Organolithiums : selectivity for synthesis / Jonathan Clayden.

Format:

Book

Author/Creator:

Clayden, Jonathan.

Series:

Tetrahedron organic chemistry series ; v. 23.

Tetrahedron organic chemistry series ; v. 23

Language:

English

Subjects (All):

Organolithium compounds--Synthesis.

Organolithium compounds.

Physical Description:

xvi, 383 pages : illustrations ; 25 cm.

Edition:

First edition.

Place of Publication:

Amsterdam ; Boston : Pergamon, 2002.

Summary:

This book, Volume 23 in the Tetrahedron Organic Chemistry series, presents organolithium chemistry from the perspective of a synthetic organic chemist, drawing from the synthetic literature to present a unified overview of how organolithiums can be used to make molecules. The development of methods for the regioselective synthesis of organolithiums has replaced their image of indiscriminate high reactivity with one of controllable and subtle selectivity. Organolithium chemistry has a central role in the selective construction of C-C bonds in both simple and complex molecules, and for example has arguably overtaken aromatic electrophilic substitution as the most powerful method for regioselective functionalisation of aromatic rings. The twin themes of reactivity and selectivity run through the book, which reviews the ways by which organolithiums may be formed and the ways in which they react. Topics include recent advances in directed metallation, reductive lithiation and organolithium cyclisation reactions, along with a discussion of organolithium stereochemistry and the role played by ligands such as (-)-sparteine. This book will be most suited to graduate students or researchers who wish to use organolithiums to construct molecules, or to understand more about organolithium stereochemistry and reactivity and the mechanisms of their reactions.

Contents:

1.2 Organolithiums in solution 2

Chapter 2 Regioselective Synthesis of Organolithiums by Deprotonation 9

2.2 Lithiation [alpha] to heteroatoms 10

2.2.1 Lithiation [alpha] to oxygen 12

2.2.2 Lithiation [alpha] to nitrogen 14

2.2.2.1 Amides 15

2.2.2.2 Benzotriazoles and other 5-membered heterocycles 20

2.2.2.3 Formamidines 20

2.2.2.4 Nitrosoamines 21

2.2.2.5 Imines 22

2.2.2.6 Isocyanides 23

2.2.2.7 Lithiation of trigonal C-H [alpha] to nitrogen 23

2.2.2.8 N-oxides and amine-boron complexes 23

2.2.3 Lithiation [alpha] to sulfur 24

2.2.4 Lithiation [alpha] to silicon 26

2.2.5 Lithiation at unfunctionalised allylic positions 26

2.3 Ortholithiation 28

2.3.1 Introduction: mechanism 28

2.3.2 Classes of directing group 34

2.3.2.1 N+O class 36

2.3.2.1.1 Secondary and tertiary amides 36

2.3.2.1.2 [alpha]-Amino alkoxides 41

2.3.2.1.3 Oxazolines 43

2.3.2.1.4 O-Carbamates 44

2.3.2.1.5 Anilides and N-aryl carbamates 45

2.3.2.2 S+O class 46

2.3.2.3 N class 50

2.3.2.3.1 Aminomethyl groups 50

2.3.2.3.2 Anilines and isocyanides 51

2.3.2.3.3 Imines, nitriles, hydrazones and nitrogen heterocycles 51

2.3.2.4 O class 53

2.3.2.4.1 Ethers and alkoxides 53

2.3.2.4.2 Ketones, esters and carboxylates 56

2.3.2.5 X class 58

2.3.3 Ortholithiation of aromatic heterocycles 59

2.3.3.1 Electron-deficient heterocycles 59

2.3.3.2 Electron-rich heterocycles 70

2.3.4 Lithiation of metal-arene complexes 71

2.3.4.1 Chromium-arene complexes 71

2.3.4.2 Ferrocenes 72

2.4 Lateral lithiation 73

2.4.1 Mechanism and regioselectivity 73

2.4.2 Classes of directing group 75

2.4.2.1 Secondary and tertiary amides 75

2.4.2.2 Nitriles 77

2.4.2.3 Oxazolines, imidazolines and tetrazoles 77

2.4.2.4 Carboxylates 77

2.4.2.5 Carboxylic esters 78

2.4.2.6 Ketones 78

2.4.2.7 Aldehydes protected as [alpha]-amino alkoxides 79

2.4.2.8 Alcohols and phenols (cresols) and their derivatives 79

2.4.2.9 Sulfur-based functional groups 81

2.4.2.10 Aniline and aminoalkylbenzene derivatives 82

2.4.2.11 Halogens 83

2.4.2.12 Lateral lithiation of heterocycles 83

2.5 Remote lithiation, and [beta]-lithiation of non-aromatic compounds 86

2.6 Superbases 87

2.7 Cooperation, competition and regioselectivity 90

Chapter 3 Regioselective Synthesis of Organolithiums by X-Li Exchange 111

3.1 Halogen-lithium exchange 111

3.1.1 Reactivity 111

3.1.2 Mechanism 118

3.1.3 Synthesis of aryllithiums 124

3.1.4 Synthesis of heteroaryllithiums 127

3.1.5 Synthesis of vinyllithiums 132

3.1.6 Synthesis of alkyllithiums 134

3.1.7 Diastereoselective halogen-lithium exchange 135

3.2 Tin-lithium exchange 136

3.3 Chalcogen-lithium exchange 139

3.3.1 Selenium-lithium exchange 139

3.3.2 Tellurium-lithium exchange 141

3.3.3 Sulfur-lithium exchange 141

3.4 Phosphorus-lithium exchange 142

Chapter 4 Regioselective Synthesis of Organolithiums by C-X Reduction 149

4.1 Reductive lithiation of alkyl and aryl halides 149

4.1.1 Reductive lithiation with lithium metal 149

4.1.2 Reductive lithiation promoted by arenes 150

4.2 Reductive lithiation of C-O bonds 154

4.3 Reductive lithiation of C-N bonds 158

4.4 Reductive lithiation of C-S bonds 159

4.4.1 Reduction of sulfides 159

4.4.2 Reduction of sulfones 164

4.5 Reductive lithiation of C-C bonds and [pi]-bonds 165

Chapter 5 Stereoselective and Stereospecific Synthesis of Organolithiums 169

5.1 Configurational stability of organolithiums 169

5.1.1 Determining configurational stability 169

5.1.2 Unfunctionalised organolithiums 175

5.1.2.1 Secondary organolithiums 175

5.1.2.2 Primary organolithiums 175

5.1.2.3 Solvent effects 176

5.1.3 Cyclopropyllithiums 176

5.1.4 Organolithiums [alpha] to oxygen 178

5.1.4.1 Simple acyclic [alpha]-alkoxy organolithiums 178

5.1.4.2 Cyclic [alpha]-alkoxy organolithiums 180

5.1.4.3 Oxiranyllithiums 183

5.1.4.4 Allylic and benzylic [alpha]-alkoxy organolithiums 184

5.1.5 Organolithiums [alpha] to nitrogen 186

5.1.5.1 Cyclic [alpha]-amino organolithiums: 3-membered rings 186

5.1.5.2 Pyrrolidinyllithiums and piperidinyllithiums: 5- and 6-membered rings 188

5.1.5.3 Lithiated formamidines 191

5.1.5.4 Acyclic [alpha]-amino organolithiums 192

5.1.5.5 Benzylic and allylic [alpha]-amino organolithiums 193

5.1.5.6 Crystallographic and theoretical data 195

5.1.6 Organolithiums [alpha] to halogens 197

5.1.7 Organolithiums [alpha] to sulfur 199

5.1.7.1 Lithiated sulfides 199

5.1.7.2 Lithiated thiocarbamates 202

5.1.7.3 Lithiated sulfones 202

5.1.7.4 Mechanism of racemisation 204

5.1.8 Organolithiums [alpha] to selenium 205

5.1.9 Organolithiums [alpha] to phosphorus 207

5.1.10 Organolithiums [alpha] to silicon 207

5.1.11 Benzyllithiums 208

5.1.11.1 Secondary benzyllithiums 208

5.1.11.2 Tertiary benzyllithiums 211

5.1.12 Vinyllithiums 212

5.2 Stereospecific synthesis of organolithiums by X-Li exchange 214

5.2.1 Tin-lithium exchange 214

5.2.1.1 Vinylstannanes 214

5.2.1.2 [alpha]-Heterosubstituted stannanes 214

5.2.1.3 Non-heterosubstituted stannanes 216

5.2.2 Halogen-lithium exchange 222

5.2.3 Selenium-lithium exchange 222

5.2.4 Sulfur-lithium exchange 223

5.2.5 Other metal-lithium exchanges 223

5.2.6 Stereospecific deprotonation 223

5.3 Diastereoselective deprotonation 224

5.3.1 Diastereoselective lateral lithiation 224

5.3.2 Diastereoselective ortholithiation 225

5.4 Enantioselective deprotonation 226

Chapter 6 Stereospecific and Stereoselective Substitution Reactions of Organolithiums 241

6.1 Stereospecific reactions of organolithium compounds 241

6.1.2 Vinyllithiums 242

6.1.3 Non-stabilised alkyllithiums 242

6.1.3.1 The general rule: retention (S[subscript E]2ret) 242

6.1.3.2 The exception - alkylation of lithiated N-alkyl pyrrolidines and piperidines: inversion (S[subscript E]2inv) 246

6.1.3.3 Rearrangements ([1,2] and [2,3], except Brook rearrangements) of unstabilised organolithiums: inversion (S[subscript E]2inv) 247

6.1.4 Stabilised alkyllithiums: retention (S[subscript E]2ret) or inversion (S[subscript E]2inv)? 249

6.1.4.1 Benzyllithiums 249

6.1.4.2 Allyllithiums 256

6.1.4.3 Rearrangements of stabilised organolithiums 257

6.2 Stereoselective substitution in the presence of chiral ligands 258

6.2.1 Introduction: Mechanisms 258

6.2.2 Chiral ligands 258

6.2.3 Enantioselective deprotonation 260

6.2.4 Enantioselective substitution 260

6.2.5 Configurational stability, stereospecificity, and dynamic resolutions 261

6.2.6 Dynamic thermodynamic resolution 262

6.2.7 Dynamic kinetic resolution 268

6.2.8 Summary: mechanisms of asymmetric functionalisation with (-)-sparteine 268

Chapter 7 Regio- and Stereoselective Addition Reactions of Organolithiums 273

7.1 Intermolecular addition to [pi] bonds: Carbolithiation 273

7.1.1 Carbolithiation of simple alkenes 273

7.1.2 Carbolithiation of conjugated alkenes and alkynes 274

7.1.3 Carbolithiation of functionalised alkenes 276

7.1.4 Enantioselective carbolithiation 280

7.2 Intramolecular addition and substitution reactions: anionic cyclisation 282

7.2.1 Anionic cyclisations onto carbonyl compounds and derivatives 282

7.2.1.1 Cyclisations of aryllithiums - Parham cyclisations 282

7.2.1.2 Cyclisations of alkenyllithiums 284

7.2.1.3 Cyclisations of alkyllithiums 286

7.2.1.4 Cyclisations of alkynyllithiums 287

7.2.2 Anionic cyclisations onto epoxides 288

7.2.3 Anionic cyclisations onto alkyl halides and similar compounds 290

7.2.4 Anionic cyclisations onto alkenes and alkynes 293

7.2.4.1 Cyclisation onto activated alkenes 293

7.2.4.2 Cyclisation onto unactivated alkenes 294

7.2.4.2.1 Cyclopentanes 301

7.2.4.2.2 Cascade reactions 308

7.2.4.2.3 Tetrahydrofurans 310

7.2.4.2.4 Pyrrolidines 312

7.2.4.2.5 Tetrahydrothiophenes 314

7.2.4.2.6 Stereoselectivity and mechanism 314

7.2.4.3 Anionic cyclisation onto allenes 321

7.2.4.4 Anionic cyclisation onto alkynes 321

7.2.4.6 Anionic cyclisation onto aromatic rings 327

Chapter 8 Organolithium Rearrangements 337

8.1 Shapiro Reaction 337

8.2 Brook Rearrangements 340

8.2.1 [1,2]-Brook Rearrangements 342

8.2.2 [1,3]-Brook Rearrangements 344

8.2.3 [1,4]-Brook Rearrangements 344

8.2.4 [1,4]-Retro-Brook rearrangements 345

8.3 [1,2]-Wittig Rearrangements 346

8.3.1 Mechanism and scope 346

8.3.2 Stereospecificity 348

8.3.3 [1,2]-Wittig rearrangements in synthesis 350

8.4 [2,3]-Wittig Rearrangements 351

8.4.1 Regioselectivity 352

8.4.2 Diastereoselectivity 354

8.4.2.1 Double bond geometry 354

8.4.2.2 Syn/anti relative stereochemistry 355

8.4.3 Stereospecificity and enantioselectivity 355

8.4.3.1 Stereospecific rearrangements of chiral allyl ethers 355

8.4.3.2 Stereoselective rearrangements with chiral auxiliaries 357

8.4.3.3 Stereospecific rearrangements of chiral organolithiums 357

8.4.4 [2,3]-Aza-Wittig rearrangements 359

Chapter 9 Organolithiums in Synthesis 365

9.1 Ochratoxin: ortholithiation and anionic Fries rearrangement 365

9.2 Corydalic acid methyl ester: lateral lithiation 366

9.3 Fredericamycin A: ortho, lateral and [alpha]-lithiation 367

9.4 ([plus or minus])-Atpenin B: metallation of an aromatic heterocycle 369

9.5 Flurbiprofen: metallation with LiCKOR superbases 370

9.6 California Red Scale Pheromone: [alpha]- and reductive lithiation 371

9.7 C1-C9 of the Bryostatins: diastereoselective bromine-lithium exchange 372

9.8 (S)-1-Methyldodecyl acetate, a Drosophila pheromone: (-)-sparteine assisted enantioselective lithiation 373

9.9 (-)-Paroxetine: (-)-sparteine-promoted asymmetric lithiation and substitution 374.

Notes:

Includes bibliographical references and index.

ISBN:

008043262X

0080432611

OCLC:

49680035