Science of Synthesis Knowledge Updates 2010 Vol. 3 (eBook)
550 Seiten
Thieme (Verlag)
978-3-13-178661-6 (ISBN)
The Science of Synthesis Editorial Board,together with the volume editors and authors, is constantly reviewing the whole field of synthetic organic chemistry as presented in Science of Synthesis and evaluating significant developments in synthetic methodology. Four annual volumes updating content across all categories ensure that you always have access to state-of-the-art synthetic methodology.
Content of this volume: Aryl Grignard Reagents, Magnesium Halides, Magnesium Halides, Magnesium Oxide, Alkoxides, and Carboxylates, Magnesium Amides, Oxazoles, Acyclic and Semicyclic O/O Acetals, 1,3-Dioxetanes and 1,3-Dioxolanes, Spiroketals, Glycosyl Oxygen Compounds (Di- and Oligosaccharides), Oligosaccharides, Acyclic Hemiacetals, Lactols, and Carbonyl Hydrates, Acyclic Hemiacetals, Lactols, and Carbonyl Hydrates.
Science of Synthesis: Knowledge Updates 2010/3 1
Title page 5
Imprint 7
Preface 8
Abstracts 10
Overview 16
Table of Contents 18
Volume 7: Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be ··· Ba) 28
7.6 Product Class 6: Magnesium Compounds 28
7.6.5.6 Aryl Grignard Reagents 28
7.6.5.6.1 Method 1: Synthesis by Reaction of Aryl Halides and Magnesium in the Presence of Lithium Chloride 28
7.6.5.6.2 Method 2: Synthesis by Halogen–Magnesium Exchange with Alkyl Grignard Reagents 29
7.6.5.6.2.1 Variation 1: Synthesis by Halogen–Magnesium Exchange with Lithium Triorganomagnesates 30
7.6.5.6.3 Method 3: Synthesis by Deprotonative ortho-Magnesiation 31
7.6.5.6.4 Method 4: Application to Synthesis of Biaryls by Dimerization 32
7.6.5.6.5 Method 5: Application to Synthesis of Amines 33
7.6.5.6.6 Method 6: Application to Addition to C--C Multiple Bonds Bearing a Directing Group 34
7.6.5.6.7 Method 7: Application to Transmetalations with Metal Halides 34
7.6.5.6.8 Method 8: Application to Addition to Carbonyl Compounds 35
7.6.5.6.8.1 Variation 1: Highly Efficient Addition of Lithium Triphenylmagnesate to Benzophenone 35
7.6.5.6.8.2 Variation 2: Zinc(II)-Catalyzed Addition of Aryl Grignard Reagents to Carbonyl Species 35
7.6.10.9 Alkyl Grignard Reagents 38
7.6.10.9.1 Method 1: Synthesis by Halogen–Magnesium Exchange 38
7.6.10.9.1.1 Variation 1: Synthesis by Sulfoxide–Magnesium Exchange 41
7.6.10.9.2 Method 2: Synthesis by Carbomagnesiation of C--C Multiple Bonds 42
7.6.10.9.3 Method 3: Application to Addition to Carbonyl Compounds 43
7.6.10.9.3.1 Variation 1: Highly Efficient Addition of Lithium Trialkylmagnesates to Acetophenone 43
7.6.10.9.3.2 Variation 2: Zinc(II)-Catalyzed Addition of Alkyl Grignard Reagents to Carbonyl Groups 44
7.6.12.13 Magnesium Halides 48
7.6.12.13.1 Method 1: Applications of Magnesium Fluoride 48
7.6.12.13.1.1 Variation 1: Magnesium Fluoride Catalyzed Knoevenagel Reactions 48
7.6.12.13.1.2 Variation 2: Magnesium Fluoride/Chiral Phosphoric Acid Catalyzed Friedel–Crafts Reactions 49
7.6.12.13.2 Method 2: Applications of Magnesium Chloride as a Lewis Acid 49
7.6.12.13.2.1 Variation 1: Magnesium Chloride Promoted Claisen Reactions 50
7.6.12.13.2.2 Variation 2: Magnesium Chloride/Potassium Borohydride Promoted Reductions 50
7.6.12.13.3 Method 3: Applications of Other Magnesium Halides as Lewis Acids 51
7.6.12.13.3.1 Variation 1: Reaction of Organometallics in the Presence of Magnesium Bromide 51
7.6.12.13.3.2 Variation 2: Magnesium Halide Promoted Dipolar Cycloaddition Reactions 52
7.6.12.13.4 Method 4: Applications of Magnesium Halide/Base Systems to Enolate Formation and Subsequent Addition Reactions 52
7.6.12.13.5 Method 5: Applications of Magnesium Halides in Morita–Baylis–Hillman Reactions 53
7.6.12.13.6 Method 6: Applications of Magnesium Iodide in Ring-Expansion Reactions 55
7.6.13.17 Magnesium Oxide, Alkoxides, and Carboxylates 58
7.6.13.17.1 Method 1: Applications of Magnesium Oxide 58
7.6.13.17.2 Method 2: Applications of Magnesium Methoxide as a Base 59
7.6.13.17.3 Method 3: Applications of Magnesium Alkoxides to the Oppenauer Oxidation 60
7.6.13.17.4 Method 4: Applications of Magnesium Alkoxides in Diastereo- and Enantioselective Reactions 61
7.6.13.17.5 Method 5: Applications of Magnesium Alkoxides in Elimination Reactions 62
7.6.13.17.6 Method 6: Applications of Magnesium Carboxylates 64
7.6.13.17.7 Method 7: Applications of Magnesium Monoperoxyphthalate 65
7.6.14 Product Subclass 14: Magnesium Amides 68
Synthesis of Product Subclass 14 68
7.6.14.1 Method 1: Synthesis of Methylmagnesium N-Cyclohexyl-N-isopropylamide 68
7.6.14.2 Method 2: Synthesis of (2,2,6,6-Tetramethylpiperidino)magnesium Chloride–Lithium Chloride Complex 69
7.6.14.3 Method 3: Synthesis of Magnesium Bis(diisopropylamide) 69
7.6.14.4 Method 4: Synthesis of Magnesium Bis(2,2,6,6-tetramethylpiperidide) 70
7.6.14.4.1 Variation 1: Synthesis of Magnesium Bis(2,2,6,6-tetramethylpiperidide)–Bis(lithium chloride) Complex 70
7.6.14.5 Method 5: Synthesis of Other Magnesium Bis(amide)s 71
7.6.14.6 Method 6: Synthesis of Chiral Magnesium Bis(dialkylamide)s 71
Applications of Product Subclass 14 in Organic Synthesis 72
7.6.14.7 Method 7: Reactions Involving Methylmagnesium N-Cyclohexyl-N-isopropylamide 72
7.6.14.8 Method 8: Reactions Involving (Diisopropylamino)magnesium Bromide 73
7.6.14.9 Method 9: Reactions Involving (2,2,6,6-Tetramethylpiperidino)magnesium Chloride–Lithium Chloride Complex 73
7.6.14.10 Method 10: Reactions Involving Magnesium Bis(diisopropylamide) 75
7.6.14.11 Method 11: Reactions Involving Magnesium Bis(2,2,6,6-tetramethylpiperidide) 76
7.6.14.12 Method 12: Reactions Involving Magnesium Bis(2,2,6,6-tetramethylpiperidide)–Bis(lithium chloride) Complex 78
7.6.14.13 Method 13: Reactions Involving Other Magnesium Bis(amide)s 79
7.6.14.14 Method 14: Reactions Involving Chiral Magnesium Bis(dialkylamide)s 80
Volume 11: Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom 84
11.12 Product Class 12: Oxazoles 84
11.12.5 Oxazoles 84
11.12.5.1 Synthesis by Ring-Closure Reactions 85
11.12.5.1.1 By Formation of One O--C and One N--C Bond 85
11.12.5.1.1.1 Fragments O--C--N and C--C 85
11.12.5.1.1.1.1 Method 1: From Vinyl Halides and Amides 85
11.12.5.1.1.2 Fragments O--C--C and C--N 87
11.12.5.1.1.2.1 Method 1: From Carbonyl Compounds and Nitriles 87
11.12.5.1.1.2.2 Method 2: From Acylcarbenes and Nitriles 92
11.12.5.1.1.2.3 Method 3: From Benzylamines and 1,3-Dicarbonyl Compounds 95
11.12.5.1.1.2.4 Method 4: From Amides and Propargylic Alcohols 96
11.12.5.1.1.3 Fragments N--C--C and C--O 97
11.12.5.1.1.3.1 Method 1: From 2-Amino-1-bromoethanesulfonamide and Acid Chlorides 97
11.12.5.1.1.4 Fragments O--C--C--N and C 99
11.12.5.1.1.4.1 Method 1: From Nitroethanones and Orthobenzoate 99
11.12.5.1.1.4.2 Method 2: From a-Cyano-ß-hydroxy Enamines and Orthoformate 100
11.12.5.1.2 By Formation of One O--C and One C--C Bond 101
11.12.5.1.2.1 Fragments C--N--C and C--O 101
11.12.5.1.2.1.1 Method 1: From Isocyanides and Acyl Chlorides 101
11.12.5.1.3 By Formation of One O--C Bond 103
11.12.5.1.3.1 Fragment O--C--N--C--C 103
11.12.5.1.3.1.1 Method 1: Cyclodehydration of a-Acylamino Aldehydes or Ketones 103
11.12.5.1.3.1.2 Method 2: From (Acylamino)acetaldehyde Dimethyl Acetals 105
11.12.5.1.3.1.3 Method 3: From Oxazolones via Friedel–Crafts Acylation and Subsequent Cyclization 106
11.12.5.1.3.1.4 Method 4: Oxazoles from N-Propargylamides 107
11.12.5.1.3.1.5 Method 5: From Enamides 120
11.12.5.1.3.1.6 Method 6: From Amides and Diazocarbonyl Compounds 122
11.12.5.1.3.2 Fragment O--C--C--N--C 124
11.12.5.1.3.2.1 Method 1: Oxidative Cyclization of Schiff Bases Derived from Glycine Methyl Ester 124
11.12.5.1.3.2.2 Method 2: From Isocyanoacetamides and Imines 124
11.12.5.1.3.2.3 Method 3: Trifluoromethanesulfonic Anhydride Mediated Cyclocondensation of N-Acyl Amino Acid Esters 126
11.12.5.1.3.2.4 Method 4: From Aldehydes and Isocyanides 127
11.12.5.2 Aromatization 129
11.12.5.2.1 Method 1: By Dehydrogenation of Dihydrooxazoles 129
11.12.5.2.2 Method 2: Elimination of Hydrogen Chloride from Dihydrooxazoles 130
11.12.5.3 Synthesis by Substituent Modification 131
11.12.5.3.1 Substitution Reactions 131
11.12.5.3.1.1 Method 1: Reactions of Metalated Oxazoles with Electrophiles 131
11.12.5.3.1.2 Method 2: Oxazoles via Substitution of Leaving Groups through Transition-Metal-Catalyzed Reactions 137
11.12.5.3.1.3 Method 3: Coupling Reactions of Oxazolones 140
11.12.5.4 Applications of Oxazoles in Organic Synthesis 141
Volume 29: Acetals: Hal/X and O/O, S, Se, Te 148
29.6 Product Class 6: Acyclic and Semicyclic O/O Acetals 148
29.6.2 Acyclic and Semicyclic O/O Acetals 148
29.6.2.1 Synthesis from Compounds of Higher Oxidation State 148
29.6.2.1.1 Method 1: Synthesis by Cycloaddition of Ketene Acetals 148
29.6.2.1.1.1 Variation 1: From Ketene Acetals and Alkenes via Cycloaddition 148
29.6.2.1.1.2 Variation 2: From Ketene Acetals and Alkynes via Cycloaddition 149
29.6.2.2 Synthesis from Compounds of the Same Oxidation State 149
29.6.2.2.1 Method 1: Synthesis from Hal/OR Acetals 149
29.6.2.2.2 Method 2: Synthesis from Aldehydes or Ketones and Alcohols 150
29.6.2.2.2.1 Variation 1: From Alcohols without Removal of Water 151
29.6.2.2.2.2 Variation 2: From Alcohols with Removal of Water by Physical Methods 153
29.6.2.2.2.3 Variation 3: From Alcohols with Removal of Water by Chemical Means 153
29.6.2.2.2.4 Variation 4: From Hemiacetals and Alkylating Agents 155
29.6.2.2.2.5 Variation 5: From Alcohols and Alkenyl Ketones 155
29.6.2.2.3 Method 3: Synthesis from Aldehydes or Ketones and Alcohol Derivatives 155
29.6.2.2.3.1 Variation 1: From Trialkyl Orthoformates 156
29.6.2.2.3.2 Variation 2: From Other Acetals 158
29.6.2.2.4 Method 4: Synthesis from Other O/O Acetals 158
29.6.2.2.4.1 Variation 1: By Exchange of Both Alkoxy Groups 158
29.6.2.2.4.2 Variation 2: By Exchange of One Alkoxy Group 159
29.6.2.2.5 Method 5: Synthesis from Acetals with Other Heteroatoms 163
29.6.2.2.5.1 Variation 1: From O/Se Acetals 163
29.6.2.2.5.2 Variation 2: From S/S Acetals 164
29.6.2.2.6 Method 6: Synthesis from Oximes 164
29.6.2.2.7 Method 7: Synthesis from Heterosubstituted Alkenes 164
29.6.2.2.7.1 Variation 1: From Acyclic Enol Ethers and Alcohols 165
29.6.2.2.7.2 Variation 2: From Cyclic Enol Ethers and Alcohols 165
29.6.2.2.7.3 Variation 3: From Allenyl Ethers and Alcohols 167
29.6.2.2.7.4 Variation 4: Dimerization of Enol Ethers 168
29.6.2.2.7.5 Variation 5: From Enol Ethers and Cyclic Carbonyl Ylides 169
29.6.2.3 Synthesis from Compounds of Lower Oxidation State 170
29.6.2.3.1 Method 1 : Synthesis from Heterosubstituted Alkanes 170
29.6.2.3.1.1 Variation 1: From Alcohols 170
29.6.2.3.1.2 Variation 2: From Alcohols and Ethers 171
29.6.2.3.1.3 Variation 3: From Alcohols and Alkyl Halides 172
29.6.2.3.2 Method 2: Synthesis from Alkynes with Electron-Withdrawing Substituents 172
29.6.2.3.3 Method 3: Synthesis from Alkenes 173
29.6.2.3.4 Method 4: Synthesis from Peroxy Esters 174
29.7 Product Class 7: 1,3-Dioxetanes and 1,3-Dioxolanes 178
29.7.3 1,3-Dioxetanes and 1,3-Dioxolanes 178
29.7.3.1 1,3-Dioxetanes 178
29.7.3.2 1,3-Dioxolanes 178
29.7.3.2.1 Method 1: Synthesis by Formation of Two C--O Bonds 180
29.7.3.2.1.1 Variation 1: Reactions of Carbonyl Compounds with 1,2-Diols 180
29.7.3.2.1.2 Variation 2: Reactions of Acetals and Ketals with 1,2-Diols 182
29.7.3.2.1.3 Variation 3: Reactions of Enol Ethers with 1,2-Diols 183
29.7.3.2.1.4 Variation 4: Reactions of Carbonyl Compounds with 1,2-Bis(trimethylsilyl) Ethers 184
29.7.3.2.1.5 Variation 5: Reactions of Epoxides with Ketones 185
29.7.3.2.1.6 Variation 6: By Double Michael Addition of 1,2-Diols to Electron-Deficient Alkynes 186
29.7.3.2.1.7 Variation 7: Reaction of 1,1-Dihalo Compounds with 1,2-Diols 188
29.7.3.2.1.8 Variation 8: Reactions of Ketones and 2-Halo Alcohols 189
29.7.3.2.2 Method 2: Synthesis by Formation of One C--O Bond 190
29.7.3.2.2.1 Variation 1: From Monoprotected 1,2-Diols 190
29.7.3.2.2.2 Variation 2: By Oxidation of Electron-Rich Arenes and Hetarenes and Cyclization 191
29.7.3.2.2.3 Variation 3: By Cyclization of Hydroxy-Substituted Enol Ethers 191
29.7.3.2.2.4 Variation 4: By Intramolecular Transacetalization 192
29.7.3.2.2.5 Variation 5: Additions to Activated Alkenes 193
29.7.3.2.3 Method 3: Exchange of Ligands on Existing Acetals 194
29.7.3.2.3.1 Variation 1: Radical Reactions 194
29.7.3.2.3.2 Variation 2: From Metalated Dioxolanes 194
29.7.3.2.3.3 Variation 3: From Ortho Esters 195
29.7.3.2.4 Method 4: Deprotection Reactions of 1,3-Dioxolanes 195
29.7.3.2.5 Method 5: Applications of Chiral 1,3-Dioxolanes in Asymmetric Synthesis 196
29.9 Product Class 9: Spiroketals 200
29.9.2 Spiroketals 200
29.9.2.1 Synthesis by Formation of Two C--O Bonds: Cyclization of Dihydroxy Ketones 200
29.9.2.1.1 Method 1: Nucleophilic Addition to Aldehydes 201
29.9.2.1.1.1 Variation 1: Using Dithiane-Stabilized Carbanions 201
29.9.2.1.1.2 Variation 2: Using Lithiated Methoxyallene Followed by Heck Reaction 202
29.9.2.1.2 Method 2: [3 + 2] Cycloaddition of Nitrile Oxides Followed by Dihydroisoxazole Hydrogenolysis 204
29.9.2.1.3 Method 3: Reductive Cross Coupling Followed by Oxidative Cleavage 206
29.9.2.1.4 Method 4: Radical Addition of Xanthates to Alkenes 208
29.9.2.1.5 Method 5: Kulinkovich Cyclopropanation of Esters Followed by Cyclopropanol Ring Opening 210
29.9.2.1.6 Method 6: Synthesis from Formyl Dianion Equivalents 211
29.9.2.1.6.1 Variation 1: Using Tosylmethyl Isocyanide Followed by Hydrolysis 211
29.9.2.1.6.2 Variation 2: Using Nitroalkanes Followed by Nef Reaction 213
29.9.2.2 Synthesis by Formation of Two C--O Bonds: Synthesis from Other Precursors 214
29.9.2.2.1 Method 1: Transition-Metal-Catalyzed Cyclizations 215
29.9.2.2.1.1 Variation 1: Palladium-Catalyzed Alkyne Cycloisomerization 215
29.9.2.2.1.2 Variation 2: Gold-Catalyzed Alkyne Cycloisomerization 217
29.9.2.2.1.3 Variation 3: Alkyne Cycloisomerization Catalyzed by Other Metals 218
29.9.2.2.1.4 Variation 4: Iron-Catalyzed Cyclization of Hydroxy Oxo Allylic Acetates 220
29.9.2.2.2 Method 2: Oxidative Cyclization of Phenols 221
29.9.2.2.3 Method 3: Oxidative Rearrangement of Alkyl Enol Ethers 223
29.9.2.2.4 Method 4: Iodoetherification of Dihydroxyalkenes Followed by Dehydroiodination 224
29.9.2.3 Synthesis by Formation of One C--O Bond and One C--C Bond 225
29.9.2.3.1 Method 1: Cycloaddition Reactions 226
29.9.2.3.1.1 Variation 1: Hetero-Diels–Alder Reactions of o-Quinomethanes 226
29.9.2.3.1.2 Variation 2: [3 + 2] Cycloadditions 229
29.9.2.3.2 Method 2: Metal-Catalyzed Cross Coupling 229
29.9.2.3.3 Method 3: Propargyl Claisen Rearrangement 231
29.9.2.4 Synthesis by Formation of One C--O Bond 232
29.9.2.4.1 Method 1: Oxidative Insertion 232
29.9.2.4.2 Method 2: Synthesis from Exocyclic Vinyl Ethers 234
29.9.2.4.2.1 Variation 1: Using Metal Carbenoids 234
29.9.2.4.2.2 Variation 2: Ring Expansion of Donor–Acceptor-Substituted Cyclopropanes 236
29.9.2.4.3 Method 3: Oxidation of Furans 238
29.9.2.4.3.1 Variation 1: Photooxygenation of Furans 238
29.9.2.4.3.2 Variation 2: Other Oxidation Reagents 239
29.9.2.4.4 Method 4: Lewis Acid Catalyzed 1,5-Hydride Transfer 240
29.9.2.5 Synthesis by Formation of One C--C Bond 241
29.9.2.5.1 Method 1: Reductive Cyclization of Cyano Acetals 241
29.9.2.5.2 Method 2: [2 + 2 + 2] Cyclotrimerization 242
29.9.2.6 Synthesis by Formation of Two C--O Bonds and One C--C Bond 243
29.9.2.6.1 Method 1: Palladium-Catalyzed Three-Component Coupling 243
29.9.2.7 Synthesis of Spiroepoxides and Related Small-Ring Spiroketals 245
29.9.2.7.1 Method 1: Synthesis by Formation of Two C--O Bonds 245
29.9.2.7.2 Method 2: Synthesis by Formation of Four C--O Bonds 246
29.9.2.7.3 Method 3: Synthesis by Formation of One C--O Bond and One C--C Bond 247
29.9.2.8 Synthesis of Trioxadispiroketals 248
29.16 Product Class 16: Glycosyl Oxygen Compounds (Di- and Oligosaccharides) 256
29.16.1 Product Subclass 1: Disaccharides 256
29.16.1.1 Synthesis of Product Subclass 1 259
29.16.1.1.1 Method 1: Synthesis from Anomeric Halides 259
29.16.1.1.1.1 Variation 1: From Fluorides 259
29.16.1.1.1.2 Variation 2: From Chlorides and Bromides 261
29.16.1.1.1.3 Variation 3: From Iodides 264
29.16.1.1.2 Method 2: Synthesis from 1-Oxygen-Substituted Derivatives 266
29.16.1.1.2.1 Variation 1: From Hemiacetals 266
29.16.1.1.2.2 Variation 2: From O-Acyl, O-Carbonyl, and Related Compounds 268
29.16.1.1.2.3 Variation 3: From O-Imidates 271
29.16.1.1.2.4 Variation 4: From Phosphites, Phosphates, and Other O--P Derivatives 277
29.16.1.1.2.5 Variation 5: From O-Sulfonyl Derivatives 280
29.16.1.1.2.6 Variation 6: By O-Transglycosidation 280
29.16.1.1.3 Method 3: Synthesis from 1-Sulfur-Substituted Derivatives 286
29.16.1.1.3.1 Variation 1: From Alkylsulfanyl and Arylsulfanyl Glycosides (Thioglycosides) 286
29.16.1.1.3.2 Variation 2: From Thioimidates 293
29.16.1.1.3.3 Variation 3: From Sulfoxides, Sulfimides, and Sulfones 296
29.16.1.1.3.4 Variation 4: From Xanthates and Related Derivatives 297
29.16.1.1.3.5 Variation 5: From Thiocyanates and Other Thio Derivatives 298
29.16.1.1.4 Method 4: Synthesis from Miscellaneous Glycosyl Donors 300
29.16.1.1.4.1 Variation 1: From Ortho Esters and Dihydrooxazoles 300
29.16.1.1.4.2 Variation 2: From 1,2-Dehydro and 1,2-Anhydro Derivatives 303
29.16.1.1.4.3 Variation 3: From Seleno- and Telluroglycosides 307
29.16.1.1.4.4 Variation 4: From 1-Diazirine Derivatives 309
29.16.1.1.5 Method 5: Synthesis by Intramolecular and Indirect Methods 309
29.16.2 Product Subclass 2: Oligosaccharides 317
29.16.2.1 Synthesis of Product Subclass 2 318
29.16.2.1.1 Method 1: Linear Synthesis 318
29.16.2.1.2 Method 2: Block Synthesis 321
29.16.2.1.3 Method 3: Synthesis by Selective Activation 331
29.16.2.1.4 Method 4: Synthesis by Two-Step Activation and In Situ Preactivation 334
29.16.2.1.5 Method 5: Armed–Disarmed and Related Chemoselective Approaches 340
29.16.2.1.5.1 Variation 1: Arming and Disarming with Neighboring Substituents 341
29.16.2.1.5.2 Variation 2: Disarming with Remote Substituents 346
29.16.2.1.5.3 Variation 3: Disarming by Torsional Effects 347
29.16.2.1.5.4 Variation 4: Reactivity-Based Programmable Strategy 351
29.16.2.1.5.5 Variation 5: Superdisarmed Building Blocks 353
29.16.2.1.5.6 Variation 6: Superarmed Glycosyl Donors 355
29.16.2.1.6 Method 6: The Active–Latent Approach 358
29.16.2.1.7 Method 7: Steric Hindrance and Temporary Deactivation 360
29.16.2.1.8 Method 8: Orthogonal and Semi-Orthogonal Strategies 366
29.16.2.1.9 Method 9: One-Pot Strategies 371
29.16.2.1.10 Method 10: Regioselective and Other Acceptor-Reactivity-Based Concepts 384
29.16.2.1.11 Method 11: Polymer-Supported Synthesis 390
29.16.2.1.11.1 Variation 1: Automated Synthesis 404
29.16.2.1.12 Method 12: Fluorous Tag Supported, Ionic Liquid Supported, and Microreactor Synthesis 408
29.16.2.1.13 Method 13: Surface-Tethered Synthesis 421
29.16.2.1.14 Method 14: Enzymatic Synthesis 423
29.16.2.1.14.1 Variation 1: Using Glycosyltransferases 423
29.16.2.1.14.2 Variation 2: Using Glycosidases (Hydrolases) 428
29.17 Product Class 17: Acyclic Hemiacetals, Lactols, and Carbonyl Hydrates 444
29.17.1 Product Subclass 1: Acyclic Hemiacetals 444
29.17.1.1 Synthesis of Product Subclass 1 444
29.17.1.1.1 Method 1: Synthesis from Aldehydes or Ketones by Addition of Alcohols 444
29.17.1.1.2 Method 2: Reduction of Esters 445
29.17.1.1.3 Method 3: Addition of Carbon Nucleophiles to Esters 446
29.17.1.1.3.1 Variation 1: Addition of Nucleophiles Bearing Stabilizing Groups 446
29.17.1.1.3.2 Variation 2: Addition of Nucleophiles Bearing Stabilizing Groups to Esters Bearing Stabilizing Groups 447
29.17.2 Product Subclass 2: Lactols 448
29.17.2.1 Synthesis of Product Subclass 2 449
29.17.2.1.1 Method 1: Reduction of Lactones 449
29.17.2.1.1.1 Variation 1: Using Diisobutylaluminum Hydride 449
29.17.2.1.1.2 Variation 2: Using Other Aluminum Hydride Reagents 450
29.17.2.1.1.3 Variation 3: Metal Hydride Catalyzed Hydrosilylation 453
29.17.2.1.1.4 Variation 4: Using Borohydride Reagents 455
29.17.2.1.2 Method 2: Addition of Carbon Nucleophiles to Lactones 456
29.17.2.1.2.1 Variation 1: Addition of Preformed Alkylmetal Reagents to Lactones 456
29.17.2.1.2.2 Variation 2: Barbier Additions to Lactones 463
29.17.2.1.3 Method 3: Oxidation of Diols 464
29.17.2.1.3.1 Variation 1: By Selective Oxidation of a Primary Hydroxy Group 465
29.17.2.1.3.2 Variation 2: By Selective Oxidation of a Secondary Hydroxy Group 468
29.17.2.1.3.3 Variation 3: By Selective Oxidation of Allylic and Benzylic Hydroxy Groups 469
29.17.2.1.4 Method 4: Reduction of Dicarbonyl Compounds 470
29.17.2.1.5 Method 5: Addition of Carbon Nucleophiles to Dicarbonyl Compounds 473
29.17.2.1.6 Method 6: Deprotection of Protected Cyclic Hemiacetals 476
29.17.2.1.6.1 Variation 1: Deprotection of O-Alkyl Lactols 476
29.17.2.1.6.2 Variation 2: Deprotection of O-Acyl Lactols 478
29.17.2.1.6.3 Variation 3: Deprotection of O-Silyl Lactols 479
29.17.2.1.7 Method 7: Synthesis From Enol Ethers 480
29.17.2.1.7.1 Variation 1: Acid-Catalyzed Hydration of Enol Ethers 480
29.17.2.1.7.2 Variation 2: Oxidation of Enol Ethers 481
29.17.2.1.8 Method 8: Oxidation of Cyclic Ethers 485
29.17.3 Product Subclass 3: Carbonyl Hydrates 486
29.17.3.1 Synthesis of Product Subclass 3 487
29.17.3.1.1 Method 1: Hydration of Carbonyl Compounds 487
29.17.3.1.1.1 Variation 1: Synthesis from Carbonyl Compounds Bearing Electron-Withdrawing Groups 487
29.17.3.1.1.2 Variation 2: Synthesis of Carbonyl Hydrates Stabilized by Hydrogen Bonding 490
29.17.3.1.1.3 Variation 3: Synthesis from Strained Ketones 491
29.17.3.1.2 Method 2: Oxidation of Activated Methyl or Methylene Groups 493
29.17.3.1.2.1 Variation 1: Oxidation Using Dimethyldioxirane 493
29.17.3.1.2.2 Variation 2: Oxidation Using Selenium Dioxide 493
29.17.3.1.2.3 Variation 3: Other Oxidations 495
29.18 Product Class 18: 1,1-Diacyloxy Compounds 502
29.18.1 Synthesis of Product Class 18 503
29.18.1.1 Acylation of Carbonyl Compounds 503
29.18.1.1.1 Method 1: Acylation of Aldehydes 503
29.18.1.1.1.1 Variation 1: Using a Lewis Acid Catalyst 503
29.18.1.1.1.2 Variation 2: In the Absence of a Catalyst 505
29.18.1.1.2 Method 2: Acylation of Ketones 506
29.18.1.1.2.1 Variation 1: Synthesis of Meldrum's Acid Using a Diacid and a Ketone 506
29.18.1.1.2.2 Variation 2: Using an Oxo Acid 508
29.18.1.1.3 Method 3: Synthesis from 1-Acyloxy-1-hydroxy Compounds, Carbonyl Hydrates, or Vinyl Esters 509
29.18.1.2 Alkylation of Carboxy Groups 513
29.18.1.2.1 Method 1: Synthesis Using Hal/Hal Acetal Electrophiles 513
29.18.1.2.2 Method 2: Synthesis Using O/Hal Acetal Electrophiles 513
29.18.1.3 Oxidative Methods 515
29.18.1.3.1 Method 1: Synthesis Using Single-Electron-Transfer Reagents 515
29.18.1.3.1.1 Variation 1: Oxidation of Benzylic Methyl and Methylene Groups 515
29.18.1.3.2 Method 2: Other Oxidations 516
29.18.1.3.2.1 Variation 1: Baeyer–Villiger Oxidation of a-Acyloxy Ketones 516
29.18.1.3.2.2 Variation 2: Oxidation of Furan Derivatives 517
29.18.1.4 Synthesis from Propargyl Esters 520
Author Index 524
Abbreviations 548
List of All Volumes 554
7.6.5.6 Aryl Grignard Reagents (Update 2010)
H. Yorimitsu
General Introduction
The conventional preparation of aryl Grignard reagents from aryl halides and magnesium metal still remains the most important and convenient available method. However, an improved Grignard method was reported in 2008 utilizing lithium chloride as an additive (see ▶ Section 7.6.5.6.1). Recently, halogen–magnesium exchange between aryl halides and alkyl Grignard reagents has been attracting increasing attention as the exchange allows for preparation of functionalized aryl Grignard reagents such as cyano- and carbonyl-substituted species (see ▶ Section 7.6.5.6.2). Furthermore, deprotonation assisted by a directing group is also emerging as a useful method for the preparation of functionalized aryl Grignard reagents (see ▶ Section 7.6.5.6.3).
7.6.5.6.1 Method 1: Synthesis by Reaction of Aryl Halides and Magnesium in the Presence of Lithium Chloride
A critical drawback of the conventional method for obtaining Grignard reagents is the requirement for higher temperatures, in the region of 30–60°C, conditions which many functional groups are unable to survive. The presence of lithium chloride has proved to promote the formation of aryl Grignard reagents, providing a milder method for the preparation of a variety of functionalized aryl Grignard species (▶ Table 1).[1] The lithium chloride mediated magnesiation requires that the magnesium should be activated with diisobutylaluminum hydride (1 mol%), and the method is powerful enough to allow the use of aryl chlorides as starting materials as well as to effect the dimagnesiation of dihaloarenes. It is worth noting that the aryl Grignard reagents complexed with lithium chloride exhibit a higher degree of reactivity toward electrophiles than the conventional aryl Grignard reagents. The functionalized Grignard reagents obtained by this procedure can participate in nucleophilic addition to carbonyl groups as well as in catalytic cross-coupling reactions.
▶ Table 1 Preparation of Arylmagnesium Halides Complexed with Lithium Chloride by Direct Insertion of Magnesium[1]
| Entry | Starting Material | Conditions | Product | Ref |
|---|
| 1 | DIBAL-H (cat.), Mg, LiCl, THF, 25°C, 30 min | [1] |
| 2 | DIBAL-H (cat.), Mg, LiCl, THF, –50°C, 3 h | [1] |
| 3 | DIBAL-H (cat.), Mg, LiCl, THF, 0–25°C, 16 h | [1] |
(2-Cyanophenyl)magnesium Bromide–Lithium Chloride Complex (▶ Table 1, Entry 1):[1]
Mg turnings (0.12 g, 5 mmol) were placed in a dry, argon-flushed Schlenk flask equipped with a magnetic stirrer and a septum. A 0.50 M soln of LiCl in THF (5.0 mL, 2.5 mmol) was added, followed by 0.1 M DIBAL-H in THF (0.2 mL, 0.02 mmol) to activate the Mg. The mixture was stirred for 5 min and 2-BrC6H4CN (0.36 g, 2.0 mmol) was then added in one portion at 25°C. The mixture was stirred for 30 min and then cannulated to a new Schlenk flask for reaction with an electrophile.
7.6.5.6.2 Method 2: Synthesis by Halogen–Magnesium Exchange with Alkyl Grignard Reagents
Since the discovery of isopropylmagnesium chloride–lithium chloride complex (1) as an extremely powerful reagent for halogen–magnesium exchange, the process has become one of the most reliable and efficient methods for preparing functionalized aryl Grignard reagents, such as (5-bromo-3-pyridyl)magnesium chloride–lithium chloride complex (2, Ar1 = 5-bromo-3-pyridyl) (▶ Scheme 1).[2] The halogen–magnesium exchange proceeds within a convenient range of temperatures (–15 to 25°C) and is applicable to large-scale preparations. It is thus outstandingly synthetically useful and, although complex 1 is readily prepared from 2-chloropropane, magnesium turnings, and lithium chloride, it is now commercially available.
▶ Scheme 1 Halogen–Magnesium Exchange with Isopropylmagnesium Chloride–Lithium Chloride Complex[2]
| Ar1 | Conditions | Ref |
|---|
| 4-NCC6H4 | THF, 0°C, 2 h | [2] |
| 2-iPrO2CC6H4 | THF/DMPU, –10°C, 3 h | [2] |
| 2-BrC6H4 | THF, –15°C, 2 h | [2] |
| 5-bromo-3-pyridyl | THF, –10°C, 15 min | [2] |
Isopropylmagnesium Chloride–Lithium Chloride Complex (1):[2]
Mg turnings (2.7 g, 0.11 mol) and anhyd LiCl (4.24 g, 0.10 mol) were placed in a flask under argon. THF (50 mL) was added, followed by slow addition of a soln of iPrCl (7.85 g, 0.10 mol) in THF (50 mL) at rt. The reaction started within a few minutes and, after the addition, the mixture was stirred for 12 h at ambient temperature. The resulting gray soln was transferred by cannula into another flask under argon to remove the remaining excess Mg. The yield of complex 1 was determined to be 95–98%.
(5-Bromo-3-pyridyl)magnesium Chloride–Lithium Chloride Complex (2, Ar1 = 5-Bromo-3-pyridyl):[2]
A 10-mL flask equipped with a magnetic stirrer and a septum was charged with a 1.05 M soln of complex 1 in THF (1.0 mL, 1.05 mmol) under argon. 3,5-Dibromopyridine (0.24 g, 1.0 mmol) was added to this mixture in one portion at –15°C. The reaction temperature was increased to –10°C and the bromine–magnesium exchange was complete in 15 min.
7.6.5.6.2.1 Variation 1: Synthesis by Halogen–Magnesium Exchange with Lithium Triorganomagnesates
Lithium triorganomagnesates are effective reagents for halogen–magnesium exchange.[3–6] The magnesium “ate” complexes are prepared by mixing an alkylmagnesium halide with 2 equivalents of an alkyllithium reagent. The reactivity is as high as that of the corresponding isopropylmagnesium chloride complex (see ▶ Section 7.6.5.6.2), and the reagents are reliable enough to use on an industrial scale.[5,6] There are many examples of magnesate-mediated halogen–magnesium exchange in modern organic synthesis.[7–10] Although all of the alkyl groups on the magnesate are potentially able to engage in exchange, as in the synthesis of triarylmagnesate 3,[10] in many cases only one of the three groups participates to give dialkyl(aryl)magnesates such as 4[3] (▶ Scheme 2).
Lithium Tris(quinolin-3-yl)magnesate (3):[10]
A 1.6 M soln of BuLi in hexanes (0.81 mL, 1.3 mmol) was added to a soln prepared from 2.0 M BuMgCl in Et2O (0.33 mL, 0.65 mmol) and toluene (2 mL) at –10°C. After the mixture had been stirred for 1 h at –10°C, a soln of 3-bromoquinoline (0.23 mL, 1.7 mmol) in toluene (2 mL) was added at –30°C. The mixture was stirred for 2.5 h at –10°C to give the product.
Lithium Dibutyl[4-(dimethylamino)phenyl]magnesate (4):[3]
A 1.6 M soln of BuLi in hexane (1.5 mL, 2.4 mmol) was added to a soln prepared from 1.0 M BuMgBr in THF (1.2 mL, 1.2 mmol) and THF (2 mL) at 0°C. After the mixture had been stirred for 10 min, a soln of 4-Me2NC6H4Br (0.20 g, 1.0 mmol) in THF (2 mL) was added dropwise. Stirring for 30 min at 0°C led to the complete formation of the product.
7.6.5.6.3 Method 3: Synthesis by Deprotonative ortho-Magnesiation
Complexes of bulky magnesium amides with lithium chloride, such as (2,2,6,6-tetramethylpiperidin-1-yl)magnesium chloride–lithium chloride complex (5) and bis(2,2,6,6-tetramethylpiperidin-1-yl)magnesium–bis(lithium chloride) complex (6), have emerged as excellent reagents for deprotonative magnesiation (▶ Table 2).[11–15] Advantageously, the reagents are more reactive than simple (2,2,6,6-tetramethylpiperidin-1-yl)magnesium halides, and the resulting arylmagnesium reagents have milder reactivity compared with those generated by lithium 2,2,6,6-tetramethylpiperidide.
▶ Table 2 Direct Magnesiation with Magnesium Amide–Lithium Chloride Complexes[11,13,15]
| Entry | Starting Material | Amide Complex | Conditions | Product | Ref |
|---|
| 1 | THF, 25°C, 2 h | [11] |
| 2 | THF, 25°C, 1... |
| Erscheint lt. Verlag | 14.5.2014 |
|---|---|
| Reihe/Serie | Science of Synthesis |
| Verlagsort | Stuttgart |
| Sprache | englisch |
| Themenwelt | Naturwissenschaften ► Chemie ► Organische Chemie |
| Technik | |
| Schlagworte | Acyclic Hemiacetals • Acyclic O/O Acetals • Alkoxides • Alkyl Grignard Reagents • Aryl Grignard Reagents • Carbonyl Hydrates • Carboxylates • Chemie • Chemische Synthese • chemistry of organic compound • chemistry reference work • chemistry synthetic methods • compound organic synthesis • Diacycloxy Compounds • Dioxetanes • Dioxolanes • Disaccharides • functional groups • Glycosyl Oxygen Compounds • Lactols • Magnesium Amides • Magnesium Halides • Magnesium Oxide • Mechanism • Method • methods in organic synthesis • methods peptide synthesis • Oligosaccharides • Organic Chemistry • organic chemistry reactions • organic chemistry review • organic chemistry synthesis • organic method • organic reaction • organic reaction mechanism • Organic Syntheses • organic synthesis • organic synthesis reference work • Organisch-chemische Synthese • Organische Chemie • oxazoles • Peptide synthesis • Practical • practical organic chemistry • Reactions • reference work • Review • review organic synthesis • review synthetic methods • Spiroketals • sprioketals • Synthese • Synthetic chemistry • Synthetic Methods • Synthetic Organic Chemistry • synthetic transformation |
| ISBN-10 | 3-13-178661-2 / 3131786612 |
| ISBN-13 | 978-3-13-178661-6 / 9783131786616 |
| Haben Sie eine Frage zum Produkt? |
PDF (Wasserzeichen)Größe: 4,6 MB
DRM: Digitales Wasserzeichen
Dieses eBook enthält ein digitales Wasserzeichen und ist damit für Sie personalisiert. Bei einer missbräuchlichen Weitergabe des eBooks an Dritte ist eine Rückverfolgung an die Quelle möglich.
Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen dafür einen PDF-Viewer - z.B. den Adobe Reader oder Adobe Digital Editions.
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen dafür einen PDF-Viewer - z.B. die kostenlose Adobe Digital Editions-App.
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
EPUB (Wasserzeichen)Größe: 19,6 MB
DRM: Digitales Wasserzeichen
Dieses eBook enthält ein digitales Wasserzeichen und ist damit für Sie personalisiert. Bei einer missbräuchlichen Weitergabe des eBooks an Dritte ist eine Rückverfolgung an die Quelle möglich.
Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen dafür die kostenlose Software Adobe Digital Editions.
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen dafür eine kostenlose App.
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
aus dem Bereich
