Science of Synthesis: Knowledge Updates 2011/4 1
Title page 5
Imprint 7
Preface 8
Abstracts 10
Overview 16
Table of Contents 18
Volume 2: Compounds of Groups 7–3 (Mn···, Cr···, V···, Ti···, Sc···, La···, Ac···) 32
2.12 Product Class 12: Organometallic Complexes of Scandium, Yttrium, and the Lanthanides 32
2.12.15 Organometallic Complexes of Scandium, Yttrium, and the Lanthanides 32
2.12.15.1 Lanthanide-Catalyzed Mukaiyama Aldol Reactions 32
2.12.15.1.1 Method 1: Non-enantioselective Formation of ß-Hydroxycarbonyls 32
2.12.15.1.2 Method 2: Enantioselective Formation of ß-Hydroxycarbonyls 35
2.12.15.1.2.1 Variation 1: In an Organic Solvent 35
2.12.15.1.2.2 Variation 2: In an Aqueous Solvent 38
2.14 Product Class 14: Group 4 Metallocene Complexes with Bis(trimethylsilyl)acetylene 42
2.14.1 Product Subclass 1: Titanocene–Bis(trimethylsilyl)acetylene Complexes 44
Synthesis of Product Subclass 1 44
2.14.1.1 Method 1: Reduction of a Dichlorobis(.5-cyclopentadienyl)titanium Derivative in the Presence of Bis(trimethylsilyl)acetylene 44
2.14.1.1.1 Variation 1: Reduction and Intramolecular Dehydrocoupling of Cyclopentadienyl Fragments 45
2.14.1.2 Method 2: Methane Elimination from Bis(.5-cyclopentadienyl)dimethyltitanium(IV) 46
Applications of Product Subclass 1 in Organometallic Reactions 46
2.14.1.3 Method 3: Reactions with Brønsted Acids 46
2.14.1.3.1 Variation 1: Reaction with Methanol 48
2.14.1.4 Method 4: Titanocene–Bis(trimethylsilyl)acetylene Complexes in the Formation of Metallacycles 49
2.14.1.4.1 Variation 1: Formation of Five-Membered Group 4 Metallacycles 49
2.14.1.4.2 Variation 2: Formation of Six-Membered Metallacycles 50
2.14.1.4.3 Variation 3: Formation of Three-Membered Aza-metallacycles 51
2.14.1.4.4 Variation 4: Formation of Four- and Five-Membered Aza-metallacycles 53
2.14.1.4.5 Variation 5: Coupling Reactions of Dichlorophosphines and the Formation of Phospha-metallacycles 55
2.14.1.4.6 Variation 6: Formation of Stiba-metallacycles 56
2.14.1.4.7 Variation 7: Formation of Four-Membered Thia-metallacycles 58
2.14.1.4.8 Variation 8: Formation of Four-Membered Selena-metallacycles 59
2.14.1.5 Method 5: Titanocene–Bis(trimethylsilyl)acetylene Complexes in Supramolecular Chemistry 59
2.14.1.5.1 Variation 1: Dehydrogenative Coupling 62
2.14.1.6 Method 6: Titanocene–Bis(trimethylsilyl)acetylene Complexes in Bond-Activation Reactions 63
2.14.1.6.1 Variation 1: Dinitrogen Activation 63
2.14.1.6.2 Variation 2: C--F Bond Activation 64
2.14.1.6.3 Variation 3: C--C Single-Bond Metathesis 65
2.14.1.7 Method 7: Catalytic Hydroamination of Alkynes 66
2.14.1.8 Method 8: Catalytic Dehydrogenation of Dimethylamine Borane 67
2.14.1.9 Method 9: Oxidation Reactions 67
2.14.1.10 Method 10: Reactions with Alkynes: Alkyne Substitution Reactions 68
2.14.1.10.1 Variation 1: Reactions with Alkynylsilanes 70
2.14.1.10.2 Variation 2: Reactions with Polyynes 70
2.14.1.11 Method 11: Lewis Base Exchange 72
2.14.1.12 Method 12: Reactions with Carbon Dioxide 72
2.14.2 Product Subclass 2: Zirconocene–Bis(trimethylsilyl)acetylene Complexes 73
Synthesis of Product Subclass 2 73
2.14.2.1 Method 1: Reduction of a Dichlorobis(.5-cyclopentadienyl)zirconium(IV) in the Presence of Bis(trimethylsilyl)acetylene 73
2.14.2.1.1 Variation 1: By Ligand Substitution 75
Applications of Product Subclass 2 in Organometallic Reactions 76
2.14.2.2 Method 2: Reactions with Brønsted Acids 76
2.14.2.3 Method 3: Reactions with Internal Alkynes 77
2.14.2.3.1 Variation 1: Alkyne Substitutions 78
2.14.2.3.2 Variation 2: Formation of Zirconacyclopenta-2,4-dienes 79
2.14.2.3.3 Variation 3: Macrocyclization 82
2.14.2.3.4 Variation 4: Formation of Pentakis(pentafluorophenyl)borole 83
2.14.2.4 Method 4: Reactions with Terminal Alkynes 84
2.14.2.5 Method 5: Reactions with Carbonyl Compounds 85
2.14.2.6 Method 6: Zirconocene–Bis(trimethylsilyl)acetylene Complexes in the Formation of Metallacycles 86
2.14.2.6.1 Variation 1: Formation of Five-Membered Metallacycles 86
2.14.2.6.2 Variation 2: Formation of Three-Membered Aza-metallacycles 87
2.14.2.6.3 Variation 3: Formation of Five-Membered Aza-metallacycles 88
2.14.2.6.4 Variation 4: Formation of Five- and Seven-Membered Oxa-metallacycles 89
2.14.2.6.5 Variation 5: Formation of Four-Membered Thia-metallacycles 90
2.14.2.7 Method 7: Zirconocene–Bis(trimethylsilyl)acetylene Complexes in Bond-Activation Reactions 91
2.14.2.7.1 Variation 1: Dinitrogen Activation 91
2.14.2.7.2 Variation 2: C--F versus C--H Bond Activation 92
2.14.2.7.3 Variation 3: C--H Bond Activation 93
2.14.3 Product Subclass 3: Hafnocene Bis(trimethylsilyl)acetylene Complexes 94
Synthesis of Product Subclass 3 94
2.14.3.1 Method 1: Reduction of a Dichlorobis(.5-cyclopentadienyl)hafnium in the Presence of Bis(trimethylsilyl)acetylene 94
2.14.3.2 Method 2: Synthesis from Dibutylbis(.5-cyclopentadienyl)hafnium(IV) 97
Applications of Product Subclass 3 in Organometallic Reactions 97
2.14.3.3 Method 3: Reactions with Alkenes 97
Volume 6: Boron Compounds 104
6.1 Product Class 1: Boron Compounds 104
6.1.7.11 Hydroxyboranes 104
6.1.7.11.1 Method 1: Synthesis by Metal-Catalyzed C--H Borylation 104
6.1.7.11.1.1 Variation 1: Aromatic C--H Borylation 104
6.1.7.11.1.2 Variation 2: Dehydrogenative Borylation 107
6.1.7.11.2 Method 2: Synthesis by Borylative Cross Coupling 108
6.1.7.11.2.1 Variation 1: Palladium-Catalyzed Borylative Cross Coupling 108
6.1.7.11.2.2 Variation 2: Nickel- and Copper-Catalyzed Borylative Cross Coupling 109
6.1.7.11.2.3 Variation 3: Metal-Free Borylative Cross Coupling 110
6.1.7.11.3 Method 3: Synthesis by Direct Borylation with Borenium Cations 111
6.1.7.11.4 Method 4: Synthesis by Addition Reactions with Diboron Species 112
6.1.7.11.4.1 Variation 1: Addition of Diboron Species to Carbonyl or Thiocarbonyl Groups, or Aldimines 113
6.1.7.11.4.2 Variation 2: ß-Boration of a,ß-Unsaturated Carbonyl Derivatives 114
6.1.7.11.5 Method 5: Synthesis by Hydrolysis of Boronates or Trifluoro(organo)borates 115
6.1.7.11.6 Method 6: Chemoselective Chemical Transformations of Parent Free Boronic Acids or Derivatives 117
6.1.7.11.7 Method 7: Applications as Catalysts or Stoichiometric Reaction Promoters 118
6.1.7.11.7.1 Variation 1: Activation of Carboxylic Acids 119
6.1.7.11.7.2 Variation 2: Activation of Alcohols 121
6.1.7.11.7.3 Variation 3: Activation of Carbonyl Groups 123
6.1.7.11.7.4 Variation 4: Use as Stoichiometric Reaction Promoters 124
6.1.7.11.8 Method 8: Applications in Carbon--Heteroatom Bond Formation 125
6.1.7.11.8.1 Variation 1: C--O Bond Formation 126
6.1.7.11.8.2 Variation 2: C--X Bond Formation (X = Halogen) 127
6.1.7.11.8.3 Variation 3: C--N Bond Formation 128
6.1.7.11.9 Method 9: Applications in C--C Bond Formation 129
6.1.7.11.9.1 Variation 1: ipso-Trifluoromethylation and ipso-Cyanation 129
6.1.7.11.9.2 Variation 2: C--H Arylation and Alkylation 130
6.1.7.11.9.3 Variation 3: Metal-Catalyzed Cross-Coupling Reactions 131
6.1.7.11.9.4 Variation 4: Addition and Substitution Reactions 133
6.1.7.11.10 Method 10: Applications as Productive Tags for Phase-Switch Purification 134
6.1.7.11.11 Method 11: Applications in Medicine and Materials Science 136
Volume 7: Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be ··· Ba) 144
7.1 Product Class 1: Aluminum Compounds 144
7.1.4.7 Aluminum Alkoxides and Phenoxides 144
7.1.4.7.1 Method 1: Synthesis by Treatment of Alkylaluminum Compounds with Phenols 144
7.1.4.7.1.1 Variation 1: Reaction To Give Aluminum–Salen Complexes and Their µ-Oxo Dimers 144
7.1.4.7.2 Method 2: Applications of Aluminum Alkoxides 145
7.1.4.7.2.1 Variation 1: Reductions 145
7.1.4.7.2.2 Variation 2: Michael Additions 145
7.1.4.7.3 Method 3: Applications of Aluminum Phenoxides 146
7.1.4.7.3.1 Variation 1: Carbonyl Additions and Reductions 146
7.1.4.7.3.2 Variation 2: Conjugate Additions 147
7.1.4.7.3.3 Variation 3: Aldol Reactions 148
7.1.4.7.3.4 Variation 4: Meerwein–Ponndorf–Verley Reactions 151
7.1.4.7.3.5 Variation 5: Oppenauer Reactions 153
7.1.4.7.3.6 Variation 6: Cycloadditions 153
7.1.4.7.3.7 Variation 7: Cyclizations 154
7.1.4.7.3.8 Variation 8: Ferrier Reactions 155
7.1.4.7.3.9 Variation 9: Claisen Rearrangements 156
7.1.4.7.3.10 Variation 10: Intramolecular Prenyl Transfer Reactions 157
7.1.4.7.3.11 Variation 11: Radical Reactions 157
7.1.4.7.3.12 Variation 12: Asymmetric Conjugate Additions 158
7.1.4.7.3.13 Variation 13: Asymmetric Acylations 159
7.1.4.7.3.14 Variation 14: Asymmetric Wagner–Meerwein-Type Rearrangements 159
7.1.4.7.3.15 Variation 15: Asymmetric Passerini-Type Reactions 160
7.1.7.15 Aluminum Amides 162
7.1.7.15.1 Method 1: Synthesis by Treatment of Alkylaluminum Compounds with Amines 162
7.1.7.15.2 Method 2: Applications in Transformation of Esters 162
7.1.7.15.3 Method 3: Applications in Transformation of Amides 163
7.1.7.15.4 Method 4: Applications in Alkylation with Aluminum Reagents 163
7.1.7.15.5 Method 5: Applications in Wagner–Meerwein-Type Rearrangements 165
7.1.7.15.6 Method 6: Applications in the Ene Reaction 167
7.1.7.15.7 Method 7: Applications in Asymmetric Aldol Cycloadditions 168
Volume 8: Compounds of Group 1 (Li ··· Cs) 170
8.1 Product Class 1: Lithium Compounds 170
8.1.29 Dearomatization Reactions Using Organolithiums 170
8.1.29.1 Intermolecular Dearomatization 170
8.1.29.1.1 Dearomatizing Additions to Aryl Rings Bearing No Further Activation 170
8.1.29.1.1.1 Method 1: Dearomatizing Addition to Naphthalenes 170
8.1.29.1.1.2 Method 2: Dearomatizing Addition to Condensed Polyaromatics 171
8.1.29.1.1.3 Method 3: Dearomatizing Addition to Pyridines and Other Electron-Deficient Heterocycles 172
8.1.29.1.2 Dearomatizing Addition to Activated Aromatic Rings 175
8.1.29.1.2.1 Method 1: Activation with 4,5-Dihydrooxazoles 175
8.1.29.1.2.1.1 Variation 1: Dearomatizing Addition to Naphthyl-4,5-dihydrooxazoles 175
8.1.29.1.2.1.2 Variation 2: Dearomatizing Addition to Pyridyl-4,5-dihydrooxazoles 177
8.1.29.1.2.1.3 Variation 3: Dearomatizing Addition to Phenyl-4,5-dihydrooxazoles 178
8.1.29.1.2.2 Method 2: Activation with Amides 180
8.1.29.1.2.2.1 Variation 1: Dearomatizing Addition to Naphthylamides 180
8.1.29.1.2.2.2 Variation 2: Dearomatizing Addition to Benzamides 181
8.1.29.1.2.3 Method 3: Activation with Aldehydes and Ketones 182
8.1.29.1.2.3.1 Variation 1: Dearomatizing Addition to Naphthyl Ketones 182
8.1.29.1.2.3.2 Variation 2: Dearomatizing Addition to Acetophenones and Benzaldehydes 182
8.1.29.1.2.4 Method 4: Activation with Esters 183
8.1.29.1.2.4.1 Variation 1: Dearomatizing Addition to Naphthyl Esters 183
8.1.29.1.2.4.2 Variation 2: Dearomatizing Addition to Benzoates 185
8.1.29.1.2.5 Method 5: Activation with Carboxylic Acids 185
8.1.29.1.2.6 Method 6: Activation with Sulfones 187
8.1.29.1.2.7 Method 7: Activation with Imines 187
8.1.29.2 Intramolecular Dearomatization (Dearomatizing Cyclization) 189
8.1.29.2.1 Dearomatizing Cyclization of Lithiated Amides 189
8.1.29.2.1.1 Method 1: Dearomatizing Cyclization of Naphthamides 189
8.1.29.2.1.1.1 Variation 1: N-Allylnaphthamides 191
8.1.29.2.1.1.2 Variation 2: Chiral N-Benzylnaphthamides 192
8.1.29.2.1.2 Method 2: Dearomatizing Cyclization of Benzamides 192
8.1.29.2.1.2.1 Variation 1: Asymmetric Dearomatizing Cyclization with Chiral Lithium Amides 194
8.1.29.2.1.2.2 Variation 2: Stereospecific Dearomatizing Cyclization of (1-Phenylethyl)benzamides 196
8.1.29.2.1.2.3 Variation 3: Dearomatizing Cyclization of N-Benzoyloxazolidines 197
8.1.29.2.1.2.4 Variation 4: Photochemical Rearrangements of the Dearomatized Products 198
8.1.29.2.1.3 Method 3: Dearomatizing Cyclization of Pyridine- and Quinolinecarboxamides 200
8.1.29.2.1.3.1 Variation 1: Cyclizations of Lithium Enolates 202
8.1.29.2.1.4 Method 4: Dearomatizing Cyclization of Electron-Rich Heterocyclic Amides 204
8.1.29.2.1.4.1 Variation 1: Pyrrolecarboxamides 204
8.1.29.2.1.4.2 Variation 2: Thiophenecarboxamides 207
8.1.29.2.2 Dearomatizing Cyclization of Other Lithiated Compounds 210
8.1.29.2.2.1 Method 1: Dearomatizing Cyclization of Lithiated Phosphinamides 210
8.1.29.2.2.2 Method 2: Dearomatizing Cyclization of Lithiated Azo Compounds 211
8.1.29.2.2.3 Method 3: Dearomatizing Cyclization of Lithiated 4,5-Dihydrooxazoles 212
8.1.29.2.2.4 Method 4: Dearomatizing Cyclization of Lithiated Sulfones 213
8.1.29.2.2.5 Method 5: [2,3]-Sigmatropic Dearomatization of Lithiated Sulfonium Salts 214
8.1.29.3 Rearrangements Proceeding via Dearomatized Intermediates 214
8.1.29.3.1 Method 1: Arylation of N-Benzylureas 214
8.1.29.3.1.1 Variation 1: Pyridylation of Ureas 216
8.1.29.3.1.2 Variation 2: Arylation of N-Allylureas 217
8.1.29.3.2 Method 2: Arylation of O-Benzyl Carbamates 218
8.1.29.3.3 Method 3: Arylation of S-Benzyl Thiocarbamates 218
8.1.30 Carbolithiation of Carbon–Carbon Multiple Bonds 222
8.1.30.1 Intermolecular Carbolithiation of C==C Bonds 222
8.1.30.1.1 Method 1: Addition of Alkyllithiums to Alkenes 223
8.1.30.1.1.1 Variation 1: Carbolithiation of Styrene Derivatives 223
8.1.30.1.1.2 Variation 2: Carbolithiation of 1-Substituted Vinylarenes 226
8.1.30.1.1.3 Variation 3: Carbolithiation of Stilbenes 228
8.1.30.1.2 Method 2: Addition of Aryl- and Hetaryllithiums to Alkenes 230
8.1.30.1.2.1 Variation 1: Halogen–Lithium Exchange 230
8.1.30.1.2.2 Variation 2: Carbolithiation with Lithium Dianions 231
8.1.30.2 Intramolecular Carbolithiation of C==C Bonds 232
8.1.30.2.1 Method 1: Addition of Alkyllithiums to Alkenes 233
8.1.30.2.1.1 Variation 1: Halogen–Lithium Exchange 233
8.1.30.2.1.2 Variation 2: Arene-Catalyzed Lithiation 234
8.1.30.2.1.3 Variation 3: Tin–Lithium Exchange 237
8.1.30.2.1.4 Variation 4: Selenium–Lithium Exchange 239
8.1.30.2.2 Method 2: Addition of Alkenyllithiums to Alkenes 240
8.1.30.2.2.1 Variation 1: Halogen–Lithium Exchange 240
8.1.30.2.2.2 Variation 2: Carbolithiation of Lithiated Double Bonds Obtained by Halogen–Lithium Exchange 242
8.1.30.2.3 Method 3: Addition of Aryl- and Hetaryllithiums to Alkenes 244
8.1.30.2.3.1 Variation 1: Formation of Five-Membered Rings 244
8.1.30.2.3.2 Variation 2: Formation of Six-Membered Rings 248
8.1.30.3 Intermolecular Carbolithiation of C==C Bonds 250
8.1.30.3.1 Method 1: Addition of Alkyl- and Aryllithiums to Alkynes 251
8.1.30.4 Intramolecular Carbolithiation of C==C Bonds 253
8.1.30.4.1 Method 1: Addition of Alkyllithiums to Alkynes 253
8.1.30.4.1.1 Variation 1: Deprotonation 254
8.1.30.4.1.2 Variation 2: Tin–Lithium Exchange 255
8.1.30.4.1.3 Variation 3: Selenium–Lithium Exchange 257
8.1.30.4.1.4 Variation 4: Halogen–Lithium Exchange 257
8.1.30.4.2 Method 2: Addition of Alkenyllithiums to Alkynes 258
8.1.30.4.2.1 Variation 1: Cyclization of Vinyllithiums onto Alkynes 258
8.1.30.4.2.2 Variation 2: Cyclization of Vinyllithiums onto Arynes 260
8.1.30.4.3 Method 3: Addition of Aryl- and Hetaryllithiums to Alkynes 261
8.1.30.4.3.1 Variation 1: Cyclization of Aryllithiums onto Alkynes 262
8.1.30.4.3.2 Variation 2: Cyclization of Aryllithiums onto Arynes 263
8.1.30.5 Inter- and Intramolecular Addition of Alkyllithiums to Arenes 265
8.1.30.5.1 Method 1: Intermolecular Dearomatizing Addition of Alkyllithiums to Arenes 265
8.1.30.5.2 Method 2: Intramolecular Dearomatizing Addition of Alkyllithiums to Arenes 266
8.1.30.6 Cascade Reactions 268
8.1.30.6.1 Method 1: Tandem Intermolecular–Intramolecular Carbolithiations 268
8.1.30.6.2 Method 2: Tandem Aminolithiation–Carbolithiation 270
8.1.30.7 Intermolecular Enantioselective Addition of Organolithiums to Alkenes 271
8.1.30.7.1 Method 1: Intermolecular Addition of Alkyllithiums to Alkenes 271
8.1.30.8 Intramolecular Enantioselective Addition of Organolithiums to Alkenes 274
8.1.30.8.1 Method 1: Intramolecular Addition of Alkyllithiums to Alkenes 275
8.1.30.8.2 Method 2: Intramolecular Addition of Aryllithiums to Alkenes 276
Volume 16: Six-Membered Hetarenes with Two Identical Heteroatoms 284
16.14 Product Class 14: Pyrazines 284
16.14.5 Pyrazines 284
16.14.5.1 Synthesis by Ring-Closure Reactions 287
16.14.5.1.1 By Formation of Four N--C Bonds 287
16.14.5.1.1.1 Fragments C--C, C--C, and Two N Fragments 287
16.14.5.1.1.1.1 Method 1: From a 1,2-Bifunctional Compound and Ammonia or Ammonium 287
16.14.5.1.2 By Formation of Three N--C Bonds 288
16.14.5.1.2.1 Fragments N--C--C, C--C, and N 288
16.14.5.1.2.1.1 Method 1: From an a-Amino Ketone, an a-Hydroxy Ketone, and Ammonium Acetate 288
16.14.5.1.3 By Formation of Two N--C Bonds 288
16.14.5.1.3.1 Fragments N--C--C--N and C--C 288
16.14.5.1.3.1.1 Method 1: From Alkane-1,2-diamines 288
16.14.5.1.3.1.2 Method 2: From Alkene-1,2-diamines 292
16.14.5.1.3.1.3 Method 3: From a-Amino Amides 293
16.14.5.1.3.1.4 Method 4: From a-Amino Nitriles 294
16.14.5.1.3.1.5 Method 5: From 1,4-Diazabutadienes 295
16.14.5.1.3.2 Fragments N--C--C and N--C--C 296
16.14.5.1.3.2.1 Method 1: By Cyclodimerization of Azirines 296
16.14.5.1.3.2.2 Method 2: By Self-Condensation 297
16.14.5.1.3.2.3 Method 3: By Condensation of Two Different a-Amino Ketones or Cyanides 299
16.14.5.1.3.3 Fragments C--C--N--C--C and N 302
16.14.5.1.3.3.1 Method 1: From ß,ß'-Difunctional Secondary Amines (or Amides) and Ammonia 302
16.14.5.1.4 By Formation of One N--C Bond 303
16.14.5.1.4.1 Fragment N--C--C--N--C--C 303
16.14.5.1.4.1.1 Method 1: Intramolecular Cyclization of a N--C--C--N--C--C Fragment 303
16.14.5.2 Synthesis by Ring Transformation 304
16.14.5.2.1 Method 1: Ring Transformation of Imidazoles 304
16.14.5.3 Aromatization 305
16.14.5.3.1 Method 1: Dehydrogenation of Dihydropyrazines 305
16.14.5.3.2 Method 2: By Elimination 306
16.14.5.4 Synthesis by Substituent Modification 307
16.14.5.4.1 Substitution of Existing Substituents 307
16.14.5.4.1.1 Of Hydrogen 307
16.14.5.4.1.1.1 Method 1: Metalation 307
16.14.5.4.1.1.2 Method 2: Acylation, Amidation, Alkylation, and Arylation 309
16.14.5.4.1.1.2.1 Variation 1: Homolytic Acylation and Amidation 309
16.14.5.4.1.1.2.2 Variation 2: Direct Alkylation and Arylation 310
16.14.5.4.1.1.2.3 Variation 3: Alkylation, Arylation, and Alkenylation of Pyrazine N-Oxides 311
16.14.5.4.1.1.3 Method 3: Halogenation 313
16.14.5.4.1.1.3.1 Variation 1: Halogenation of Pyrazinamines 313
16.14.5.4.1.1.3.2 Variation 2: Halogenation of Pyrazinols 315
16.14.5.4.1.1.3.3 Variation 3: Deoxidative Chlorination of Pyrazine N-Oxides 316
16.14.5.4.1.1.4 Method 4: Nitration 317
16.14.5.4.1.2 Of Metals 317
16.14.5.4.1.3 Of Carbon Functionalities 319
16.14.5.4.1.3.1 Method 1: Decarboxylation, Decyanation, and Debenzylation 319
16.14.5.4.1.4 Of Halogen 320
16.14.5.4.1.4.1 Method 1: Reduction 320
16.14.5.4.1.4.2 Method 2: Metalation 321
16.14.5.4.1.4.3 Method 3: Alkylation, Arylation, and Related Reactions 323
16.14.5.4.1.4.3.1 Variation 1: Grignard Reaction and Related Reactions 323
16.14.5.4.1.4.3.2 Variation 2: Suzuki–Miyaura Cross-Coupling Reaction and Related Reactions 324
16.14.5.4.1.4.3.3 Variation 3: Negishi Cross-Coupling Reaction and Related Reactions 332
16.14.5.4.1.4.3.4 Variation 4: Stille Cross-Coupling Reaction and Related Reactions 333
16.14.5.4.1.4.3.5 Variation 5: Other Cross-Coupling Reactions for Arylation 335
16.14.5.4.1.4.4 Method 4: Alkenylation and Related Reactions 335
16.14.5.4.1.4.5 Method 5: Alkynylation and Related Reactions 338
16.14.5.4.1.4.6 Method 6: Functionalized Methylation 339
16.14.5.4.1.4.7 Method 7: Cyanation and Carbonylation 341
16.14.5.4.1.4.8 Method 8: Halogenation 343
16.14.5.4.1.4.9 Method 9: Hydroxylation, Alkoxylation, and Sulfanylation 343
16.14.5.4.1.4.10 Method 10: Amination, Azidation, and Phosphonation 347
16.14.5.4.1.5 Of Oxygen and Sulfur Functionalities 351
16.14.5.4.1.5.1 Method 1: Deoxygenation of N-Oxides and Reductive Removal of Oxygen Functionalities 351
16.14.5.4.1.5.2 Method 2: Halogenation 352
16.14.5.4.1.5.3 Method 3: O-Sulfonylation 353
16.14.5.4.1.5.4 Method 4: Alkylation and Arylation 354
16.14.5.4.1.6 Of Nitrogen Functionalities 356
16.14.5.4.1.6.1 Method 1: Halopyrazines, Pyrazinols, and Methoxypyrazines from Aminopyrazines 32
16.14.5.4.2 Addition Reactions 356
16.14.5.4.2.1 Method 1: N-Alkylation and N-Arylation 356
16.14.5.4.2.2 Method 2: N-Oxidation 358
16.14.5.4.3 Rearrangement of Substituents 359
16.14.5.4.3.1 Method 1: Hofmann or Curtius Rearrangement 359
16.14.5.4.4 Modification of Substituents 359
16.14.5.4.4.1 Method 1: Degradation of Condensed Pyrazines 359
16.14.5.4.4.2 Method 2: Modification of Carbon Substituents 361
16.14.5.4.4.3 Method 3: Modification of Nitrogen and Chalcogen Substituents 365
Volume 17: Six-Membered Hetarenes with Two Unlike or More than Two Heteroatoms and Fully Unsaturated Larger-Ring Heterocycles 376
17.3 Product Class 3: Six-Membered Hetarenes with More than Three Heteroatoms 376
17.3.4 Six-Membered Hetarenes with More than Three Heteroatoms 376
17.3.4.1 1,2,3,4-Tetrazines 376
17.3.4.1.1 Method 1: Synthesis of 1,2,3,4-Tetrazine N-Oxides 377
17.3.4.1.1.1 Variation 1: Via Nitration 377
17.3.4.2 1,2,3,5-Tetrazines 379
17.3.4.3 1,2,4,5-Tetrazines 379
17.3.4.3.1 Synthesis by Ring-Closure Reactions 380
17.3.4.3.1.1 By Formation of Four N--C Bonds 380
17.3.4.3.1.1.1 Fragments N--N, N--N, and Two C Fragments 380
17.3.4.3.1.1.1.1 Method 1: Dimerization of Activated Hydrazidic Acid Derivatives 380
17.3.4.3.1.1.1.1.1 Variation 1: From Nitriles 380
17.3.4.3.1.1.1.1.2 Variation 2: From Carboxylic Acid Derivatives 383
17.3.4.3.1.2 By Formation of Two N--C Bonds 385
17.3.4.3.1.2.1 Fragments C--N--N--C and N--N 385
17.3.4.3.1.2.1.1 Method 1: Oxidation of Dihydrotetrazines 385
17.3.4.3.2 Aromatization 385
17.3.4.3.3 Synthesis by Substituent Modification 385
17.3.4.3.3.1 Substitution of Existing Substituents 385
17.3.4.3.3.1.1 Of Heteroatoms 385
17.3.4.3.3.1.1.1 Method 1: Substitution of Halogen Substituents 386
17.3.4.3.3.1.1.1.1 Variation 1: Nucleophilic Aromatic Substitution 386
17.3.4.3.3.1.1.1.2 Variation 2: Palladium-Catalyzed Coupling 392
17.3.4.3.3.1.1.2 Method 2: Substitution of Sulfur Substituents 393
17.3.4.3.3.1.1.2.1 Variation 1: Nucleophilic Substitution 393
17.3.4.3.3.1.1.2.2 Variation 2: Palladium-Catalyzed Coupling 393
17.3.4.3.3.1.1.3 Method 3: Substitution of Nitrogen Substituents 395
17.3.4.3.3.2 Modification of Substituents 401
Volume 19: Three Carbon--Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives 408
19.5 Product Class 5: Nitriles 408
19.5.16 Asymmetric Synthesis of Nitriles 408
19.5.16.1 Introduction of the Cyano Group by Addition to a Carbonyl Group 408
19.5.16.1.1 Method 1: Catalytic Asymmetric Cyanation of Aldehydes 408
19.5.16.1.1.1 Variation 1: Use of Enzymes 408
19.5.16.1.1.2 Variation 2: Use of Chiral Titanium Complexes as Catalysts 409
19.5.16.1.1.3 Variation 3: Use of Chiral Aluminum Complexes as Catalysts 414
19.5.16.1.1.4 Variation 4: Use of Chiral Yttrium Complexes as Catalysts 417
19.5.16.1.1.5 Variation 5: Use of Chiral Ruthenium Complexes as Catalysts 418
19.5.16.1.1.6 Variation 6: Use of Chiral Boron-Based Catalysts 419
19.5.16.1.1.7 Variation 7: Use of Chiral Vanadium-Based Catalysts 420
19.5.16.1.1.8 Variation 8: Use of Chiral Bases as Catalysts 422
19.5.16.1.2 Method 2: Catalytic Asymmetric Cyanation of Ketones 425
19.5.16.1.2.1 Variation 1: Use of Enzymes 425
19.5.16.1.2.2 Variation 2: Use of Chiral Titanium Complexes as Catalysts 426
19.5.16.1.2.3 Variation 3: Use of Chiral Aluminum Complexes as Catalysts 427
19.5.16.1.2.4 Variation 4: Use of a Chiral Gadolinium Complex as Catalyst 430
19.5.16.1.2.5 Variation 5: Use of Chiral Ruthenium Complexes as Catalysts 430
19.5.16.1.2.6 Variation 6: Use of Chiral Organic Salts 431
19.5.16.1.2.7 Variation 7: Use of Chiral Organocatalysts 433
19.5.16.2 Introduction of the Cyano Group by Addition to an Imino Group 437
19.5.16.2.1 Asymmetric Synthesis of a-Aminonitriles Derived from Aldimines 437
19.5.16.2.1.1 Method 1: Asymmetric Strecker Reactions with Chiral Auxiliaries 437
19.5.16.2.1.1.1 Variation 1: Use of Chiral Sulfinamides 437
19.5.16.2.1.1.2 Variation 2: Use of Chiral Hydrazones 438
19.5.16.2.1.2 Method 2: Catalytic Asymmetric Cyanation of Aldimines 439
19.5.16.2.1.2.1 Variation 1: Use of Chiral Aluminum Complexes as Catalysts 32
19.5.16.2.1.2.2 Variation 2: Use of Chiral Titanium Complexes as Catalysts 441
19.5.16.2.1.2.3 Variation 3: Use of Chiral Lanthanide Complexes as Catalysts 443
19.5.16.2.1.2.4 Variation 4: Use of Chiral Thioureas as Catalysts 32
19.5.16.2.1.2.5 Variation 5: Use of Chiral BINOL–Phosphoric Acids as Catalysts 446
19.5.16.2.1.2.6 Variation 6: Use of Chiral Quaternary Ammonium Salts as Catalysts 32
19.5.16.2.1.2.7 Variation 7: Use of a Chiral Bisformamide as Catalyst 449
19.5.16.2.1.2.8 Variation 8: Use of a Chiral N,N'-Dioxide as Catalyst 450
19.5.16.2.2 Asymmetric Synthesis of a-Aminonitriles Derived from Ketimines 451
19.5.16.2.2.1 Method 1: Asymmetric Strecker Reactions with Chiral Auxiliaries 451
19.5.16.2.2.1.1 Variation 1: Use of Chiral Sulfinamides 451
19.5.16.2.2.2 Method 2: Catalytic Asymmetric Cyanation of Ketimines 452
19.5.16.2.2.2.1 Variation 1: Use of Chiral Thioureas as Catalysts 452
19.5.16.2.2.2.2 Variation 2: Use of Chiral Titanium Complexes as Catalysts 453
19.5.16.2.2.2.3 Variation 3: Use of Chiral Gadolinium Complexes as Catalysts 454
19.5.16.2.2.2.4 Variation 4: Use of Chiral N,N'-Dioxides as Catalysts 455
19.5.16.2.2.2.5 Variation 5: Use of Chiral Sodium 1,1'-Binaphthalene-2,2'-diyl Phosphate as Catalyst 457
19.5.16.3 Introduction of the Cyano Group by Conjugate Addition 458
19.5.16.3.1 Method 1: Use of a Chiral Auxiliary 459
19.5.16.3.2 Method 2: Use of Chiral Aluminum Complexes as Catalysts 460
19.5.16.3.3 Method 3: Use of Chiral Gadolinium Complexes as Catalysts 461
19.5.16.3.4 Method 4: Use of Chiral Strontium Complexes as Catalysts 465
19.5.16.3.5 Method 5: Use of Chiral Titanium Complexes as Catalysts 466
19.5.16.3.6 Method 6: Use of Chiral Ruthenium Complexes as Catalysts 467
19.5.16.3.7 Method 7: Use of Chiral Organic Salts 468
19.5.16.4 Introduction of the Cyano Group by Hydrocyanation of Alkenes 471
19.5.16.4.1 Method 1: Use of Chiral Nickel Complexes as Catalysts 471
Volume 27: Heteroatom Analogues of Aldehydes and Ketones 476
27.15 Product Class 15: Oximes 476
27.15.1 Synthesis of Product Class 15 476
27.15.1.1 Method 1: Condensation of Carbonyl Compounds and Hydroxylamine 476
27.15.1.2 Method 2: Nitrosation 477
27.15.1.2.1 Variation 1: Electrophilic Nitrosation of Active Methylene Compounds 478
27.15.1.2.2 Variation 2: Electrophilic Nitrosation of Alkenes 479
27.15.1.2.3 Variation 3: Radical Nitrosation 480
27.15.1.3 Method 3: Oxidation of Amino Compounds 481
27.15.1.3.1 Variation 1: Oxidation of Hydroxylamines 481
27.15.1.3.2 Variation 2: Oxidation of Primary Amines 482
27.15.1.4 Method 4: Reduction of Nitro and Nitroso Compounds 483
27.15.1.4.1 Variation 1: Reduction of Nitroalkanes 483
27.15.1.4.2 Variation 2: Reduction of Conjugated Nitroalkenes 485
27.15.1.4.3 Variation 3: Reduction of gem-Chloronitroso Compounds 485
27.15.1.5 Method 5: Additional Methods 486
27.15.2 Applications of Product Class 15 in Organic Synthesis 488
27.15.2.1 Method 1: Formal Substitution with Cleavage of the O--N Bond 488
27.15.2.1.1 Variation 1: Via Oxidative Addition to Transition Metals 489
27.15.2.1.2 Variation 2: With Nucleophiles 491
27.15.2.1.3 Variation 3: Via Radical Intermediates 494
27.15.2.2 Method 2: Formal Elimination 497
27.15.2.2.1 Variation 1: Generation of 1,3-Dipoles 497
27.15.2.2.2 Variation 2: Conversion into Nitriles 499
27.15.2.2.3 Variation 3: Regeneration of Carbonyl Compounds 501
27.15.2.3 Method 3: Addition Reactions 502
27.15.2.3.1 Variation 1: Reduction to Primary Amines 502
27.15.2.3.2 Variation 2: Reduction to Hydroxylamines 503
27.15.2.3.3 Variation 3: With Radicals 504
27.15.2.3.4 Variation 4: With Carbon Nucleophiles 505
27.15.2.4 Method 4: Rearrangements 506
27.15.2.4.1 Variation 1: Beckmann Rearrangement 506
27.15.2.4.2 Variation 2: Neber Reaction 509
27.15.2.5 Method 5: Reactions with Retention of the Oxime Moiety 510
27.15.2.5.1 Variation 1: E/Z-Isomerization 510
27.15.2.5.2 Variation 2: a-Alkylation 511
27.15.2.5.3 Variation 3: Radical Reactions of Sulfonyloxime Ethers 512
27.15.2.6 Method 6: Directing Group for C--H Functionalization 513
27.15.2.7 Method 7: Additional Reactions 517
Author Index 532
Abbreviations 564
List of All Volumes 570
2.12.15 Organometallic Complexes of Scandium, Yttrium, and the Lanthanides (Update 2011)
P. Dissanayake, D. J. Averill, and M. J. Allen
2.12.15.1 Lanthanide-Catalyzed Mukaiyama Aldol Reactions
This chapter summarizes the use of lanthanide-containing catalysts for Mukaiyama aldol reactions since 1987. In this chapter, reactions are categorized as follows: (1) non-enantio-selective formation of β-hydroxycarbonyls (▶ Section 2.12.15.1.1), (2) enantioselective formation of β-hydroxycarbonyls in an organic solvent (▶ Section 2.12.15.1.2.1), and (3) enantioselective formation of β-hydroxycarbonyls in an aqueous solvent (▶ Section 2.12.15.1.2.2).
2.12.15.1.1 Method 1: Non-enantioselective Formation of β-Hydroxycarbonyls
Lanthanide-catalyzed Mukaiyama aldol reactions between aldehydes 1 and the methyl trimethylsilyl acetal 2, to obtain Mukaiyama aldol products 3, were first reported using lanthanide(III) chlorides (▶ Scheme 1).[1] Furthermore, the reactions also proceed smoothly at room temperature when lanthanide(III) bromides are used as catalysts.[2] In addition to lanthanides in the +3 oxidation state, samarium(II) iodide can also be used as an efficient catalyst for this reaction, and the samarium(II) iodide precatalyst is stable enough to be stored under argon without oxidation (▶ Scheme 1).[3]
▶ Scheme 1 Mukaiyama Aldol Reactions Catalyzed by Lanthanide Catalysts[1]
| R1 | Catalyst | Temp (°C) | Time | Yielda (%) | Ref |
| Ph | SmCl3 | rt | 12 h | 66 | 28 | [1] |
| Ph | CeCl3 | rt | 24 h | 61 | 27 | [1] |
| Ph | LaCl3 | rt | 4 d | 21 | 42 | [1] |
| (CH2)4Me | SmCl3 | rt | 36 h | 47 | 16 | [1] |
| 4-MeOC6H4 | LnBr3 (THF)2.6 | rt | 2 hb,c | 86 | n.r. | [2] |
| 3-O2NC6H4 | LnBr3 (THF)2.6 | rt | 4 hb,d | n.r. | 83 | [2] |
| 4-MeOC6H4 | SmI2 (THF)2 | –78 | 5 min | 95 | n.r. | [3] |
| 4-MeOC6H4 | SmI3 (THF)3 | –78 | 5 min | 95 | n.r. | [3] |
| Ph | SmI2(THF)2 | –78 | 5 min | 95 | n.r. | [3] |
| (CH2)6Me | SmI2(THF)2 | –20 | 4.5 h | 90 | n.r. | [3] |
| b Catalyst prepared from mischmetal. |
| c LnBr3 (THF)2.6 (20 mol%). |
| d LnBr3 (THF)2.6 (10 mol%). |
Another variation of the lanthanide-catalyzed Mukaiyama aldol reaction is carried out in aqueous media using a catalytic amount of ytterbium(III) trifluoromethanesulfonate. These aqueous reactions between formaldehyde and silyl enol ethers 5 yield hydroxymethylated adducts 6 as shown in ▶ Scheme 2.[4]
▶ Scheme 2 Mukaiyama Aldol Reactions Catalyzed by Ytterbium(III) Trifluoromethanesulfonate under Aqueous Conditions[4]
In addition to using cosolvents with water, lanthanide Lewis acid–surfactant combined precatalysts are used for Mukaiyama aldol reactions in water (▶ Schemes 3 and 4).[5,6] The reaction between benzaldehyde and silyl enol ether 7 to yield aldol adduct 8 (▶ Scheme 3) suggests that the amount of surfactant, sodium dodecyl sulfate, influences the reaction yield. The aqueous Mukaiyama aldol reactions of α,β-epoxyaldehydes 9 with silyl enol ether 10 to yield adducts 11 have also been reported using sodium dodecyl sulfate (▶ Scheme 4).[6]
▶ Scheme 3 Mukaiyama Aldol Reaction Catalyzed by an Ytterbium(III) Trifluoromethanesulfonate–Surfactant Combined Precatalyst[5]
| Sodium Dodecyl Sulfate (equiv) | Yield (%) | Ref |
▶ Scheme 4 Mukaiyama Aldol Reactions Catalyzed by Lanthanide(III) Trifluoromethanesulfonate–Surfactant Combined Precatalysts[6]
| R1 | R2 | Ln(OTf)3 | dr (anti/syn) | Yield (%) | Ref |
| H | CH2OTBDPS | Eu(OTf)3 | 90:10 | 25 | [6] |
| H | CH2OTBDPS | La(OTf)3 | 91:9 | 46 | [6] |
| H | CH2OTBDPS | Yb(OTf)3 | 94:6 | 33 | [6] |
| CH2OTBDPS | H | La(OTf)3 | 67:33 | 33 | [6] |
| H | OBn | La(OTf)3 | 90:10 | 35a | [6] |
| a Starting material was used as a racemic mixture of R,R- and S,S-stereoisomers. |
Methyl 2,2-Dimethyl-3-(trimethylsiloxy)alkanoates 3 and Methyl 3-Hydroxy-2,2-dimethylalkanoates 4; General Procedure Using Lanthanide(III) Chlorides or Bromides:[1,2]
Aldehyde 1 and silyl enol ether 2 were added to a suspension of LnX3 (0.05 or 0.10 equiv) in CH2Cl2 under argon at ambient temperature. After the reaction was complete the solvent was removed under reduced pressure. The crude material obtained was purified by flash chromatography (silica gel).
Methyl 2,2-Dimethyl-3-(trimethylsiloxy)alkanoates 3 and Methyl 3-Hydroxy-2,2-dimethylalkanoates 4; General Procedure Using Samarium(II) or Samarium (III) Iodide:[3]
Methods A and B allow the preparation of β-hydroxycarbonyls 4 using SmI2. Method B is preferred when silyl ethers 3 are desired.
Method A: A 0.10 M soln of SmI2 in THF (1.0 mL) was concentrated under reduced pressure to give SmI2 (THF)2 as a blue powder. Alternatively, SmI2 (THF)2 (55 mg, 0.10 mmol) was weighed in a glovebox. This precatalyst, or SmI3 (THF)3 if desired, was suspended in CH2Cl2 (5 mL), and silyl acetal 2 (2.2–3.0 mmol) was added followed by the aldehyde 1 (2.0 mmol). The resulting yellow soln was stirred under argon. The mixture was hydrolyzed with 0.1 M HCl (5 mL) and extracted with Et2O. The extracts were washed with H2O and dried (MgSO4). After removal of the solvent, the product was purified by flash chromatography (silica gel).
Method B: Method A was followed, but instead of adding HCl the reaction was stopped by the addition of hexane (50 mL), which precipitated samarium salts. After filtration through Celite, the solvents were removed under reduced pressure, and purification by flash chromatography (silica gel) afforded the desired product.
3-Hydroxycarbonyl Compounds 6; General Procedure:[4]
CAUTION:
Formaldehyde is a probable human carcinogen, a severe eye, skin, and respiratory tract irritant, and a skin sensitizer.
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