystallization: C, 52.88; H, 5.27; N, 6.27. Found: C, 52.51; H, 5.30; N, 6.59.

Synthesis of RuCl2(PPh3)2(C6H4(PMe2)C(Ph)NH) 6-9: To a toluene

(10 mL) solution of 5 (47 mg, 0.05 mmol,) was added PPh3 (12 mg, 0.07 mmol). The solution was stirred overnight. The solution was dried in vacuo, washed with 5 mL of diethyl ether. Yield: 85 %.

1 2 31 1 H NMR (CD2Cl2): 7.67-7.77(m, 39H), 6.10 (br, 1H), 1.02 (d, JH-H = 8.8 Hz, 6H); P{ H} 2 2 13 1 NMR (CD2Cl2) : 27.5 (t, JP-P = 27.5 Hz, 1P), 24.5 (d, JP-P = 27.5 Hz, 2P); C{ H} NMR

(CD2Cl2): 137.4, 137.3, 134.5, 134.4, 134.1, 133.8, 133.6, 129.5, 129, 128.7, 128.6, 128.5, 128.3,

127.9, 127.0, 126.9, 126.8, 126.3, 18.8, 8.3; EA: Calc. for C51H46NP3Cl2Ru: C, 62.53; H, 4.70; N,1.28. Found: C, 62.86; H, 5.35; N, 1.06. X-Ray quality crystals were grown from cooling a saturated bromobenzene solution.

114

Synthesis of RuCl2(SIMes)(CHPh)(iPr2PN=CPh2) 6-1: A CH2Cl2

solution (5 mL) of 2 (30mg, 1 mmol, 1 eq) was added to a CH2Cl2

solution (5 ml) of RuCl2(py)(SIMes)(CHPh) (73 mg, 1 mmol, 1 eq). The reaction was stirred for 2 h while the brown reaction mixture changed to deep green. Pentane (10 mL) was added and the reaction mixture was cooled to -35C. Overnight green crystals were formed. (Yield: 70 mg, 0.86 mmol, 86 %).

1 H NMR (CD2Cl2): 19.13(s, 1H, Ru=CH), 7.76-7.94(br, 2H, Ph), 7.16-7.40(11H, m, Ph), 6.87-

6.94(m, 4H, Ph), 6.22-6.49(br, 2H, Ph), 4.03(t, 2H, J = 9.9Hz, CH2), 3.87(t, 2H, J = 9.9Hz,

CH2), 2.62(s, 6H, CH3), 2.23(s, 9H, CH3), 2.02(s, 3H, CH3), 0.54-0.62(m, 6H, CH(CH3)2), 0.30- 31 1 13 1 0.50(br, 6H, CH(CH3)2) P{ H} NMR (CD2Cl2) 89.8 C{ H} NMR (CD2Cl2): 301.7-302.3(m, Ru=CH), 220.8, 219.9, 171.1, 170.9, 151.3, 140.5, 140.4, 139.4, 138.9, 138.0, 137.5, 137.2, 135.2, 132.0, 129.7, 129.7, 128.9, 128.0, 127.8, 52.2, 51.9, 26.7, 21.1, 21.09, 20.2, 18.9, 18.6,

18.2; EA: Calc. for C47H56N3PCl2Ru: C, 65.19; H , 6.52; N, 4.85. Found: C, 64.96; H, 6.68; N, 4.68. X-Ray quality crystals were grown from cooling a saturated bromobenzene solution.

Synthesis of RuCl2(PPh3)2(HN=C(Ph)C6H4) 6-12: To a

1,2-dichloroethane (20 ml) solution of RuH(PPh3)3Cl (290 mg, 0.30 mmol) was added benzophenone imine (60 mg, 0.33 mmol). The solution was heated overnight in a Schlenk flask at 70°C, The solution was removed in vacuo, washed with 50 ml of diethyl ether and 50 ml of pentane. Yield:

71 %, µeff = 1.20 BM, X-ray quality crystals were grown from a layered solution of dichloromethane and cyclohexane. EA: Calc. for C49H40NP2Cl2Ru: C, 67.12; H, 4.60; N,1.60. Found: C, 67.03; H, 5.03; N, 1.77.

115

Synthesis of [PdI2(Ph2PN=CPh2)]2 6-10: To a

bromobenzene (5 ml) solution of PdI2

(72 mg, 0.20 mmol) was added Ph2PN=CPh2 (73 mg, 0.20 mmol). The solution was heated to 100°C and mixed overnight. The resulting solution was filtered and the initial turbid brown/yellow solution turned light orange over the course of 24 hours. The solution was removed in vacuo, washed with 10 mL of diethyl ether, and recrystallized from dichloromethane.

1 H NMR (C5D5N): 8.50, 8.12, 8.08, 8.06, 7.84, 7.82, 7.36, 7.34, 7.31, 7.29, 7.19, 7.17, 7.16, 31 1 13 1 7.12, 7.01, 6.98, 6.68, 6.66, 6.65. P{ H} NMR (C5D5N): 52.9. C{ H} NMR (C5D5N): 181.2, 181.16, 153.6, 149.9, 139.3, 139.18, 139.1, 138.42, 136.9, 133.5, 133.4, 128.3, 127.6, 127.51.

116

6.4.4 X-ray Crystallography

6.4.4.1 X-Ray Data Collection and Reduction

6.4.4.2 X-Ray Data Solution and Refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations. 118 The heavy atom positions were determined using direct methods employing the SHELXTL direct methods routine. The remaining non-hydrogen atoms were located from successive difference Fourier map calculations. The refinements were carried out by using full-matrix least squares techniques 2 2 2 on F, minimizing the function  (Fo–Fc) where the weight  is defined as 4Fo /2 (Fo ) and Fo and Fc are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C-H bond length of 0.95 Å. H-atom temperature factors were fixed at 1.20 times the isotropic temperature factor of the C-atom to which they are bonded. The H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance.

117

6.4.4.3 Tables of Crystallographic Data

Table 6.4.1 - Select Crystallographic Data for 6-1, 6-2, and 6-4 6-1 6-2 6-4

Formula C47H56Cl2N3PRu C90H78Cl12N2 P4Ru2 C66H62Cl4N2P4Ru2 Formula weight 865.89 1938.96 1351.00 Crystal System monoclinic monoclinic triclinic

Space group P21/c C2/c P-1 a(Å) 11.7266(7) 25.477(2) 10.0277(4) b(Å) 19.7505(14) 12.7495(10) 12.3376(5) c(Å) 19.5819(14) 28.088(2) 14.2100(5) α(deg) 90.00 90.00 98.147(2) β(deg) 107.349(3) 103.210(5) 110.240(2) γ(deg) 90.00 90.00 110.453(2) V(Å3) 4329.0(5) 8882.0(12) 8882.0(12) Z 4 4 1 d(calc)gcm-3 1.329 1.450 1.521 R(int) 0.0590 0.0900 0.0350 Abs coeff,μ,mm-1 0.558 0.819 0.845 Data collected 38912 85843 42278 2 >2(FO ) 9734 6341 11200 Variables 497 496 476 R(>2) 0.0367 0.0530 0.0271

Rw 0.0878 0.1546 0.0667 GOF 1.028 0.945 1.008

118

Table 6.4.2 - Select Crystallographic Data for 6-5, 6-6, and 6-7 6-5 6-6 6-7

Formula C63H55Cl2N5 P2Ru C29H34Cl2N3PRu C30H34Cl4N3PRu Formula weight 1116.03 627.53 710.44 Crystal System monoclinic monoclinic orthorhombic

Space group P21/c P21/n Pbca a(Å) 10.6627(5) 9.0765(9) 15.4539(12) b(Å) 17.9387(8) 46.734(5) 18.3795(15) c(Å) 28.2348(12) 13.7877(14) 21.2573(16) α(deg) 90.00 90.00 90.00 β(deg) 92.259(2) 108.453(6) 90.00 γ(deg) 90.00 90.00 90.00 V(Å3) 5396.4(4) 5547.7(10) 6037.8(8) Z 4 8 8 d(calc)gcm-3 1.374 1.503 1.563 R(int) 0.0365 0.1516 0.0703 Abs coeff,μ,mm-1 0.495 0.839 0.952 Data collected 78203 49302 78740 2 >2(FO ) 15702 7009 6424 Variables 662 657 365

Rw 0.1084 0.1219 0.1559 GOF 1.036 1.007 1.071

119

Table 6.4.3 - Select Crystallographic Data for 6-9, 6-10, and 6-11 6-9 6-10 6-11

Formula C120H102Br3Cl4N2P6Ru2 C50H40I4N2P2Pd2 C38H31Cl2NOP2Fe Formula weight 2341.53 1451.27 689.37 Crystal System monoclinic Triclinic monoclinic

Space group P21/n P-1 P21/n a(Å) 17.1587(7) 10.9772(9) 10.0439(6) b(Å) 14.9111(6) 11.3048(9) 18.1578(9) c(Å) 20.5139(8) 13.1470(11) 18.4031(10) α(deg) 90.00 76.710(4) 90.00 β(deg) 99.453(2) 85.900(4) 98.514(3) γ(deg) 90.00 61.697(3) 90.00 V(Å3) 5177.3(4) 1396.6(2) 3319.3(3) Z 2 2 4 d(calc)gcm-3 1.502 1.886 1.725 R(int) 0.0681 0.0312 0.0919 Abs coeff,μ,mm-1 1.697 3.140 3.109 Data collected 110057 64476 42811 2 >2(FO ) 8777 13645 5864 Variables 640 298 410

Rw 0.1313 0.0799 0.2646 GOF 1.038 1.031 1.029

120

Table 6.4.4 - Select Crystallographic Data for 6-12 6-12

Formula C49H40Cl2NP2Ru Formula weight 876.73 Crystal System orthorhombic

Space group P212121 a(Å) 12.1208(5) b(Å) 14.9206(6) c(Å) 22.2574(8) α(deg) 90.00 β(deg) 90.00 γ(deg) 90.00 V(Å3) 4025.2(3) Z 4 d(calc)gcm-3 1.447 R(int) 0.0461 Abs coeff,μ,mm-1 0.638 Data collected 68210 2 >2(FO ) 16116 Variables 500

Rw 0.0640 GOF 1.025

121

6.4.5 Supplementary NMR Data

122

Figure 6.4.1 - Clean NMR spectras in lieu of EA of 6-8. Top 1H NMR, middle 31P NMR, and bottom 13C NMR

123

Figure 6.4.2 - Clean NMR spectras of 6-5 in lieu of EA. Top 1H NMR, middle 31P NMR, and bottom 13C NMR

124

Figure 6.4.3 - Overlaid NMR spectra of RuiPrpy dimer. Top 1H NMR mixture of cis and trans isomers. Bottom 1H NMR of cis pyridine

125

Chapter 7 P,N Catalytic Hydrogenation

7 7.1 Introduction

7.1.1 Hydrogenation

Catalytic hydrogenation of unsaturated compounds began with the discovery by Sabatier in 1897 that traces of nickel could mediate the catalytic addition of hydrogen to olefins. This discovery of the use of Ni as a heterogeneous catalyst culminated in a share of the 1912 Nobel Prize with Grignard. The onset of organometallic chemistry and the discoveries of Ru and Rh based hydrogenation catalysts by Wilkinson and others in the 1960s prompted the evolution of homogeneous transition metal based hydrogenation catalysts for a variety of substrates. Wilkinson discovered his namesake catalyst, Wilkinson's catalyst, and published several articles in the mid-1960s demonstrating their use as olefin hydrogenation catalysts.122,231-236 Wilkinson's catalyst, chlorotris(triphenylphosphine)rhodium(I), is a square planar complex. A simplified catalytic cycle is shown in Scheme 7.1.1. These catalysts operated by the interaction of hydrogen with the metal to effect oxidative addition affording intermediate dihydride complexes.124,237,238 Such a species may then insert an unsaturated substrate followed by reductive elimination to afford the reduced species.

126

Scheme 7.1.1 - Wilkinson's catalyst transition metal hydrogenation catalytic cycle.

7.1.2 Transfer Hydrogenation

A divergent strategy to catalytically hydrogenate an unsaturated substrate is the use of a sacrificial hydrogenation source in place of molecular hydrogenation, so called transfer hydrogenation. While this transfer hydrogenation may be used to hydrogenate a wide range of functionalities, the applications towards ketone hydrogenation have seen the majority of investigation. The typical source of a stoichiometric amount of hydrogen is iso-propanol. The use of iso-propanol is desirable due to the fact that iso-propanol is in itself inexpensive and non-toxic, furthermore, the byproduct, acetone, is similarly benign. The transfer hydrogenation is further promoted in the majority of instances with a greater than stoichiometric ratio of base. t Typical bases include K2CO3, NaOH, KOH, and KO Bu. The presence of an NH or NH2 in the auxiliaries is crucial for catalytic activity; the corresponding dialkylamino analogues are totally ineffective.128 The transfer hydrogenation of acetophenone has become the defacto standard for a first analysis of the catalytic competency of a newly synthesized catalyst. The transfer hydrogenation to produce 1-phenylethanol is outlined in Scheme 7.1.2.

127

Scheme 7.1.2 -- General transfer hydrogenation of acetophenone to 1-phenylethanol.

Fryzuk et al. observed in the early 1980s that making the use of appropriate ligands one could observe the ligand-assisted heterolytic splitting of hydrogen.239-241 This work was contained to organometallic amide complexes supported by rhodium and iridium. However, the importance was only begun to be realized when Crabtree et al. proposed its importance but the H2 activation remained stoichiometric and contained to rhodium and iridium.124,242 In the 1990s Noyori discovered that transition metal complexes incorporating amido-ligands effect heterolytic cleavage of hydrogen.128,131 The initial systems were based on ruthenium and displayed unprecedented activity towards the reduction of prochiral ketones and imines. Since this time, a significant amount of research has been focused towards transition metal mediated transfer hydrogenation. The transition metals which have garnered the most interest since this time have been primarily ruthenium, rhodium, and iridium, with a recent interest in iron chemistry. As for the subject of auxiliary ligand framework, this has focused on phosphorus-nitrogen based bidentate, tridentate and tetradentate ligands.243 Notable examples of auxiliary ligands are shown in Scheme 7.1.3.

Scheme 7.1.3 - Selection of ligands which promote catalytic transfer hydrogenation.

The typical use of base promotes the transition metal catalysis. The use of base results in a metal hydride (Scheme 7.1.4). Outer sphere transfer of the proton, typically from the nitrogen containing supporting ligand, and hydride to a substrate afford the hydrogenation.128,131

128

Scheme 7.1.4 - Mechanism of base-mediated transfer hydrogenation.

129

7.2 Results and Discussion

The novel complexes synthesized and characterized in Chapter 6 contained a unique bidentate ligand with latent functionality contained in an imine functionality. While similar ligand sets have been prepared, such a ligand framework with an imine NH donor coordinated to a ruthenium center has not been reported. Similar ligands prepared have been applied to a variety of catalytic applications as described, however, the effectiveness towards hydrogenation was of particular interest for us.

7.2.1 Hydrogenation

The ability to apply the complexes described in Chapter 6 towards olefin hydrogenation was of particular interest. The direct exposure of complex 6-5 to 4 atmospheres of H2 pressure in dichloromethane at both room temperature and 50°C did not result in a reaction. Analysis of a 1 J-Young NMR tube containing both H2 and complex 6-5 displayed only the original H NMR resonances as well as the peak for dissolved H2. Upon release of H2 pressure and degassing of the solvent mixture the 1H NMR spectrum was identical to the starting material.

Efforts were undertaken to generate a Ru-hydride complex based on complex 6-5. Lithium triethylborohydride and silanes were mixed with complex 6-5. The reaction with lithium triethylborohydride did not result in a reaction. Upon work-up the starting materials could be recovered almost quantitatively. The reaction with silane did result in a reaction. However, the reaction resulted in a complex mixture of products which were not possible to separate. With these results in mind, efforts changed towards utilizing the inherent functionality of the P-N ligand of complex 6-5.

7.2.2 Transfer Hydrogenation

7.2.2.1 Dimer Catalysis

The development of a high yielding, scalable preparation of a unique ruthenium P-N complex prompted the investigation towards potential applications in catalysis. The investigation began with the study of the ruthenium dimers. While the dimers exhibit virtually no solubility in non-coordination organic solvents, iso-propanol, with an alcohol functional group, may offer the possibility of cleaving the ruthenium chloride bridged dimer. The addition of 6-2 to a scintillation vial containing 5 ml of iso-propanol did not initially stimulate solubility. However,

130 over the course of an hour the formerly clear and colourless solution with a suspended orange solid turned light orange implying at least some solubility. The solubility was not exhibited to the extent which a DCM:pyridine mixture displays.

For the catalytic examination, a catalyst to base to substrate, ratio of 1:5:500 was chosen for all of the catalytic testing. The substrate chosen was acetophenone. The catalyst was mixed with iso-propanol and allowed to stir for 5 minutes. Following this delay, 5 molar equivalents of KOtBu were added followed immediately by 500 molar equivalents of substrate. The reaction was run in a Schlenk reaction flask equipped with a rubber septum. This allowed for the withdrawal of reaction aliquots at specific times. At these times the aliquot was passed through a short plug of silica in an attempt to remove residual catalyst and phosphines. Following this the samples were analyzed using a GC:MS to determined the ratio of converted acetophenone to 1-phenylethanol. The reactions were completed in parallel at both room temperature and 50°C in an attempt to obtain nearly identical conditions excluding temperature.

The first potential pre-catalyst analyzed was 6-2, the ruthenium phenyl phosphine substituted complex. Following the addition of 6-2 to iso-propanol at room temperature a slight dissolution of 6-2 was observed. The addition of KOtBu and substrate did not display a visual difference. Following the reaction via GC/MS, the chromatogram showed no detectable conversion within 5 minutes and only 6 % conversion within 1 hour (Figure 7.2.1). Analysis of the reaction after 12 hours yielded a conversion of 28 %. Solid catalyst was still observed within the reaction mixture after 12 hours.

Completion of the reaction at 50°C showed nearly undetectable conversion. The reaction was not visually dissimilar from catalysis at room temperature. Analysis of the reaction mixture after 12 hours showed approximately 3 % conversion (Figure 7.2.1).

131

Figure 7.2.1 - Transfer hydrogenation of acetophenone employing pre catalyst 6-2 at both room temperature and 50°C.

The second potential pre-catalyst analyzed was 6-4, the ruthenium methyl phosphine substituted complex. Following the addition of 6-4 to iso-propanol at room temperature, dissolution of 6-4 was observed. The addition of KOt-Bu and substrate did, in this instance, display a visual difference. While in the case of 6-2 the reaction mixture remained pale orange, this reaction turned a deeper orange colour. Following the reaction via GC/MS, the chromatogram showed a 3 % conversion within 5 minutes and only 29 % conversion within 1 hour (Figure 7.2.2). Analysis of the reaction after 12 hours yielded a conversion of 58 %. Solid catalyst was still observed within the reaction mixture after 12 hours, however, less than was observed from the catalysis based on 6-4.

Completion of catalysis employing pre-catalyst 6-4 at 50°C resulted in detectable hydrogenation, as opposed to catalysis employing pre-catalyst 6-2 at 50°C. The reaction was not visually dissimilar from catalysis at room temperature. Analysis of the reaction mixture after 12 hours showed conversion of 22 %. Similar to the results of catalysis based on 6-2, catalytic activity

132 was lower at elevated temperature. In the case of pre-catalyst 6-4, the catalytic activity was approximately two-fifths at an elevated temperature.

The observation of greater catalytic turnover of pre-catalyst 6-4 is consistent with the greater solubility of 6-4 with respect to pre-catalyst 6-2.

Figure 7.2.2 - Transfer hydrogenation of acetophenone employing pre catalyst 6-2 at both room temperature and 50°C.

133

7.2.2.2 Monomer Catalysis

The dimers previously employed in the transfer hydrogenation of acetophenone were shown in Chapter six to afford high yielding monomers in the presence of pyridine of an auxiliary ligand. As opposed to the dimers, upon the preparation of an iso-propanol solution of ruthenium P-N monomers 6-5 and 6-8, the complexes were easily solubilised. The solutions are clear, colourless, orange mixtures, with no apparent residual solid. Furthermore, to test the effect of the addition of KOt-Bu, a prepared catalyst and base solution was extremely soluble and afforded a deep red solution. The catalytic conditions were identical to those in the transfer hydrogenation in which the ruthenium P-N dimers were tested.

The ruthenium phenyl monomer 6-5 was dissolved in 2 ml of iso-propanol to yield an orange solution. Upon the addition of 5 equivalents of KOtBu there was an instantaneous colour change from orange to deep red. Immediately thereafter the substrate acetophenone was injected into the reaction. At this point there was no further visual change of the reaction mixture. Analysis of the reaction mixture by GC/MS showed remarkable differences in the catalytic viability. The reaction was again run in parallel at room temperature and at 50°C.

First, the analysis of the transfer hydrogenation using pre-catalyst 6-5 at room temperature showed 25 % conversion within 5 minutes (Figure 7.2.3). Within 30 minutes the conversion was 34 % and after the course of 12 hours the conversion was determined to be 52 %. After the first hour the conversion is nearly plateaued with only a 12 % increase in conversion over the subsequent 11 hours. Secondly, the catalysis at 50°C mirrored the results obtained from transfer hydrogenation using the ruthenium P-N dimers as the results from the catalysis at 50°C gave lower yields, at least initially. Initial conversion employing pre-catalyst 6-5 at 50°C gave a yield of 12 % after 5 minutes. The yield improved to 30 % within 30 minutes and after 12 hours the reaction mixture was analysed to give a catalytic conversion of 60 %. As opposed to catalysis employing the ruthenium P-N dimers, there was an 8 % improved overall yield at 50°C using complex 6-5 at 50°C as opposed to room temperature.

134

Figure 7.2.3 - Transfer hydrogenation of acetophenone employing pre catalyst 6-5 at both room temperature and 50°C.

The final screening of potential pre-catalysts for the transfer hydrogenation utilized the ruthenium P-N monomer 6-8. Following the addition of iso-propanol, complex 6-8 was found to have the greatest solubility in iso-propanol, likewise, following the addition of KOtBu the resulting product was found to be exceptionally soluble.

Following the transfer hydrogenation catalysis based on 6-8 at room temperature via GC/MS the chromatogram showed a 9 % conversion within 5 minutes and 66 % conversion within 1 hour (Figure 7.2.4). Analysis of the reaction after 12 hours yielded a conversion of 76 %. As previously stated, the catalysis using 6-8 was conducted as well at 50°C. Unlike all of the previous catalytic testing, the result of using pre-catalyst 6-8 at 50C demonstrated improved catalytic performance, exceptionally better than all previous examples. At 50°C the GC/MS chromatogram displayed a 60 % conversion within 5 minutes. The conversion, essentially, completes within 30 minutes to yield 73 % conversion of acetophenone to 1-phenylethanol. The

135 observation of the reaction mixture over the course of the following eleven and a half hours increased the conversion by 5 %.

Figure 7.2.4 - Transfer hydrogenation of acetophenone employing pre catalyst 6-8 at both room temperature and 50°C.

136

7.3 Experimental

7.3.1 General Considerations

All manipulations were carried out under an atmosphere of dry, O2-free N2 employing a MBraun glove box and a Schlenk vacuum-line. Solvents were purified by stirring with sodium and distilled into thick-walled Schlenk glass flasks equipped with Teflon-valve stopcocks. All solvents were thoroughly degassed after purification (repeated freeze-pump-thaw cycles). The catalytic conversion was analyzed employing GC/MS.

All common organic reagents were purified by conventional methods unless otherwise noted. The metal complexes were prepared by literature methods. All other reagents were purchased from Aldrich and were used as received.

7.3.2 Typical Reduction Protocol

In a glovebox pre-catalyst 6-8 (5 mg, 6.5 µmol) was added to a Schlenk flask containing 2 ml of iso-propanol. The Schlenk flask was sealed with a rubber septum and removed to a Schlenk line. A pre-prepared solution of iso-propanol and KOtBu was transferred to the reaction vessel via cannula. Immediately thereafter, acetophenone (300 mg, 3.31 mmol) was injected into the reaction mixture. At the detailed times, aliquots (approximately 0.05 ml) were removed from the catalytic mixture via syringe. The aliquot was quickly passed through a Pasteur pipette plug of silica (approximately 4-5 cm). The sample was then diluted in dichloromethane and analyzed via GC/MS. The conversion was determined by comparison of the integral of the benzophenone peak, 4.98 minutes, and the appearance of 1-phenylethanol, 10.09 minutes.

137

7.4 Conclusion

A preliminary investigation of the potential for complexes 6-2, 6-4, 6-5, and 6-8 to catalyze transfer hydrogenation was completed. While complexes 6-2 and 6-4 were insoluble they were tested and yielded the expected result of little catalytic activity. However, complexes 6-4 and 6-6 were found to be more competent in the catalytic transfer hydrogenation of acetophenone from iso-propanol. The most active catalyst was determined to be 6-6 which reached near maximum conversion of 75% within 5 minutes. While no further catalytic reactions were carried out with respect to catalyst optimization, it may be warranted for catalyst 6-8.

138

Chapter 8 Tridentate phosphinimine ruthenium complexes

8 « 8.1 Introduction

Transition metal pincer complexes have demonstrated the ability to facilitate unique reactivity and found use in a wide variety of applications. Ruthenium pincer ligands, as described in the chapter 1 introduction, have allowed access to and applications of highly reactive species which have lead to a variety of unique and useful catalytic processes. While the PCP pincer ligands have attracted greater interest, PNP ligands have also allowed access to unique reactivity. 244-247 248-250 Phosphines generally are the donor functionalities which have seen the greatest interest. However, the work described herein sought to investigate for the first time pincer type chemistry involving NNN pincer ligands wherein the trans donors are phosphinimines and the central donor has a secondary amine functionality.

Phosphinimines provide unique properties, both steric and electronic, which differ from phosphine donors.251 They are generally considered to be more basic than phosphines and show greater similarity to N-heterocyclic carbenes in terms of basicity. 252,253 This is shown in chapter 5 of this thesis. Their steric properties differ as well. Phosphines display their steric bulk proximal to the metal center whereas phosphinimines, which retain significant steric bulk, display their steric bulk less proximal to the metal center providing a larger pocket for reactivity at the metal center. Transition metal phosphinimine pincer complexes have received little attention as opposed to monodentate and bidentate phosphinimine complexes which have been more extensively studied.251,254-257 The majority of the published work was carried out concurrently with the work described herein within the Stephan research group.

Within the Stephan research group work has primarily been carried out with respect to group 10 metal complexes. The first example of a coordination complex was to a palladium center using a NCN ligand with a metallated aryl ring as the central donor.258 Following this work the scope of the coordination chemistry was expanded to nickel and the range of ligands was also expanded.259 Examples of the coordination complexes are shown in Figure 8.1.1.

139

Figure 8.1.1 - Examples of coordination complexes based on phosphinimine pincer complexes.

Following the coordination chemistry unique reactivity was observed.260 The ligand was found to be non-innocent with the respect to the reaction with trityl tetrakis(pentafluorophenyl)borate yielding an ionic ligand.(Figure 8.1.2) Furthermore, it was shown that bimetallic nickel complexes could be prepared via careful control of reaction conditions and stoichiometry. Figure 8.1.2 Subsequently, it was found that the oxidative addition to nickel(0) complexes was possible and the could be isolated and characterized. Figure 8.1.2

Figure 8.1.2 - Unique reactivity observed with group 10 phosphinimine pincer complexes.

Two additional examples were published by Hayes et al. using more intricate ligand frameworks. The first example employed a pincer type framework employing a carbazole derivative. This was applied to a lutetium center to isolate and study dialkyl species.261 (Figure 8.1.3) Subsequent to this report, a dibenzofuran derivative was published.262,263 The dibenzofuran ligands were complexed to an alkyl zinc center which were later tested for lactide polymerization activity.

140

Figure 8.1.3 - Two additional examples of tridentate phosphinimine pincer complexes.

8.2 Results and Discussion

8.2.1 Complex Synthesis

Using a modified literature procedure the synthesis of HN(CH2CH2N=PPh3)2 was carried out (Scheme 8.2.1). The 31P NMR spectrum of 8-1 displayed a signal at 27.9 ppm and the 1H NMR indicated the clean formation of the ligand. However, to obtain a satisfactory elemental analysis successive recrystallizations were required indicating contamination by an NMR silent compound. Nonetheless, the synthesis of metal complexes was attempted.

Scheme 8.2.1 - Phosphorane synthesis of phosphinimine pincer ligand 8-1.

Stirring a 1 : 1 mixture of 8-1 and first generation Grubbs catalyst in dichloromethane or bromobenzene resulted in the decomposition of the ruthenium starting material and an intractable mixture. However, mixing 8-1 and first generation Grubbs catalyst in tetrahydrofuran resulted in the precipitation of a green microcrystalline solid from the THF solution (Scheme 8.2.2). The isolation of the precipitate via filtration gave a yield of 84 %. Analysis of the mixture by NMR spectroscopy showed a new peak in the 31P spectra at 39.4 ppm. The 1H NMR spectrum displayed a variety of new signals, however, the new signal at 18.67 ppm proved to the most diagnostic. The peak at 18.67 ppm could be assigned to the formation of a new ruthenium alkylidene. The NMR spectroscopic data confirmed symmetry within the complex based on the 1H NMR. In an attempt to unambiguously determine the structure, a single crystal X-ray structure was determined. Unfortunately, the molecular structure determined proved to be highly

141 disordered and of low quality. This was determined to be caused by contamination by bromide anions and likely a result of the ligand synthesis.

Scheme 8.2.2 - Synthesis of a ruthenium phosphinimine pincer complex with an alkylidene.

To this end, a variation of the Staudinger reaction was employed. The reaction of bis(2-chloroethyl)amine·hydrochloride with sodium azide cleanly yielded bis(azidoethyl)amine. Subsequently, the mixing of bis(azidoethyl)amine and triphenylphosphine yielded pure crystals of 8-1. (Scheme 8.2.3)

Scheme 8.2.3 - Azide synthesis of phosphinimine pincer ligand.

The formation of 8-2 from 8-1 synthesized via the diazido route yielded highly pure samples. A single crystal X-ray structure study unambiguously confirmed the structure as a distorted square pyramidal arrangement with the alkylidene functionality at the apex (Figure 8.2.1). The phosphinimine pincer is meridionally coordinated to the ruthenium (II) center with a single chloride coordinated trans to the NH of the phosphinimine ligand. The complex is cationic with an outer-sphere chloride anion. The ruthenium phosphinimine bond lengths are 2.058(2) Å and 2.068(2) Å with the HN-Ru bond length is 2.081(3) Å. The Ru-Cl bond length is 2.3821(8) Å. Finally, of note the ruthenium alkylidene bond length is 1.844(3) Å which compares to a 1.836(2) Å found in second generation Grubbs catalyst.264

142

Figure 8.2.1 - POV-Ray Depiction of 8-2. C: black, Ru: hunter green, Cl: green, P: orange, N aquamarine. HN and CHPh hydrogen atoms refined and included.

While it could not be determined if both chloride anions were coordinated in solution, the observation of a solid state five coordinate ruthenium species was intriguing. The vacant coordination site on the ruthenium center may allow the coordination of a substrate facilitating catalysis. However, the vacant coordination site was trans to the alkylidene whereas a cis conformation is a necessary condition for catalytic turnover. Therefore a rearrangement of the ruthenium complex would be necessary for catalysis.265

Following the isolation of 8-2 several reactions were carried out to assess its reactivity. The reaction of 8-2 with silver triflate, tris(pentafluorophenyl)borane, and trityl tetrakis(pentafluorophenyl)borate did not result in the synthesis of an isolable species. The monitoring of the reactions via 1H NMR spectroscopy consistently resulted in the disappearance of the signal at 18.67 ppm which corresponded to the ruthenium alkylidene. The complex showed stability over the course of at least 24 hours in a dichloromethane solution. Upon exposure to air a dichloromethane solution turned slowly from deep green to yellow, indicating decomposition.

143

8.2.2 Preliminary Catalytic Screening

Following the catalytic screening protocols outlined in the introduction, the complex 8-2 was tested for catalytic activity in the RCM of diethyldiallylmalonate. A solution of 8-2 was prepared in an NMR tube to which a sufficient amount of diethyldiallylmalonate was injected to equate to a 5 mol% catalyst solution. Upon initial injection of substrate no visible change was detectable. The course of the reaction was monitored by 1H NMR spectroscopy by the comparison of the signal at 2.61 ppm, with that in the product at 2.98 ppm. Over the course of one hour the conversion approximated 8 % (Figure 8.2.2). Following this the conversion increased to 33 % within 4 hours and increased little to 38 % over the course of 12 hours. The peak in conversion at approximately 33 % coincided with a color change from deep green to light yellow.

40 35 30 25 Conversion 20 (%) 15 10 5 0 0 2 4 6 8 10 12 14 Time (hours)

Figure 8.2.2 - The RCM of diethyldiallylmalonate by 8-2.

While the activity was moderate, it showed the highest activity of published tridentate ligand systems. The previous tris(pyrazolyl)borate systems published by Grubbs et al. demonstrated full conversion only with catalyst loading in excess of 20 mol%. However, this was inadequate so higher activities were sought. Warming of the reaction yielded little change and, in general, hastened decomposition. As previously stated, the reaction of 8-2 with halide scavengers did not yield isolable products but the crude mixtures were nevertheless screened. If activity was observed then greater efforts to isolate such species may be pursued. The crude reaction

144 mixtures from 8-2 and halide scavenges did not produced enhanced activity, as well, the results were highly inconsistent.

145

8.3 Conclusions

A new type of alkylidene containing ruthenium pincer type complex has been prepared. The complex was found to be cationic in the solid state with an uncoordinated chloride counter-anion. It was thought that the vacant coordination site may facilitate the application of the ruthenium phosphinimine complex to olefin metathesis. Furthermore, the complex was found to be stable in solution.

The complex was able to catalyze the ring closing metathesis of diethyldiallylmalonate. The peak conversion was found to be 38 % with a 5 mol% catalyst loading. Efforts to increase the turnover numbers were unsuccessful. The complex was noted to be unstable during the catalyst cycle and the decomposition should be further investigated.

146

8.4 Experimental

8.4.1 General Considerations

All preparations were performed under an atmosphere of dry, O2-free N2 employing both

Schlenk line techniques and a MBraun Labmaster inert atmosphere glove box. Solvents (CH2Cl2,

Et2O and pentane) were purified employing a Grubbs’ type column system manufactured by

Innovative Technology. 1,2-Dichloroethane was dried over CaH2 and distilled under a nitrogen atmosphere. Solvents were stored in the glove box over 4 Å molecular sieves. Molecular sieves (4 Å) were purchased from Aldrich Chemical Company and dried at 150 °C under vacuum for 48 h prior to use. All glassware was dried overnight at 120 °C and evacuated for 1 h prior to use. The metal precursors were purchased from Strem Chemicals. All other chemicals were purchased from Aldrich Chemical Co. and used without further purification. 1H, 13C{1H}, and 31P{1H} NMR spectroscopy spectra were recorded on Varian 400 MHz and Bruker 400 MHz 1 13 1 spectrometers. H and C{ H} NMR spectra are referenced to SiMe4 using the residual solvent 31 1 peak impurity of the given solvent. P{ H} NMR spectra were referenced to 85% H3PO4.

147

8.4.2 Synthesis

Synthesis of 8-1: Ph3PBr2 (10.0 g, 23.7 mmol) in CH2Cl2

(200 mL) was added to a solution of HN(CH2CH2NH2)2

(1.27 mL, 11.8 mol) in 60 mL of 1 : 1 CH2Cl2/NEt3 at -10 °C. The mixture was stirred at room temperature for 1 h and the solvent removed in vacuo. The residue was suspended in THF

(100 mL) and cooled to -10 °C. K[N(SiMe3)2] (4.71 g, 23.6 mmol) in THF (50 mL) was added, stirred at room temperature for 30 min and the volatiles removed in vacuo. The residue was then redissolved in THF and the addition of K[N(SiMe3)2] (4.71 g, 23.6 mmol) repeated. The solution was finally filtered through Celite and the solvent removed in vacuo. The residue was triturated with ether (100 mL), the resulting solid was collected filtered and dried in vacuo.

1 Yield: 5.20 g (70%). H NMR (C6D6): 7.78 (m, 12H, Ph); 7.01 (m, 18H, Ph); 3.68 (m, 4H, CH2), 3 31 1 13 1 3.28 (t, JHH = 5.8 Hz, 4H, CH2). P{ H} NMR(C6D6): 5.9. C{ H} NMR(C6D6): 134.0, 132.6,

130.6, 128.8, 55.4, 45.6. Anal. Calcd. for C40H39N3P2: C, 77.03; H, 6.30; N, 6.74. Found: C, 77.15; H, 6.51; N, 6.63.

Synthesis of 8-1: Caution: All synthesis were performed using glassware without ground glass joints. The heating of the reaction mixture was performed behind a blast shield. Furthermore, 8-1 was handled only in solution.

A mixture of bis(2-chloroethyl)amine·hydrochloride (1.20 g, 6.72 mmol, 1eq.) and sodium azide (2.20 g, 33.8 mmol, 5 eq.) was heated in DMF at 70°C for 12 hours. The solution was neutralized by the addition of an aqueous potassium hydroxide solution until the solution tested basic. The extraction of the solution with diethyl ether, drying of the solution with magnesium sulfate, and removal of the solvent yielded a yellow oil (bis(azidoethyl)amine). Yield 76 %. The NMR was not obtained due to instability of the diazide product and used in the following synthetic steps without problems.

Subsequently, bis(azidoethyl)amine (0.1 g, 0.65 mmol, 1 eq.) and triphenylphosphine (0.341 g, 1.30 mmol, 2 eq.) were dissolved in toluene (10 mL). After mixing the solution for approximately 20 minutes, or until the evolution of nitrogen ceased, the solution was warmed to 60°C and stirred for 4 hours. Removal of the solvent in vacuo yielded white crystal of 8-1.

148

Synthesis of 8-2: 8-1 (125 mg, 1 eq.) was added to a THF (5 mL) solution of first generation Grubbs catalyst (165 mg, 1eq.). Stirring for 2 hours resulted in the formation of a dark green precipitate. The solution was filtered, washed with THF (3 x 2 mL), and dried in vacuo. X-ray quality crystals were obtained from the slow diffusion of pentane into a saturated dichloromethane solution. Yield 84 %

1 3 H NMR (CD2Cl2): 18.67 (1H, CHPh, s), 7.94 (2H, Ph, d, JHH = 7.7 Hz), 7.55 - 7.47 (18H, Ph, 3 m), 7.35 - 7.30 (12H, Ph, m) 7.19 (2H, Ph, t, JHH = 7.8 Hz), 6.96 (1H, Ph, br), 3.25 (2H, CH2, 31 13 br), 3.17 (2H, CH2, m), 2.75 (2H, CH2, m), 2.46 (2H, CH2, m) P NMR (CD2Cl2): 39.4 C

NMR (CD2Cl2): 271.5, 155.2, 133.7, 133.6, 133.6, 132.1, 129.1, 128.3, 128.2, 128.1, 127.8, 126.8, 125.3, 58.6, 58.5, 58.2

Catalytic Testing Protocol: An NMR tube was charged inside a glovebox with catalyst

(0.80 µmol, 5.0 mol%) and CD2Cl2 (1.0 mL). An injection of diethyldiallylmalonate was added. Data points were collected over an appropriate period of time using a Bruker 400 NMR. The conversion to the ring closed product was determined by comparing the ratio of the integrals of the methylene protons in the starting material, 2.61ppm (dt), with those in the product, 2.98 ppm (s).

149

8.4.3 X-ray Crystallography

8.4.3.1 X-Ray Data Collection and Reduction

8.4.3.2 X-Ray Data Solution and Refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations. 118 The heavy atom positions were determined using direct methods employing the SHELXTL direct methods routine. The remaining non-hydrogen atoms were located from successive difference Fourier map calculations. The refinements were carried out by using full-matrix least squares techniques 2 2 2 on F, minimizing the function  (Fo–Fc) where the weight  is defined as 4Fo /2 (Fo ) and Fo and Fc are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C-H bond length of 0.95 Å. H-atom temperature factors were fixed at 1.20 times the isotropic temperature factor of the C-atom to which they are bonded. The H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance.

150

Table 8.4.1 - Select Crystallographic Data for 8-2 (8-2)

Formula C47H46Cl2N3P2 Ru Formula weight 886.78 Crystal System monoclinic

Space group P21/c a(Å) 16.0901(10) b(Å) 11.7627(6) c(Å) 22.3522(12) α(deg) 90.00 β(deg) 91.271(3) γ(deg) 90.00 V(Å3) 4229.4(4) Z 4 d(calc)gcm-3 1.393 R(int) 0.0511 Abs coeff,μ,mm-1 0.609 Data collected 12144 2 >2(FO ) 10212 Variables 504 R(>2) 0.0599

Rw 0.0807 GOF 0.986

151

Chapter 9 Summary and Future Work 9.1 Summary

I have presented results herein which have sought to expand the scope of ruthenium coordination chemistry and associated catalysis. The work was guided by the overall goal to develop new olefin metathesis catalysts for the modification of nitrile butadiene rubber and a desire to expand the scope of ruthenium coordination chemistry and the reactivity of associated ruthenium alkylidene species. The investigations described herein have shown unique reactivity derived from ruthenium alkylidene compounds, the development of new ligand sets, and new olefin metathesis catalysts.

Chapter 2 concerns the application of bis(imino)pyridine ligands to a ruthenium center and the synthesis of a ruthenium alkylidene containing molecule. It was found that it was possible to synthesize a ruthenium complex with a TMS alkylidene functional group but preliminary testing revealed that complex to be ineffective for catalytic olefin metathesis. The converse reaction to install a bis(imino)pyridine onto a ruthenium center already containing a alkylidene functional facilitates a unique reaction wherein the alkylidene is transferred to the supposed enamine tautomer of the bis(imino)pyridine to give a cyclopropane. Following upon this investigation of bis(imino)pyridine ligands interaction with ruthenium centers, their potential reduction to the corresponding bis(amino)pyridine ligand was investigated. Such a molecule has been long sought to complete direct polymerization comparison studies with the aforementioned bis(imino)pyridine metal complexes which display exceptional late metal olefin polymerization activities.

In chapters 3 and 4, the development of a new class of heterocyclic phosphinimines is considered. The synthesis, characterization and properties are fully considered and described herein. A library of potential ligands was synthesized and it was demonstrated that the sterics and the electronics could be varied. During the course of assessing the heterocyclic phosphinimines, it was determined that, while the molecules were resistant to decomposition in the presence of oxygen, a facile decomposition pathway was operable with respect to water. Exposure of a solution of heterocyclic phosphinimine to water, either directly or humid air,

152 resulted, within minutes, in the complete decomposition of the heterocycle. The decomposition product was determined and the pathway considered. Furthermore, the coordination chemistry was investigated. While the ultimate goal of developing ruthenium coordination chemistry was unsuccessful, the coordination chemistry of silver and gold was investigated. It was determined that the silver and gold coordination chemistry was analogous to that observed in silver and gold N-heterocyclic coordination chemistry.

Chapters 6 and 7 involved the development of ruthenium phosphino-imine coordination chemistry and its potential application to catalysis. During the initial investigations of ruthenium coordination chemistry, analogues of second generation Grubbs catalysts were prepared with a phosphino-imine auxiliary ligand in place of a traditional tricyclohexylphosphine auxiliary ligand. It was determined that the catalytic activity was comparable to those found with second generation Grubbs catalyst. With this in mind, and the coordination to ruthenium shown to be accessible, a further investigation into ruthenium coordination chemistry was undertaken. While at room temperature clean coordination chemistry was found to be inaccessible upon exposing the mixture to thermal duress, a unique reaction was discovered. The reaction of a ruthenium center and a phosphino-imine cleanly cleaves the P-N bond and resulted in the formation of a new P,N bidentate ligand. The template reaction was found to work in three cases and yielded chloride-bridged dimers containing the new P,N bidentate ligand. The coordination chemistry was expanded to include several monomers. The new ruthenium complexes were then tested for their ability to facilitate catalytic hydrogenation. The complexes were found to not catalyze olefin hydrogenation and no analogues could be synthesized to this end. However, the complexes were found to be able to catalyze the transfer hydrogenation of acetophenone to 1-phenylethanol. The monomeric complex derived from the methyl substituted phosphino-imine was found to be the most capable in the catalysis.

Chapter 8 involved the synthesis and evaluation of tridentate phosphinimine ligands for use in catalytic olefin metathesis. A ruthenium alkylidene complex was prepared with a tridentate phosphinimine ligand consisting of phenyl substituents. The complex was found to be stable in solution and a single crystal X-ray diffraction study was performed. The coordination geometry was determined to be square pyramidal with the alkylidene group in the apical position. Preliminary catalytic screening was performed and the catalyst was found to be moderately active.

153

The initial approach to investigate the use of novel monodentate and bidentate ligands, as well as, the general use of tridentate ligands has afforded a large volume of new ruthenium chemistry. The successful implementation of this strategy and thoughtful consideration of the results presented herein has stimulated significant progress towards the goal of new olefin metathesis catalysts.

154

9.2 Future Work

The application of the work begun herein would be of interest to further investigation. While the coordination chemistry and subsequent reactivity described in chapter 2 need no further investigation, the implications do warrant further consideration. Assuming that the suggested formation of a transient enamine is involved in the formation of the resulting cyclopropane derivative observed, the general concept of transient enamine cyclopropanation may be examined. Cyclopropanation of olefins with a diazo reagent by a ruthenium center is a well known reaction and, as previously stated, there is no literature consideration of transient enamine cyclopropanation. Such a reaction, if conceivable, may provide access to unique organic molecules.

The application of frustrated Lewis pair chemistry to bis(imino)pyridine ligands has, for the first time, allowed the synthesis of the amino analogue. While, at this time, advances in frustrated Lewis pair chemistry have not allowed for enantioselective reductions such reductions were should be pursued in the future. The enantioselective reduction and subsequent coordination to transition metals would provide a selective catalytic pocket. In the case of early transition metal catalysis, the polymerization of propylene may be attempted. Analogous to this work the enantioselective reduction of diimines would provide access to valuable chiral diimines. One such envisioned application is the atom economical and low cost synthesis of chiral N-heterocyclic carbenes.

The heterocyclic phosphinimines developed in chapter 4 were investigated for silver and gold chemistry with respect to coordination chemistry. The subsequent catalytic chemistry was not considered. This is especially true with respect to gold chemistry which has been shown to promote a variety of organic transformations with a large number of these involving N-heterocyclic carbene auxiliary ligands. Furthermore, while the ability to coordinate to a ruthenium center has been largely ruled out with a large variety of screening reactions, the remainder of the d-block is open for investigation. Depending of the metal involved, such heterocyclic phosphinimines may be able to promote a wide range of transformations. Preliminary testing of palladium chemistry yielded the isolation of a new palladium dimer based on heterocyclic phosphinimines.

155

The thermal rearrangement of phosphino-imines described in chapter 6 has the potential to be further exploited in the preparation of unique and otherwise difficult to prepare metal complexes. A narrow range of phosphino-imines have been investigated. The synthesis of phosphino-imines containing latent functionalities may prove interesting. If ruthenium based ligand rearrangements proceed with phosphino-imines containing latent functionalities further development of the ruthenium complexes would be possible. Furthermore, the preliminary screening for catalytic transfer hydrogenation would benefit from more detailed investigation. The fate of the catalyst would be of interest to elecudate to determine logical modifications to enhance catalytic activity.

Finally, it would be of great interest to expand the scope of tridentate phosphinimine ruthenium chemistry. One example has been reported herein. A more detailed investigation into the catalyst decomposition pathway would be desirable. This knowledge may allow for the design of improved catalysts. Furthermore, the potential coordination of tridentate phosphinimine ligands on different ruthenium centers may provide additional insight. To date, only the coordination of cyclohexyl tridentate phosphinimines has been successful. The resulting metal complexes are six coordinate with end on bound dinitrogen.

156

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Curriculum Vitae

Education PhD, Inorganic Chemistry, 2012 University of Toronto, Toronto, ON, Canada  Thesis title: “Ligand Development Directed Towards Applications in Late Metal Catalysis”  Adviser: Professor Douglas Stephan

Honors Bachelor of Science, Chemistry, 2007 Dalhousie University, Halifax, NS, Canada  Thesis title: “Si-Co-C Negative Electrode Materials Prepared by Mechanochemical Synthesis for Li-ion Batteries”  Adviser: Professor Jeffrey Dahn

Research Experience University of Toronto, Toronto, ON, Canada September 2007 - October 2012 Doctor of Philosophy  Primarily developed new pro-ligands and applied these towards late metal catalysis  Screened above mentioned catalysts for applications in olefin metathesis and olefin hydrogenation  “Frustrated Lewis Pairs” catalysis, early metal olefin polymerization  Gained extensive experience in inert atmosphere chemistry . Glovebox and Schlenk techniques  Characterization techniques such as multi-nuclei NMR, IR, elemental analysis, UV-Vis, GPC  Managed single crystal service for research group . Trained users, maintenance, collection and solution for >400 structures  Work sponsored by multi-national corporation, prepared and presented regular updates to company

Dalhousie University, Halifax, NS, Canada 2005-2007 Summer Internships and Honours Research Project  Prepared and characterized novel negative electrode materials for use in Li-ion batteries  Solid state synthesis, primarily ball milling  Extensive powder X-ray diffraction studies and Rietveld analysis  Prepared and tested coin cell batteries  Work sponsored by multi-national corporation, prepared and presented regular updates to company

Teaching Experience  Laboratory Instructor 2007 - 2011 o First year undergraduate chemistry o First year computational chemistry o Second year organic chemistry  Advanced first year chemistry tutorials 2007 - 2010 o Taught 150 students 3 hours per week o Prepared lectures, wrote exams, and graded all class work

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Computer Experience  Proficient in MS Windows, Mac OS, MS Word, MS Excel, MS Powerpoint  Proficient in ChemDraw, SHELXTL, Platon, Bruker Diffractometer Software, Cambridge Structural Database, SciFinder  Experience in Gaussian

Publications  C.C. Brown, D.W. Stephan, Ruthenium Phosphinimine Complexes; Coordination and Reactivity, in preparation.  C.C. Brown, D.W. Stephan, Rearrangements of Phosphinoimines to Ruthenium Phosphine-Imine Chelate Complexes, Dalton Trans., 41, 9431-9438.  C.B. Caputo, S.J. Geier, E.Y. Ouyang, C. Kreitner, C.C. Brown, D.W. Stephan, Chloro- and Phenoxy-Phosphines in Frustrated Lewis Pair Additions to Alkynes, Dalton Trans., 41, 237-242 (Hot article, Cover Invited).  D.W. Stephan, S. Greenberg, T.W. Graham, P.A. Chase, J.J. Hastie, S.J. Geier, J.M. Farrell, C.C. Brown, Z.M. Heiden, G.C. Welch, M. Ullrich, Metal-Free Catalytic Hydrogenation of Polar Substances by Frustrated Lewis Pairs, Inorg. Chem., 50, 12338-12348 (Forum article, Invited).  M.A. Dureen, C.C. Brown, D.W. Stephan, Titanium "Constrained Geometry" Complexes with Pendant Arene Groups, Dalton Trans. 40, 2861-2867 (Invited).  M.A. Dureen, C.C. Brown, D.W. Stephan, Deprotonation and Addition Reactions of Frustrated Lewis Pairs with Alkynes Alkynes, Organometallics, 29, 6594-6607.  M.A. Dureen, C.C. Brown, D.W. Stephan, Additions of Enamines and Pyrroles and B(C6F5)3 "Frustrated Lewis Pairs" to Alkynes, Organometallics, 29, 6622-6632.  M.P. Boone, C.C. Brown, T.A. Ancelet, D.W. Stephan, Interconversion of Ruthenium- O(CH2CH2PCy2)2 Alkylidene and Alkylidyne-Hydride Complexes, Organometallics, 29, 4369- 4374.  C.C. Brown, C. Glotzbach, D.W. Stephan, Ag(I) and Au(I) Complexes of Sterically Crowded Cyclic Phosphinimine Ligands, Dalton Trans. 39, 9626-9632 (Hot Article).  C.C. Brown, D.W. Stephan, Cyclopropanation of Ru-Diimino-Pyridine Ligand Complexes, Dalton Trans. 39, 7211-7213.

Conference Presentations  C.C. Brown, D.W. Stephan, Abstracts of Papers, 94th CSC, Montreal, QC, Canada, June 5-9, 2011 Pages 1065  C.C. Brown, D.W. Stephan, Abstracts of Papers, PacificChem2010, Honolulu, Hi, United States, Dec 15th-20th, 2010 ID #397  C.C. Brown, D.W. Stephan, Abstracts of Papers, 93rd CSC, Toronto, ON, Canada, May 29th- June 2nd, 2010 Page 4  C.C. Brown, D.W. Stephan, Abstracts of Papers, 239th ACS National Meeting, San Francisco, CA, United States, March 21-25, 2010 Pages INOR-481