Second, Revised and Enlarged Edition. VCH Verlagsgesellschaft mbH.
D-69451 Weinheim (Federal Republic of Germany), 1994. – 444 p.
This book was written for the advanced chemistry student and for the research chemist. Its purpose is to convey knowledge about concepts, methods, starting materials, and target molecules that play important roles in modem organic syntheses. Moreover, it shows the application of this knowledge to retrosynthetic analysis and gives an introduction to the design of synthetic plans.
Important concepts are summarized at the beginning of each chapter. They include:
the synthon approach;
systematic evaluation of the arrangement of functionality;
methods for achieving regio- and stereoselectivity in carbon-carbon bond formation and functional group conversions;
strategies for enforcing thermodynamically unfavourable reactions, and new ideas which lead to the development of target molecules and supramolecular systems
beyond natural compounds.
The synthetic methods described were selected under the aspects of applicability, simplicity, and didactic value. Applicability implies that the method has been used in complex syntheses. Simplicity means that the method is not too time-consuming. Finally, didactic value is judged by some principles of selectivity control which we wanted to demonstrate. A list of commercially available starting materials tells the synthetic chemist what industry can do for him, and a selection of complex synthetic procedures shows what he may aim for.
Contents
Abbreviations
Synthons in the Synthesis of Carbon Chains and Carbocycles
Introduction and Summary
Electron Donors (Nucleophiles)
Alkylating and d1-Synthons
d2-Synthons
d3-Synthons
dn-Synthons
Electron Acceptors (Electrophiles, a-Synthons)
Umpolung
Introduction of Non-functional Alkyl and Reactive AIM Groups
Formation of Alkenes and Alkynes
Alkanes, Alkenes, and Alkynes via Coupling Reactions
Alcohols and Epoxides
Aldehydes, Ketones, and Carboxylic Acids
1,2-Diiunctional Compounds
1,3-Difunctional Compounds
1,4-Difunctional Compounds
1,5-Difunctional Compounds
Carbocycles
Cyclopropane and Cyclopropene Derivatives
Cyclobutane Derivatives
Cyclopentane Derivatives
Cyclohexane and Cyclohexene Derivatives
1,6-Difunctional Compounds
Acid Catalyzed Cyclizations
Bridged Carbocycles
Selective Functional Group Interconversions (FGI)
Introduction and Summary
Reduction
Hydrogenation of Carbon-Carbon Multiple Bonds and
Cyclopropane Rings
Reduction of Aldehydes, Ketones, and Carboxylic Acid Derivatives
Reduction of Nitrogen Compounds
Reductive Cleavage of Carbon-Heteroatom and
Heteroatom-Oxygen Bonds
Oxidation
Oxidation of Non-functional Carbon Atoms
Oxidation of Carbon Atoms in Carbon-Carbon Multiple Bonds
Oxidation of Alcohols to Aldehydes, Ketones, and Carboxylic Acids
Oxidative Rearrangement and Cleavage of Ketones and Aldehydes
Olefin Syntheses by Dehydrogenation and Other Elimination
Reactions
Synthesis of Carboxylic Acid Derivatives
Nitrogen Heterocycles
Protection of Functional Groups
Reactive Carbon-Hydrogen and Carbon-Carbon Bonds
Alcoholic Hydroxyl Groups
Ammo Groups
Carboxyl Groups
Aldehyde and Keto Groups
Phosphate Groups
Enantio- and Diastereoselective Hydrolysis and Condensation Reactions
Halides and Sulfides
Retro-Synthetic Analysis of Simple Organic Compounds
Introduction and Summary
Starting Materials
Monofunctional Open-Chain Reagents
Difunctional, Trifunctional, and Oligofunctional
Open-Chain Reagents
Silicon and Phosphorus Reagents
Nonaromatic Carbocyclic Reagents
Aromatic and Heterocyclic Compounds
Retro-Synthetic Analysis (= "Antithesis")
Antithesis of Achiral and Chiral Open-Chain Target Molecules
Mono- and Bicyclic Target Molecules
Bridged Polycyclic Molecules
Summary of Antithetical Analysis of Simple Molecules
Leaing from Research Papers
Methods in the Construction of Complex Molecules
Syntheses by Functional Group Interconversions (Condensation Reactions)
Oligonucleotides
Diester and Triester Methods
Phosphite and Solid-Phase Methods
Combined Chemical-Enzymatic Syntheses
Peptides
Stages of Peptide Synthesis
Solid-Phase Peptide Synthesis
Solution (= Liquid-Phase) Methods for Peptide Synthesis
Peptide Fragment Condensation
Macrocyclic Peptides and Depsipeptides
Recombinant Bacteria for Protein Engineering
Macro-Heterdcycles
High-Dilution Methods
Template Reactions
Stepwise Condensations
The "Zip-Reaction"
Porphyrins, Chlorophyll a, and Corrins
Porphyrins and Porphyrinogens
Chlorophyll a — Comprehension of Structural Features
and Synthesis
Corrins
Carbohydrates
"Chiral Pool" Carbohydrates
Monomer Syntheses
Protecting Groups
Di- and Oligosaccharide Synthesis
Syntheses Using Carbohydrates as Chiral Educts ("Chirons").
Prostaglandis
Partial Synthesis of PGE2 and PGF2 from PGA2
Total Syntheses of PGF Intermediates
Steroids
Total Syntheses
Vitamin D: the Exocyclic Diene and the 17-Side Chain
Oxidation, Dehydrogenation, and Fluorination of Steroids
Chemical Reactivity
Alkaloids
Nucleophilic Substitutions with Amines
Mannich Reactions
Coupling of Phenol Derivatives and Aryl Coupling
Electrocyclic Reactions
Self-Reproduction of Chirality
Synthetic Drugs
Benzene Derivatives with a Nitrogen Containing Side-Chain .
Nitrogen Heterocycles
Antibiotics
?-Lactams
Tetracyclines
Macrolides
Esoteric Polycyclic Hydrocarbons
(CH)4
(СH)6
(CH)8
(CH)10
Methylene-Bridged [4n + 2]-Annulenes
(CH)20: Dodecahedrane and Pagodane
Kekulene, C48H24
Cyclocarbons C6n via Carbon Oxides С8nО2n, (n = 3, 4, 5)
Concepts in Nanometer Size Architecture
Nucleic Acids
DNA with a Site-Specifically, Covalently Bound Mutagen
Cationic Oligonucleotides
A Synthetic Scissor for Sequence-Specific DNA Cleavage
Hexose Oligonucleotides
DNA Helicates with a Central Copper(I) Ion Wire
Kemps' Acid: Enzyme-Cleft and Self-Replication Models
Enzyme-Cleft Models with Convergent Functional Groups
A Synthetic Self-Replicating System
Covalent and Non-Covalent Porphyrin Assemblies
Molecular Assemblies of Amphiphiles
Vesicle Membranes
Helical Micellar Fibers
Covalent Micelles: Dendritic Polymers
Covalent Vesicles: Carcerands and Fullerenes
Appendix: Prochirality
References
Index
This book was written for the advanced chemistry student and for the research chemist. Its purpose is to convey knowledge about concepts, methods, starting materials, and target molecules that play important roles in modem organic syntheses. Moreover, it shows the application of this knowledge to retrosynthetic analysis and gives an introduction to the design of synthetic plans.
Important concepts are summarized at the beginning of each chapter. They include:
the synthon approach;
systematic evaluation of the arrangement of functionality;
methods for achieving regio- and stereoselectivity in carbon-carbon bond formation and functional group conversions;
strategies for enforcing thermodynamically unfavourable reactions, and new ideas which lead to the development of target molecules and supramolecular systems
beyond natural compounds.
The synthetic methods described were selected under the aspects of applicability, simplicity, and didactic value. Applicability implies that the method has been used in complex syntheses. Simplicity means that the method is not too time-consuming. Finally, didactic value is judged by some principles of selectivity control which we wanted to demonstrate. A list of commercially available starting materials tells the synthetic chemist what industry can do for him, and a selection of complex synthetic procedures shows what he may aim for.
Contents
Abbreviations
Synthons in the Synthesis of Carbon Chains and Carbocycles
Introduction and Summary
Electron Donors (Nucleophiles)
Alkylating and d1-Synthons
d2-Synthons
d3-Synthons
dn-Synthons
Electron Acceptors (Electrophiles, a-Synthons)
Umpolung
Introduction of Non-functional Alkyl and Reactive AIM Groups
Formation of Alkenes and Alkynes
Alkanes, Alkenes, and Alkynes via Coupling Reactions
Alcohols and Epoxides
Aldehydes, Ketones, and Carboxylic Acids
1,2-Diiunctional Compounds
1,3-Difunctional Compounds
1,4-Difunctional Compounds
1,5-Difunctional Compounds
Carbocycles
Cyclopropane and Cyclopropene Derivatives
Cyclobutane Derivatives
Cyclopentane Derivatives
Cyclohexane and Cyclohexene Derivatives
1,6-Difunctional Compounds
Acid Catalyzed Cyclizations
Bridged Carbocycles
Selective Functional Group Interconversions (FGI)
Introduction and Summary
Reduction
Hydrogenation of Carbon-Carbon Multiple Bonds and
Cyclopropane Rings
Reduction of Aldehydes, Ketones, and Carboxylic Acid Derivatives
Reduction of Nitrogen Compounds
Reductive Cleavage of Carbon-Heteroatom and
Heteroatom-Oxygen Bonds
Oxidation
Oxidation of Non-functional Carbon Atoms
Oxidation of Carbon Atoms in Carbon-Carbon Multiple Bonds
Oxidation of Alcohols to Aldehydes, Ketones, and Carboxylic Acids
Oxidative Rearrangement and Cleavage of Ketones and Aldehydes
Olefin Syntheses by Dehydrogenation and Other Elimination
Reactions
Synthesis of Carboxylic Acid Derivatives
Nitrogen Heterocycles
Protection of Functional Groups
Reactive Carbon-Hydrogen and Carbon-Carbon Bonds
Alcoholic Hydroxyl Groups
Ammo Groups
Carboxyl Groups
Aldehyde and Keto Groups
Phosphate Groups
Enantio- and Diastereoselective Hydrolysis and Condensation Reactions
Halides and Sulfides
Retro-Synthetic Analysis of Simple Organic Compounds
Introduction and Summary
Starting Materials
Monofunctional Open-Chain Reagents
Difunctional, Trifunctional, and Oligofunctional
Open-Chain Reagents
Silicon and Phosphorus Reagents
Nonaromatic Carbocyclic Reagents
Aromatic and Heterocyclic Compounds
Retro-Synthetic Analysis (= "Antithesis")
Antithesis of Achiral and Chiral Open-Chain Target Molecules
Mono- and Bicyclic Target Molecules
Bridged Polycyclic Molecules
Summary of Antithetical Analysis of Simple Molecules
Leaing from Research Papers
Methods in the Construction of Complex Molecules
Syntheses by Functional Group Interconversions (Condensation Reactions)
Oligonucleotides
Diester and Triester Methods
Phosphite and Solid-Phase Methods
Combined Chemical-Enzymatic Syntheses
Peptides
Stages of Peptide Synthesis
Solid-Phase Peptide Synthesis
Solution (= Liquid-Phase) Methods for Peptide Synthesis
Peptide Fragment Condensation
Macrocyclic Peptides and Depsipeptides
Recombinant Bacteria for Protein Engineering
Macro-Heterdcycles
High-Dilution Methods
Template Reactions
Stepwise Condensations
The "Zip-Reaction"
Porphyrins, Chlorophyll a, and Corrins
Porphyrins and Porphyrinogens
Chlorophyll a — Comprehension of Structural Features
and Synthesis
Corrins
Carbohydrates
"Chiral Pool" Carbohydrates
Monomer Syntheses
Protecting Groups
Di- and Oligosaccharide Synthesis
Syntheses Using Carbohydrates as Chiral Educts ("Chirons").
Prostaglandis
Partial Synthesis of PGE2 and PGF2 from PGA2
Total Syntheses of PGF Intermediates
Steroids
Total Syntheses
Vitamin D: the Exocyclic Diene and the 17-Side Chain
Oxidation, Dehydrogenation, and Fluorination of Steroids
Chemical Reactivity
Alkaloids
Nucleophilic Substitutions with Amines
Mannich Reactions
Coupling of Phenol Derivatives and Aryl Coupling
Electrocyclic Reactions
Self-Reproduction of Chirality
Synthetic Drugs
Benzene Derivatives with a Nitrogen Containing Side-Chain .
Nitrogen Heterocycles
Antibiotics
?-Lactams
Tetracyclines
Macrolides
Esoteric Polycyclic Hydrocarbons
(CH)4
(СH)6
(CH)8
(CH)10
Methylene-Bridged [4n + 2]-Annulenes
(CH)20: Dodecahedrane and Pagodane
Kekulene, C48H24
Cyclocarbons C6n via Carbon Oxides С8nО2n, (n = 3, 4, 5)
Concepts in Nanometer Size Architecture
Nucleic Acids
DNA with a Site-Specifically, Covalently Bound Mutagen
Cationic Oligonucleotides
A Synthetic Scissor for Sequence-Specific DNA Cleavage
Hexose Oligonucleotides
DNA Helicates with a Central Copper(I) Ion Wire
Kemps' Acid: Enzyme-Cleft and Self-Replication Models
Enzyme-Cleft Models with Convergent Functional Groups
A Synthetic Self-Replicating System
Covalent and Non-Covalent Porphyrin Assemblies
Molecular Assemblies of Amphiphiles
Vesicle Membranes
Helical Micellar Fibers
Covalent Micelles: Dendritic Polymers
Covalent Vesicles: Carcerands and Fullerenes
Appendix: Prochirality
References
Index