Comprehensive Organic Reactions in Aqueous Media

Chao-Jun Li, PhD, is Professor at McGill University in Canada. Professor Li began teaching at Tulane University in 1994 and received an NSF CAREER Award for work done from 1998–2002, the Outstanding Young Oversea Scientist Award from the NSFC in 2001, and the U.S. Presidential Green Chemistry Challenge Award in Academia for 2001. Dr. Li moved to McGill University in 2003 and received a Canada Research Chair in Green Chemistry (Tier I). He coauthored the popular first edition of Organic Reactions in Aqueous Media (Wiley). Tak-Hang Chan, PhD, is Professor Emeritus at McGill University in Canada and Chair Professor of Organic Chemistry at the Hong Kong Polytechnic University in Hong Kong. In 1993, Professor Chan received the prestigious R.U. Lemieux Award of the Canadian Society of Chemistry. A pioneer in green chemistry, he is a Fellow of the Royal Society of Canada and holds Honorary Professorships at Academia Sinica, Peking University, and Lanzhou University. He was coauthor of the first edition.

Preface to the Second Edition xv

1 Introduction 1

1.1 The Structure and Forms of Water 3

1.2 Properties of Water 4

1.3 Solvation 6

1.4 Hydrophobic Effect 6

1.5 Salt Effect 8

1.6 Water Under Extreme Conditions 9

References 13

2 Alkanes 15

2.1 Oxygenation of Alkanes 15

2.2 Halogenation of Alkanes 20

2.3 Formation of Carbon–Carbon Bonds 20

2.4 DH Exchange of Alkanes in Water 21

References 22

3 Alkenes 25

3.1 Reduction 25

3.1.1 Hydrogenation 25

3.2 Electrophilic Additions 28

3.2.1 Reaction with Halogen 28

3.2.2 Reaction with Hydrogen Halides 28

3.2.3 Addition of Water 29

3.2.4 OxymercurationOxymetalation 29

3.2.5 Epoxidation 30

3.2.6 Dihydroxylation and Hydroxylamination 35

3.2.7 Wacker’s Oxidation 40

3.2.8 Oxidative C=C Bond Cleavage 43

3.2.9 C–C Bond Formations 46

3.3 Radical Reactions of Alkenes 47

3.3.1 Radical Polymerization of Alkenes 47

3.3.2 Radical Additions 48

3.3.3 Radical Cyclization 49

3.4 Carbene Reactions 50

3.4.1 The Generation of Carbenes in Aqueous Medium 50

3.4.2 The Stability of Carbenes 50

3.4.3 The Reaction of Carbenes with Alkenes in Aqueous Medium 51

3.5 Alkene Isomerization 52

3.6 Transition-Metal Catalyzed C–C Formation Reactions 53

3.6.1 Polymerizations 53

3.6.2 Heck Reactions and Related VinylationArylation 54

3.6.3 Hydrovinylation 56

3.6.4 Reaction with Arenes 56

3.6.5 Hydroformylation 57

3.6.6 Reaction with Alkynes 58

3.6.7 Carbonylation 60

3.6.8 Cycloaddition Reactions of Alkenes 60

3.7 Olefin Metathesis 60

3.7.1 Ring-Opening Metathesis Polymerization (romp) 61

3.7.2 Ring-Closing Metathesis (RCM) 62

3.8 Reaction of Allylic C–H Bond 64

3.8.1 Allylic Oxidation 64

3.8.2 C–C Bond Formations 65

References 66

4 Alkynes 77

4.1 Reaction of Terminal Alkynes 77

4.1.1 Alkyne Oxidative Dimerization 77

4.1.2 Alkyne-Alkyne Addition 78

4.1.3 Reaction of Alkynes with Organic Halides 81

4.1.4 Reaction of Alkynes with Carbonyl Compounds 93

4.1.5 Reaction of Alkynes with C=N Compounds 94

4.1.6 Conjugate Addition with Terminal Alkynes 97

4.2 Additions of C≡C bonds 98

4.2.1 Reduction  98

4.2.2 Addition of Water 98

4.2.3 Addition of Alcohols and Amines 100

4.2.4 Hydrosilation and Hydrometalations 102

4.2.5 Addition of Aryls 104

4.2.6 Carbonylation of Internal Alkynes 107

4.2.7 Other Additions to Alkynes 109

4.3 Transition-Metal Catalyzed Cycloadditions 109

4.3.1 Pauson-Khand-Type Reactions 109

4.3.2 [2 + 2 + 2] Cyclotrimerization 111

4.3.3 [2 + 2 + 2] Alkyne-Nitrile Cyclotrimerization 114

4.3.4 [3 + 2] 1,3-Dipolar Cycloaddition  114

4.3.5 [4 + 2] Cycloaddition 118

4.3.6 [5 + 2] Cycloaddition 119

4.3.7 Other Cycloadditions 119

4.4 Other Reactions 121

References 121

5 Alcohols, Phenols, Ethers, Thiols, and Thioethers 129

5.1 Oxidation of Alcohols 129

5.1.1 Diol Cleavage 134

5.2 SubstitutionsElimination 134

5.3 Addition of Alcohols, Phenols, and Thiols to Alkene and Alkyne Bonds 137

5.4 Addition of Alcohols to C=O Bonds: Esterification and Acetal Formations 137

5.5 Reaction of Ethers and Cyclic Ethers 138

5.5.1 Ethers and Cyclic Ethers 138

5.5.2 Reactions of Epoxides in Water and “Click Chemistry” 139

5.6 Reaction of Sulfur Compounds 141

5.6.1 Oxidation of Thiols and Thioethers 141

5.6.2 Reduction of Disulfides 142

5.6.3 Native Chemical Ligation for Peptide Synthesis 143

5.6.4 Other Reactions 143

References 144

6 Organic Halides 151

6.1 General 151

6.2 Reduction 151

6.3 Elimination Reactions 154

6.4 Nucleophilic Substitutions 154

6.4.1 Substituted by Heteroatoms 154

6.4.2 Carbon–Carbon Bond Formations 158

6.5 Reductive Coupling 161

6.5.1 Wurtz-Type Coupling 161

6.5.2 Ullmann-Type Coupling and Related Reactions 163

6.6 Carbonylation of Organic Halides 164

6.6.1 Carbonylation of Alkyl Halides 164

6.6.2 Carbonylation of Allylic and Benzylic Halides 165

6.6.3 Carbonylation of Aryl Halides 165

6.7 Transition-Metal Catalyzed Coupling Reactions 166

6.7.1 The Heck Coupling 166

6.7.2 The Suzuki Coupling 167

6.7.3 The Stille Coupling 172

6.7.4 Other Transition-Metal Catalyzed Couplings 173

References 174

7 Aromatic Compounds 181

7.1 General 181

7.2 Substitution Reactions 182

7.2.1 Electrophilic Substitutions 182

7.2.2 Friedel-Crafts C–C Bond Formations 183

7.2.3 Other Substitution Reactions 189

7.3 Oxidation Reactions 190

7.3.1 Simple Oxidation 190

7.3.2 Oxidative Coupling 191

7.4 Reductions 192

References 193

8 Aldehdye and Ketones 197

8.1 Reduction 197

8.1.1 Hydrogenation 197

8.1.2 Other Reductions 198

8.2 Oxidation 204

8.3 Nucleophilic Addition: C–C Bond Formation 206

8.3.1 Allylation 206

8.3.2 Propargylation 238

8.3.3 Cyclopentadienylation 242

8.3.4 Benzylation 242

8.3.5 ArylationVinylation 244

8.3.6 Alkynylation 246

8.3.7 Alkylation  246

8.3.8 Reformatsky-Type Reaction 246

8.3.9 Direct Aldol Reaction 248

8.3.10 Mukaiyama Aldol Reaction 252

8.3.11 Hydrogen Cyanide Addition 258

8.3.12 Wittig Reactions 259

8.4 Pinacol Coupling 261

8.5 Other Reactions (Halogenation and Oxidation of α-H) 262

References 263

9 Carboxylic Acids and Derivatives 279

9.1 General 279

9.1.1 Reaction of α-Hydrogen 279

9.1.2 Reduction 279

9.2 Carboxylic Acids 280

9.2.1 EsterificationAmidation 280

9.2.2 Decarboxylation 287

9.3 Carboxylic Acid Derivatives 287

9.3.1 Esters and Thiol Esters 287

9.3.2 Acid Halides and Anhydrides 288

9.3.3 Amides 289

9.3.4 Nitriles 289

References 290

10 Conjugated Carbonyl Compounds 293

10.1 Reduction 293

10.1.1 Hydrogenation 293

10.1.2 Asymmetric Hydrogenation 295

10.1.3 Reduction by Other Methods 296

10.2 Epoxidation, Dihydroxylation, Hydroxyamination 297

10.3 Conjugate Addition: Heteroatom 298

10.4 C–C Bond Formation 301

10.4.1 Addition of Hydrogen Cyanide 302

10.4.2 Addition of α-Carbonyl Compounds 302

10.4.3 Addition of Allyl Groups 304

10.4.4 Addition of Alkyl Groups 305

10.4.5 Addition of Vinyl and Aryl Groups 307

10.4.6 Addition of Alkynyl Groups 310

10.4.7 Other Conjugate Additions 310

10.5 Other Reactions 310

10.5.1 Reductive Coupling 310

10.5.2 Baylis-Hillman Reactions 311

10.5.3 γ-Addition of Alkynoates 314

References 315

11 Nitrogen Compounds 321

11.1 Amines 321

11.1.1 Alkylation 321

11.1.2 Diazotization and Nitrosation 322

11.1.3 Oxidation 323

11.1.4 Reaction with Carbonyl Compounds 326

11.2 Imines 327

11.2.1 Reductions 327

11.2.2 Nucleophilic Additions 329

11.2.3 Reductive Coupling 342

11.3 Diazo Compounds 343

11.3.1 Substitution 343

11.3.2 Reduction 343

11.3.3 Cyclopropanation 344

11.3.4 Coupling Reaction 346

11.4 Azides 346

11.4.1 Substitution 346

11.4.2 Click Chemistry 347

11.5 Nitro Compounds 349

References 349

12 Pericyclic Reactions 355

12.1 Introduction 355

12.2 Diels-Alder Reactions 357

12.2.1 Lewis-Acid Catalysis 360

12.2.2 Asymmetric Diels-Alder Reactions 367

12.2.3 Theoretical and Mechanistic Studies 371

12.2.4 Synthetic Applications 374

12.2.5 Hetero-Diels-Alder Reactions 382

12.2.6 Asymmetric Hetero-Diels-Alder Reactions 388

12.2.7 Other Cyclization Reactions 390

12.3 Sigmatropic Rearrangements 392

12.3.1 Claisen Rearrangements 392

12.3.2 Cope Rearrangements 397

12.4 Photochemical Cycloaddition Reactions 398

References 399

Index 409