Greene's Protective Groups in Organic Synthesis

Peter G.M. Wuts is a Distinguished Scientist at Kalexsyn, Inc. in Kalamazoo, Michigan.

Preface to the Fifth Edition xi

Preface to the Fourth Edition xiii

Preface to the Third Edition xv

Preface to the Second Edition xvii

Preface to the First Edition xix

Abbreviations xxi

1. The Role of Protective Groups in Organic Synthesis 1

Properties of a Protective Group 1

Historical Development 2

Development of New Protective Groups 2

Selection of a Protective Group from This Book 4

Synthesis of Complex Substances: Two Examples (As used in the Synthesis of Himastatin and Palytoxin) of the Selection Introduction and Removal of Protective Groups 5

Synthesis of Himastatin 5

Synthesis of Palytoxin Carboxylic Acid 9

2. Protection for the Hydroxyl Group Including 12- and 13-Diols 17

Ethers 26

Substituted Methyl Ethers 33

Substituted Ethyl Ethers 87

Methoxy-Substituted Benzyl Ethers 146

Silyl Ethers 201

Esters 271

Bisfluorous Chain-Type Propanoate (Bfp–OR) Ester 307

Proximity-Assisted Deprotection for Ester Cleavage 329

Miscellaneous Esters 336

Sulfonates Sulfenates and Sulfinates as Protective Groups for Alcohols 337

Carbonates 347

Carbamates 371

Protection for 12- and 13-Diols 375

Monoprotection of Diols 375

Cyclic Acetals and Ketals 385

Chiral Ketones 446

Cyclic Orthoesters 447

Silyl Derivatives 456

Cyclic Carbonates 465

Cyclic Boronates 468

3. Protection for Phenols and Catechols 472

Protection for Phenols 475

Ethers 475

Silyl Ethers 522

Esters 528

Carbonates 535

Carbamates 538

Phosphinates 540

Sulfonates 541

Protection for Catechols (12-Dihydroxybenzenes) 545

Cyclic Acetals and Ketals 545

Cyclic Esters 551

Protection for 2-Hydroxybenzenethiols 552

4. Protection for the Carbonyl Group 554

Acetals and Ketals 559

Acyclic Acetals and Ketals 559

Cyclic Acetals and Ketals 576

Chiral Acetals and Ketals 611

Dithio Acetals and Ketals 615

Cyclic Dithio Acetals and Ketals 620

Monothio Acetals and Ketals 644

Diseleno Acetals and Ketals 649

Miscellaneous Derivatives 650

O-Substituted Cyanohydrins 650

Substituted Hydrazones 654

Oxime Derivatives 661

12-Adducts to Aldehydes and Ketones 669

Cyclic Derivatives 674

Protection of the Carbonyl Group as Enolate Anions Enol Ethers Enamines and Imines 676

Monoprotection of Dicarbonyl Compounds 679

Selective Protection of α- and β-Diketones 679

Cyclic Ketals Monothio and Dithio Ketals 684

5. Protection for the Carboxyl Group 686

Esters 692

General Preparation of Esters 692

General Cleavage of Esters 699

Transesterification 704

Enzymatically Cleavable Esters 711

Substituted Methyl Esters 723

2-Substituted Ethyl Esters 739

26-Dialkylphenyl Esters 768

Substituted Benzyl Esters 775

Silyl Esters 792

Activated Esters 796

Miscellaneous Derivatives 799

Stannyl Esters 812

Amides and Hydrazides 812

Amides 820

Hydrazides 825

Protection of Sulfonic Acids 828

Protection of Boronic Acids 831

6. Protection for the Thiol Group 837

Thioethers 841

S-Diphenylmethyl Substituted S-Diphenylmethyl and S-Triphenylmethyl Thioethers 855

Substituted S-Methyl Derivatives: Monothio Dithio and Aminothio Acetals 864

Substituted S-Ethyl Derivatives 875

Silyl Thioethers 880

Thioesters 881

Thiocarbonate Derivatives 883

Thiocarbamate Derivatives 885

Miscellaneous Derivatives 886

Unsymmetrical Disulfides 886

Sulfenyl Derivatives 888

Protection for Dithiols: Dithio Acetals and Ketals 891

Protection for Sulfides 892

S–P Derivatives 893

Protection for the Amino Thiol Group 894

7. Protection for the Amino Group 895

Carbamates 907

Substituted Ethyl Carbamates 921

Carbamates Cleaved by a 16-Elimination 977

Carbamates Cleaved by β-Elimination 979

Photolytically Cleaved Carbamates 983

Miscellaneous Carbamates 987

Urea-Type Derivatives 989

Amides 990

Assisted Cleavage of Amides 1007

Bisprotection of Amines 1009

Special –Nh Protective Groups 1025

N-Alkyl and N-Aryl Amines 1025

Imine Derivatives 1060

Enamine Derivatives 1069

Quaternary Ammonium Salts 1072

N-Heteroatom Derivatives 1073

N-Metal Derivatives 1073

N-N Derivatives 1078

N-P Derivatives 1083

N-Si Derivatives 1086

N-S Derivatives 1088

Protection of Amino Alcohols 1116

Protection for Imidazoles Pyrroles Indoles and Other Aromatic

Heterocycles 1120

N-Sulfonyl Derivatives 1120

Carbamates 1124

N-Alkyl and N-Aryl Derivatives 1129

N-Trialkylsilylamines R2N–SiR03 1131

N-Allylamine CH2.CHCH2NR2 1131

N-Benzylamine (Bn–NR2) PhCH2–NR2 1132

Amino Acetal Derivatives 1137

Amides 1141

Protection for the Amide –NH 1151

Protection for the Sulfonamide –NH 1182

8. Protection for the Alkyne –CH 1194

9. Protection for the Phosphate Group 1203

Some General Methods for Phosphate Ester Formation 1209

Removal of Protective Groups from Phosphorus 1210

Alkyl Phosphates 1214

Phosphates Cleaved by Cyclodeesterification 1223

2-Substituted Ethyl Phosphates 1228

Haloethyl Phosphates 1236

Benzyl Phosphates 1239

Phenyl Phosphates 1246

Photochemically Cleaved Phosphate Protective Groups 1254

Amidates 1258

Miscellaneous Derivatives 1261

10. Reactivities Reagents and Reactivity Charts 1263

Reactivities 1263

Reagents 1264

Reactivity Charts 1267

Reactivity Chart 1. Protection for Hydroxyl Group: Ethers 1269

Reactivity Chart 2. Protection for Hydroxyl Group: Esters 1274

Reactivity Chart 3. Protection for 12- and 13-Diols 1278

Reactivity Chart 4. Protection for Phenols and Catechols 1282

Reactivity Chart 5. Protection for the Carbonyl Group 1286

Reactivity Chart 6. Protection for the Carboxyl Group 1290

Reactivity Chart 7. Protection for the Thiol Group 1294

Reactivity Chart 8. Protection for the Amino Group: Carbamates 1298

Reactivity Chart 9. Protection for the Amino Group: Amides 1302

Reactivity Chart 10. Protection for the Amino Group: Special –NH Protective Groups 1306

Reactivity Chart 11. Selective Deprotection of Silyl Ethers 1311

Index 1333