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Multicomponent Reactions in Organic Synthesis

1. Aufl.

von: Jieping Zhu, Qian Wang, Meixiang Wang
160,99 €
Verlag:	Wiley-VCH (D)
Format:	PDF
Veröffentl.:	15.10.2014
ISBN/EAN:	9783527678198
Sprache:	englisch
Anzahl Seiten:	512

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Beschreibungen

Titelbeschreibung

Comprehensive and up-to-date, this book focuses on the latest advances in the field, such as newly developed techniques, more environmentally benign processes, broadened scopes, and completely novel MCRs. In addition to carbene-promoted MCRs and frequently applied metal-catalyzed MCRs, it also covers recently developed catalytic enantioselective variants as well as MCR in drug discovery and for the synthesis of heterocyclic molecules and macrocycles. Edited by the leading experts and with a list of authors reading like a "who's who" in multicomponent reaction chemistry, this is definitely a must-have for every synthetic organic chemist as well as medicinal chemists working in academia and pharmaceutical companies.

Inhaltsverzeichnis

List of Contributors XIII Preface XVII 1 General Introduction to MCRs: Past, Present, and Future 1 Alexander Dömling and AlAnod D. AlQahtani 1.1 Introduction 1 1.2 Advances in Chemistry 2 1.3 Total Syntheses 4 1.4 Applications in Pharmaceutical and Agrochemical Industry 4 1.5 Materials 10 1.6 Outlook 10 References 11 2 Discovery of MCRs 13 Eelco Ruijter and Romano V.A. Orru 2.1 General Introduction 13 2.2 The Concept 14 2.3 The Reaction Design Concept 15 2.3.1 Single Reactant Replacement 17 2.3.2 Modular Reaction Sequences 19 2.3.3 Condition-Based Divergence 21 2.3.4 Union of MCRs 23 2.4 Multicomponent Reactions and Biocatalysis 23 2.4.1 Multicomponent Reactions and (Dynamic) Enzymatic Kinetic Resolution 26 2.4.2 Multicomponent Reactions and Enzymatic Desymmetrization 29 2.5 Multicomponent Reactions in Green Pharmaceutical Production 31 2.6 Conclusions 36 Acknowledgments 36 References 36 3 Aryne-Based Multicomponent Reactions 39 Hiroto Yoshida 3.1 Introduction 39 3.2 Multicomponent Reactions of Arynes via Electrophilic Coupling 41 3.2.1 Multicomponent Reactions under Neutral Conditions 42 3.2.1.1 Isocyanide-Based Multicomponent Reactions 42 3.2.1.2 Imine-Based Multicomponent Reactions 46 3.2.1.3 Amine-Based Multicomponent Reactions 47 3.2.1.4 Carbonyl Compound-Based Multicomponent Reactions 49 3.2.1.5 Ether-Based Multicomponent Reactions 50 3.2.1.6 Miscellaneous 53 3.2.2 Multicomponent Reactions under Basic Conditions 53 3.3 Transition Metal-Catalyzed Multicomponent Reactions of Arynes 60 3.3.1 Annulations 60 3.3.2 Cross-Coupling-Type Reactions 65 3.3.3 Mizoroki–Heck-Type Reactions 65 3.3.4 Insertion into σ-Bond 65 3.4 Concluding Remarks 69 References 69 4 Ugi–Smiles and Passerini–Smiles Couplings 73 Laurent El Kaïm and Laurence Grimaud 4.1 Introduction 73 4.1.1 Carboxylic Acid Surrogates in Ugi Reactions 75 4.1.2 Smiles Rearrangements 76 4.2 Scope and Limitations 77 4.2.1 Phenols and Thiophenols 77 4.2.2 Six-Membered Ring Hydroxy Heteroaromatics and Related Mercaptans 84 4.2.3 Five-Membered Ring Hydroxy Heteroaromatic and Related Mercaptans 88 4.2.4 Related Couplings with Enol Derivatives 90 4.2.5 The Joullié–Smiles Coupling 90 4.2.6 The Passerini–Smiles Reaction 91 4.3 Ugi–Smiles Postcondensations 94 4.3.1 Postcondensations Involving Reduction of the Nitro Group 94 4.3.2 Transformations of Ugi–Smiles Thioamides 96 4.3.3 Postcondensations Involving Transition Metal-Catalyzed Processes 97 4.3.4 Reactivity of the Peptidyl Unit 101 4.3.5 Radical Reactions 103 4.3.6 Cycloaddition 103 4.4 Conclusions 105 References 105 5 1,3-Dicarbonyls in Multicomponent Reactions 109 Xavier Bugaut, Thierry Constantieux, Yoann Coquerel, and Jean Rodriguez 5.1 Introduction 109 5.2 Achiral and Racemic MCRs 111 5.2.1 Involving One Pronucleophilic Reactive Site 111 5.2.2 Involving Two Reactive Sites 115 5.2.2.1 Two Nucleophilic Sites 115 5.2.2.2 One Pronucleophilic Site and One Electrophilic Site 120 5.2.3 Involving Three Reactive Sites 134 5.2.4 Involving Four Reactive Sites 139 5.3 Enantioselective MCRs 142 5.3.1 Involving One Reactive Site 143 5.3.2 Involving Two Reactive Sites 146 5.3.3 Involving Three Reactive Sites 149 5.4 Conclusions and Outlook 150 References 151 6 Functionalization of Heterocycles by MCRs 159 Esther Vicente-García, Nicola Kielland, and Rodolfo Lavilla 6.1 Introduction 159 6.2 Mannich-Type Reactions and Related Processes 160 6.3 β-Dicarbonyl Chemistry 164 6.4 Hetero-Diels–Alder Cycloadditions and Related Processes 166 6.5 Metal-Mediated Processes 168 6.6 Isocyanide-Based Reactions 171 6.7 Dipole-Mediated Processes 175 6.8 Conclusions 176 Acknowledgments 178 References 178 7 Diazoacetate and Related Metal-Stabilized Carbene Species in MCRs 183 Dong Xing and Wenhao Hu 7.1 Introduction 183 7.2 MCRs via Carbonyl or Azomethine Ylide-Involved 1,3-Dipolar Cycloadditions 184 7.2.1 Azomethine Ylide 184 7.2.2 Carbonyl Ylide 185 7.3 MCRs via Electrophilic Trapping of Protic Onium Ylides 187 7.3.1 Initial Development 187 7.3.2 Asymmetric Examples 190 7.3.2.1 Chiral Reagent Induction 190 7.3.2.2 Chiral Dirhodium(II) Catalysis 190 7.3.2.3 Enantioselective Synergistic Catalysis 190 7.3.3 MCRs Followed by Tandem Cyclizations 196 7.4 MCRs via Electrophilic Trapping of Zwitterionic Intermediates 198 7.5 MCRs via Metal Carbene Migratory Insertion 199 7.6 Summary and Outlook 203 References 204 8 Metal-Catalyzed Multicomponent Synthesis of Heterocycles 207 Fabio Lorenzini, Jevgenijs Tjutrins, Jeffrey S. Quesnel, and Bruce A. Arndtsen 8.1 Introduction 207 8.2 Multicomponent Cross-Coupling and Carbonylation Reactions 208 8.2.1 Cyclization with Alkyne- or Alkene-Containing Nucleophiles 208 8.2.2 Cyclization via Palladium–Allyl Complexes 210 8.2.3 Fused-Ring Heterocycles for ortho-Substituted Arene Building Blocks 211 8.2.4 Multicomponent Cyclocarbonylations 214 8.2.5 Cyclization of Cross-Coupling Reaction Products 216 8.2.6 C-H Functionalization in Multicomponent Reactions 218 8.3 Metallacycles in Multicomponent Reactions 221 8.4 Multicomponent Reactions via 1,3-Dipolar Cycloaddition 223 8.5 Concluding Remarks 227 References 227 9 Macrocycles from Multicomponent Reactions 231 Ludger A. Wessjohann, Ricardo A.W. Neves Filho, Alfredo R. Puentes, and Micjel C. Morejon 9.1 Introduction 231 9.2 IMCR-Based Macrocyclizations of Single Bifunctional Building Blocks 237 9.3 Multiple MCR-Based Macrocyclizations of Bifunctional Building Blocks 245 9.4 IMCR-Based Macrocyclizations of Trifunctionalized Building Blocks (MiB-3D) 256 9.5 Sequential IMCR-Based Macrocyclizations of Multiple Bifunctional Building Blocks 259 9.6 Final Remarks and Future Perspectives 261 References 261 10 Multicomponent Reactions under Oxidative Conditions 265 Andrea Basso, Lisa Moni, and Renata Riva 10.1 Introduction 265 10.2 Multicomponent Reactions Involving In Situ Oxidation of One Substrate 266 10.2.1 Isocyanide-Based Multicomponent Reactions 266 10.2.1.1 Passerini Reactions 266 10.2.1.2 Ugi Reactions with In Situ Oxidation of Alcohols 271 10.2.1.3 Ugi Reaction with In Situ Oxidation of Secondary Amines 273 10.2.1.4 Ugi–Smiles Reaction with In Situ Oxidation of Secondary Amines 275 10.2.1.5 Ugi-Type Reactions by In Situ Oxidation of Tertiary Amines 277 10.2.1.6 Synthesis of Other Derivatives 279 10.2.2 Other Multicomponent Reactions 280 10.3 Multicomponent Reactions Involving Oxidation of a Reaction Intermediate 284 10.3.1 Reactions without Transition Metal-Mediated Oxidation 285 10.3.2 Reactions Mediated by Transition Metal Catalysis 292 10.4 Multicomponent Reactions Involving Oxidants as Lewis Acids 295 10.5 Conclusions 297 References 297 11 Allenes in Multicomponent Synthesis of Heterocycles 301 Hans-Ulrich Reissig and Reinhold Zimmer 11.1 Introduction 301 11.2 Reactions with 1,2-Propadiene and Unactivated Allenes 302 11.2.1 Palladium-Catalyzed Multicomponent Reactions 302 11.2.2 Copper-, Nickel-, and Rhodium-Promoted Multicomponent Reactions 310 11.2.3 Multicomponent Reactions without Transition Metals 314 11.3 Reactions with Acceptor-Substituted Allenes 316 11.3.1 Catalyzed Multicomponent Reactions 316 11.3.2 Uncatalyzed Multicomponent Reactions 318 11.4 Reactions with Donor-Substituted Allenes 323 11.5 Conclusions 329 List of Abbreviations 329 References 329 12 Alkynes in Multicomponent Synthesis of Heterocycles 333 Thomas J.J. Müller and Konstantin Deilhof 12.1 Introduction 333 12.2 σ-Nucleophilic Reactivity of Alkynes 335 12.2.1 Acetylide Additions to Electrophiles 335 12.2.1.1 Alkyne–Aldehyde–Amine Condensation – A3-Coupling 335 12.2.1.2 Alkyne–(Hetero)Aryl Halide (Sonogashira) Coupling as Key Reaction 337 12.2.2 Conversion of Terminal Alkynes into Electrophiles as Key Reactions 341 12.3 π-Nucleophilic Reactivity of Alkynes 345 12.4 Alkynes as Electrophilic Partners 351 12.5 Alkynes in Cycloadditions 356 12.5.1 Alkynes as Dipolarophiles 356 12.5.2 Alkynes in Cu(I)-Catalyzed 1,3-Dipolar Azide–Alkyne Cycloaddition 358 12.5.3 Alkynes as Dienophiles in MCRs 366 12.6 Alkynes as Reaction Partners in Organometallic MCRs 370 12.7 Conclusions 374 List of Abbreviations 374 Acknowledgment 375 References 375 13 Anhydride-Based Multicomponent Reactions 379 Kevin S. Martin, Jared T. Shaw, and Ashkaan Younai 13.1 Introduction 379 13.2 Quinolones and Related Heterocycles from Homophthalic and Isatoic Anhydrides 380 13.2.1 Introduction: Reactivity of Homophthalic and Isatoic Anhydrides 380 13.2.2 Imine–Anhydride Reactions of Homophthalic Anhydride 380 13.2.3 MCRs Employing Homophthalic Anhydride 382 13.2.4 Imine–Anhydride Reactions of Isatoic Anhydride 383 13.3 α,β-Unsaturated Cyclic Anhydrides: MCRs Involving Conjugate Addition and Cycloaddition Reactions 385 13.3.1 Maleic Anhydride MCRs 385 13.3.2 MCRs of Itaconic Anhydrides 388 13.3.3 Diels–Alder Reactions 390 13.4 MCRs of Cyclic Anhydrides in Annulation Reactions and Related Processes 392 13.4.1 MCR-Based Annulations: Succinic and Phthalic Anhydrides 393 13.5 MCRs of Acyclic Anhydrides 395 13.6 Conclusions 398 References 399 14 Free-Radical Multicomponent Processes 401 Virginie Liautard and Yannick Landais 14.1 Introduction 401 14.2 MCRs Involving Addition Across Olefin C.C Bonds 402 14.2.1 Addition of Aryl Radicals to Olefins 402 14.2.2 MCRs Using Sulfonyl Derivatives as Terminal Trap 404 14.2.3 Carboallylation of Electron-Poor Olefins 406 14.2.4 Carbohydroxylation, Sulfenylation, and Phosphorylation of Olefins 407 14.2.5 Radical Addition to Olefins Using Photoredox Catalysis 410 14.2.6 MCRs Based on Radical–Polar Crossover Processes 414 14.3 Free-Radical Carbonylation 419 14.3.1 Alkyl Halide Carbonylation 419 14.3.2 Metal-Mediated Atom-Transfer Radical Carbonylation 420 14.3.3 Alkane Carbonylation 421 14.3.4 Miscellaneous Carbonylation Reactions 423 14.4 Free-Radical Oxygenation 424 14.5 MCRs Involving Addition Across π-C.N Bonds 427 14.5.1 Free-Radical Strecker Process 427 14.5.2 Free-Radical Mannich-Type Processes 429 14.6 Miscellaneous Free-Radical Multicomponent Reactions 432 14.7 Conclusions 434 References 435 15 Chiral Phosphoric Acid-Catalyzed Asymmetric Multicomponent Reactions 439 Xiang Wu and Liu-Zhu Gong 15.1 Introduction 439 15.2 Mannich Reaction 439 15.3 Ugi-Type Reaction 442 15.4 Biginelli Reaction 444 15.5 Aza-Diels–Alder Reaction 446 15.6 1,3-Dipolar Cycloaddition 454 15.7 Hantzsch Dihydropyridine Synthesis 458 15.8 The Combination of Metal and Chiral Phosphoric Acid for Multicomponent Reaction 459 15.9 Other Phosphoric Acid-Catalyzed Multicomponent Reactions 465 15.10 Summary 467 References 467 Index 471

Autorenportrait

Jieping Zhu received his BSc degree from Hanzhou Normal University (P.R. China) and his MSc degree from Lanzhou University (P.R. China) under the guidance of Prof. Y.-L. Li. He obtained his PhD from the Universite Paris XI, France, under the supervision of Prof. H.-P. Husson and Prof. J. C. Quirion. After 18 months post-doctoral research with Prof. Sir D. H. R. Barton at Texas A&M University in USA, he joined the Institut de Chimie des Substances Naturelles (CNRS, France) as Charge de Recherche and was promoted to Director of Research 2nd class in 2000 and then 1st class in 2006. He moved to Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland, in 2010 as a full professor. His main research interests center on the development of novel synthetic methods, their application in the synthesis of bioactive natural products, and the design of novel multicomponent reactions. He has published over 220 research articles and the well-received book "Multicomponenet Reactions" (Wiley-VCH, 2005). Qian Wang received her BSc and MSc degree from Lanzhou University (P.R. China) under the guidance of Prof. Y. Li. She obtained her PhD degree from Chinese University of Hong Kong under the supervision of Prof. H.N.C. Wong. After several post-doctoral stays in Switzerland and in France, she joined the Institut de Chimie des Substances Naturelles (CNRS, France) as a research engineer. In 2010, she moved to Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland, as a research scientist. Mei-Xiang Wang received a BSc degree in chemistry from Fudan University, Shanghai. After spending three years at the General Research Institute of Non-ferrous Metals (GRINM, Beijing) as a research associate, he joined the Institute of Chemistry, Chinese Academy of Sciences (ICCAS) at Beijing as a research student. He obtained his master degree and PhD in 1989 and 1992, respectively under the supervision of Prof. Z.-T. Huang. In the next 17 years, he worked at ICCAS ranking from assistant professor, associate professor to professor. During 2000 to 2004, he served as the Director of ICCAS and Center for Molecular Science, Chinese Academy of Sciences. Since May 2009, he has been a professor of chemistry at Tsinghua University in Beijing. He has published over 150 research articles and his research interests include enantioselective biotransformations using whole cell catalysts and selective organic reactions for the synthesis of natural products and bioactive compounds.

Back cover copy

Multicomponent reactions (MCR) have emerged as a versatile and powerful methodology for the synthesis of complex molecules with often biologically relevant scaffold structures. Since fewer chemicals and solvents, as well as less energy are required, these reactions represent an environmentally-friendly alternative to standard synthetic protocols in organic chemistry and drug discovery. Edited by leading experts and with a list of authors reading like a "who's who" in MCR chemistry, this timely work focuses on the latest advances in the field. In addition to chapters classified according to the key substrate used, radical and frequently applied metal-catalyzed MCRs, it also covers recently developed catalytic enantioselective variants as well as applications in the synthesis of heterocyclic molecules and macrocycles. A comprehensive overview for every synthetic organic chemist as well as medicinal chemists working in academia and pharmaceutical companies.