Practical Synthetic Organic Chemistry: Reactions, Principles, and Techniques

Practical Synthetic Organic Chemistry: Reactions, Principles, and Techniques
Contents
List of Contributors
Preface
1 Aliphatic Nucleophilic Substitution
	1.1 Introduction
	1.2 Oxygen Nucleophiles
	1.3 Phosphorus Nucleophiles
	1.4 Sulfur Nucleophiles
	1.5 Nitrogen Nucleophiles
	1.6 Halogen Nucleophiles
	1.7 Carbon Nucleophiles
	1.8 Nucleophilic Substitution at a Sulfonyl Sulfur Atom
2 Addition to Carbon-Heteroatom Multiple Bonds
	2.1 Introduction
	2.2 Addition of Water to Aldehydes and Ketones: Formation of Hydrates
	2.3 Addition of Bisulfite to Aldehydes and Ketones
	2.4 The Addition of Alcohols to Aldehydes and Ketones: Acetal Formation
	2.5 The Addition of Thiols to Aldehydes and Ketones: S,S-Acetal Formation
	2.6 Reductive Etherification
	2.7 Addition of NH3, RNH2, and R2NH
	2.8 Formation of Hydrazones
	2.9 Formation of Oximes
	2.10 The Formation of gem-Dihalides from Aldehydes and Ketones
	2.11 The Aldol Reaction
	2.12 Allylorganometallics: Stannane, Borane, and Silane
	2.13 The Nozaki–Hiyama–Kishi Reaction
	2.14 Addition of Transition Metal Alkynylides to Carbonyl Compounds
	2.15 Addition of Organometallic Reagents to Carbonyls
	2.16 Addition of Conjugated Alkenes to Aldehydes: the Baylis–Hillman Reaction
	2.17 The Reformatsky Reaction
	2.18 The Wittig Reaction
	2.19 Horner–Wadsworth–Emmons Reaction
	2.20 Peterson Olefination
	2.21 Julia–Lythgoe Olefination
	2.22 Tebbe Methylenation
	2.23 The Mannich Reaction
	2.24 The Strecker Reaction
	2.25 Hydrolysis of Carbon–Nitrogen Double Bonds
	2.26 Conversion of Carboxylic Acids to Acyl Chlorides
	2.27 Synthesis of Acyl Fluorides from Carboxylic Acids
	2.28 Formation of Amides from Carboxylic Acids
	2.29 Formation of Amides from Esters
	2.30 Hydrolysis of Acyl Halides
	2.31 Conversion of Carboxylic Acids to Esters
	2.32 Hydrolysis of Amides
	2.33 Conversion of N-Acyloxazolidinones to Other Carboxyl Derivatives
	2.34 Alcoholysis of Amides
	2.35 Hydrolysis of Esters
	2.36 Transesterification
	2.37 Alkyl Thiol Addition to Esters
	2.38 Addition of Organometallic Reagents to Carboxylic Acid Derivatives
	2.39 The Kulinkovich Cyclopropanation
	2.40 Synthesis of Acyl Cyanides
	2.41 The Ritter Reaction
	2.42 Thorpe Reaction
	2.43 Addition of Organometallic Reagents to Nitriles
	2.44 Conversion of Nitriles to Amides, Esters, and Carboxylic Acids
	2.45 Conversion of Nitriles to Thioamides
	2.46 The Addition of Ammonia or Amines to Nitriles
	2.47 The Addition of Alcohol to Nitriles
	2.48 Alkyl Thiol Addition to Nitriles
	2.49 The Blaise Reaction
	2.50 The Addition of Alcohols to Isocyanates
	2.51 The Addition of Amines and Amides to Isocyanates
	2.52 The Formation of Xanthates
	2.53 The Addition of Amines to Carbon Dioxide
	2.54 The Addition of Amines to Carbon Disulfide
	2.55 Addition of Organometallic Reagents to Carbon Dioxide
3 Addition to Carbon–Carbon Multiple Bonds
	3.1 Introduction
	3.2 Hydrogen–Halogen Addition (Hydrohalogenation)
	3.3 Hydrogen–Oxygen Addition
	3.4 Hydrogen–Nitrogen Addition (Hydroamination)
	3.5 Hydrogen–Carbon Addition (Hydroalkylation)
	3.6 Halogen–Halogen Addition
	3.7 Hydroxy–Halogen Addition
	3.8 Amino–Halogen Addition
	3.9 Carbon–Halogen Addition
	3.10 Oxygen–Oxygen Addition
	3.11 Oxygen–Nitrogen Addition
	3.12 Nitrogen–Nitrogen Addition
	3.13 Carbon–Oxygen Addition
	3.14 Carbon–Nitrogen Addition
	3.15 Carbon–Carbon Addition
4 Nucleophilic Aromatic Substitution
	4.1 Introduction
	4.2 Oxygen Nucleophiles
	4.3 Sulfur Nucleophiles
	4.4 Nitrogen Nucleophiles
	4.5 Halogen Nucleophiles
	4.6 Carbon Nucleophiles
	4.7 ortho-Arynes
5 Electrophilic Aromatic Substitution
	5.1 Introduction
	5.2 Nitrogen Electrophiles
	5.3 Sulfur Electrophiles
	5.4 Halogenation
	5.5 Carbon Electrophiles
6 Selected Catalytic Reactions
	6.1 Introduction
	6.2 Organoboron Reagents: The Suzuki–Miyaura Coupling
	6.3 Organomagnesium Reagents: Kumada–Corriu Coupling
	6.4 Organozinc Reagents: Negishi Coupling
	6.5 Cross-Electrophile Coupling
	6.6 Organotin Reagents: The Stille Coupling (Migita-Stille Reaction)
	6.7 Cross-Coupling Reactions with Organosilicon Compounds
	6.8 Metal-catalyzed Coupling of Alkynes (Sonogashira Coupling)
	6.9 Metal-Catalyzed Coupling of Alkenes (Heck Coupling)
	6.10 Enolate Arylations
	6.11 Pd- and Cu-Catalyzed Aryl C—N Bond Formation
	6.12 Pd- and Cu-Catalyzed Aryl C—O Bond Formation
	6.13 Pd- and Cu-Catalyzed Aryl C—S Bond Formation
	6.14 Aryl C—B Bond Formation
	6.15 Pd-Catalyzed Aryl C—CN Bond Formation
	6.16 Metal-Catalyzed Allylic Substitution
	6.17 CatalyticMetal-Mediated Methods for Fluorination
	6.18 Selected Metal-Mediated C—H Functionalization
	6.19 C—X Bond Forming Reactions via Borrowed Hydrogen Methodologies
	6.20 Alkene and Alkyne Metathesis Reactions
	6.21 Organocatalysis
7 Rearrangements
	7.1 Introduction
	7.2 [1,2]-Rearrangements
	7.3 Other Rearrangements
	7.4 Miscellaneous Migrations
8 Eliminations
	8.1 Introduction
	8.2 Formation of Alkenes
	8.3 Formation of Dienes
	8.4 Formation of Alkynes
	8.5 Formation of C=N bonds
	8.6 Formation of Nitriles
	8.7 Formation of Ketenes and Related Compounds
	8.8 Fragmentations
	8.9 Dehydrating Reagents
9 Reductions
	9.1 Introduction
	9.2 Reduction of C—C Bonds
	9.3 Reduction of C—N Bonds
	9.4 Reduction of C—O Bonds
	9.5 Reduction of C—S Bonds
	9.6 Reduction of C—X Bonds
	9.7 Reduction of Heteroatom–Heteroatom Bonds
10 Oxidations
	10.1 Introduction
	10.2 Oxidation of C—C Single and Double Bonds
	10.3 Oxidation of C—H Bonds
	10.4 Oxidation of Carbon–Oxygen Bonds and at Carbon Bearing an Oxygen Substituent
	10.5 Oxidation of Aldehydes to Carboxylic Acids and Derivatives
	10.6 Oxidation of Carbon–Nitrogen Bonds and at Carbon Bearing a Nitrogen Substituent
	10.7 Oxidation of Nitrogen Functionalities
	10.8 Oxidation of Sulfur and at Carbon Adjacent to Sulfur
	10.9 Oxidation of Other Functionality
11 Selected Free Radical Reactions
	11.1 Introduction
	11.2 Radical Reactions via Chemical Initiation
	11.3 Photoredox Catalysis
	11.4 Electrochemical Methods
12 Synthesis of “Nucleophilic” Organometallic Reagents
	12.1 Introduction
	12.2 Synthesis of “Nucleophilic” Organometallic Reagents
	12.3 Strategies for Metalating Heterocycles
	12.4 Reactions of “Nucleophilic” Organometallic Reagents
13 Synthesis of Common Aromatic Heterocycles
	13.1 Introduction
	13.2 Pyrroles
	13.3 Indoles
	13.4 2-Indolinones (Oxindoles)
	13.5 Isatins (2,3-Indolindiones)
	13.6 Carbazoles
	13.7 Pyrazoles
	13.8 Indazoles
	13.9 Imidazoles and Benzimidazoles
	13.10 1,2,3-Triazoles and Benzotriazole
	13.11 1,2,4-Triazoles
	13.12 Tetrazoles
	13.13 Dihydropyridines
	13.14 Pyridines
	13.15 Quinolines
	13.16 Quinolinones and 2-Hydroxyquinolines
	13.17 Isoquinolines
	13.18 Isoquinolinones
	13.19 Quinolones (4-Hydroxyquinolines)
	13.20 Pyrimidines and Pyrimidones
	13.21 Quinazolines and Quinazolinones
	13.22 Pyrazines and Quinoxalines
	13.23 Pyridazines, Phtalazines, and Cinnolines
	13.24 1,2,4-Triazines
	13.25 Furans and Benzofurans
	13.26 Benzopyran-4-One (Chromen-4-One, Flavone) and Xanthone
	13.27 Coumarins
	13.28 Thiophenes and Benzothiophenes
	13.29 Isoxazoles and Benzisoxazoles
	13.30 Oxazoles and Benzoxazoles
	13.31 Isothiazoles and Benzisothiazoles
	13.32 Thiazoles and Benzothiazoles
	13.33 1,2,4-Oxadiazoles
	13.34 1,3,4-Oxadiazoles
14 Access to Chirality
	14.1 Introduction
	14.2 Using the Chiral Pool
	14.3 Classical Resolutions
	14.4 Dynamic Kinetic Resolutions
	14.5 Desymmetrization of Meso Compounds
	14.6 Chiral Chromatography
15 Biocatalysis
	15.1 Introduction
	15.2 Group Transfer Reactions
	15.3 Reductions
	15.4 Oxidations
	15.5 C—C Bond Forming Reactions
	15.6 Future Developments
16 Green Chemistry
	16.1 Introduction
	16.2 Green Chemistry Metrics
	16.3 Solvent and Reagent Selection
	16.4 Green Reactions/Reagents
	16.5 Examples of Green Methods and Reagents for Common Reaction Types
	16.6 Predictive Tools to Design for Green Chemistry
	16.7 Green Chemistry Improvements in Process Development
17 Continuous Chemistry
	17.1 Introduction
	17.2 Aliphatic Nucleophilic Substitutions
	17.3 Additions to C—Het Multiple Bonds
	17.4 Addition to C—C Multiple Bonds
	17.5 Nucleophilic Aromatic Substitutions
	17.6 Electrophilic Aromatic Substitution
	17.7 Catalysis
	17.8 Rearrangements
	17.9 Eliminations
	17.10 Reductions
	17.11 Oxidations
	17.12 Free Radical Reactions
	17.13 Syntheses of Organometallic Reagents
	17.14 Synthesis of Aromatic Heterocycles
	17.15 Access to Chirality
	17.16 Biotransformations
18 General Solvent Properties
	18.1 Introduction
	18.2 Definitions and Acronyms
	18.3 Solvent Properties
	18.4 Mutual Solubility of Water and Organic Solvents
	18.5 Other Useful Information on Solvents
	18.6 Solvent Safety
	18.7 Risk Phrases Used in the Countries of EU
19 Practical Chemistry Concepts Tips for the Practicing Chemist or Things They Don’t Teach You in School
	19.1 Introduction
	19.2 Reaction Execution
	19.3 Solvents and Reagents
	19.4 Isolation
	19.5 Analysis
Subject Index
Combo Index