Ligand Design in Metal Chemistry

Mark Stradiotto, Department of Chemistry, Dalhousie University, Canada Rylan Lundgren, Department of Chemistry, University of Alberta, Canada Both professors have a well-established track-record of working in the field of organometallic ligand design and catalysis, and have published extensively on the subjects of metal-catalyzed cross-coupling, novel transition-metal bond activation, and asymmetric catalysis. They are co-inventors of the now commercialized DalPhos ligand family and have broad experience of the  field of ligand design. Professor Stradiotto has worked in the field of organometallic chemistry for the past fourteen years. Professor Lundgren earned his PhD under the supervision of Prof Stradiotto at Dalhousie University in 2010. Following a PDF at MIT and Caltech with Prof. Greg Fu, Rylan accepted a faculty position at the University of Alberta (Canada).

List of Contributors xii

Foreword by Stephen L. Buchwald xiv

Foreword by David Milstein xvi

 Preface xvii

1 Key Concepts in Ligand Design: An Introduction 1
Rylan J. Lundgren and Mark Stradiotto

1.1 Introduction 1

1.2 Covalent bond classification and elementary bonding concepts 2

1.3 Reactive versus ancillary ligands 4

1.4 Strong‐ and weak‐field ligands 4

1.5 Trans effect 6

1.6 Tolman electronic parameter 6

1.7 Pearson acid base concept 8

1.8 Multidenticity, ligand bite angle, and hemilability 8

1.9 Quantifying ligand steric properties 10

1.10 Cooperative and redox non‐innocent ligands 12

1.11 Conclusion 12

References 13

2 Catalyst Structure and Cis–Trans Selectivity in Ruthenium‐based Olefin Metathesis 15
Brendan L. Quigley and Robert H. Grubbs

2.1 Introduction 15

2.2 Metathesis reactions and mechanism 17

2.2.1 Types of metathesis reactions 17

2.2.2 Mechanism of Ru‐catalyzed olefin metathesis 19

2.2.3 Metallacycle geometry 19

2.2.4 Influencing syn–anti preference of metallacycles 22

2.3 Catalyst structure and E/Z selectivity 24

2.3.1 Trends in key catalysts 24

2.3.2 Catalysts with unsymmetrical NHCs 26

2.3.3 Catalysts with alternative NHC ligands 29

2.3.4 Variation of the anionic ligands 31

2.4 Z‐selective Ru‐based metathesis catalysts 33

2.4.1 Thiophenolate‐based Z‐selective catalysts 33

2.4.2 Dithiolate‐based Z‐selective catalysts 34

2.5 Cyclometallated Z‐selective metathesis catalysts 36

2.5.1 Initial discovery 36

2.5.2 Model for selectivity 37

2.5.3 Variation of the anionic ligand 38

2.5.4 Variation of the aryl group 40

2.5.5 Variation of the cyclometallated NHC substituent 41

2.5.6 Reactivity of cyclometallated Z‐selective catalysts 42

2.6 Conclusions and future outlook 42

References 43

3 Ligands for Iridium‐catalyzed Asymmetric Hydrogenation of Challenging Substrates 46
Marc‐André Müller and Andreas Pfaltz

3.1 Asymmetric hydrogenation 46

3.2 Iridium catalysts based on heterobidentate ligands 49

3.3 Mechanistic studies and derivation of a model for the enantioselective step 57

3.4 Conclusion 63

References 64

4 Spiro Ligands for Asymmetric Catalysis 66
Shou‐Fei Zhu and Qi‐Lin Zhou

4.1 Development of chiral spiro ligands 66

4.2 Asymmetric hydrogenation 73

4.2.1 Rh‐catalyzed hydrogenation of enamides 73

4.2.2 Rh‐ or Ir‐catalyzed hydrogenation of enamines 73

4.2.3 Ir‐catalyzed hydrogenation of α,β‐unsaturated carboxylic acids 75

4.2.4 Ir‐catalyzed hydrogenation of olefins directed by the carboxy group 78

4.2.5 Ir‐catalyzed hydrogenation of conjugate ketones 79

4.2.6 Ir‐catalyzed hydrogenation of ketones 80

4.2.7 Ru‐catalyzed hydrogenation of racemic 2‐substituted aldehydes via dynamic kinetic resolution 81

4.2.8 Ru‐catalyzed hydrogenation of racemic 2‐substituted ketones via DKR 82

4.2.9 Ir‐catalyzed hydrogenation of imines 84

4.3 Carbon–carbon bond‐forming reactions 85

4.3.1 Ni‐catalyzed hydrovinylation of olefins 85

4.3.2 Rh‐catalyzed hydroacylation 85

4.3.3 Rh‐catalyzed arylation of carbonyl compounds and imines 86

4.3.4 Pd‐catalyzed umpolung allylation reactions of aldehydes, ketones, and imines 87

4.3.5 Ni‐catalyzed three‐component coupling reaction 87

4.3.6 Au‐catalyzed Mannich reactions of azlactones 89

4.3.7 Rh‐catalyzed hydrosilylation/cyclization reaction 89

4.3.8 Au‐catalyzed [2 + 2] cycloaddition 90

4.3.9 Au‐catalyzed cyclopropanation 91

4.3.10 Pd‐catalyzed Heck reactions 91

4.4 Carbon–heteroatom bond‐forming reactions 91

4.4.1 Cu‐catalyzed N─H bond insertion reactions 91

4.4.2 Cu‐, Fe‐, or Pd‐catalzyed O─H insertion reactions 93

4.4.3 Cu‐catalyzed S─H, Si─H and B─H insertion reactions 95

4.4.4 Pd‐catalyzed allylic amination 95

4.4.5 Pd‐catalyzed allylic cyclization reactions with allenes 97

4.4.6 Pd‐catalyzed alkene carboamination reactions 98

4.5 Conclusion 98

References 98

5 Application of Sterically Demanding Phosphine Ligands in Palladium‐Catalyzed Cross‐Coupling leading to C(sp2)─E Bond Formation (E = NH2 , OH, and F) 104
Mark Stradiotto and Rylan J. Lundgren

5.1 Introduction 104

5.1.1 General mechanistic overview and ancillary ligand design considerations 105

5.1.2 Reactivity challenges 107

5.2 Palladium‐catalyzed selective monoarylation of ammonia 108

5.2.1 Initial development 109

5.2.2 Applications in heterocycle synthesis 110

5.2.3 Application of Buchwald palladacycles and imidazole‐derived monophosphines 112

5.2.4 Heterobidentate κ2‐P,N ligands: chemoselectivity and room temperature reactions 115

5.2.5 Summary 117

5.3 Palladium‐catalyzed selective hydroxylation of (hetero)aryl halides 117

5.3.1 Initial development 118

5.3.2 Application of alternative ligand classes 120

5.3.3 Summary 122

5.4 Palladium‐catalyzed nucleophilic fluorination of (hetero)aryl (pseudo)halides 123

5.4.1 Development of palladium‐catalyzed C(sp2)─F coupling employing (hetero)aryl triflates 124

5.4.2 Discovery of biaryl monophosphine ancillary ligand modification 125

5.4.3 Extending reactivity to (hetero)aryl bromides and iodides 127

5.4.4 Summary 128

5.5 Conclusions and outlook 129

Acknowledgments 130

References 131

6 Pd‐N‐Heterocyclic Carbene Complexes in Cross‐Coupling Applications 134
Jennifer Lyn Farmer, Matthew Pompeo, and Michael G. Organ

6.1 Introduction 134

6.2 N‐heterocyclic carbenes as ligands for catalysis 135

6.3 The relationship between N‐heterocyclic carbene structure and reactivity 136

6.3.1 Steric parameters of NHC ligands 136

6.3.2 Electronic parameters of NHC ligands 138

6.3.3 Tuning the electronic properties of NHC ligands 139

6.4 Cross‐coupling reactions leading to C─C bonds that proceed through transmetalation 140

6.5 Kumada–Tamao–Corriu 141

6.6 Suzuki–Miyaura 148

6.6.1 The formation of tetra‐ortho‐substituted (hetero)biaryl compounds 149

6.6.2 Enantioselective Suzuki–Miyaura coupling 153

6.6.3 Formation of sp3─sp3 or sp2 ─sp3 bonds 156

6.6.4 The formation of (poly)heteroaryl compounds 158

6.7 Negishi coupling 163

6.7.1 Mechanistic studies: investigating the role of additives and the nature of the active transmetalating species 166

6.7.2 Selective cross‐coupling of secondary organozinc reagents 168

6.8 Conclusion 170

References 171

7 Redox Non‐innocent Ligands: Reactivity and Catalysis 176
Bas de Bruin, Pauline Gualco, and Nanda D. Paul

7.1 Introduction 176

7.2 Strategy I. Redox non‐innocent ligands used to modify the Lewis acid–base properties of the metal 179

7.3 Strategy II. Redox non‐innocent ligands as electron reservoirs 181

7.4 Strategy III. Cooperative ligand‐centered reactivity based on redox active ligands 192

7.5 Strategy IV. Cooperative substrate‐centered radical‐type reactivity based on redox non‐innocent substrates 195

7.6 Conclusion 200

References 201

8 Ligands for Iron‐based Homogeneous Catalysts for the Asymmetric Hydrogenation of Ketones and Imines 205
Demyan E. Prokopchuk, Samantha A. M. Smith, and Robert H. Morris

8.1 Introduction: from ligands for ruthenium to ligands for iron 205

8.1.1 Ligand design elements in precious metal homogeneous catalysts for asymmetric direct hydrogenation and asymmetric transfer hydrogenation 205

8.1.2 Effective ligands for iron‐catalyzed ketone and imine reduction 212

8.1.3 Ligand design elements for iron catalysts 213

8.2 First generation iron catalysts with symmetrical [6.5.6]‐P‐N‐N‐P ligands 216

8.2.1 Synthetic routes to ADH and ATH iron catalysts 217

8.2.2 Catalyst properties and mechanism of reaction 218

8.3 Second generation iron catalysts with symmetrical [5.5.5]‐P‐N‐N‐P ligands 220

8.3.1 Synthesis of second generation ATH catalysts 220

8.3.2 Asymmetric transfer hydrogenation catalytic properties and mechanism 222

8.3.3 Substrate scope 226

8.4 Third generation iron catalysts with unsymmetrical [5.5.5]‐P‐NH‐N‐Pʹ ligands 227

8.4.1 Synthesis of bis(tridentate)iron complexes and P‐NH‐NH2 ligands 227

8.4.2 Template‐assisted synthesis of iron P‐NH‐N‐Pʹ complexes 228

8.4.3 Selected catalytic properties 229

8.4.4 Mechanism 230

8.5 Conclusions 231

Acknowledgments 232

References 232

9 Ambiphilic Ligands: Unusual Coordination and Reactivity Arising from Lewis Acid Moieties 237
Ghenwa Bouhadir and Didier Bourissou

9.1 Introduction 237

9.2 Design and structure of ambiphilic ligands 238

9.3 Coordination of ambiphilic ligands 242

9.3.1 Complexes featuring a pendant Lewis acid 242

9.3.2 Bridging coordination involving M → Lewis acid interactions 243

9.3.3 Bridging coordination of M─X bonds 248

9.3.4 Ionization of M─X bonds 250

9.4 Reactivity of metallic complexes deriving from ambiphilic ligands 251

9.4.1 Lewis acid enhancement effect in Si─Si and C─C coupling reactions 251

9.4.2 Hydrogenation, hydrogen transfer and hydrosilylation reactions assisted by boranes 255

9.4.3 Activation/functionalization of N2 and CO 262

9.5 Conclusions and outlook 264

References 266

10 Ligand Design in Enantioselective Ring‐opening Polymerization of Lactide 270
Kimberly M. Osten, Dinesh C. Aluthge, and Parisa Mehrkhodavandi

10.1 Introduction 270

10.1.1 Tacticity in PLA 271

10.1.2 Metal catalysts for the ROP of lactide 272

10.1.3 Ligand design in the enantioselective polymerization of racemic lactide 274

10.2 Indium and zinc complexes bearing chiral diaminophenolate ligands 292

10.2.1 Zinc catalysts supported by chiral diaminophenolate ligands 292

10.2.2 The first indium catalyst for lactide polymerization 294

10.2.3 Polymerization of cyclic esters with first generation catalyst 295

10.2.4 Ligand modifications 296

10.3 Dinuclear indium complexes bearing chiral salen‐type ligands 297

10.3.1 Chiral indium salen complexes 297

10.3.2 Polymerization studies 297

10.4 Conclusions and future directions 301

References 302

11 Modern Applications of Trispyrazolylborate Ligands in Coinage Metal Catalysis 308
Ana Caballero, M. Mar Díaz‐Requejo, Manuel R. Fructos, Juan Urbano, and Pedro J. Pérez

11.1 Introduction 308

11.2 Trispyrazolylborate ligands: main features 310

11.3 Catalytic Systems Based on TpXMl Complexes (M = Cu, Ag) 311

11.3.1 Carbene addition reactions 312

11.3.2 Carbene insertion reactions 314

11.3.3 Nitrene addition reactions 319

11.3.4 Nitrene insertion reactions 321

11.3.5 Oxo transfer reactions 322

11.3.6 Atom transfer radical reactions 324

11.4 Conclusions 326

Acknowledgments 326

References 327

12 Ligand Design in Modern Lanthanide Chemistry 330
David P. Mills and Stephen T. Liddle

12.1 Introduction and scope of the review 330

12.2 C‐donor ligands 333

12.2.1 Silylalkyls 333

12.2.2 Terphenyls 335

12.2.3 Substituted cyclopentadienyls 336

12.2.4 Constrained geometry cyclopentadienyls 338

12.2.5 Benzene complexes 340

12.2.6 Zerovalent arenes 342

12.2.7 Tethered N‐heterocyclic carbenes 343

12.3 N‐donor ligands 344

12.3.1 Hexamethyldisilazide 344

12.3.2 Substituted trispyrazolylborates 347

12.3.3 Silyl‐substituted triamidoamine, [N(CH2Ch2NSiMe2But)3]3– 348

12.3.4 NacNac, {N(Dipp)C(Me)CHC(Me)N(Dipp)}− 349

12.4 P‐donor ligands 349

12.4.1 Phospholides 349

12.5 Multiple bonds 350

12.5.1 Ln═CR2 350

12.5.2 Ln ═ NR 354

12.5.3 Ln ═ O 355

12.6 Conclusions 356

Notes 357

References 357

13 Tight Bite Angle N,O‐Chelates. Amidates, Ureates and Beyond 364
Scott A. Ryken, Philippa R. Payne, and Laurel L. Schafer

13.1 Introduction 364

13.1.1 N,O‐Proligands 366

13.1.2 Preparing metal complexes 367

13.2 Applications in reactivity and catalysis 377

13.2.1 Polymerizations 377

13.2.2 Hydrofunctionalization 385

13.3 Conclusions 400

References 401

Index 406