Organocatalytic Cycloadditions for Synthesis of Carbo- and Heterocycles

A comprehensive resource to the development and recent progress of zwitterion-oriented cycloadditions promoted by organoamines, organophosphines, N-heterocyclic carbenes

Organocatalytic Cycloadditions for Synthesis of Carbo- and Heterocycles offers a clear explanationto thedevelopment of and the information on the latest research pertaining to zwitterion-oriented cycloadditions promoted by organoamines, organophosphines, N-heterocyclic carbenes. The authors—noted experts in the field—include a comprehensive review to the investigations of the reaction mechanisms and explore the synthesis of different products from the same starting materials. 

Filled with illustrative examples and designed to be accessible, the text shows how to control the chemo-, regio- and stereoselectivity and explains the further design of novel cycloaddition reactions catalyzed by organoamines and organophosphines based on zwitterion-oriented synthetic strategy. This important text:

• Explains why the formation of carbo- and heterocycles is a key transformation in organic synthesis.
• Offers a clear description to the development of zwitterion-oriented cycloadditions promoted by organoamines, organophosphines, N-heterocyclic carbenes, and explores the latest research
• Contains the most current examples involving synthetic transformations of organocatalytic cycloadducts
• Includes contributions from noted experts in the field of organic synthesis

Written for organic chemists, pharmaceutical chemists, chemists in industry, graduates, and librarians, Organocatalytic Cycloadditions for Synthesis of Carbo- and Heterocyclesis is the essential guide to the topic.

Min Shi is the vice director of State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (SIOC, CAS). Having obtained his PhD degree in 1991 at Osaka University, Japan, he had his postdoctoral research experience with Prof. Kenneth M. Nicholas at University of Oklahoma (1995-6) and worked as an ERATO Researcher in Japan Science and Technology Corporation (1996-8). Then, he was appointed as a full professor at SIOC since 1998. He has authored over 500 scientific publications, and his current research interests are on photochemistry, total synthesis of natural products, asymmetric synthesis, Morita-Baylis-Hillman reaction, and fixation of CO₂ using transition metal catalyst.

Yin Wei received her PhD from Ludwig-Maximilians-Universität in München (Germany) in 2009 under the direction of Professor Hendrik Zipse. Subsequently she joined Professor Min Shi's group at SIOC, CAS, and was promoted to Associate Professor in 2012. She has authored over 100 scientific publications, and she is mainly working on the theoretical studies of organocatalysis.

Mei-Xin Zhao received her PhD from Institute of Chemistry, Chinese Academy of Sciences (ICCAS) in 2002 under the supervision of Professor Zhi-Tang Huang. She then worked at ICCAS and joined Professor Mei-Xiang Wang's group as Assistant Professor. During 2004 – 2006, she was a postdoctoral fellow with Professor Yian Shi at Colorado State University, USA and then was appointed as Associate Professor of Organic Chemistry at East China University of Science and Technology. Her current research interests include asymmetric catalysis and new synthetic methods for the novel heterocyclic compounds.

Jun Zhang received his PhD in 2006 under the supervision of Professor Guo-Xin Jin at Fudan University, China. During 2006–2009, he was a postdoctoral fellow in the research group of Professor Andy Hor at the National University of Singapore. Then he was appointed as Associate Professor of organic chemistry at East China University of Science and Technology. His research focuses on the development of novel organometallic catalysts and study on the reaction mechanism.

Preface ix

1 Introduction to Organocatalytic Cycloaddition Reaction 1
Yin Wei and Min Shi

1.1 General Introduction 1

1.2 General Mechanistic Insights into Cycloadditions Catalyzed by Nucleophilic Organocatalysts 2

1.2.1 Mechanisms for Common Organoamine�-catalyzed Cycloaddition Reactions 2

1.2.2 Mechanisms for Common Organophosphine�-catalyzed Cycloaddition Reactions 11

1.2.3 Cycloaddition Reaction Modes Influenced By Catalysts 19

References 22

2 Organoamines�-catalyzed Cycloadditions 25
Mei�-Xin Zhao and Min Shi

2.1 Introduction 25

2.2 [2+2] Cycloadditions 26

2.2.1 Ketene and Their Analogs Involved [2+2] Cycloadditions 26

2.2.1.1 [2+2] Cycloadditions for the Synthesis of β�-Lactones 26

2.2.1.2 [2+2] Cycloadditions for the Synthesis of β�]Lactams 39

2.2.1.3 [2+2] Cycloadditions for the Synthesis of Other Four�]membered Heterocycles 48

2.2.2 Allenoates and Their Analogs Involved [2+2] Cycloadditions 50

2.2.2.1 [2+2] Cycloadditions of Allenoates and Their Analogs with Imines 51

2.2.2.2 [2+2] Cycloadditions of Allenoates with Ketones 52

2.2.2.3 [2+2] Cycloadditions of Allenoates with Other Activated Double Bonds 56

2.3 [3+2] Cycloadditions 57

2.3.1 Ketenes and Their Analogs Involved [3+2] Cycloadditions 57

2.3.2 MBH Adducts Derivatives (MBHADs) Involved [3+2] Cycloadditions 59

2.3.3 Other Substrates Involved [3+2] Cycloadditions 67

2.4 [4+2] Cycloadditions 70

2.4.1 Ketene�]involved [4+2] Cycloadditions 70

2.4.1.1 Ketene as Dienophile�]involved [4+2] Cycloadditions 70

2.4.1.2 Vinyl Ketene as Diene�]Involved [4+2] Cycloadditions 83

2.4.2 Allenoates Involved [4+2] Cycloadditions 86

2.4.2.1 Allenoates Acting as a Two�]carbon Synthon in [4+2] Cycloadditions 86

2.4.2.2 Allenoate Acting as a Four�]carbon Synthon in [4+2] Cycloadditions 97

2.4.3 MBHADs Involved [4+2] Cycloaddition 99

2.5 Other Cycloaddition Reactions 102

2.5.1 [2+1] Cycloadditions 102

2.5.2 [3+3] Formal Cycloadditions 107

2.5.3 Domino Reactions 117

2.5.4 Miscellaneous Cycloaddition Reactions 125

2.6 Summary 131

References 132

3 Organophosphines�-Catalyzed Cycloaddition Reactions 141
Yin Wei and Min Shi

3.1 Introduction 141

3.2 Phosphine�]catalyzed [2+2] Cycloaddition Reactions 142

3.3 Phosphine�]catalyzed [3+n] Cycloaddition 145

3.3.1 Phosphine�]catalyzed [3+2] Cycloaddition 145

3.3.1.1 Phosphine�]catalyzed [3+2] Cycloaddition of Allenes with Alkenes and its Asymmetric Variant 145

3.3.1.2 Phosphine�]catalyzed [3+2] Cycloaddition of Allenes with Imines and its Asymmetric Variant 161

3.3.1.3 Phosphine�]catalyzed [3+2] Cycloaddition of Allenes with Other Electrophiles 171

3.3.1.4 Phosphine�]catalyzed [3+2] Cycloaddition of Morita–Baylis–Hillman Alcohol Derivatives (MBHADs) with Electrophiles and its Asymmetric Variant 173

3.3.1.5 Phosphine�-catalyzed [3+2] Cycloaddition of Activated Alkynes with Electrophiles and its Asymmetric Variant 181

3.3.2 Phosphine�]catalyzed [3+3] Cycloaddition of Electron�]deficient π�-systems with Electrophiles and its Asymmetric Variant 184

3.4 Phosphine�]catalyzed [4+n] Cycloaddition 188

3.4.1 Phosphine�]catalyzed [4+2] Cycloaddition and its Asymmetric Variant 188

3.4.1.1 Phosphine�-catalyzed [4+2] Cycloaddition of Allenes with Other Electrophiles and its Asymmetric Variant 188

3.4.1.2 Phosphine�-catalyzed [4+2] Cycloaddition of Alkynes with Other Electrophiles 201

3.4.2 Phosphine�-catalyzed [4+1] Cycloaddition and its Asymmetric Variant 202

3.4.3 Phosphine�-catalyzed [4+3] Cycloaddition and its Asymmetric Variant 208

3.5 Phosphine�-catalyzed Domino Reactions 212

3.6 Miscellaneous Reactions 228

3.7 Summary 232

References 232

4 N�]Heterocyclic Carbenes Catalyzed Cycloadditions 237
Jun Zhang and Min Shi

4.1 Introduction 237

4.2 NHC�]catalyzed [4+2] Cycloaddition Reaction 237

4.3 NHC�]catalyzed [2+2] Cycloaddition Reaction 276

4.4 NHC�-catalyzed [3+2] Cycloaddition Reaction 284

4.5 NHC�-catalyzed [2+2+2] Cycloaddition Reaction 297

4.6 NHC�-catalyzed Domino Reactions 302

4.7 Summary 305

References 305

5 Synthetic Transformations of Organocatalytic Cycloadducts 309
Yin Wei and Min Shi

5.1 Introduction 309

5.2 Synthetic Applications of Organoamine�-catalyzed Cycloaddition Reactions 309

5.2.1 Synthetic Applications of [2+2] Cycloadduct β�-Lactones 309

5.2.2 Total Synthesis of Schulzeines 315

5.2.3 Total synthesis of HPA�-12 319

5.2.4 Total Syntheses of Inthomycins 320

5.2.5 Total Synthesis of Siphonarienal 324

5.2.6 Total Syntheses of Siphonarienolone and Siphonarienedione 325

5.2.7 Total Synthesis of (+)�-Maculalactone A 326

5.2.8 Synthesis of the C21–C34�-segment of Aplyronines 327

5.2.9 Formal Synthesis of the α1a Adrenergic Receptor Antagonist 330

5.2.10 Formal Synthesis of Calyxin I 332

5.2.11 Formal Synthesis of Platencin 332

5.2.12 Total Synthesis of (−)�-Patchouli Alcohol 335

5.3 Synthetic Applications of OrganoPhosphine�-catalyzed Cycloaddition Reactions 336

5.3.1 Synthesis of Pentabromopseudilin 336

5.3.2 Total Synthesis of (−)�-Hinesol 338

5.3.3 Total Synthesis of (±)�-Hirsutene 339

5.3.4 Total Synthesis of (±)�-Ricciocarpin A 340

5.3.5 Total Synthesis of (+)�-Geniposide 342

5.3.6 Formal Synthesis of (±)�-Allosecurinine 342

5.3.7 Formal Synthesis of (+)�-Trachelanthamidine 344

5.3.8 Total Synthesis of (+)�-Ibophyllidine 345

5.3.9 Total Synthesis of (−)�-Actinophyllic Acid 346

5.3.10 Formal Synthesis of (+)�-Alstonerine 349

5.3.11 Total Synthesis of (+)�-Hirsutine 351

5.3.12 Formal Synthesis of Reserpine 352

5.3.13 Other Synthetic Applications of Phosphine�-catalyzed [3+2] Cycloadditions 354

5.3.14 Synthetic Applications of Phosphine�-catalyzed [3+3] Cycloaddition 358

5.3.15 Synthetic Applications of Phosphine�-catalyzed [4+2] Cycloaddition 359

5.3.16 Synthetic Applications of Phosphine�-catalyzed [4+1] Cycloaddition 364

5.3.17 Synthetic Applications of Phosphine�-catalyzed [4+3] Cycloaddition 364

5.4 Summary 365

References 365

Index 369

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