Greene's Protective Groups in Organic Synthesis, 2 Volume Set

6th Auflage
ISBN: 978-1-394-23316-8
Verlag: Wiley

Buch, Englisch, 1696 Seiten, Format (B × H): 211 mm x 257 mm, Gewicht: 3311 g

Integral, reliable, and comprehensive guidance for chemists performing the complex syntheses required for the formation and cleavage of protective groups

Organic synthesis is the preparation and creation of organic compounds for use in natural products, pharmaceuticals, and other molecules. The synthesis of molecules having multiple functional groups often requires the use of ‘protective groups’ to achieve site selectivity in a chemical reaction within a molecule bearing multiple sites of reactivity. Protective groups are installed temporarily to prevent unwanted reactions at a particular site, while transforming a different functional group. Once they have served their function, they are removed to expose the original group. Without a thorough understanding of the methods required to install and remove them, the design of a synthesis of a molecule having multiple functional groups in most cases is effectively impossible.

Greene’s Protective Groups in Organic Synthesis, 6th Edition is the definitive compilation of protective groups, their classification, and their application in a wide array of situations. With a long tradition of comprehensive coverage, organized on the basis of the functional group in need of protection and subsequent deprotection, it is an essential reference and resource for all chemists involved in organic syntheses. Now fully updated to reflect the current state of the art, it remains an indispensable resource for generating life-changing organic products. This edition contains a new chapter on how protective groups effect reactivity and selectivity in carbohydrate chemistry.

Readers of the sixth edition of Greene’s Protective Groups in Organic Synthesis will also find: - Methodology for planning selectivity in organic syntheses
- Detailed discussion of all major functional groups including ethers, amides, and phenols
- A discussion of the impact of protective groups on reactivity in carbohydrates

Greene’s Protective Groups in Organic Synthesis is ideal for synthetic organic chemists or medicinal chemists in academia, industry — pharmaceuticals, food, agrochemicals, and biotech — or government agencies.

Autoren/Hrsg.

Wuts, Peter G M

Fachgebiete

• Naturwissenschaften Chemie Organische Chemie
• Naturwissenschaften Chemie Chemie Allgemein Pharmazeutische Chemie, Medizinische Chemie

Inhaltsverzeichnis

Preface xiii

Abbreviations xv

Volume 1

1. The Role of Protective Groups in Organic Synthesis 1

Properties of a Protective Group 1

Historical Development 1

Development of New Protective Groups 2

Selection of a Protective Group from This Book 3

Synthesis of Complex Substances. Two Examples (As Used in the Synthesis of Himastatin and Palytoxin) of the Selection Introduction and Removal of Protective Groups 4

Synthesis of Himastatin 4

Synthesis of Palytoxin Carboxylic Acid 8

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

Ethers 22

Substituted Methyl Ethers 30

Substituted Ethyl Ethers 78

Methoxy- Substituted Benzyl Ethers 136

Silyl Ethers 191

Migration of Silyl Groups 193

Cleavage 226

Esters 254

Proximity Assisted Deprotection for Ester Cleavage 313

Miscellaneous Esters 320

Sulfonates Sulfenates and Sulfinates as Protective Groups for Alcohols 321

Carbonates 330

Carbamate Protection of Alcohols 356

Protection for 12- and 13- Diols 359

Monoprotection of Diols 360

Cyclic Acetals and Ketals 383

Chiral Ketones 443

Cyclic Ortho Esters 444

Silyl Derivatives 452

Cyclic Carbonates 461

Cyclic Boronates 464

3. Protection for Phenols and Catechols 469

Protection for Phenols and Catechols 472

Ethers 472

Silyl Ethers 518

Esters 524

Carbonates 530

Carbamates 533

Phosphinates 534

Sulfonates 535

Protection for Catechols (12- Dihydroxybenzenes) 540

Cyclic Acetals and Ketals 540

Cyclic Esters 545

Protection for 2- Hydroxybenzenethiols 546

4. Protection for the Carbonyl Group 549

Acetals and Ketals 553

Acyclic Acetals and Ketals 553

Cyclic Acetals and Ketals 568

Chiral Acetals and Ketals 600

Dithio Acetals and Ketals 604

Acyclic Dithio Acetals and Ketals 604

Cyclic Dithio Acetals and Ketals 609

Monothio Acetals and Ketals 628

Acyclic Monothio Acetals and Ketals 628

Cyclic Monothio Acetals and Ketals 631

Miscellaneous Derivatives 634

O- Substituted Cyanohydrins 634

Substituted Hydrazones 637

12- Adducts to Aldehydes and Ketones 650

Protection of the Carbonyl Group as an Enolate Anions Enol Ethers Enamines and Imines 657

Lithium Diisopropylamide (LDA) 657

Monoprotection of Dicarbonyl Compounds 659

Selective Protection of a- and ß- Diketones 659

Cyclic Ketals Monothio and Dithio Ketals 664

5. Protection for the Carboxyl Group 667

Esters 674

General Preparations of Esters 674

General Cleavage of Esters 679

Transesterification 683

Enzymatically Cleavable Esters 690

Substituted Methyl Esters 700

2- Substituted Ethyl Esters 719

Substituted Benzyl Esters 752

Silyl Esters 773

Activated Esters 777

Miscellaneous Derivatives 779

Stannyl Esters 791

Amides and Hydrazides 792

Amides 800

Protection of Sulfonic Acids 808

Protection of Boronic Acids 812

6. Protection for the Thiol Group 819

Thioethers 822

S- Diphenylmethyl Substituted S- Diphenylmethyl and S- Triphenylmethyl Thioethers 838

4- Methoxytrityl (Mtt–SR) Thioether 842

Substituted S- Methyl Derivatives: Monothio Dithio and Aminothio Acetals 846

Substituted S- Ethyl Derivatives 858

Silyl Thioethers 864

Thioesters 864

Thiocarbonate Derivatives 866

Thiocarbamate Derivatives 868

Miscellaneous Derivatives 869

Unsymmetrical Disulfides 869

Sulfenyl Derivatives 871

Protection for Dithiols: Dithio Acetals and Ketals 874

Protection for Sulfides 875

S–P Derivatives 876

Protection for the Amino Thiol Group 877

Protection for Selenols 877

Volume 2

7. Protection for the Amino Group 879

Introduction to Amines 891

Carbamates 891

Substituted Ethyl Carbamates 905

Carbamates Cleaved by a 16- Elimination 957

Cleavage by ß- Elimination 959

Photolytically Cleaved Carbamates 964

Miscellaneous Carbamates 970

Urea- Type Derivatives 972

Amides 973

Transamidation 974

Assisted Cleavage of Amides 991

Amide Cleavage Induced by Nitro Group Reduction 991

Amide Cleavage Induced by Release of an Alcohol 992

Amides Cleaved by Other Chemical Reactions 992

Bisprotection of Amines 993

Special –NH Protective Groups 1010

N- Alkyl and N- Aryl Amines 1010

Imine Derivatives 1042

Enamine Derivatives 1050

N- Heteroatom Derivatives 1053

N- Metal Derivatives 1054

N- N Derivatives 1057

N- P Derivatives 1063

N- Si Derivatives 1066

N- S Derivatives 1067

N- Sulfenyl Derivatives 1067

Protection of Amino Alcohols 1096

Protection for Imidazoles Pyrroles Indoles and Other Aromatic Heterocycles 1101

N- Sulfonyl Derivatives 1101

Carbamates 1105

N- Alkyl and N- Aryl Derivatives 1110

Amino Acetal Derivatives 1118

Amides 1122

Protection for the Amide -NH 1132

Amides 1132

Protection for the Sulfonamide -NH 1164

8. Protection for the Alkyne -CH 1177

9. Protection for the Phosphate Group 1185

Introduction 1188

Some General Methods for Phosphate Ester Formation 1190

Removal of Protective Groups from Phosphorus 1191

Alkyl Phosphates 1195

Phosphates Cleaved by Cyclodeesterification 1203

2- Substituted Ethyl Phosphates 1208

Haloethyl Phosphates 1215

Benzyl Phosphates 1218

Phenyl Phosphates 1224

Photochemically Cleaved Phosphate Protective Groups 1231

Amidates 1234

Miscellaneous Derivatives 1237

10. Protecting Group Effects in Carbohydrate Chemistry 1239

Introduction 1240

Early Observations Protecting Group- Induced Reactivity 1242

Relative Reactivities 1244

Fraser–Reid’s Concept of Armed and Disarmed 1251

Examples of How Protecting Groups Arm and Disarm Glycosides 1252

Aglycone Transfer 1263

Participating Groups 1266

Ester at the C- 2 Hydroxyl 1266

Esters at Positions Other Than 2 1278

Ethers Primarily at the C- 2 Hydroxyl 1302

Conformational Restriction 1329

Benzylidene Group and other Acetals 1329

Directing Effect of Silylene Groups 1343

Carbonates as Conformational Restrictors 1364

Orthoester Conformational Restriction 1372

Silyl Groups: Conformational and Reactivity Effect 1376

Studies on the Conformational Flip Using Silyl Groups 1377

Amino Sugar Protection 1393

Imine Protection 1394

Protection of the NH2 as An Azide 1399

Imide Protection 1405

Oxazolidinones 1408

Introduction to the Formation of Sialyl Glycosides 1425

Amides and Their Effects 1429

Protecting Group Effects in the Glycosylation of 2- Deoxy Sugars 1446

Furanosides 1474

Protecting Group Effects on Acceptors 1494

C- Glycosylation 1522

Sphingolipids 1529

Introduction 1529

11. Reactivities Reagents and Reactivity Charts 1537

Reactivities 1537

Reagents 1538

Reactivity Charts 1540

Reactivity Chart 1. Protection for Hydroxyl Group: Ethers 1542

Reactivity Chart 2. Protection for Hydroxyl Group: Esters 1546

Reactivity Chart 3. Protection for 12- and 13- Diols 1550

Reactivity Chart 4. Protection for Phenols and Catechols 1554

Reactivity Chart 5. Protection for the Carbonyl Group 1558

Reactivity Chart 6. Protection for the Carboxyl Group 1562

Reactivity Chart 7. Protection for the Thiol Group 1566

Reactivity Chart 8. Protection for the Amino Group: Carbamates 1570

Reactivity Chart 9. Protection for the Amino Group: Amides 1574

Reactivity Chart 10. Protection for the Amino Group: Special -NH Protective Groups 1578

Reactivity Chart 11. Selective Deprotection of Silyl Ethers 1582

Index 1603

Über Autor(innen)

Peter G. M. Wuts, PhD, is a renowned organic chemist, currently working as a chemistry consultant for both the biotech and the legal community. He continues a 50-year career in academia and the pharmaceutical industry.