The design of ancillary ligands used to modify the structural and reactivity properties of metal complexes has evolved into a rapidly expanding sub-discipline in inorganic and organometallic chemistry. Ancillary ligand design has figured directly in the discovery of new bonding motifs and stoichiometric reactivity, as well as in the development of new catalytic protocols that have had widespread positive impact on chemical synthesis on benchtop and industrial scales.

Ligand Design in Metal Chemistry presents a collection of cutting-edge contributions from leaders in the field of ligand design, encompassing a broad spectrum of ancillary ligand classes and reactivity applications. Topics covered include:

Key concepts in ligand designRedox non-innocent ligandsLigands for selective alkene metathesisLigands in cross-couplingLigand design in polymerizationLigand design in modern lanthanide chemistryCooperative metal-ligand reactivityP,N Ligands for enantioselective hydrogenationSpiro-cyclic ligands in asymmetric catalysis

This book will be a valuable reference for academic researchers and industry practitioners working in the field of ligand design, as well as those who work in the many areas in which the impact of ancillary ligand design has proven significant, for example synthetic organic chemistry, catalysis, medicinal chemistry,  polymer science and materials 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 weakfield 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 noninnocent ligands 12

1.11 Conclusion 12

References 13

2 Catalyst Structure and CisTrans Selectivity in Rutheniumbased 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 Rucatalyzed olefin metathesis 19

2.2.3 Metallacycle geometry 19

2.2.4 Influencing synanti 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 Zselective Rubased metathesis catalysts 33

2.4.1 Thiophenolatebased Zselective catalysts 33

2.4.2 Dithiolatebased Zselective catalysts 34

2.5 Cyclometallated Zselective 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 Zselective catalysts 42

2.6 Conclusions and future outlook 42

References 43

3 Ligands for Iridiumcatalyzed Asymmetric Hydrogenation of Challenging Substrates 46
MarcAndré 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
ShouFei Zhu and QiLin Zhou

4.1 Development of chiral spiro ligands 66

4.2 Asymmetric hydrogenation 73

4.2.1 Rhcatalyzed hydrogenation of enamides 73

4.2.2 Rh or Ircatalyzed hydrogenation of enamines 73

4.2.3 Ircatalyzed hydrogenation of ,unsaturated carboxylic acids 75

4.2.4 Ircatalyzed hydrogenation of olefins directed by the carboxy group 78

4.2.5 Ircatalyzed hydrogenation of conjugate ketones 79

4.2.6 Ircatalyzed hydrogenation of ketones 80

4.2.7 Rucatalyzed hydrogenation of racemic 2substituted aldehydes via dynamic kinetic resolution 81

4.2.8 Rucatalyzed hydrogenation of racemic 2substituted ketones via DKR 82

4.2.9 Ircatalyzed hydrogenation of imines 84

4.3 Carboncarbon bondforming reactions 85

4.3.1 Nicatalyzed hydrovinylation of olefins 85

4.3.2 Rhcatalyzed hydroacylation 85

4.3.3 Rhcatalyzed arylation of carbonyl compounds and imines 86

4.3.4 Pdcatalyzed umpolung allylation reactions of aldehydes, ketones, and imines 87

4.3.5 Nicatalyzed threecomponent coupling reaction 87

4.3.6 Aucatalyzed Mannich reactions of azlactones 89

4.3.7 Rhcatalyzed hydrosilylation/cyclization reaction 89

4.3.8 Aucatalyzed [2 + 2] cycloaddition 90

4.3.9 Aucatalyzed cyclopropanation 91

4.3.10 Pdcatalyzed Heck reactions 91

4.4 Carbonheteroatom bondforming reactions 91

4.4.1 Cucatalyzed NH bond insertion reactions 91

4.4.2 Cu, Fe, or Pdcatalzyed OH insertion reactions 93

4.4.3 Cucatalyzed SH, SiH and BH insertion reactions 95

4.4.4 Pdcatalyzed allylic amination 95

4.4.5 Pdcatalyzed allylic cyclization reactions with allenes 97

4.4.6 Pdcatalyzed alkene carboamination reactions 98

4.5 Conclusion 98

References 98

5 Application of Sterically Demanding Phosphine Ligands in PalladiumCatalyzed CrossCoupling 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 Palladiumcatalyzed 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 imidazolederived monophosphines 112

5.2.4 Heterobidentate 2P,N ligands: chemoselectivity and room temperature reactions 115

5.2.5 Summary 117

5.3 Palladiumcatalyzed 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 Palladiumcatalyzed nucleophilic fluorination of (hetero)aryl (pseudo)halides 123

5.4.1 Development of palladiumcatalyzed 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 PdNHeterocyclic Carbene Complexes in CrossCoupling Applications 134
Jennifer Lyn Farmer, Matthew Pompeo, and Michael G. Organ

6.1 Introduction 134

6.2 Nheterocyclic carbenes as ligands for catalysis 135

6.3 The relationship between Nheterocyclic 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 Crosscoupling reactions leading to CC bonds that proceed through transmetalation 140

6.5 KumadaTamaoCorriu 141

6.6 SuzukiMiyaura 148

6.6.1 The formation of tetraorthosubstituted (hetero)biaryl compounds 149

6.6.2 Enantioselective SuzukiMiyaura coupling 153

6.6.3 Formation of sp3sp3 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 crosscoupling of secondary organozinc reagents 168

6.8 Conclusion 170

References 171

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

7.1 Introduction 176

7.2 Strategy I. Redox noninnocent ligands used to modify the Lewis acidbase properties of the metal 179

7.3 Strategy II. Redox noninnocent ligands as electron reservoirs 181

7.4 Strategy III. Cooperative ligandcentered reactivity based on redox active ligands 192

7.5 Strategy IV. Cooperative substratecentered radicaltype reactivity based on redox noninnocent substrates 195

7.6 Conclusion 200

References 201

8 Ligands for Ironbased 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 ironcatalyzed 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]PNNP 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]PNNP 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]PNHNP ligands 227

8.4.1 Synthesis of bis(tridentate)iron complexes and PNHNH2 ligands 227

8.4.2 Templateassisted synthesis of iron PNHNP 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 MX bonds 248

9.3.4 Ionization of MX bonds 250

9.4 Reactivity of metallic complexes deriving from ambiphilic ligands 251

9.4.1 Lewis acid enhancement effect in SiSi and CC 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 Ringopening 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 salentype 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 DíazRequejo, 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 Cdonor 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 Nheterocyclic carbenes 343

12.3 Ndonor ligands 344

12.3.1 Hexamethyldisilazide 344

12.3.2 Substituted trispyrazolylborates 347

12.3.3 Silylsubstituted triamidoamine, [N(CH2Ch2NSiMe2But)3]3 348

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

12.4 Pdonor ligands 349

12.4.1 Phospholides 349

12.5 Multiple bonds 350

12.5.1 LnCR2 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,OChelates. Amidates, Ureates and Beyond 364
Scott A. Ryken, Philippa R. Payne, and Laurel L. Schafer

13.1 Introduction 364

13.1.1 N,OProligands 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