Protecting Groups

Front Cover
Chart
Preface
Contents
Chapter 1 - Protecting Groups: An Overview
1.1 - Death, Taxes and Protecting Groups
1.2 - Deprotection: The Concept of Orthogonal Sets
1.2.1 - Protecting Groups Cleaved by Basic Solvolysis
1.2.2 - Protecting Groups Cleaved by Acid
1.2.3 - Protecting Groups Cleaved by Heavy Metals
1.2.4 - Protecting Groups Cleaved by Fluoride Ions
1.2.5 - Protecting Groups Cleaved by Reductive Elimination
1.2.6 - Protecting Groups Cleaved by β-Elimination Reactions
1.2.7 - Protecting Groups Cleaved by Hydrogenolysis
1.2.8 - Protecting Groups Cleaved by Oxidation
1.2.9 - Protecting Groups Cleaved by Dissolving Metal Reductions
1.2.10 - Protecting Groups Cleaved by Nucleophilic Substitution
1.2.11 - Protecting Groups Cleaved by Transition Metal Catalysis
1.2.12 - Protecting Groups Cleaved by Light
1.2.13 - Protecting Groups Cleaved by Enzymes
1.3 - Relay Deprotection
1.4 - Transprotection
1.5 - Mutual Protection
1.6 - Temporary Protection
1.7 - Protecting Groups are Not-So-Innocent Bystanders
1.7.1 - Neighbouring group Participation
1.7.2 - Conformational and Electronic Effects
1.7.3 - Co-ordination Effects
1.8 - Protecting Groups and Solid-Phase Synthesis
1.9 - Reviews
1.9.1 - General Reviews on Protecting Groups
1.9.2 - Reviews on Enzyme-Labile Protecting Groups
1.9.3 - Reviews on Photo-Labile Protecting Groups
1.9.4 - Reviews on Linkers in Solid-Phase Synthesis
1.9.5 - Reviews on the Synthesis of Complex Targets Including Discussion of Protecting Group Problems and Strategies
References
Chapter 2 - Carbonyl Protecting Groups
2.1 - Introduction
2.2 - O,O-Acetals
2.2.1 - Cyclic Acetals
2.2.2 - O,O-Acetals in Asymmetric Synthesis
2.2.3 - Acyclic O,O-Acetals
2.3 - S,S-Acetals
2.4 - O,S-Acetals
2.5 - N,O-Acetals
2.6 - Cyanohydrins
2.7 - Orthoester Derivatives
2.7.1 - O,O,O-Orthoesters
2.7.2 - O,S,S-Orthoesters
2.7.3 - S,S,S-Orthoesters
2.8 - Oxazolines
2.9 - Reviews
2.9.1 - Reviews Concerning the Preparation of O,O-Acetals and Their Use as Protecting Groups
2.9.2 - Reviews Concerning the Mechanism for Hydrolysis of Acetals
2.9.3 - Reviews Concerning O,O-Acetals as Reactive Functionality
2.9.4 - Reviews Concerning the Preparation, Chemistry, and Hydrolysis of O,S- and S,S-Acetals
2.9.5 - Reviews Concerning the Synthesis and Reactions of N,O-Acetals and Their Use in Asymmetric Synthesis
2.9.6 - Reviews Concerning the Chemistry of Orthoesters and Oxazolines
References
Chapter 3 - Diol Protecting Groups
3.1 - Introduction
3.2 - O,O-Acetals
3.2.1 - Isopropylidene Acetals
3.2.2 - Cyclopentylidene and Cyclohexylidene Acetals
3.2.3 - The Arylmethylene Acetal Family
3.2.4 - Methylene Acetals
3.2.5 - Diphenylmethylene Acetals
3.3 - 1,2-Diacetals
3.3.1 - Dispoke Derivatives
3.3.2 - Cyclohexane-1,2-diacetals
3.3.3 - Butane-2,3-diacetals
3.4 - Silylene Derivatives
3.5 - 1,1,3,3-Tetraisopropyldisiloxanylidene Derivatives
3.6 - N,O-Acetals for the Protection of 1,2- and 1,3-Amino Alcohols
3.7 - Reviews
3.7.1 - Reviews Concerning the Protection of 1,2- and 1,3-Diols
3.7.2 - Reviews Concerning Acetal Derivatives of Carbohydrates
3.7.3 - Reviews Concerning 1,2-Diacetals
3.7.4 - Reviews Concerning N,O-Acetals
References
Chapter 4 - Hydroxyl Protecting Groups
4.1 - Introduction
4.2 - Silyl Ethers
4.2.1 - Trimethylsilyl (TMS) Ethers
4.2.2 - Triethylsilyl (TES) Ethers
4.2.3 - tert-Butyldimethylsilyl (TBS) Ethers
4.2.4 - tert-Butyldiphenylsilyl (TBDPS) Ethers
4.2.5 - Triisopropylsilyl (TIPS) Ethers
4.2.6 - Diethylisopropylsilyl (DEIPS) Ethers
4.2.7 - Thexyldimethylsilyl (TDS) Ethers
4.2.8 - Triphenylsilyl (TPS) Ethers
4.2.9 - Di-tert-butylmethylsilyl (DTBMS) Ethers
4.3 - Alkyl Ethers
4.3.1 - Methyl Ethers
4.3.2 - tert-Butyl Ethers
4.3.3 - Benzyl Ethers (Bn)
4.3.4 - p-Methoxybenzyl (PMB) and 3,4-Di-methoxybenzyl (DMB) Ethers
4.3.5 - Trityl (Tr) Ethers
4.3.6 - Allyl Ethers and Allyloxycarbonyl Derivatives
4.4 - Alkoxymethyl Ethers
4.4.1 - Methoxymethyl (MOM) Ethers
4.4.2 - 2-Methoxyethoxymethyl (MEM) Ethers
4.4.3 - Benzyloxymethyl (BOM) and Related Ethers
4.4.4 - p-Methoxybenzyloxymethyl (PMBM) Ethers
4.4.5 - 2-(Trimethylsilyl)ethoxymethyl (SER) Ethers
4.5 - Tetrahydropyranyl (THP) and Related Ethers
4.6 - Methylthiomethyl (MTM) Ethers
4.7 - Esters
4.7.1 - Acetate Esters (Ac)
4.7.2 - Benzoate Esters (Bz)
4.7.3 - Pivalate Esters (R)
4.7.4 - Methoxyacetate Esters
4.7.5 - Chloroacetate Esters
4.7.6 - Levulinate Esters (Lev)
4.8 - Carbonates
4.8.1 - Benzyl Carbonates (RO-CBz)
4.8.2 - p-Nitrobenzyl Carbonates (RO-COOPNB)
4.8.3 - tert-Butyl Carbonates (RO-Boc)
4.8.4 - 2,2,2-Trichloroethyl Carbonates (RO-Troc)
4.8.5 - 2-(Trimethylsilyl)ethyl Carbonates (RO-Teoc)
4.8.6 - Allyl Carbonates (RO-Aloc)
4.9 - Reviews
4.9.1 - General Reviews Concerning the Protection of Hydroxyls
4.9.2 - Reviews Concerning Enzyme-Mediated Esterification and Hydrolysis of Esters
4.9.3 - Reviews Concerning Organosilicon and Organotin Chemistry Relevant to Hydroxyl Protection
References
Chapter 5 - Thiol Protecting Groups
5.1 - Introduction
5.2 - Thioether Derivatives
5.2.1 - tert-Butyl Thioethers
5.2.2 - Benzyl and Substituted Benzyl Thioethers
5.2.3 - Trityl (Tr) Thioethers
5.2.4 - 2-(Trimethylsilyl)ethyl (TMSE) Thioethers
5.2.5 - 2-Cyanoethyl Thioethers
5.2.6 - 9-Fluorenylmethyl (Fm) Thioethers
5.3 - Thiocarbonate Derivatives
5.4 - Disulfides as Protecting Groups and Targets
5.5 - Reviews
5.5.1 - Reviews Concerning the Protection of Thiols
5.5.2 - Reviews Concerning the Chemistry of Thiols and Disulfides
References
Chapter 6 - Carboxyl Protecting Groups
6.1 - Introduction
6.2 - General Comments on the Esterification of Carboxylic Acids
6.3 - Methyl Esters and Derivatives
6.3.1 - Methyl Esters
6.3.2 - tert-Butyl Esters
6.3.3 - Benzyl Esters
6.3.4 - Allyl Esters
6.3.5 - Phenacyl Esters
6.4 - Alkoxyalkyl Esters
6.5 - Esters Cleaved by β-Elimination Reactions
6.5.1 - 2,2,2-Trichloroethyl Esters
6.5.2 - 2-(Trimethylsilyl)ethyl (TMSE) Esters
6.5.3 - 2-Tosylethyl Esters and Related Base-Labile Groups
6.6 - Silyl Esters
6.7 - Reviews
6.7.1 - Reviews Concerning the Specific Use of Esters as Protecting Groups
6.7.2 - Reviews Concerning the Preparation of Esters
6.7.3 - Reviews Concerning Techniques for Facilitating Esterification
6.7.4 - Reviews Concerning the Use as Allyl Esters in Carboxyl Protection
6.7.5 - Reviews Concerning the Nucleophilic Cleavage of Esters
References
Chapter 7 - Phosphate Protecting Groups
7.1 - Introduction
7.2 - The reaction of Phosphate Esters with Nucleophiles
7.3 - Alkyl Esters
7.3.1 - Methyl and Isopropyl Esters
7.3.2 - tert-Butyl Esters
7.3.3 - Benzyl Esters
7.3.4 - Allyl Esters
7.3.5 - 3\',5\'-Dimethoxybenzoin Esters
7.3.6 - p-Hydroxyphenacyl Esters
7.4 - Esters Cleaved by β-Elimination Reactions
7.4.1 - 2-Cyanoethyl Esters
7.4.2 - 9-Fluorenylmethyl Esters
7.4.3 - 2-(Trimethylsilyl)ethyl Esters
7.4.4 - 2-(Methylsulfonyl)ethyl Esters and Related Base-Label Groups
7.4.5 - 2,2,2-Trichloroethyl Esters
7.5 - Reviews
7.5.1 - Reviews Concerning Protection for the Phosphate Group
7.5.2 - Reviews Concerning the Mechanism of Nucleophilic Substitution in Phosphate Esters
References
Chapter 8 - Amino Protecting Groups
8.1 - Introduction
8.2 - Imides and Amides
8.2.1 - Phthaloyl (Phth) and Tetrachlorophthaloyl (TCP)
8.2.2 - Dithiasuccinyl (Dts)
8.2.3 - Trifluoroacetyl
8.2.4 - Relay Deprotection of N-Acyl Derivatives
8.3 - Carbamates
8.3.1 - Methoxy- and Ethoxycarbonyl
8.3.2 - tert-Butoxycarbonyl (Boc)
8.3.3 - Benzyloxycarbonyl (Z or Cbz)
8.3.4 - Allyloxycarbonyl (Aloc)
8.3.5 - 9-Fluorenylmethoxycarbonyl (Fmoc)
8.3.6 - 2-(Trimethylsilyl)ethoxycarbonyl (Teoc)
8.3.7 - 2,2,2-Trichloroethoxycarbonyl (Troc)
8.4 - Sulfonyl Derivatives
8.4.1 - Arylsulfonyl Derivatives
8.4.2 - 2-(Trimethylsilyl)ethylsulfonyl (SES) Derivatives
8.5 - N-Sulfenyl Derivatives
8.6 - N-Alkyl Derivatives
8.6.1 - N,O-Acetals
8.6.2 - Triazinanones
8.6.3 - Benzyl (Bn) and Diphenylmethyl (Dpm)
8.6.4 - Trityl (Tr) and 9-Phentlfluorenyl (PhFl)
8.6.5 - Allyl
8.7 - N-Silyl Derivatives
8.8 - Imine and Enamine Derivatives
8.8.1 - N-Bis(methylthio)methylene
8.8.2 - N-Diphenylmethylene
8.9 - Special Cases
8.9.1 - Orthogonal Protecting Groups for the Synthesis of Polyamines
8.9.2 - Protecting Groups for Guanidines
8.9.3 - Protecting Groups for Indoles, Pyrroles and Imidazoles
8.10 - Reviews
8.10.1 - General Reviews on Amino Protecting Groups
8.10.2 - Reviews Concerning N-Protection in the Synthesis of α-Amino Aldehydes and Ketones
8.10.3 - Reviews Concerning N-Protection in the Synthesis of β-Lactams
8.10.4 - Reviews Concerning N-Functional Groups Pertinent to Their Role as Protecting Groups
8.10.5 - Reviews Concerning the Synthesis of Natural Guanidine Derivatives
8.10.6 - Reviews Concerning the Synthesis of Natural Polyamines
References
Epilogue
Index