Organic Synthesis
- 5th Edition - September 9, 2024
- Author: Michael Smith
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 1 5 8 6 7 - 4
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 1 5 8 6 8 - 1
**2025 Textbook and Academic Authors Association (TAA) Textbook Excellence "Texty" Award Winner**Organic Synthesis, Fifth Edition provides a reaction-based approach to… Read more
**2025 Textbook and Academic Authors Association (TAA) Textbook Excellence "Texty" Award Winner**
Organic Synthesis, Fifth Edition provides a reaction-based approach to this important branch of organic chemistry. Updated and accessible, this eagerly-awaited revision offers a comprehensive foundation for graduate students coming from disparate backgrounds and knowledge levels, providing them with critical working knowledge of basic reactions, stereochemistry, and conformational principles. This reliable resource uniquely incorporates molecular modeling content, problems, and visualizations, and includes reaction examples and homework problems drawn from the latest in the current literature.
There have been advancements in organic reactions, particularly organometallic reactions, and there is a need to show how these advancements have influenced current organic synthesis. The goal is to revise and update the reaction examples taken from the synthesis literature from 2017 to 2023. The reactions illustrate those used most often in modern organic synthesis, but these new examples will show their current relevance. Where new approaches and reactions have been developed for organic synthesis, examples have been added as new material.
- Provides new content, reaction examples, and study problems from recent research
- Features improved organization, new art, and new chapter content on process chemistry and green organic chemistry
- Includes revised homework for each chapter, with new examples and questions
Graduate students in Organic Chemistry, undergraduate Chemistry majors in advanced undergraduate courses, Organic Chemists working in the pharmaceutical industry
1 Retrosynthesis, Stereochemistry, And Conformations
1.1. Introduction
1.2. The Disconnection Protocol
1.3. Bond Proximity and Implications for Chemical Reactions
1.4. Stereochemistry
1.5. Conformations
1.6. Conclusion HOMEWORK
2 Acids And Bases and Addition Reactions
2.1. Introduction
2.2. Brønsted-Lowry Acids and Bases
2.3. Lewis Acids
2.4 Hard-Soft Acid-Base Theory
2.5. Acid-Base Reactions in Organic Chemistry
2.5. Addition Reactions
2.6. Conclusion HOMEWORK
3 Functional Group Exchange Reactions. Aliphatic and Aromatic Substitution, and Elimination Reactions
3.1. Introduction
3.2. Aliphatic Substitution Reactions
3.3. Heteroatom-Stabilized Carbocations
3.4. Substitution by Halogen
3.5. Elimination Reactions
3.6. Characteristics Of Substitution and Elimination Reactions
3.7. Syn-Elimination Reactions
3.8. 1,3-Elimination (Decarboxylation)
3.9. 1,3-Elimination (Grob Fragmentation)
3.10. Aromatic Substitution HOMEWORK
4 Acids, Bases, And Functional Group Exchange Reactions. Acyl Addition and Acyl Substitution
4.1. Introduction
4.2. Nucleophilic Acyl Addition and Substitution
4.3. Conjugate Addition
4.4. Functional Group Manipulation by Rearrangement
4.5. Macrocyclic Compounds
4.6. Conclusion HOMEWORK
5 Functional Groups Exchange Reactions. Protecting Groups
5.1. Introduction
5.2. When Are Protecting Groups Needed?
5.3. Protecting Groups for Alcohols, Carbonyls, And Amines
5.4. Conclusion HOMEWORK
6 Functional Group Exchange Reactions. Oxidations
6.1. Introduction
6.2. Alcohols To Carbonyls (CH-OH ® C=O)
6.3. Formation of Phenols and Quinones
6.4. Oxidation of Alkenes to Epoxides
6.5. Conversion of Alkenes to Diols (C=C ® CHOH-CHOH)
6.6. Baeyer-Villiger Oxidation (RCOR' ® RCO2R')
6.7. Oxidative Bond Cleavage (C=C ® C=O + O=C)
6.8. Oxidation Of Alkyl or Alkenyl Fragments (CH ® C=O or C—OH)
6.9. Oxidation Of Sulfur, Selenium, And Nitrogen
6.10. Conclusion HOMEWORK
7 Functional Group Exchange Reactions. Reductions
7.1. Introduction
7.2. The Nature of Hydride Reducing Agents
7.3. Borane and Aluminum Hydride
7.4. Sodium Borohydride
7.5. Alternative Metal Borohydrides (Li, Zn, Ce)
7.6. Lithium Aluminum Hydride
7.7. Hydride Reducing Agents with Electron-Releasing Groups
7.8. Hydride Reducing Agents with Electron-Withdrawing Groups
7.9. Stereoselectivity In Reductions
7.10. Catalytic Hydrogenation
7.11. Dissolving Metal Reductions
7.12. Nonmetallic Reducing Agents
7.13. Conclusion HOMEWORK
8 SYNTHETIC STRATEGIES
8.1. Introduction
8.2. Target Selection
8.3. Retrosynthesis
8.4. Synthetic Strategies
8.5. The Strategic Bond Approach
8.6. Strategic Bonds in Rings
8.7. Selected Synthetic Strategies: Ra current popular target
8.8. Biomimetic Approach to Retrosynthesis
8.9. The Chiral Template Approach
8.10. Degradation Techniques as a Tool for Retrosynthesis
8.11. Computer Generated Strategies
8.12. Conclusion HOMEWORK
9 Functional Group Exchange Reactions. Hydroboration
9.1. Introduction
9.2. Preparation of Alkyl Boranes
9.3. Preparation of Alkenylboranes
9.4. Formation of Oxygen-Containing Functional Groups
9.5. Other Functional Group Exchange Reactions
9.6. Conclusion HOMEWORK
10 Functional Group Exchange Reactions. Selectivity
10.1. Introduction
10.2. Stereocontrol In Acyclic Systems
10.3. Stereocontrol In Cyclic Systems
10.4. Neighboring Group Effects and Chelation Effects
10.5. Acyclic Stereocontrol Via Cyclic Precursors
10.6. Baldwin's Rules for Ring Closure
10.7. Conclusion HOMEWORK
11 Carbon-Carbon Bond-Forming Reactions. Cyanide, Alkyne Anions, Grignard Reagents, and Organolithium Reagents
11.1. Introduction
11.2. Cyanide
11.3. Alkyne Anions (R-CºC:-)
11.4 Grignard Reagents (C—Mg)
11.5. Grignard Reagents. Reduction, Organocerium Reagents, and Enolization
11.6. Organolithium Reagents (C—Li)
11.7. Conclusion HOMEWORK
12 Carbon–Carbon Bond-Forming Reactions. Stabilized Carbanions, Organocuprates, and Ylids
12.1. Introduction
12.2. Sulfur Stabilized Carbanions and Umpolung
12.3. Organocopper Reagents (C—Cu)
12.4. Phenolic Carbanions
12.5. Ylids
12.6. Transition Metal Olefination Reagents
12.7. Silane Reagents
12.8. Conclusion HOMEWORK
13 Carbon-Carbon Bond-Forming Reactions. Enolate Anions
13.1. Introduction
13.2. Formation Of Enolate Anions
13.3. Reactions Of Enolate Anions with Electrophiles
13.4. Enolate Condensation Reactions
13.5. Stereoselective Enolate Reactions
13.6. Enamines
13.7. Michael Addition and Related Reactions
13.8. Enolate Reactions of a Halo Carbonyl Derivatives HOMEWORK
14 Pericyclic Reactions. The Diels–Alder Reaction
14.1. Introduction
14.2. Frontier Molecular Orbital Theory
14.3. HOMO, LUMO Energies and Orbital Coefficients
14.4. Allowed and Forbidden Reactions
14.5. The Diels-Alder Reaction
14.6. Rate Enhancement in Diels-Alder Reactions
14.7. Intramolecular Diels-Alder Reactions
14.8. Inverse Electron Demand and The Retro Diels-Alder Reactions
14.9. Heteroatom Diels-Alder Reactions
14.10. Enantioselective Diels-Alder Reactions
14.11. Conclusion
15 Pericyclic Reactions: [m+n]-Cycloadditions, Sigmatropic Rearrangements, Electrocyclic and Ene Reactions
15.1. Introduction
15.2. [2+2]-Cycloaddition Reactions
15.3. Electrocyclic Reactions
15.4. [3+2]-Cycloaddition Reactions
15.5. (m+n]-Cycloaddition Reactions
15.5. Sigmatropic Rearrangements
15.6. The Ene Reaction
15.7. Conclusion HOMEWORK
16 Carbon-Carbon Bond-Forming Reactions. Carbocation and Oxocarbenium Ion Intermediates
16.1. Introduction
16.2. Carbocations
16.3. Carbocations and Carbon–Carbon Bond Forming Reactions
16.4. Friedel-Crafts Reactions
16.5. Friedel-Crafts Reactions: Formation of Heteroatom–Containing Derivatives
16.6. Conclusion HOMEWORK
17 Formation Of Carbon-Carbon Bonds Via Radicals and Carbenes
17.1. Introduction
17.2. Structure Of Radicals
17.3. Formation Of Radicals by Thermolysis
17.4. Photochemical Formation of Radicals
17.5. Reactions Of Free Radicals
17.6. Intermolecular Radical Reactions
17.7. Intramolecular Radical Reactions (Radical Cyclization)
17.8. Metal-Induced Radical Reactions
17.9. Carbenes And Carbenoids
17.10. Conclusion HOMEWORK
18 Metal-Mediated, Carbon-Carbon Bond-Forming Reactions
18.1. Introduction
18.2. Copper-Catalyzed Coupling Reactions
18.3. p-Allyl Palladium Complexes
18.4. Named Palladium-Catalyzed Coupling Reactions
18.5. p-Allyl Nickel Complexes
18.6. Metathesis Reactions
18.7. Pauson-Khand Reaction
18.8. Organometallic Compounds as Carbanionic Reagents
18.9. Electrophilic Iron Complexes
18.10. Conclusion HOMEWORK
19 Combinatorial And Process Chemistry
19.1. Combinatorial Chemistry
19.2. Process Chemistry
19.3. Continuous Flow Synthesis
19.4. Conclusion HOMEWORK
General Index
Disconnection Index
1.1. Introduction
1.2. The Disconnection Protocol
1.3. Bond Proximity and Implications for Chemical Reactions
1.4. Stereochemistry
1.5. Conformations
1.6. Conclusion HOMEWORK
2 Acids And Bases and Addition Reactions
2.1. Introduction
2.2. Brønsted-Lowry Acids and Bases
2.3. Lewis Acids
2.4 Hard-Soft Acid-Base Theory
2.5. Acid-Base Reactions in Organic Chemistry
2.5. Addition Reactions
2.6. Conclusion HOMEWORK
3 Functional Group Exchange Reactions. Aliphatic and Aromatic Substitution, and Elimination Reactions
3.1. Introduction
3.2. Aliphatic Substitution Reactions
3.3. Heteroatom-Stabilized Carbocations
3.4. Substitution by Halogen
3.5. Elimination Reactions
3.6. Characteristics Of Substitution and Elimination Reactions
3.7. Syn-Elimination Reactions
3.8. 1,3-Elimination (Decarboxylation)
3.9. 1,3-Elimination (Grob Fragmentation)
3.10. Aromatic Substitution HOMEWORK
4 Acids, Bases, And Functional Group Exchange Reactions. Acyl Addition and Acyl Substitution
4.1. Introduction
4.2. Nucleophilic Acyl Addition and Substitution
4.3. Conjugate Addition
4.4. Functional Group Manipulation by Rearrangement
4.5. Macrocyclic Compounds
4.6. Conclusion HOMEWORK
5 Functional Groups Exchange Reactions. Protecting Groups
5.1. Introduction
5.2. When Are Protecting Groups Needed?
5.3. Protecting Groups for Alcohols, Carbonyls, And Amines
5.4. Conclusion HOMEWORK
6 Functional Group Exchange Reactions. Oxidations
6.1. Introduction
6.2. Alcohols To Carbonyls (CH-OH ® C=O)
6.3. Formation of Phenols and Quinones
6.4. Oxidation of Alkenes to Epoxides
6.5. Conversion of Alkenes to Diols (C=C ® CHOH-CHOH)
6.6. Baeyer-Villiger Oxidation (RCOR' ® RCO2R')
6.7. Oxidative Bond Cleavage (C=C ® C=O + O=C)
6.8. Oxidation Of Alkyl or Alkenyl Fragments (CH ® C=O or C—OH)
6.9. Oxidation Of Sulfur, Selenium, And Nitrogen
6.10. Conclusion HOMEWORK
7 Functional Group Exchange Reactions. Reductions
7.1. Introduction
7.2. The Nature of Hydride Reducing Agents
7.3. Borane and Aluminum Hydride
7.4. Sodium Borohydride
7.5. Alternative Metal Borohydrides (Li, Zn, Ce)
7.6. Lithium Aluminum Hydride
7.7. Hydride Reducing Agents with Electron-Releasing Groups
7.8. Hydride Reducing Agents with Electron-Withdrawing Groups
7.9. Stereoselectivity In Reductions
7.10. Catalytic Hydrogenation
7.11. Dissolving Metal Reductions
7.12. Nonmetallic Reducing Agents
7.13. Conclusion HOMEWORK
8 SYNTHETIC STRATEGIES
8.1. Introduction
8.2. Target Selection
8.3. Retrosynthesis
8.4. Synthetic Strategies
8.5. The Strategic Bond Approach
8.6. Strategic Bonds in Rings
8.7. Selected Synthetic Strategies: Ra current popular target
8.8. Biomimetic Approach to Retrosynthesis
8.9. The Chiral Template Approach
8.10. Degradation Techniques as a Tool for Retrosynthesis
8.11. Computer Generated Strategies
8.12. Conclusion HOMEWORK
9 Functional Group Exchange Reactions. Hydroboration
9.1. Introduction
9.2. Preparation of Alkyl Boranes
9.3. Preparation of Alkenylboranes
9.4. Formation of Oxygen-Containing Functional Groups
9.5. Other Functional Group Exchange Reactions
9.6. Conclusion HOMEWORK
10 Functional Group Exchange Reactions. Selectivity
10.1. Introduction
10.2. Stereocontrol In Acyclic Systems
10.3. Stereocontrol In Cyclic Systems
10.4. Neighboring Group Effects and Chelation Effects
10.5. Acyclic Stereocontrol Via Cyclic Precursors
10.6. Baldwin's Rules for Ring Closure
10.7. Conclusion HOMEWORK
11 Carbon-Carbon Bond-Forming Reactions. Cyanide, Alkyne Anions, Grignard Reagents, and Organolithium Reagents
11.1. Introduction
11.2. Cyanide
11.3. Alkyne Anions (R-CºC:-)
11.4 Grignard Reagents (C—Mg)
11.5. Grignard Reagents. Reduction, Organocerium Reagents, and Enolization
11.6. Organolithium Reagents (C—Li)
11.7. Conclusion HOMEWORK
12 Carbon–Carbon Bond-Forming Reactions. Stabilized Carbanions, Organocuprates, and Ylids
12.1. Introduction
12.2. Sulfur Stabilized Carbanions and Umpolung
12.3. Organocopper Reagents (C—Cu)
12.4. Phenolic Carbanions
12.5. Ylids
12.6. Transition Metal Olefination Reagents
12.7. Silane Reagents
12.8. Conclusion HOMEWORK
13 Carbon-Carbon Bond-Forming Reactions. Enolate Anions
13.1. Introduction
13.2. Formation Of Enolate Anions
13.3. Reactions Of Enolate Anions with Electrophiles
13.4. Enolate Condensation Reactions
13.5. Stereoselective Enolate Reactions
13.6. Enamines
13.7. Michael Addition and Related Reactions
13.8. Enolate Reactions of a Halo Carbonyl Derivatives HOMEWORK
14 Pericyclic Reactions. The Diels–Alder Reaction
14.1. Introduction
14.2. Frontier Molecular Orbital Theory
14.3. HOMO, LUMO Energies and Orbital Coefficients
14.4. Allowed and Forbidden Reactions
14.5. The Diels-Alder Reaction
14.6. Rate Enhancement in Diels-Alder Reactions
14.7. Intramolecular Diels-Alder Reactions
14.8. Inverse Electron Demand and The Retro Diels-Alder Reactions
14.9. Heteroatom Diels-Alder Reactions
14.10. Enantioselective Diels-Alder Reactions
14.11. Conclusion
15 Pericyclic Reactions: [m+n]-Cycloadditions, Sigmatropic Rearrangements, Electrocyclic and Ene Reactions
15.1. Introduction
15.2. [2+2]-Cycloaddition Reactions
15.3. Electrocyclic Reactions
15.4. [3+2]-Cycloaddition Reactions
15.5. (m+n]-Cycloaddition Reactions
15.5. Sigmatropic Rearrangements
15.6. The Ene Reaction
15.7. Conclusion HOMEWORK
16 Carbon-Carbon Bond-Forming Reactions. Carbocation and Oxocarbenium Ion Intermediates
16.1. Introduction
16.2. Carbocations
16.3. Carbocations and Carbon–Carbon Bond Forming Reactions
16.4. Friedel-Crafts Reactions
16.5. Friedel-Crafts Reactions: Formation of Heteroatom–Containing Derivatives
16.6. Conclusion HOMEWORK
17 Formation Of Carbon-Carbon Bonds Via Radicals and Carbenes
17.1. Introduction
17.2. Structure Of Radicals
17.3. Formation Of Radicals by Thermolysis
17.4. Photochemical Formation of Radicals
17.5. Reactions Of Free Radicals
17.6. Intermolecular Radical Reactions
17.7. Intramolecular Radical Reactions (Radical Cyclization)
17.8. Metal-Induced Radical Reactions
17.9. Carbenes And Carbenoids
17.10. Conclusion HOMEWORK
18 Metal-Mediated, Carbon-Carbon Bond-Forming Reactions
18.1. Introduction
18.2. Copper-Catalyzed Coupling Reactions
18.3. p-Allyl Palladium Complexes
18.4. Named Palladium-Catalyzed Coupling Reactions
18.5. p-Allyl Nickel Complexes
18.6. Metathesis Reactions
18.7. Pauson-Khand Reaction
18.8. Organometallic Compounds as Carbanionic Reagents
18.9. Electrophilic Iron Complexes
18.10. Conclusion HOMEWORK
19 Combinatorial And Process Chemistry
19.1. Combinatorial Chemistry
19.2. Process Chemistry
19.3. Continuous Flow Synthesis
19.4. Conclusion HOMEWORK
General Index
Disconnection Index
- Edition: 5
- Published: September 9, 2024
- Language: English
MS
Michael Smith
Professor Michael B. Smith received an A.A. from Ferrum College in 1967 and a BS in chemistry from Virginia Polytechnic Institute in 1969. After working for 3 years at the Newport News Shipbuilding and Dry Dock Co. in New- port News VA as an analytical chemist, he entered graduate school at Purdue University. He received a PhD in Organic Chemistry in 1977. He spent 1 year as a faculty research associate at the Arizona State University with Professor G. Robert Pettit, working on the isolation of cytotoxic principles from plants and sponges. He spent a second year of postdoctoral work with Professor Sidney M. Hecht at the Massachusetts Insti- tute of Technology, working on the synthesis of bleomycin A2.
Smith began his academic career at the University of Connecticut in 1979, where he is currently professor of chemistry. In addition to this research, he is the author of the fifth, sixth, and seventh editions of March’s Advanced Organic Chemistry. He is also the author of an undergraduate textbook in organic chemistry titled Organic Chemistry. An Acid-Base Approach, now in its second edition. He is the editor of the Compendium of Organic Synthetic Methods, Volumes 6–13. He is the author of Organic Chemistry: Two Semesters, in its second edition, which is an outline of undergraduate organic chemistry to be used as a study guide for the first organic course. He has authored a research monograph titled Synthesis of Non-alpha Amino Acids, in its second edition.
Affiliations and expertise
Department of Chemistry, University of Connecticut, USARead Organic Synthesis on ScienceDirect