Science of Synthesis: Stereoselective Synthesis Vol. 2 (eBook)

Science of Synthesis: Stereoselective Synthesis 2 – Stereoselective Reactions of Carbonyl and Imino Groups 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 44
2.1 Reduction of Carbonyl Groups: Hydrogenation 52
2.1.1 Diastereoselective Hydrogenation of Carbonyl Groups 54
2.1.1.1 Diastereoselection Based on Steric Hindrance 54
2.1.1.2 Diastereoselection through Chelate Intermediates 57
2.1.2 Enantioselective Hydrogenation of Carbonyl Groups 59
2.1.2.1 Hydrogenation of Functionalized Ketones 59
2.1.2.1.1 Hydrogenation of ß-Keto Esters 59
2.1.2.1.2 Hydrogenation of a-Substituted ß-Keto Esters: Dynamic Kinetic Resolution 67
2.1.2.1.3 Hydrogenation of a-Keto Esters 69
2.1.2.1.4 Hydrogenation of Miscellaneous Substrates 71
2.1.2.2 Hydrogenation of Simple Ketones 73
2.1.2.2.1 Hydrogenation of Aromatic Ketones 73
2.1.2.2.2 Hydrogenation of Unsaturated Ketones (Alkenyl Alkyl Ketones) 89
2.1.2.2.3 Hydrogenation of Alkyl Ketones 92
2.1.2.2.4 Hydrogenation of Acylsilanes 95
2.2 Reduction of Carbonyl Groups: Transfer Hydrogenation, Hydrosilylation, Catalytic Hydroboration, and Reduction with Borohydrides, Aluminum Hydrides, or Boranes 102
2.2.1 Transfer Hydrogenation 102
2.2.1.1 The Meerwein--Ponndorf--Verley Reduction of Ketones 103
2.2.1.1.1 Diastereoselective Reduction 103
2.2.1.1.2 Enantioselective Reduction 108
2.2.1.2 Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Group 8 and 9 Metal Complexes 108
2.2.1.2.1 Reduction in Organic Solvents 108
2.2.1.2.2 Reduction in Water 121
2.2.1.2.3 Immobilized Catalysts 124
2.2.1.2.4 Biomimetic Reduction 125
2.2.2 Hydrosilylation of Ketones 127
2.2.2.1 Hydrosilylation Catalyzed by Rhodium Complexes 128
2.2.2.2 Titanium Hydride Catalyzed Hydrosilylation 132
2.2.2.3 Copper Hydride Catalyzed Hydrosilylation 133
2.2.2.4 Organocatalytic Hydrosilylation 136
2.2.2.4.1 Diastereoselective Reduction 136
2.2.2.4.2 Enantioselective Reduction 138
2.2.3 Asymmetric Catalytic Hydroboration 139
2.2.3.1 Hydroboration of Ketones Catalyzed by Oxazaborolidines 139
2.2.3.2 Hydroboration of Functionalized Ketones Catalyzed by Oxazaborolidines 145
2.2.3.3 Hydroboration of Ketones Catalyzed by (Aminoalkoxy)boranes and Aminoborates 149
2.2.4 Reduction with Borohydrides, Aluminum Hydrides, and Boranes 153
2.2.4.1 Diastereoselective Reduction of Ketones 153
2.2.4.2 Enantioselective Reduction of Aldehydes and Ketones 157
2.3 Enzymatic Reduction of Carbonyl Groups 176
2.3.1 Alcohol Dehydrogenases (Ketoreductases): The Enzymes for Carbonyl Reduction 177
2.3.1.1 Reduction of Ketones Mediated by Wild-Type Whole Cells, Engineered Whole Cells, Enzyme Preparations, and Immobilized Enzymes 178
2.3.1.1.1 Whole-Cell Reductions with Wild-Type Organisms 179
2.3.1.1.2 Enzymes from Genetically Engineered Organisms 183
2.3.1.1.3 Comparison of Enzyme Formulations 184
2.3.1.1.4 General Aspects of Working with Whole Cells and Enzyme Preparations 185
2.3.1.2 Availability of Alcohol Dehydrogenases 186
2.3.1.3 Selection of an Alcohol Dehydrogenase 186
2.3.2 Selection of Reaction Conditions 187
2.3.2.1 Cofactor Regeneration Systems 187
2.3.2.1.1 Cofactor Regeneration by Glucose Dehydrogenase 187
2.3.2.1.2 Cofactor Regeneration by Formate Dehydrogenase 189
2.3.2.1.3 Coupled Substrate for Cofactor Regeneration 190
2.3.2.1.4 Other Methods for Cofactor Regeneration 192
2.3.2.1.5 Comparison of Cofactor Regeneration Systems 193
2.3.2.1.6 Choice of Cofactor Regeneration Systems 193
2.3.2.2 Reaction Media for Enzymatic Ketone Reductions 194
2.3.2.3 Optimization of Reaction Conditions 195
2.3.3 Special Applications of Alcohol Dehydrogenases 197
2.3.4 Substrate Spectrum of Alcohol Dehydrogenases 198
2.3.4.1 Reduction of Aldehydes 199
2.3.4.2 Reduction of Aromatic Ketones 199
2.3.4.2.1 Acetophenones Substituted on the Aromatic Ring 199
2.3.4.2.2 Acetophenones Substituted on the Methyl Group 203
2.3.4.2.3 Diaryl Ketones 208
2.3.4.2.4 Other Aromatic Compounds 209
2.3.4.3 Dialkyl, Alkyl Alkenyl, and Alkyl Alkynyl Ketones 212
2.3.4.4 Cyclic Ketones 218
2.3.4.5 a-Keto and ß-Keto Acid Derivatives 220
2.3.4.6 Diketones 226
2.3.4.7 Stereoselective Reactions on Chiral or Racemic Substrates 230
2.3.5 Outlook 243
2.4 Oxidative Deracemization 252
2.4.1 Deracemization via Oxidative Kinetic Resolution 252
2.4.1.1 Kinetic Resolution of Secondary Alcohols via Transfer Hydrogenation 253
2.4.1.2 Kinetic Resolution Using Molecular Oxygen as Terminal Oxidant 256
2.4.1.2.1 Oxidative Kinetic Resolution of Activated Secondary Alcohols 257
2.4.1.2.1.1 Using Palladium Catalysts 257
2.4.1.2.1.2 Using Ruthenium Catalysts 261
2.4.1.2.1.3 Using Iridium Catalysts 262
2.4.1.2.2 Oxidative Kinetic Resolution of a-Hydroxy Esters, Amides, Thioesters, and Phosphonates 263
2.4.1.3 Kinetic Resolution of Secondary Alcohols via Nitroxyl Radical Based Systems 267
2.4.1.3.1 Electrochemical Oxidation 267
2.4.1.3.2 Reoxidation by Bulk Oxidants 268
2.4.1.4 Kinetic Resolution of Secondary Alcohols Using Manganese--Salen Complexes 271
2.4.1.5 Biocatalytic Kinetic Resolution of Secondary Alcohols 274
2.4.1.6 Biocatalytic Kinetic Resolution of Amino Acids and Amines 276
2.4.2 Deracemization via Oxidation--Reduction Coupled Processes 279
2.4.2.1 Chemical and Chemo-Enzymatic Deracemization of Secondary Alcohols 279
2.4.2.2 Biocatalytic Deracemization of Secondary Alcohols 282
2.4.2.3 Deracemization of Amino Acids and Amines 285
2.4.2.3.1 Deracemization of a-Amino Acids 286
2.4.2.3.2 Deracemization of Primary, Secondary, and Tertiary Amines 287
2.5 Stereoselective Reduction of Imino Groups 294
2.5.1 Asymmetric Hydrogenation of C==N Bonds with Metal Catalysts 295
2.5.1.1 Asymmetric Hydrogenation of Acyclic N-Arylimines 296
2.5.1.2 Asymmetric Hydrogenation of a-Imino Esters 302
2.5.1.3 Asymmetric Hydrogenation of Acyclic N-Alkylimines 304
2.5.1.4 Asymmetric Hydrogenation of Cyclic Imines 306
2.5.1.5 Asymmetric Hydrogenation of Miscellaneous C==N--X Compounds 309
2.5.2 Asymmetric Transfer Hydrogenation of C==N Bonds with Metal Catalysts 312
2.5.2.1 Asymmetric Transfer Hydrogenation of Imines with Metal Catalysts in Organic Media 312
2.5.2.2 Asymmetric Transfer Hydrogenation of Cyclic Imines with Metal Catalysts in Water 315
2.5.2.3 Asymmetric Transfer Hydrogenation of Quinolines with Metal Catalysts in Water 317
2.5.3 Asymmetric Transfer Hydrogenation of C==N Bonds with Organocatalysts 319
2.5.3.1 Organocatalytic Asymmetric Transfer Hydrogenation of Acyclic Imines 319
2.5.3.2 Organocatalytic Asymmetric Transfer Hydrogenation of a-Imino Esters 320
2.5.3.3 Organocatalytic Asymmetric Transfer Hydrogenation of Cyclic Imines 323
2.5.4 Hydroboration of C==N Bonds 324
2.5.5 Hydrosilylation of C==N Bonds 326
2.5.5.1 Asymmetric Hydrosilylation of Imines with Metal Catalysts 326
2.5.5.2 Asymmetric Hydrosilylation of Imines with Organocatalysts 328
2.5.6 Reductive Amination of C==O Bonds 330
2.5.6.1 Via Hydrogenation 331
2.5.6.1.1 Asymmetric Direct Reductive Amination of Ketones 331
2.5.6.1.2 Asymmetric Direct Reductive Amination of ß-Keto Amides 334
2.5.6.1.3 Asymmetric Direct Reductive Amination of ß-Keto Esters 335
2.5.6.2 Via Transfer Hydrogenation with Metal Catalysts 336
2.5.6.2.1 Asymmetric Direct Reductive Amination of Ketones with Ammonium Formate 336
2.5.6.3 Via Transfer Hydrogenation with Organocatalysts 338
2.5.6.3.1 Asymmetric Direct Reductive Amination of Ketones with Hantzsch Esters 338
2.5.6.3.2 Asymmetric Direct Reductive Amination of Aldehydes 340
2.5.6.4 Via Hydroboronation 342
2.5.6.4.1 Direct Reductive Amination with Sodium Triacetoxyborohydride 342
2.5.6.5 Via Hydrosilylation 344
2.5.6.5.1 Asymmetric Direct Reductive Amination of ß-Hydroxy Ketones 344
2.5.6.6 Via Biocatalysts 345
2.5.6.6.1 Asymmetric Direct Reductive Amination of Ketones with Ammonium Formate 346
2.6 Epoxidation and Aziridination of Carbonyl Groups and Imines 354
2.6.1 Epoxidation of Carbonyl Compounds 354
2.6.1.1 Addition of Sulfur Ylides 354
2.6.1.1.1 Catalytic Sulfur Ylide Epoxidations 356
2.6.1.1.2 Stoichiometric Sulfur Ylide Epoxidations 360
2.6.1.2 Addition of Ylides Other than Sulfur Ylides 364
2.6.1.2.1 Arsonium Ylides 364
2.6.1.2.2 Telluronium Ylides 364
2.6.1.2.3 Ammonium Ylides 365
2.6.1.3 Addition of Heteroatom-Substituted Anions to Carbonyl Compounds (Excluding the Darzens Reaction) 366
2.6.1.3.1 Epoxidation with a-Halo Sulfonyl Compounds 367
2.6.1.3.2 Epoxidation with a-Halo Sulfinyl Compounds 369
2.6.1.4 Addition of Diazo Compounds to Carbonyl Compounds 370
2.6.2 Aziridination of Carbonyl Compounds 374
2.6.2.1 Aziridination with Guanidinium Ylides 374
2.6.3 Aziridination of Imines 375
2.6.3.1 Addition of Sulfur Ylides 375
2.6.3.1.1 Addition of Achiral Ylides to Achiral Imines 375
2.6.3.1.2 Addition of Achiral Ylides to Chiral Imines 378
2.6.3.1.3 Addition of Chiral Ylides to Achiral Imines 379
2.6.3.2 Addition of Ylides Other than Sulfur Ylides 381
2.6.3.2.1 Synthesis of Aziridines by Addition of Ammonium Ylides to Imines 381
2.6.3.3 Addition of Diazo Compounds to Imines 382
2.6.3.3.1 Lewis Acid Activation of the Imine 382
2.6.3.3.2 Brønsted Acid Activation of the Imine 384
2.6.3.4 Addition of Heteroatom-Substituted Anions to Imines (Excluding the Darzens Reaction) 385
2.6.3.4.1 Synthesis of Propargylic Aziridines by Addition of Allenylzinc Compounds to Imines 385
2.7 Alkylation of Carbonyl and Imino Groups 392
2.7.1 Diastereoselective Addition 392
2.7.1.1 Addition to Chiral Aldehydes 392
2.7.1.1.1 Alkylation of Aldehydes with a Stereogenic Center at the a-Position 392
2.7.1.1.2 Alkylation of Aldehydes with a Stereogenic Center at the ß-Position 399
2.7.1.1.3 Alkylation of Aldehydes with a Stereogenic Element at Other Positions 399
2.7.1.1.4 Alkylation Using the Darzens Reaction 402
2.7.1.2 Addition to Chiral Aldimines 402
2.7.1.2.1 Alkylation of Imines with Stereogenic Elements at the N-Substituent 402
2.7.1.2.2 Alkylation of Imines with Stereogenic Elements at the C-Substituent 406
2.7.1.2.3 Alkylation Using the Darzens Reaction with Imines with Stereogenic Elements at the N-Substituent 407
2.7.1.3 Addition to Chiral Ketones 407
2.7.1.3.1 Using Cyclic Ketones 407
2.7.1.3.2 Using Acyclic Ketones 408
2.7.1.4 Addition to Chiral Keto Imines 411
2.7.1.5 Addition of Chiral Nucleophiles 412
2.7.1.5.1 Using Chiral Organometallics and Aldehydes 412
2.7.1.5.2 Using the Darzens Reaction with Aldehydes 414
2.7.1.5.3 Using Chiral Organometallics and Ketones 416
2.7.2 Enantioselective Addition 417
2.7.2.1 Modulated Reactions 417
2.7.2.1.1 Using Aldehydes 417
2.7.2.1.2 Using Aldimines 421
2.7.2.1.3 Using Ketone Derivatives 423
2.7.2.2 Catalytic Reactions 425
2.7.2.2.1 Using Achiral Aldehydes and Amino Alcohols as Ligands 425
2.7.2.2.2 Using Achiral Aldehydes and Diamine Derivatives as Ligands 428
2.7.2.2.3 Using Achiral Aldehydes and Diol Derivatives as Ligands 431
2.7.2.2.4 Using Achiral Ketones 434
2.7.2.2.5 Using the Darzens Reaction 436
2.8 Allylation of Carbonyl and Imino Groups 444
2.8.1 Enantioselective Allylation of Aldehydes 446
2.8.1.1 Allylation Using Chiral Allylmetal Reagents 446
2.8.1.1.1 Using Chiral Allylborane and Allylboronate Reagents 446
2.8.1.1.2 Using Chiral Allyltitanium Reagents 451
2.8.1.1.3 Using Chiral Allylsilane Reagents 453
2.8.1.2 Allylation Using Achiral Allyl Sources with Chiral Catalysts 455
2.8.1.2.1 Using Chiral Lewis Base Catalysts with Allyl- and Crotyltrichlorosilane Reagents 456
2.8.1.2.2 Using Chiral Iridium Catalysts with Allyl Acetates 457
2.8.2 Enantioselective Allylation of Ketones 459
2.8.2.1 Allylation Using Chiral Allylmetal Reagents 459
2.8.2.1.1 Using Chiral Allylborane and Allylboronate Reagents 459
2.8.2.1.2 Using Chiral Allylsilane Reagents 461
2.8.2.2 Allylation Using Achiral Allyl Sources with Chiral Catalysts 462
2.8.2.2.1 Using Chiral Silver Catalysts with Allylsilane Reagents 463
2.8.2.2.2 Using Chiral Diol Catalysts with Allylboronate Reagents 464
2.8.3 Enantioselective Allylation of Aldimines 466
2.8.3.1 Allylation Using Chiral Imines 466
2.8.3.1.1 Using Chiral Imines with Allylindium Reagents 467
2.8.3.1.2 Using Chiral Imines with Allylzinc Reagents 468
2.8.3.2 Allylation Using Chiral Allylmetal Reagents 469
2.8.3.2.1 Using Chiral Allylsilane Reagents 469
2.8.3.2.2 Using Chiral Allylboronate Reagents 473
2.8.3.3 Allylation Using Achiral Allyl Sources with Chiral Catalysts 475
2.8.3.3.1 Using Chiral Sulfoxide Catalysts with Allyl- and Crotyltrichlorosilane Reagents 475
2.8.3.3.2 Using Chiral Palladium Catalysts with Allylsilane Reagents 476
2.8.3.3.3 Using Chiral Catalysts with Allylindium Reagents 478
2.8.3.3.4 Using Chiral Diol Catalysts with Allylboronate Reagents 480
2.8.4 Enantioselective Allylation of Ketimines 482
2.8.4.1 Allylation Using Chiral Imines 482
2.8.4.1.1 Using Chiral Imines with Allyl Grignard Reagents 482
2.8.4.1.2 Using Chiral Imines with Allylzinc Reagents 483
2.8.4.2 Allylation Using Chiral Allylmetal Reagents 484
2.8.4.2.1 Using Chiral Allylsilane Reagents 485
2.9 Arylation and Alkenylation of Carbonyl and Imino Groups 492
2.9.1 Arylation of Carbonyl and Imino Groups 492
2.9.1.1 Arylation of Aldehydes 492
2.9.1.1.1 Aryl Additions Using Aryl Sources Based on Zinc 493
2.9.1.1.2 Aryl Additions Using Aryl Sources Based on Boron 498
2.9.1.1.3 Aryl Additions Using Haloarenes 501
2.9.1.2 Arylation of Ketones 509
2.9.1.2.1 Diphenylzinc Additions 509
2.9.1.2.2 Aryl Additions with Organoaluminum Reagents 512
2.9.1.3 Arylation of Imines 514
2.9.1.3.1 Arylation of Imines with Arylboronic Acids and Arylboroxins 514
2.9.2 Alkenylation of Carbonyl and Imino Groups 518
2.9.2.1 Alkenylation of Aldehydes 518
2.9.2.1.1 Alkenylation with Organozinc Reagents through Hydroboration--Transmetalation of Alkynes 518
2.9.2.1.2 Alkenylation with Boronic Acids 523
2.9.2.1.3 Copper-Catalyzed Additions of Alkenyl(trimethoxy)silanes 523
2.9.2.1.4 Chromium-Catalyzed Alkenylation (Nozaki--Hiyama--Kishi Reaction) 525
2.9.2.1.5 Reductive Coupling of Aldehydes and Alkynes 526
2.9.2.2 Alkenylation of Ketones 527
2.9.2.2.1 Enantioselective Addition of Alkenylzinc Reagents 528
2.9.2.2.2 Enantioselective Addition of Alkenylaluminum Reagents 531
2.9.2.3 Alkenylation of Imines 531
2.9.2.3.1 Rhodium-Catalyzed Coupling of Acetylene 532
2.9.2.3.2 Iridium-Catalyzed Coupling of Alkynes 532
2.9.2.3.3 Rhodium-Catalyzed Addition of Alkenyltrifluoroborates 533
2.10 Alkynylation of Carbonyl and Imino Groups 540
2.10.1 Enantioselective Addition of Acetylide Nucleophiles to Carbonyl Compounds 540
2.10.1.1 Enantioselective Addition of Terminal Alkynes to Aliphatic Aldehydes via Zinc(II) Salts 541
2.10.1.1.1 Stoichiometric Zinc(II)-Mediated Enantioselective Alkynylations 542
2.10.1.1.2 Catalytic, Asymmetric Additions of Alkynes to Aliphatic Aldehydes via Zinc(II) Salts 545
2.10.1.2 Catalytic Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes 548
2.10.1.3 Enantioselective Addition of Terminal Alkynes to Ketones 550
2.10.1.3.1 Enantioselective Addition of Terminal Alkynes to a-Oxo Esters 551
2.10.1.3.2 Enantioselective Addition of Terminal Alkynes to Unactivated Ketones 554
2.10.2 Enantioselective Addition of Metal Alkynylides to Imino Groups 560
2.11 Hydrocyanation, Cyanosilylation, and Hydrophosphonylation of Carbonyl and Imino Groups 574
2.11.1 Hydrocyanation of Carbonyl and Imino Groups 574
2.11.1.1 Addition to Carbonyls 575
2.11.1.1.1 Using Chiral Metal Catalysts 575
2.11.1.1.1.1 Using a Vanadium--Salalen Catalyst and Acetone Cyanohydrin 575
2.11.1.1.1.2 Using a Dimeric Vanadium--Salen Catalyst with Potassium Cyanide 576
2.11.1.1.2 Using Organocatalysts 578
2.11.1.1.2.1 Using a Dipeptide Catalyst 578
2.11.1.1.3 Using Enzymes 579
2.11.1.1.3.1 Using an (R)-Oxynitrilase under Microaqueous Conditions 580
2.11.1.1.3.2 Using an (S)-Oxynitrilase from Manihot esculenta (Cassava) 583
2.11.1.1.3.3 Using an (S)-Oxynitrilase from Sorghum bicolor Shoots 584
2.11.1.2 Addition to Imines (Strecker Reaction) 585
2.11.1.2.1 Using Chiral Metal Catalysts 586
2.11.1.2.1.1 Using an Aluminum--Salen Catalyst 586
2.11.1.2.1.2 Using Gadolinium and a Glucose-Derived Chiral Ligand 587
2.11.1.2.1.3 Using a Binuclear Zirconium--1,1'-Bi-2-naphthol Catalyst 588
2.11.1.2.2 Using Organocatalysts 590
2.11.1.2.2.1 Using a Thiourea Catalyst 590
2.11.1.2.2.2 Using a Quaternary Ammonium Salt as a Phase-Transfer Catalyst 592
2.11.1.2.2.3 Using a Chiral 1,1'-Bi-2-naphthol Phosphate 593
2.11.2 Cyanosilylation of Carbonyl and Imino Groups 594
2.11.2.1 Addition to Carbonyls 595
2.11.2.1.1 Using Chiral Metal Catalysts 595
2.11.2.1.1.1 Using a Chiral Ruthenium Catalyst and Lithium Carbonate 595
2.11.2.1.1.2 Using an (S)-3,3'-Bis[(dialkylamino)methyl]-1,1'-bi-2-naphthol/Dimethylaluminum Chloride System 596
2.11.2.1.1.3 Using Gadolinium and a Glucose-Derived Chiral Ligand 598
2.11.2.1.1.4 Using a Synthetic Peptide and Aluminum 599
2.11.2.1.2 Using Organocatalysts 600
2.11.2.1.2.1 Using a Thiourea Catalyst 600
2.11.2.1.2.2 Using an Amino Acid Salt 601
2.11.2.2 Addition to Imines (Strecker Reaction) 602
2.11.2.2.1 Using Chiral Metal Catalysts 603
2.11.2.2.1.1 Using a Cinchonine--2,2'-Biphenol--Titanium Catalyst System 603
2.11.2.2.1.2 Using a Titanium and N-Salicyl-ß-amino Alcohol System 605
2.11.2.2.1.3 Using Gadolinium and a Glucose-Derived Chiral Ligand 606
2.11.2.2.2 Using Organocatalysts 608
2.11.2.2.2.1 Using a Thiourea Catalyst 608
2.11.2.2.2.2 Using a Chiral N,N'-Dioxide for Three-Component Strecker Reactions 609
2.11.2.3 Addition to N-Heterocycles (Reissert Reaction) 610
2.11.2.3.1 Using Aluminum and a 1,1'-Bi-2-naphthol Bis(phosphine oxide) Ligand 610
2.11.3 Hydrophosphonylation of Carbonyl and Imino Groups 613
2.11.3.1 Addition to Aldehydes 613
2.11.3.1.1 Using Chiral Metal Catalysts 613
2.11.3.1.1.1 Using an Aluminum--Salalen Catalyst 614
2.11.3.1.1.2 Using an Aluminum--Schiff Base Catalyst 615
2.11.3.1.1.3 Using a Titanium Bifunctional Mixed Catalyst 616
2.11.3.2 Addition to Imines 617
2.11.3.2.1 Using Chiral Metal Catalysts 617
2.11.3.2.1.1 Using an Aluminum--Salalen Catalyst 618
2.11.3.2.1.2 Using an Aluminum--Bis(quinolinato) Catalyst 619
2.11.3.2.2 Using Organocatalysts 621
2.11.3.2.2.1 Using a Thiourea--Schiff Base Catalyst 621
2.11.3.2.2.2 Using a Cinchona Alkaloid 623
2.12 Asymmetric Mukaiyama Aldol Reaction 628
2.12.1 Asymmetric Mukaiyama Aldol Reaction Using Chiral Aldehydes or Chiral Silyl Enol Ethers 642
2.12.1.1 Reactions with Chiral Aldehydes 642
2.12.1.2 Reactions with Chiral Silyl Enol Ethers 644
2.12.2 Chiral Ligand/Metal Complex Catalysis of the Mukaiyama Aldol Reaction 645
2.12.2.1 Reactions with Chiral Titanium Catalysts 645
2.12.2.2 Reactions with Chiral Zirconium Catalysts 646
2.12.2.3 Reactions with Chiral Boron Catalysts 646
2.12.2.4 Reactions with Chiral Copper Catalysts 648
2.12.2.5 Reactions with Chiral Tin Catalysts 649
2.12.2.6 Reactions with Chiral Scandium Catalysts 650
2.12.2.7 Reaction with a Chiral Silver Catalyst 651
2.12.3 Organocatalysis of the Mukaiyama Aldol Reaction 652
2.12.3.1 Lewis Base Catalyzed Reactions 652
2.12.3.2 Brønsted Acid Catalyzed Reactions 654
2.12.3.3 Reactions Catalyzed by Hydrogen-Bonding Molecules 654
2.12.4 Asymmetric Mukaiyama Aldol Reaction in Aqueous Media 655
2.12.4.1 Reactions Using Chiral Metal Trifluoromethanesulfonate Complexes 655
2.12.4.2 Reactions Using Chiral Iron Catalysts 657
2.12.5 Asymmetric Vinylogous Mukaiyama Aldol Reaction 658
2.12.5.1 Reactions Using Chiral Copper Catalysts 658
2.12.5.2 Reactions Using a Lewis Base 660
2.13 Direct Aldol Reactions 664
2.13.1 Direct Diastereoselective Aldol Reactions 665
2.13.1.1 Reactions Using Ketone Donors 665
2.13.1.2 Reactions Using Other Donors 668
2.13.2 Direct Enantioselective Aldol Reactions 671
2.13.2.1 Catalyzed Reactions of Enolates 671
2.13.2.1.1 Reactions Using Methyl Ketone Donors 671
2.13.2.1.1.1 Reactions Catalyzed by Chiral Metal Complexes 671
2.13.2.1.2 Reactions Using Methylene Ketone Donors 677
2.13.2.1.2.1 Reactions Catalyzed by a Titanium Complex 677
2.13.2.1.3 Reactions Using Other Ketone Donors 678
2.13.2.1.3.1 Reactions Catalyzed by Chiral Metal Complexes 678
2.13.2.1.4 Reactions Using Ester Donors 682
2.13.2.1.4.1 Reactions of Ethyl Diazoacetate Catalyzed by a Magnesium Complex 683
2.13.2.1.4.2 Reactions of a Glycine Schiff Base Catalyzed by a Chiral Quaternary Ammonium Salt 684
2.13.2.1.5 Reactions Using Other Donors 685
2.13.2.1.5.1 Reactions of Thioamides Catalyzed by a Copper Catalyst 685
2.13.2.1.5.2 Reactions of N-Propanoylthiazolidinethiones Catalyzed by a Nickel Complex 687
2.13.2.2 Catalyzed Reactions of Enamines 689
2.13.2.2.1 Reactions Using Ketone Donors 690
2.13.2.2.1.1 Reactions Catalyzed by Proline 690
2.13.2.2.1.2 Reactions Catalyzed by Proline Derivatives 693
2.13.2.2.1.3 Reactions Catalyzed by Other Amine Organocatalysts 695
2.13.2.2.2 Reactions Using Aldehyde Donors 699
2.13.2.2.2.1 Reactions Catalyzed by Proline 699
2.13.2.2.2.2 Reactions Catalyzed by a Proline--Surfactant Organocatalyst 702
2.13.2.2.2.3 Reactions Catalyzed by an Axially Chiral Amino Sulfonamide 704
2.13.2.3 Nitroaldol Reactions 704
2.13.2.3.1 Reactions Catalyzed by Chiral Lanthanum Complexes 705
2.13.2.3.2 Reactions Catalyzed by a Chiral Zinc(II) Complex 708
2.13.2.3.3 Reactions Catalyzed by a Chiral Copper(II) Complex 711
2.13.2.3.4 Reactions Catalyzed by Organocatalysts 712
2.14 Enzymatic Direct Aldol Additions 720
2.14.1 Aldol Addition of Dihydroxyacetone Phosphate to Aldehydes 721
2.14.1.1 Methods of Dihydroxyacetone Phosphate Synthesis 722
2.14.1.1.1 Dihydroxyacetone Phosphate from Chemical Synthesis 722
2.14.1.1.2 Dihydroxyacetone Phosphate from d-Fructose 1,6-Bisphosphate 724
2.14.1.1.3 Dihydroxyacetone Phosphate from Sucrose via “Artificial Metabolism” 725
2.14.1.1.4 Dihydroxyacetone Phosphate from Dihydroxyacetone 728
2.14.1.1.5 Dihydroxyacetone Phosphate from Glycerol and Analogues 731
2.14.1.1.6 In Situ Generation of Dihydroxyacetone Phosphate Mimics from Dihydroxyacetone 733
2.14.1.2 Aldol Addition of Dihydroxyacetone Phosphate to Aliphatic and Haloaliphatic Aldehydes 735
2.14.1.3 Aldol Addition of Dihydroxyacetone Phosphate to Hydroxy-Containing Aldehydes 736
2.14.1.4 Aldol Addition of Dihydroxyacetone Phosphate to Thiol-Containing Aldehydes 742
2.14.1.5 Aldol Addition of Dihydroxyacetone Phosphate to Nitrogen-Containing Aldehydes 744
2.14.1.6 Aldol Addition of Dihydroxyacetone Phosphate to Dialdehydes (“Tandem” Aldolization) 752
2.14.1.7 Aldol Addition of Dihydroxyacetone Phosphate to Other Aldehydes 753
2.14.1.8 Aldol Addition of Dihydroxyacetone Phosphate Analogues to Aldehydes 754
2.14.2 Aldol Addition of 1-Hydroxyalkan-2-ones to Aldehydes 755
2.14.3 Transfer of a Hydroxyacetyl Moiety to Aldehydes 758
2.14.4 Aldol Addition of Pyruvate to Aldehydes 760
2.14.4.1 Aldol Addition of Pyruvate to N-Acetyl-d-mannosamine and Analogues 761
2.14.4.2 Aldol Addition of Pyruvate to d-Arabinose and Analogues 764
2.14.4.3 Aldol Addition of Pyruvate to Aldehydes 765
2.14.5 Aldol Addition of Glycine to Aldehydes 767
2.14.6 Self- and Cross-Aldol Reactions of Acetaldehyde 770
2.14.6.1 Aldol Addition of Acetaldehyde, Acetone, and Fluoroacetone to Aldehydes 770
2.14.6.2 Sequential Two-Step Aldol Additions of Acetaldehyde to Aldehydes 771
2.14.7 Self- and Cross-Aldol Reactions of Glycolaldehyde 772
2.15 Asymmetric Morita--Baylis--Hillman Reaction and Its Aza Analogue 778
2.15.1 Nucleophilic Chiral Amine Catalysis 781
2.15.1.1 Use of Cinchona Alkaloid Based Catalysts 782
2.15.1.2 Use of 1,1'-Bi-2-naphthylamine- and 1,1'-Bi-2-naphthol-Based Bifunctional Catalysts 793
2.15.1.3 Use of Proline-Based Catalysts 796
2.15.1.3.1 Proline-Catalyzed Morita--Baylis--Hillman Reactions 796
2.15.1.3.2 Proline-Catalyzed Aza-Morita--Baylis--Hillman Reaction 802
2.15.2 Combination of Chiral Acid and Achiral Lewis Base 805
2.15.2.1 Use of Chiral Lewis Acids 805
2.15.2.2 Use of Chiral Brønsted Acids 807
2.15.2.2.1 Use of Chiral Thioureas 807
2.15.2.2.2 Use of 1,1'-Bi-2-naphthol 812
2.15.3 Phosphine Catalysis 813
2.15.3.1 Chiral Tertiary Phosphine Catalysis 813
2.15.3.2 Bifunctional Chiral Phosphines 815
2.15.4 Reaction in Chiral Ionic Liquids 821
2.15.5 Summary and Outlook 822
2.16 Mannich Reaction 828
2.16.1 Synthesis of ß-Amino Ester and ß-Amino Amide Products 828
2.16.1.1 Additions to Aldimines 828
2.16.1.1.1 Zirconium(IV)--Bis(1,1'-bi-2-naphthol) Catalysis 828
2.16.1.1.2 Thiourea Hydrogen-Bond Catalysis 829
2.16.1.2 Additions to Aldimines and Ketimines 831
2.16.1.2.1 Addition of Ester Enolates to N-(tert-Butylsulfinyl)imines 831
2.16.1.3 Additions to Ketimines 832
2.16.1.3.1 Copper(I)--Phosphine Catalysis 832
2.16.1.3.2 Chiral Silicon Lewis Acid Promoted Addition 834
2.16.2 Synthesis of ß-Amino Ketone Products 835
2.16.2.1 Unsubstituted Additions 835
2.16.2.1.1 Silver-Catalyzed Additions of Enol Ethers 835
2.16.2.2 syn-Selective Additions 836
2.16.2.2.1 Amino Acid Catalyzed Reactions 836
2.16.2.2.2 Yttrium-Catalyzed Reaction of a-Hydroxy Ketones 840
2.16.2.3 anti-Selective Additions 841
2.16.2.3.1 Designed Amino Acid Catalysis 841
2.16.2.3.2 Proline-Catalyzed anti-Selective Mannich Reactions of Cyclic Imines 843
2.16.2.3.3 Brønsted Acid Catalyzed anti-Selective Mannich Reaction 844
2.16.2.3.4 Synthesis of anti-1,2-Amino Alcohols 845
2.16.3 Addition of Malonates and ß-Keto Esters 846
2.16.3.1 Thiourea-Functionalized Cinchona Alkaloid Catalysis 846
2.16.3.2 Cinchona Alkaloid Derived Phase-Transfer Catalysis 848
2.16.3.3 Phosphoric Acid/Metal Phosphate Catalysis 849
2.16.3.4 Metal Catalysis 852
2.16.3.4.1 Lithium Binaphtholate Salt Catalysis 852
2.16.3.4.2 Cationic Palladium--Aqua Catalysis 853
2.16.4 Additions of Aldehydes 854
2.16.4.1 Acetaldehyde as Nucleophile 854
2.16.4.2 syn-Selective Additions 856
2.16.4.3 anti-Selective Additions 858
2.16.4.4 Additions to Special Imines 860
2.16.4.4.1 Addition to Formyl Imines 860
2.16.4.4.2 Addition to Ketimines 861
2.16.5 Vinylogous Mannich Reaction 862
2.16.5.1 anti-Selective Addition of Siloxyfurans 862
2.16.5.2 syn-Selective Vinylogous Mannich Reactions 864
2.16.5.3 Brønsted Acid Catalyzed Mannich Reaction of Acyclic Silyl Dienolates 865
2.16.6 Nitro-Mannich Reaction 867
2.16.6.1 syn-Selective and Unsubstituted Nitro-Mannich Reactions 867
2.16.6.2 anti-Selective Nitro-Mannich Reactions 868
2.16.6.3 Reactions Giving Highly Substituted Products 869
2.16.7 Synthesis of 1,2-Diamines 870
2.16.7.1 Synthesis of syn-1,2-Diamines 870
2.16.7.2 Synthesis with Switchable Selectivity 871
2.16.8 Additions to Nitrogen-Containing Heterocycles 873
2.16.8.1 Addition to Isoquinolines 873
2.16.8.2 Addition to ß-Carbolines 874
2.17 Asymmetric Benzoin and Stetter Reactions 878
2.17.1 Asymmetric Intermolecular Benzoin Reactions of Aryl Aldehydes 881
2.17.1.1 Homodimerization of Aryl Aldehydes Catalyzed by N-Heterocyclic Carbenes 881
2.17.1.2 Homodimerization of Aryl Aldehydes by Enzyme Catalysis 882
2.17.1.3 Heterodimerization of Aryl Aldehydes by Enzyme Catalysis 883
2.17.1.4 Heterodimerization of Aryl Aldehydes Catalyzed by Metallophosphites 884
2.17.1.5 Aldehyde--Imine Cross Coupling Catalyzed by N-Heterocyclic Carbenes 886
2.17.2 Asymmetric Intramolecular Benzoin Reactions 887
2.17.2.1 Aldehyde--Ketone Crossed Benzoin Reactions Catalyzed by N-Heterocyclic Carbenes 887
2.17.3 Asymmetric Intramolecular Stetter Reactions Catalyzed by N-Heterocyclic Carbenes 891
2.17.3.1 Asymmetric Intramolecular Stetter Reaction of Aryl Aldehydes 891
2.17.3.2 Asymmetric Intramolecular Stetter Reaction of Aliphatic Aldehydes 894
2.17.3.3 Formation of Quaternary Stereocenters 895
2.17.3.4 Desymmetrization of Cyclohexadienones 897
2.17.4 Asymmetric Intermolecular Stetter Reactions Catalyzed by N-Heterocyclic Carbenes 898
2.17.4.1 Reactions of Aryl Aldehydes with 1,3-Diarylprop-2-en-1-ones 898
2.17.4.2 Reactions of Glyoxamides with Alkylidenemalonates 899
2.17.4.3 Reactions of Hetaryl Aldehydes with Arylmethylenemalonates 901
2.17.4.4 Reactions of Hetaryl Aldehydes with Nitroalkenes 902
2.17.5 Asymmetric Intermolecular Acylation of a,ß-Unsaturated Amides Catalyzed by Metallophosphites 903
2.18 Asymmetric Synthesis of Spiroketals, Bisspiroketals, and Spiroaminals 906
2.18.1 Spiroketals 907
2.18.1.1 5,5-Spiroketals 907
2.18.1.1.1 Tandem Oxidative Deprotection/Cyclization toward Norhalichondrin 907
2.18.1.2 5,6-Spiroketals 909
2.18.1.2.1 Heteroatom Diels--Alder Approach to Berkelic Acid 909
2.18.1.2.2 Tandem Aromatic Addition to Aldehyde/Ketalization toward Berkelic Acid 911
2.18.1.2.3 Acidic Conditions/Aprotic Solvent toward Pectenotoxin 912
2.18.1.2.4 2,3-Dichloro-5,6-dicyanobenzo-1,4-quinone-Mediated Deprotection Approach to Pectenotoxin-2 913
2.18.1.2.5 Anionic Cyclization toward Pectenotoxin 913
2.18.1.2.6 Spirodiepoxide Ring Opening toward Pectenotoxin 914
2.18.1.2.7 Acid-Mediated Michael Addition toward Calyculin 915
2.18.1.2.8 Heterogeneous Acidic Cyclization toward Rubromycin 916
2.18.1.2.9 Pummerer-Type Michael Addition toward Rubromycin 917
2.18.1.2.10 Baeyer--Villiger Method for Spiroketal Formation 918
2.18.1.3 6,6-Spiroketals 919
2.18.1.3.1 Heteroatom Diels--Alder/Ketal Reorganization Strategy to Monensin 919
2.18.1.3.2 Heteroatom Diels--Alder Approach toward Reveromycin 920
2.18.1.3.3 Acid-Catalyzed, Protic Solvent Spiroketalization toward Spirofungin 922
2.18.1.3.4 Tethering Restriction To Control Spiroketalization toward Spirofungin 923
2.18.1.3.5 Anionic Cyclization toward Spirofungin 923
2.18.1.3.6 Tandem Sulfone Alkylation/Sulfinic Acid Extrusion toward Milbemycin 924
2.18.1.3.7 Acid-Catalyzed, Protic Solvent Spiroketalization toward Milbemycin 925
2.18.1.3.8 Exploration into Hydrogen Bonding and Acid Selection in the Control of Spiroketalization toward Spongistatin/Altohyrtin 925
2.18.1.3.9 Protic Acid Promoted Michael Addition toward Spongistatin/Altohyrtin 927
2.18.1.3.10 Iodoetherification toward Spongistatin/Altohyrtin 928
2.18.1.3.11 Ring-Closing Metathesis toward Aigialospirol 929
2.18.1.3.12 Reagent-Controlled Opening of Enol Ether Epoxides toward Spiroketals 930
2.18.2 Bisspiroketals 931
2.18.2.1 5,5,6-Bisspiroketals 932
2.18.2.1.1 Radical-Based Oxidative Cyclization toward Spirolides 932
2.18.2.2 6,5,6-Bisspiroketals 934
2.18.2.2.1 Use of Neighboring-Group Effects in Bisspiroketal Formation toward Pinnatoxin 934
2.18.2.2.2 Base-Catalyzed Michael Addition toward Pinnatoxin 935
2.18.2.2.3 Utility of Kinetic and Thermodynamic Conditions toward Azaspiracid 936
2.18.2.2.4 Acid-Catalyzed, Protic Solvent Bisspiroketalization toward Azaspiracid 939
2.18.2.2.5 Utility of Hydrogen Bonding in Bisspiroketalization toward Azaspiracid 940
2.18.2.2.6 Acid-Catalyzed, Protic Solvent Bisspiroketalization toward Azaspiracid 941
2.18.2.2.7 Acid-Mediated Heteroatom Michael Approach toward Azaspiracid 942
2.18.2.2.8 Tandem Iodoetherification/Lewis Acid Catalyzed Cyclization toward Azaspiracid 943
2.18.2.3 6,6,5-Bisspiroketals 944
2.18.2.3.1 Acid-Catalyzed Cyclization of Allenyl Enol Ethers toward Salinomycin 944
2.18.3 Spiroaminals 946
2.18.3.1 5,6-Spiroaminals 946
2.18.3.1.1 Tandem Azide Hydrogenation/Spiroaminal Formation toward Azaspiracid 946
2.18.3.1.2 Steric Effects in Spiroaminal Formation toward Azaspiracid 948
2.18.3.1.3 Lewis Acid Mediated Spiroaminal Formation toward Azaspiracid 949
2.18.3.1.4 Tandem Staudinger/Aza-Wittig Strategy toward Azaspiracid 950
2.18.3.1.5 Iodolactonization toward Spiroaminals 950
2.18.3.2 6,6-Spiroaminals 951
2.18.3.2.1 Acid-Catalyzed, Protic Solvent Spiroaminal Formation toward Sanglifehrin 951
2.18.3.2.2 Acid-Catalyzed Spiroaminal Formation toward Sanglifehrin 951
Keyword Index 958
Author Index 1010
Abbreviations 1054
List of All Volumes 1060