Science of Synthesis: Stereoselective Synthesis Vol. 1 (eBook)

Science of Synthesis: Stereoselective Synthesis 1 – Stereoselective Reactions of Carbon—Carbon Double Bonds 1
Organizational Structure of Science of Synthesis 2
Science of Synthesis Reference Library 3
Title page 5
Imprint 7
Preface 8
Volume Editors' Preface 10
Stereoselective Synthesis Volumes 12
Abstracts 14
Overview 24
Table of Contents 26
Introduction 42
1.1 Dihydroxylation, Aminohydroxylation, Diamination, and Dibromination of Carbon--Carbon Double Bonds 46
1.1.1 1,2-Dihydroxylation of Alkenes 46
1.1.1.1 Ruthenium-Catalyzed 1,2-Dihydroxylation of Alkenes 47
1.1.1.2 Sharpless Asymmetric Dihydroxylation of Alkenes 51
1.1.1.3 Secondary Cycle Catalysis 67
1.1.2 Ketohydroxylation of Alkenes 71
1.1.3 1,2-Diboration of Alkenes 74
1.1.4 1,2-Dibromination of Alkenes 74
1.1.5 1,2-Aminohydroxylation of Alkenes 75
1.1.5.1 Tethered Aminohydroxylation of Alkenes 85
1.1.6 Ketamination of Alkenes 91
1.1.7 1,2-Aminoacetoxylation and 1,2-Aminoalkoxylation of Alkenes 92
1.1.8 1,2-Diamination of Alkenes 95
1.1.8.1 Palladium- and Nickel-Catalyzed Diamination of Alkenes 95
1.1.8.2 Copper-Catalyzed Diamination of Alkenes 102
1.1.9 Summary 104
1.2 Epoxidation of Carbon--Carbon Double Bonds 110
1.2.1 Enantioselective Epoxidation of Allylic Alcohols and Related Substrates 111
1.2.1.1 Titanium/Tartrate-Catalyzed Enantioselective Epoxidation 111
1.2.1.1.1 Kinetic Resolution of Secondary Allylic Alcohols 114
1.2.1.1.2 Desymmetrization 117
1.2.1.2 Zirconium-Catalyzed Enantioselective Epoxidation of Homoallylic Alcohols 118
1.2.1.3 Vanadium-Catalyzed Enantioselective Epoxidation 118
1.2.1.3.1 Enantioselective Epoxidation of Homoallylic Alcohols 120
1.2.1.3.2 Kinetic Resolution of Racemic Secondary Allylic Alcohols and Homoallylic Alcohols 121
1.2.1.3.3 Desymmetrization 122
1.2.1.4 Niobium-Catalyzed Enantioselective Epoxidation 122
1.2.2 Enantioselective Epoxidation of Nonfunctionalized Alkenes 123
1.2.2.1 Manganese-Catalyzed Enantioselective Epoxidation 123
1.2.2.2 Iron-Catalyzed Enantioselective Epoxidation 128
1.2.2.3 Ruthenium-Catalyzed Enantioselective Epoxidation 132
1.2.2.4 Titanium-Catalyzed Enantioselective Epoxidation 135
1.2.2.4.1 Using Titanium--Salalen Complexes 135
1.2.2.4.2 Using a Titanium--Salan Complex 138
1.2.2.4.3 Using a Titanium Complex of a Proline-Derived Salan 139
1.2.2.5 Molybdenum-Catalyzed Enantioselective Epoxidation 140
1.2.2.6 Platinum-Catalyzed Enantioselective Epoxidation 142
1.2.2.7 Chiral Ketone Catalyzed Enantioselective Epoxidation 144
1.2.2.7.1 Using Yang's Ketone 145
1.2.2.7.2 Using Shi's Ketone 146
1.2.2.7.2.1 With Hydrogen Peroxide 149
1.2.2.7.3 Miscellaneous Methods 150
1.2.2.8 Chiral Iminium Salt Catalyzed Enantioselective Epoxidation 151
1.2.2.9 Chiral Peracid Catalyzed Enantioselective Epoxidation 152
1.2.3 Enzymatic Epoxidation 153
1.2.3.1 Using Cytochrome P450 154
1.2.3.2 Using Styrene Monooxygenase 156
1.2.3.3 Using Chloroperoxidase 157
1.3 Epoxidation of Enones by Nucleophilic Oxidation 164
1.3.1 Poly(amino acid)-Catalyzed Epoxidation 166
1.3.1.1 Three-Phase Conditions 166
1.3.1.2 Two-Phase Conditions 169
1.3.1.3 Triphasic/Phase-Transfer-Catalyzed Conditions and Scale Up 170
1.3.1.4 Homogeneous Catalytic Epoxidation 171
1.3.1.4.1 Mechanistic Considerations 172
1.3.2 Chiral-Ligand Metal--Peroxide Systems 173
1.3.2.1 Zinc-Mediated Asymmetric Epoxidation 173
1.3.2.2 Lanthanide--1,1'-Bi-2-naphthol Systems 174
1.3.2.2.1 With the Addition of Triphenylarsine Oxide 174
1.3.2.2.2 With the Addition of a Triarylphosphine Oxide 175
1.3.3 Other Organocatalyzed Epoxidations 178
1.3.3.1 Phase-Transfer Conditions 178
1.3.3.1.1 Dimeric Phase-Transfer Catalysts 182
1.3.3.1.2 Binaphthyl Phase-Transfer Catalysts 183
1.3.3.2 Homogeneous Conditions 184
1.3.3.2.1 Pyrrolidine-Based Catalysts 184
1.3.3.2.2 Cinchona Alkaloid Based Catalysts 187
1.3.4 Epoxidations with Chiral Dioxiranes 191
1.4 Aziridination 196
1.4.1 Stoichiometric Methods 196
1.4.1.1 Using Chiral Auxiliaries 196
1.4.1.2 Using Chiral Nitrido--Manganese Complexes 199
1.4.1.3 Electrochemical Aziridination 200
1.4.2 Homogeneous Catalytic Methods 202
1.4.2.1 Using Metal Complexes 202
1.4.2.1.1 Using Chiral Copper Complexes 202
1.4.2.1.2 Using Chiral Ruthenium Complexes 206
1.4.2.1.3 Using Chiral Cobalt Complexes 208
1.4.2.2 Using Organocatalysts 209
1.4.2.2.1 Using Quaternary Salts of Cinchona Alkaloids 209
1.4.2.2.2 Iminium--Enamine Catalysis 210
1.4.2.3 Using Chiral Lewis Acids 215
1.4.2.4 Using Intramolecular Substrate Control 218
1.4.3 Heterogeneous Catalytic Methods 221
1.4.3.1 Asymmetric Aziridination Using CuHY Zeolites 222
1.5 Hydrogenation of Carbon--Carbon Double Bonds 226
1.5.1 Reduction of Didehydroamino Acid Derivatives 233
1.5.1.1 Reduction of a,ß-Didehydroamino Acids and Esters 233
1.5.1.1.1 Using Ligands with a Chiral Carbon-Based Backbone 246
1.5.1.1.2 Using P-Chiral Ligands 250
1.5.1.1.3 Using Ferrocene-Based Ligands 250
1.5.1.1.4 Using Ligands with Chirality Based on Atropisomerism 251
1.5.1.2 Reduction of ß-Hydroxy Didehydroamino Acid Derivatives 253
1.5.1.2.1 Using Ferrocene-Based Ligands 253
1.5.1.3 Reduction of Enamide Phosphonates 254
1.5.1.3.1 Using Ligands with a Chiral Carbon-Based Backbone 254
1.5.2 Reduction of Enamides 254
1.5.2.1 Using Ligands with a Chiral Carbon-Based Backbone 260
1.5.2.2 Using P-Chiral Ligands 261
1.5.2.3 Using Ferrocene-Based Ligands 261
1.5.2.4 Using Ligands with Chirality Based on Atropisomerism 262
1.5.3 Reduction To Give ß-Amino Acid Derivatives 262
1.5.3.1 Using Ligands with a Chiral Carbon-Based Backbone 265
1.5.3.2 Using P-Chiral Ligands 265
1.5.3.3 Using Ferrocene-Based Ligands 265
1.5.3.4 Using Ligands with Chirality Based on Atropisomerism 266
1.5.4 Reduction of ß-Alkoxy Enamides 267
1.5.4.1 Using Ligands with a Chiral Carbon-Based Backbone 268
1.5.4.2 Using P-Chiral Ligands 269
1.5.5 Reduction of a,ß-Unsaturated Carbonyl Systems 269
1.5.5.1 Reduction of a,ß-Unsaturated Acid Derivatives 269
1.5.5.1.1 Using Ligands with a Chiral Carbon-Based Backbone 270
1.5.5.1.2 Using Ferrocene-Based Ligands 271
1.5.5.1.3 Using Ligands with Chirality Based on Atropisomerism 271
1.5.5.2 Reduction of Itaconic (Methylenesuccinic) Acids and Derivatives 272
1.5.5.2.1 Using Ligands with a Chiral Carbon-Based Backbone 275
1.5.5.2.2 Using P-Chiral Ligands 276
1.5.5.2.3 Using Ferrocene-Based Ligands 276
1.5.5.2.4 Using Ligands with Chirality Based on Atropisomerism 277
1.5.5.3 Reduction of Other a,ß-Unsaturated Carbonyl Systems 278
1.5.5.3.1 Using Ligands with Chirality Based on Atropisomerism 278
1.5.6 Reduction of Other Vinyl Systems 278
1.5.6.1 Reduction of Alkenenitriles 278
1.5.6.1.1 Using Ligands with a Chiral Carbon-Based Backbone 278
1.5.6.2 Reduction of Enol Esters 279
1.5.6.2.1 Using Ligands with a Chiral Carbon-Based Backbone 279
1.5.6.2.2 Using P-Chiral Ligands 283
1.5.6.2.3 Using Ferrocene-Based Ligands 283
1.5.6.2.4 Using Ligands with Chirality Based on Atropisomerism 284
1.5.6.3 Reduction of Enol Ethers 284
1.5.6.3.1 Using Ligands with Chirality Based on Atropisomerism 284
1.5.6.4 Reduction of Enol Carbamates 285
1.5.6.4.1 Using Ligands with Chirality Based on Atropisomerism 285
1.5.7 Reduction of Allylic Systems 285
1.5.7.1 Using Ligands with a Chiral Carbon-Based Backbone 285
1.5.7.2 Using Ligands with Chirality Based on Atropisomerism 286
1.5.8 Reduction of Isolated Alkenes 287
1.5.8.1 Using Ligands with a Chiral Carbon-Based Backbone 287
1.5.8.2 Using Ligands with Chirality Based on Atropisomerism 292
1.6 Hydrogenation of Arenes and Hetarenes 298
1.6.1 Catalytic Asymmetric Hydrogenation of Quinoline Derivatives 298
1.6.1.1 Transition-Metal-Catalyzed Enantioselective Hydrogenation 299
1.6.1.1.1 Iridium-Catalyzed Asymmetric Hydrogenation 299
1.6.1.1.2 Ruthenium-Catalyzed Asymmetric Hydrogenation 310
1.6.1.1.3 Rhodium-Catalyzed Asymmetric Hydrogenation 313
1.6.1.2 Organocatalyzed Enantioselective Transfer Hydrogenation 314
1.6.1.2.1 Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation 314
1.6.2 Catalytic Asymmetric Hydrogenation of Indole Derivatives 317
1.6.2.1 Rhodium-Catalyzed Asymmetric Hydrogenation 317
1.6.2.2 Ruthenium-Catalyzed Asymmetric Hydrogenation 318
1.6.3 Catalytic Asymmetric Hydrogenation of Pyrrole Derivatives 319
1.6.3.1 Rhodium-Catalyzed Asymmetric Hydrogenation 319
1.6.4 Catalytic Asymmetric Hydrogenation of Pyridine Derivatives 321
1.6.4.1 Catalytic Diastereoselective Hydrogenation 321
1.6.4.2 Transition-Metal-Catalyzed Enantioselective Hydrogenation 321
1.6.4.2.1 Rhodium-Catalyzed Asymmetric Hydrogenation 321
1.6.4.2.2 Iridium-Catalyzed Asymmetric Hydrogenation 322
1.6.4.2.3 Heterogeneous Asymmetric Hydrogenation 324
1.6.4.3 Organocatalyzed Enantioselective Transfer Hydrogenation 324
1.6.5 Catalytic Asymmetric Hydrogenation of Isoquinoline Derivatives 325
1.6.5.1 Iridium-Catalyzed Asymmetric Hydrogenation 325
1.6.6 Catalytic Asymmetric Hydrogenation of Furan Derivatives 326
1.6.6.1 Transition-Metal-Catalyzed Enantioselective Hydrogenation 326
1.6.6.1.1 Ruthenium-Catalyzed Asymmetric Hydrogenation 327
1.6.6.1.2 Rhodium-Catalyzed Asymmetric Hydrogenation 327
1.6.6.1.3 Iridium-Catalyzed Asymmetric Hydrogenation 328
1.6.7 Catalytic Asymmetric Hydrogenation of Quinoxaline Derivatives 329
1.6.7.1 Ruthenium-Catalyzed Asymmetric Hydrogenation 329
1.6.7.2 Rhodium-Catalyzed Asymmetric Hydrogenation 331
1.6.7.3 Iridium-Catalyzed Asymmetric Hydrogenation 331
1.6.8 Asymmetric Hydrogenation of Arenes 333
1.6.9 Summary and Outlook 333
1.7 Stereoselective Hydroboration and Diboration of Carbon--Carbon Double Bonds 336
1.7.1 Stoichiometric Asymmetric Hydroboration 336
1.7.2 Catalytic Asymmetric Hydroboration 338
1.7.2.1 Reagents and Catalysts 339
1.7.2.2 Catalytic Diastereoselective Hydroboration 341
1.7.2.3 Catalytic Enantioselective Hydroboration 342
1.7.2.3.1 Hydroboration of Styrenes Using Rhodium--BINAP 343
1.7.2.3.1.1 C--O Bond Formation 343
1.7.2.3.1.2 C--C Bond Formation 344
1.7.2.3.2 Hydroboration of Styrenes Using Rhodium--QUINAP 347
1.7.2.3.2.1 C--O Bond Formation 347
1.7.2.3.2.2 C--N Bond Formation 350
1.7.2.3.3 Hydroboration of Cyclopropenes 352
1.7.2.3.4 Hydroboration of 2,3-Diazabicyclo[2.2.1]hept-5-enes 352
1.7.2.3.5 Hydroboration of ß,.-Unsaturated Amides 353
1.7.3 Catalytic Asymmetric Diboration 354
1.7.3.1 Catalytic Diboration of Alkenes 355
1.7.3.2 Catalytic Diboration: Conjugate Additions 358
1.8 Carbometalation of Carbon--Carbon Double Bonds 366
1.8.1 General Considerations and Historical Aspects 366
1.8.2 The Carbolithiation Reaction 367
1.8.2.1 Intramolecular Carbolithiation of Alkenes: Stereoselectivity and Mechanism 367
1.8.2.1.1 Carbolithiation of Unsaturated Alkyllithiums 369
1.8.2.1.1.1 Halogen--Lithium Exchange 369
1.8.2.1.1.2 Tin--Lithium Exchange 372
1.8.2.1.1.3 Reductive Lithiation of Alkyl Phenyl Sulfides 375
1.8.2.1.1.4 Selenium--Lithium Exchange 378
1.8.2.1.1.5 Hydrogen--Lithium Exchange 378
1.8.2.1.1.6 Miscellaneous Methods 382
1.8.2.1.2 Carbolithiation of Unsaturated Vinyl(aryl)lithiums 383
1.8.2.2 Intermolecular Carbolithiation of Alkenes 388
1.8.3 The Carbomagnesiation Reaction 398
1.8.3.1 Intramolecular Carbomagnesiation of Alkenes 398
1.8.3.2 Intermolecular Carbomagnesiation of Alkenes 400
1.8.3.2.1 Noncatalyzed Carbomagnesiation of Alkenes 400
1.8.3.2.2 Catalyzed Carbomagnesiation of Alkenes 401
1.8.4 The Carbozincation Reaction 407
1.8.4.1 Intramolecular Carbozincation of Alkenes 407
1.8.4.1.1 Noncatalyzed Carbozincation of Alkenes 407
1.8.4.1.2 Catalyzed Carbozincation of Alkenes 426
1.8.4.2 Intermolecular Carbozincation of Alkenes 427
1.8.4.2.1 Noncatalyzed Carbozincation of Alkenes 427
1.8.4.2.2 Catalyzed Carbozincation of Alkenes 428
1.8.4.2.3 Allylzincation of Alkenylmetals 430
1.8.4.2.4 Carbometalation of Zinc Enolates and Azaenolates 437
1.8.5 The Carbocupration Reaction 439
1.8.5.1 Intermolecular Carbocupration Reactions 439
1.8.6 The Carboalumination Reaction 443
1.8.6.1 Intermolecular Catalyzed Carboalumination 443
1.9 Hydroformylation, Hydrocarbonylation, Hydrocyanation, and Hydroacylation of Carbon--Carbon Double Bonds 450
1.9.1 Rhodium-Catalyzed Hydroformylation 450
1.9.1.1 History 450
1.9.1.2 Safety Aspects 451
1.9.1.3 Kinetic Features 452
1.9.1.4 Catalyst Formation 453
1.9.1.5 Incubation by Impurities Dormant States
1.9.1.6 Hydroformylation Using Phosphine Ligands 458
1.9.1.7 Hydroformylation Using Phosphine--Phosphite Ligands 468
1.9.1.8 Hydroformylation Using Phosphite Ligands 469
1.9.1.9 Hydroformylation Using Phosphorus Amide/Amidite Ligands 473
1.9.2 Palladium-Catalyzed Carbonylation 475
1.9.2.1 Carbonylation Using Monophosphine Ligands 478
1.9.2.2 Carbonylation Using Diphosphine Ligands 484
1.9.3 Hydrocyanation 490
1.9.3.1 Hydrocyanation Using Phosphite Ligands 491
1.9.3.2 Hydrocyanation Using Other Ligands 492
1.9.4 Hydroacylation 495
1.9.4.1 Intramolecular Hydroacylation 495
1.9.4.2 Intermolecular Hydroacylation 499
1.9.4.2.1 Intermolecular Hydroacylation Using Achiral Catalysts 499
1.9.4.2.2 Intermolecular Hydroacylation Using Chiral Catalysts 507
1.10 Hydrovinylation and Hydroarylation of Carbon--Carbon Double Bonds 518
1.10.1 Transition-Metal-Catalyzed Heterodimerization of Alkenes (Hydrovinylation) 518
1.10.1.1 Hydrovinylation of Alkenes 519
1.10.1.2 Asymmetric Hydrovinylation of 1,3-Dienes 523
1.10.1.2.1 Nickel-Catalyzed Hydrovinylation of 1,3-Dienes (1,2-Addition) 524
1.10.1.2.2 Cobalt-Catalyzed Asymmetric Hydrovinylation of 1,3-Dienes (1,4-Addition) 525
1.10.2 Transition-Metal-Catalyzed Intramolecular Dimerization of Alkenes (Cycloisomerization) 526
1.10.2.1 Rhodium-Catalyzed Cycloisomerization of 1,5-Dienes to Cyclopentanes 527
1.10.2.2 Nickel-Catalyzed Cycloisomerization of 1,6-Dienes to Cyclopentanes 528
1.10.3 Transition-Metal-Catalyzed Hydroarylation of Alkenes 529
1.10.3.1 Hydroarylation with Aryl Imines 531
1.10.3.2 Hydroarylation with Imidazoles 534
1.10.3.3 Hydroarylation with 2-Substituted 1H-Indoles 536
1.10.4 Organocatalytic Inter- and Intramolecular Hydroarylation of Alkenes 538
1.10.4.1 Hydroarylation of a,ß-Unsaturated Aldehydes 539
1.10.4.1.1 Intermolecular Hydroarylation of a,ß-Unsaturated Aldehydes 541
1.10.4.1.2 Intramolecular Hydroarylation of a,ß-Unsaturated Aldehydes 544
1.10.4.2 Hydroarylation of a,ß-Unsaturated Ketones 545
1.10.4.2.1 Hydroarylation of Alkyl Vinyl Ketones and Aryl Vinyl Ketones 546
1.10.4.2.2 Hydroarylation of a,ß-Unsaturated Acyl Esters and Acylphosphonates 548
1.10.4.3 Hydroarylation of Nitroalkenes 551
1.10.4.4 Hydroarylation of Enamines 554
1.11 Reductive Coupling and Cyclization of Carbon--Carbon Multiple Bonds 562
1.11.1 Asymmetric Intermolecular Reductive Coupling of Alkynes and Aldehydes 563
1.11.1.1 Nickel-Catalyzed Preparation of Allylic Alcohols Using a Phosphine Ligand and Triethylborane 563
1.11.1.2 Nickel-Catalyzed Preparation of Allylic Alcohols Using an N-Heterocyclic Carbene Ligand and a Silane 565
1.11.2 Cyclization (Intramolecular Coupling) of Alkynyl Aldehydes 566
1.11.2.1 Nickel-Catalyzed, Organozinc-Mediated Alkylative Cyclization 566
1.11.2.2 Nickel-Catalyzed, Silane-Mediated Reductive Cyclization 567
1.11.2.3 Nickel-Catalyzed Reductive Macrocyclization 569
1.11.2.4 Rhodium-Catalyzed, Hydrogen-Mediated Enantioselective Reductive Cyclization 570
1.11.3 Carbonyl Z-Dienylation via Reductive Coupling of Two Alkyne Units 571
1.11.4 Diastereoselective Preparation of anti-1,2-Diols 574
1.11.4.1 Nickel-Catalyzed Reductive Coupling of Alkynes and a-Oxy Aldehydes 574
1.11.4.2 Nickel-Catalyzed Addition of Alkynylsilanes to a-Siloxy Aldehydes 575
1.11.5 Intermolecular Reductive Coupling of Alkynes and Imines 576
1.11.5.1 Nickel-Catalyzed Allylic Amine Synthesis via Three-Component Coupling of Alkynes, Imines, and Triethylborane 576
1.11.5.2 Iridium-Catalyzed Hydrogenative Coupling of Alkynes and N-(Arylsulfonyl)imines 580
1.11.6 Nickel-Catalyzed Reductive Coupling of Alkynes and Epoxides 581
1.11.6.1 Intermolecular Coupling of Alkynes and Epoxides 581
1.11.6.2 Reductive Cyclization of Alkynes and Epoxides 582
1.11.7 Reductive Coupling of 1,3-Enynes and Carbonyl Electrophiles 583
1.11.7.1 Nickel-Catalyzed Preparation of Dienyl Alcohols via Coupling of 1,3-Enynes and Aldehydes or Ketones 583
1.11.7.2 Enantioselective Reductive Coupling of 1,3-Enynes and a-Oxo Esters To Form Dienyl a-Hydroxy Esters 586
1.11.7.3 Preparation of Chiral Dienyl Alcohols via Enantioselective Reductive Coupling of 1,3-Enynes and Heteroaromatic Aldehydes or Ketones 589
1.11.8 Reductive Coupling of an Alkyne and Aldehyde Directed by a 1,6-Tethered Alkene 591
1.11.9 Nickel-Catalyzed Coupling of 1,3-Dienes and Aldehydes 592
1.11.9.1 Formation of Homoallylic Alcohol Derivatives via Triethylsilane-Mediated Reductive Coupling of 1,3-Dienes and Aldehydes 592
1.11.9.2 Formation of Homoallylic Alcohols via Alkylative Coupling of 1,3-Dienes and Aldehydes 593
1.11.9.3 1,3-anti-Selective Homoallylation of Aldehydes Mediated by Triethylborane 595
1.11.9.4 Enantioselective Homoallylation Catalyzed by Nickel Complexes of Spiro Phosphoramidites 597
1.11.10 Nickel-Catalyzed Synthesis of Z-Allylic Alcohols via Reductive Coupling of Chiral Allenes, Aromatic Aldehydes, and Silanes 599
1.11.11 Intermolecular Reductive Aldol Reactions Mediated by Elemental Hydrogen 600
1.11.11.1 Diastereo- and Enantioselective Aldol Coupling of Vinyl Ketones and Aldehydes 600
1.11.11.2 Formation of syn-Stereotriads by Aldol Coupling of Vinyl Ketones and a-Amino Aldehydes 602
1.11.12 Reductive Coupling of Alkynes and Activated Alkenes 603
1.11.12.1 Nickel-Catalyzed Coupling of Alkynes and Enones To Form .,d-Unsaturated Ketones 603
1.11.12.2 Cobalt-Catalyzed Reductive Coupling of Alkynes and Enals, Enones, or Ester Enoates To Form .,d-Unsaturated Products 605
1.11.13 Enantioselective Reductive Cyclization of 1,6-Enynes 607
1.12 Conjugate Addition Reactions 612
1.12.1 Conjugate Addition of Carbon Nucleophiles 612
1.12.1.1 Addition of Organometallic Reagents 612
1.12.1.1.1 Diastereoselective Addition 612
1.12.1.1.2 Enantioselective Addition 617
1.12.1.1.2.1 Grignard Reagents 617
1.12.1.1.2.2 Organozinc Reagents 621
1.12.1.1.2.3 Aluminum Reagents 627
1.12.1.1.2.4 Arylboron Reagents 629
1.12.1.2 Addition of Stabilized Carbanions 635
1.12.1.2.1 Using Metal Catalysis 635
1.12.1.2.1.1 Addition of 1,3-Diones 636
1.12.1.2.1.2 Addition of ß-Keto Esters 636
1.12.1.2.1.3 Addition of Malonates 640
1.12.1.2.1.4 Addition of Cyanide 642
1.12.1.2.1.5 Addition of Other Michael Donors 644
1.12.1.2.2 Using Organocatalysis 647
1.12.1.2.2.1 Addition to Nitroalkenes 648
1.12.1.2.2.2 Addition to Enals and Enones 653
1.12.1.2.2.3 Addition to Other Activated Acceptors 658
1.12.1.2.3 Using Biocatalysis 660
1.12.2 Conjugate Addition of Nitrogen Nucleophiles 661
1.12.2.1 Diastereoselective Addition 662
1.12.2.2 Using Metal Catalysis 665
1.12.2.2.1 Addition of Hydrazoic Acid and N-Heterocycles 665
1.12.2.2.2 Addition of O-Alkylhydroxylamines to Enones 671
1.12.2.2.3 Addition of N-Alkylhydroxylamines and Hydrazines 672
1.12.2.2.4 Addition of Aromatic Amines 674
1.12.2.3 Using Organocatalysis 677
1.12.2.3.1 Addition of Siloxy- and Alkoxyamines 677
1.12.2.3.2 Addition of N-Heterocycles 679
1.12.2.3.3 Intramolecular Aza-Michael Reactions 681
1.12.2.4 Using Biocatalysis 683
1.12.2.4.1 Use of Hydrolases 683
1.12.2.4.2 Use of Ammonia Lyases 684
1.12.2.4.3 Use of Other Enzymes 687
1.12.3 Conjugate Addition of Oxygen Nucleophiles 689
1.12.3.1 Diastereoselective Addition 689
1.12.3.2 Using Metal Catalysis 693
1.12.3.2.1 Addition of Oximes 693
1.12.3.2.2 Intramolecular Oxy-Michael Reactions 694
1.12.3.3 Using Organocatalysis 695
1.12.3.3.1 Phase-Transfer Catalysis 695
1.12.3.3.2 Addition of Oximes 695
1.12.3.3.3 Addition of Peroxides 697
1.12.3.3.4 Addition of Boronic Acids 704
1.12.3.4 Using Biocatalysis 705
1.12.4 Conjugate Addition of Sulfur Nucleophiles 706
1.12.4.1 Diastereoselective Addition 707
1.12.4.2 Using Metal Catalysis 709
1.12.4.3 Using Organocatalysis 709
1.12.4.4 Using Biocatalysis 713
1.12.5 Conjugate Addition of Other Heteroatoms 715
1.12.5.1 Addition of P--H 715
1.12.5.1.1 Using Organocatalysis 715
1.12.5.1.2 Using Metal Catalysis 719
1.12.5.2 Conjugate Addition by Silicon and Boron Reagents 720
1.13 Hydroamination, Hydrophosphination, Hydrophosphinylation, and Hydrophosphonylation of Carbon--Carbon Double Bonds 730
1.13.1 Hydroamination of Simple Alkenes 731
1.13.1.1 Intermolecular Addition of Cyclic Ureas 731
1.13.1.2 Cyclization of Aminoalkenes 732
1.13.1.2.1 Using Chiral Alkali Metal Based Catalysts 732
1.13.1.2.2 Using Chiral Rare Earth Metal Based Catalysts 733
1.13.1.2.3 Using Chiral Group 4 Metal Based Catalysts 742
1.13.1.2.4 Using Chiral Late Transition Metal Based Catalysts 744
1.13.1.2.5 Kinetic Resolution of Chiral Aminoalkenes 745
1.13.2 Hydroamination of Vinylarenes and 1,3-Dienes 748
1.13.2.1 Intermolecular Additions 748
1.13.2.1.1 Palladium-Catalyzed Intermolecular Hydroamination 748
1.13.2.2 Intramolecular Processes 750
1.13.2.2.1 Using Chiral Rare Earth Metal Based Catalysts 750
1.13.2.2.2 Using Chiral Alkali Metal Based Catalysts 751
1.13.3 Hydroamination of Strained Alkenes 751
1.13.3.1 Iridium-Catalyzed Addition of Amines to Norbornene Derviatives 751
1.13.4 Hydroamination of Allenes 753
1.13.4.1 Via Chirality Transfer from an Enantiopure Allene 753
1.13.4.2 Cyclization of Aminoallenes 755
1.13.4.2.1 Using Chiral Gold-Based Catalysts 755
1.13.4.2.2 Dynamic Kinetic Resolution of Aminoallenes via Enantioselective Hydroamination/Cyclization 756
1.13.5 Alternative, Indirect Methods 758
1.13.5.1 Tandem Processes Involving Hydroamination of Alkynes 758
1.13.5.1.1 Tandem Hydroamination/Reduction 759
1.13.5.1.2 Tandem Hydroamination/Hydrosilylation 760
1.13.5.2 Cyclization of Aminoalkynes 761
1.13.5.3 Hydroboration/Amination of Alkenes 762
1.13.5.4 Hydrozirconation/Iodination of Aminoalkenes 763
1.13.6 Hydrophosphinylation, Hydrophosphonylation, and Hydrophosphination 764
1.13.6.1 Hydrophosphinylations of Chiral Alkenes 764
1.13.6.2 Hydrophosphonylation of Styrene and Norbornene 765
1.13.6.3 Hydrophosphination/Cyclization of Phosphinoalkenes 766
1.14 Cyclopropanation Reactions 772
1.14.1 Intermolecular Cyclopropanation Reactions Using Zinc Carbenoids 772
1.14.1.1 Zinc Reagents for Stereoselective Reactions 773
1.14.1.1.1 a-Substituted Halomethylzinc Carbenoids: Reagent-Based Diastereoselectivity 774
1.14.1.2 Diastereoselective Cyclopropanation Reactions of Chiral Alkenes 776
1.14.1.2.1 Diastereoselective Cyclopropanation of Cyclic Chiral Alkenes 777
1.14.1.2.2 Diastereoselective Cyclopropanation of Acyclic Chiral Alkenes 778
1.14.1.3 Enantioselective Cyclopropanation Reactions Using Stoichiometric Chiral Addititives 786
1.14.1.4 Enantioselective Cyclopropanation Reactions Using Substoichiometric Chiral Addititives 794
1.14.2 Intramolecular Cyclopropanation Using Carbenoids 799
1.14.3 Intermolecular Cyclopropanation Using Metal Carbenes 800
1.14.3.1 Using Metal Carbenes Bearing One Electron-Withdrawing Group 801
1.14.3.2 Using Metal Carbenes Bearing Two Electron-Withdrawing Groups 812
1.14.3.3 Using Metal Carbenes Bearing One Electron-Withdrawing Group and One Electron-Donating Group 820
1.14.4 Intramolecular Cyclopropanation Using Metal Carbenes 827
1.14.4.1 Synthesis of Carbocyclic Bicyclo Ring Systems 827
1.14.4.2 Synthesis of Heterocyclic Bicyclo Ring Systems 830
1.14.5 Cyclopropanation Using Michael-Initiated Ring-Closure Reactions 835
1.14.5.1 Diastereoselective Cyclopropanation Using Michael-Initiated Ring Closure 835
1.14.5.2 Enantioselective Cyclopropanation Using Michael-Initiated Ring Closure 836
1.14.5.2.1 Enantioselective Cyclopropanation Using Chiral Ylides 836
1.14.5.2.2 Nucleophilic Activation Using a Chiral Catalyst 837
1.14.5.2.3 Electrophilic Activation Using Chiral Catalysts 841
1.14.6 Cyclopropane Formation by Ring-Closure Reactions 844
1.14.6.1 Ring-Opening Reaction of Oxiranes 844
1.14.6.2 Miscellaneous Methods 845
1.14.7 Cyclopropane Formation by Ring-Contraction Reactions 846
1.14.8 Miscellaneous Methods 848
1.14.8.1 Kulinkovich Cyclopropanation 848
1.14.8.2 Epoxide Methylene Transfer Cyclopropanation 849
1.14.8.3 p-Allylpalladium Cyclopropanation 850
1.14.8.4 Gold(I)-Catalyzed Cyclopropanation 851
1.15 Enantioselective and Diastereoselective Alkene Metathesis 860
1.15.1 Enantioselective Alkene Metathesis 860
1.15.1.1 Asymmetric Ring-Closing Metathesis (ARCM) 860
1.15.1.1.1 Kinetic Resolution of Dienes 861
1.15.1.1.2 Desymmetrization of meso-Trienes 862
1.15.1.2 Tandem Asymmetric Ring-Opening/Cross Metathesis (AROM/CM) or Tandem Asymmetric Ring-Opening/Ring-Closing Metathesis (AROM/RCM) 870
1.15.1.2.1 Ring Opening of Strained Rings 870
1.15.1.2.2 Ring Opening of Cyclopentenes 877
1.15.1.3 Asymmetric Cross Metathesis (ACM) 879
1.15.1.4 Asymmetric Ene--Yne Metathesis (AEYM) 880
1.15.2 Diastereoselective Alkene Metathesis 882
1.15.2.1 Diastereoselective Ring-Opening Metathesis (via Hydrogen Bonding) 882
1.15.2.2 Diastereoselective Ring-Closing Metathesis 883
1.15.2.2.1 Diastereoselective Ring Closing To Form Five-, Six-, and Seven-Membered Rings and Macrocyclic Ring-Closing Reactions 883
1.15.2.2.2 Diastereoselective Ring-Closing Reactions Using Temporary Tethers 892
1.15.2.3 E/Z-Selective Cross Metathesis 893
1.15.2.3.1 Solvent Effects 894
1.15.2.3.2 Substrate-Selective Cross Metathesis 896
1.15.2.3.3 Z-Selective Alkene and Ene--Yne Metathesis 904
1.16 Addition of Free Radicals to Carbon--Carbon Multiple Bonds 914
1.16.1 Diastereoselective Radical Addition to Electron-Deficient Carbon--Carbon Multiple Bonds 914
1.16.1.1 Substrate-Controlled Intermolecular Diastereoselective Reactions 914
1.16.1.2 Chiral Auxiliary Controlled Intermolecular Diastereoselective Reactions 916
1.16.1.3 Intramolecular Radical Conjugate Additions 918
1.16.1.4 Radical-Polar Crossover Reactions 921
1.16.1.5 Annulation Reactions 923
1.16.1.6 Tandem Reactions 923
1.16.1.7 Applications in Total Synthesis 925
1.16.2 Diastereoselective Radical Addition to Electron-Rich Carbon--Carbon Multiple Bonds 926
1.16.2.1 Intermolecular Addition 926
1.16.2.2 Intramolecular Addition 927
1.16.3 Tin-Free Radical Reactions 928
1.16.3.1 Samarium(II) Iodide Mediated Radical Reactions 929
1.16.3.2 Borane-Mediated Radical Reactions 930
1.16.3.3 Zinc-Mediated Radical Reactions 931
1.16.3.4 Manganese-Mediated Radical Reactions 931
1.16.3.5 Nickel-Mediated Radical Reactions 932
1.16.3.6 Titanium-Mediated Radical Reactions 932
1.16.4 Radical-Mediated Atom-Transfer Reactions 934
1.16.4.1 Intermolecular Addition 934
1.16.4.2 Cyclization Reactions 935
1.16.5 Enantioselective Radical Reactions 936
1.16.5.1 Chiral Lewis Acid Mediated Reactions 937
1.16.5.2 Enantioselective Fragmentation Reactions 947
1.16.5.3 Enantioselective Intermolecular Tandem Radical Reactions 950
1.16.5.4 Enantioselective Radical Reactions Mediated by Samarium and Titanium 952
1.16.5.5 Enantioselective Radical Cyclizations 954
1.16.5.6 Organocatalysis 956
1.17 Asymmetric Hydrosilylation of Carbon--Carbon Double Bonds 964
1.17.1 Asymmetric Hydrosilylation of Styrenes 966
1.17.2 Asymmetric Hydrosilylation of Alkyl-Substituted Alkenes 969
1.17.3 Asymmetric Hydrosilylation of 1,3-Dienes 974
1.17.4 Asymmetric Cyclization/Hydrosilylation of Enynes 978
Keyword Index 982
Author Index 1034
Abbreviations 1070
List of All Volumes 1076