Asymmetric Dearomatization Reactions

  • ID: 3615625
  • Book
  • 424 Pages
  • John Wiley and Sons Ltd
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The first comprehensive account of the rapidly growing field of asymmetric dearomatization reactions with a focus on catalytic methods.

It introduces the concept of dearomatization and describes recent progress in asymmetric reaction procedures with different catalyst systems, such as organocatalysts, transition metal catalysts, and enzymes. Chapters on dearomatizations of electron–deficient aromatic rings, dearomatization reactions via transition metal–catalyzed cross–couplings as well as dearomatization strategies in the synthesis of complex natural products are also included.

Written by pioneers in the field, this is a highly valuable source of information not only for professional synthetic chemists in academia and industry but also for all those are interested in asymmetric methodologies and organic synthesis in general.
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List of Contributors XIII

Preface XVII

1 Introduction 1Wei Zhang and Shu–Li You

1.1 Why Asymmetric Dearomatization Reactions? 1

1.2 Discovery of Aromatic Compounds and Dearomatization Reactions 1

1.3 Development of Dearomatization Reactions 3

1.4 Asymmetric Dearomatization Reactions 7

References 8

2 Asymmetric Dearomatization with Chiral Auxiliaries and Reagents 9E. Peter Kündig

2.1 Introduction 9

2.2 Chiral –Bound Auxiliaries 9

2.2.1 Oxazolines 9

2.2.2 Imines, Oxazolidines, and Hydrazones 15

2.2.3 Chiral Ethers and Amines 16

2.3 Diastereospecific Anionic Cyclizations 20

2.4 Use of Chiral Reagents 21

2.4.1 Chiral Bases in Dearomatizing Cyclizations 21

2.4.2 Chiral Nucleophiles 23

2.4.3 Chiral Ligands in Enantioselective Nucleophilic Additions 23

2.5 Chiral –Complexes 26

2.5.1 Planar Chiral 6–Arene Complexes 26

2.5.2 6–Arene Complexes with a Chiral Ligand 28

2.5.3 Complexes with Stereogenic Metal Centers 29

2.6 Conclusion 30

References 30

3 Organocatalytic Asymmetric Transfer Hydrogenation of (Hetero)Arenes 33Gaëlle Mingat and Magnus Rueping

3.1 Introduction 33

3.2 Organocatalytic Asymmetric Transfer Hydrogenation of Heteroaromatics 34

3.2.1 Quinolines 34

3.2.1.1 Proof–of–Concept 34

3.2.1.2 2–Substituted Quinolines 35

3.2.1.3 4–Substituted Quinolines 40

3.2.1.4 3–Substituted Quinolines 41

3.2.1.5 2,3–Disubstituted Quinolines 42

3.2.1.6 Spiro–Tetrahydroquinolines 45

3.2.2 Benzoxazines, Benzothiazines, and Benzoxazinones 47

3.2.3 Benzodiazepines and Benzodiazepinones 49

3.2.4 Pyridines 51

3.2.5 3H–Indoles 51

3.2.6 Quinoxalines and Quinoxalinones 52

3.3 Organocatalytic Asymmetric Transfer Hydrogenation in Aqueous Solution 53

3.4 Cascade Reactions 54

3.4.1 Introduction 54

3.4.2 In situ Generation of the Heteroarene 54

3.4.3 Dearomatization of Pyridine/Asymmetric aza–Friedel Crafts Alkylation Cascade 56

3.4.4 Combining Photochemistry and Brønsted Acid Catalysis 57

3.4.4.1 Quinolines 57

3.4.4.2 Pyrylium ions 58

3.5 Cooperative and Relay Catalysis: Combining Brønsted Acid– and Metal–Catalysis 59

3.5.1 Introduction 59

3.5.2 Improvements in Transfer Hydrogenation 60

3.5.2.1 Regenerable Hydrogen Sources 60

3.5.2.2 Asymmetric Relay Catalysis (ARC) 62

3.5.3 Cooperative Metal Brønsted Acid Catalysis 63

3.6 Summary and Conclusion 65

References 66

4 Transition–Metal–Catalyzed Asymmetric Hydrogenation of Aromatics 69Ryoichi Kuwano

4.1 Introduction 69

4.2 Catalytic Asymmetric Hydrogenation of Five–Membered Heteroarenes 71

4.2.1 Catalytic Asymmetric Hydrogenation of Azoles and Indoles 71

4.2.1.1 Rhodium–Catalyzed Asymmetric Hydrogenation of Indoles 71

4.2.1.2 Ruthenium–Catalyzed Asymmetric Hydrogenation of Azoles 73

4.2.1.3 Palladium–Catalyzed Asymmetric Hydrogenation of Azoles 75

4.2.1.4 Iridium–Catalyzed Asymmetric Hydrogenation of Indoles 77

4.2.2 Catalytic Asymmetric Hydrogenation of Oxygen–Containing Heteroarenes 77

4.2.3 Catalytic Asymmetric Hydrogenation of Sulfur–Containing Heteroarenes 79

4.3 Catalytic Asymmetric Hydrogenation of Six–Membered Heteroarenes 79

4.3.1 Catalytic Asymmetric Hydrogenation of Azines 80

4.3.1.1 Iridium–Catalyzed Asymmetric Hydrogenation of Pyridines 80

4.3.1.2 Iridium–Catalyzed Asymmetric Hydrogenation of Pyrimidines 81

4.3.2 Catalytic Asymmetric Hydrogenation of Benzo–Fused Azines 82

4.3.2.1 Iridium–Catalyzed Asymmetric Hydrogenation of Quinolines 82

4.3.2.2 Ruthenium–Catalyzed Asymmetric Hydrogenation of Quinolines 85

4.3.2.3 Iridium–Catalyzed Asymmetric Hydrogenation of Isoquinolines 87

4.3.2.4 Iridium–Catalyzed Asymmetric Hydrogenation of Quinoxalines 89

4.3.2.5 Ruthenium–Catalyzed Asymmetric Hydrogenation of Quinoxalines 90

4.3.2.6 Iron–Catalyzed Asymmetric Hydrogenation of Quinoxalines 92

4.3.2.7 Catalytic Asymmetric Hydrogenation of Miscellaneous Six–Membered Heteroarenes 92

4.3.3 Catalytic Asymmetric Reduction of Quinolines with Reducing Agents Other Than H2 94

4.4 Catalytic Asymmetric Hydrogenation of Carbocyclic Arenes 95

4.4.1 Ruthenium–Catalyzed Asymmetric Hydrogenation of Carbocycles in Benzo–Fused Heteroarenes 96

4.4.2 Ruthenium–Catalyzed Asymmetric Hydrogenation of Naphthalenes 97

4.5 Summary and Conclusion 97

References 98

5 Stepwise Asymmetric Dearomatization of Phenols 103Qing Gu

5.1 Introduction 103

5.2 Stepwise Asymmetric Dearomatization of Phenols 103

5.2.1 Asymmetric [4+2] Reaction 103

5.2.2 Asymmetric Heck Reaction 106

5.2.3 Asymmetric (Hetero) Michael Reaction 108

5.2.4 Asymmetric Stetter Reaction 119

5.2.5 Asymmetric Rauhut Currier Reaction 120

5.2.6 Asymmetric 1,6–Dienyne Cyclized Reaction 122

5.3 Conclusion and Perspective 126

References 127

6 Asymmetric Oxidative Dearomatization Reaction 129Muhammet Uyanik and Kazuaki Ishihara

6.1 Introduction 129

6.2 Diastereoselective Oxidative Dearomatization using Chiral Auxiliaries 129

6.3 Enantioselective Oxidative Dearomatization using Chiral Reagents or Catalysts 132

6.3.1 Chiral Transition Metal Complexes 132

6.3.2 Chiral Hypervalent Iodines(III, V) and Hypoiodites(I) 139

6.4 Conclusions and Perspectives 148

References 149

7 Asymmetric Dearomatization via Cycloaddition Reaction 153Sarah E. Reisman, Madeleine E. Kieffer, and Haoxuan Wang

7.1 Introduction 153

7.2 [2+1] Cycloaddition 153

7.2.1 Asymmetric Büchner Reaction 153

7.2.2 Cyclopropanation of Heterocyclic Compounds 155

7.3 [3+2] Cycloaddition 156

7.4 [3+3] Cycloaddition 161

7.5 [4+2] Cycloaddition 163

7.6 [4+3] Cycloaddition 170

7.7 Conclusion 173

References 173

8 Organocatalytic Asymmetric Dearomatization Reactions 175Susana S. Lopez, Sri K. Nimmagadda, and Jon C. Antilla

8.1 Introduction 175

8.2 Diels Alder 175

8.3 Oxidative Dearomatization 179

8.4 Cascade Reactions 186

8.5 Stepwise 193

8.6 Nucleophilic Dearomatization 200

8.7 Summary and Conclusion 204

References 205

9 Dearomatization via Transition–Metal–Catalyzed Allylic Substitution Reactions 207Tetsuhiro Nemoto and Yasumasa Hamada

9.1 Introduction 207

9.2 Dearomatization of Indoles and Pyrroles via Transition–Metal–Catalyzed Allylic Substitution Reactions 208

9.3 Dearomatization of Phenols via Transition–Metal–Catalyzed Allylic Substitution Reactions 216

9.4 Dearomatization of Phenols and Indoles via Activation of Propargyl Carbonates with Pd Catalyst 221

9.5 Conclusion 226

References 226

10 Dearomatization via Transition–Metal–Catalyzed Cross–Coupling Reactions 229Robin B. Bedford

10.1 Introduction: From Cross–Coupling to Catalytic Dearomatization 229

10.2 Dearomatization of Phenolic Substrates 231

10.3 Dearomatization of Nitrogen–Containing Substrates 240

10.4 Conclusion and Outlook 244

References 245

11 Dearomatization Reactions of Electron–Deficient Aromatic Rings 247Chihiro Tsukano and Yoshiji Takemoto

11.1 Introduction 247

11.2 Dearomatization of Activated Pyridines and Other Electron–Deficient Heterocycles 248

11.2.1 Dearomatization via Alkyl Pyridinium Salts 248

11.2.1.1 Reduction with Borohydrides 248

11.2.1.2 Reduction with Na2S2O4 249

11.2.1.3 Reduction with Other Reducing Agents 250

11.2.1.4 Nucleophilic Addition of Grignard Reagents 251

11.2.1.5 Nucleophilic Addition of Cyanide 252

11.2.1.6 Addition of Other Carbon Nucleophiles 252

11.2.2 Dearomatization via Alkoxycarbonylpyridinium Salts 253

11.2.2.1 Reduction with Hydride Nucleophiles 254

11.2.2.2 Addition of Metal Nucleophiles, Including Grignard Reagents 255

11.2.2.3 Addition of Enolates and Related Carbon Nucleophiles 261

11.2.2.4 Nucleophilic Addition of Cyanide 264

11.2.2.5 Addition of Other Nucleophiles 265

11.2.3 Dearomatization via Acyl Pyridinium Salts 266

11.2.3.1 Reduction with Hydride Reducing Agents 266

11.2.3.2 Addition of Metal Nucleophiles Including Grignard Reagents 269

11.2.3.3 Addition of Enolates and Related Carbon Nucleophiles 270

11.2.4 Dearomatization through Other Pyridinium Cations 270

11.3 Summary and Conclusion 274

References 274

12 Asymmetric Dearomatization Under Enzymatic Conditions 279Simon E. Lewis

12.1 Introduction 279

12.2 Dearomatizing Arene cis–Dihydroxylation 280

12.2.1 Early Development 280

12.2.2 Types of Arene Dioxygenase 281

12.2.3 Substrate Scope and Regioselectivity 283

12.2.3.1 Monocyclic Substituted Benzene Substrates (Excluding Biaryls) 299

12.2.3.2 Biaryl Substrates 299

12.2.3.3 Naphthalene Substrates 299

12.2.3.4 Benzoic Acid Substrates 299

12.2.3.5 Heterocyclic Substrates (Mono– and Bicyclic) 300

12.2.3.6 Bicyclic Carbocyclic Substrates (Other than Naphthalenes) 300

12.2.3.7 Tricyclic Substrates (Carbo– and Heterocyclic) 300

12.2.4 Availability of Arene cis–Diols 300

12.2.5 Uses in Synthesis 302

12.2.5.1 Total Synthesis 302

12.2.5.2 Pharmaceuticals and Agrochemicals 315

12.2.5.3 Polymers 317

12.2.5.4 Flavors and Fragrances 320

12.2.5.5 Dyes 321

12.2.5.6 Ligands and MOFs 321

12.2.6 Increasing the Substrate Scope 324

12.2.7 Accessing Both Enantiomeric Series 326

12.2.8 Improvements to the Production Process 328

12.3 Dearomatizing Arene Epoxidation 328

12.4 Dearomatizing Arene Reduction 330

12.5 Summary and Conclusion 330

List of Abbreviations 331

References 332

13 Total Synthesis of Complex Natural Products via Dearomatization 347Weiqing Xie and Dawei Ma

13.1 Introduction 347

13.2 Natural Products Synthesis via Oxidative Dearomatization 348

13.2.1 Enzymatic Dihydroxylative Dearomatization of Arene 348

13.2.2 Oxidative Dearomatization of Phenol 349

13.2.3 Oxidative Cycloisomerization Reaction of Phenol 355

13.2.4 Oxidative Dearomatization of Indole in Synthesis of Natural Products 357

13.3 Dearomatization via Cycloaddition in Synthesis of Natural Products 360

13.4 Dearomatization via Nucleophilic Addition in Synthesis of Natural Products 367

13.5 Reductive Dearomatization in Synthesis of Natural Products 367

13.6 Dearomatization via Electrophilic Addition in Synthesis of Natural Products 369

13.7 Dearomatization via Intramolecular Arylation in Natural Products Synthesis 371

13.8 Summary and Perspective 373

References 374

14 Miscellaneous Asymmetric Dearomatization Reactions 379Wei Zhang and Shu–Li You

14.1 Introduction 379

14.2 Miscellaneous Asymmetric Dearomatization Reactions 379

14.3 Conclusions and Perspectives 388

References 388

Index 391

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Shu–Li You is a professor at the State Key Laboratory of Organometallic Chemistry at the Shanghai Institute of Organic Chemistry (SIOC). He received his BSc in chemistry from Nankai University, Tianjin, China, in 1996 and obtained his PhD from SIOC in 2001 under the supervision of Prof. Li–Xin Dai. He then did postdoctoral studies with Prof. Jeffery W. Kelly at The Scripps Research Institute, La Jolla, California. He worked at the Genomics Institute of the Novartis Research Foundation as a Principal Investigator from 2004 before returning to SIOC in 2006.

He has published over 170 peer–reviewed papers, 5 book chapters, and filed over 30 Chinese patents as a co–inventor. He is the recipient of many awards, e.g. the Chinese Chemical Society (CCS)–Wiley Young Chemist Award (2007), Thieme Chemistry Journals Award (2010), The National Science Fund for Distinguished Young Scholars (2010), AstraZeneca Excellence in Chemistry Award (2011), CAS Teaching Excellence Award (2012, 2013, 2014), Roche Chinese Young Investigator Award (2014), WuXi PharmaTech Life Science and Chemistry Award (2014), and RSC Merck Award (2015). His research interests mainly focus on enantioselective direct C–H bond functionalization and catalytic asymmetric dearomatization (CADA) reactions.
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