Modern Alkyne Chemistry: Catalytic and Atom-Economic Transformations

A comprehensive and up-to-date overview of alkyne chemistry, taking into account the progress made over the last two decades. The experienced editors are renowned world leaders in the field, while the list of contributors reads like a "Who's Who" of synthetic organic chemistry. The result is a valuable reference not only for organic chemists at universities and in the chemical industry, but also for biologists and material scientists involved in the modern synthesis of organic compounds and materials.

Table of Contents:
List of Contributors XIII Preface XVII 1 Introduction 1 Chao-Jun Li and Barry M. Trost 1.1 History of Alkynes 1 1.2 Structure and Properties of Alkynes 2 1.3 Classical Reactions of Alkynes 2 1.4 Modern Reactions 4 1.5 Conclusion 6 References 7 Part I Catalytic Isomerization of Alkynes 9 2 Redox Isomerization of Propargyl Alcohols to Enones 11 Barry M. Trost 2.1 Introduction 11 2.2 Base Catalysis 12 2.3 Ru Catalyzed 15 2.4 Rh Catalysis 20 2.5 Palladium Catalysis 22 2.6 Miscellaneous 24 2.7 Conclusions 25 References 25 3 Carbophilic Cycloisomerization Reactions of Enynes and Domino Processes 27 Jean-Pierre Genet, Patrick Y. Toullec, and Véronique Michelet 3.1 Introduction and Reactivity Principles 27 3.1.1 The Reactivity of Carbophilic Lewis Acids in the Presence of Enyne Substrates 27 3.2 Skeletal Rearrangement Reactions in the Absence of Nucleophiles 28 3.2.1 Synthesis of Dienes (1,3- and 1,4-Dienes) 28 3.2.2 Cycloisomerization Reactions Involving Activated Alkene Partners: Conia-Ene Reaction and Related Transformations 32 3.2.3 Formation of Bicyclic Derivatives 37 3.2.3.1 Formation of Bicyclopropanes 37 3.2.3.2 Formation of Bicyclobutenes 41 3.2.3.3 Formation of Larger Rings via Cycloisomerization- Rearrangements 42 3.3 Enyne Domino Processes 44 3.3.1 Domino Enyne Cycloisomerization–Nucleophile Addition Reactions 44 3.3.1.1 Oxygen and Nitrogen Nucleophiles 45 3.3.1.2 Carbon Nucleophiles 54 3.4 Conclusion 61 References 62 4 Alkyne Metathesis in Organic Synthesis 69 Alois Fürstner 4.1 Introduction 69 4.2 Mechanistic Background and Classical Catalyst Systems 70 4.3 State-of-the-Art Catalysts 75 4.4 Basic Reaction Formats and Substrate Scope 80 4.5 Selected Applications 85 4.5.1 Dehydrohomoancepsenolide 85 4.5.2 Olfactory Macrolides 86 4.5.3 Haliclonacyclamine C 87 4.5.4 Hybridalactone 88 4.5.5 Cruentaren A 88 4.5.6 The Tubulin-Inhibitor WF-1360F 89 4.5.7 Neurymenolide A 91 4.5.8 Leiodermatolide 91 4.5.9 Tulearin C 94 4.5.10 The Antibiotic A26771B 95 4.5.11 Lactimidomycin 96 4.5.12 Citreofuran 97 4.5.13 Polycavernoside 98 4.5.14 Amphidinolide F 99 4.5.15 Spirastrellolide F Methyl Ester 101 4.6 Conclusions 102 References 108 Part II Catalytic Cycloaddition Reactions 113 5 Alkyne–Azide Reactions 115 Sanne Schoffelen and Morten Meldal 5.1 Introduction 115 5.2 Reviews on Cu-Catalyzed Azide–Alkyne Cycloaddition 117 5.3 Mechanistic Considerations on the Cu(1) Catalysis 118 5.4 The Substrates for CuAAC 121 5.5 The Environment 124 5.6 Modified 1,2,3-Triazoles and CuAAC Side Reactions 125 5.6.1 Oxidative Couplings of Cu(1)–Triazole Complexes 125 5.6.2 Reactions in the 5-Position of Triazoles 125 5.6.3 Side Reactions due to Substrate Instability 126 5.7 The Catalyst 126 5.7.1 Recent Ligands and their Influence on Cu(1) Catalysis 126 5.7.2 Catalyst Structure–Activity Relationship 128 5.7.3 In Situ Generated CuAAC: Electro-, Photo-, and Self-Induced “Click” 130 5.8 Optimizing Conditions for CuAAC Reactions 131 5.9 CuAAC in Biological Applications 132 5.10 Biocompatibility of the CuAAC Reaction 133 References 137 6 Catalytic Cycloaddition Reactions 143 Fiona R. Truscott, Giovanni Maestri, Raphael Rodriguez, and Max Malacria 6.1 Introduction 143 6.2 (2 + 2) Cycloaddition 143 6.3 (3 + 2) and (2 + 1) Cycloaddition 145 6.4 (4 + 2) Cycloaddition 146 6.5 (5 + 1) and (4 + 1) Cycloadditions 149 6.6 (5 + 2) Cycloaddition 150 6.7 (6 + 2) Cycloaddition 152 6.8 (2 + 2 + 1) Cycloaddition 153 6.9 (2 + 2 + 2) Cycloaddition 155 6.10 (3 + 2 + 1) Cycloaddition 158 6.11 (3 + 2 + 2) Cycloaddition 159 6.12 (4 + 2 + 1) and (4 + 2 + 2) Cycloaddition 160 6.13 (4 + 3 + 2) Cycloaddition 163 6.14 (5 + 2 + 1) and (5 + 1 + 2 + 1) Cycloadditions 163 6.15 (2 + 2 + 1 + 1) and (2 + 2 + 2 + 1) Cycloadditions 164 6.16 (2 + 2 + 2 + 2) Cycloaddition 165 6.17 Conclusions 166 References 166 Part III Catalytic Nucleophilic Additions and Substitutions 171 7 Catalytic Conjugate Additions of Alkynes 173 Naoya Kumagai and Masakatsu Shibasaki 7.1 Introduction 173 7.2 Metal Alkynylides as Nucleophiles 173 7.2.1 Conjugate Addition of Metal Alkynylides 173 7.2.1.1 Conjugate Addition of Metal Alkynylides to s-cis α,β-Enones 173 7.2.1.2 Conjugate Addition of Metal Alkynylides with a Catalytic Promoter 176 7.2.1.3 Conjugate Addition of Metal Alkynylides with Stoichiometric Promoters 177 7.2.2 Enantioselective Conjugate Addition of Metal Alkynylides 178 7.2.2.1 Use of a Stoichiometric Amount of Chiral Sources 178 7.2.2.2 Catalytic Enantioselective Conjugate Addition of Metal Alkynylides 180 7.3 Direct Use of Terminal Alkynes as Pronucleophiles 182 7.3.1 Direct Catalytic Conjugate Addition of Terminal Alkynes 182 7.3.1.1 Introduction 182 7.3.1.2 Addition to Vinyl Ketones and Acrylates 182 7.3.1.3 Addition to β-Substituted α,β-Enones 184 7.3.2 Enantioselective Direct Catalytic Conjugate Addition of Terminal Alkynes 188 7.4 Summary and Conclusions 196 References 196 8 Catalytic Enantioselective Addition of Terminal Alkynes to Carbonyls 201 Barry M. Trost and Mark J. Bartlett 8.1 Introduction 201 8.2 Metallation of Terminal Alkynes: Formation of Alkynyl Nucleophiles 203 8.2.1 Deprotonation of Terminal Alkynes 203 8.2.2 Oxidative Insertion and Ligand Exchange: Formal Metallation of Terminal Alkynes 205 8.3 Ligand-Catalyzed Alkyne Additions with Stoichiometric Quantities of Metal 207 8.3.1 Addition of Alkynylzinc Nucleophiles to Aldehydes, Ketones, and Imines 207 8.3.2 Titanium-Catalyzed Alkynylation of Aldehydes and Ketones 217 8.3.3 Asymmetric Boron-Catalyzed Alkyne Additions to Aldehydes 222 8.4 Alkyne Additions with Catalytic Amounts of Metal 222 8.4.1 Asymmetric Alkyne Additions to Aldehydes and Ketones Catalyzed by Zinc Salts 222 8.4.2 Indium-Catalyzed Alkyne Additions to Aldehydes 224 8.4.3 Chromium-Catalyzed Alkynylation of Aldehydes with Haloacetylenes 225 8.4.4 Copper-Catalyzed Alkynylation of Aldehydes and Trifluoromethyl Ketones 227 8.4.5 Palladium-Catalyzed Additions to α,β-Unsaturated Carbonyls and Trifluoropyruvate 229 8.4.6 Enantioselective Ruthenium-Catalyzed Alkynylation of Aldehydes 230 8.4.7 Rhodium-Catalyzed Alkynylation of α-Ketoesters 231 8.5 Concluding Remarks 232 References 233 9 Catalytic Nucleophilic Addition of Alkynes to Imines: The A3 (Aldehyde–Alkyne–Amine) Coupling 239 Nick Uhlig, Woo-Jin Yoo, Liang Zhao, and Chao-Jun Li 9.1 A3 Couplings Involving Primary Amines 239 9.2 A3 Couplings Involving Secondary Amines 242 9.3 Alkyne Additions with Reusable Catalysts 244 9.4 Asymmetric Alkyne Addition Reactions 246 9.4.1 Asymmetric A3-Type Couplings with Primary Amines 246 9.4.2 Asymmetric A3-Type Couplings with Secondary Amines 250 9.5 Alkyne Additions to Imines in Tandem Reactions 251 9.5.1 A3 Coupling with Tandem Cycloisomerizations Involving the Alkyne Triple Bond 252 9.5.2 Tandem Processes Involving Other Transformations of the Alkyne Triple Bond 257 9.5.3 Tandem Processes Involving Decarboxylations 259 9.5.4 Tandem Processes Involving Both the Amine and the Alkyne 260 9.6 Conclusion 262 References 263 10 The Sonogashira Reaction 269 Rafael Chinchilla and Carmen Ná jera 10.1 Introduction 269 10.2 Palladium–Phosphorous Catalysts 270 10.2.1 Unsupported Palladium–Phosphorous Catalysts 270 10.2.1.1 Copper-Cocatalyzed Reactions 270 10.2.1.2 Copper-Free Reactions 273 10.2.2 Supported Palladium–Phosphorous Catalysts 274 10.2.2.1 Copper-Cocatalyzed Reactions 274 10.2.2.2 Copper-Free Reactions 275 10.3 Palladium–Nitrogen Catalysts 276 10.3.1 Unsupported Palladium–Nitrogen Catalysts 276 10.3.2 Supported Palladium–Nitrogen Catalysts 277 10.4 N-Heterocyclic Carbene (NHC)-Palladium Catalysts 278 10.4.1 Unsupported NHC-Palladium Catalysts 278 10.4.2 Supported NHC-Palladium Catalysts 279 10.5 Palladacycles as Catalysts 280 10.5.1 Unsupported Palladacycles as Catalysts 280 10.5.2 Supported Palladacycles as Catalysts 281 10.6 Ligand-Free Palladium Salts as Catalysts 282 10.6.1 Unsupported Ligand-Free Palladium Salts as Catalysts 282 10.6.2 Supported Ligand-Free Palladium Salts as Catalysts 283 10.7 Palladium Nanoparticles as Catalysts 283 10.7.1 Unimmobilized Palladium Nanoparticles as Catalysts 283 10.7.2 Immobilized Palladium Nanoparticles as Catalysts 284 10.7.2.1 Copper-Cocatalyzed Reactions 285 10.7.2.2 Copper-Free Reactions 285 10.8 Non-Palladium-Based Catalysts 287 10.9 Mechanistic Considerations 289 10.10 Summary and Conclusions 291 References 291 Part IV Other Reactions 299 11 Catalytic Dimerization of Alkynes 301 Sergio E. Garc´ıa-Garrido 11.1 Introduction 301 11.2 Dimerization of Alkynes Catalyzed by Iron, Ruthenium, and Osmium Complexes 302 11.2.1 Homo-Coupling of Terminal Alkynes 302 11.2.2 Cross-Dimerization of Alkynes 310 11.3 Dimerization of Alkynes Catalyzed by Cobalt, Rhodium, and Iridium Complexes 311 11.3.1 Homo-Coupling of Terminal Alkynes 311 11.3.2 Cross-Dimerization of Alkynes 315 11.4 Dimerization of Alkynes Catalyzed by Nickel, Palladium, and Platinum Complexes 317 11.4.1 Homo-Coupling of Terminal Alkynes 317 11.4.2 Cross-Dimerization of Alkynes 320 11.5 Dimerization of Alkynes Catalyzed by Group 3, Lanthanide, and Actinide Complexes 322 11.6 Dimerization of Alkynes Catalyzed by Titanium, Zirconium, and Hafnium Complexes 325 11.7 Dimerization of Alkynes Catalyzed by Other Compounds 326 11.8 Summary and Conclusions 327 Acknowledgments 327 References 328 12 The Oxidative Dimerization of Acetylenes and Related Reactions: Synthesis and Applications of Conjugated 1,3-Diynes 335 Jean-Philip Lumb 12.1 Introduction 335 12.2 Syntheses of Conjugated 1,3-Diynes 336 12.3 Scope and Limitation of the Alkyne Dimerization Reaction 338 12.3.1 Choice of Copper Salt 338 12.3.2 Choice of Solvent 339 12.3.3 Substituents on the Alkyne and Basic Additives 339 12.3.4 Additional Metals 340 12.4 Scope and Limitation of Copper-Catalyzed Hetero-Coupling Reactions 340 12.5 The Cadiot–Chodkiewicz Reaction 341 12.6 Palladium-Catalyzed Acetylenic Coupling Reactions 343 12.7 Alternative Methods for the Synthesis of Diynes 344 12.8 Mechanism of Alkyne Homo-Coupling Reactions 344 12.9 Mechanism of Alkyne Hetero-Coupling Reactions 347 12.10 Utility of 1,3-Diynes in the Synthesis of Natural Products 349 12.11 Synthetic Utility of Conjugated 1,3-Diynes 351 12.12 Utility of 1,3-Diynes in Materials Science 355 12.13 Conclusion 359 References 359 13 The Alkyne Zipper Reaction in Asymmetric Synthesis 365 Kenneth Avocetien, Yu Li, and George A. O’Doherty 13.1 Introduction 365 13.2 Mechanism of KNH2/NH3 Isomerization 366 13.3 Mechanism of KAPA Isomerization 368 13.4 Applications in Natural Products 370 13.4.1 Galacto-Sugar γ-Lactones 371 13.4.2 Galacto-Sugar δ-Lactones 371 13.4.3 (-)–Apicularen A 371 13.4.4 Milbemycin β3 373 13.4.5 Cryptocaryols A and B 373 13.4.6 Tricolozin A 374 13.4.7 Elenic Acid 376 13.4.8 Daumone 377 13.4.9 (+)–Broussonetine G 379 13.4.10 Cladospolides A, B, C, iso-Cladospolide B and (ent) Cladospolide D 379 13.4.11 Shingolipid Analogs 384 13.4.12 Irciniasulfonic Acids 386 13.4.13 Clathculins A and B 386 13.4.14 Cephalosporolide H 387 13.4.15 (+)–Aspicilin 389 13.4.16 Merremoside D 389 13.4.17 Aspergillide B 392 13.5 Conclusion 393 References 393 Index 395