Organic reactions in water have proven a useful synthetic tool, and provide cost-efficient, safe, and environmentally friendly alternatives to organic-solvent based reactions. This field has been greatly expanded over the last decade, and currently there are many diverse applications in both industry and academic laboratories.

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

An extensive update of the classic reference on organic reactions in water Published almost a decade ago, the first edition has served as the guide for research in this burgeoning field. Due to the cost, safety, efficiency, and environmental friendliness of water as a solvent, there are many new applications in industry and academic laboratories. More than forty percent of this extensively updated second edition covers new reactions. For ease of reference, it is organized by functional groups. A core reference, Comprehensive Organic Reactions in Aqueous Media, Second Edition: Provides the most comprehensive coverage of aqueous organicreactions available Covers the basic principles and theory and progresses to applications Includes alkanes, alkenes, aromatics, electrophilic substitutions, carbonyls, alpha, beta-unsaturated carbonyls, carbon-nitrogen bonds, organic halides, pericyclic reactions, photochemical reactions, click chemistry, and multi-step syntheses? Provides examples of applications in industry This is the premier reference for chemists and chemical engineers in industry or research, as well as for students in advanced-level courses.