Multicomponent Reactions in Organic Synthesis

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.

Autorentext
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.

Klappentext
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.

Inhalt

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 MizorokiHeck-Type Reactions 65

3.3.4 Insertion into -Bond 65

3.4 Concluding Remarks 69

References 69

4 UgiSmiles and PasseriniSmiles 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 JoulliéSmiles Coupling 90

4.2.6 The PasseriniSmiles Reaction 91

4.3 UgiSmiles Postcondensations 94

4.3.1 Postcondensations Involving Reduction of the Nitro Group 94

4.3.2 Transformations of UgiSmiles 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...