Methods and Applications of Cycloaddition Reactions in Organic Syntheses E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1314

Veröffentlichungsjahr: 2013

Beschreibung

Advanced tools for developing new functional materials and applications in chemical research, pharmaceuticals, and materials science

Cycloadditions are among the most useful tools for organic chemists, enabling them to build carbocyclic and heterocyclic structures. These structures can then be used to develop a broad range of functional materials, including pharmaceuticals, agrochemicals, dyes, and optics. With contributions from an international team of leading experts and pioneers in cycloaddition chemistry, this book brings together and reviews recent advances, trends, and emerging research in the field.

Methods and Applications of Cycloaddition Reactions in Organic Syntheses focuses on two component cycloadditions, with chapters covering such topics as:

• N1 unit transfer reaction to C–C double bonds
• [3+2] Cycloaddition of α, β-unsaturated metal-carbene complexes
• Formal [3+3] cycloaddition approach to natural product synthesis
• Development of new methods for the construction of heterocycles based on cycloaddition reaction of 1,3-dipoles
• Cycloreversion approach for preparation of large π-conjugated compounds
• Transition metal-catalyzed or mediated [5+1] cycloadditions

Readers will learn methods for seamlessly executing important reactions such as Diels-Alder and stereoselective dipolar reactions in order to fabricate heterocyclic compounds, natural products, and functional molecules. The book not only features cutting-edge topics, but also important background information, such as the contributors’ process for developing new methodologies, to help novices become fully adept in the field. References at the end of each chapter lead to original research papers and reviews for facilitating further investigation of individual topics.

Covering the state of the science and technology, Methods and Applications of Cycloaddition Reactions in Organic Syntheses enables synthetic organic chemists to advance their research and develop new functional materials and applications in chemical research, pharmaceuticals, and materials science.

Leseprobe

Contents

Cover

Title Page

Copyright

Preface

Contributors

Part I: [2+1] Cycloaddition

Chapter 1: [2+1]-Type Cyclopropanation Reactions

1.1 Introduction

1.2 Cyclopropanation Reaction Via Michael-Induced Ring Closure Reaction

1.3 Simmons–Smith Cyclopropanation and Related Reactions

1.4 Diazoalkanes with Transition Metal Catalysts

1.5 Cycloisomerization with Transition Metal Catalysts

1.6 Kulinkovich Reactions

1.7 Miscellaneous [2+1]-Type of Cyclopropanation Reactions

References

Chapter 2: N1 Unit Transfer Reaction to C–C Double Bonds

2.1 Introduction

2.2 Aziridination with Azides

2.3 Aziridination with Iminoiodinanes

2.4 Aziridination with N-Haloamine Salts

2.5 Aziridination with Other N1 Unit

2.6 Conclusions

References

Part II: [2+2] Cycloaddition

Chapter 3: Lewis Base Catalyzed Asymmetric Formal [2+2] Cycloadditions

3.1 Introduction

3.2 β-Lactams: Formal [2+2] Cycloadditions Involving Imines

3.3 β-Lactones I: Formal [2+2] Cycloadditions Involving Aldehydes/Ketones

3.4 β-Lactones II: Formal [2+2] Cycloaddition of Ketenes Leading to Ketene Dimers

3.5 Miscellaneous Formal [2+2] Asymmetric Cycloaddition Processes

3.6 Conclusions

References

Part III: [2+2] and [4+2]/[2+2] Cycloaddition

Chapter 4: Catalytic [2+2] Cycloaddition of Silyl Enol Ethers

4.1 Introduction

4.2 Catalytic [2+2] Cycloaddition Reactions of Silyl Enol Ethers by Lewis Acid Catalyst

4.3 Catalytic [2+2] Cycloaddition Reactions of Silyl Enol Ethers by Brønsted Acid

4.4 Multicomponent Reaction: Cascade [4+2]-[2+2] Cycloaddition Reaction

4.5 [2+2] Cycloaddition Reactions Using a Flow Microreactor System

4.6 Conclusions

References

Part IV: [3+2] Cycloaddition

Chapter 5: [3+2] Cycloaddition of α,β-Unsaturated Metal–Carbene Complexes

5.1 Introduction

5.2 [3+2] Cycloaddition of α,β-Unsaturated Fischer Carbene Complexes as a C2-Building Block

5.3 [3+2] Cycloaddition of α,β-Unsaturated Fischer Carbene Complexes as a C3-Building Block

5.4 Intramolecular [3+2] Cycloaddition of Ruthenium–Alkenyl Carbene Complex: A Nonmetathetic Behavior of Grubbs Catalyst

5.5 Conclusions

References

Chapter 6: Geometry-Controlled Cycloaddition of C-Alkoxycarbonyl Nitrones: Synthetic Studies on Nonproteinogenic Amino Acids

6.1 Introduction

6.2 Selective Activation of (Z)-Isomers of C-Alkoxycarbonylnitrones

6.3 Tandem Transesterification and Intramolecular Cycloaddition of C-Alkoxycarbonylnitrones with Allyl Alcohols

6.4 Chiral and (E)-Geometry-Fixed Nitrone

6.5 Conclusions

References

Chapter 7: Recent Advances in Catalytic Asymmetric 1,3-Dipolar Cycloadditions of Azomethine Imines, Nitrile Oxides, Diazoalkanes, and Carbonyl Ylides

7.1 Introduction

7.2 Asymmetric Cycloaddition of Azomethine Imine

7.3 Asymmetric Cycloaddition of Diazoalkane

7.4 Asymmetric Cycloaddition of Nitrile Oxide

7.5 Asymmetric Cycloaddition of Carbonyl Ylide

7.6 Conclusions

References

Chapter 8: Condensation of Primary Nitro Compounds to Isoxazole Derivatives: Stoichiometric to Catalytic

8.1 Introduction

8.2 Catalytic Condensation of “Active” Nitro Compounds

8.3 Copper Catalysis and Condensation of Nitroalkanes

8.4 Mechanism for Activated Nitro Compounds

8.5 Synthetic Applications and Tabular Survey

Acknowledgments

References

Chapter 9: Carbamoylnitrile Oxide and Inverse Electron-Demand 1,3-Dipolar Cycloaddition

9.1 Introduction

9.2 Diverse Reactivity of Nitroisoxazolone Derivatives

9.3 Cycloaddition of Carbamoylnitrile Oxide in Aqueous Media

9.4 Mechanistic Study on Generation of Nitrile Oxide

9.5 Isolation of 1,2,4-Oxadiazole Derivative

9.6 Optimization of Reaction Conditions for Preparation of 5-Methyloxadiazole

9.7 Syntheses of Other 3-Carbamoyl-1,2,4-Oxadiazoles

9.8 Activation of a Nitrile by a Carbamoyl Group

9.9 Cycloaddition of Nitrile Oxide with 1,3-Dicarbonyl Compounds

9.10 Activation of Keto Ester by Coordination with Metal Ions

9.11 Cycloaddition with Other 1,3-Dicarbonyl Compounds

9.12 Summary

References

Part V: [3+2], [3+3], and [4+2] Cycloaddition

Chapter 10: Cycloaddition Reactions of Small Rings

10.1 Introduction

10.2 Use of Organometallic Complexes in the [3+2] Cycloaddition Reaction with Cyclopropanes

10.3 Use of Dicobalt Complexes in the [4+2] Cycloaddition Reaction with Cyclobutanes

10.4 Other Dipolar Cycloaddition Reactions

10.5 Use of [3+3] Dipolar Cycloadditions in the Synthesis of Oxazine Derivatives

10.6 Intramolecular [3+2] Cycloaddition Reactions

10.7 Synthesis of Tetrahydrofuran Derivatives via the [3+2] Cycloaddition Reaction

10.8 Applications of [3+2] Cycloaddition Reaction to Natural Products

10.9 Synthesis of Pyrrolidines and Pyrazolines Derivatives via the Cycloaddition Reaction

10.10 A Radical Approach Toward the Cycloaddition of Activated Cyclopropane Diesters

10.11 Summary

References

Part VI: [3+2] and [5+1] Cycloaddition

Chapter 11: Development of New Methods for the Construction of Heterocycles Based on Cycloaddition Reaction of 1,3-Dipoles

11.1 Introduction

11.2 Asymmetric 1,3-Dipolar Cycloadditions Based on Chiral Multinucleating System Utilizing Tartaric Acid Esters

11.3 Asymmetric Diels–Alder Reactions

11.4 Synthesis Heterocycles Via Stepwise Addition–Cyclization Strategy and Related Transformation

11.5 Novel [5+1] Cycloaddition Reaction of C, N-Cyclic N ′-Acyl Azomethine Imines with Isocyanides

11.6 Summary

References

Part VII: [3+3] Cycloaddition

Chapter 12: A Formal [3+3] Cycloaddition Approach to Natural Product Synthesis

12.1 Introduction

12.2 A Formal OXA-[3+3] Cycloaddition

12.3 A Formal AZA -[3+3] Cycloaddition

12.4 Conclusions

References

Part VIII: [4+2] Cycloaddition

Chapter 13: [4+2] Cycloaddition Chemistry of Substituted Furans

13.1 Introduction

13.2 [4+2] Cycloaddition Reactions of Furans

13.3 Diels–Alder Reactions of 2-Silyloxyfurans

13.4 Diels–Alder Reactions of 2-Amidofurans

13.5 Use of Furans for Natural Product Synthesis

13.6 [4+2] Cycloadditions of Silyloxyfurans for Total Synthesis

13.7 Conclusions

References

Chapter 14: Synthesis of Substituted Oligoacenes via Diels–Alder Reactions and Substituent Effects on Molecular Structure, Packing Arrangement, and Solid-State Optical Properties

14.1 Introduction

14.2 Substituted Anthracenes

14.3 Substituted Tetracenes

14.4 Substituted Pentacenes

References

Chapter 15: Cycloreversion Approach for Preparation of Large π-Conjugated Compounds

15.1 Introduction

15.2 π-System Expansion of Porphyrinoids

15.3 π-Expansion of Porphyrazines and Phthalocyanines

15.4 π-Fusion of Porphyrin Oligomers

15.5 π-Fusion of Porphyrin and Polycyclic Aromatic Hydrocarbons

15.6 π-Expansion of Boron-Dipyrromethenes

15.7 π-Fusion of BODIPYs

15.8 π-Expansion of Miscellaneous Compounds Based on Bcod-Fused Pyrroles

15.9 π-System Construction of Acenes

15.10 Concluding Remarks

References

Part IX: [4+2]/[3+2] Cycloaddition

Chapter 16: Tandem [4+2]/[3+2] Cycloadditions

16.1 Introduction

16.2 Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes

16.3 Tandem [4+2]/[3+2] Cycloadditions of 1,3,4-Oxadiazoles

16.4 Conclusions and Outlook

References

Part X: [5+1] Cycloaddition

Chapter 17: Transition Metal-Catalyzed or -Mediated [5+1] Cycloadditions

17.1 Introduction

17.2 Iron-Mediated [5+1] Cycloadditions

17.3 Cobalt-Mediated or -Catalyzed [5+1] Cycloadditions

17.4 Rhodium-Catalyzed [5+1] Cycloadditions

17.5 Other Metal-Mediated or -Catalyzed [5+1] Cycloadditions

17.6 Summary

References

Part XI: [4+3] Cycloaddition

Chapter 18: [4+3] Cycloadditions of Enolsilane Derivatives

18.1 Introduction

18.2 Applications of Enolsilane Derivatives for [4+3] Cycloadditions in Synthesis

18.3 Conclusions

References

Chapter 19: Application of the [4+3] Cycloaddition Reaction to the Synthesis of Natural Products

19.1 Introduction

19.2 Natural Products Synthesis via Intermolecular [4+3] Cycloaddition Reactions

19.3 Natural Product Synthesis via Intramolecular [4+3] Cycloaddition Reactions

19.4 Conclusions and Prospects

Acknowledgments

References

Part XII: [5+2] Cycloaddition

Chapter 20: Recent Developments in the [5+2] Cycloaddition

20.1 Introduction

20.2 Metal-Catalyzed [5+2] Cycloadditions of Vinylcyclopropanes and π-Systems

20.3 [5+2] Cycloadditions of Metal-Containing 5C Components

20.4 [5+2] Cycloadditions of Oxidopyrylium Ions

20.5 [5+2] Cycloadditions of Oxidopyridinium Ions

20.6 Photocycloadditions

20.7 Domino [5+2] Cycloaddition Reactions

20.8 Conclusions

References

Index

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Library of Congress Cataloging-in-Publication Data:

Methods and applications of cycloaddition reactions in organic syntheses / [edited by] Nagatoshi Nishiwaki, Kochi University of Technology, Kami, Kochi, Japan.

pages cm

Includes bibliographical references and index.

ISBN 978-1-118-29988-3 (cloth)

1. Organic compounds–Synthesis. 2. Ring formation (Chemistry) I. Nishiwaki, Nagatoshi, 1963- editor of compilation.

QD262.M54 2014

547′.27–dc23

2013023528

Preface

Synthesis of complex cyclic compounds is necessary for the development of functional materials such as biologically active compounds (medicines and agrochemicals), dyes, and optical materials. Demand for the development of smart and powerful methods for elaborate syntheses is continuing to grow. In this context, cycloaddition reactions have figured prominently as one class of the fundamental synthetic methodologies, in which versatile cyclic structures can be constructed along with the formation of two bonds, all in a single manipulation. While cycloaddition has been energetically studied for a considerable period of time, as evidenced by many publications of books and reviews, this chemistry is still attractive even now as a means of meeting a variety of demands. Hence, this is an opportune time to gather recent advances, trends, and current research interests in cycloaddition chemistry into a single book.

We now present this book, which deals with two-component cycloadditions (we refer to other good books with regard to more than three-component cycloadditions). The reaction modes of the cycloaddition mentioned here are [2 + 1], [2 + 2], [3 + 2], [3 + 3], [4 + 2], [5 + 1], [4 + 3], [5 + 2], and their combinations, by which various kinds of cyclic compounds are prepared, ranging between three and seven members. The contributors to these chapters are active authorities and energetic midcareer chemists at the leading edge of cycloaddition chemistry. I am grateful for their positive and valuable response to my invitation to contribute and for their cooperation as colleagues and friends.

This book includes not only cutting-edge topics but also the background of each area. The contributors' processes of developing new methodologies are also included, which should be of interest to graduate students, postdoctoral fellows, and those teaching specialized topics to recent graduates. Of course, the wide coverage should be stimulating, helpful, and informative for active researchers at the frontier. I hope the book will stimulate the generation of many ideas for future theoretical and experimental research in the cycloaddition chemistry.

Nagatoshi Nishiwaki

Kochi University of Technology

Kami, Kochi, Japan

May 2013

Contributors

Manabu Abe, Department of Chemistry, Graduate School of Science, Hiroshima University; Institute for Molecular Science; JST-CREST, Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan

Haruyasu Asahara, School of Environmental Science and Engineering, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan

Ramil Y. Baiazitov, PTC Therapeutics, Inc., South Plainfield, NJ 07080, USA

Scott Bur, Department of Chemistry, Gustavus Adolphus College, Saint Peter, MN 56082, USA

Pauline Chiu, Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong, China

Steven D. R. Christie, Department of Chemistry, Loughborough University, Loughborough LE11 3TU, UK

Hervé Clavier, Aix Marseille Universit??, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France

Jun Deng, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China

Scott E. Denmark, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

Francesco De Sarlo, Dipartimento di chimica “Ugo Schiff”, Universit?? degli studi di Firenze, 50019 Sesto Fiorentino, Firenze, Italy

James Douglas, EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK

Xu-Fei Fu, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

Michael Harmata, Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211, USA

Richard P. Hsung, Division of Pharmaceutical Sciences and School of Pharmacy, University of Wisconsin at Madison, Madison, WI 53705, USA

Kennosuke Itoh, Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Wakasato, Nagano 380-8553, Japan

Darin E. Jones, Department of Chemistry, University of Arkansas-Little Rock, Little Rock, AR 72204, USA

Akio Kamimura, Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8611, Japan

Chitoshi Kitamura, Department of Materials Science, School of Engineering, The University of Shiga Prefecture, Hassaka-cho, Hikone, Shiga 522-8533, Japan

Kensuke Kiyokawa, Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan

Sarah Y. Y. Lam, Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong, China

Fabrizio Machetti, Istituto di chimica dei composti organometallici, Consiglio nazionale delle ricerche, 50019 Sesto Fiorentino, Firenze, Italy

Satoshi Minakata, Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan

Louis C. Morrill, EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK

Nagatoshi Nishiwaki, School of Environmental Science and Engineering, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan

Albert Padwa, Department of Chemistry, Emory University, Atlanta, GA 30322, USA

Hélène Pellissier, Aix Marseille Universit??, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France

Edward Richmond, EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK

Andrew D. Smith, EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK

Takahiro Soeta, Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Hiroyuki Suga, Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Nagano 380-8553, Japan

Ryukichi Takagi, Department of Chemistry, Graduate School of Science, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan

Kiyosei Takasu, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan

Youhei Takeda, Frontier Research Base for Global Young Researchers, Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan

Osamu Tamura, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan

Yutaka Ukaji, Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Hidemitsu Uno, Graduate School of Science and Engineering, Ehime University, Bunkyo-cho 2-5, Matsuyama, Ehime 790-8577, Japan

Xiao-Na Wang, Division of Pharmaceutical Sciences and School of Pharmacy, University of Wisconsin at Madison, Madison, WI 53705, USA

Hayley T. A. Watson, Department of Chemistry, Loughborough University, Loughborough LE11 3TU, UK

Yosuke Yamaoka, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Zhi-Xiang Yu, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

1

[2+1]-Type Cyclopropanation Reactions

Akio Kamimura

Yamaguchi University, Ube, Yamaguchi, Japan

1.1 Introduction

1.2 Cyclopropanation Reaction via Michael-Induced Ring Closure Reaction

1.2.1 Introduction

1.2.2 Halo-Substituted Nucleophiles in MIRC Reaction

1.2.3 Ylides for Cyclopropanation

1.3 Simmons–Smith Cyclopropanation and Related Reactions

1.3.1 Introduction

1.3.2 The Simmons–Smith Reaction with Zinc Reagents

1.4 Diazoalkanes with Transition Metal Catalysts

1.4.1 Introduction

1.4.2 Rhodium-Catalyzed Reactions

1.4.3 Copper-Catalyzed Reactions

1.4.4 Ruthenium-Catalyzed Reactions

1.4.5 Cobalt- and Iron-Catalyzed Reactions

1.4.6 Other Transition Metal-Catalyzed Reactions

1.4.7 Cyclopropanation Without Transition Metal Catalysts

1.4.8 Cyclopropanation of Dihalocarbenes

1.5 Cycloisomerization with Transition Metal Catalysts

1.5.1 Introduction

1.5.2 Gold Complex-Catalyzed Reactions

1.5.3 Palladium Complex-Catalyzed Reactions

1.5.4 Platinum Complex-Catalyzed Reactions

1.5.5 Ruthenium Complex-Catalyzed Reactions

1.5.6 Other Metal Complex-Catalyzed Reactions

1.6 Kulinkovich Reactions

1.6.1 Introduction

1.6.2 The Kulinkovich Reaction to Esters, Ketones, and Amides

1.6.3 Kulinkovich Reaction to Nitriles

1.6.4 Other Ti-Mediated Cyclopropanation Reactions

1.7 Miscellaneous [2+1]-Type of Cyclopropanation Reactions

References

1.1 Introduction

Cyclopropane is often present in natural and biologically active products. Alternatively, the cyclopropane structure has been used as parts for the modification of such products. It has a high ring strain because of its bond angle, and this property facilitates unique reactions. The formation of cyclopropanes has been the focus of considerable study and many reviews are available [1]. Among the methods reported in these reviews, [2+1]-type cycloaddition by carbenoids is a representative strategy [2]. In this chapter, we collected recent representative examples of [2+1]-type cyclopropanation reactions. We reviewed and classified the literature from the past decade into six categories: Michael-induced ring closure (MIRC), the Simmons–Smith reaction, reactions by carbenes from diazoalkanes catalyzed/noncatalyzed by transition metals, cycloisomerization reactions by transition metal catalysts, the Kulinkovich reaction, and miscellaneous reactions. Since this chapter focuses on [2+1]-type cycloaddition, we excluded γ-elimination-type cyclopropanations from a single molecule. The asymmetric synthesis of cyclopropanes, which is a topic of interest among synthetic chemists, is discussed in each category. Although we carefully reviewed the literature, it could be possible we may have missed some citations owing to the significant amount of related studies.

1.2 Cyclopropanation Reaction Via Michael-Induced Ring Closure Reaction

1.2.1 Introduction

Cyclopropanes are prepared by the nucleophilic attack on electron-deficient alkenes followed by intramolecular nucleophilic substitution. This occurs when the nucleophile or electron-deficient alkene contains a leaving group at an appropriate position. This type of reaction is called the MIRC [3] and is frequently employed for cyclopropanation. There are two types of MIRC reactions, which are expressed by Equations 1.1 and 1.2.

(1.1)

(1.2)

Equation 1.1 shows an MIRC reaction with an electron-drawing alkene containing a leaving group, which reacts with a nucleophile that is generated under reaction conditions. In this case, all carbons in cyclopropane originate from the alkene. Equation 1.2 is an MIRC reaction with a nucleophile containing a leaving group. Cyclopropane formed in this sequence contains two carbons from the alkene and one carbon from the nucleophile. Because this chapter focuses on [2+1] cycloaddition, we will concentrate on the latter case of MIRC cyclopropanation.

The leaving group is typically halogen if the nucleophile is derived from active methylene compounds or nitro compounds. α-Halo enolates are used for this reaction. The reaction is usually performed in a one-pot procedure; however, a two-step sequence with the oxidation of conjugate adducts, intermediates for cyclopropanation, can occasionally afford good results. Recently, organocatalysts have been employed in catalytic asymmetric cyclopropanation. Ylides are another species frequently used in MIRC cyclopropanation. Sulfur ylides are most frequently used; however, phosphorous, arsenic, selenium, tellurium, and iodonium ylides are also useful.

1.2.2 Halo-Substituted Nucleophiles in MIRC Reaction

Active methylene compounds are very reactive nucleophiles and their halo-derivatives are actively used for catalytic asymmetric cyclopropanation through the MIRC process. Rios and coworkers demonstrated catalytic asymmetric cyclopropanation between 2-bromo malonate and unsaturated aldehydes in the presence of proline-derived organocatalyst () [4]. The reaction smoothly progressed in chloroform at room temperature (rt) and highly enantioselective cyclopropanation was achieved.