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Volume 8:Compounds of Group 1 (Li…Cs)
Volume 8a
8.1 Lithium Compounds
Keyword Index
Author Index
Abbreviations
Volume 8b
8.2 Sodium Compounds
8.3 Potassium Compounds
8.4 Rubidium and Cesium Compounds
Keyword Index
Author Index
Abbreviations
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Science of Synthesis Original Edition Volume 8a © Georg Thieme Verlag KG
Volume 8a:Compounds of Group 1 (Li…Cs)
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V
Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XV
IntroductionM. Majewski and V. Snieckus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
8.1 Product Class 1: Lithium CompoundsM. Majewski and V. Snieckus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
8.1.1 Product Subclass 1: Lithium MetalR. K. Dieter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
8.1.2 Product Subclass 2: Lithium HydrideU. Wietelmann . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.1.3 Product Subclass 3: Lithium Halides, Lithium Cyanide,and Related SaltsU. Wietelmann . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
8.1.4 Product Subclass 4: Lithium–Oxygen CompoundsU. Wietelmann . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
8.1.5 Product Subclass 5: Lithium–Sulfur, –Selenium,and –Tellurium CompoundsU. Wietelmann . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
8.1.6 Product Subclass 6: Lithium AmidesJ. Eames . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
8.1.7 Product Subclass 7: Alkyllithium and Cycloalkyllithium CompoundsL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
8.1.8 Product Subclass 8: Alkenyllithium CompoundsL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
8.1.9 Product Subclass 9: Allenyllithium CompoundsL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
8.1.10 Product Subclass 10: Lithium AcetylidesL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
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8.1.11 Product Subclass 11: Lithium Alkynolates, Alkynethiolates,and AlkyneselenolatesL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
8.1.12 Product Subclass 12: Allyllithium CompoundsL. Brandsma and J. W. Zwikker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
8.1.13 Product Subclass 13: Benzyllithium Compounds and(Lithiomethyl)hetarenesJ. N. Reed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
8.1.14 Product Subclass 14: Aryllithium and Hetaryllithium CompoundsG. W. Gribble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
8.1.15 Product Subclass 15: Æ-Lithiocarboxylic Acids andRelated Lithium Compounds (Including Enolates)J. R. Green . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
8.1.16 Product Subclass 16: �-Lithiocarboxylic Acids andRelated Lithium CompoundsD. Caine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
8.1.17 Product Subclass 17: Æ-Lithio Aldehydes, Æ-Lithio Ketones,and Related CompoundsD. Caine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
8.1.18 Product Subclass 18: �-Lithio Aldehydes, �-Lithio Ketones,and Related CompoundsD. Caine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
8.1.19 Product Subclass 19: sp3-Hybridized Æ-Lithio Ethers and O-CarbamatesS. MacNeil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 637
8.1.20 Product Subclass 20: Æ-Lithio SulfoxidesT. Durst and M. Khodaei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
8.1.21 Product Subclass 21: Æ-LithioaminesR. E. Gawley, S. O�Connor, and R. Klein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677
8.1.22 Product Subclass 22: Lithium NitronatesN. Ono . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759
8.1.23 Product Subclass 23: ª-Lithio Ethers and Related CompoundsD. Caine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
8.1.24 Product Subclass 24: Carbamoyllithium and TrihalomethyllithiumCompoundsC. Metallinos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
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8.1.25 Product Subclass 25: Tris(organosulfanyl)- andTris(organoselanyl)methyllithium CompoundsC. N�jera and M. Yus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 805
8.1.26 Product Subclass 26: Bis(organosulfanyl)- andBis(organoselanyl)methyllithium CompoundsC. N�jera and M. Yus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
8.1.27 Product Subclass 27: Æ-Lithio Vinyl EthersR. W. Friesen and C. F. Sturino . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841
Keyword Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxiii
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . lxxxv
Overview XIII
Science of Synthesis Original Edition Volume 8a © Georg Thieme Verlag KG
Science of Synthesis Original Edition Volume 8a © Georg Thieme Verlag KG
Table of Contents
IntroductionM. Majewski and V. Snieckus
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
8.1 Product Class 1: Lithium CompoundsM. Majewski and V. Snieckus
8.1 Product Class 1: Lithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
8.1.1 Product Subclass 1: Lithium MetalR. K. Dieter
8.1.1 Product Subclass 1: Lithium Metal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Applications of Product Subclass 1 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 44
8.1.1.1 Method 1: Synthesis of C-Li or Si-Li Groups and Their Reactions withCarbon Electrophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
8.1.1.1.1 Variation 1: Reductive Halogen–Metal Exchange . . . . . . . . . . . . . . . . . . . . . . . 448.1.1.1.2 Variation 2: Reductive Metalation of Carbon-Chalcogen and C-N Bonds 558.1.1.1.3 Variation 3: Reductive Metalation of Aryl C-H, Diarylmethylene C-H,
Terminal Alkyne C-H, Vinyl C-H, C=C, and Strained C-CBonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
8.1.1.2 Method 2: Synthesis of the C-Li Bond Followed by Protonation,Coupling, or Elimination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
8.1.1.2.1 Variation 1: From Carbon-Heteroatom and Selected C-C Bonds . . . . . . . . 678.1.1.2.2 Variation 2: Birch Reductions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838.1.1.2.3 Variation 3: Heteroaromatic Birch Reductions . . . . . . . . . . . . . . . . . . . . . . . . . . 968.1.1.2.4 Variation 4: Styrenes, 1,3-Dienes, and Alkynes . . . . . . . . . . . . . . . . . . . . . . . . . . 1018.1.1.3 Method 3: Synthesis of X-Li Bonds (X = O, N, S, P) . . . . . . . . . . . . . . . . . . . . 1078.1.1.3.1 Variation 1: Reductive Metalation of Alcohols, Amines, Thiols, Phosphines,
and X-X Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1078.1.1.3.2 Variation 2: Reduction of C=O and C=N Bonds . . . . . . . . . . . . . . . . . . . . . . . . . 1098.1.1.3.3 Variation 3: Reduction of �-, Strained C-C, or C-X Bonds Æ
to a Carbonyl Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
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8.1.2 Product Subclass 2: Lithium HydrideU. Wietelmann
8.1.2 Product Subclass 2: Lithium Hydride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Applications of Product Subclass 2 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 133
8.1.2.1 Method 1: Reactions as a Base . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1338.1.2.2 Method 2: Superactive Lithium Hydride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1348.1.2.3 Method 3: Other Lithium Hydride Activation Methods . . . . . . . . . . . . . . . . . 135
8.1.3 Product Subclass 3: Lithium Halides, Lithium Cyanide, and Related SaltsU. Wietelmann
8.1.3 Product Subclass 3: Lithium Halides, Lithium Cyanide, and Related Salts 139
Applications of Product Subclass 3 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 139
8.1.3.1 Method 1: Organic Salt Solutions as Reaction Media . . . . . . . . . . . . . . . . . . . 1398.1.3.2 Method 2: Effects on Main Group Organometallic Chemistry . . . . . . . . . . . 1408.1.3.2.1 Variation 1: Salt Effects in Enolate and Similar Chemistry . . . . . . . . . . . . . . . . 1418.1.3.2.2 Variation 2: Protonation of Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1448.1.3.2.3 Variation 3: Lithium Salt Effects in Grignard Chemistry . . . . . . . . . . . . . . . . . . 1458.1.3.3 Method 3: Effects on Transition-Metal Chemistry . . . . . . . . . . . . . . . . . . . . . . 1468.1.3.3.1 Variation 1: Palladium-Catalyzed Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1478.1.3.3.2 Variation 2: Organocopper Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1488.1.3.3.3 Variation 3: Reactions of Other Transition Metals . . . . . . . . . . . . . . . . . . . . . . . 1498.1.3.4 Method 4: Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1498.1.3.4.1 Variation 1: Cycloaddition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1498.1.3.4.2 Variation 2: Addition to Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 1518.1.3.4.3 Variation 3: Miscellaneous Additions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1538.1.3.5 Method 5: Single-Bond Cleavage Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 1538.1.3.6 Method 6: Condensation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1568.1.3.7 Method 7: Elimination Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1588.1.3.8 Method 8: Hydride Reductions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1588.1.3.9 Method 9: Lithium Salts as Sources for Halogens or Cyanide . . . . . . . . . . . 159
8.1.4 Product Subclass 4: Lithium–Oxygen CompoundsU. Wietelmann
8.1.4 Product Subclass 4: Lithium–Oxygen Compounds . . . . . . . . . . . . . . . . . . . . . . . 165
Applications of Product Subclass 4 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 165
8.1.4.1 Method 1: Reactions Using Lithium Hydroxide . . . . . . . . . . . . . . . . . . . . . . . . 1658.1.4.2 Method 2: Reactions Using Lithium Carbonate . . . . . . . . . . . . . . . . . . . . . . . . 1668.1.4.3 Method 3: Use of Lithium Hydroperoxide and Related Reagents . . . . . . . . 1668.1.4.4 Method 4: Reactions Using Lithium Acetate . . . . . . . . . . . . . . . . . . . . . . . . . . . 1678.1.4.5 Method 5: Reactions Using Lithium Alkoxides . . . . . . . . . . . . . . . . . . . . . . . . . 1688.1.4.5.1 Variation 1: Elimination and Condensation Reactions . . . . . . . . . . . . . . . . . . . 1688.1.4.5.2 Variation 2: Oxidation Reactions with Copper(II) Bromide–Lithium
tert-Butoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
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8.1.5 Product Subclass 5: Lithium–Sulfur, –Selenium,and –Tellurium CompoundsU. Wietelmann
8.1.5 Product Subclass 5: Lithium–Sulfur, –Selenium,and –Tellurium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Applications of Product Subclass 5 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 171
8.1.6 Product Subclass 6: Lithium AmidesJ. Eames
8.1.6 Product Subclass 6: Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
Synthesis of Product Subclass 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
8.1.6.1 Method 1: Lithium Amide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1748.1.6.2 Method 2: Lithium Ethylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1758.1.6.3 Method 3: Lithium Pyrrolidide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1758.1.6.4 Method 4: Lithium Diethylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1778.1.6.5 Method 5: Lithium Dicyclohexylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1788.1.6.6 Method 6: Lithium Diisopropylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1798.1.6.6.1 Variation 1: By Deprotonation of Diisopropylamine by Butyllithium . . . . . . 1808.1.6.6.2 Variation 2: By Reaction of Diisopropylamine with Lithium . . . . . . . . . . . . . . 1808.1.6.7 Method 7: Lithium 2,2,6,6-Tetramethylpiperidide . . . . . . . . . . . . . . . . . . . . . 1818.1.6.8 Method 8: Lithium Isopropylcyclohexylamide . . . . . . . . . . . . . . . . . . . . . . . . . 1828.1.6.9 Method 9: Lithium 3-Aminopropylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1838.1.6.10 Method 10: Lithium Hexamethyldisilazanide . . . . . . . . . . . . . . . . . . . . . . . . . . . 1848.1.6.11 Method 11: Lithium Benzyl(trimethylsilyl)amide . . . . . . . . . . . . . . . . . . . . . . . . 1848.1.6.12 Method 12: Tetradentate Chiral Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . 1858.1.6.13 Method 13: Lithium (R)-(1-Phenylethyl)(2,2,2-trifluoroethyl)amide . . . . . . 1878.1.6.14 Method 14: Lithium (3S)-3-(1-Piperidylmethyl)-1,2,3,4-tetrahydro-
isoquinolin-2-ide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1888.1.6.15 Method 15: Lithium (S)-Benzyl(1-phenylethyl)amide . . . . . . . . . . . . . . . . . . . . 1908.1.6.16 Method 16: The Dilithium Salt of 1-(Methylamino)-1-phenylpropan-2-ol 1908.1.6.17 Method 17: Lithium Methyl[(1R,2S)-1-phenyl-2-pyrrolidin-
1-ylpropyl]amide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1918.1.6.18 Method 18: Lithium (1S,2S)-1,2-Diphenyl-N,N¢-bis[(1R)-1-phenylethyl]-
ethane-1,2-diamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1938.1.6.19 Method 19: Lithium Bis[(S)-1-phenylethyl]amide . . . . . . . . . . . . . . . . . . . . . . . 1948.1.6.20 Method 20: Lithium (S)-2-(Pyrrolidin-1-ylmethyl)pyrrolidide . . . . . . . . . . . . . 1948.1.6.21 Method 21: Lithium (2S,3aS,7aS)-2-(Pyrrolidin-1-ylmethyl)octahydro-
1H-indol-1-ide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1948.1.6.22 Method 22: Lithium (1R,2R)-N,N¢-Bis(2-methoxyethyl)cyclohexane-
1,2-diamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1978.1.6.23 Method 23: The Lithium Salt of (1S,3R,4R)-3-(Pyrrolidin-1-ylmethyl)-
2-azabicyclo[2.2.1]heptane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1988.1.6.24 Method 24: Lithium (S)-Benzyl[2-(4-methylpiperazin-1-yl)-
1-phenylethyl]amide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
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8.1.6.25 Method 25: Lithium (S)-(Diphenylmethyl)(1-benzylpyrrolidin-3-yl)amide 203
Applications of Product Subclass 6 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 204
8.1.6.26 Method 26: Deprotonation of Carbonyl Compounds To GiveLithium Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
8.1.6.27 Method 27: Enantioselective Deprotonation of Ketones byChiral Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
8.1.6.28 Method 28: Deprotonation of Ketones by Lithium Hexamethyldisilazanidein the Synthesis of Diazo Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . 214
8.1.6.29 Method 29: Deprotonation of Terminal Alkynes by Lithium Amide . . . . . . . 2158.1.6.30 Method 30: Deprotonation of an Epoxide by Lithium Diethylamide . . . . . . 2168.1.6.31 Method 31: Desymmetrization of meso-Epoxides by Deprotonation by
Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2178.1.6.32 Method 32: Kinetic Resolution of Racemic Epoxides by Deprotonation by
Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2218.1.6.33 Method 33: Isomerization of an Epoxide to an Allylic Alcohol by
Deprotonation by Lithium Diethylamide . . . . . . . . . . . . . . . . . . . . 2218.1.6.34 Method 34: Deprotonation of a Nitrile by Lithium Diisopropylamide . . . . . 2228.1.6.35 Method 35: Carbene Formation by Deprotonation Reactions of
Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2238.1.6.36 Method 36: Desymmetrization of an Amide by Deprotonation Using
Lithium Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2248.1.6.37 Method 37: Desymmetrization of a meso-Phospholane Oxide by
Deprotonation by a Lithium Amide . . . . . . . . . . . . . . . . . . . . . . . . . 2258.1.6.38 Method 38: Nucleophilic Addition Involving Lithium Amides . . . . . . . . . . . . 2278.1.6.38.1 Variation 1: Nucleophilic Addition Involving Lithium Diisopropylamide . . . 2278.1.6.38.2 Variation 2: Diastereoselective Conjugate Addition with
Lithium Benzyl(1-phenylethyl)amide . . . . . . . . . . . . . . . . . . . . . . . 2288.1.6.39 Method 39: Hydride Transfer Involving Lithium Amides . . . . . . . . . . . . . . . . . 2308.1.6.39.1 Variation 1: Hydride Transfer by Lithium Diisopropylamide . . . . . . . . . . . . . . 2308.1.6.39.2 Variation 2: Hydride Transfer by Lithium (S)-Benzyl[2-(4-methyl-
piperazin-1-yl)-1-phenylethyl]amide . . . . . . . . . . . . . . . . . . . . . . . 2318.1.6.40 Method 40: Additional Applications of Chiral Lithium Amides . . . . . . . . . . . 2318.1.6.40.1 Variation 1: Enantioselective Addition of Butyllithium Mediated by
a Chiral Lithium Amide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2318.1.6.40.2 Variation 2: Enantioselective Protonation of a Prostereogenic Enolate . . . 232
8.1.7 Product Subclass 7: Alkyllithium and Cycloalkyllithium CompoundsL. Brandsma and J. W. Zwikker
8.1.7 Product Subclass 7: Alkyllithium and Cycloalkyllithium Compounds . . . . . 243
Synthesis of Product Subclass 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
8.1.7.1 Method 1: Reaction of Halogenides with Lithium . . . . . . . . . . . . . . . . . . . . . . 2448.1.7.2 Method 2: Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2468.1.7.3 Method 3: Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2468.1.7.4 Methods 4: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
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Applications of Product Subclass 7 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 247
8.1.7.5 Method 5: Replacement of Lithium by Other Metals . . . . . . . . . . . . . . . . . . . 2478.1.7.6 Method 6: Addition of Alkyllithium to Unsaturated Carbon Compounds
(Carbolithiation) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2488.1.7.6.1 Variation 1: Cyclization of Unsaturated Lithium Compounds
(Cyclocarbolithiation) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
8.1.8 Product Subclass 8: Alkenyllithium CompoundsL. Brandsma and J. W. Zwikker
8.1.8 Product Subclass 8: Alkenyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Synthesis of Product Subclass 8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
8.1.8.1 Method 1: Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2538.1.8.1.1 Variation 1: Deprotonation with Alkyllithium Reagents . . . . . . . . . . . . . . . . . . 2548.1.8.1.2 Variation 2: Deprotonation with Superbasic Reagents . . . . . . . . . . . . . . . . . . . 2568.1.8.1.3 Variation 3: Deprotonation with Lithium Dialkylamides . . . . . . . . . . . . . . . . . 2578.1.8.2 Method 2: Halogen–Metal Exchange Using Alkyllithium Reagents . . . . . . 2598.1.8.3 Method 3: Reaction of Alkenyl Halides with Lithium . . . . . . . . . . . . . . . . . . . 2618.1.8.4 Method 4: Tin–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2628.1.8.5 Method 5: Reaction of (Arylsulfonyl)hydrazones with
Alkyllithium Reagents (Shapiro Reaction) . . . . . . . . . . . . . . . . . . . 2638.1.8.6 Methods 6: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
Applications of Product Subclass 8 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 265
8.1.8.7 Method 7: Replacement of Lithium by Other Metals . . . . . . . . . . . . . . . . . . . 2658.1.8.8 Method 8: Formation of C-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2668.1.8.8.1 Variation 1: Reaction with Heterocumulenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 2668.1.8.8.2 Variation 2: Acylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2668.1.8.8.3 Variation 3: Alkylation and Related Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 2678.1.8.8.4 Variations 4: Additional Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
8.1.9 Product Subclass 9: Allenyllithium CompoundsL. Brandsma and J. W. Zwikker
8.1.9 Product Subclass 9: Allenyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Synthesis of Product Subclass 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
8.1.9.1 Method 1: Deprotonation of Allenes with Butyllithium . . . . . . . . . . . . . . . . . 2728.1.9.1.1 Variation 1: Deprotonation of Allenes with Lithium Amides . . . . . . . . . . . . . 2738.1.9.2 Method 2: Metalation of Alkynes with Butyllithium . . . . . . . . . . . . . . . . . . . . 2748.1.9.3 Method 3: Metalation of Alkynes with Butyllithium–N,N,N¢,N¢-Tetra-
methylethylenediamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2768.1.9.4 Method 4: Metalation of Alkynes with Butyllithium–Potassium
tert-Butoxide Followed by Addition of Lithium Bromide . . . . . . 2778.1.9.5 Method 5: 1,4-Addition of Lithium Compounds to Enynes . . . . . . . . . . . . . 278
Applications of Product Subclass 9 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 278
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8.1.9.6 Method 6: Replacement of Lithium by Other Metals . . . . . . . . . . . . . . . . . . . 2788.1.9.7 Method 7: Formation of C-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2798.1.9.7.1 Variation 1: Reactions with Heterocumulenes . . . . . . . . . . . . . . . . . . . . . . . . . . 2798.1.9.7.2 Variation 2: Reactions with Acylating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 2798.1.9.7.3 Variation 3: Reactions with Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . 2808.1.9.7.4 Variation 4: Reaction with Alkylating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 2808.1.9.8 Methods 8: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
8.1.10 Product Subclass 10: Lithium AcetylidesL. Brandsma and J. W. Zwikker
8.1.10 Product Subclass 10: Lithium Acetylides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Synthesis of Product Subclass 10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
8.1.10.1 Method 1: Metalation with Lithium in Liquid Ammonia . . . . . . . . . . . . . . . . 2878.1.10.2 Method 2: Metalation with Lithium Amide in Liquid Ammonia . . . . . . . . . 2878.1.10.2.1 Variation 1: Dehydrohalogenation with Lithium Amide . . . . . . . . . . . . . . . . . . 2888.1.10.3 Method 3: Metalation with Lithium Dialkylamides . . . . . . . . . . . . . . . . . . . . . 2888.1.10.3.1 Variation 1: Elimination Reactions with Lithium Dialkylamides . . . . . . . . . . . 2898.1.10.4 Method 4: Metalation with Alkyllithium Reagents . . . . . . . . . . . . . . . . . . . . . 2898.1.10.5 Method 5: Dehalogenation with Alkyllithium Reagents . . . . . . . . . . . . . . . . 2908.1.10.6 Method 6: Rearrangement of Terminally Lithiated Allenes . . . . . . . . . . . . . . 2918.1.10.7 Methods 7: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Applications of Product Subclass 10 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 292
8.1.10.8 Method 8: Replacement of Lithium by Other Metals . . . . . . . . . . . . . . . . . . . 2928.1.10.9 Method 9: Formation of C-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2928.1.10.9.1 Variation 1: Reactions with Heterocumulenes . . . . . . . . . . . . . . . . . . . . . . . . . . 2928.1.10.9.2 Variation 2: Acylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2948.1.10.9.3 Variation 3: Reactions with Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . 2968.1.10.9.4 Variation 4: Reaction with Cyanogen Chloride . . . . . . . . . . . . . . . . . . . . . . . . . . 2978.1.10.9.5 Variation 5: Reactions with Alkylating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . 2978.1.10.10 Method 10: Formation of Carbon-Heteroatom Bonds . . . . . . . . . . . . . . . . . . 2998.1.10.10.1 Variation 1: Reaction with Halogenating Agents . . . . . . . . . . . . . . . . . . . . . . . . 2998.1.10.10.2 Variation 2: Sulfanylation, Sulfinylation, and Related Reactions . . . . . . . . . . 3018.1.10.10.3 Variation 3: Silylation and Stannylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
8.1.11 Product Subclass 11: Lithium Alkynolates, Alkynethiolates,and AlkyneselenolatesL. Brandsma and J. W. Zwikker
8.1.11 Product Subclass 11: Lithium Alkynolates, Alkynethiolates,and Alkyneselenolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Synthesis of Product Subclass 11 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
8.1.11.1 Method 1: Insertion of Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3058.1.11.2 Method 2: Lithium Alkynolates by Cyclofragmentation of Heterocycles 3068.1.11.3 Method 3: Lithium Alkynethiolates from 1,2,3-Thiadiazoles . . . . . . . . . . . . 307
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8.1.11.4 Method 4: Lithium Alkynolates from Æ,Æ-Dibromo or Æ-Halo Ketones . . 3078.1.11.5 Methods 5: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Applications of Product Subclass 11 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 308
8.1.11.6 Method 6: Functionalization of Lithium Alkynolates . . . . . . . . . . . . . . . . . . . 3088.1.11.7 Method 7: Functionalization of Lithium Alkynethiolates and
Alkyneselenolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3098.1.11.8 Method 8: Protonation–Addition Reactions with Lithium Alkynolates . . . 3108.1.11.9 Method 9: Protonation–Addition Reactions with Lithium Alkynethiolates 310
8.1.12 Product Subclass 12: Allyllithium CompoundsL. Brandsma and J. W. Zwikker
8.1.12 Product Subclass 12: Allyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Synthesis of Product Subclass 12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
8.1.12.1 Method 1: Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3148.1.12.1.1 Variation 1: Deprotonation with Alkyllithium Reagents . . . . . . . . . . . . . . . . . . 3158.1.12.1.2 Variation 2: Deprotonation Using the Superbase
Butyllithium–Potassium tert-Butoxide . . . . . . . . . . . . . . . . . . . . . . 3178.1.12.1.3 Variation 3: Lithiation with Lithium Dialkylamides . . . . . . . . . . . . . . . . . . . . . . 3208.1.12.2 Methods 2: Additional Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Applications of Product Subclass 12 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 321
8.1.12.3 Method 3: Replacement of Lithium by Other Metals . . . . . . . . . . . . . . . . . . . 3218.1.12.4 Method 4: Formation of C-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3228.1.12.4.1 Variation 1: Reactions with Heterocumulenes . . . . . . . . . . . . . . . . . . . . . . . . . . 3228.1.12.4.2 Variation 2: Reactions with Alkylating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . 3238.1.12.4.3 Variation 3: Reactions with Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . 3248.1.12.5 Method 5: Formation of Carbon-Heteroatom Bonds . . . . . . . . . . . . . . . . . . 325
8.1.13 Product Subclass 13: Benzyllithium Compounds and(Lithiomethyl)hetarenesJ. N. Reed
8.1.13 Product Subclass 13: Benzyllithium Compounds and(Lithiomethyl)hetarenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Synthesis of Product Subclass 13 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
8.1.13.1 Method 1: Deprotonation of Benzylic Carbons . . . . . . . . . . . . . . . . . . . . . . . . 3298.1.13.1.1 Variation 1: Of Unactivated Benzylic Carbons . . . . . . . . . . . . . . . . . . . . . . . . . . . 3308.1.13.1.2 Variation 2: Of Benzylic Carbons Activated by an Æ-Substituent . . . . . . . . . 3318.1.13.1.3 Variation 3: Heteroatom-Facilitated Lateral Lithiation . . . . . . . . . . . . . . . . . . . 3368.1.13.2 Method 2: Heteroatom–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3428.1.13.2.1 Variation 1: Tin–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3428.1.13.2.2 Variation 2: Selenium–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3458.1.13.3 Method 3: Reductive Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3478.1.13.3.1 Variation 1: Using Lithium Metal and Naphthalene . . . . . . . . . . . . . . . . . . . . . . 3478.1.13.3.2 Variation 2: Using Lithium Metal and 4,4¢-Di-tert-butylbiphenyl . . . . . . . . . . 348
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8.1.13.4 Method 4: Carbolithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3508.1.13.4.1 Variation 1: Of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3508.1.13.4.2 Variation 2: Of Alkynes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
8.1.14 Product Subclass 14: Aryllithium and Hetaryllithium CompoundsG. W. Gribble
8.1.14 Product Subclass 14: Aryllithium and Hetaryllithium Compounds . . . . . . . . 357
Synthesis of Product Subclass 14 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
8.1.14.1 Method 1: Aryllithium Compounds by Halogen–Lithium Exchange . . . . . 3578.1.14.1.1 Variation 1: From Aryl Fluorides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3588.1.14.1.2 Variation 2: From Aryl Chlorides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3588.1.14.1.3 Variation 3: From Aryl Bromides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3598.1.14.1.4 Variation 4: From Aryl Iodides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3618.1.14.2 Method 2: Aryllithium Compounds by Directed ortho-Lithiation . . . . . . . . 3618.1.14.2.1 Variation 1: Amine Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . . . . . . 3628.1.14.2.2 Variation 2: Amide Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . . . . . . 3648.1.14.2.3 Variation 3: Alkoxy Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . . . . . . 3658.1.14.2.4 Variation 4: Halogen Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . . . . 3678.1.14.2.5 Variation 5: Sulfur-Based Directed ortho-Lithiation Groups . . . . . . . . . . . . . . 3698.1.14.2.6 Variation 6: Other Carbonyl Directed ortho-Lithiation Groups . . . . . . . . . . . . 3708.1.14.2.7 Variation 7: Phosphorus Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . 3718.1.14.2.8 Variation 8: Other Nitrogen Directed ortho-Lithiation Groups . . . . . . . . . . . . 3728.1.14.2.9 Variation 9: Other Directed ortho-Lithiation Groups . . . . . . . . . . . . . . . . . . . . . 3738.1.14.3 Method 3: Furyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3748.1.14.3.1 Variation 1: By Direct Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3748.1.14.3.2 Variation 2: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3758.1.14.3.3 Variation 3: By Directed ortho-Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3758.1.14.4 Method 4: Thienyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3768.1.14.4.1 Variation 1: By Direct Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3768.1.14.4.2 Variation 2: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3778.1.14.4.3 Variation 3: By Directed ortho-Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3788.1.14.5 Method 5: Pyrrolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3798.1.14.5.1 Variation 1: By Direct Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3798.1.14.5.2 Variation 2: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3808.1.14.5.3 Variation 3: By Directed ortho-Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3818.1.14.6 Method 6: Imidazolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3818.1.14.6.1 Variation 1: By Direct Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3818.1.14.6.2 Variation 2: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3828.1.14.7 Method 7: Oxazolyllithium and Isoxazolyllithium Compounds . . . . . . . . . . 3838.1.14.7.1 Variation 1: Lithiation of Oxazoles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3838.1.14.7.2 Variation 2: Lithiation of Isoxazoles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3848.1.14.8 Method 8: Pyrazolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3848.1.14.9 Method 9: Thiazolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3858.1.14.10 Method 10: Benzofuryllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3868.1.14.11 Method 11: Benzothienyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 3868.1.14.12 Method 12: Indolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
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8.1.14.12.1 Variation 1: By Direct Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3878.1.14.12.2 Variation 2: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3898.1.14.12.3 Variation 3: By Directed ortho-Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3918.1.14.13 Method 13: Pyridyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3928.1.14.13.1 Variation 1: By Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3938.1.14.13.2 Variation 2: By Directed ortho-Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3958.1.14.14 Method 14: Quinolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3988.1.14.15 Method 15: Diazinyllithium, Benzodiazinyllithium,
and Other Azinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . 3998.1.14.15.1 Variation 1: Pyrazinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3998.1.14.15.2 Variation 2: Pyrimidyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4008.1.14.15.3 Variation 3: Pyridazinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4018.1.14.15.4 Variation 4: Benzodiazinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 4028.1.14.15.5 Variation 5: Other Azinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 4028.1.14.16 Method 16: Other Azolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 4038.1.14.17 Method 17: Dibenzo-Fused Hetaryllithium Compounds . . . . . . . . . . . . . . . . . 4048.1.14.17.1 Variation 1: Dibenzofuryllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 4048.1.14.17.2 Variation 2: Dibenzothienyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . 4058.1.14.17.3 Variation 3: Carbazolyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4058.1.14.17.4 Variation 4: Dibenzo[1,4]dioxinyllithium Compounds . . . . . . . . . . . . . . . . . . . 4068.1.14.17.5 Variation 5: Thianthrenyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 4078.1.14.17.6 Variation 6: Phenothiazinyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . 4078.1.14.17.7 Variation 7: Dibenzo[b,f]azepinyllithium Compounds . . . . . . . . . . . . . . . . . . . 4078.1.14.17.8 Variation 8: Pyrido[3,4-b]indolyllithium Compounds . . . . . . . . . . . . . . . . . . . . 408
Applications of Product Subclass 14 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 408
8.1.14.18 Method 18: Aryne Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4098.1.14.19 Method 19: Functional Group Interchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4098.1.14.20 Method 20: Transmetalation and Coupling Reactions . . . . . . . . . . . . . . . . . . . 4108.1.14.21 Method 21: Aryllithium Compounds in Ring Formation and
Heterocycle Construction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4128.1.14.22 Method 22: Natural Product Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
8.1.15 Product Subclass 15: Æ-Lithiocarboxylic Acids and Related LithiumCompounds (Including Enolates)J. R. Green
8.1.15 Product Subclass 15: Æ-Lithiocarboxylic Acids and Related LithiumCompounds (Including Enolates) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Synthesis of Product Subclass 15 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
8.1.15.1 Method 1: Enolate Generation by Direct Deprotonation ofAlkanoic Acid Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
8.1.15.2 Method 2: Enolate Generation by Nucleophilic Attack on Ketene Acetals 4308.1.15.3 Method 3: Enolate Generation by Conjugate Addition or Reduction . . . . 4308.1.15.4 Method 4: Enolate Generation by Reduction or Metal–Halogen Exchange
of Æ-Substituted Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Applications of Product Subclass 15 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 434
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8.1.15.5 Method 5: Electrophile Incorporation: Protonation (C-Li fi C-H) . . . . . . 4348.1.15.6 Method 6: Electrophile Incorporation: Alkylation (C-Li fi C-C) . . . . . . . . 4368.1.15.6.1 Variation 1: Arylation and Vinylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4418.1.15.7 Method 7: Electrophile Incorporation: Heteroatom Incorporation
(C-Li fi C-X) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4448.1.15.7.1 Variation 1: Silylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4448.1.15.7.2 Variation 2: Hydroxylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4468.1.15.7.3 Variation 3: Amination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4488.1.15.7.4 Variation 4: Halogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4508.1.15.8 Method 8: Electrophile Incorporation: Reaction with Carbonyl
Compounds and Imines (C-Li fi C-C-X) . . . . . . . . . . . . . . . . . . 4528.1.15.9 Method 9: Electrophile Incorporation: Epoxides and Aziridines
(C-Li fi C-C-C-X) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4588.1.15.10 Method 10: Electrophile Incorporation: Coupling Reactions;
Enolate Dimerization (C-Li fi C-C-C=X) . . . . . . . . . . . . . . . . . . 4618.1.15.11 Method 11: Electrophile Incorporation: Reaction with Carboxy
Compounds (C-Li fi C-C=X) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4638.1.15.12 Method 12: Electrophile Incorporation: Michael Addition
(C-Li fi C-C-C-C=X) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4688.1.15.13 Method 13: Enolate Rearrangements: Claisen and
Related Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4738.1.15.14 Method 14: Enolate Rearrangements: [2,3]-Wittig Rearrangements of
Dienolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4778.1.15.15 Method 15: Enolate Rearrangements: Reactions with Nucleophiles:
Formation of Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
8.1.16 Product Subclass 16: �-Lithiocarboxylic Acids and Related LithiumCompoundsD. Caine
8.1.16 Product Subclass 16: �-Lithiocarboxylic Acids and Related LithiumCompounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Synthesis of Product Subclass 16 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
8.1.16.1 Method 1: Arene-Catalyzed Reductive Lithiations of�-Halogenated Carboxylates and 3-Arylpropenoates . . . . . . . . 487
8.1.16.2 Method 2: Tin–Lithium Exchange of �-Stannyl Carboxamides . . . . . . . . . . 4908.1.16.3 Method 3: Hydrogen–Lithium Exchange of Carboxylates and
Carboxamides Containing Carbanion-Stabilizing Groups atthe �-Position . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
8.1.16.3.1 Variation 1: Hydrogen–Lithium Exchange of �-PhenylsulfonylatedOrtho Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
8.1.16.4 Method 4: Addition of Alkyllithium Reagents to LithiatedCinnamic Acids and Cinnamyl Amides . . . . . . . . . . . . . . . . . . . . . . 496
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8.1.17 Product Subclass 17: Æ-Lithio Aldehydes, Æ-Lithio Ketones,and Related CompoundsD. Caine
8.1.17 Product Subclass 17: Æ-Lithio Aldehydes, Æ-Lithio Ketones,and Related Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Synthesis of Product Subclass 17 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 502
8.1.17.1 Preformed Lithium Enolates of Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . 502
8.1.17.1.1 Method 1: Deprotonation of Carbonyl Compounds withLithium Dialkylamides and Other Strong Bases . . . . . . . . . . . . . . 502
8.1.17.1.1.1 Variation 1: Regioselective Synthesis of Kinetic (Less Substituted) Enolatesof Æ-Substituted Unsymmetrical Saturated Ketones . . . . . . . . . 504
8.1.17.1.1.2 Variation 2: Regioselective Synthesis of Thermodynamic Enolates ofÆ-Substituted Unsymmetrical Saturated Ketones . . . . . . . . . . . 509
8.1.17.1.1.3 Variation 3: Kinetic and Thermodynamic Lithium Enolates ofUnsymmetrical Æ- and Æ¢-Dimethylene Ketones . . . . . . . . . . . . 510
8.1.17.1.1.4 Variation 4: Stereoselective Synthesis of E- or Z-Isomers ofAcyclic Ketone Lithium Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
8.1.17.1.1.5 Variation 5: Enantioselective Synthesis of Lithium Enolates byDeprotonation of Prochiral Ketones with Chiral,Nonracemic Lithium Amide Bases . . . . . . . . . . . . . . . . . . . . . . . . . . 516
8.1.17.1.1.6 Variation 6: Kinetic Deprotonation of Æ,�-Unsaturated Ketones . . . . . . . . . 5198.1.17.1.2 Method 2: Regio- and Stereoselective Formation of Lithium Enolates
by Indirect Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5228.1.17.1.2.1 Variation 1: Lithium/Liquid Ammonia Reduction of
Æ,�-Unsaturated Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5228.1.17.1.2.2 Variation 2: Lithium/Liquid Ammonia Reduction of Ketones with
Leaving Groups at the Æ-Position . . . . . . . . . . . . . . . . . . . . . . . . . . 5248.1.17.1.2.3 Variation 3: Conjugate Addition of Lithium Dialkylcuprate Reagents to
Æ,�-Unsaturated Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5258.1.17.1.2.4 Variation 4: Generation of Lithium Enolates from Enol Derivatives of
Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5268.1.17.1.2.5 Variation 5: Generation of Lithium Enolates by Miscellaneous Methods . . 5278.1.17.1.3 Method 3: Alkylations of Preformed Lithium Enolates . . . . . . . . . . . . . . . . . . 5278.1.17.1.3.1 Variation 1: Intermolecular Alkylations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5298.1.17.1.3.2 Variation 2: Stereochemistry of Intermolecular Alkylation of
Lithium Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5328.1.17.1.3.3 Variation 3: Intramolecular Alkylations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5378.1.17.1.4 Method 4: Directed Aldol Reactions of Preformed Lithium Enolates . . . . . 5388.1.17.1.4.1 Variation 1: Aldol Reactions of Lithium Z-Enolates . . . . . . . . . . . . . . . . . . . . . . 5408.1.17.1.4.2 Variation 2: Diastereofacial Selectivity of Aldol Reactions of Chiral,
Nonracemic Lithium Z-Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5418.1.17.1.4.3 Variation 3: Aldol Reactions of Lithium E-Enolates . . . . . . . . . . . . . . . . . . . . . . 5428.1.17.1.4.4 Variation 4: Aldol Reactions of Lithium Enolates with Chiral Aldehydes . . . 5438.1.17.1.4.5 Variation 5: Asymmetric Aldol Reactions Using Chiral Lithium Amide Bases 5468.1.17.1.4.6 Variation 6: Reactions of Preformed Lithium Enolates with
Preformed Iminium Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548
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8.1.17.1.5 Method 5: Michael Reactions of Preformed Lithium Enolates . . . . . . . . . . . 5488.1.17.1.5.1 Variation 1: Michael Reactions of Preformed Lithium E- and Z-Enolates
with Æ,�-Unsaturated Ketones and Esters . . . . . . . . . . . . . . . . . . 5498.1.17.1.5.2 Variation 2: Intermolecular Reactions of Preformed Lithium Enolates with
Various Michael Acceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5518.1.17.1.5.3 Variation 3: Sequential Michael Reactions of Preformed Lithium
Cross-Conjugated Dienolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5538.1.17.1.6 Method 6: C-Acylation Reactions of Preformed Lithium Enolates . . . . . . . 5558.1.17.1.7 Method 7: Reactions of Lithium Enolates at Carbon with
Heteroatom Electrophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5598.1.17.1.7.1 Variation 1: C-Hydroxylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5598.1.17.1.7.2 Variation 2: Sulfenylation, Selenenylation, and Halogenation Reactions . . 5628.1.17.1.8 Method 8: Diastereo- and Enantioselective Kinetic Protonation of
Lithium Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5678.1.17.1.8.1 Variation 1: Diastereoselective Protonation of Chiral Enolates . . . . . . . . . . . 5678.1.17.1.8.2 Variation 2: Enantioselective Protonation of Achiral Lithium Enolates . . . . 5698.1.17.1.8.3 Variation 3: Catalytic Enantioselective Protonation of
Achiral Lithium Enolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5718.1.17.1.9 Method 9: Transmetalation of Lithium Enolates . . . . . . . . . . . . . . . . . . . . . . . 5728.1.17.1.9.1 Variation 1: Lithium–Main Group Metal Exchange . . . . . . . . . . . . . . . . . . . . . . 5738.1.17.1.9.2 Variation 2: Lithium–Transition Metal Exchange . . . . . . . . . . . . . . . . . . . . . . . . 574
8.1.17.2 Dilithium and Mixed Lithium/Sodium Dienolates of �-Dicarbonyl Compounds 574
8.1.17.2.1 Method 1: Preparation of Dilithium and Lithium/Sodium Dienolates of�-Dicarbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 575
8.1.17.2.2 Method 2: ª-Alkylation of Dilithium or Lithium/Sodium Dienolates of�-Dicarbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577
8.1.17.2.3 Method 3: Aldol, Acylation, and Michael Reactions of Dilithium andLithium/Sodium Dienolates of �-Dicarbonyl Compounds . . . . 580
8.1.17.3 Lithium Azaenolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
8.1.17.3.1 Method 1: Deprotonations of Aldimines and Ketimines withLithium Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
8.1.17.3.2 Method 2: Deprotonation of Hydrazones with Lithium Bases . . . . . . . . . . . 5868.1.17.3.3 Method 3: Deprotonation of Oximes and Oxime Ethers with
Alkyllithium Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5888.1.17.3.4 Method 4: Special Methods for Synthesis of Lithium Azaenolates . . . . . . . 5898.1.17.3.5 Method 5: C-Alkylation of Lithium Azaenolates . . . . . . . . . . . . . . . . . . . . . . . . 5908.1.17.3.5.1 Variation 1: Alkylation of Azaenolates of Imines . . . . . . . . . . . . . . . . . . . . . . . . 5908.1.17.3.5.2 Variation 2: Stereoselective Alkylation of Azaenolates of Imines . . . . . . . . . 5918.1.17.3.5.3 Variation 3: Alkylation of Azaenolates of Hydrazones . . . . . . . . . . . . . . . . . . . 5948.1.17.3.6 Method 6: Aldol Reactions of Lithium Azaenolates . . . . . . . . . . . . . . . . . . . . . 5978.1.17.3.6.1 Variation 1: Aldol Reactions of Lithium Azaenolates of Imines . . . . . . . . . . . 5978.1.17.3.6.2 Variation 2: Aldol Reactions of Lithium Azaenolates of Hydrazones . . . . . . 5988.1.17.3.7 Method 7: Acylation of Lithium Azaenolates . . . . . . . . . . . . . . . . . . . . . . . . . . 6008.1.17.3.8 Method 8: Michael Additions of Lithium Azaenolates . . . . . . . . . . . . . . . . . . 6018.1.17.3.9 Method 9: Reactions of Lithium Azaenolates with Selected
Heteroatom Electrophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604
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8.1.18 Product Subclass 18: �-Lithio Aldehydes, �-Lithio Ketones,and Related CompoundsD. Caine
8.1.18 Product Subclass 18: �-Lithio Aldehydes, �-Lithio Ketones,and Related Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
Synthesis of Product Subclass 18 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
8.1.18.1 Method 1: Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6198.1.18.2 Method 2: Reductive Lithiation of Halides and Phenyl Sulfides with
Lithium Arene Radical Anions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6228.1.18.3 Method 3: Lithium Homoenolate Equivalents by
Tellurium–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6258.1.18.4 Method 4: Æ¢- or Æ-Enolate-Protected Lithium Homoenolates:
Dianionic Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6268.1.18.4.1 Variation 1: Preparation of �-Lithio Lithium Æ¢-Enolates . . . . . . . . . . . . . . . . . 6268.1.18.4.2 Variation 2: Preparation of �-Lithio Lithium Æ-Enolates . . . . . . . . . . . . . . . . . . 6288.1.18.5 Method 5: Carbolithiation of Protected Æ,�-Unsaturated Aldehydes . . . . 6308.1.18.6 Method 6: Hydrogen–Lithium Exchange of Acetals and Ketals Containing
Carbanion-Stabilizing Groups at the �-Position . . . . . . . . . . . . . 631
8.1.19 Product Subclass 19: sp3-Hybridized Æ-Lithio Ethers and O-CarbamatesS. MacNeil
8.1.19 Product Subclass 19: sp3-Hybridized Æ-Lithio Ethers and O-Carbamates . . 637
Synthesis of Product Subclass 19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 637
8.1.19.1 Method 1: Substitution of Hydrogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6378.1.19.1.1 Variation 1: Stereospecific Deprotonation at Chiral, Nonracemic Centers 6378.1.19.1.2 Variation 2: Diastereoselective Deprotonation by Substrate Control . . . . . 6388.1.19.1.3 Variation 3: Enantioselective Deprotonation/Kinetic Resolution Induced
by Chiral Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6398.1.19.1.4 Variation 4: Chiral Base Induced Deprotonation . . . . . . . . . . . . . . . . . . . . . . . . 6428.1.19.2 Method 2: Substitution of Tin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6428.1.19.3 Method 3: Reductive Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6438.1.19.3.1 Variation 1: Reductive Lithiation of Cl-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . 6438.1.19.3.2 Variation 2: Reductive Lithiation of S-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . 6448.1.19.3.3 Variation 3: Reductive Lithiation of C-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . 6458.1.19.4 Method 4: Carbolithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646
Applications of Product Subclass 19 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 647
8.1.19.5 Method 5: Electrophilic Quench of Æ-Lithio Oxygen Compounds . . . . . . . 6478.1.19.5.1 Variation 1: Æ-Lithio Oxygen Compounds as Homoenolate Equivalents . . 6478.1.19.6 Method 6: Rearrangements of Æ-Lithio Oxygen Compounds . . . . . . . . . . . 6498.1.19.6.1 Variation 1: [1,2]-Wittig Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6498.1.19.6.2 Variation 2: [2,3]-Wittig Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6508.1.19.6.3 Variation 3: Rearrangements of Æ-Lithio Epoxides . . . . . . . . . . . . . . . . . . . . . . 653
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8.1.20 Product Subclass 20: Æ-Lithio SulfoxidesT. Durst and M. Khodaei
8.1.20 Product Subclass 20: Æ-Lithio Sulfoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
Synthesis of Product Subclass 20 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
8.1.20.1 Method 1: Lithiation of Sulfoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
Applications of Product Subclass 20 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 663
8.1.20.2 Method 2: Alkylation of Æ-Lithio Sulfoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6668.1.20.3 Method 3: Reaction with Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . . 6678.1.20.4 Method 4: Reaction with Imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6718.1.20.5 Method 5: Acylation of Æ-Lithio Sulfoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6728.1.20.6 Method 6: Michael Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
8.1.21 Product Subclass 21: Æ-LithioaminesR. E. Gawley, S. O�Connor, and R. Klein
8.1.21 Product Subclass 21: Æ-Lithioamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677
Synthesis and Applications of Product Subclass 21 . . . . . . . . . . . . . . . . . . . . . . . . . . 682
8.1.21.1 Synthesis and Applications of Unstabilized Æ-Lithioamines . . . . . . . . . . . . . . . . . . 682
8.1.21.1.1 Method 1: Deprotonation and Electrophilic Substitution . . . . . . . . . . . . . . . 6838.1.21.1.2 Method 2: Transmetalation and Electrophilic Substitution . . . . . . . . . . . . . . 6848.1.21.1.2.1 Variation 1: Synthesis of a Horner–Wittig Reagent . . . . . . . . . . . . . . . . . . . . . . 6848.1.21.1.2.2 Variation 2: Addition of 2-Lithio-3-methyl-1-tritylaziridine to
Benzaldehyde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6858.1.21.1.2.3 Variation 3: Electrophilic Substitutions of 2-Lithio-1-methylpyrrolidine
and 2-Lithio-1-methylpiperidine (Racemic) . . . . . . . . . . . . . . . . . 6858.1.21.1.2.4 Variation 4: Electrophilic Substitution of 2-Lithiopyrrolidine and
2-Lithiopiperidine (Scalemic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6878.1.21.1.2.5 Variation 5: Transmetalation and Electrophilic Substitution of
a 1-Allyl-2-lithiopyrrolidine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6888.1.21.1.2.6 Variation 6: Transmetalation and Enantioselective Electrophilic
Substitution by Dynamic Thermodynamic Resolution . . . . . . . 6898.1.21.1.3 Method 3: Transmetalation and Sigmatropic Rearrangement . . . . . . . . . . . 6908.1.21.1.4 Method 4: Transmetalation and Anionic Cyclization . . . . . . . . . . . . . . . . . . . . 6928.1.21.1.4.1 Variation 1: Synthesis of Pyrrolidines and Bicyclic Amines . . . . . . . . . . . . . . . 6928.1.21.1.4.2 Variation 2: Synthesis of (+)-Pseudoheliotridane via
a Scalemic Organolithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6938.1.21.1.4.3 Variation 3: Tandem Cyclization/Ring Opening . . . . . . . . . . . . . . . . . . . . . . . . . 6948.1.21.1.4.4 Variation 4: Cyclizations onto Naphthyl Dihydrooxazoles . . . . . . . . . . . . . . . . 6948.1.21.1.4.5 Variation 5: Intramolecular Michael Addition onto an Indole Ester . . . . . . . 6958.1.21.1.5 Method 5: Reductive Lithiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6968.1.21.1.5.1 Variation 1: Reduction and Electrophilic Substitution of
Æ-Sulfinyl Aziridines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6968.1.21.1.5.2 Variation 2: Sulfide Reduction and Anionic Cyclization . . . . . . . . . . . . . . . . . . 697
8.1.21.2 Synthesis and Applications of Dipole-Stabilized Æ-Lithioamines . . . . . . . . . . . . . 697
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8.1.21.2.1 Method 1: Deprotonation and Electrophilic Substitution . . . . . . . . . . . . . . . 6998.1.21.2.1.1 Variation 1: Deprotonation of a Piperidine tert-Butylformamidine,
Transmetalation to Copper, and Electrophilic Substitution . . . 6998.1.21.2.1.2 Variation 2: Deprotonation of N-tert-Butoxycarbonylpyrrolidine and
Electrophilic Substitution with Tributyltin Chloride . . . . . . . . . . 7008.1.21.2.1.3 Variation 3: Deprotonation of N-tert-Butoxycarbonyl-N-methyl-
isobutylamine and Addition to Benzaldehyde . . . . . . . . . . . . . . . 7018.1.21.2.1.4 Variation 4: Preferential Deprotonation of N-tert-Butoxycarbonyl-
N-ethylcyclopropanamine at the Cyclopropyl Methineover the Ethyl Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701
8.1.21.2.1.5 Variation 5: Ring Contraction of 1-tert-Butoxycarbonyl-4-chloro-2-lithiopiperidine to a Cyclopropyl Intermediate,Followed by Deprotonation and Electrophilic Substitution . . . 702
8.1.21.2.1.6 Variation 6: Deprotonation and Palladium-Catalyzed Arylation . . . . . . . . . . 7038.1.21.2.1.7 Variation 7: Asymmetric Deprotonation Using a Chiral Base,
and Addition to Benzophenone . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7048.1.21.2.1.8 Variation 8: Asymmetric Deprotonation Using a Chiral Base:
Transmetalation with Copper, and Vinylation . . . . . . . . . . . . . . . 7058.1.21.2.1.9 Variation 9: Regio- and Stereoselective Deprotonation and
Electrophilic Substitution of Imidazolidines . . . . . . . . . . . . . . . . . 7068.1.21.2.2 Method 2: Transmetalation and Electrophilic Substitution . . . . . . . . . . . . . . 7068.1.21.2.2.1 Variation 1: Transmetalation from Tin to Lithium and then Copper,
with 1,4-Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7068.1.21.2.2.2 Variation 2: Transmetalation from Tin to Lithium: Lithiation
at Sites Not Available by Deprotonation . . . . . . . . . . . . . . . . . . . . 7078.1.21.2.2.3 Variation 3: Transmetalation of Organostannanes and Asymmetric
Transformation of the First Kind: Synthesis of 11C-EnrichedL-Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 708
8.1.21.2.2.4 Variation 4: Transmetalation of Æ-Stannylcarbamates and Additionto Aldehydes; Synthon of a Primary Æ-Lithioamine . . . . . . . . . . 710
8.1.21.2.3 Method 3: Transmetalation of Stannyl Ureas with 1,2-Acyl Migration . . . 7118.1.21.2.4 Method 4: Reductive Lithiation of Aminonitriles to Tertiary
Æ-Lithioamines and Electrophilic Substitution . . . . . . . . . . . . . . . 711
8.1.21.3 Synthesis and Applications of Mesomerically Stabilized Æ-Lithioamines . . . . . . 712
8.1.21.3.1 Method 1: Deprotonation of a Chiral Allylic Amine Followed byStereoselective Alkylation and Hydrolysis(Aldehyde Homoenolate Synthon) . . . . . . . . . . . . . . . . . . . . . . . . . 713
8.1.21.3.2 Method 2: Transmetalation of a Chiral Allylic Amine Followed byStereoselective Alkylation and Hydrolysis(Ketone Homoenolate Synthon) . . . . . . . . . . . . . . . . . . . . . . . . . . . 714
8.1.21.3.3 Method 3: Transmetalation of N-(Tributylstannyl)methaniminesFollowed by Cycloaddition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715
8.1.21.4 Synthesis and Applications of Dipole- and Mesomerically StabilizedÆ-Lithioamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 716
8.1.21.4.1 Method 1: Deprotonation of Achiral Substrates with an Achiral Base . . . . 7178.1.21.4.1.1 Variation 1: Preferential Deprotonation of Benzylic Protons with
Spontaneous Intramolecular Cyclization . . . . . . . . . . . . . . . . . . . . 717
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8.1.21.4.1.2 Variation 2: Dilithiation of N-tert-Butoxycarbonylbenzylamine and1,2-Addition to Acrolein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 717
8.1.21.4.1.3 Variation 3: Dilithiation of tert-Butyl Allylcarbamate, Transmetalation toZinc, and Addition to Aldehydes and Ketones . . . . . . . . . . . . . . . 718
8.1.21.4.1.4 Variation 4: Deprotonation of Tetrahydroisoquinoline Pivalamides,Transmetalation to Magnesium, and Addition to Aldehyde . . 719
8.1.21.4.1.5 Variation 5: Deprotonation of N-Benzyl-N-(tert-butoxycarbonyl)-4-methoxyaniline, Addition to Imines and SpontaneousCyclization to Imidazolidinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . 720
8.1.21.4.1.6 Variation 6: Regioselective Deprotonation andAza-[2,3]-Wittig Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
8.1.21.4.2 Method 2: Deprotonation of Chiral Substrates . . . . . . . . . . . . . . . . . . . . . . . . . 7218.1.21.4.2.1 Variation 1: Deprotonation and Alkylation of N-Benzyloxazolidinones . . . . 7218.1.21.4.2.2 Variation 2: Deprotonation of Chiral Tetrahydroisoquinolinyl
Formamidine: Asymmetric Synthesis of Isoquinoline Alkaloids 7228.1.21.4.2.3 Variation 3: Deprotonation of Hexahydropyrido[3,4-b]indole
Formamidines: Asymmetric Synthesis of Indole Alkaloids . . . . 7248.1.21.4.2.4 Variation 4: Deprotonation of Dihydrooxazole-Substituted Tetrahydro-
isoquinolines: Asymmetric Synthesis of Isoquinolines andMorphinan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 725
8.1.21.4.2.5 Variation 5: Deprotonation of Chiral Tetrahydroisoquinolines,Transmetalation to Magnesium, and Addition to Aldehydes:Asymmetric Synthesis of Phthalideisoquinoline Alkaloids . . . . 727
8.1.21.4.2.6 Variation 6: Æ,Æ¢-Dialkylation of Dihydroisoindole . . . . . . . . . . . . . . . . . . . . . . 7288.1.21.4.2.7 Variation 7: C2-Symmetric Dialkylation of Chiral Formamidinyl
Binaphthoazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7298.1.21.4.3 Method 3: Deprotonation of Achiral Substrates with Chiral Base . . . . . . . . 7298.1.21.4.3.1 Variation 1: Asymmetric Regioselective Deprotonation of Allylic and
Benzylic Positions over Alkyl Positions in tert-Butyl Carba-mates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 730
8.1.21.4.3.2 Variation 2: Asymmetric Deprotonation of N-Benzyl-N-tert-butoxy-carbonyl-4-methoxyaniline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731
8.1.21.4.3.3 Variation 3: Asymmetric Deprotonation of N-Benzyl-N-tert-butoxy-carbonyl-4-methoxyaniline and 1,4-Addition to Enones . . . . . 732
8.1.21.4.3.4 Variation 4: Deprotonation of N-tert-Butoxycarbonyl-4-methoxy-N-[(2E)-3-phenylprop-2-enyl]aniline and Electrophilic Substitution:Synthesis of Either R- or S-Homoenolate Synthons . . . . . . . . . . 733
8.1.21.4.3.5 Variation 5: Electrophilic Substitution of Aldehyde HomoenolateSynthons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 734
8.1.21.4.3.6 Variation 6: Asymmetric Deprotonation, Transmetalation to Aluminum orTitanium, and Addition to Aldehydes . . . . . . . . . . . . . . . . . . . . . . . 735
8.1.21.4.3.7 Variation 7: Asymmetric Deprotonation and ReverseAza-Brook Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
8.1.21.4.3.8 Variation 8: Asymmetric Deprotonation and Dearomatizing Cyclization ofÆ-Lithio Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
8.1.21.4.3.9 Variation 9: Asymmetric Deprotonation and Alkylation ofa Tricarbonylchromium–Benzyl Imine Complex . . . . . . . . . . . . . 738
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8.1.21.5 Synthesis and Applications of Dipole- and Heteroatom-StabilizedÆ-Lithioamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 739
8.1.21.5.1 Method 1: Oxygen- and tert-Butoxycarbonyl-Stabilized Æ-Lithioamines 7398.1.21.5.2 Method 2: Sulfur- and Dipole-Stabilized Æ-Lithioamines . . . . . . . . . . . . . . . . 7408.1.21.5.2.1 Variation 1: Asymmetric Corey–Seebach Synthesis of Æ-Hydroxyaldehydes
Using a Diphenylvalinol-Derived Oxazolidinone . . . . . . . . . . . . . 7408.1.21.5.2.2 Variation 2: Asymmetric Corey–Seebach Synthesis of Æ-Hydroxyaldehydes
Using a Camphor-Derived Oxazolidinone . . . . . . . . . . . . . . . . . . . 7418.1.21.5.3 Method 3: Nitrogen- and tert-Butoxycarbonyl-Stabilized Æ-Lithioamines 742
8.1.21.6 Synthesis and Applications of Non-Enolate Nitrogen Ylides . . . . . . . . . . . . . . . . . . 743
8.1.21.6.1 Method 1: Lewis Acid Activation of an Amine . . . . . . . . . . . . . . . . . . . . . . . . . 7438.1.21.6.1.1 Variation 1: Activation of an Æ-Aminoorganostannane with
Boron Trifluoride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7438.1.21.6.1.2 Variation 2: Activation of a Cyclic Amine with Boron Trifluoride,
Deprotonation, Double Transmetalation, and Alkylation . . . . . 7448.1.21.6.1.3 Variation 3: Activation of an Aziridine with Borane, Deprotonation and
Alkylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7458.1.21.6.1.4 Variation 4: Activation of a Benzylic Amine or Tetrahydroisoquinoline with
Borane, Deprotonation and Alkylation . . . . . . . . . . . . . . . . . . . . . . 7468.1.21.6.1.5 Variation 5: Activation of Dihydroisoindole with Borane:
Group-Selective Deprotonation with a Chiral Base,and Electrophilic Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
8.1.21.6.2 Method 2: Sigmatropic Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7508.1.21.6.2.1 Variation 1: Transmetalation of a 2-Tributylstannylammonium Ion and
[2,3]-Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7508.1.21.6.2.2 Variation 2: Activation and [2,3]-Rearrangement of
N-Allyltetrahydroisoquinoline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 751
8.1.22 Product Subclass 22: Lithium NitronatesN. Ono
8.1.22 Product Subclass 22: Lithium Nitronates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759
Synthesis of Product Subclass 22 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759
8.1.22.1 Method 1: Deprotonation of Nitroalkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7598.1.22.2 Method 2: Double Deprotonation of Nitroalkanes . . . . . . . . . . . . . . . . . . . . . 7608.1.22.3 Method 3: Addition of Nucleophiles to Nitroalkenes . . . . . . . . . . . . . . . . . . . 760
Applications of Product Subclass 22 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 762
8.1.22.4 Method 4: Nitroaldol Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7628.1.22.4.1 Variation 1: Nitro-Mannich Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7658.1.22.4.2 Variation 2: Michael Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7658.1.22.5 Method 5: Acylation of Nitroalkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7658.1.22.6 Method 6: Alkylation of Nitroalkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7668.1.22.6.1 Variation 1: Alkylation via Radicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7678.1.22.6.2 Variation 2: Transition-Metal-Catalyzed Alkylation of Nitroalkanes . . . . . . . 7698.1.22.6.3 Variation 3: Arylation of Nitro Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7708.1.22.7 Method 7: Introduction of Heteroatoms into Nitroalkanes . . . . . . . . . . . . . 771
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8.1.23 Product Subclass 23: ª-Lithio Ethers and Related CompoundsD. Caine
8.1.23 Product Subclass 23: ª-Lithio Ethers and Related Compounds . . . . . . . . . . . . 775
Synthesis of Product Subclass 23 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776
8.1.23.1 Method 1: Reductive Lithiation of Halide and Phenyl Sulfide DerivativesContaining Neutral (Uncharged) Alkoxy and OtherSubstituents at the ª-Position . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776
8.1.23.1.1 Variation 1: Reductive Lithiation with Lithium Metal . . . . . . . . . . . . . . . . . . . . 7768.1.23.1.2 Variation 2: Reductive Lithiations with Lithium Arene Radical Anions . . . . . 7778.1.23.2 Method 2: Reductive Lithiation of ª-Oxido and Related
ª-Amido Halides and Phenyl Sulfides . . . . . . . . . . . . . . . . . . . . . . . 7798.1.23.2.1 Variation 1: Reductive Lithiation with Lithium Metal . . . . . . . . . . . . . . . . . . . . 7808.1.23.2.2 Variation 2: Reductive Lithiation with Lithium Arene Radical Anions . . . . . 7818.1.23.3 Method 3: Halogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7838.1.23.4 Method 4: Metal–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7848.1.23.4.1 Variation 1: Selenium–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7848.1.23.4.2 Variation 2: Tin–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7858.1.23.5 Method 5: Hydrogen–Lithium Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7878.1.23.6 Method 6: Reductive Cleavage of Four-Membered Heterocycles by
Lithium Arene Radical Anions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7888.1.23.7 Method 7: Addition of Organolithium Reagents to Allylic Systems . . . . . . 790
8.1.24 Product Subclass 24: Carbamoyllithium andTrihalomethyllithium CompoundsC. Metallinos
8.1.24 Product Subclass 24: Carbamoyllithium andTrihalomethyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
Synthesis of Product Subclass 24 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
8.1.24.1 Carbamoyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
8.1.24.1.1 Method 1: Deprotonation of Formyl Hydrogen in Formamides . . . . . . . . . 7968.1.24.1.1.1 Variation 1: Using Lithium Diisopropylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . 7968.1.24.1.1.2 Variation 2: Using tert-Butyllithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7968.1.24.1.2 Method 2: Reaction of Lithium Amide Bases and Carbon Monoxide . . . . . 7978.1.24.1.2.1 Variation 1: Using Lithium Amide Bases and Carbon Monoxide . . . . . . . . . . 7978.1.24.1.2.2 Variation 2: Using Lithium Bis(carbamoyl)cuprates and Carbon Monoxide 7988.1.24.1.3 Method 3: Transmetalation of Carbamoylmercury and
Carbamoyltellurium Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7998.1.24.1.3.1 Variation 1: Using Bis(N,N-dialkylcarbamoyl)mercury Reagents . . . . . . . . . . 7998.1.24.1.3.2 Variation 2: Using N,N-Dialkylcarbamoyltellurium Reagents . . . . . . . . . . . . . 800
8.1.24.2 Trihalomethyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800
8.1.24.2.1 Method 1: Deprotonation of Chloroform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801
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8.1.25 Product Subclass 25: Tris(organosulfanyl)- and Tris(organoselanyl)-methyllithium CompoundsC. N�jera and M. Yus
8.1.25 Product Subclass 25: Tris(organosulfanyl)- and Tris(organoselanyl)-methyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 805
Synthesis and Applications of Product Subclass 25 . . . . . . . . . . . . . . . . . . . . . . . . . 805
8.1.25.1 Method 1: Alkylation Reactions of Tris(methylsulfanyl)- andTris(phenylsulfanyl)methyllithium . . . . . . . . . . . . . . . . . . . . . . . . . . 805
8.1.25.1.1 Variation 1: Reaction with Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . 8078.1.25.1.2 Variation 2: Michael-Type Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8088.1.25.2 Method 2: Synthesis of Other Sulfur-Containing Triheterosubstituted
Methyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8108.1.25.3 Method 3: Synthesis of Tris(methylselanyl)- and
Tris(phenylselanyl)methyllithium . . . . . . . . . . . . . . . . . . . . . . . . . . . 810
8.1.26 Product Subclass 26: Bis(organosulfanyl)- andBis(organoselanyl)methyllithium CompoundsC. N�jera and M. Yus
8.1.26 Product Subclass 26: Bis(organosulfanyl)- andBis(organoselanyl)methyllithium Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
Synthesis and Applications of Product Subclass 26 . . . . . . . . . . . . . . . . . . . . . . . . . 813
8.1.26.1 Method 1: Synthesis of Bis(methylsulfanyl)methyllithium . . . . . . . . . . . . . . 8138.1.26.2 Method 2: Synthesis of 1,3-Dithian-2-yllithium and Reaction with
Alkyl Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8148.1.26.2.1 Variation 1: Reaction with Epoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8158.1.26.2.2 Variation 2: Reaction with Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . 8178.1.26.2.3 Variation 3: Michael-Type Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8188.1.26.2.4 Variation 4: Acylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8198.1.26.3 Method 3: Synthesis and Alkylation Reactions of Bis(phenylsulfanyl)-
methyllithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8198.1.26.3.1 Variation 1: Reaction with Carbonyl Compounds and
Their Æ,�-Unsaturated Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . 8208.1.26.4 Method 4: Synthesis of Other Cyclic 2-Lithio Dithioacetals . . . . . . . . . . . . . 8218.1.26.5 Method 5: Synthesis of Æ-Lithio Æ-Organosulfanyl Ethers . . . . . . . . . . . . . . 8228.1.26.5.1 Variation 1: Methoxy(phenylsulfanyl)methyllithium . . . . . . . . . . . . . . . . . . . . . 8228.1.26.5.2 Variation 2: 1,3-Oxathian-2-yllithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8238.1.26.6 Method 6: Synthesis of Æ-Lithio Æ-Arylsulfonyl Ethers . . . . . . . . . . . . . . . . . . 8258.1.26.6.1 Variation 1: 2-(Arylsulfonyl)oxiran-2-yllithiums . . . . . . . . . . . . . . . . . . . . . . . . . 8268.1.26.6.2 Variation 2: 2-(Arylsulfonyl)tetrahydropyran-2-yllithiums . . . . . . . . . . . . . . . . 8278.1.26.7 Method 7: Synthesis and Alkylation Reactions of Æ-Lithio
Æ-Organosulfanyl and Æ-Lithio Æ-Organosulfinyl Sulfoxides . . 8288.1.26.7.1 Variation 1: Reaction with Carbonyl Compounds and
Their Æ,�-Unsaturated Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . 8308.1.26.8 Method 8: Synthesis and Reactions of Æ-Lithio Æ-Organosulfanyl Sulfones 8318.1.26.9 Method 9: Synthesis and Reactions of Æ-Lithio Selenoacetals . . . . . . . . . . . 833
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8.1.27 Product Subclass 27: Æ-Lithio Vinyl EthersR. W. Friesen and C. F. Sturino
8.1.27 Product Subclass 27: Æ-Lithio Vinyl Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841
Synthesis of Product Subclass 27 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841
8.1.27.1 Method 1: Deprotonation of Vinyl Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8428.1.27.1.1 Variation 1: Deprotonation of Acyclic and Cyclic Vinyl Ethers . . . . . . . . . . . . 8428.1.27.1.2 Variation 2: Deprotonation of Allenyl Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8468.1.27.2 Method 2: Transmetalation of (Æ-Alkoxyvinyl)stannanes . . . . . . . . . . . . . . . 8478.1.27.3 Method 3: Lithium–Halogen Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Applications of Product Subclass 27 in Organic Synthesis . . . . . . . . . . . . . . . . . . . 850
8.1.27.4 Method 4: Synthesis of Æ-Alkoxyvinyl Organometallic Compounds . . . . . 8508.1.27.4.1 Variation 1: Vinylstannanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8508.1.27.4.2 Variation 2: Vinylsilanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8518.1.27.5 Method 5: Synthesis of 2-Aryldihydropyrrolohydrazines . . . . . . . . . . . . . . . . 8538.1.27.6 Method 6: Æ-Difluoro Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8548.1.27.7 Method 7: Synthesis of ª-Oxo Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8558.1.27.8 Method 8: Synthesis of Æ-Hydroxy Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . 8568.1.27.9 Method 9: Synthesis of Substituted 1,4-Dioxins . . . . . . . . . . . . . . . . . . . . . . . 8588.1.27.10 Method 10: Synthesis of �- and ª-Hydroxyalkenes . . . . . . . . . . . . . . . . . . . . . . 859
Keyword Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxiii
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . lxxxv
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