Science of Synthesis: Water in Organic Synthesis (eBook)

Science of Synthesis: Water in Organic Synthesis 1
Organizational Structure of Science of Synthesis 2
Science of Synthesis Reference Library 3
Title page 5
Imprint 7
Preface 8
Volume Editor's Preface 10
Abstracts 12
Overview 28
Table of Contents 32
1 Introduction 54
1.1 Water-Compatible Lewis Acids 54
1.2 Lewis Acid--Surfactant Combined Catalysts for Organic Reactions in Water 58
2 Structure and Properties of Water 70
2.1 The Single Water Molecule 71
2.2 Liquid Water 73
2.3 Water as a Reaction Medium for Organic Synthesis 77
2.4 Thermodynamics of Hydration 78
2.5 Solvent Properties of Water 79
2.5.1 The Size of the Water Molecule 79
2.5.2 Polarizability 80
2.5.3 Solvent Polarity Indicators 81
2.5.4 Solvatochromic Solvent Parameters 82
2.5.5 The Solvatochromic Comparison Method: Linear Solvation Energy Relationships 83
2.5.6 Cohesive Energy Density 85
2.5.7 Internal Pressure 85
2.5.8 The Ionic Product of Water: Proton and Hydroxide Ion Mobilities 85
2.5.9 Water at High and Low Temperatures and Pressures 86
2.5.10 Water and Deuterium Oxide 87
2.6 Aqueous Electrolyte Solutions 88
2.6.1 Ionic Hydration: Hydration Numbers 88
2.6.2 Dynamics of Ion Hydration 90
2.7 Hydrophobic Effects 91
2.7.1 Hydrophobic Hydration 92
2.7.2 Hydrophobic Interactions 94
2.8 Organic Reactivity in Water 95
2.8.1 Catalysis in Water 95
2.8.2 Micellar Catalysis 96
2.8.3 Hydrophobic Effects on Reactivity: Initial-State versus Transition-State Effects 97
2.8.4 Effects of Additives on Reactivity in Water 99
2.8.4.1 Salt Effects 99
2.8.4.2 Cosolvent Effects 99
2.8.5 Reactions on Water 100
2.8.6 Reactions in Supercritical Water 100
2.8.7 Water as a Green Solvent 101
2.9 Epilogue 101
3 Aqueous Media: Reactions of C--C Multiple Bonds 106
3.1 Asymmetric Oxidation Reactions: Sulfoxidation, Epoxidation, Dihydroxylation, and Aminohydroxylation 106
3.1.1 Catalyst Tuning by Water 107
3.1.1.1 Enantioselective Oxidation of Sulfides Using a Water-Modified Titanium/Tartrate Catalyst 107
3.1.1.2 Asymmetric Aerobic Epoxidation Using a Water-Bound Ruthenium--Salen Complex as Catalyst 107
3.1.2 Enantioselective Oxidation of Sulfides under Aqueous Conditions 108
3.1.2.1 Enantioselective Oxidation of Sulfides Using Chiral Metal--Schiff Base Catalysts 108
3.1.2.1.1 Vanadium-Catalyzed Oxidation 108
3.1.2.1.2 Iron-Catalyzed Oxidation 109
3.1.2.2 Enantioselective Oxidation of Sulfides Using Metallosalen and Related Complexes as Catalysts 110
3.1.2.2.1 Manganese--Salen-Catalyzed Oxidation 110
3.1.2.2.2 Titanium--Salen-Catalyzed Oxidation 110
3.1.2.2.3 Aluminum--Salalen-Catalyzed Oxidation 111
3.1.2.3 Asymmetric Oxidation of Sulfides in Water 112
3.1.2.3.1 Platinum-Catalyzed Asymmetric Oxidation of Sulfides 112
3.1.2.3.2 Iron--Salan-Catalyzed Oxidation 113
3.1.3 Enantioselective Epoxidation 114
3.1.3.1 Asymmetric Epoxidation of Allylic Alcohols 115
3.1.3.1.1 Asymmetric Epoxidation of Allylic Alcohols under Aqueous Conditions 115
3.1.3.1.2 Asymmetric Epoxidation of Allylic Alcohols Using Aqueous Hydrogen Peroxide 116
3.1.3.2 Asymmetric Epoxidation of Unfunctionalized Alkenes 117
3.1.3.2.1 Metalloporphyrin-Catalyzed Enantioselective Epoxidation 117
3.1.3.2.2 Enantioselective Epoxidation Using Metal--Salen/Salalen/Salan Complexes as Catalyst 118
3.1.3.2.2.1 Bioinspired Enantioselective Epoxidation Using Manganese--Salalen or Manganese--Salen Complexes as Catalyst 119
3.1.3.2.2.2 Enantioselective Epoxidation Using Titanium--Salalen or Titanium--Salan Complexes as Catalyst 120
3.1.3.2.3 Iron-Catalyzed Enantioselective Epoxidation 124
3.1.3.2.4 Ruthenium-Catalyzed Enantioselective Epoxidation 124
3.1.3.2.5 Platinum-Catalyzed Enantioselective Epoxidation 125
3.1.3.3 Enantioselective Epoxidation Using Organic Compounds as Catalysts 127
3.1.3.3.1 Chiral Ketone Catalyzed Enantioselective Epoxidation 127
3.1.3.3.2 Enantioselective Epoxidation of Electron-Deficient Alkenes Using Organocatalysts 129
3.1.3.3.2.1 Polyamino Acid Catalyzed Asymmetric Epoxidation 129
3.1.3.3.2.2 Phase-Transfer Catalyst Mediated Epoxidation 130
3.1.3.3.2.3 Amine-Catalyzed Asymmetric Epoxidation 132
3.1.4 Enantioselective Dihydroxylation 134
3.1.4.1 Osmium-Catalyzed Enantioselective Dihydroxylation 134
3.1.4.2 Iron-Catalyzed Enantioselective Dihydroxylation 141
3.1.5 Enantioselective Aminohydroxylation 141
3.1.6 Conclusions 144
3.2 Hydrogenation of Alkenes, Alkynes, Arenes, and Hetarenes 148
3.2.1 Catalysts and General Techniques for Hydrogenations in Water 148
3.2.2 Hydrogenation of Alkenes 149
3.2.2.1 Alkanes by Hydrogenation of Alkenes with Water-Soluble Analogues of Wilkinson's Catalyst 150
3.2.2.1.1 Using Preprepared Rhodium(I)--Sulfonated Triphenylphosphine Catalysts 150
3.2.2.1.2 Using In Situ Prepared Rhodium(I)--Sulfonated Triphenylphosphine Catalysts 150
3.2.2.1.3 Using In Situ Prepared Rhodium(I) Catalysts in Microemulsions 152
3.2.2.2 Alkanes by Hydrogenation of Alkenes with Rhodium(I)-Based Catalysts Attached to Proteins 153
3.2.2.3 Alkanes by Hydrogenation of Alkenes with Ruthenium(II) Catalysts 153
3.2.2.4 Alkanes by Hydrogenation of Alkenes with Polymer-Stabilized Colloidal Metal Catalysts 154
3.2.2.4.1 Using an In Situ Prepared Palladium--Poly(vinylpyrrolidone) Catalyst 154
3.2.2.4.2 Using a Preprepared Palladium--Poly(vinylpyrrolidone) Catalyst 155
3.2.2.5 Isotope Labeling by Hydrogenation in Water 156
3.2.3 Asymmetric Hydrogenation of Alkenes 157
3.2.3.1 Chiral Alkanes by Hydrogenation of Prochiral Alkenes Catalyzed by Rhodium(I) Complexes 158
3.2.3.2 Chiral Alkanes by Hydrogenation of Prochiral Alkenes Catalyzed by Ruthenium(II) Complexes 160
3.2.3.2.1 In Homogeneous Aqueous Solution with a Ruthenium(II)--Tetrasulfonated 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl Catalyst 160
3.2.3.2.2 Alkanoic Acids by Hydrogenation of Alkenoic Acids with a Water-Soluble Chiral Ruthenium(II)--Bisphosphine Catalyst 161
3.2.4 Hydrogenation of Dienes 161
3.2.4.1 Alkenes by Selective Hydrogenation of Dienes with Potassium Pentacyanohydridocobaltate(III) 161
3.2.4.2 Alkenoic Acids by Selective Hydrogenation of Hexa-2,4-dienoic Acid with a Ruthenium(II)--Sulfonated Phosphine Catalyst 162
3.2.5 Hydrogenation of Polymers 163
3.2.5.1 Modified Elastomers by Hydrogenation of Polymers 163
3.2.6 Hydrogenation of Alkynes 165
3.2.6.1 Alkenes by Selective Hydrogenation of Alkynes 165
3.2.6.1.1 Hydrogenation of Pent-2-yne with Polymer-Stabilized Metal Colloids 165
3.2.6.1.2 Hydrogenation of Diphenylacetylene with a Ruthenium(II)--Sulfonated Triphenylphosphine Catalyst 166
3.2.7 Hydrogenation of Arenes and Hetarenes 167
3.2.7.1 Hydrogenation of Benzene Derivatives with a Homogeneous Ruthenium-Based Catalyst 167
3.2.7.2 Hydrogenation of Aromatics with Stabilized Metal Nanoparticles 168
3.2.7.2.1 Arene Hydrogenation Catalyzed by Aqueous Solutions of Rhodium(III) Chloride Trihydrate and Aliquat 336 168
3.2.7.2.2 Arene Hydrogenation Catalyzed by Aqueous Solutions of Rhodium(III) Chloride and N-Alkyl-N-(2-hydroxyethyl)-N,N-dimethylammonium Surfactants 168
3.2.7.2.3 Hydrogenation of Arenes with Poly(N-vinylpyrrolidone)-Stabilized Ruthenium Nanoparticles 169
3.2.7.2.4 4-Propylcyclohexanols by Stereoselective Hydrogenation of 4-Propylphenols (Lignin Degradation Model Compounds) 170
3.2.7.2.5 Hydrogenation of Hetarenes with Water-Soluble Ruthenium(II) Complexes 171
3.3 Hydroformylation and Related Reactions 174
3.3.1 Background to Hydroformylation and Related Reactions 176
3.3.2 Ligands for Hydroformylation in Aqueous Media 176
3.3.3 Hydroformylation in Aqueous Media 180
3.3.3.1 Hydroformylation of Higher Alkenes 184
3.3.3.2 Hydroformylation of Functionalized Alkenes 192
3.3.3.3 Asymmetric Hydroformylation Reactions 193
3.3.3.4 Laboratory Techniques 195
3.3.3.4.1 Biphasic Hydroformylation under Batch Conditions 195
3.3.3.4.2 Biphasic Hydroformylation under Continuous Conditions 196
3.3.4 Supported Aqueous-Phase Hydroformylation 197
3.3.5 Hydrocarboxylation in Aqueous Media 200
3.4 Conjugate Addition Reactions 208
3.4.1 C--H Bond Formation 208
3.4.1.1 Metal-Complex-Mediated Conjugate Reduction 208
3.4.1.2 Metal-Free Catalytic Conjugate Reduction of Enals 209
3.4.2 C--C Bond Formation 211
3.4.2.1 Addition of Alkyl Groups in C--C Bond Formation 211
3.4.2.1.1 Radical-Mediated Addition of Alkyl Groups 211
3.4.2.1.2 Metal-Complex-Mediated Addition of Alkyl Groups 212
3.4.2.1.3 Metal-Free Catalytic Addition of Alkyl Groups 213
3.4.2.2 Addition of Alkenyl and Aryl Groups in C--C Bond Formation 216
3.4.2.2.1 Catalyst-Free Addition of Aryl Groups 216
3.4.2.2.2 Metal-Complex-Catalyzed Addition of Alkenyl and Aryl Groups 217
3.4.2.2.2.1 Addition of Alkenyl and Aryl Groups to Carbonyl Compounds 217
3.4.2.2.2.2 Asymmetric Addition of Aryl Groups to Carbonyl Compounds 219
3.4.2.2.2.3 Addition of Indoles to Electron-Deficient Alkenes 220
3.4.2.2.3 Metal-Free Catalytic Addition of Aryl Groups 222
3.4.2.2.3.1 Brønsted Acid Catalyzed Addition of Indoles to Electron-Deficient Alkenes 222
3.4.2.2.3.2 Asymmetric Addition of Pyrroles and Indoles to Enals via Iminium Catalysis 223
3.4.2.3 Addition of Alkynyl Groups in C--C Bond Formation 224
3.4.2.3.1 Metal-Complex-Catalyzed Addition of Alkynyl Groups 224
3.4.2.4 Addition of Carbonyl Compounds in C--C Bond Formation 227
3.4.2.4.1 Catalyst-Free Addition of Carbonyl Compounds 227
3.4.2.4.2 Metal-Complex-Catalyzed Addition of Carbonyl Compounds to Enones 227
3.4.2.4.3 Metal-Free Catalytic Addition of Carbonyl Compounds 229
3.4.2.4.3.1 Addition of Carbonyl Compounds to Enals or Enones via Iminium Catalysis 229
3.4.2.4.3.2 Addition of Carbonyl Compounds to a,ß-Unsaturated Esters via Enamine Catalysis 232
3.4.2.4.3.3 Addition of Carbonyl Compounds to Nitroalkenes via Enamine Catalysis 233
3.4.2.4.3.4 Addition of Carbonyl Compounds Using Other Metal-Free Catalysts 239
3.4.3 C--N Bond Formation 241
3.4.3.1 Catalyst-Free Addition in C--N Bond Formation 241
3.4.3.1.1 Addition of Amines to Enones 241
3.4.3.1.2 Addition of Amines to a,ß-Unsaturated Carboxylic Acid Derivatives 242
3.4.3.1.3 Addition of Amines to Acrylonitrile 244
3.4.3.1.4 Addition of Amines to Nitro, Phosphonate, and Sulfonate Derivatives 246
3.4.3.2 Metal-Complex-Catalyzed Addition in C--N Bond Formation 248
3.4.3.3 Metal-Free Catalytic Addition in C--N Bond Formation 249
3.4.4 C--O Bond Formation 251
3.4.4.1 Metal-Free Catalytic Addition in C--O Bond Formation 251
3.4.4.1.1 Phosphine-Catalyzed Hydration 251
3.4.4.1.2 Asymmetric Addition of Alcohols to Enals via Iminium Catalysis 251
3.4.5 C--S and C--Se Bond Formation 252
3.4.5.1 Catalyst-Free Addition in C--S Bond Formation 252
3.4.5.1.1 Addition of Thiols to Enones and Quinones 252
3.4.5.1.2 Addition of Thiols to a,ß-Unsaturated Carboxylic Acid Derivatives 254
3.4.5.1.3 Addition of Thiols to Acrylonitrile 257
3.4.5.1.4 Addition of Thiols to Nitroalkenes 258
3.4.5.2 Catalytic Addition in C--S Bond Formation 259
3.4.5.3 C--Se Bond Formation: Reaction of Zinc Selenolates 260
3.5 Cyclopropanation Reactions 264
3.5.1 Transition-Metal-Catalyzed Reaction of Diazo Compounds 264
3.5.1.1 Reaction Using Water-Soluble Catalysts 265
3.5.1.1.1 Using pybox--Ruthenium Catalysts 265
3.5.1.1.2 Using Metalloporphyrin Catalysts 266
3.5.1.2 Using Diazo Esters in Biphasic Media 269
3.5.1.3 In Situ Generation of the Diazo Reagent 271
3.5.2 Triphenylarsine-Catalyzed Cyclopropanation 274
3.5.3 Radical Reaction from Halogenated Compounds and Zinc Powder 275
3.6 Metathesis Reactions 278
3.6.1 Aqueous Alkene Metathesis Using Poorly Defined Catalytic Systems 280
3.6.1.1 Polymerization of 7-Oxabicyclo[2.2.1]hept-2-ene Derivatives 280
3.6.1.2 Polymerization of 7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate Derivatives 280
3.6.2 Aqueous Alkene Metathesis Using Water-Insoluble Well-Defined Catalysts 282
3.6.2.1 Applications in Homogeneous Aqueous Solutions 282
3.6.2.1.1 Ring-Closing Metathesis Using Ruthenium-Based Defined Catalysts in Homogeneous Water/Organic Solvent Mixtures 282
3.6.2.1.2 Cross Metathesis Using Ruthenium-Based Defined Catalysts in Homogeneous Water/Organic Solvent Mixtures 283
3.6.2.2 Applications in Water-Containing Heterogeneous Mixtures 284
3.6.2.2.1 Metathesis in the Presence of Water without a Cosolvent, Additives, or Surfactants 284
3.6.2.3 Metathesis in Aqueous Emulsions 285
3.6.2.3.1 Ring-Opening Metathesis Polymerization in Aqueous Emulsions 285
3.6.2.3.1.1 Ring-Opening Polymerization Using Dodecyltrimethylammonium Bromide as a Surfactant 285
3.6.2.3.1.1.1 Polymerization of Bicyclo[2.2.1]hept-2-enes and 7-Oxa Derivatives 285
3.6.2.3.1.1.2 Polymerization of Bicyclo[2.2.1]hept-5-ene-2-carboxamides and 7-Oxa Derivatives 286
3.6.2.3.1.1.3 Polymerization of Vancomycin-Based Oligomers 287
3.6.2.3.1.2 Polymerization Using Sodium Dodecyl Sulfate as a Surfactant 288
3.6.2.3.1.2.1 Polymerization of Bicyclo[2.2.1]hept-2-ene 288
3.6.2.3.1.2.2 Polymerization of Cyclooctadiene and Cyclooctene 288
3.6.2.3.1.3 Polymerizations Using Acacia Gum as a Surfactant 288
3.6.2.3.2 Ring-Closing Metathesis and Cross Metathesis in Aqueous Emulsions 289
3.6.2.3.2.1 Ring-Closing Metathesis and Cross Metathesis in Aqueous Emulsions Using Surfactants 289
3.6.2.3.2.1.1 Ring-Closing Metathesis of Diethyl 2,2-Diallylmalonate Using Sodium Dodecyl Sulfate 289
3.6.2.3.2.1.2 Homo-Cross Metathesis of Vancomycin Derivatives Using Dodecyltrimethylammonium Bromide 289
3.6.2.3.2.1.3 Cross Metathesis Using Polyoxyethanyl a-Tocopheryl Sebacate 290
3.6.2.3.2.1.4 Ring-Closing Metathesis Using Polyoxyethanyl a-Tocopheryl Sebacate 291
3.6.2.3.2.1.5 Ring-Closing Metathesis and Cross Metathesis in the Presence of Calix[n]arenes 292
3.6.2.3.2.2 Ring-Closing Metathesis and Cross Metathesis in Aqueous Emulsions Using Other Methods 292
3.6.2.3.2.2.1 Non-Water-Soluble Catalysts Embedded in Poly(dimethylsiloxane) 292
3.6.2.3.2.2.2 Ring-Closing Metathesis and Cross Metathesis Using Dendrimers 293
3.6.2.4 Applications of Water-Insoluble Catalysts for Protein Modification 295
3.6.2.4.1 Cross Metathesis with SBL-156Sac 295
3.6.2.4.2 Intramolecular Alkene Metathesis in O-Crotylserine Containing cpVenus-2TAG 296
3.6.3 Tagged Metathesis Catalysts 296
3.6.3.1 Catalysts Tagged to Hydrophilic Polymers 296
3.6.3.2 Small-Molecule Polar Catalysts 300
3.6.3.3 Applications in Heterogeneous Aqueous Media 305
4 Aqueous Media: Reactions of Carbonyl and Imino Groups 310
4.1 Reduction of Carbonyl and Imino Groups 310
4.1.1 Reduction of Carbonyl Groups 310
4.1.1.1 Hydrogenation of Carbonyl Groups 310
4.1.1.1.1 Nonasymmetric Hydrogenation of Aldehydes and Ketones 310
4.1.1.1.2 Hydrogenation of Carbon Dioxide 315
4.1.1.1.3 Asymmetric Hydrogenation of Ketones 317
4.1.1.2 Transfer Hydrogenation of Carbonyl Groups 318
4.1.1.2.1 Nonasymmetric Transfer Hydrogenation 321
4.1.1.2.2 Asymmetric Transfer Hydrogenation 325
4.1.1.2.2.1 Of Ketones with Molecular Catalysts 325
4.1.1.2.2.2 Of Ketones with Immobilized Catalysts 329
4.1.1.2.2.3 Of Ketones by Biomimetic Reduction 332
4.1.1.2.2.4 Of Functionalized Ketones 335
4.1.2 Reduction of Imino Groups 339
4.1.2.1 Hydrogenation of Imino Groups 339
4.1.2.1.1 Nonasymmetric Hydrogenation 339
4.1.2.1.2 Asymmetric Hydrogenation 341
4.1.2.2 Transfer Hydrogenation of Imino Groups 343
4.1.2.2.1 With Water-Soluble Catalysts 343
4.1.2.2.2 With Water-Insoluble Catalysts 344
4.2 Alkylation, Allylation, and Benzylation of Carbonyl and Imino Groups 354
4.2.1 Metal-Mediated Alkylation of Carbonyl and Imino Groups 354
4.2.1.1 Alkylation of Carbonyl Groups 354
4.2.1.1.1 Metal-Mediated Alkylation Reactions with Alkyl Halides 354
4.2.1.1.2 Metal-Mediated Reformatsky-Type Reactions 356
4.2.1.2 Alkylation of Imino Groups 357
4.2.2 Metal-Mediated Allylation of Carbonyl and Imino Groups 359
4.2.2.1 Allylation of Carbonyl Groups 360
4.2.2.1.1 Mediated by Zinc 360
4.2.2.1.2 Mediated by Tin 361
4.2.2.1.3 Mediated by Indium 364
4.2.2.1.4 Mediated by Other Metals 372
4.2.2.1.5 Regio- and Stereoselectivity 373
4.2.2.1.6 Asymmetric Allylation 378
4.2.2.2 Allylation of Imino Groups 378
4.2.3 Metal-Mediated Benzylation of Carbonyl and Imino Groups 380
4.3 Arylation, Vinylation, and Alkynylation of Carbonyl and Imino Groups 386
4.3.1 Arylation and Vinylation of Carbonyl and Imino Groups 386
4.3.1.1 Arylation and Vinylation of Aldehydes 386
4.3.1.2 Arylation and Vinylation of Imino Groups 389
4.3.1.2.1 Asymmetric Arylation of Imino Groups 390
4.3.2 Alkynylation of Carbonyl and Imino Groups 391
4.3.2.1 Alkynylation of Carbonyl Compounds 392
4.3.2.1.1 Alkynylation of Aldehydes 392
4.3.2.1.2 Alkynylation of Acid Chlorides 396
4.3.2.1.3 Alkynylation of Ketones 397
4.3.2.2 Alkynylation of Imino Groups 398
4.3.2.2.1 Alkynylation of Imines 398
4.3.2.2.2 Alkynylation of Iminium Ions 400
4.3.2.2.3 Alkynylation of Acylimines or Acyliminium Ions 402
4.4 Aldol Reaction 406
4.4.1 Indirect Catalytic Aldol Addition Reactions 406
4.4.1.1 Mukaiyama-Type Aldol Reactions 407
4.4.1.1.1 Application of Bis(4,5-dihydrooxazole) Ligands 408
4.4.1.1.2 Application of Crown Ether Type Ligands 409
4.4.1.1.3 Europium-Catalyzed Mukaiyama Aldol Reactions 411
4.4.1.1.4 Application of a Trost-Type Semicrown Ligand 412
4.4.1.1.5 Application of Iron(II) and Zinc(II) Complexes 413
4.4.1.1.6 Hydroxymethylation of Silyl Enol Ethers 414
4.4.2 Direct Catalytic Aldol Reactions 416
4.4.2.1 Enamine-Based Direct Aldol Reactions 417
4.4.2.1.1 Synthesis of 2-[Aryl(hydroxy)methyl]cycloalkanones 418
4.4.2.1.2 Synthesis of 4-Aryl-4-hydroxybutan-2-ones 422
4.4.2.1.3 Synthesis of syn-a-Methyl-ß-hydroxy Ketones 423
4.4.2.1.4 Synthesis of Alcohols Containing a Quaternary Carbon Atom 423
4.4.2.1.5 Synthesis of 1,4-Dihydroxylated Ketones 425
4.4.2.1.6 Synthesis of syn-3,4-Dihydroxylated Ketones 426
4.4.2.1.7 Synthesis of 1,3,4-Trihydroxylated Ketones 427
4.4.2.1.8 Synthesis of 1,3-Dihydroxylated Compounds 430
4.4.2.1.9 Synthesis of Erythrose and Threose Derivatives 431
4.4.2.2 Direct Aldol Reactions Assisted by Chiral Metal Complexes 433
4.4.2.2.1 Synthesis of Hydroxymethyl Ketones 434
4.5 Mannich Reaction and Baylis--Hillman Reaction 438
4.5.1 Mannich Reaction 438
4.5.1.1 Reaction Catalyzed by Organometals 439
4.5.1.1.1 Lewis Acids 439
4.5.1.1.1.1 Reaction Using a Preformed Imine or a Preformed Enolate 439
4.5.1.1.1.2 One-Pot Three-Component Reaction 442
4.5.1.1.1.3 Stereoselective Methods 444
4.5.1.1.2 Lewis Bases 448
4.5.1.2 Reaction Catalyzed by Brønsted Acids or Bases 449
4.5.1.2.1 Brønsted Acids 449
4.5.1.2.2 Brønsted Bases 453
4.5.1.2.3 Enantioselective Methods 453
4.5.1.3 Chiral Amine Catalysis via an Enamine Intermediate 456
4.5.1.3.1 syn-Selective Mannich Reaction 458
4.5.1.3.2 anti-Selective Mannich Reaction 466
4.5.1.3.3 Application in Total Synthesis 469
4.5.1.4 Autocatalysis 471
4.5.1.5 Biocatalyzed Mannich Reaction 472
4.5.2 Baylis--Hillman Reaction 473
4.5.2.1 Stereoselective Baylis--Hillman Reaction 479
4.5.2.2 Biocatalyzed Baylis--Hillman Reaction 483
5 Aqueous Media: Cyclization, Rearrangement, Substitution, Cross Coupling, Oxidation, and Other Reactions 486
5.1 Cycloaddition and Cyclization Reactions 486
5.1.1 Cycloadditions 487
5.1.1.1 Diels--Alder Cycloadditions 487
5.1.1.1.1 Hetero-Diels--Alder Cycloadditions 495
5.1.1.1.2 Lewis Acid Catalyzed Diels--Alder Cycloadditions 501
5.1.1.2 1,3-Dipolar Cycloadditions 507
5.1.1.2.1 Nitrile Imine Cycloadditions 508
5.1.1.2.2 Nitrile Oxide Cycloadditions 510
5.1.1.2.3 Diazo Compound Cycloadditions 515
5.1.1.2.4 Azide Cycloadditions 516
5.1.1.2.5 Azomethine Ylide Cycloadditions 520
5.1.1.2.6 Nitrone Cycloadditions 521
5.1.2 Cyclization Reactions 523
5.1.2.1 Barbier-Type Cyclizations 523
5.1.2.2 Epoxide-Opening Cascade Cyclizations 526
5.1.2.3 Radical Cyclizations 527
5.2 Pericyclic Rearrangements: Sigmatropic, Electrocyclic, and Ene Reactions 534
5.2.1 Sigmatropic Rearrangement 534
5.2.1.1 Claisen Rearrangement 534
5.2.1.1.1 First Examples in Water 535
5.2.1.1.2 Rearrangement of Allyl Vinyl Ethers 536
5.2.1.1.3 Rearrangement of Allyl Aryl Ethers 538
5.2.1.1.4 Claisen Rearrangement Coupled with Other Reactions 540
5.2.1.1.5 Aza-Claisen Rearrangements 543
5.2.1.2 Cope Rearrangement 546
5.2.1.2.1 Rearrangement of Compounds Containing a Hydrophilic Group 547
5.2.1.2.2 Catalyzed Rearrangement 547
5.2.1.2.3 Aza-Cope Rearrangement 548
5.2.1.3 [1,5] Rearrangement 548
5.2.1.4 [2,3] Rearrangement 549
5.2.1.4.1 Rearrangement of Allyl Sulfoxides 549
5.2.1.4.2 Rearrangement of Sulfonium and Ammonium Ylides 550
5.2.2 Electrocyclic Rearrangement 553
5.2.2.1 4p-Electrocyclic Rearrangement 553
5.2.2.2 6p-Electrocyclic Rearrangement 554
5.2.3 Ene Reaction 555
5.2.3.1 Photoinduced Reaction 556
5.2.3.2 Aza-Ene Reaction 557
5.2.3.3 Ene-Like Reaction 558
5.2.3.4 Catalyzed Reactions 559
5.3 Allylic and Aromatic Substitution Reactions 564
5.3.1 Allylic Substitution 564
5.3.1.1 Palladium-Catalyzed Substitution 564
5.3.1.1.1 Using Water-Soluble Ligands 564
5.3.1.1.1.1 Substitution of Allylic Esters 565
5.3.1.1.1.1.1 Intermolecular Allylic Substitution 565
5.3.1.1.1.1.2 Intramolecular Allylic Substitution 566
5.3.1.1.1.2 Substitution of Allylic Alcohols 567
5.3.1.1.2 Using Amphiphilic Polymeric Ligands 568
5.3.1.1.3 Using Additives 570
5.3.1.1.4 Miscellaneous Metal-Catalyzed Systems 572
5.3.1.2 Metal-Mediated Substitution 574
5.3.1.3 Allylic Substitution with Calixarene Catalysts 574
5.3.1.4 Asymmetric Allylic Substitution 575
5.3.1.4.1 Substitution of Acyclic Allylic Systems 575
5.3.1.4.2 Substitution of Cyclic Allylic Systems 576
5.3.2 Aromatic Substitution 578
5.3.2.1 Electrophilic Aromatic Substitution 578
5.3.2.1.1 Electrophilic Substitution of Indoles 578
5.3.2.1.1.1 Synthesis of Bis(indolyl)methanes 578
5.3.2.1.1.2 Synthesis of 3-Substituted Indoles 580
5.3.2.1.1.2.1 Nucleophilic Addition of Indoles 580
5.3.2.1.1.2.2 Michael Addition of Indoles 580
5.3.2.1.2 Electrophilic Substitution of Benzenes 581
5.3.2.1.2.1 Indium-Catalyzed Aromatic Substitution 581
5.3.2.1.2.2 Sulfonic Acid Catalyzed Aromatic Substitution 582
5.3.2.2 Nucleophilic Aromatic Substitution 583
5.3.2.2.1 Intermolecular C--N and C--S Bond-Forming Substitution 583
5.3.2.2.2 Intramolecular C--N and C--S Bond-Forming Substitution 584
5.4 Cross-Coupling and Heck Reactions 588
5.4.1 Palladium-Catalyzed Coupling Reactions 588
5.4.1.1 C--C Bond-Forming Reactions 589
5.4.1.1.1 Mizoroki--Heck Reaction 589
5.4.1.1.1.1 Aqueous Ligand-Free Palladium-Catalyzed Heck Coupling 590
5.4.1.1.1.2 Aqueous Heck Coupling Catalyzed by Palladium--Nitrogen Complexes 591
5.4.1.1.1.3 Aqueous Palladium-Catalyzed Heck Coupling Employing Hydrophobic Phosphine Ligands 592
5.4.1.1.1.4 Aqueous Palladium-Catalyzed Heck Couplings Employing Hydrophilic Phosphine Ligands 594
5.4.1.1.1.5 Aqueous Palladacycle-Catalyzed Heck Coupling 594
5.4.1.1.1.6 Aqueous Heck Couplings Catalyzed by Supported Palladium Complexes 595
5.4.1.1.2 Suzuki--Miyaura Coupling 598
5.4.1.1.2.1 Aqueous Ligand-Free Palladium-Catalyzed Suzuki--Miyaura Coupling 598
5.4.1.1.2.2 Aqueous Suzuki--Miyaura Coupling Catalyzed by Palladium--Nitrogen Complexes 599
5.4.1.1.2.3 Aqueous Palladium-Catalyzed Suzuki--Miyaura Coupling Employing Hydrophobic Phosphine or N-Heterocyclic Carbene Ligands 600
5.4.1.1.2.4 Palladium-Catalyzed Suzuki--Miyaura Coupling Employing Hydrophilic Ligands 602
5.4.1.1.2.5 Aqueous Palladacycle-Catalyzed Suzuki--Miyaura Coupling 603
5.4.1.1.2.6 Aqueous Suzuki--Miyaura Couplings Catalyzed by Supported Palladium Complexes 605
5.4.1.1.3 Sonogashira Coupling 608
5.4.1.1.3.1 Aqueous Ligand-Free Palladium-Catalyzed Sonogashira Coupling 608
5.4.1.1.3.2 Aqueous Sonogashira Coupling Catalyzed by Palladium--Nitrogen Complexes 609
5.4.1.1.3.3 Aqueous Sonogashira Coupling Employing Hydrophobic Phosphine Ligands 609
5.4.1.1.3.4 Aqueous Sonogashira Coupling Catalyzed by Supported Palladium Complexes 610
5.4.1.1.4 Hiyama Coupling 612
5.4.1.1.4.1 Aqueous Ligand-Free Palladium-Catalyzed Hiyama Coupling 612
5.4.1.1.4.2 Aqueous Hiyama Coupling Catalyzed by Palladium--Nitrogen Complexes 612
5.4.1.1.4.3 Aqueous Hiyama Coupling Catalyzed by Palladium--Phosphine Complexes 613
5.4.1.1.4.4 Aqueous Oxime Palladacycle Catalyzed Hiyama Coupling 614
5.4.1.1.5 Kosugi--Migita--Stille Coupling 616
5.4.1.1.6 Ullmann-Type Coupling 616
5.4.1.1.7 Negishi Coupling 617
5.4.1.1.8 C--H Activation 618
5.4.1.1.9 Cyanation Reactions 619
5.4.1.2 Carbon--Heteroatom Bond-Forming Reactions 620
5.4.1.2.1 Buchwald--Hartwig Amination 620
5.4.2 Copper-Catalyzed Cross-Coupling Reactions 622
5.4.2.1 C--C Bond-Forming Reactions 622
5.4.2.1.1 Sonogashira--Hagihara Reaction 622
5.4.2.1.2 Cyanation Reactions 623
5.4.2.2 Carbon--Heteroatom Bond-Forming Reactions 623
5.4.2.2.1 Aqueous Copper-Catalyzed C--N Bond-Forming Reactions 623
5.4.2.2.2 Aqueous Copper-Catalyzed C--S Bond-Forming Reactions 625
5.4.2.2.3 Aqueous Copper-Catalyzed C--O Bond-Forming Reactions 625
5.5 Ring Opening of Epoxides and Aziridines 632
5.5.1 Ring-Opening Reactions of Epoxides 632
5.5.1.1 Epoxide Ring Opening with Oxygen Nucleophiles 632
5.5.1.1.1 Noncatalyzed Epoxide Ring Opening 632
5.5.1.1.2 Small Organic Molecule Catalyzed Epoxide Ring Opening 633
5.5.1.1.3 Metal-Catalyzed Epoxide Ring Opening 634
5.5.1.1.3.1 Using Zirconium(IV) Tetrakis(dodecyl sulfate) 634
5.5.1.1.3.2 Using Cobalt--Salen Complexes 634
5.5.1.1.3.3 Using Scandium--Chiral Bipyridine Complexes 635
5.5.1.2 Epoxide Ring Opening with Nitrogen Nucleophiles 636
5.5.1.2.1 Epoxide Ring Opening with Amines 636
5.5.1.2.1.1 Noncatalyzed Epoxide Ring Opening with Amines in Water 636
5.5.1.2.1.2 Small Organic Molecule Catalyzed Aminolysis 638
5.5.1.2.1.3 Metal-Catalyzed Aminolysis 639
5.5.1.2.1.4 Aminolysis Catalyzed by Chiral Lewis Acids 640
5.5.1.2.2 Epoxide Ring Opening with Azide 642
5.5.1.2.2.1 Metal-Catalyzed Azidolysis 642
5.5.1.2.2.1.1 Using Zirconium(IV) Tetrakis(dodecyl sulfate) 642
5.5.1.2.2.1.2 Using Copper(II) Nitrate 643
5.5.1.2.3 Epoxide Ring Opening with Other Nitrogen-Containing Nucleophiles 643
5.5.1.3 Epoxide Ring Opening with Thiols 644
5.5.1.3.1 Noncatalyzed Epoxide Ring Opening with Thiols 644
5.5.1.3.2 Metal-Catalyzed Epoxide Ring Opening with Thiols 645
5.5.1.3.2.1 Using Indium(III) Chloride 645
5.5.1.3.2.2 Using Scandium(III) Tris(dodecyl sulfate) 646
5.5.1.4 Epoxide Ring Opening with Carbon Nucleophiles 647
5.5.2 Ring-Opening Reactions of Aziridines 647
5.5.2.1 Aziridine Ring Opening with Oxygen Nucleophiles 647
5.5.2.1.1 Noncatalyzed Aziridine Ring Opening with Oxygen Nucleophiles 647
5.5.2.1.2 Aziridine Ring Opening with Oxygen Nucleophiles Promoted by Tributylphosphine and Silica Gel 648
5.5.2.2 Aziridine Ring Opening with Nitrogen Nucleophiles 649
5.5.2.2.1 Noncatalyzed Aziridine Ring Opening with Nitrogen Nucleophiles 649
5.5.2.2.2 Small Organic Molecule Catalyzed Aziridine Ring Opening with Nitrogen Nucleophiles 649
5.5.2.3 Aziridine Ring Opening with Sulfur Nucleophiles 650
5.6 Asymmetric a-Functionalization of Carbonyl Compounds and Alkylation of Enolates 654
5.6.1 Asymmetric Alkylation 654
5.6.1.1 Asymmetric Benzylation of Glycine Derivatives for the Synthesis of Phenylalanine Derivatives 654
5.6.1.1.1 Asymmetric Alkylation of Glycine Derivatives for the Synthesis of a-Alkyl-a-amino Acids 657
5.6.1.2 Asymmetric a-Alkylation of Ketones 657
5.6.1.3 Asymmetric Alkylation of ß-Keto Esters 658
5.6.1.4 Asymmetric Alkylation of Diaryloxazolidine-2,4-diones 659
5.6.1.5 Asymmetric a-Alkylation of Aldehydes with Alcohols 660
5.6.2 Asymmetric Alkenylation and Alkynylation 660
5.6.2.1 Asymmetric Alkenylation of ß-Keto Esters 660
5.6.2.1.1 Asymmetric Alkynylation of ß-Keto Esters 662
5.6.3 Asymmetric Oxidation 662
5.6.3.1 Asymmetric a-Hydroxylation of Ketones 662
5.6.3.2 Asymmetric a-Oxyamination of Aldehydes 663
5.6.4 Asymmetric Amination 664
5.6.4.1 Asymmetric Amination of ß-Keto Esters 664
5.6.5 Asymmetric Fluorination 665
5.6.5.1 Asymmetric Fluorination of ß-Keto Esters 665
5.7 Oxidation of Alcohols, Allylic and Benzylic Oxidation, Oxidation of Sulfides 670
5.7.1 Water-Soluble Ligands 671
5.7.2 Biomimetic Metalloporphyrins and Metallophthalocyanines 672
5.7.3 Enzymatic Oxidations: Oxidoreductases 673
5.7.4 Alcohol Oxidations in Aqueous Media 673
5.7.4.1 Tungsten(VI) Catalysts 674
5.7.4.2 Palladium--Diamine Complexes as Catalysts 676
5.7.4.3 Noble Metal Nanoparticles as Quasi-homogeneous Catalysts 680
5.7.4.4 Ruthenium and Manganese Catalysts 681
5.7.4.5 Organocatalysts: Hypervalent Iodine Compounds and Stable N-Oxyl Radicals 681
5.7.4.6 Enzymatic Oxidation of Alcohols 684
5.7.5 Benzylic and Allylic Oxidations in Water 685
5.7.5.1 Benzylic Oxidations 685
5.7.5.2 Allylic Oxidations 686
5.7.6 Sulfoxidations in Water 687
5.7.6.1 Tungsten- and Vanadium-Catalyzed Oxidations with Hydrogen Peroxide 687
5.7.6.2 Enantioselective Sulfoxidation with Enzymes 689
5.7.6.3 Flavins as Organocatalysts for Sulfoxidation 691
5.7.7 Concluding Remarks 692
5.8 Free-Radical Reactions 698
5.8.1 Reductive Processes 699
5.8.1.1 Reductions with Metal Hydrides 699
5.8.1.2 Reduction with Phosphinic Acid and Its Derivatives 705
5.8.1.3 Reductions with Trialkylboranes 715
5.8.1.3.1 With Trialkylborane--Water Complexes 715
5.8.1.3.2 Triethylborane-Mediated Radical Addition to a C==N Bond 718
5.8.1.4 Reduction with Inorganic Reducing Agents 719
5.8.2 Atom Transfer Processes 722
5.8.3 Fragmentation Processes 727
5.9 Polymerization 732
5.9.1 Living Radical Polymerization 733
5.9.1.1 Nitroxide-Mediated Polymerization 734
5.9.1.2 Metal-Catalyzed Living Radical Polymerization or Atom-Transfer Radical Polymerization 734
5.9.1.3 Reversible Addition--Fragmentation Chain-Transfer Polymerization 735
5.9.2 Living Radical Suspension Polymerization 735
5.9.2.1 Iron-Catalyzed Living Radical Polymerization 735
5.9.2.2 Copper-Catalyzed Living Radical Polymerization 736
5.9.3 Living Radical Mini-emulsion Polymerization 737
5.9.3.1 Mini-emulsion with Reverse Atom-Transfer Radical Polymerization 738
5.9.3.2 Mini-emulsion with AGET Atom-Transfer Radical Polymerization 739
5.9.3.3 Mini-emulsion with Nitroxide-Mediated Polymerization 740
5.9.4 Living Radical Emulsion Polymerization 742
5.9.4.1 Emulsion with Nitroxide-Mediated Polymerization 742
5.9.4.2 Emulsion with Reversible Addition--Fragmentation Chain-Transfer Polymerization 744
5.9.5 Homogeneous Aqueous Living Radical Polymerization 745
5.9.5.1 Homogeneous Aqueous Atom-Transfer Radical Polymerization 746
5.9.5.2 Homogeneous Aqueous Reversible Addition--Fragmentation Chain-Transfer Polymerization 747
6 Special Techniques with Water 750
6.1 Organic Synthesis “On Water” 750
6.1.1 On-Water Reactions 752
6.1.1.1 Diels--Alder Reactions 752
6.1.1.2 Dipolar Cycloadditions 755
6.1.1.3 Cycloadditions of Azodicarboxylates 761
6.1.1.4 Claisen Rearrangement 763
6.1.1.5 Passerini and Ugi Reactions 765
6.1.1.6 Nucleophilic Opening of Three-Membered Rings 768
6.1.1.7 Nucleophilic Substitution Reactions 773
6.1.1.8 Transformations Catalyzed by Transition Metals 775
6.1.1.9 Metal-Free Carbon--Carbon Bond-Forming Processes 784
6.1.1.10 Bromination Reactions 787
6.1.1.11 Oxidations and Reductions 790
6.1.2 Theoretical Studies 794
6.1.3 Concluding Remarks 797
6.2 Sub- and Supercritical Water 802
6.2.1 Properties of Water 803
6.2.1.1 Macroscopic Properties 803
6.2.1.2 Microscopic Properties 804
6.2.1.3 Special Aspects of Heterogeneous Catalysis 805
6.2.2 Synthesis Reactions 806
6.2.2.1 Hydrolysis/Water Addition Reactions 806
6.2.2.2 Condensation/Water Elimination Reactions 808
6.2.2.3 Addition Reactions 810
6.2.2.3.1 Hydroformylation 810
6.2.2.3.2 Diels--Alder Reaction 810
6.2.2.3.3 Other Addition and Coupling Reactions 811
6.2.2.4 Rearrangements 813
6.2.2.5 Oxidations 815
6.2.2.6 Reductions 816
6.2.2.6.1 Using Formic Acid/Formates 816
6.2.2.6.2 Using Hydrogen and a Noble Metal Catalyst 816
6.2.2.6.3 Using Zinc 817
6.2.3 Summary 817
6.2.4 Outlook 818
6.2.5 Conclusion 818
6.3 ß-Cyclodextrin Chemistry in Water 826
6.3.1 Cyclodextrins as Mass-Transfer Additives or Organocatalysts for Organic Synthesis in Water 827
6.3.1.1 Glycoside Hydrolysis Using Modified a- and ß-Cyclodextrin Dicyanohydrins in Water 827
6.3.1.2 Oxidation of Benzylic Alcohols 829
6.3.1.3 Deprotection of Aromatic Acetals under Neutral Conditions Using ß-Cyclodextrin in Water 830
6.3.1.4 Cyclodextrin-Promoted Synthesis of 3,4,5-Trisubstituted Furan-2(5H)-ones 831
6.3.1.5 ß-Cyclodextrin-Catalyzed Strecker Synthesis of a-Aminonitriles in Water 832
6.3.1.6 Synthesis of 3-Hydroxy-3-(1H-indol-3-yl)-1,3-dihydro-2H-indol-2-ones under Neutral Conditions in Water 833
6.3.1.7 Synthesis of Pyrrole-Substituted 1,3-Dihydro-2H-indol-2-ones 834
6.3.1.8 Friedel--Crafts Alkylation of Indoles 835
6.3.1.9 Supramolecular Synthesis of Selenazoles Using Selenourea in Water 836
6.3.1.10 Cyclodextrin-Promoted Nucleophilic Opening of Oxiranes 837
6.3.1.11 Cyclodextrin-Promoted Michael Reactions of Thiols to Conjugated Alkenes 838
6.3.1.12 Cyclodextrin-Promoted Mild Oxidation of Alcohols with 1-Hydroxy-1,2-benziodoxol-3(1H)-one 1-Oxide 839
6.3.1.13 Synthesis of Thiiranes from Oxiranes in the Presence of ß-Cyclodextrin in Water 841
6.3.2 Cyclodextrins as Organocatalyst Solubilizers 842
6.3.2.1 For Organocatalysts with an Adamantyl Subunit 842
6.3.2.2 For Organocatalysts with a 4-tert-Butylphenyl Subunit 844
6.3.3 Cyclodextrins as Mass-Transfer Additives in Aqueous Organometallic Catalysis 845
6.3.4 Cyclodextrins as Ligands for Metal-Catalyzed Reactions 850
6.3.5 Cyclodextrins as Stabilizers of Water-Soluble Noble Metal Nanoparticles 850
6.3.6 Cyclodextrins as Dispersing Agents of Catalytically Active Solids 853
6.3.6.1 Cyclodextrins as Dispersing Agents of Supported Metals 853
6.3.6.2 Cyclodextrins as Dispersing Agents of Metallic Powder 855
7 Industrial Application 860
7.1 Hydroformylation 860
7.1.2 Immobilized Oxo Catalysts 862
7.1.3 Biphasic Catalyst System 863
7.1.4 Ruhrchemie/Rhône-Poulenc Process 865
7.1.4.1 Reaction 865
7.1.4.2 Recycle and Recovery of the Aqueous Catalyst 869
7.1.4.2.1 Recycle 869
7.1.4.2.2 Recovery 872
7.1.4.3 Economics of the Process 875
7.1.4.4 Environmental Aspects 876
7.1.5 Conclusions 878
7.2 Industrial Applications Other than Hydroformylation 884
7.2.1 Classical Reactions 885
7.2.1.1 Hydrolysis 885
7.2.1.2 Hydration 886
7.2.1.3 Homogeneous Mixed-Solvent Systems 886
7.2.1.4 Heterogeneous Mixed-Solvent Systems 887
7.2.2 Metal-Catalyzed Reactions 888
7.2.2.1 Palladium-Catalyzed Coupling Reactions 888
7.2.2.2 Palladium-Catalyzed Telomerization of Butadiene 890
7.2.2.3 Lewis Acid Catalysis 890
7.2.3 Enzymatic Reactions 890
7.2.3.1 Synthesis of Tamiflu 890
7.2.3.2 Synthesis of Statins (Lipitor and Crestor) 891
7.2.3.3 Synthesis of LY300164 893
7.2.3.4 Synthesis of Pregabalin 893
7.2.3.5 Synthesis of 6-Aminopenicillanic Acid 894
7.2.3.6 Synthesis of Rhinovirus Protease Inhibitor Intermediates 895
7.2.3.7 Synthesis of a GABA Inhibitor 895
7.2.3.8 Synthesis of an HIV Protease Inhibitor 895
7.2.3.9 Synthesis of Pelitrexol 896
7.2.4 Other Reactions 897
7.2.5 Conclusions and Perspectives 902
8 Perspective: The New World of Organic Chemistry Using Water as Solvent 908
8 Perspective: The New World of Organic Chemistry Using Water as Solvent 908
8.1 Palladium-Catalyzed Allylic Amination Using Aqueous Ammonia 908
8.2 Aldehyde Allylation with Allylboronates in Aqueous Media 911
8.3 Catalytic Use of Indium(0) for C--C Bond Transformations in Water 914
8.4 Conclusions and Outlook 918
Keyword Index 922
Author Index 970
Abbreviations 1008
List of All Volumes 1014