Organic Reaction Mechanisms 2014 E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Serie: Organic Reaction Mechanisms
• Sprache: Englisch

Seitenzahl: 1833

Veröffentlichungsjahr: 2017

Beschreibung

Organic Reaction Mechanisms 2014, the 50th annual volume in this highly successful and unique series, surveys research on organic reaction mechanisms described in the available literature dated 2014. The following classes of organic reaction mechanisms are comprehensively reviewed:

• Reaction of Aldehydes and Ketones and their Derivatives
• Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives
• Oxidation and Reduction
• Carbenes and Nitrenes
• Nucleophilic Aromatic Substitution
• Electrophilic Aromatic Substitution
• Carbocations
• Nucleophilic Aliphatic Substitution
• Carbanions and Electrophilic Aliphatic Substitution
• Elimination Reactions
• Polar Addition Reactions
• Cycloaddition Reactions
• Molecular Rearrangements

An experienced team of authors compile these reviews every year, so that the reader can rely on a continuing quality of selection and presentation. This volume includes a 5-year cumulative index.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

Contributors

Preface

Chapter 1: Reactions of Aldehydes and Ketones and their Derivatives

References

Chapter 2: Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives

Intermolecular Catalysis and Reactions

Intramolecular Catalysis and Neighbouring Group Participation

Association-Prefaced Catalysis

Biologically Significant Reactions

References

Chapter 3: Oxidation and Reduction

References

Chapter 4: Carbenes and Nitrenes

References

Chapter 5: Aromatic Substitution

References

Chapter 6: Carbocations

References

Chapter 7: Nucleophilic Aliphatic Substitution

References

Chapter 8: Carbanions and Electrophilic Aliphatic Substitution

References

Chapter 9: Elimination Reactions

References

Chapter 10: Addition Reactions: Polar Addition

References

Chapter 11: Addition Reactions: Cycloaddition

References

Chapter 12: Molecular Rearrangements

References

Author Index

Cumulative Subject Index, 2010-2014

End User License Agreement

Pages

v

vii

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

361

362

363

364

365

367

368

369

370

371

372

373

374

375

376

377

378

379

380

381

382

383

384

385

386

387

388

389

390

391

392

393

394

395

396

397

398

399

400

401

402

403

404

405

406

407

408

409

410

411

412

413

414

415

416

417

418

419

420

421

423

424

425

426

427

428

429

430

431

432

433

434

435

436

437

438

439

440

441

442

443

444

445

446

447

448

449

450

451

452

453

454

455

456

457

458

459

460

461

462

463

464

465

466

467

468

469

470

471

472

473

474

475

476

477

478

479

480

481

482

483

484

485

486

487

488

489

490

491

492

493

494

495

496

497

498

499

500

501

502

503

504

505

506

507

508

509

510

511

512

513

514

515

516

517

518

519

520

521

522

523

524

525

526

527

528

529

530

531

532

533

534

535

536

537

538

539

540

541

542

543

544

545

546

547

548

549

550

551

552

553

554

555

556

557

558

559

560

561

562

563

564

565

566

567

568

569

570

571

572

573

574

575

576

577

578

579

580

583

584

585

586

587

588

589

590

591

592

593

594

595

596

597

598

599

600

601

602

603

604

605

606

607

608

609

610

611

612

613

614

615

616

617

618

619

620

621

622

623

624

625

626

627

628

629

630

631

632

633

634

635

636

637

638

639

640

641

642

643

644

645

646

647

648

649

650

651

652

653

654

655

656

657

658

659

660

661

662

663

664

665

666

667

668

669

670

671

672

673

674

675

676

677

678

679

680

681

682

683

684

685

686

687

688

689

690

691

692

693

694

695

696

697

698

699

700

701

702

703

704

705

706

707

708

709

710

713

714

715

716

717

718

719

720

721

722

723

724

725

726

727

728

729

730

731

732

733

734

735

736

737

738

739

740

741

742

743

744

745

746

747

748

749

750

751

752

753

754

755

756

757

758

759

760

761

763

764

765

766

767

768

769

770

771

772

773

774

775

776

777

778

779

780

781

782

783

784

785

786

787

788

789

790

791

792

793

794

795

796

797

798

799

800

801

802

803

804

805

806

807

808

809

810

811

812

813

814

815

816

817

818

819

820

821

822

823

824

825

826

827

828

829

830

831

832

833

834

835

836

837

838

839

840

841

842

843

844

845

846

847

848

849

850

851

852

853

854

855

856

857

858

859

860

861

862

863

864

865

866

867

868

869

870

871

872

873

874

875

876

877

878

879

880

881

882

883

884

885

886

887

888

889

890

891

892

893

894

895

896

897

898

899

900

901

902

903

904

905

906

907

908

909

910

911

912

913

914

915

916

917

918

919

920

921

922

923

924

925

926

927

928

929

930

931

932

933

934

935

936

937

938

939

940

941

942

943

944

945

946

947

948

949

950

951

952

953

954

955

956

957

958

959

960

961

962

963

964

965

966

967

968

969

970

971

972

973

974

975

976

977

978

979

980

981

982

983

984

985

986

987

988

989

990

991

992

993

994

995

996

997

998

999

1000

1001

1002

1003

1004

1005

1006

1007

1008

1009

1010

1011

Guide

Cover

Table of Contents

Preface

Begin Reading

List of Illustrations

Chapter 2: Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives

Scheme 2.1

Scheme 2.2

Scheme 2.3

Scheme 2.4

Scheme 2.5

Scheme 2.6

Scheme 2.7

Scheme 2.8

Scheme 2.9

Scheme 2.10

Scheme 2.11

Scheme 2.12

Scheme 2.13

Scheme 2.14

Scheme 2.15

Scheme 2.16

Scheme 2.17

Scheme 2.18

Scheme 2.19

Scheme 2.20

Scheme 2.21

Scheme 2.22

Scheme 2.23

Scheme 2.24

Scheme 2.25

Scheme 2.26

Scheme 2.27

Scheme 2.28

Scheme 2.29

Scheme 2.30

Scheme 2.31

Scheme 2.32

Scheme 2.33

Chapter 3: Oxidation and Reduction

Scheme 3.1

Scheme 3.2

Scheme 3.3

Scheme 3.4

Scheme 3.5

Scheme 3.6

Scheme 3.7

Scheme 3.8

Scheme 3.9

Scheme 3.10

Scheme 3.11

Scheme 3.12

Scheme 3.13

Scheme 3.14

Scheme 3.15

Scheme 3.16

Scheme 3.17

Scheme 3.18

Scheme 3.19

Scheme 3.20

Scheme 3.21

Scheme 3.22

Scheme 3.23

Scheme 3.24

Scheme 3.25

Scheme 3.26

Scheme 3.27

Scheme 3.28

Scheme 3.29

Scheme 3.30

Scheme 3.31

Scheme 3.32

Scheme 3.33

Scheme 3.34

Scheme 3.35

Scheme 3.36

Scheme 3.37

Scheme 3.38

Scheme 3.39

Scheme 3.40

Scheme 3.41

Scheme 3.42

Scheme 3.43

Scheme 3.44

Scheme 3.45

Scheme 3.46

Scheme 3.47

Scheme 3.48

Scheme 3.49

Scheme 3.50

Scheme 3.51

Scheme 3.52

Scheme 3.53

Scheme 3.54

Scheme 3.55

Scheme 3.56

Scheme 3.57

Scheme 3.58

Chapter 4: Carbenes and Nitrenes

Scheme 4.1

Scheme 4.2

Scheme 4.3

Scheme 4.4

Scheme 4.5

Scheme 4.6

Scheme 4.7

Scheme 4.8

Scheme 4.9

Scheme 4.10

Scheme 4.11

Scheme 4.12

Scheme 4.13

Chapter 5: Aromatic Substitution

Scheme 5.1

Scheme 5.2

Scheme 5.3

Scheme 5.4

Scheme 5.5

Scheme 5.6

Scheme 5.7

Scheme 5.8

Scheme 5.9

Scheme 5.10

Scheme 5.11

Scheme 5.12

Scheme 5.13

Scheme 5.14

Scheme 5.15

Scheme 5.16

Scheme 5.17

Scheme 5.18

Scheme 5.19

Scheme 5.20

Scheme 5.21

Scheme 5.22

Scheme 5.23

Chapter 6: Carbocations

Scheme 6.1

Scheme 6.2

Scheme 6.3

Scheme 6.4

Scheme 6.5

Scheme 6.6

Scheme 6.7

Scheme 6.8

Scheme 6.9

Scheme 6.10

Scheme 6.11

Scheme 6.12

Scheme 6.13

Scheme 6.14

Scheme 6.15

Scheme 6.16

Scheme 6.17

Scheme 6.18

Scheme 6.19

Scheme 6.20

Scheme 6.21

Scheme 6.22

Scheme 6.23

Scheme 6.24

Scheme 6.25

Scheme 6.26

Scheme 6.27

Scheme 6.28

Scheme 6.29

Scheme 6.30

Scheme 6.31

Scheme 6.32

Scheme 6.33

Scheme 6.34

Chapter 7: Nucleophilic Aliphatic Substitution

Scheme 7.1

Scheme 7.2

Scheme 7.3

Scheme 7.4

Scheme 7.5

Scheme 7.6

Scheme 7.7

Scheme 7.8

Scheme 7.9

Scheme 7.10

Scheme 7.11

Scheme 7.12

Scheme 7.13

Scheme 7.14

Scheme 7.15

Scheme 7.16

Scheme 7.17

Scheme 7.18

Scheme 7.19

Scheme 7.20

Scheme 7.21

Scheme 7.22

Scheme 7.23

Scheme 7.24

Scheme 7.25

Scheme 7.26

Scheme 7.27

Scheme 7.28

Scheme 7.29

Scheme 7.30

Scheme 7.31

Scheme 7.32

Scheme 7.33

Scheme 7.34

Scheme 7.35

Scheme 7.36

Scheme 7.37

Scheme 7.38

Chapter 8: Carbanions and Electrophilic Aliphatic Substitution

Scheme 8.1

Scheme 8.2

Scheme 8.3

Scheme 8.4

Scheme 8.5

Scheme 8.6

Scheme 8.7

Scheme 8.8

Scheme 8.9

Scheme 8.10

Scheme 8.11

Scheme 8.12

Scheme 8.13

Scheme 8.14

Scheme 8.15

Scheme 8.16

Scheme 8.17

Chapter 9: Elimination Reactions

Scheme 9.1

Scheme 9.2

Scheme 9.3

Scheme 9.4

Scheme 9.5

Scheme 9.6

Scheme 9.7

Chapter 10: Addition Reactions: Polar Addition

Scheme 10.1

Scheme 10.2

Scheme 10.3

Scheme 10.4

Scheme 10.5

Scheme 10.6

Scheme 10.7

Scheme 10.8

Scheme 10.9

Scheme 10.10

Scheme 10.11

Scheme 10.12

Scheme 10.13

Scheme 10.14

Chapter 11: Addition Reactions: Cycloaddition

Scheme 1.1

Scheme 1.2

Scheme 1.3

Scheme 1.4

Scheme 1.5

Scheme 1.6

Scheme 1.7

Scheme 1.8

Scheme 1.9

Scheme 1.10

Scheme 1.11

Scheme 1.12

Scheme 1.13

Scheme 1.14

Scheme 1.15

Scheme 1.16

Scheme 1.17

Scheme 1.18

Scheme 1.19

Scheme 1.20

Scheme 1.21

Scheme 1.22

Scheme 1.23

Scheme 1.24

Scheme 1.25

Scheme 1.26

Scheme 1.27

Scheme 1.28

Scheme 1.29

Scheme 1.30

Scheme 1.31

Scheme 1.32

Scheme 1.33

Scheme 1.34

Scheme 1.35

Scheme 1.36

Scheme 1.37

Scheme 1.38

Scheme 1.39

Scheme 1.40

Scheme 1.41

Scheme 1.42

Scheme 1.43

Scheme 1.44

Scheme 1.45

Scheme 1.46

Scheme 1.47

Scheme 1.48

Scheme 1.49

Scheme 1.50

Scheme 1.51

Scheme 1.52

Chapter 12: Molecular Rearrangements

Scheme 12.1

Scheme 12.2

Scheme 12.3

Scheme 12.4

Scheme 12.5

Scheme 12.6

Scheme 12.7

Scheme 12.8

Scheme 12.9

Scheme 12.10

Scheme 12.11

Scheme 12.12

Scheme 12.13

Scheme 12.14

Scheme 12.15

Scheme 12.16

Scheme 12.17

Scheme 12.18

Scheme 12.19

Scheme 12.20

Scheme 12.21

Scheme 12.22

Scheme 12.23

Scheme 12.24

Scheme 12.25

Scheme 12.26

Scheme 12.27

Scheme 12.28

Scheme 12.29

Scheme 12.30

Scheme 12.31

Scheme 12.32

Scheme 12.33

Scheme 12.34

Scheme 12.35

Scheme 12.36

Scheme 12.37

Scheme 12.38

Scheme 12.39

Scheme 12.40

Scheme 12.41

Scheme 12.42

Scheme 12.43

Scheme 12.44

Scheme 12.45

Scheme 12.46

Scheme 12.47

Scheme 12.48

Scheme 12.49

Scheme 12.50

Scheme 12.51

Scheme 12.52

Scheme 12.53

Scheme 12.54

Scheme 12.55

Scheme 12.56

Scheme 12.57

Scheme 12.58

Scheme 12.59

Scheme 12.60

Scheme 12.61

Scheme 12.62

Scheme 12.63

Scheme 12.64

Scheme 12.65

Scheme 12.66

Scheme 12.67

Scheme 12.68

Scheme 12.69

Scheme 12.70

Scheme 12.71

Scheme 12.72

Scheme 12.73

Scheme 12.74

Scheme 12.75

Scheme 12.76

Scheme 12.77

Scheme 12.78

Scheme 12.79

Scheme 12.80

Scheme 12.81

Scheme 12.82

Scheme 12.83

Scheme 12.84

Scheme 12.85

Scheme 12.86

Scheme 12.87

Scheme 12.88

Scheme 12.89

Scheme 12.90

Scheme 12.91

Scheme 12.92

Scheme 12.93

Scheme 12.94

Scheme 12.95

Scheme 12.96

Scheme 12.97

Scheme 12.98

Scheme 12.99

Scheme 12.100

Scheme 12.101

Scheme 12.102

Scheme 12.103

Scheme 12.104

Scheme 12.105

Scheme 12.106

Scheme 12.107

Scheme 12.108

Scheme 12.109

Scheme 12.110

Scheme 12.111

Scheme 12.112

Scheme 12.113

Scheme 12.114

Scheme 12.115

Scheme 12.116

Scheme 12.117

Scheme 12.118

Scheme 12.119

Scheme 12.120

Scheme 12.121

Scheme 12.122

Scheme 12.123

Scheme 12.124

Scheme 12.125

Scheme 12.126

Scheme 12.127

Scheme 12.128

Scheme 12.129

Scheme 12.130

Scheme 12.131

Scheme 12.132

Scheme 12.133

Scheme 12.134

Scheme 12.135

Scheme 12.136

Scheme 12.137

Scheme 12.138

Scheme 12.139

Scheme 12.140

Scheme 12.141

Scheme 12.142

Scheme 12.143

Scheme 12.144

Scheme 12.145

Scheme 12.146

Scheme 12.147

Scheme 12.148

Scheme 12.149

Scheme 12.150

Scheme 12.151

Scheme 12.152

Scheme 12.153

Scheme 12.154

Scheme 12.155

Scheme 12.156

Scheme 12.157

Scheme 12.158

Scheme 12.159

Scheme 12.160

Scheme 12.161

Scheme 12.162

Scheme 12.163

Scheme 12.164

Scheme 12.165

Scheme 12.166

Scheme 12.167

Scheme 12.168

Scheme 12.169

Scheme 12.170

Scheme 12.171

Scheme 12.172

Scheme 12.173

Scheme 12.174

Scheme 12.175

Scheme 12.176

Scheme 12.177

Scheme 12.178

Scheme 12.179

Scheme 12.180

Scheme 12.181

Scheme 12.182

Scheme 12.183

Scheme 12.184

Scheme 12.185

Scheme 12.186

Scheme 12.187

Scheme 12.188

Scheme 12.189

Scheme 12.190

Scheme 12.191

Scheme 12.192

Scheme 12.193

Scheme 12.194

Scheme 12.195

Scheme 12.196

Scheme 12.197

Scheme 12.198

Scheme 12.199

Scheme 12.200

Scheme 12.201

Scheme 12.202

Scheme 12.203

Scheme 12.204

Scheme 12.205

Scheme 12.206

Scheme 12.207

Scheme 12.208

Scheme 12.209

Scheme 12.210

Scheme 12.211

Scheme 12.212

Scheme 12.213

Scheme 12.214

Scheme 12.215

Scheme 12.216

Scheme 12.217

Scheme 12.218

Scheme 12.219

Scheme 12.220

Scheme 12.221

Scheme 12.222

Scheme 12.223

Scheme 12.224

Scheme 12.225

Scheme 12.226

Scheme 12.227

Scheme 12.228

Scheme 12.229

Scheme 12.230

Scheme 12.231

Scheme 12.232

Scheme 12.233

Scheme 12.234

Scheme 12.235

Scheme 12.236

Scheme 12.237

Scheme 12.238

Scheme 12.239

Scheme 12.240

Scheme 12.241

Scheme 12.242

Scheme 12.243

Scheme 12.244

Scheme 12.245

Scheme 12.246

Scheme 12.247

Scheme 12.248

Scheme 12.249

Scheme 12.250

Scheme 12.251

Organic Reaction Mechanisms . 2014

An annual survey covering the literature dated January to December 2014

Edited by

A. C. Knipe

University of Ulster Northern Ireland

This edition first published 2018

© 2018 John Wiley & Sons Ltd

Registered office

John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom

For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com.

The right of A. C. Knipe to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. It is sold on the understanding that the publisher is not engaged in rendering professional services and neither the publisher nor the author shall be liable for damages arising herefrom. If professional advice or other expert assistance is required, the services of a competent professional should be sought.

The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom.

Library of Congress Catalog Card Number 66-23143

British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

Print ISBN: 978-1-118-94179-9

Contributors

K. K. BANERJI

Faculty of Science, National Law University, Mandore, Jodhpur 342304, India

C. T. BEDFORD

Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK

M. L. BIRSA

Faculty of Chemistry, ‘Al. I. Cuza’ University of Iasi, Bd. Carol I, 11, Iasi 700506, Romania

S. CHASSAING

Institut des Technologies Avancées en sciences du Vivant (ITAV), CNRS, Université de Toulouse, 1 Place Pierre Potier, 31106 Toulouse Cedex 1, France

J. M. COXON

Department of Chemistry, University of Canterbury, Christchurch, New Zealand

M. R. CRAMPTON

Department of Chemistry, University of Durham, Durham, DH1 3LE, UK

N. DENNIS

3 Camphorlaurel Crt, Stretton, Brisbane, Queensland 4116, Australia

E. GRAS

Laboratoire de Chimie de Coordination, CNRS – Université de Toulouse, 205 Route de Narbonne 31077, Toulouse Cedex 4, France

D. A. KLUMPP

Department of Chemistry, Northern Illinois University, DeKalb, IL 60115, USA

A. C. KNIPE

Faculty of Life and Health Sciences, University of Ulster, Coleraine, Northern Ireland

P. KOČOVSKÝ

Department of Organic Chemistry, Charles University, 12843 Prague 2, Czech Republic

Department of Organic Chemistry, Stockholm SE 10691, Stockholm University, Sweden

B. A. MURRAY

Department of Science, Institute of Technology Tallaght (ITT Dublin), Dublin D24 FKT9, Ireland

Preface

The present volume, the fiftieth in the series, surveys research on organic reaction mechanisms described in the available literature dated 2014. In order to limit the size of the volume, it is necessary to exclude or restrict overlap with other publications which review specialist areas (e.g. photochemical reactions, biosynthesis, enzymology, electrochemistry, organometallic chemistry, surface chemistry, and heterogeneous catalysis). In order to minimize duplication, while ensuring a comprehensive coverage, the editor conducts a survey of all relevant literature and allocates publications to appropriate chapters. While a particular reference may be allocated to more than one chapter, it is assumed that readers will be aware of the alternative chapters to which a borderline topic of interest may have been preferentially assigned.

All chapters have been written by members of a team of experienced ORM contributors who have submitted authoritative reviews over many years. We are naturally pleased to benefit from such commitment and consequent awareness of developing trends in the title area. Particularly noteworthy in recent years has been a major impact on directed organic synthesis through mechanistic studies which enable optimization of ligand design for highly selective transition metal catalysts.

In view of the considerable interest in application of stereoselective reactions to organic synthesis, we now provide indication, in the margin, of reactions which occur with significant diastereomeric or enantiomeric excess (de or ee).

Although every effort was made to reduce the delay between title year and publication date, circumstances beyond the editor's control again resulted in late arrival of a substantial chapter which made it impossible to regain our optimum production schedule.

I wish to thank the staff of John Wiley & Sons and our expert contributors for their efforts to ensure that the review standards of this series are sustained.

A. C. K.

Chapter 1Reactions of Aldehydes and Ketones and their Derivatives

B. A. Murray

Department of Science, Institute of Technology Tallaght (ITT Dublin), Dublin, Ireland

Formation and Reactions of Acetals and Related Species

Reactions of Glucosides

Reactions of Ketenes and Keteniminium Species

Formation and Reactions of Nitrogen Derivatives

Imines: Synthesis, and General and Iminium Chemistry

Reduction and Oxidation of Imines

Mannich, Mannich-type, and Nitro-Mannich Reactions

Addition of Organometallics to Imines

Arylations, Alkenylations, Allylations, and Alkynylations of Imines

Other Additions to Imines

Aza-Baylis–Hillman Reactions of Imines, and their Morita Variants

Staudinger and Aza-Henry Reactions, and Additions Involving Nitriles

Insertion Reactions of Imines

Cycloadditions of Imines

Miscellaneous Reactions of Imines

Oximes, Oxime Ethers, and Oxime Esters

Hydrazones and Related Species

Nitrones and Related Species

C−C Bond Formation and Fission: Aldol and Related Reactions

Reviews of Aldols, and General Reviews of Asymmetric Catalysis

Asymmetric Aldols Catalysed by Proline and its Derivatives

Asymmetric Aldols Catalysed by Other Amino Acids and their Derivatives

Asymmetric Aldols Catalysed by Other Organocatalysts

Other Asymmetric Aldols

The Mukaiyama Aldol

The Henry (Nitroaldol) Reaction

The Baylis–Hillman Reaction and its Morita Variant

Other Aldol and Aldol-type Reactions

Allylation and Related Reactions

Alkynylations

The Stetter Reaction and the Benzoin Condensation

Michael Additions and Related Reactions

Miscellaneous Condensations

Other Addition Reactions

Addition of Organozincs

Arylations

Addition of Other Organometallics, Including Grignards

The Wittig and Related Reactions

Hydroacylations

Hydrosilylations

Addition of Nitrile-containing Species

Phosphonylation and Related Reactions

Enolization, Reactions of Enolates, and Related Reactions

α

-Substitutions

Oxidation and Reduction of Carbonyl Compounds

Oxidation of Aldehydes to Acids

Oxidation of Aldehydes to Esters, Amides, and Related Functional Groups

Baeyer–Villiger Oxidation

Miscellaneous Oxidative Processes

Reduction Reactions

Stereoselective Reduction Reactions

Other Reactions

References

Formation and Reactions of Acetals and Related Species

1,11-Dihydroxy-undec-9-en-5-one derivatives (1; R = H, Me) undergo a novel and highly stereoselective palladium(II)-catalysed intramolecular cyclization via unstable hemiacetal intermediates, to give spiroketals (2).1

Conversion of aldehydes (RCHO) to their cyclic dithioacetals (3; X = R) has been simplified by the use of 2-chloro-1,3-dithiane (3; X = Cl) in dichloroethane at 50 °C, employing a simple iron catalyst, FeCl3. A single-electron transfer (SET) mechanism is proposed.2

Unsaturated spiroacetal (5) has been prepared as a single regioisomer with de > 96% from a cyclic acetonide (4) with an appropriate alkyne–alcohol tether; the arrowed oxygen is lost with the extrusion of acetone. Catalysed by gold(I), the reaction also works for non-cyclic alkyne–triol chains, but much less cleanly. The acetone → acetonide preparative step can be considered to be a regioselectivity regulator, masking the 1,3-diol's alcohol groups.3

N-Boc-protected amino acid esters derived from serine and threonine forms (natural and unnatural) combine with tetramethoxyalkanes [1,2-diacetals: R1−{C(OMe)2}2−R2] to give chiral bi- and tri-cyclic N,O-acetals in high diasteriomeric excess (de), via an intramolecular trans-carbamoylation cascade.4

2-Substituted and 2,2-disubstituted 1,3-diols, HO−CH2−CR1R2−CH2OH, have been desymmetrized through their para-methoxy benzylidene acetals (6), using dimethyldioxirane (DMDO) to form an intermediate orthoester (7), followed by proton transfer using a chiral phosphoric acid to deliver the monoester product (8). Density functional theory (DFT) calculations indicate that the DMDO oxidation step is rate-determining, and a suitable auxiliary – a buttressed BINOL-phosphoric acid – gives yields/ee up to 99/95%.5

DFT has been used to study the thermal racemization of spiropyrans.6

Based on the reaction of a quinone monoacetal (9) with methylhydroxylamine hydrochloride (MeNHOH·HCl) to give a bridged isoxazolidine (10a) via a double hetero-Michael addition, the analogous diaza process was attempted, using the appropriate hydrazine MeNHNHMe(·2HCl) in refluxing acetonitrile. Surprisingly, this gave a new nucleophilic chlorination to yield a substituted chlorophenol (11) regio-selectively, presumably via acid-catalysed methoxide loss and chloride attack, or vice versa. The intended bridged pyrazolidines (10b) could be accessed via base catalysis in a protic solvent.7

Trimethylsilyl triflate is an efficient Lewis acid catalyst for oxygen-to-carbon rearrangement of vinyl and ketene acetals (12 and 13) to give chain-extended ketones or esters, respectively, giving fair yields in 30 min in dichloromethane (DCM) at −78 °C, with 0.01 mol% trimethylsilyl trifluoromethanesulfonate (TMSOTf). The method has been applied to stereoselective synthesis of C-glycosides from the corresponding anomeric vinyl ethers. Starter (12) can be prepared by methenylation of the corresponding acetal-ester with Tebbe's reagent, and (13) via elimination of an appropriate β-iodo-acetal.8

Selective Heck arylation of acrolein diethyl acetal in water has been achieved by appropriate choice of base: sodium acetate favours reaction with cinnamaldehydes, while diisopropylamine works with 3-propionic esters. In the presence of such a base, the ligands in the [Pd(NH3)4]Cl2 catalyst are exchanged.9

Alkynyldimethylaluminium reagents, derived from terminal alkynes and trimethylaluminium, doubly add to N,N-disubstituted formamides, or to the corresponding O,O-acetals, while similar N,O-acetals undergo mono-addition.10

Alkynylation of N,O-acetals and related pro-electrophiles has been carried out using Au(I) carbophilic catalysts, LAuX, with specific counteranions, X− = −OTf or −NTf2.11

A study of nucleophilic substitutions of five-membered ring acetals bearing fused rings indicates that subtle changes in the structure of the latter can dramatically affect de. An unconstraining ring allowed selectivity comparable to a non-fused analogue, with ‘inside’ attack on the oxocarbenium ion, but if the second ring included at least one oxygen, the de fell considerably. DFT-calculated transition states (TSs) for the addition of allyltrimethylsilane correlated with the results, which are also compared with the better known six-membered series.12

An experimental and theoretical study examines why silylated nucleobase additions to acyclic α-alkoxythiacarbenium intermediates proceed with high 1,2-syn stereocontrol, opposite to that expected for the corresponding activated aldehydes. The acyclic thioaminals formed undergo intramolecular cyclizations to provide nucleoside analogues.13

A new oxidant, N-chloroisonipecotamide, has been characterized and tested with benzaldehyde di-n-alkyl acetals in acetonitrile: kinetic orders are first and zero, respectively.14

An easily prepared and handled palladium(II) complex has been used for the deprotection of acetals and dioxolanes while leaving acid-sensitive groups unaffected.15

For reports on acetals termed ‘aziridine aldehyde dimers’, see the Ugi reaction under ‘Imines: Synthesis and General and Iminium Ion Chemistry’ section. For preparation of bicyclic acetals via an acetalization/oxa-Michael process, see ‘Michael Additions and Related Reactions’ section.

Reactions of Glucosides

The ‘formose reaction’, in which formaldehyde is dimerized to glycolaldehyde (HOCH2CHO) and onward to sugar-like substances, is a candidate for prebiotic simple sugars. Though a mechanism was proposed by Breslow in 1959,16a it has remained controversial. New deuterium studies have clarified the route, retaining the original intermediates but changing some connecting steps. Glycolaldehyde formation is autocatalytic, and deuterium is not readily incorporated16b: this is inconsistent with enolization pathways, and the original author now puts the relevant isomerizations down to hydride shifts.16c

6-Deoxy-l-hexoses are rare but biologically important. All eight have now been prepared as their thioglycoside glycosyl donors, starting from l-rhamnose or l-fucose, using protecting-group manipulations and highly selective epimerizations. The following trends are observed: (i) cis-diols can be prepared using stereoselective reduction of a ketone with a chelating α-substituent, and (ii) trans-diols can be prepared via Mitsonobu reaction or stereoselective reduction without a chelating α-substituent.17

In an organocatalytic approach, which mimics dihydroxyacetone phosphate aldolases, de novo syntheses of 1-deoxy-d-ketohexoses and d-ketohexoses have been carried out using chiral diamide catalysts, and hydroxy- or dihydroxy-acetone, respectively, with the (R)-isomer of glyceraldehyde acetonide. This enamine-based C3 + C3 methodology also works for the l-series, using the (S)-acetonide. The authors also note that the enamine process faces competition: simple achiral 1°, 2°, and 3° amines also catalyse the reactions, giving syn-aldols.18

A short review (63 references) examines a number of unusual enzymatic glycoside cleavage mechanisms that differ significantly from the classical Koshland retaining and inverting glycosidases. Typically, they cleave glycosides by mechanisms involving either elimination or hydration, and – in contrast to the exclusively cationic TSs of Koshland – they can involve development of either positive or negative charge in the TS. Some can cleave otherwise resistant thioglycosides. As some of these enzymes are sourced from pathogens, their selective inhibition may facilitate effective treatments of the related diseases with minimal side effects.19

N-Benzylgalactonoamidine exhibits characteristics of a TS analogue for enzymatic hydrolysis of aryl-β-d-galactopyranosides; its inhibition constants for a range of substrates range from 12 to 56 nM.20

A DFT investigation of anomeric equilibration in sugars via oxocarbenium ions has examined the reaction series from an α-covalent triflate intermediate to the corresponding α-contact ion pair, the solvent-separated ion pair, and on to the β-analogues. Attempting geometry optimization of ion pairs without solvent resulted in re-formation of the covalent α- and β-triflates, but as few as four DCM molecules provided sufficient stabilization. Gibbs activation energies for the formation of the contact ion pairs were calculated as 10.4 and 13.5 kcal mol−1 for α- and β-, respectively.21

Ab initio molecular dynamics has been employed to model the ring-opening and isomerization of glucose to fructose, catalysed by chromium(III) chloride. The hydride shift is the overall rate-limiting step.22

Mechanisms of glycosylation have been reviewed, with a focus on computation, covering neighbouring group and solvent effects, the influence of the conformational flexibility of the glycosyl donor on reactivity/selectivity, and endo- versus exo-cyclic cleavage of pyranosides.23

Linear and branched α-glucans have been synthesized using hydrogen-bond-mediated aglycone delivery (HAD), where pyridylmethyl or pyridylcarbonyl substituents are employed remotely. Linear cases from di- to penta-saccharides were achieved with complete stereoselectivity in all glycosylations, but the method may be affected by the increased bulk of the glycosyl acceptor. Branched structures proved more problematic.24

Nucleophilic substitution reactions of tetrahydropyran acetals (14) with H2C=C(OPh)OTMS are promoted by TMS-triflate, with significant solvent effects: polar solvents favour SN1 products, and non-polar favour SN2. Trichloroethylene was identified as the solvent most likely to give SN2 products in both C- and O-glycosylations.25

An attempt to promote highly α-selective glycosylation by six-ring neighbouring group participation has studied glycosyl donors with novel 2-iodo- and 2-(phenylseleno)-ethyl ether protecting groups. While participation was not seen for the iodo-ethyl ether case, the seleno-substituent did show participation (as shown by the observation of cyclic intermediates by low-T NMR), but even here it was not enough to prevent a significant flux to β-product.26

The use of aryl and alkyl sulfenyl triflates as promoters of glycosylation has been reviewed.27

Difficulties in using triflic anhydride to mediate direct dehydrative glycosylation have been overcome by using a strained olefin such as β-pinene as an acid scavenger.28

Phenyl(trifluoroethyl)iodonium triflimide, Ph−I+−CH2CH2CF3−NTf2, is an air- and water-soluble activator of thioglycosides, allowing glycosylation at ambient temperature in good to very high yields, and high de in some cases, over a wide range of donors, including sensitive 2- and 6-deoxy sugars.29

3,3-Difluoroxindole (15, ‘HOFox’) has been used to mediate glycosylation. Both the in situ synthesis of OFox glycosyl donors and activation thereof can be performed regeneratively, so only catalytic amounts of the OFox imidate donor and Lewis acid activator are required.30

The combination of AuCl3 and phenylacetylene promotes both Ferrier rearrangement of glycols with nucleophiles, and also O-glycosylation of 1-O-acetyl sugars.31

The kinetics of the hydrolytic cleavage of non-terminal α-glycosidic bonds in cyclodextrins have been measured in DMSO–water mixtures and compared to those of d-maltose. In particular, the yield of 5-hydroxymethyl-2-furaldehyde was monitored with a view to optimizing green routes to its generation from biomass.32

Following the screening of 26 representative metal salts, strontium dichloride emerged as the most efficient co-catalyst for acidic hydrolysis of methyl glycosides, with short reaction times, high yields, and fewer by-products.33

Cellobiose can be hydrolysed to glucose in ionic liquids (ILs). An ab initio quantum study suggests an SN1-type mechanism, and the energetics are compared with those of gas phase and aqueous solution.34

A review attempts to develop a comprehensive kinetic and mechanistic picture of the conversion of pentoses to furfural in aqueous acidic media, although the variations in the specific conditions of each study examined make concise comparison difficult.35

d-Glucose has been converted to 5-hydroxymethylfurfural in DMSO at 150 °C, using an acidic IL, namely 1-(1-propylsulfonic)-3-methylimidazolium chloride, as catalyst. The mechanism has been studied by visible spectroscopy and 1H and 13C NMR, including the use of glucose labelled at C(1) or C(2). Glucose is isomerized to fructose via the complexation of the open-chain form with the imidazolium cation. Yields are low, being limited by the formation of humin.36

The condensation and dehydration reactions of glucose in DMSO have been studied computationally and compared with experiment: the reactions are initiated by protonation of C(1)−OH and C(2)−OH, respectively. While the mechanisms are similar to those in aqueous solution, the magnitudes of the barriers are quite solvent-dependent.37

Direct umpolung of glycals with ketones has been carried out using samarium diiodide: for the hexose series, the allyl samarium reagent produced is highly stereoselective, reacting with ketones at the C(3) position anti to a C(4) substituent.38

3,4,6-Tri-O-acetyl-d-galactal is selectively converted to 1-O-aryl-2-deoxy derivatives or chiral bridged benzopyrans depending on reaction conditions, using Al(OTf)3 catalysis, with easy onward access to chiral chromenes and chromans.39

Tosylation of l-rhamnose, followed by reduction and acetylation, yields 2,3,4-triacetyl-1,6-dideoxy-l-mannose and tetraacetyl-3,6-dideoxy-l-mannitol; the mechanism has been probed via DFT.40

A titrimetric method has been used to study the kinetics of palladium(II)-catalysed oxidation of d-(+)-galactose by cerium(IV) in aqueous acid from 308 to 333 K. Arabinose and formic acid are the main products.41

The kinetics of the ruthenium(III)-catalysed oxidation of d-arabinose by N-bromophthalimide were measured in acid from 303 to 323 K: the main products are erythronic and formic acids.42

The kinetics of oxidation of d-(+)-trehalose by N-bromoacetamide has been studied in acid solution over a range of temperatures. Using a rhodium(III) pentachloride catalyst, the order is one with respect to substrate, catalyst, oxidant, and hydronium ion, with arabinonic and formic acids as the main products.43

The kinetics of the oxidation of glucose and fructose by N-chloronicotinamide has been studied in alkaline solution from 308 to 328 K, giving gluconate and formate, respectively; 1,2-enediol intermediates are discussed.44 A similar study using N-bromonicotinamide in alkaline solution has found the rates for glucose to be first order in alkali concentration, but the fructose exhibits inverse first order.45

Ruthenium(III)-catalysed oxidation of xylose by potassium bromate has been studied from 30 to 45 °C in both acidic and alkaline media. In acid, the order in bromate is one at low concentration, but then saturates, and pH has negligible effect, which is also found in base. D2O also has little effect on the rate.46

The kinetics of iodate oxidation of lactose have been studied in aqueous alkaline medium, using an iridium(III) catalyst.47

The kinetics of the oxidation of galactose by cerium(IV) has been studied in acid from 308 to 328 K.48

The kinetics of oxidation of several simple saccharides by alkaline permanganate have been studied spectrophotometrically. An enediol intermediate complex is proposed, and the reactivity order is glucose ∼ galactose > maltose > fructose > sucrose49; a similar study of lactose has been performed.50

The kinetics of ruthenium(III)-catalysed oxidation of maltose by potassium permanganate in acid show orders 1, 0, 1, and 1, respectively. A spectrophotometric study suggests [Ru(H2O)4O]2+ as the active Ru(III) species.51

Several reports under ‘Formation and Reactions of Acetals and Related Species’ section are relevant to glucosides, and synthesis of a new carbohydrated-related skeleton is reported under ‘Other Asymmetric Aldols’ section.

Reactions of Ketenes and Keteniminium Species

A synthetic exploration of the possibilities provided by ynimines, R1−C≡C−N=CR2R3, under anionic conditions highlights their use as precursors of metalated ketenimines via in situ reaction with organolithium or other strong bases. Onward reaction with various electrophiles provides nitriles, α,β-unsaturated nitriles, and α,β-unsaturated amides.52

Given the role of 3° amines in generating ketenes and in catalysing their reactions, and their degradation in some reactions, an experimental and computational study of reaction of such aliphatic amines with aryl ketenes, 4-X-C6H4−CH=C=O, has been carried out. Using typical photogeneration of a ketene with triethylamine in acetonitrile at 25 °C, triethylamine attack on the carbonyl gives a zwitterion, Ar−CH=C(O−)−+NEt3, which loses an ethyl cation (quaternizing external triethylamine), giving an enolate-type intermediate which protonates to give amide ArCH2CONEt2. For the parent compound (X = H), ketene decay is ∼8 times faster than formation of amide, while a nitro group accelerates the decay (×400) and even more dramatically slows the amide formation (÷5000). Among other amines examined, N-methyldialkyls strongly prefer methyl loss by displacement, isopropyl loss involves elimination, while DABCO forms a long-lived zwitterion, helping to explain how cinchona alkaloids can add to ketenes with zwitterion formation and promote subsequent stereoselective additions even in the presence of triethylamine. The dealkylation process is also found for reaction of tertiary amines with the much more stable diphenyl ketene.53

A phase space approach has been used to explore mechanisms of ketene isomerization.54

Quantum chemical methods have been used to study the dimerization of alkyl ketenes.55

Silyl ketene imines (e.g. 16a) have been electrophilically trifluoromethylated using hypervalent iodine reagents (16b; X = C=O or CMe2) to give quaternary α-trifluoromethyl nitriles (17); the latter are easily transformable into a range of useful organofluorine building blocks. The reaction gives yields up to 89% in a day at ambient temperature, using a vanadium(IV)-salen catalyst, without solvent.56

The first report of the formation of a 1,3,5-dioxathiane in a ketene reaction describes the reaction of two moles of diphenylketene with adamantanethione to give 2,4-bis(diphenylmethylidene)-1,3,5-dioxathiane (18) via ketene-thione zwitterions.57

A range of heterocyclic ketene aminals (19a; n = 0−3), which have two nucleophilic centres (arrowed), form adducts with ninhydrin, with further isomerization under kinetic or thermodynamic control, and a significant dependence on the solvent. The possible role of the amidine tautomer (19b) is discussed.58

Tertiary amides bearing at least one α-hydrogen (20), when treated with hindered base and triflic anhydride in refluxing chloroform, give keteniminium salts (21). When R1 = H (i.e. an ‘aldo’-keteniminium), these react with acetylene to give cyclobuteniminium salts (22): these in turn are dienophiles in Diels–Alder reactions, and better than cyclobutenones.59

Formation and Reactions of Nitrogen Derivatives

Imines: Synthesis, and General and Iminium Chemistry

A new general organocatalytic method for the preparation of aldimines from aldehydes and amines uses pyrrolidine without acids or metals. Yields are close to quantitative, covering virtually all types of imines: N-alkyl, -aryl, -sulfinyl, -sulfonyl, and -phosphinoyl. Aldehydes employed were typically aromatic (or cinnamyl), though aliphatic aldehydes did work for the N-sulfinyl cases, with t-butyl-sulfinamide proving more successful than para-tolyl.60

N-Sulfonyl imines, Ar−CH=N−Ts, have been prepared from aldehydes and chloramine-T (Na+ −NClTs), using proline as organocatalyst, in aqueous medium at ambient temperature; enals are particularly reactive, including aliphatic cases.61

A systematic NMR study of the effect of ILs on reactivity examined imine formation from 1-aminohexane and either benzaldehyde or para-methoxy benzaldehyde in d3-acetonitrile, with controlled amounts of 1-butyl-3-methylimidazolium salts or other ILs. ILs increased the reaction rate constant in proportion to their mole fraction, and temperature variation allowed separation of enthalpic and entropic contributions, which varied with the salt used. The approach should enhance the predictability of the effects of varying the IL cation, anion, and concentration.62

A ruthenium(II) NNN-pincer complex catalyses direct coupling of 1° alcohols and 1° amines in air, to give imines. For example, benzyl alcohol and benzylamine gives 97% yield of PhCH=NCH2Ph in 12 h in toluene at 70 °C, using 0.01 mol% catalyst. The first step is considered to be dehydrogenation of the alcohol to the aldehyde (which requires oxygen), with the aldehyde remaining bound to the metal: this can be observed in the absence of amine. Stereoselective versions are being explored.63

N-Alkylation can be achieved by the oxidation of primary alcohols to aldehydes, condensation of the latter with the amine, and subsequent reduction of the imine product. The copper(II)-catalyst variant has been studied by DFT: the first two steps are significantly uphill, but the imine reduction acts as the driving force. The calculated turnover frequency agrees well with the experimental value.64

With a view to better understand poly(hexahydrotriazine) polymers from reactions of diamines with formaldehyde, an experimental and computational study of the monoamine version of formation of cyclic hemiaminals (23) – via the imine, R−N=CH2 – has been undertaken. Mechanisms involving water-promoted sequential condensations are preferred to amine catalyses, and results explain the higher reactivity of electron-rich amines. In contrast, trifluoromethylamine is markedly less reactive.65

AM1 and DFT methods have been applied to the mechanism of reaction of phenylpropan-2-one with ethylamine.66

Triflic acid catalyses the reaction of aldehydes with 2-vinylaniline to give substituted quinolines; a similar reaction with biphenyl-2-amine gives substituted phenanthridines. Both proceed via imine formation, protonation, and then cyclization.67

Addition of 1° amines to α,β-unsaturated aldehydes and ketones to produce imines can proceed with either 1,2- or 1,4-addition. An in situ IR and NMR study, combined with DFT, has been used to identify what governs the selectivity. 1,2-Addition predominates, typically under kinetic control, and exceptions such as methyl vinyl ketone have been explained in terms of conformational effects. The in situ methodologies are particularly useful, given the instability of the imines towards hydrolysis, polymerization, and so on.68

Kinetics of the formation of 2-HO−C6H4−CH=N−C6H4-4-Me, from salicylaldehyde and 4-toluidine,69 of the 5-chloro-derivative N-(5-chloro-salicylidene)-4-methylaniline,70 and of the Schiff bases from salicylaldehyde with meta-chloro-71 and para-chloro-aniline72 have all been studied in ethanol from 303 to 318 K.

A kinetic and mechanistic study of Schiff base formation from the reaction of l-α-glutamic acid with pyridoxal shows that subsequent hydrolysis completes the transamination; that is, yields pyridoxamine and α-ketoglutaric acid. Reaction of l-glutamine with pyridoxal has also been studied.73

The mechanisms of reaction of benzaldehyde with 4-amino-4H-1,2,4-triazole to give Schiff base, via a hemaminal, have been probed computationally.74

Enantioselective methodologies using N-carbamoyl-imines have been reviewed (153 references): key advantages include their increased reactivity towards nucleophiles, and the relative ease of later removal of the carbamoyl moiety.75

Imine metathesis is catalysed by 1° aliphatic amines, and a kinetic NMR study of transiminations of both aromatic–aromatic and aromatic–aliphatic imines in organic solvents at ambient temperature indicates that these exchange reactions are fast enough to allow them to catalyse the metathesis in the absence of acid or metal catalysis. Hammett plots generated by varying the ortho-substituent of benzaldimines are non-linear, with both donating (OMe) and withdrawing (NO2) substituents retarding the process. This somewhat unusual ‘concave-down’ plot is attributed to a change in the rate-determining step. The results hold promise for the generation of dynamic combinatorial libraries under the conditions employed.76

The use of imine and iminium precursors as versatile intermediates in enantioselective catalysis has been reviewed (127 references).77

A range of N,N′-cyclic azomethine imines (24) undergo phosphination and hydrophosphonylation with diarylphosphinoxides or dialkylphosphites, using chiral squaramide catalysts derived from dihydroquinine, in yields/ee up to 99/99%.78 Aromatic cases (e.g. 24; R = Ph) allow easy access to dinitrogen-fused heterocycles via a phosphine-catalysed 3 + 2-cycloaddition to bis(phenylsulfonyl)alkenes.79

C,N-Cyclic-N′-acyl azomethine imines (25) undergo ring expansion to 3-benzazepines (26) using sulfonium ylide generated in situ from a suitable salt, for example, PhSMe2+ BF4−.80

An azomethine imine (27) undergoes rhodium(III)-catalysed C−H alkynylation at the ortho-position, using an alkynylated hypervalent iodine reagent. The azomethine imine acts as a masked aldehyde directing group, easily converted back to aldehyde by hydrolysis. Without the methyl group ‘blocker’ on the aromatic ring, both ortho positions react. The method also overcomes the poor directing effect of the aldehyde.81

An N-heterocycle (NHC)-catalysed 3 + 4-cycloaddition of azomethine imines and enals generates dinitrogen-fused seven-membered heterocycles in high de/ee. The method also kinetically resolves the imines.82

Bromodifluoromethylation of iminium ions with TMS–CF2Br has been described. The iminium ions are generated in situ from aldehydes, 2° amines, proton sponge, and silyl triflate. TMS–CF2Br can be activated with HMPA at ambient temperature to generate difluorocarbene, which converts to bromodifluoromethyl carbanion in the presence of excess bromide. Similar chloro- and iodo-difluoromethylations are also reported.83

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) has been used to characterize intermediates in the Ugi and Ugi–Smiles reactions and the related Mumm rearrangement.84a A key nitrilium ion intermediate is described, and the Ugi–Smiles mechanism is characterized as ionic, with an earlier theoretical investigation of a hemiaminal intermediate84b being discussed. No evidence for such a hemiaminal was found, supporting the Ugi–Smiles reaction as being essentially mechanistically identical to the Ugi.

The ‘aziridine aldehyde dimer’ [(R)-28] reacts with l-proline and t-butyl isocyanide to give a chiral piperazinone (29). The kinetics of this Ugi-type multi-component reaction are first order in dimer (28) and zero order in other species. DFT calculations indicate selective formation of a Z-iminium ion.85

Another aziridine aldehyde dimer [(S)-30] undergoes a ‘disrupted’ Ugi reaction with an amino acid [R1HN−C(R2)−CO2H, R = H, Ar, alkyl] and an isocyanide (R3N≡C) to give piperazinones: trans- if R1 = H, and cis- for aryl/alkyl.86

The three-component Ugi reaction of an aldehyde, an amine, and an isocyanide has been catalysed by a range of BOROX catalysts (31) in fair to good ee. The BOROX methodology was conveniently screened using a catalyst ‘library’ prepared by combination of borane (as its dimethyl sulfide complex), water, an alcohol (ROH), an amine, and a chiral biaryl diol. An ion pair between a chiral boroxinate anion and an achiral iminium ion is proposed as the catalytically active species.87

Aryl aldehydes react with TMS-azide in the presence of a Lewis acid catalyst to generate azidocarbenium ion intermediates [Ar−CH=N−N2+]; these can be trapped in one pot with nucleophiles to give azides Ar−CH(Nu)−N3. The nucleophile could be the azide itself (from TMS-azide), giving a gem-diazido-product, ArCH(N3)2, easily reducible to mono-azide (i.e. ArCH2N3) with triethylsilane. An enantioselective variant is also reported, as is the preparation of β-azido-dicarbonyl compounds. Schmidt rearrangement does not intervene.88

Reduction and Oxidation of Imines

A short review examines a metal-organo cooperative approach to asymmetric hydrogenation of imines, using a chiral phosphoric acid and an iridium complex.89

Unprotected NH imines of substituted acetophenones – prepared as their hydrochloride salts, Ar−C(Me)=NH2+Cl− – have been asymmetrically hydrogenated to give the corresponding amine salts in yields/ee up to 97/95%. A standard rhodium catalyst [Rh(cod)Cl]2 and a bisphosphinyl-ferrocene with a pendant chiral thiourea effect the transformation, with hydrogen-bonding dual activation from the auxiliary, including anion binding of the chloride. Further mechanistic investigation by counterion variation, 1H NMR, and deuterium labelling is also reported.90

A range of Mo(0) and W(0) trisphosphine-substituted nitrosyl hydride complexes (32) have been prepared and tested as catalysts of hydrogenation of imines, using an acidic co-catalyst [H(Et2O)2][B(C6F5)4]. An ‘ionic hydrogenation mechanism’ is proposed, with heterocyclic splitting of molecular hydrogen followed by ‘proton before hydride’ transfers. This is supported by linear Hammett plots for a series of para,para′-disubstituted benzylideneaniline substrates, Ar1−CH=N−Ar2, where ρ values of −10.5 and +0.86 were found for the C- and N-sides, respectively. Iminium intermediates were observed, there was a linear dependence on p(H2), and a dynamic kinetic isotope effect of 1.38 was measured. H2 addition is proposed to be rate-limiting.91

NHC complexes of zincocenes and dizincocenes catalyse hydrogenation of imines and ketones, respectively.92

An experimental and computational study has examined the effect of arene variation in the use of Noyori's [RuCl(TsDPEN)(η6-arene)] catalysts for transfer hydrogenation of 3,4-dihydroisoquinolines.93

An unusual chiral cationic Lewis base, a quaternized picolinamide-cinchona organocatalyst, efficiently adds trichlorosilane to ketone imines, reducing them to the amines in good yield and up to 91% ee, sometimes in 15 min with 0.5 mol% loading.94

Other uses involving trichlorosilane include 2-pyridoyl esters of d-glucosamine derivatives catalysing the reduction of N-Boc aryl aldimines with good yields and fair ees,95 a new organocatalyst combining a carbohydrate and N-formyl-l-valine giving yields/ee up to 98/94% in the reduction of arylidene anilines,96 and a new chiral axial amide N,N′-dioxide derived from l-tryptophan, reducing ketimines in good ee.97

α-Silylimines undergo Meerwein–Ponndorf–Verley (MPV)-type reduction to α-silylamines in high ee using a chiral lithium amide; the authors have modified their previously proposed chair-like six-membered TS98a in the light of the current results,98b and used DFT to further clarify the mechanism.

Malonate-imine (33), derived from dimethyl malonate and two moles of salicylaldehyde, was expected to reductively ring-close to the corresponding benzoxazine on treatment with borohydride in methanol. Instead, a boramide (34) is formed, with loss of the malonate moiety. X-ray crystallography indicates cis-fusion of the rings, with B and N atoms approximately tetrahedral. The B−O(Me) bond is very short (1.42 Å), yet the methoxy is easily lost in positive-electrospray MS. In solution, (34) exhibits a solvent-dependent cis–trans equilibrium. Loss of the malonate probably occurs early on, as direct reaction of salicylaldehyde and its unsubstituted imine with NaBH4 also yields (34).99

A ruthenium-catalysed reductive methylation of nitrogen employs carbon dioxide and molecular hydrogen as C and H sources: starting from aldimine R1−N=CHR2, a ruthenium(triphos) catalyst delivers an N-methylamine, R1−N(Me)−CH2R2, in up to 99% yield, using the two gases at 20 and 60 atm, respectively. The reaction can also be performed in situ, starting from the amine R1NH2 and aldehyde R2CHO, demonstrating excellent atom and step economy.100

The kinetics of the oxidation of diaryl ketimine (35) by cerium(IV) in aqueous sulfuric acid indicate a first-order dependence on substrate and oxidant. Ionic strength and solvent effects are reported, as well as activation parameters.101

An isomer (36) has been similarly studied kinetically over a range of temperatures.102

Mannich, Mannich-type, and Nitro-Mannich Reactions

Single and double A3-coupling Mannich reactions of terminal alkynes, pyrrolidine, and formaldehyde are catalysed by copper(I)-biphenylphosphine complexes. The catalysis has been compared with that by the less effective gold(I) complexes.103

A cyclic imine (37) undergoes direct Mannich reaction with methyl alkyl ketones in up to 97% ee, using an alkaloid-derived 1°–3° diamine organocatalyst. The regioselectivity is under steric control, with the reaction occurring at the methyl side of the ketone.104

The mechanism of the enantioselective Mannich reaction catalysed by hydrogen-bond-donor bifunctional organocatalysts – chiral amino-(thio)ureas (38; X = O, S) – has been investigated by tethering on a β-dicarbonyl moiety to generate a binary complex to act as a model of a catalyst and nucleophile, the so-called ‘snap-shot structural analysis’. While the urea might be expected to form individual hydrogen bonds to the two carbonyls, X-ray crystallography of two models [diketone (X = Ph) and keto-ester (X = OMe)] clearly showed a double-hydrogen-bond interaction to one carbonyl (39). In another case with an amino substituent on the urea, an ammonium-enolate intermediate could be directly observed by X-ray crystallography and in solution by NMR. Nucleophilic reactions of imines with the binary-complex models have also been carried out.105

Aliphatic, aromatic, and heteroaromatic N-Boc aldimines undergo enantioselective Mannich reaction with β