1 - Science of Synthesis: Knowledge Updates 2010/3 [Seite 1]
1.1 - Title page [Seite 5]
1.2 - Imprint [Seite 7]
1.3 - Preface [Seite 8]
1.4 - Abstracts [Seite 10]
1.5 - Overview [Seite 16]
1.6 - Table of Contents [Seite 18]
1.7 - Volume 7: Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be ··· Ba) [Seite 28]
1.7.1 - 7.6 Product Class 6: Magnesium Compounds [Seite 28]
1.7.1.1 - 7.6.5.6 Aryl Grignard Reagents [Seite 28]
1.7.1.1.1 - 7.6.5.6.1 Method 1: Synthesis by Reaction of Aryl Halides and Magnesium in the Presence of Lithium Chloride [Seite 28]
1.7.1.1.2 - 7.6.5.6.2 Method 2: Synthesis by Halogen-Magnesium Exchange with Alkyl Grignard Reagents [Seite 29]
1.7.1.1.2.1 - 7.6.5.6.2.1 Variation 1: Synthesis by Halogen-Magnesium Exchange with Lithium Triorganomagnesates [Seite 30]
1.7.1.1.3 - 7.6.5.6.3 Method 3: Synthesis by Deprotonative ortho-Magnesiation [Seite 31]
1.7.1.1.4 - 7.6.5.6.4 Method 4: Application to Synthesis of Biaryls by Dimerization [Seite 32]
1.7.1.1.5 - 7.6.5.6.5 Method 5: Application to Synthesis of Amines [Seite 33]
1.7.1.1.6 - 7.6.5.6.6 Method 6: Application to Addition to C--C Multiple Bonds Bearing a Directing Group [Seite 34]
1.7.1.1.7 - 7.6.5.6.7 Method 7: Application to Transmetalations with Metal Halides [Seite 34]
1.7.1.1.8 - 7.6.5.6.8 Method 8: Application to Addition to Carbonyl Compounds [Seite 35]
1.7.1.1.8.1 - 7.6.5.6.8.1 Variation 1: Highly Efficient Addition of Lithium Triphenylmagnesate to Benzophenone [Seite 35]
1.7.1.1.8.2 - 7.6.5.6.8.2 Variation 2: Zinc(II)-Catalyzed Addition of Aryl Grignard Reagents to Carbonyl Species [Seite 35]
1.7.1.2 - 7.6.10.9 Alkyl Grignard Reagents [Seite 38]
1.7.1.2.1 - 7.6.10.9.1 Method 1: Synthesis by Halogen-Magnesium Exchange [Seite 38]
1.7.1.2.1.1 - 7.6.10.9.1.1 Variation 1: Synthesis by Sulfoxide-Magnesium Exchange [Seite 41]
1.7.1.2.2 - 7.6.10.9.2 Method 2: Synthesis by Carbomagnesiation of C--C Multiple Bonds [Seite 42]
1.7.1.2.3 - 7.6.10.9.3 Method 3: Application to Addition to Carbonyl Compounds [Seite 43]
1.7.1.2.3.1 - 7.6.10.9.3.1 Variation 1: Highly Efficient Addition of Lithium Trialkylmagnesates to Acetophenone [Seite 43]
1.7.1.2.3.2 - 7.6.10.9.3.2 Variation 2: Zinc(II)-Catalyzed Addition of Alkyl Grignard Reagents to Carbonyl Groups [Seite 44]
1.7.1.3 - 7.6.12.13 Magnesium Halides [Seite 48]
1.7.1.3.1 - 7.6.12.13.1 Method 1: Applications of Magnesium Fluoride [Seite 48]
1.7.1.3.1.1 - 7.6.12.13.1.1 Variation 1: Magnesium Fluoride Catalyzed Knoevenagel Reactions [Seite 48]
1.7.1.3.1.2 - 7.6.12.13.1.2 Variation 2: Magnesium Fluoride/Chiral Phosphoric Acid Catalyzed Friedel-Crafts Reactions [Seite 49]
1.7.1.3.2 - 7.6.12.13.2 Method 2: Applications of Magnesium Chloride as a Lewis Acid [Seite 49]
1.7.1.3.2.1 - 7.6.12.13.2.1 Variation 1: Magnesium Chloride Promoted Claisen Reactions [Seite 50]
1.7.1.3.2.2 - 7.6.12.13.2.2 Variation 2: Magnesium Chloride/Potassium Borohydride Promoted Reductions [Seite 50]
1.7.1.3.3 - 7.6.12.13.3 Method 3: Applications of Other Magnesium Halides as Lewis Acids [Seite 51]
1.7.1.3.3.1 - 7.6.12.13.3.1 Variation 1: Reaction of Organometallics in the Presence of Magnesium Bromide [Seite 51]
1.7.1.3.3.2 - 7.6.12.13.3.2 Variation 2: Magnesium Halide Promoted Dipolar Cycloaddition Reactions [Seite 52]
1.7.1.3.4 - 7.6.12.13.4 Method 4: Applications of Magnesium Halide/Base Systems to Enolate Formation and Subsequent Addition Reactions [Seite 52]
1.7.1.3.5 - 7.6.12.13.5 Method 5: Applications of Magnesium Halides in Morita-Baylis-Hillman Reactions [Seite 53]
1.7.1.3.6 - 7.6.12.13.6 Method 6: Applications of Magnesium Iodide in Ring-Expansion Reactions [Seite 55]
1.7.1.4 - 7.6.13.17 Magnesium Oxide, Alkoxides, and Carboxylates [Seite 58]
1.7.1.4.1 - 7.6.13.17.1 Method 1: Applications of Magnesium Oxide [Seite 58]
1.7.1.4.2 - 7.6.13.17.2 Method 2: Applications of Magnesium Methoxide as a Base [Seite 59]
1.7.1.4.3 - 7.6.13.17.3 Method 3: Applications of Magnesium Alkoxides to the Oppenauer Oxidation [Seite 60]
1.7.1.4.4 - 7.6.13.17.4 Method 4: Applications of Magnesium Alkoxides in Diastereo- and Enantioselective Reactions [Seite 61]
1.7.1.4.5 - 7.6.13.17.5 Method 5: Applications of Magnesium Alkoxides in Elimination Reactions [Seite 62]
1.7.1.4.6 - 7.6.13.17.6 Method 6: Applications of Magnesium Carboxylates [Seite 64]
1.7.1.4.7 - 7.6.13.17.7 Method 7: Applications of Magnesium Monoperoxyphthalate [Seite 65]
1.7.1.5 - 7.6.14 Product Subclass 14: Magnesium Amides [Seite 68]
1.7.1.5.1 - Synthesis of Product Subclass 14 [Seite 68]
1.7.1.5.1.1 - 7.6.14.1 Method 1: Synthesis of Methylmagnesium N-Cyclohexyl-N-isopropylamide [Seite 68]
1.7.1.5.1.2 - 7.6.14.2 Method 2: Synthesis of (2,2,6,6-Tetramethylpiperidino)magnesium Chloride-Lithium Chloride Complex [Seite 69]
1.7.1.5.1.3 - 7.6.14.3 Method 3: Synthesis of Magnesium Bis(diisopropylamide) [Seite 69]
1.7.1.5.1.4 - 7.6.14.4 Method 4: Synthesis of Magnesium Bis(2,2,6,6-tetramethylpiperidide) [Seite 70]
1.7.1.5.1.4.1 - 7.6.14.4.1 Variation 1: Synthesis of Magnesium Bis(2,2,6,6-tetramethylpiperidide)-Bis(lithium chloride) Complex [Seite 70]
1.7.1.5.1.5 - 7.6.14.5 Method 5: Synthesis of Other Magnesium Bis(amide)s [Seite 71]
1.7.1.5.1.6 - 7.6.14.6 Method 6: Synthesis of Chiral Magnesium Bis(dialkylamide)s [Seite 71]
1.7.1.5.2 - Applications of Product Subclass 14 in Organic Synthesis [Seite 72]
1.7.1.5.2.1 - 7.6.14.7 Method 7: Reactions Involving Methylmagnesium N-Cyclohexyl-N-isopropylamide [Seite 72]
1.7.1.5.2.2 - 7.6.14.8 Method 8: Reactions Involving (Diisopropylamino)magnesium Bromide [Seite 73]
1.7.1.5.2.3 - 7.6.14.9 Method 9: Reactions Involving (2,2,6,6-Tetramethylpiperidino)magnesium Chloride-Lithium Chloride Complex [Seite 73]
1.7.1.5.2.4 - 7.6.14.10 Method 10: Reactions Involving Magnesium Bis(diisopropylamide) [Seite 75]
1.7.1.5.2.5 - 7.6.14.11 Method 11: Reactions Involving Magnesium Bis(2,2,6,6-tetramethylpiperidide) [Seite 76]
1.7.1.5.2.6 - 7.6.14.12 Method 12: Reactions Involving Magnesium Bis(2,2,6,6-tetramethylpiperidide)-Bis(lithium chloride) Complex [Seite 78]
1.7.1.5.2.7 - 7.6.14.13 Method 13: Reactions Involving Other Magnesium Bis(amide)s [Seite 79]
1.7.1.5.2.8 - 7.6.14.14 Method 14: Reactions Involving Chiral Magnesium Bis(dialkylamide)s [Seite 80]
1.8 - Volume 11: Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom [Seite 84]
1.8.1 - 11.12 Product Class 12: Oxazoles [Seite 84]
1.8.1.1 - 11.12.5 Oxazoles [Seite 84]
1.8.1.1.1 - 11.12.5.1 Synthesis by Ring-Closure Reactions [Seite 85]
1.8.1.1.1.1 - 11.12.5.1.1 By Formation of One O--C and One N--C Bond [Seite 85]
1.8.1.1.1.1.1 - 11.12.5.1.1.1 Fragments O--C--N and C--C [Seite 85]
1.8.1.1.1.1.1.1 - 11.12.5.1.1.1.1 Method 1: From Vinyl Halides and Amides [Seite 85]
1.8.1.1.1.1.2 - 11.12.5.1.1.2 Fragments O--C--C and C--N [Seite 87]
1.8.1.1.1.1.2.1 - 11.12.5.1.1.2.1 Method 1: From Carbonyl Compounds and Nitriles [Seite 87]
1.8.1.1.1.1.2.2 - 11.12.5.1.1.2.2 Method 2: From Acylcarbenes and Nitriles [Seite 92]
1.8.1.1.1.1.2.3 - 11.12.5.1.1.2.3 Method 3: From Benzylamines and 1,3-Dicarbonyl Compounds [Seite 95]
1.8.1.1.1.1.2.4 - 11.12.5.1.1.2.4 Method 4: From Amides and Propargylic Alcohols [Seite 96]
1.8.1.1.1.1.3 - 11.12.5.1.1.3 Fragments N--C--C and C--O [Seite 97]
1.8.1.1.1.1.3.1 - 11.12.5.1.1.3.1 Method 1: From 2-Amino-1-bromoethanesulfonamide and Acid Chlorides [Seite 97]
1.8.1.1.1.1.4 - 11.12.5.1.1.4 Fragments O--C--C--N and C [Seite 99]
1.8.1.1.1.1.4.1 - 11.12.5.1.1.4.1 Method 1: From Nitroethanones and Orthobenzoate [Seite 99]
1.8.1.1.1.1.4.2 - 11.12.5.1.1.4.2 Method 2: From a-Cyano-ß-hydroxy Enamines and Orthoformate [Seite 100]
1.8.1.1.1.2 - 11.12.5.1.2 By Formation of One O--C and One C--C Bond [Seite 101]
1.8.1.1.1.2.1 - 11.12.5.1.2.1 Fragments C--N--C and C--O [Seite 101]
1.8.1.1.1.2.1.1 - 11.12.5.1.2.1.1 Method 1: From Isocyanides and Acyl Chlorides [Seite 101]
1.8.1.1.1.3 - 11.12.5.1.3 By Formation of One O--C Bond [Seite 103]
1.8.1.1.1.3.1 - 11.12.5.1.3.1 Fragment O--C--N--C--C [Seite 103]
1.8.1.1.1.3.1.1 - 11.12.5.1.3.1.1 Method 1: Cyclodehydration of a-Acylamino Aldehydes or Ketones [Seite 103]
1.8.1.1.1.3.1.2 - 11.12.5.1.3.1.2 Method 2: From (Acylamino)acetaldehyde Dimethyl Acetals [Seite 105]
1.8.1.1.1.3.1.3 - 11.12.5.1.3.1.3 Method 3: From Oxazolones via Friedel-Crafts Acylation and Subsequent Cyclization [Seite 106]
1.8.1.1.1.3.1.4 - 11.12.5.1.3.1.4 Method 4: Oxazoles from N-Propargylamides [Seite 107]
1.8.1.1.1.3.1.5 - 11.12.5.1.3.1.5 Method 5: From Enamides [Seite 120]
1.8.1.1.1.3.1.6 - 11.12.5.1.3.1.6 Method 6: From Amides and Diazocarbonyl Compounds [Seite 122]
1.8.1.1.1.3.2 - 11.12.5.1.3.2 Fragment O--C--C--N--C [Seite 124]
1.8.1.1.1.3.2.1 - 11.12.5.1.3.2.1 Method 1: Oxidative Cyclization of Schiff Bases Derived from Glycine Methyl Ester [Seite 124]
1.8.1.1.1.3.2.2 - 11.12.5.1.3.2.2 Method 2: From Isocyanoacetamides and Imines [Seite 124]
1.8.1.1.1.3.2.3 - 11.12.5.1.3.2.3 Method 3: Trifluoromethanesulfonic Anhydride Mediated Cyclocondensation of N-Acyl Amino Acid Esters [Seite 126]
1.8.1.1.1.3.2.4 - 11.12.5.1.3.2.4 Method 4: From Aldehydes and Isocyanides [Seite 127]
1.8.1.1.2 - 11.12.5.2 Aromatization [Seite 129]
1.8.1.1.2.1 - 11.12.5.2.1 Method 1: By Dehydrogenation of Dihydrooxazoles [Seite 129]
1.8.1.1.2.2 - 11.12.5.2.2 Method 2: Elimination of Hydrogen Chloride from Dihydrooxazoles [Seite 130]
1.8.1.1.3 - 11.12.5.3 Synthesis by Substituent Modification [Seite 131]
1.8.1.1.3.1 - 11.12.5.3.1 Substitution Reactions [Seite 131]
1.8.1.1.3.1.1 - 11.12.5.3.1.1 Method 1: Reactions of Metalated Oxazoles with Electrophiles [Seite 131]
1.8.1.1.3.1.2 - 11.12.5.3.1.2 Method 2: Oxazoles via Substitution of Leaving Groups through Transition-Metal-Catalyzed Reactions [Seite 137]
1.8.1.1.3.1.3 - 11.12.5.3.1.3 Method 3: Coupling Reactions of Oxazolones [Seite 140]
1.8.1.1.4 - 11.12.5.4 Applications of Oxazoles in Organic Synthesis [Seite 141]
1.9 - Volume 29: Acetals: Hal/X and O/O, S, Se, Te [Seite 148]
1.9.1 - 29.6 Product Class 6: Acyclic and Semicyclic O/O Acetals [Seite 148]
1.9.1.1 - 29.6.2 Acyclic and Semicyclic O/O Acetals [Seite 148]
1.9.1.1.1 - 29.6.2.1 Synthesis from Compounds of Higher Oxidation State [Seite 148]
1.9.1.1.1.1 - 29.6.2.1.1 Method 1: Synthesis by Cycloaddition of Ketene Acetals [Seite 148]
1.9.1.1.1.1.1 - 29.6.2.1.1.1 Variation 1: From Ketene Acetals and Alkenes via Cycloaddition [Seite 148]
1.9.1.1.1.1.2 - 29.6.2.1.1.2 Variation 2: From Ketene Acetals and Alkynes via Cycloaddition [Seite 149]
1.9.1.1.2 - 29.6.2.2 Synthesis from Compounds of the Same Oxidation State [Seite 149]
1.9.1.1.2.1 - 29.6.2.2.1 Method 1: Synthesis from Hal/OR Acetals [Seite 149]
1.9.1.1.2.2 - 29.6.2.2.2 Method 2: Synthesis from Aldehydes or Ketones and Alcohols [Seite 150]
1.9.1.1.2.2.1 - 29.6.2.2.2.1 Variation 1: From Alcohols without Removal of Water [Seite 151]
1.9.1.1.2.2.2 - 29.6.2.2.2.2 Variation 2: From Alcohols with Removal of Water by Physical Methods [Seite 153]
1.9.1.1.2.2.3 - 29.6.2.2.2.3 Variation 3: From Alcohols with Removal of Water by Chemical Means [Seite 153]
1.9.1.1.2.2.4 - 29.6.2.2.2.4 Variation 4: From Hemiacetals and Alkylating Agents [Seite 155]
1.9.1.1.2.2.5 - 29.6.2.2.2.5 Variation 5: From Alcohols and Alkenyl Ketones [Seite 155]
1.9.1.1.2.3 - 29.6.2.2.3 Method 3: Synthesis from Aldehydes or Ketones and Alcohol Derivatives [Seite 155]
1.9.1.1.2.3.1 - 29.6.2.2.3.1 Variation 1: From Trialkyl Orthoformates [Seite 156]
1.9.1.1.2.3.2 - 29.6.2.2.3.2 Variation 2: From Other Acetals [Seite 158]
1.9.1.1.2.4 - 29.6.2.2.4 Method 4: Synthesis from Other O/O Acetals [Seite 158]
1.9.1.1.2.4.1 - 29.6.2.2.4.1 Variation 1: By Exchange of Both Alkoxy Groups [Seite 158]
1.9.1.1.2.4.2 - 29.6.2.2.4.2 Variation 2: By Exchange of One Alkoxy Group [Seite 159]
1.9.1.1.2.5 - 29.6.2.2.5 Method 5: Synthesis from Acetals with Other Heteroatoms [Seite 163]
1.9.1.1.2.5.1 - 29.6.2.2.5.1 Variation 1: From O/Se Acetals [Seite 163]
1.9.1.1.2.5.2 - 29.6.2.2.5.2 Variation 2: From S/S Acetals [Seite 164]
1.9.1.1.2.6 - 29.6.2.2.6 Method 6: Synthesis from Oximes [Seite 164]
1.9.1.1.2.7 - 29.6.2.2.7 Method 7: Synthesis from Heterosubstituted Alkenes [Seite 164]
1.9.1.1.2.7.1 - 29.6.2.2.7.1 Variation 1: From Acyclic Enol Ethers and Alcohols [Seite 165]
1.9.1.1.2.7.2 - 29.6.2.2.7.2 Variation 2: From Cyclic Enol Ethers and Alcohols [Seite 165]
1.9.1.1.2.7.3 - 29.6.2.2.7.3 Variation 3: From Allenyl Ethers and Alcohols [Seite 167]
1.9.1.1.2.7.4 - 29.6.2.2.7.4 Variation 4: Dimerization of Enol Ethers [Seite 168]
1.9.1.1.2.7.5 - 29.6.2.2.7.5 Variation 5: From Enol Ethers and Cyclic Carbonyl Ylides [Seite 169]
1.9.1.1.3 - 29.6.2.3 Synthesis from Compounds of Lower Oxidation State [Seite 170]
1.9.1.1.3.1 - 29.6.2.3.1 Method 1 : Synthesis from Heterosubstituted Alkanes [Seite 170]
1.9.1.1.3.1.1 - 29.6.2.3.1.1 Variation 1: From Alcohols [Seite 170]
1.9.1.1.3.1.2 - 29.6.2.3.1.2 Variation 2: From Alcohols and Ethers [Seite 171]
1.9.1.1.3.1.3 - 29.6.2.3.1.3 Variation 3: From Alcohols and Alkyl Halides [Seite 172]
1.9.1.1.3.2 - 29.6.2.3.2 Method 2: Synthesis from Alkynes with Electron-Withdrawing Substituents [Seite 172]
1.9.1.1.3.3 - 29.6.2.3.3 Method 3: Synthesis from Alkenes [Seite 173]
1.9.1.1.3.4 - 29.6.2.3.4 Method 4: Synthesis from Peroxy Esters [Seite 174]
1.9.2 - 29.7 Product Class 7: 1,3-Dioxetanes and 1,3-Dioxolanes [Seite 178]
1.9.2.1 - 29.7.3 1,3-Dioxetanes and 1,3-Dioxolanes [Seite 178]
1.9.2.1.1 - 29.7.3.1 1,3-Dioxetanes [Seite 178]
1.9.2.1.2 - 29.7.3.2 1,3-Dioxolanes [Seite 178]
1.9.2.1.2.1 - 29.7.3.2.1 Method 1: Synthesis by Formation of Two C--O Bonds [Seite 180]
1.9.2.1.2.1.1 - 29.7.3.2.1.1 Variation 1: Reactions of Carbonyl Compounds with 1,2-Diols [Seite 180]
1.9.2.1.2.1.2 - 29.7.3.2.1.2 Variation 2: Reactions of Acetals and Ketals with 1,2-Diols [Seite 182]
1.9.2.1.2.1.3 - 29.7.3.2.1.3 Variation 3: Reactions of Enol Ethers with 1,2-Diols [Seite 183]
1.9.2.1.2.1.4 - 29.7.3.2.1.4 Variation 4: Reactions of Carbonyl Compounds with 1,2-Bis(trimethylsilyl) Ethers [Seite 184]
1.9.2.1.2.1.5 - 29.7.3.2.1.5 Variation 5: Reactions of Epoxides with Ketones [Seite 185]
1.9.2.1.2.1.6 - 29.7.3.2.1.6 Variation 6: By Double Michael Addition of 1,2-Diols to Electron-Deficient Alkynes [Seite 186]
1.9.2.1.2.1.7 - 29.7.3.2.1.7 Variation 7: Reaction of 1,1-Dihalo Compounds with 1,2-Diols [Seite 188]
1.9.2.1.2.1.8 - 29.7.3.2.1.8 Variation 8: Reactions of Ketones and 2-Halo Alcohols [Seite 189]
1.9.2.1.2.2 - 29.7.3.2.2 Method 2: Synthesis by Formation of One C--O Bond [Seite 190]
1.9.2.1.2.2.1 - 29.7.3.2.2.1 Variation 1: From Monoprotected 1,2-Diols [Seite 190]
1.9.2.1.2.2.2 - 29.7.3.2.2.2 Variation 2: By Oxidation of Electron-Rich Arenes and Hetarenes and Cyclization [Seite 191]
1.9.2.1.2.2.3 - 29.7.3.2.2.3 Variation 3: By Cyclization of Hydroxy-Substituted Enol Ethers [Seite 191]
1.9.2.1.2.2.4 - 29.7.3.2.2.4 Variation 4: By Intramolecular Transacetalization [Seite 192]
1.9.2.1.2.2.5 - 29.7.3.2.2.5 Variation 5: Additions to Activated Alkenes [Seite 193]
1.9.2.1.2.3 - 29.7.3.2.3 Method 3: Exchange of Ligands on Existing Acetals [Seite 194]
1.9.2.1.2.3.1 - 29.7.3.2.3.1 Variation 1: Radical Reactions [Seite 194]
1.9.2.1.2.3.2 - 29.7.3.2.3.2 Variation 2: From Metalated Dioxolanes [Seite 194]
1.9.2.1.2.3.3 - 29.7.3.2.3.3 Variation 3: From Ortho Esters [Seite 195]
1.9.2.1.2.4 - 29.7.3.2.4 Method 4: Deprotection Reactions of 1,3-Dioxolanes [Seite 195]
1.9.2.1.2.5 - 29.7.3.2.5 Method 5: Applications of Chiral 1,3-Dioxolanes in Asymmetric Synthesis [Seite 196]
1.9.3 - 29.9 Product Class 9: Spiroketals [Seite 200]
1.9.3.1 - 29.9.2 Spiroketals [Seite 200]
1.9.3.1.1 - 29.9.2.1 Synthesis by Formation of Two C--O Bonds: Cyclization of Dihydroxy Ketones [Seite 200]
1.9.3.1.1.1 - 29.9.2.1.1 Method 1: Nucleophilic Addition to Aldehydes [Seite 201]
1.9.3.1.1.1.1 - 29.9.2.1.1.1 Variation 1: Using Dithiane-Stabilized Carbanions [Seite 201]
1.9.3.1.1.1.2 - 29.9.2.1.1.2 Variation 2: Using Lithiated Methoxyallene Followed by Heck Reaction [Seite 202]
1.9.3.1.1.2 - 29.9.2.1.2 Method 2: [3 + 2] Cycloaddition of Nitrile Oxides Followed by Dihydroisoxazole Hydrogenolysis [Seite 204]
1.9.3.1.1.3 - 29.9.2.1.3 Method 3: Reductive Cross Coupling Followed by Oxidative Cleavage [Seite 206]
1.9.3.1.1.4 - 29.9.2.1.4 Method 4: Radical Addition of Xanthates to Alkenes [Seite 208]
1.9.3.1.1.5 - 29.9.2.1.5 Method 5: Kulinkovich Cyclopropanation of Esters Followed by Cyclopropanol Ring Opening [Seite 210]
1.9.3.1.1.6 - 29.9.2.1.6 Method 6: Synthesis from Formyl Dianion Equivalents [Seite 211]
1.9.3.1.1.6.1 - 29.9.2.1.6.1 Variation 1: Using Tosylmethyl Isocyanide Followed by Hydrolysis [Seite 211]
1.9.3.1.1.6.2 - 29.9.2.1.6.2 Variation 2: Using Nitroalkanes Followed by Nef Reaction [Seite 213]
1.9.3.1.2 - 29.9.2.2 Synthesis by Formation of Two C--O Bonds: Synthesis from Other Precursors [Seite 214]
1.9.3.1.2.1 - 29.9.2.2.1 Method 1: Transition-Metal-Catalyzed Cyclizations [Seite 215]
1.9.3.1.2.1.1 - 29.9.2.2.1.1 Variation 1: Palladium-Catalyzed Alkyne Cycloisomerization [Seite 215]
1.9.3.1.2.1.2 - 29.9.2.2.1.2 Variation 2: Gold-Catalyzed Alkyne Cycloisomerization [Seite 217]
1.9.3.1.2.1.3 - 29.9.2.2.1.3 Variation 3: Alkyne Cycloisomerization Catalyzed by Other Metals [Seite 218]
1.9.3.1.2.1.4 - 29.9.2.2.1.4 Variation 4: Iron-Catalyzed Cyclization of Hydroxy Oxo Allylic Acetates [Seite 220]
1.9.3.1.2.2 - 29.9.2.2.2 Method 2: Oxidative Cyclization of Phenols [Seite 221]
1.9.3.1.2.3 - 29.9.2.2.3 Method 3: Oxidative Rearrangement of Alkyl Enol Ethers [Seite 223]
1.9.3.1.2.4 - 29.9.2.2.4 Method 4: Iodoetherification of Dihydroxyalkenes Followed by Dehydroiodination [Seite 224]
1.9.3.1.3 - 29.9.2.3 Synthesis by Formation of One C--O Bond and One C--C Bond [Seite 225]
1.9.3.1.3.1 - 29.9.2.3.1 Method 1: Cycloaddition Reactions [Seite 226]
1.9.3.1.3.1.1 - 29.9.2.3.1.1 Variation 1: Hetero-Diels-Alder Reactions of o-Quinomethanes [Seite 226]
1.9.3.1.3.1.2 - 29.9.2.3.1.2 Variation 2: [3 + 2] Cycloadditions [Seite 229]
1.9.3.1.3.2 - 29.9.2.3.2 Method 2: Metal-Catalyzed Cross Coupling [Seite 229]
1.9.3.1.3.3 - 29.9.2.3.3 Method 3: Propargyl Claisen Rearrangement [Seite 231]
1.9.3.1.4 - 29.9.2.4 Synthesis by Formation of One C--O Bond [Seite 232]
1.9.3.1.4.1 - 29.9.2.4.1 Method 1: Oxidative Insertion [Seite 232]
1.9.3.1.4.2 - 29.9.2.4.2 Method 2: Synthesis from Exocyclic Vinyl Ethers [Seite 234]
1.9.3.1.4.2.1 - 29.9.2.4.2.1 Variation 1: Using Metal Carbenoids [Seite 234]
1.9.3.1.4.2.2 - 29.9.2.4.2.2 Variation 2: Ring Expansion of Donor-Acceptor-Substituted Cyclopropanes [Seite 236]
1.9.3.1.4.3 - 29.9.2.4.3 Method 3: Oxidation of Furans [Seite 238]
1.9.3.1.4.3.1 - 29.9.2.4.3.1 Variation 1: Photooxygenation of Furans [Seite 238]
1.9.3.1.4.3.2 - 29.9.2.4.3.2 Variation 2: Other Oxidation Reagents [Seite 239]
1.9.3.1.4.4 - 29.9.2.4.4 Method 4: Lewis Acid Catalyzed 1,5-Hydride Transfer [Seite 240]
1.9.3.1.5 - 29.9.2.5 Synthesis by Formation of One C--C Bond [Seite 241]
1.9.3.1.5.1 - 29.9.2.5.1 Method 1: Reductive Cyclization of Cyano Acetals [Seite 241]
1.9.3.1.5.2 - 29.9.2.5.2 Method 2: [2 + 2 + 2] Cyclotrimerization [Seite 242]
1.9.3.1.6 - 29.9.2.6 Synthesis by Formation of Two C--O Bonds and One C--C Bond [Seite 243]
1.9.3.1.6.1 - 29.9.2.6.1 Method 1: Palladium-Catalyzed Three-Component Coupling [Seite 243]
1.9.3.1.7 - 29.9.2.7 Synthesis of Spiroepoxides and Related Small-Ring Spiroketals [Seite 245]
1.9.3.1.7.1 - 29.9.2.7.1 Method 1: Synthesis by Formation of Two C--O Bonds [Seite 245]
1.9.3.1.7.2 - 29.9.2.7.2 Method 2: Synthesis by Formation of Four C--O Bonds [Seite 246]
1.9.3.1.7.3 - 29.9.2.7.3 Method 3: Synthesis by Formation of One C--O Bond and One C--C Bond [Seite 247]
1.9.3.1.8 - 29.9.2.8 Synthesis of Trioxadispiroketals [Seite 248]
1.9.4 - 29.16 Product Class 16: Glycosyl Oxygen Compounds (Di- and Oligosaccharides) [Seite 256]
1.9.4.1 - 29.16.1 Product Subclass 1: Disaccharides [Seite 256]
1.9.4.1.1 - 29.16.1.1 Synthesis of Product Subclass 1 [Seite 259]
1.9.4.1.1.1 - 29.16.1.1.1 Method 1: Synthesis from Anomeric Halides [Seite 259]
1.9.4.1.1.1.1 - 29.16.1.1.1.1 Variation 1: From Fluorides [Seite 259]
1.9.4.1.1.1.2 - 29.16.1.1.1.2 Variation 2: From Chlorides and Bromides [Seite 261]
1.9.4.1.1.1.3 - 29.16.1.1.1.3 Variation 3: From Iodides [Seite 264]
1.9.4.1.1.2 - 29.16.1.1.2 Method 2: Synthesis from 1-Oxygen-Substituted Derivatives [Seite 266]
1.9.4.1.1.2.1 - 29.16.1.1.2.1 Variation 1: From Hemiacetals [Seite 266]
1.9.4.1.1.2.2 - 29.16.1.1.2.2 Variation 2: From O-Acyl, O-Carbonyl, and Related Compounds [Seite 268]
1.9.4.1.1.2.3 - 29.16.1.1.2.3 Variation 3: From O-Imidates [Seite 271]
1.9.4.1.1.2.4 - 29.16.1.1.2.4 Variation 4: From Phosphites, Phosphates, and Other O--P Derivatives [Seite 277]
1.9.4.1.1.2.5 - 29.16.1.1.2.5 Variation 5: From O-Sulfonyl Derivatives [Seite 280]
1.9.4.1.1.2.6 - 29.16.1.1.2.6 Variation 6: By O-Transglycosidation [Seite 280]
1.9.4.1.1.3 - 29.16.1.1.3 Method 3: Synthesis from 1-Sulfur-Substituted Derivatives [Seite 286]
1.9.4.1.1.3.1 - 29.16.1.1.3.1 Variation 1: From Alkylsulfanyl and Arylsulfanyl Glycosides (Thioglycosides) [Seite 286]
1.9.4.1.1.3.2 - 29.16.1.1.3.2 Variation 2: From Thioimidates [Seite 293]
1.9.4.1.1.3.3 - 29.16.1.1.3.3 Variation 3: From Sulfoxides, Sulfimides, and Sulfones [Seite 296]
1.9.4.1.1.3.4 - 29.16.1.1.3.4 Variation 4: From Xanthates and Related Derivatives [Seite 297]
1.9.4.1.1.3.5 - 29.16.1.1.3.5 Variation 5: From Thiocyanates and Other Thio Derivatives [Seite 298]
1.9.4.1.1.4 - 29.16.1.1.4 Method 4: Synthesis from Miscellaneous Glycosyl Donors [Seite 300]
1.9.4.1.1.4.1 - 29.16.1.1.4.1 Variation 1: From Ortho Esters and Dihydrooxazoles [Seite 300]
1.9.4.1.1.4.2 - 29.16.1.1.4.2 Variation 2: From 1,2-Dehydro and 1,2-Anhydro Derivatives [Seite 303]
1.9.4.1.1.4.3 - 29.16.1.1.4.3 Variation 3: From Seleno- and Telluroglycosides [Seite 307]
1.9.4.1.1.4.4 - 29.16.1.1.4.4 Variation 4: From 1-Diazirine Derivatives [Seite 309]
1.9.4.1.1.5 - 29.16.1.1.5 Method 5: Synthesis by Intramolecular and Indirect Methods [Seite 309]
1.9.4.2 - 29.16.2 Product Subclass 2: Oligosaccharides [Seite 317]
1.9.4.2.1 - 29.16.2.1 Synthesis of Product Subclass 2 [Seite 318]
1.9.4.2.1.1 - 29.16.2.1.1 Method 1: Linear Synthesis [Seite 318]
1.9.4.2.1.2 - 29.16.2.1.2 Method 2: Block Synthesis [Seite 321]
1.9.4.2.1.3 - 29.16.2.1.3 Method 3: Synthesis by Selective Activation [Seite 331]
1.9.4.2.1.4 - 29.16.2.1.4 Method 4: Synthesis by Two-Step Activation and In Situ Preactivation [Seite 334]
1.9.4.2.1.5 - 29.16.2.1.5 Method 5: Armed-Disarmed and Related Chemoselective Approaches [Seite 340]
1.9.4.2.1.5.1 - 29.16.2.1.5.1 Variation 1: Arming and Disarming with Neighboring Substituents [Seite 341]
1.9.4.2.1.5.2 - 29.16.2.1.5.2 Variation 2: Disarming with Remote Substituents [Seite 346]
1.9.4.2.1.5.3 - 29.16.2.1.5.3 Variation 3: Disarming by Torsional Effects [Seite 347]
1.9.4.2.1.5.4 - 29.16.2.1.5.4 Variation 4: Reactivity-Based Programmable Strategy [Seite 351]
1.9.4.2.1.5.5 - 29.16.2.1.5.5 Variation 5: Superdisarmed Building Blocks [Seite 353]
1.9.4.2.1.5.6 - 29.16.2.1.5.6 Variation 6: Superarmed Glycosyl Donors [Seite 355]
1.9.4.2.1.6 - 29.16.2.1.6 Method 6: The Active-Latent Approach [Seite 358]
1.9.4.2.1.7 - 29.16.2.1.7 Method 7: Steric Hindrance and Temporary Deactivation [Seite 360]
1.9.4.2.1.8 - 29.16.2.1.8 Method 8: Orthogonal and Semi-Orthogonal Strategies [Seite 366]
1.9.4.2.1.9 - 29.16.2.1.9 Method 9: One-Pot Strategies [Seite 371]
1.9.4.2.1.10 - 29.16.2.1.10 Method 10: Regioselective and Other Acceptor-Reactivity-Based Concepts [Seite 384]
1.9.4.2.1.11 - 29.16.2.1.11 Method 11: Polymer-Supported Synthesis [Seite 390]
1.9.4.2.1.11.1 - 29.16.2.1.11.1 Variation 1: Automated Synthesis [Seite 404]
1.9.4.2.1.12 - 29.16.2.1.12 Method 12: Fluorous Tag Supported, Ionic Liquid Supported, and Microreactor Synthesis [Seite 408]
1.9.4.2.1.13 - 29.16.2.1.13 Method 13: Surface-Tethered Synthesis [Seite 421]
1.9.4.2.1.14 - 29.16.2.1.14 Method 14: Enzymatic Synthesis [Seite 423]
1.9.4.2.1.14.1 - 29.16.2.1.14.1 Variation 1: Using Glycosyltransferases [Seite 423]
1.9.4.2.1.14.2 - 29.16.2.1.14.2 Variation 2: Using Glycosidases (Hydrolases) [Seite 428]
1.9.5 - 29.17 Product Class 17: Acyclic Hemiacetals, Lactols, and Carbonyl Hydrates [Seite 444]
1.9.5.1 - 29.17.1 Product Subclass 1: Acyclic Hemiacetals [Seite 444]
1.9.5.1.1 - 29.17.1.1 Synthesis of Product Subclass 1 [Seite 444]
1.9.5.1.1.1 - 29.17.1.1.1 Method 1: Synthesis from Aldehydes or Ketones by Addition of Alcohols [Seite 444]
1.9.5.1.1.2 - 29.17.1.1.2 Method 2: Reduction of Esters [Seite 445]
1.9.5.1.1.3 - 29.17.1.1.3 Method 3: Addition of Carbon Nucleophiles to Esters [Seite 446]
1.9.5.1.1.3.1 - 29.17.1.1.3.1 Variation 1: Addition of Nucleophiles Bearing Stabilizing Groups [Seite 446]
1.9.5.1.1.3.2 - 29.17.1.1.3.2 Variation 2: Addition of Nucleophiles Bearing Stabilizing Groups to Esters Bearing Stabilizing Groups [Seite 447]
1.9.5.2 - 29.17.2 Product Subclass 2: Lactols [Seite 448]
1.9.5.2.1 - 29.17.2.1 Synthesis of Product Subclass 2 [Seite 449]
1.9.5.2.1.1 - 29.17.2.1.1 Method 1: Reduction of Lactones [Seite 449]
1.9.5.2.1.1.1 - 29.17.2.1.1.1 Variation 1: Using Diisobutylaluminum Hydride [Seite 449]
1.9.5.2.1.1.2 - 29.17.2.1.1.2 Variation 2: Using Other Aluminum Hydride Reagents [Seite 450]
1.9.5.2.1.1.3 - 29.17.2.1.1.3 Variation 3: Metal Hydride Catalyzed Hydrosilylation [Seite 453]
1.9.5.2.1.1.4 - 29.17.2.1.1.4 Variation 4: Using Borohydride Reagents [Seite 455]
1.9.5.2.1.2 - 29.17.2.1.2 Method 2: Addition of Carbon Nucleophiles to Lactones [Seite 456]
1.9.5.2.1.2.1 - 29.17.2.1.2.1 Variation 1: Addition of Preformed Alkylmetal Reagents to Lactones [Seite 456]
1.9.5.2.1.2.2 - 29.17.2.1.2.2 Variation 2: Barbier Additions to Lactones [Seite 463]
1.9.5.2.1.3 - 29.17.2.1.3 Method 3: Oxidation of Diols [Seite 464]
1.9.5.2.1.3.1 - 29.17.2.1.3.1 Variation 1: By Selective Oxidation of a Primary Hydroxy Group [Seite 465]
1.9.5.2.1.3.2 - 29.17.2.1.3.2 Variation 2: By Selective Oxidation of a Secondary Hydroxy Group [Seite 468]
1.9.5.2.1.3.3 - 29.17.2.1.3.3 Variation 3: By Selective Oxidation of Allylic and Benzylic Hydroxy Groups [Seite 469]
1.9.5.2.1.4 - 29.17.2.1.4 Method 4: Reduction of Dicarbonyl Compounds [Seite 470]
1.9.5.2.1.5 - 29.17.2.1.5 Method 5: Addition of Carbon Nucleophiles to Dicarbonyl Compounds [Seite 473]
1.9.5.2.1.6 - 29.17.2.1.6 Method 6: Deprotection of Protected Cyclic Hemiacetals [Seite 476]
1.9.5.2.1.6.1 - 29.17.2.1.6.1 Variation 1: Deprotection of O-Alkyl Lactols [Seite 476]
1.9.5.2.1.6.2 - 29.17.2.1.6.2 Variation 2: Deprotection of O-Acyl Lactols [Seite 478]
1.9.5.2.1.6.3 - 29.17.2.1.6.3 Variation 3: Deprotection of O-Silyl Lactols [Seite 479]
1.9.5.2.1.7 - 29.17.2.1.7 Method 7: Synthesis From Enol Ethers [Seite 480]
1.9.5.2.1.7.1 - 29.17.2.1.7.1 Variation 1: Acid-Catalyzed Hydration of Enol Ethers [Seite 480]
1.9.5.2.1.7.2 - 29.17.2.1.7.2 Variation 2: Oxidation of Enol Ethers [Seite 481]
1.9.5.2.1.8 - 29.17.2.1.8 Method 8: Oxidation of Cyclic Ethers [Seite 485]
1.9.5.3 - 29.17.3 Product Subclass 3: Carbonyl Hydrates [Seite 486]
1.9.5.3.1 - 29.17.3.1 Synthesis of Product Subclass 3 [Seite 487]
1.9.5.3.1.1 - 29.17.3.1.1 Method 1: Hydration of Carbonyl Compounds [Seite 487]
1.9.5.3.1.1.1 - 29.17.3.1.1.1 Variation 1: Synthesis from Carbonyl Compounds Bearing Electron-Withdrawing Groups [Seite 487]
1.9.5.3.1.1.2 - 29.17.3.1.1.2 Variation 2: Synthesis of Carbonyl Hydrates Stabilized by Hydrogen Bonding [Seite 490]
1.9.5.3.1.1.3 - 29.17.3.1.1.3 Variation 3: Synthesis from Strained Ketones [Seite 491]
1.9.5.3.1.2 - 29.17.3.1.2 Method 2: Oxidation of Activated Methyl or Methylene Groups [Seite 493]
1.9.5.3.1.2.1 - 29.17.3.1.2.1 Variation 1: Oxidation Using Dimethyldioxirane [Seite 493]
1.9.5.3.1.2.2 - 29.17.3.1.2.2 Variation 2: Oxidation Using Selenium Dioxide [Seite 493]
1.9.5.3.1.2.3 - 29.17.3.1.2.3 Variation 3: Other Oxidations [Seite 495]
1.9.6 - 29.18 Product Class 18: 1,1-Diacyloxy Compounds [Seite 502]
1.9.6.1 - 29.18.1 Synthesis of Product Class 18 [Seite 503]
1.9.6.1.1 - 29.18.1.1 Acylation of Carbonyl Compounds [Seite 503]
1.9.6.1.1.1 - 29.18.1.1.1 Method 1: Acylation of Aldehydes [Seite 503]
1.9.6.1.1.1.1 - 29.18.1.1.1.1 Variation 1: Using a Lewis Acid Catalyst [Seite 503]
1.9.6.1.1.1.2 - 29.18.1.1.1.2 Variation 2: In the Absence of a Catalyst [Seite 505]
1.9.6.1.1.2 - 29.18.1.1.2 Method 2: Acylation of Ketones [Seite 506]
1.9.6.1.1.2.1 - 29.18.1.1.2.1 Variation 1: Synthesis of Meldrum's Acid Using a Diacid and a Ketone [Seite 506]
1.9.6.1.1.2.2 - 29.18.1.1.2.2 Variation 2: Using an Oxo Acid [Seite 508]
1.9.6.1.1.3 - 29.18.1.1.3 Method 3: Synthesis from 1-Acyloxy-1-hydroxy Compounds, Carbonyl Hydrates, or Vinyl Esters [Seite 509]
1.9.6.1.2 - 29.18.1.2 Alkylation of Carboxy Groups [Seite 513]
1.9.6.1.2.1 - 29.18.1.2.1 Method 1: Synthesis Using Hal/Hal Acetal Electrophiles [Seite 513]
1.9.6.1.2.2 - 29.18.1.2.2 Method 2: Synthesis Using O/Hal Acetal Electrophiles [Seite 513]
1.9.6.1.3 - 29.18.1.3 Oxidative Methods [Seite 515]
1.9.6.1.3.1 - 29.18.1.3.1 Method 1: Synthesis Using Single-Electron-Transfer Reagents [Seite 515]
1.9.6.1.3.1.1 - 29.18.1.3.1.1 Variation 1: Oxidation of Benzylic Methyl and Methylene Groups [Seite 515]
1.9.6.1.3.2 - 29.18.1.3.2 Method 2: Other Oxidations [Seite 516]
1.9.6.1.3.2.1 - 29.18.1.3.2.1 Variation 1: Baeyer-Villiger Oxidation of a-Acyloxy Ketones [Seite 516]
1.9.6.1.3.2.2 - 29.18.1.3.2.2 Variation 2: Oxidation of Furan Derivatives [Seite 517]
1.9.6.1.4 - 29.18.1.4 Synthesis from Propargyl Esters [Seite 520]
1.10 - Author Index [Seite 524]
1.11 - Abbreviations [Seite 548]
1.12 - List of All Volumes [Seite 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).
▶ Scheme 2 Bromine–Magnesium Exchange with Lithium Tributylmagnesate[3,10]
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...
