Practical Synthetic Organic Chemistry

Name: Practical Synthetic Organic Chemistry | Reactions, Principles, and Techniques
Brand: Wiley
Price: 116.99 EUR
Availability: OnlineOnly

Reactions, Principles, and Techniques

Stéphane Caron(Herausgeber*in)

Wiley (Verlag)

2. Auflage

Erschienen am 31. Januar 2020

848 Seiten

E-Book

PDF mit Adobe-DRM

Systemvoraussetzungen

978-1-119-44888-4 (ISBN)

116,99 €inkl. 7% MwSt.

Systemvoraussetzungen

für PDF mit Adobe-DRM

E-Book Einzellizenz

Als Download verfügbar

Beschreibung

Weitere Details

Weitere Ausgaben

Person

Inhalt

Cover
Title Page
Copyright
Contents
List of Contributors
Preface
Chapter 1 Aliphatic Nucleophilic Substitution
1.1 Introduction
1.2 Oxygen Nucleophiles
1.2.1 Reactions with Water
1.2.1.1 Hydrolysis of Alkyl Halides
1.2.1.2 Hydrolysis of gem-Dihalides
1.2.1.3 Hydrolysis of 1,1,1-Trihalides
1.2.1.4 Hydrolysis of Alkyl Esters of Inorganic Acids
1.2.1.5 Hydrolysis of Diazo Ketones
1.2.1.6 Hydrolysis of Acetals, Enol Ethers, and Related Compounds
1.2.1.7 Hydrolysis of Silyl Enol Ethers
1.2.1.8 Hydrolysis of Silyl Ethers
1.2.1.9 Hydrolysis of Epoxides
1.2.2 Reactions with Alcohols
1.2.2.1 Preparation of Ethers from Alkyl Halides
1.2.2.2 Preparation of Methyl Ethers
1.2.2.3 Preparation of Ethers from Alkyl Sulfonates
1.2.2.4 Iodoetherification
1.2.2.5 Preparation of Silyl Ethers
1.2.2.6 Cleavage of Silyl Ethers with Alcohols
1.2.2.7 Transetherification
1.2.2.8 Preparation of Epoxides
1.2.2.9 Reaction of Alcohols with Epoxides
1.2.2.10 The Reaction of Alcohols with Diazo Compounds
1.2.2.11 Preparation of Ethers via Dehydration of Alcohols
1.2.2.12 Addition of Alcohols to Boron, Phosphorous, and Titanium
1.2.3 Reactions with Carboxylates
1.2.3.1 Alkylation of Carboxylic Acid Salts
1.2.3.2 Iodolactonization
1.2.3.3 Preparation of Silyl Esters
1.2.3.4 Preparation of Mixed Organic-Inorganic Anhydrides
1.2.3.5 Cleavage of Ethers with Acetic Anhydride
1.2.3.6 Alkylation of Carboxylic Acids and Enols with Diazo Compounds
1.2.4 Reactions with Other Oxygen Nucleophiles
1.2.4.1 Formation of Silyl Enol Ethers and Silyl Ketene Acetals
1.2.4.2 Formation of Enol Triflates
1.2.4.3 Formation of Oxonium Salts
1.2.4.4 Reactions of Carbonyl Compounds with Oxonium Salts
1.2.4.5 Preparation of Hydroperoxides and Peroxyethers
1.2.4.6 Alkylation of Oximes
1.3 Phosphorus Nucleophiles
1.3.1 Preparation of Reagents for Wittig Reactions
1.4 Sulfur Nucleophiles
1.4.1 Reactions with Thiols
1.4.1.1 Preparation of Thioethers
1.4.1.2 Cleavage of Arylmethyl Ethers
1.4.2 Alkylation of Sulfides
1.4.3 Reactions with Other Sulfur Nucleophiles
1.4.3.1 Preparation of Thiols
1.4.3.2 Formation of Bunte Salts
1.4.3.3 Alkylation of Sulfinic Acid Salts
1.4.3.4 Attack by Sulfite Ion
1.4.3.5 Preparation of Alkyl Thiocyanates
1.5 Nitrogen Nucleophiles
1.5.1 Amine Alkylation
1.5.1.1 Amine Alkylation with Alkyl Halides and Onium Salts
1.5.1.2 Amine Alkylation with Inorganic Esters
1.5.1.3 Amine Alkylation with Alcohols
1.5.1.4 Amine Alkylation with Diazo Compounds
1.5.1.5 Transamination
1.5.1.6 Amine Alkylation with Epoxides
1.5.1.7 Amine Alkylation with Cyclic Carbonates
1.5.1.8 Preparation of 1° Amines via Hexamethyldisilazane
1.5.1.9 Preparation of Isocyanides ("Isonitriles")
1.5.1.10 Methylation of Amines, the Eschweiler-Clarke reaction
1.5.1.11 Preparation Sulfenamides
1.5.2 N-Alkylation of Amides, Lactams, Imides, and Carbamates
1.5.2.1 Alkylation with Alkyl Halides
1.5.2.2 Alkylation with Alkyl Sulfonates and Derivatives
1.5.3 Other Nitrogen Nucleophiles
1.5.3.1 Nitrite Nucleophiles: Preparation of Nitro Compounds
1.5.3.2 Azide Nucleophiles
1.5.3.3 Isocyanates and Isothiocyanates as Nucleophiles
1.6 Halogen Nucleophiles
1.6.1 Attack by Halides at Alkyl Carbon or Silicon
1.6.1.1 Halide Exchange
1.6.1.2 Preparation of Halides from Sulfonic Acid Esters
1.6.1.3 Preparation of Alkyl Halides from Alcohols
1.6.1.4 Preparation of Alkyl Halides from Ethers
1.6.1.5 Preparation of Alkyl Halides from Epoxides
1.6.1.6 Cleavage of Alkyl Ethers with Halide Ion
1.6.1.7 Cleavage of Silyl Ethers and Silyl Enol Ethers with Halide Ion
1.6.1.8 Cleavage of Carboxylic Acid and Sulfonic Acid Esters with Halide Ion
1.6.1.9 Preparation of Halides from &rmalpha
-Diazo Carbonyl Compounds
1.6.1.10 Preparation of Cyanamides
1.7 Carbon Nucleophiles
1.7.1 Attack by Carbon at Alkyl Carbon
1.7.1.1 Direct Coupling of Alkyl Halides
1.7.1.2 Reactions of Organometallic Reagents with Alkyl Halides
1.7.1.3 Couplings of Allylic and Propargylic Halides
1.7.1.4 Couplings of Organometallic Reagents with Sulfonate Esters
1.7.1.5 Couplings Involving Alcohols
1.7.1.6 Reactions of Organometallic Reagents with Allylic Esters and Carbonates
1.7.1.7 Reactions of Organometallic Reagents with Epoxides
1.7.1.8 Alkylation of Malonate and Acetoacetate Derivatives
1.7.1.9 Alkylation of Aldehydes, Ketones, Nitriles, and Carboxylic Esters
1.7.1.10 Alkylation of Carboxylic Acid Salts
1.7.1.11 Alkylation &rmalpha
to a Heteroatom
1.7.1.12 Alkylation &rmalpha
to a Masked Carboxylic Acid
1.7.1.13 Alkylation at Alkynyl Carbon
1.7.1.14 Alkylation of Cyanide Ion - Preparation of Nitriles
1.8 Nucleophilic Substitution at a Sulfonyl Sulfur Atom
1.8.1 Attack by Oxygen
1.8.1.1 Hydrolysis of Sulfonic Acid Derivatives
1.8.1.2 Formation of Sulfonate Esters
1.8.2 Attack by Nitrogen
1.8.2.1 Formation of Sulfonamides
1.8.3 Attack by Halogen
1.8.3.1 Formation of Sulfonyl Halides
1.8.4 Attack by Carbon
1.8.4.1 Preparation of Sulfones
Chapter 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
2.7.1 The Addition of Amines to Aldehydes and Ketones: Imine and Oxime Formation
2.7.2 Redox Neutral Amination
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
2.11.1 Ketene and Silyl Enol Ether Addition to Aldehydes
2.11.2 Silyl Enol Ether Addition to Aldehydes: The Mukaiyama Aldol
2.11.3 Ketene Silyl Acetal and Thioacetal Addition to Aldehydes
2.12 Allylorganometallics: Stannane, Borane, and Silane
2.12.1 Allylsilane Additions
2.12.2 Allylborane Additions
2.12.3 Allylstannane Additions
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
2.15.1 Using Organolithium Reagents
2.15.2 Using Organomagnesium Reagents
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
2.26.1 Procedures Using Oxalyl Chloride in the Absence of DMF
2.26.2 Procedures Using Thionyl Chloride in the Absence of DMF
2.26.3 Procedures Using a Halogenating Agent and DMF
2.26.4 Procedures Using Vilsmeier Reagent
2.27 Synthesis of Acyl Fluorides from Carboxylic Acids
2.28 Formation of Amides from Carboxylic Acids
2.28.1 Direct Coupling of Carboxylic Acids and Amines
2.28.2 Via Acid Chlorides
2.28.3 Via Acyl Imidazoles (Imidazolides)
2.28.4 Via Acyl Imidazolium Ions
2.28.5 Via Anhydrides
2.29 Formation of Amides from Esters
2.30 Hydrolysis of Acyl Halides
2.31 Conversion of Carboxylic Acids to Esters
2.31.1 Fisher Esterification
2.31.2 Widmer's Method for the Synthesis of t-Butyl Esters
2.31.3 Via Acid Chlorides
2.31.4 Via Acyl Imidazoles (Imidazolides)
2.31.5 Using Carbodiimides
2.31.6 Via Anhydrides
2.31.7 Miscellaneous Methods
2.32 Hydrolysis of Amides
2.32.1 Under Acidic Conditions
2.32.2 Under Basic Conditions
2.32.3 Under Oxidative Conditions
2.32.4 Miscellaneous Methods
2.33 Conversion of N-Acyloxazolidinones to Other Carboxyl Derivatives
2.34 Alcoholysis of Amides
2.35 Hydrolysis of Esters
2.35.1 Under Basic Conditions
2.35.2 Under Acidic Conditions
2.35.3 Miscellaneous Methods
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
2.40.1 Using Trimethylsilyl Cyanide
2.40.2 Using Copper (I) Cyanide
2.40.3 Miscellaneous Methods
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
2.44.1 Hydrolysis of Nitriles Under Acidic Conditions
2.44.2 Hydrolysis of Nitriles Under Basic Conditions
2.44.3 Hydrolysis of Nitriles Under Oxidative Conditions
2.44.4 Enzymatic Hydrolysis of Nitriles
2.44.5 Miscellaneous
2.45 Conversion of Nitriles to Thioamides
2.45.1 Conversion of Nitriles to Aldehydes
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
Chapter 3 Addition to Carbon-Carbon Multiple Bonds
3.1 Introduction
3.2 Hydrogen-Halogen Addition (Hydrohalogenation)
3.2.1 Hydrohalogenation of Olefins
3.2.2 Hydrohalogenation of Alkynes
3.3 Hydrogen-Oxygen Addition
3.3.1 Addition of H-OH (Hydration)
3.3.1.1 Hydration of Olefins
3.3.1.2 Hydration of Acetylenes
3.3.2 Addition of H-OR (Hydroalkoxylation)
3.3.2.1 Addition of H-OR to Olefins
3.3.2.2 Addition of H-OR to Acetylenes
3.4 Hydrogen-Nitrogen Addition (Hydroamination)
3.4.1 Hydroamination of Olefins
3.4.2 Hydroamination of Acetylenes and Allenes
3.5 Hydrogen-Carbon Addition (Hydroalkylation)
3.5.1 Direct Hydrogen-Alkyl Addition
3.5.2 Hydrogen-Allyl Addition (Alder Ene Reaction)
3.5.3 Hydrogen-Malonate/Enolate Addition (Michael Reaction)
3.5.4 Hydrogen-Alkyl Addition, Stork Enamine Reaction
3.5.5 Hydrogen-Alkyl Addition, Metal-Catalyzed
3.5.6 Hydroformylation/Hydroacylation
3.5.7 Nazarov Cyclization
3.5.8 Radical-Mediated C-H Addition
3.6 Halogen-Halogen Addition
3.7 Hydroxy-Halogen Addition
3.8 Amino-Halogen Addition
3.9 Carbon-Halogen Addition
3.9.1 Alkyl-Halogen Addition
3.9.2 Acyl-Halogen Addition
3.10 Oxygen-Oxygen Addition
3.10.1 Dihydroxylation of Olefins
3.10.2 Keto-Hydroxylation of Olefins
3.10.3 Dihydroxylation of Acetylenes
3.10.4 Epoxidation
3.10.5 Singlet Oxygen Addition to Dienes
3.11 Oxygen-Nitrogen Addition
3.12 Nitrogen-Nitrogen Addition
3.12.1 Aziridination
3.12.2 N-N Addition to Olefins
3.12.3 Triazines from Azide-Olefin Cycloaddition
3.12.4 N-N Addition to Dienes (1,4)
3.13 Carbon-Oxygen Addition
3.13.1 Carbon-Oxygen Addition to Olefins (1,2)
3.13.1.1 [2+2] Cycloadditions of Olefins and Carbonyl Compounds
3.13.1.2 Nitrone-Olefin [3+2] Cycloadditions
3.13.1.3 Noncycloaddition Carbon-Oxygen Additions
3.13.2 Carbon-Oxygen Addition to Dienes (1,4)
3.13.2.1 Hetero Diels-Alder Cycloaddition
3.14 Carbon-Nitrogen Addition
3.14.1 Carbon-Nitrogen Addition to Olefins
3.14.2 Carbon-Nitrogen Addition to Alkynes
3.14.3 Carbon-Nitrogen Addition to Dienes
3.15 Carbon-Carbon Addition
3.15.1 [4+2] Cycloaddition: Diels-Alder Reaction
3.15.1.1 Intermolecular, Nonsubstituted
3.15.1.2 Intermolecular, Heteroatom-substituted Dienophile
3.15.1.3 Intermolecular, Heteroatomsubstituted Diene
3.15.1.4 Intermolecular, Aqueous Media
3.15.1.5 Intermolecular, Aromatic Product
3.15.1.6 Intermolecular, Lewis Acid-Catalyzed
3.15.1.7 Intermolecular, Inverse-electron Demand
3.15.1.8 Intermolecular, Benzyne as Dienophile
3.15.1.9 Intramolecular Examples
3.15.1.10 Asymmetric Examples
3.15.2 [2+2] Cycloaddition
3.15.3 [3+2] Cycloaddition
3.15.4 Carbene Addition (Cyclopropanation)
3.15.5 [4+3] Cycloadditions
3.15.6 Conjugate Addition-Alkylation
3.15.7 Bis-Alkoxycarbonylation
3.15.8 Cascade Cyclizations
Chapter 4 Nucleophilic Aromatic Substitution
4.1 Introduction
4.2 Oxygen Nucleophiles
4.2.1 Preparation of Phenols
4.2.2 Preparation of Aryl Ethers
4.2.3 Preparation of Diaryl Ethers
4.3 Sulfur Nucleophiles
4.3.1 Preparation of Aryl Thioethers
4.3.2 Preparation of Diaryl Thioethers
4.3.3 Other Sulfur Nucleophiles
4.4 Nitrogen Nucleophiles
4.4.1 Preparation of Anilines
4.4.2 Preparation of Aryl Amines
4.4.3 Preparation of Diaryl Amines
4.4.4 Other Nitrogen Nucleophiles
4.5 Halogen Nucleophiles
4.5.1 Reaction of Diazonium Salts
4.5.2 Preparation of 2-Halopyridines and Derivatives
4.6 Carbon Nucleophiles
4.6.1 Cyanide as a Nucleophile
4.6.2 Malonates as Nucleophiles
4.6.3 Other Carbon Nucleophiles
4.7 ortho-Arynes
Chapter 5 Electrophilic Aromatic Substitution
5.1 Introduction
5.2 Nitrogen Electrophiles
5.2.1 Nitration
5.2.2 Nitrosation
5.2.3 Diazonium Coupling
5.3 Sulfur Electrophiles
5.3.1 Sulfonation
5.3.2 Halosulfonation
5.3.3 Sulfurization
5.3.4 Sulfinylation
5.3.5 Sulfonylation
5.3.6 Thiocyanation
5.4 Halogenation
5.4.1 Fluorination
5.4.2 Chlorination
5.4.3 Bromination
5.4.4 Iodination
5.5 Carbon Electrophiles
5.5.1 Friedel-Crafts Alkylation
5.5.2 Friedel-Crafts Arylation
5.5.3 Claisen Rearrangement
5.5.4 Formylation
5.5.5 Hydroxyalkylation
5.5.6 Haloalkylation
5.5.7 Aminoalkylation
5.5.8 Thioalkylation
5.5.9 Friedel-Crafts Acylation
5.5.10 Fries Rearrangement
5.5.11 Carboxylation
5.5.12 Amidation
5.5.13 Thioamidation and Thioesterification
5.5.14 Cyanation
Chapter 6 Selected Catalytic Reactions
6.1 Introduction
6.2 Organoboron Reagents: The Suzuki-Miyaura Coupling
6.2.1 Preparation of Biaryls
6.2.2 Preparation of Alkynyl-Substituted Arenes
6.2.3 Preparation of Vinyl-Substituted Arenes
6.2.4 Preparation of Dienes
6.2.5 Preparation of Alkyl-Substituted Arenes
6.2.6 Preparation of Alkyl-Substituted Alkenes
6.2.7 Preparation of Alkanes
6.3 Organomagnesium Reagents: Kumada-Corriu Coupling
6.3.1 Preparation of Biaryls
6.3.2 Preparation of Vinyl-Substituted Arenes
6.3.3 Preparation of Aryl-Alkyl Bonds
6.3.4 Preparation of Vinyl-Alkyl Bonds
6.4 Organozinc Reagents: Negishi Coupling
6.4.1 Preparation of Biaryls
6.4.2 Preparation of Aryl-Alkyl Bonds
6.4.3 Preparation of Alkanes
6.4.4 Preparation of 1,3-Dienes
6.4.5 Preparation of Ketones
6.5 Cross-Electrophile Coupling
6.6 Organotin Reagents: The Stille Coupling (Migita-Stille Reaction)
6.6.1 Preparation of Biaryls
6.6.2 Preparation of Vinyl-Substituted Arenes
6.6.3 Preparation of 1,3-Dienes
6.6.4 Preparation of Alkyl-Substituted Alkenes
6.7 Cross-Coupling Reactions with Organosilicon Compounds
6.8 Metal-catalyzed Coupling of Alkynes (Sonogashira Coupling)
6.8.1 Reaction with Aryl Halides
6.8.2 Preparation of Enynes
6.9 Metal-Catalyzed Coupling of Alkenes (Heck Coupling)
6.9.1 Formation of Aryl Alkenes
6.9.2 Formation of Dienes
6.9.3 Reductive Heck
6.9.4 Oxidative Heck
6.10 Enolate Arylations
6.10.1 a-Arylation of Ketones
6.10.2 a-Arylation of Esters
6.10.3 a-Arylation of Amides
6.10.4 a-Arylation of Nitrile
6.11 Pd- and Cu-Catalyzed Aryl C-N Bond Formation
6.11.1 Alkyl Amine as Nucleophile
6.11.2 Aryl Amine as Nucleophile
6.11.3 Amides as Nucleophile
6.11.4 Other Amine as Nucleophile
6.11.5 Coupling with Ammonia Surrogate
6.11.6 Oxidative Coupling
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
6.14.1 Aryl Bromides and Iodides
6.14.2 Vinyl Bromide
6.14.3 Aryl Chlorides and Triflates
6.15 Pd-Catalyzed Aryl C-CN Bond Formation
6.16 Metal-Catalyzed Allylic Substitution
6.16.1 Carbon Nucleophiles
6.16.2 Nitrogen Nucleophiles
6.16.3 Oxygen Nucleophiles
6.17 Catalytic Metal-Mediated Methods for Fluorination
6.17.1 Aryl Fluorination
6.17.2 Vinyl Fluorides
6.17.3 a-Fluorination of Carbonyl Compounds
6.17.4 Difluoromethylation (-CF2R)
6.17.5 Trifluoromethylation (-CF3)
6.17.6 Emerging Methods for Metal-Catalyzed Fluorination
6.17.7 Summary and Outlook for Metal-Catalyzed Fluorination
6.18 Selected Metal-Mediated C-H Functionalization
6.18.1 Introduction
6.18.2 Metal-Catalyzed, Directed C-H Functionalization
6.18.2.1 Ru-Catalyzed Methods
6.18.2.2 Palladium-Catalyzed Methods
6.18.2.3 Rhodium-Catalyzed Methods
6.18.3 Metal-Catalyzed Undirected C-H Functionalization
6.18.3.1 Formation of C-B Bonds
6.18.3.2 Formation of C-Si Bonds
6.18.3.3 Formation of C-C Bonds
6.19 C-X Bond Forming Reactions via Borrowed Hydrogen Methodologies
6.19.1 Introduction
6.19.2 C-C Bond formation
6.19.2.1 Allylation/Crotylation
6.19.2.2 Alkylation of Aromatics
6.19.3 Redox Neutral Homologation of Alcohols
6.19.4 Ketone Functionalization
6.19.5 C-N Bond Formation
6.19.5.1 Primary Amines
6.19.5.2 Secondary Amines
6.19.5.3 Tertiary Amines
6.20 Alkene and Alkyne Metathesis Reactions
6.20.1 Introduction
6.20.2 Ring-closing Metathesis
6.20.2.1 Alkene Ring-Closing Metathesis
6.20.2.2 Alkyne Ring-Closing Metathesis
6.20.2.3 Enyne Ring-closing Metathesis
6.20.2.4 Z-Selective Olefin Metathesis
6.20.3 Cross-Metathesis
6.20.3.1 Alkene Cross-Metathesis
6.20.3.2 Alkane Cross-Metathesis
6.20.3.3 Alkyne Cross-Metathesis
6.20.4 Metathesis Polymerization
6.21 Organocatalysis
6.21.1 Introduction
6.21.2 Phase Transfer Catalysis
6.21.2.1 Carbon Alkylation
6.21.2.2 Heteroatom Alkylation
6.21.2.3 Conjugate Additions of Carbon Nucleophiles
6.21.2.4 Addition of Heteroatom Nucleophiles
6.21.3 Amino Organocatalysis via Iminium and Enamine Intermediates
6.21.3.1 Iminium Catalysis: Conjugate Addition
6.21.3.2 Iminium Catalysis: Cycloadditions
6.21.3.3 Enamine Catalysis: Aldol/Mannich
6.21.4 Nucleophilic Catalysis
6.21.4.1 Acyl Transfer Reactions
6.21.4.2 Reactions Proceeding via Acyl Anion Equivalents
6.21.4.3 Morita-Baylis-Hillman Reactions
Chapter 7 Rearrangements
7.1 Introduction
7.2 [1,2]-Rearrangements
7.2.1 Carbon-to-Carbon Migrations of Carbon and Hydrogen
7.2.1.1 Wagner-Meerwein and Related Reactions
7.2.1.2 Pinacol Rearrangement: Vicinal Diols to Ketones or Aldehydes
7.2.1.3 Expansion and Contraction of Rings
7.2.1.4 Rearrangements of Ketones and Aldehydes
7.2.1.5 Dienone to Phenol Rearrangement
7.2.1.6 Benzil to Benzilic Acid Rearrangement
7.2.1.7 Favorskii Rearrangement: Anionic Rearrangement of a-Haloketones
7.2.1.8 Arndt-Eistert Synthesis: Homologation of Carboxylic Acids via Wolff Rearrangement of a-Diazoketones
7.2.1.9 Homologation of Aldehydes and Ketones
7.2.1.10 Fritsch-Buttenberg-Wiechell Rearrangement: Acetylenes from 1,1-Disubstituted Olefins
7.2.1.11 Other Carbon-to-Carbon Migrations of Carbon
7.2.1.12 Other Carbon-to-Carbon Migrations of Hydrogen
7.2.2 Carbon-to-Carbon Migrations of Other Groups
7.2.2.1 Migration of Halogen, Hydroxy, Amino, and Other Groups
7.2.2.2 Neber Rearrangement: Carbon-to-Carbon Migration of Nitrogen of Activated Oximes
7.2.2.3 Payne Rearrangement: Rearrangement of a-Hydroxyepoxides
7.2.3 Carbon-to-Nitrogen Migrations of Carbon
7.2.3.1 Hofmann Rearrangement: Primary Amides to Amines or Carbamates
7.2.3.2 Curtius Rearrangement: Acyl Azides to Amines or Carbamates
7.2.3.3 Lossen Rearrangement: Hydroxamic Imides to Amines or Carbamates
7.2.3.4 Schmidt Rearrangement: Ketones to Amides
7.2.3.5 Beckmann Rearrangement: Oximes to Amides
7.2.3.6 Stieglitz Rearrangements and Related Reactions: Cationic C to N Migration of Carbon
7.2.4 Carbon to Oxygen Migrations of Carbon
7.2.4.1 Baeyer-Villiger Oxidation: Ketones or Aldehydes to Esters
7.2.5 Heteroatom to Carbon Migrations
7.2.5.1 Stevens Rearrangement - [1,2]-Rearrangement of N, O, or S Ylides with Migration of Carbon
7.2.5.2 [1,2]-Meisenheimer Rearrangement - Rearrangement of R3NO to R2NOR
7.2.5.3 Other Heteroatom to Carbon Rearrangements
7.2.6 Carbon to Heteroatom Rearrangements
7.2.6.1 Brook Rearrangement, Carbon-to-Oxygen Migration of Silicon
7.3 Other Rearrangements
7.3.1 Electrocyclic Rearrangements
7.3.1.1 Rearrangements of Cyclobutenes and 1,3-Cyclohexadienes
7.3.1.2 Stilbenes to Phenanthrenes
7.3.2 Sigmatropic Rearrangements
7.3.2.1 Cyclopropylimine Rearrangement
7.3.2.2 Cyclopropanes to Allenes: The Skattebøl and Related Rearrangements
7.3.2.3 Cope Rearrangement
7.3.2.4 Claisen Rearrangement
7.3.2.5 Fischer Indole Synthesis
7.3.2.6 Boekelheide Rearrangement: 2-Alkylpyridine N-Oxide Rearrangements
7.3.2.7 [2,3]-Wittig Rearrangement: O-to-C Shift of Carbon
7.3.2.8 [2,3]-Meisenheimer Rearrangement: N-to-O Migration of Carbon in Tertiary N-Oxides
7.3.2.9 [2,3]-Sulfoxide, Selenoxide, and Sulfilimine Rearrangements
7.3.2.10 Sommelet-Hauser Rearrangement and Related Reactions - [2,3]-Sigmatropic Rearrangements of Ylides
7.3.2.11 Benzidine Rearrangement
7.3.2.12 Overman Rearrangement
7.3.2.13 Propargyl O-to-N Migration
7.3.3 Other Cyclic Rearrangements
7.3.3.1 Di-p-Methane and Related Rearrangements
7.3.4 Acyclic Rearrangements
7.3.4.1 Migration of Double Bonds
7.3.4.2 Hydride Shifts
7.3.4.3 Newman-Kwart Rearrangement - O-phenylthiocarbanate to S-phenylcarbamate
7.3.4.4 Nitrosamide Decomposition
7.3.4.5 The Achmatowitz Reaction: Oxidative Furan Rearrangement
7.4 Miscellaneous Migrations
7.4.1 Hunsdiecker
7.4.2 Jocic
7.4.3 Smiles/Truce-Smiles
7.4.4 Dakin-West-Dimroth
7.4.5 Meinwald
Chapter 8 Eliminations
8.1 Introduction
8.2 Formation of Alkenes
8.2.1 Elimination of Alcohols
8.2.2 Elimination of Ethers
8.2.3 Elimination of Esters
8.2.4 Elimination of Xanthates
8.2.5 Elimination of Ammonium or Sulfonium Salts
8.2.6 Elimination of N-Oxides
8.2.7 Elimination of Diazonium Salts
8.2.8 Elimination of Hydrazones
8.2.9 Elimination of Sulfoxides and Selenoxides
8.2.10 Elimination of Halides
8.2.11 Elimination of Nitriles
8.2.12 Elimination to an Electron-withdrawing Group
8.2.13 Elimination of Diol Derivatives
8.2.14 Elimination of Epoxides and Episulfides
8.2.15 Elimination of &rmalpha
-Halo Sulfones
8.2.16 Elimination of Aziridines
8.2.17 Elimination of Dihalides
8.2.18 Elimination of Haloethers
8.2.19 Elimination of Hydroxy- or Haloacids
8.2.20 Elimination of Hydroxysulfones
8.2.21 Elimination of ß-Silyl Alcohols
8.2.22 Elimination of ß-Silyl Esters, Sulfides, and Su
8.3 Formation of Dienes
8.3.1 From Allylic Systems
8.3.2 From 1,4-Dihalo-2-butenes
8.3.3 From Diols
8.3.4 From -Elimination
8.3.5 From Sulfolenes
8.3.6 Via Retro Diels-Alder Reactions
8.3.7 From Extrusion of CO
8.4 Formation of Alkynes
8.4.1 From Ketones
8.4.2 From Bis(hydrazones)
8.4.3 From Dihalides
8.4.4 From Vinyl Halides
8.4.5 From Elimination of Sulfones
8.5 Formation of C=N bonds
8.5.1 Carbodiimides from Ureas
8.6 Formation of Nitriles
8.6.1 Nitriles from Amides
8.6.2 Nitriles from Cleavage of N-O Bonds
8.6.3 Isonitriles from Formamides
8.7 Formation of Ketenes and Related Compounds
8.7.1 Ketenes
8.7.2 Isocyanates and Isothiocyanates
8.7.3 Ketimines
8.8 Fragmentations
8.8.1 Grob Fragmentations
8.8.2 Eschenmoser Fragmentations
8.8.3 Formation of Arenes
8.8.4 Extrusion of N2
8.8.5 Extrusion of S
8.8.6 Multicomponent Extrusions
8.9 Dehydrating Reagents
Chapter 9 Reductions
9.1 Introduction
9.2 Reduction of C-C Bonds
9.2.1 Reduction of Alkynes
9.2.1.1 Reduction of Alkynes to Alkenes
9.2.1.2 Reduction of Alkynes to Alkanes
9.2.2 Reduction of Alkenes
9.2.2.1 Reduction of Alkenes to Alkanes Without Facial Selectivity
9.2.2.2 Reduction of Alkenes to Alkanes with Facial Selectivity
9.2.3 Reduction of Aromatic Rings and Heterocycles
9.2.3.1 Reduction of Benzene and Naphthalene Rings
9.2.3.2 Reduction of Pyridines and Quinolines
9.2.3.3 Reduction of Pyrroles and Indoles
9.2.3.4 Reduction of Furans
9.2.4 Conjugate Reductions
9.2.4.1 Reduction of Conjugated Alkynes
9.2.4.2 Reduction of , -Unsaturated Acids and Derivatives
9.2.4.3 Reduction of Enones
9.3 Reduction of C-N Bonds
9.3.1 Reduction of Nitriles to Imines or Aldehydes
9.3.2 Reduction of Nitriles to Primary Amines
9.3.3 Reduction of Imines or Imine Derivatives
9.3.3.1 Achiral Reductions
9.3.3.2 Substrate Control in Stereoselective Reductions
9.3.3.3 Enantioselective Reductions
9.3.4 Reduction of Hydrazones to Alkanes
9.3.5 Reduction of Carbon-Nitrogen Single Bonds
9.3.5.1 Reduction of Benzylic Amines
9.3.5.2 Reduction of Aromatic Carbon-Nitrogen Single Bonds
9.3.5.3 Reduction of Aliphatic Nitro Groups
9.4 Reduction of C-O Bonds
9.4.1 Reduction of Carboxylic Acid Derivatives
9.4.1.1 Reduction of Esters to Aldehydes
9.4.1.2 Reduction of Esters to Primary Alcohols
9.4.1.3 Reduction of Carboxylic Acids to Primary Alcohols
9.4.1.4 Reduction of Anhydrides and Mixed Anhydrides to Aldehydes
9.4.1.5 Reduction of Anhydrides and Mixed Anhydrides to Primary Alcohols
9.4.1.6 Reduction of Amides and Imides to Aldehydes
9.4.1.7 Reduction of Amides to Alkylamines
9.4.1.8 Reduction of Carbamates to N-Methylamines
9.4.2 Reduction of Aldehydes and Ketones to Alcohols
9.4.2.1 Reduction with Hydride Donors
9.4.2.2 Meerwein-Ponndorf-Verley Reaction
9.4.2.3 Reduction via Catalytic Hydrogenation
9.4.2.4 Biocatalytic Routes to Reduction of Aldehydes and Ketones
9.4.2.5 Aldol-Tishchenko Reaction
9.4.2.6 Reduction of Acetals and Ketals
9.4.3 Reduction of Ketones to Alkanes
9.4.3.1 Wolff-Kishner Reduction
9.4.3.2 Clemmensen Reduction
9.4.3.3 Silane-Mediated Reduction
9.4.4 Reduction of Alcohols to Alkanes
9.4.4.1 Reduction of Aliphatic Alcohols
9.4.4.2 Reduction of Benzylic Alcohols
9.4.4.3 Reduction of Benzylic Ethers
9.5 Reduction of C-S Bonds
9.5.1 Reduction of Alkyl Sulfides, Sulfoxides, and Sulfones
9.5.2 Reduction of Vinyl Sulfides, Sulfoxides, and Sulfones
9.5.3 Reduction of Aryl Sulfides, Sulfoxides, and Sulfones
9.5.4 Reduction of Thioketones
9.5.5 Reduction of Thioesters and Thioamides
9.5.6 Reduction of Miscellaneous Thiocarbonyls
9.6 Reduction of C-X Bonds
9.6.1 Alkyl Halide Reductions
9.6.2 Acid Halides to Aldehydes
9.6.3 Vinyl Halide Reductions
9.6.4 Aryl Halide Reductions
9.7 Reduction of Heteroatom-Heteroatom Bonds
9.7.1 Reduction of Nitrogen-Nitrogen Bonds
9.7.1.1 Reduction of Azides
9.7.2 Reduction of Nitrogen-Oxygen Bonds
9.7.2.1 Reduction of Nitro Groups to Amines
9.7.2.2 Partial Reduction of Aromatic Nitro Compounds
9.7.2.3 Partial Reduction of Aliphatic Nitro Compounds
9.7.3 Reduction of Oxygen-Oxygen Bonds
9.7.3.1 Reduction of Peroxides
9.7.3.2 Reduction of Ozonides
9.7.4 Reduction of Oxygen-Sulfur Bonds
9.7.4.1 Reduction of Sulfones to Sulfides
9.7.4.2 Reduction of Sulfoxides to Sulfides
9.7.5 Reduction of Disulfides to Thiols
9.7.6 Reduction of Phosphine Oxides to Phosphines
Chapter 10 Oxidations
10.1 Introduction
10.2 Oxidation of C-C Single and Double Bonds
10.2.1 Oxidative Cleavage of Glycols -Aminoalcohols, -Hydroxyaldehydes and Ketones, and Related Compounds
10.2.2 Ozonolysis
10.2.2.1 Ozonolysis Followed by Reduction to the Alcohol
10.2.2.2 Ozonolysis to the Ketone or Aldehyde Oxidation State
10.2.2.3 Ozonolysis Resulting in Carboxylic Acids or Esters
10.2.2.4 Ozonolysis Followed by Criegee Rearrangement
10.2.3 Oxidative Cleavage of Double Bonds and Aromatic Rings
10.2.4 Oxidative Cleavage of Alkyl Groups from Rings
10.2.5 Oxidative Decarboxylation
10.2.6 Oxidative Decyanation
10.2.7 Oxidation of Olefins to Aldehydes and Ketones
10.3 Oxidation of C-H Bonds
10.3.1 Aromatization of Six-Membered Rings
10.3.2 Dehydrogenations Yielding Carbon-Carbon Bonds
10.3.3 Halogenation &rmalpha
to a Ketone or Aldehyde, or Carboxylic Acid
10.3.3.1 Chlorination
10.3.3.2 Bromination
10.3.3.3 Iodination
10.3.3.4 Fluorination
10.3.3.5 Haloform Reaction
10.3.3.6 Cleavage of Ketones with MNH2
10.3.4 Oxygenation to a Ketone, Aldehyde, or Carboxylic Acid
10.3.5 Introduction of Nitrogen to a Ketone, Aldehyde, or Carboxylic Acid
10.3.5.1 Aliphatic Diazonium Coupling
10.3.5.2 Nitrosation of Activated Carbon-Hydrogen Bonds
10.3.5.3 Formation of Diazo Compounds
10.3.5.4 Amination to a Carbonyl
10.3.6 Sulfenation and Selenylation of Ketones, Aldehydes, and Esters
10.3.7 Sulfonylation of Aldehydes, Ketones, and Acids
10.3.8 Allylic and Benzylic Halogenation
10.3.8.1 Oxygenations
10.3.8.2 Allylic Amination
10.3.9 Nitrene Insertion into Carbon-Hydrogen Bonds
10.4 Oxidation of Carbon-Oxygen Bonds and at Carbon Bearing an Oxygen Substituent
10.4.1 Oxidation of Alcohols to Aldehydes and Ketones
10.4.1.1 TEMPO-Mediated Processes
10.4.1.2 Moffatt and Modified-Moffatt Processes
10.4.1.3 Metal-Mediated Processes
10.4.1.4 Alternative Methods
10.4.1.5 Oxidation of Benzylic and Allylic Alcohols
10.4.1.6 Oxidation of Diols to Lactones, Selective Oxidation of Primary or Secondary Alcohols
10.4.2 Oxidation of Primary Alcohols to Carboxylic Acids
10.4.2.1 TEMPO/Sodium Chlorite Oxidation of Alcohols to Carboxylic Acids and Derivatives
10.4.2.2 Metal-Mediated Oxidation of Alcohols to Carboxylic Acids and Derivatives
10.5 Oxidation of Aldehydes to Carboxylic Acids and Derivatives
10.5.1 Sodium Chlorite Oxidation of Aldehydes to Carboxylic Acids and Derivatives
10.5.1.1 Hydrogen Peroxide Oxidation of Aldehydes to Carboxylic Acids and Derivatives
10.5.1.2 Metal-Mediated Oxidations of Aldehydes to Carboxylic Acids and Derivatives
10.5.1.3 Oxidation of Bisulfite Adducts
10.5.2 Oxidation of Carboxylic Acids to Peroxyacids
10.5.3 Oxidation of Phenols and Anilines to Quinones
10.5.4 Oxidation &rmalpha
to Oxygen and Nitrogen
10.6 Oxidation of Carbon-Nitrogen Bonds and at Carbon Bearing a Nitrogen Substituent
10.6.1 Dehydrogenation of Amines to Imines and Nitriles
10.6.1.1 Oxidation to Nitrogen
10.6.1.2 Oxidation of Aldoximes and Hydrazones of Aldehydes
10.7 Oxidation of Nitrogen Functionalities
10.7.1 Diazotization of Amines
10.7.2 Oxidations of Hydrazines and Hydrazones
10.7.3 Amination of Nitrogen
10.7.4 Oxidation of Amines to Azo or Azoxy Compounds
10.7.5 Oxidation of Primary Amines to Hydroxylamines
10.7.6 Oxidation of Nitrogen to Nitroso Compounds
10.7.6.1 Nitrone Formation
10.7.6.2 Oxidation of Hydroxylamine to Nitroso Compounds
10.7.7 Nitrosation of Secondary Amines and Amides
10.7.8 Oxidation of Primary Amines, Oximes, or Nitroso Compounds to Nitro Compounds
10.7.9 Oxidation of Tertiary Amines to Amine Oxides and Elimination to Form Imines
10.7.10 Oxidation of Pyridines to Pyridine N-Oxides
10.7.11 Halogenation or Sulfination of Amines and Amides
10.8 Oxidation of Sulfur and at Carbon Adjacent to Sulfur
10.8.1 Pummerer Rerrangement
10.8.2 Formation of -Halosulfides
10.8.3 Halogenation of Sulfoxides, Sulfones, and Phosphine Oxides
10.8.4 Oxidation of Mercaptans and Other Sulfur Compounds to Sulfonic Acids or Sulfonyl Chlorides
10.8.4.1 Peroxide-Based Oxidations
10.8.4.2 Chlorine Oxidations
10.8.5 Oxidation of Sulfides to Sulfoxides and Sulfones
10.8.5.1 Oxidation of a Sulfide to a Sulfoxide
10.8.5.2 Oxidation of a Sulfide to a Sulfone
10.8.5.3 Oxidation of Selenides
10.8.6 Oxidation of Mercaptans to Disulfides
10.9 Oxidation of Other Functionality
10.9.1 Oxidation of Primary Halides
10.9.2 Oxidation of C-Si Bonds: The Tamao Oxidation
Chapter 11 Selected Free Radical Reactions
11.1 Introduction
11.1.1 Radical Reactions Discussed in Other Chapters
11.2 Radical Reactions via Chemical Initiation
11.2.1 Radical Cyclizations
11.2.2 Atom Transfer Radical Cyclizations
11.2.3 Radical Allylation
11.2.3.1 Keck Radical Allylation
11.2.3.2 Tin-Free Radical Allylations
11.2.4 Remote Functionalization Reactions
11.2.5 Barton Nitrite Ester Reaction
11.2.5.1 Hofmann-Löffler-Freytag Reaction
11.2.6 Hypohalite Reaction
11.2.7 The Hunsdiecker Reaction
11.2.7.1 Barton Modification of the Hunsdiecker Reaction
11.2.7.2 Suárez Modification of the Hunsdiecker Reaction
11.2.7.3 Catalytic Hunsdiecker Reaction with , -Unsaturated Carboxylic Acids
11.2.7.4 Nitro-Hunsdiecker Reaction
11.2.8 The Minisci Reaction
11.2.9 Radical Conjugate Additions
11.2.9.1 Intramolecular Radical Conjugate Additions
11.2.9.2 Intermolecular Radical Conjugate Additions
11.2.10 -Scission Reactions
11.2.11 Free Radical Polymerization
11.3 Photoredox Catalysis
11.3.1 Dual Catalytic Cross-coupling Reactions
11.3.2 Photoredox Minisci Reactions
11.3.3 Photoredox Conjugate Addition
11.3.4 Photoredox Rearrangements
11.3.5 Photoredox Cycloadditions
11.3.6 Photoredox Net Oxidations and Reductions
11.3.6.1 Oxidations
11.3.6.2 Reductions
11.4 Electrochemical Methods
11.4.1 Anodic Decarboxylations: Kolbe and Non-Kolbe Reactions
11.4.2 The Shono Oxidation
11.4.3 Electrochemical Reduction of Alkyl Halides
11.4.4 Indirect Electrolysis Reactions
11.4.5 Oxidation and Reduction at Sulfur
Chapter 12 Synthesis of "Nucleophilic" Organometallic Reagents
12.1 Introduction
12.2 Synthesis of "Nucleophilic" Organometallic Reagents
12.2.1 Lithium
12.2.1.1 Deprotonation
12.2.1.2 Metal-Halogen Exchange
12.2.1.3 Metal-Metal Exchange
12.2.2 Boron
12.2.2.1 Hydroboration
12.2.2.2 Metal-Metal Exchange
12.2.2.3 Cross-coupling with R2B-BR2
12.2.2.4 C-H Borylation
12.2.2.5 Other
12.2.3 Magnesium
12.2.3.1 Metal-Halogen Exchange
12.2.3.2 Metal-Metal Exchange
12.2.3.3 Hydromagnesiation
12.2.3.4 Carbomagnesiation
12.2.4 Aluminum
12.2.4.1 Metal-Halogen Exchange
12.2.4.2 Carboalumination
12.2.4.3 Hydroalumination
12.2.4.4 Metal-Metal Exchange
12.2.5 Silicon
12.2.5.1 Metal-Metal Exchange
12.2.5.2 Hydrosilylation
12.2.5.3 Metal-Halogen Exchange
12.2.5.4 C-H Silylation
12.2.5.5 Use of Nucleophilic Silicon Reagents
12.2.6 Titanium
12.2.6.1 Metal-Metal Exchange
12.2.6.2 Other
12.2.7 Chromium
12.2.7.1 Metal-Halogen and Metal-Metal Exchange
12.2.8 Manganese
12.2.8.1 Metal-Metal Exchange
12.2.9 Iron
12.2.9.1 Metal-Halogen Exchange
12.2.10 Copper
12.2.10.1 Metal-Metal Exchange
12.2.11 Zinc
12.2.11.1 Metal-Halogen Exchange
12.2.11.2 Metal-Metal Exchange
12.2.11.3 Other
12.2.12 Zirconium
12.2.12.1 Hydrozirconation
12.2.13 Indium
12.2.14 Tin
12.2.14.1 Metal-Metal Exchange
12.2.14.2 Nucleophilic Sn
12.2.14.3 Cross-coupling with R3Sn-SnR3
12.2.14.4 Hydrostannation
12.2.14.5 Electrophilic Tin
12.2.15 Cerium
12.2.16 Bismuth
12.3 Strategies for Metalating Heterocycles
12.3.1 Strategies for Metalating Five-Membered Heterocycles
12.3.2 Strategies for Metalating Six-Membered Heterocycles
12.4 Reactions of "Nucleophilic" Organometallic Reagents
12.4.1 Uncatalyzed C-M to C-O
12.4.2 Uncatalyzed C-M to C-S or C-Se
12.4.3 Uncatalyzed C-M to C-X
12.4.4 Uncatalyzed C-M to C-N
Chapter 13 Synthesis of Common Aromatic Heterocycles
13.1 Introduction
13.2 Pyrroles
13.2.1 Condensation of 1,4-Dicarbonyls with a Primary Amine
13.2.2 Condensation of 1,3-Dicarbonyls with an -Aminocarbonyl Compound
13.2.3 Dipolar Cycloaddition
13.3 Indoles
13.3.1 Fisher Indole Synthesis
13.3.2 Intramolecular Condensation of Anilines with Phenacyl Derivatives
13.3.3 Cycloelimination of Enamines
13.3.4 Aldol and Michael Additions
13.3.5 Alkylation of an Aniline
13.3.6 Addition of Vinyl Grignard Reagents to Nitrobenzene Derivatives
13.4 2-Indolinones (Oxindoles)
13.4.1 Lactamization
13.4.2 Friedel-Crafts Alkylation
13.4.3 C-H Insertion
13.5 Isatins (2,3-Indolindiones)
13.5.1 Cyclization of Isonitrosoacetanilides
13.5.2 Friedel-Crafts Acylation
13.6 Carbazoles
13.6.1 Oxidation of an Indole
13.6.2 Reductive Cyclization of a Nitro-Biphenyl Derivative
13.7 Pyrazoles
13.7.1 Condensation of a Hydrazine with a 1,3-Dicarbonyl Derivative
13.7.2 Condensation of a Hydrazine with a Michael Acceptor
13.8 Indazoles
13.8.1 Nucleophilic Aromatic Substitution of Arylhydrazones
13.8.2 Diazotization of a Toluidine
13.8.3 Metal-Mediated Cyclization
13.9 Imidazoles and Benzimidazoles
13.9.1 Condensation of a 1,2-Diamine with a Carboxylic Acid
13.9.2 Condensation of an Amidine with a Halocarbonyl Derivative
13.9.3 Condensation of 1,4-Dicarbonyls with an Amine
13.9.4 Condensation of 1,2-Dicarbonyls with an Aldehyde and Ammonia
13.10 1,2,3-Triazoles and Benzotriazole
13.10.1 Dipolar Cycloaddition of Azides with an Alkynes
13.10.2 Dipolar Cycloaddition of Azides with Enolates
13.10.3 Diazaotization of o-Dianilines
13.11 1,2,4-Triazoles
13.11.1 Cyclodehydration
13.12 Tetrazoles
13.12.1 Cycloaddition of an Azide and a Nitrile
13.12.2 Activation of an Amide and Addition of an Azide
13.13 Dihydropyridines
13.13.1 Reaction of Ketoesters and Aldehydes in the Presence of Ammonia
13.13.2 Reaction of Aminocrotonates with Aldehydes and ß-Ketoesters
13.14 Pyridines
13.14.1 Condensation of a 1,3-Dicarbonyl Derivative with a Cyanoacetamide
13.14.2 Condensation of Enolates with Enaminoesters
13.14.3 Condensation of a 1,5-Dicarbonyl Compound with Ammonia
13.15 Quinolines
13.15.1 Friedländer Quinoline Synthesis
13.15.2 Addition to Isatins
13.15.3 Electrophilic Aromatic Substitution
13.15.4 Intramolecular Cyclization of an Iminium Ion
13.16 Quinolinones and 2-Hydroxyquinolines
13.16.1 Electrophilic Cyclization
13.16.2 Intramolecular Aldol Ring Closure
13.16.3 Intramolecular Condensation
13.16.4 Oxidation of a Quinoline
13.17 Isoquinolines
13.17.1 Intramolecular Cyclization of Imidoyl Chlorides
13.17.2 Intramolecular Cyclization of an Oxonium Ion
13.17.3 Condensation of Phenacyl Derivatives with Ammonia
13.18 Isoquinolinones
13.18.1 Benzamide Imine Condensation
13.18.2 Amide Cyclization
13.19 Quinolones (4-Hydroxyquinolines)
13.19.1 Electrophilic Cyclization
13.19.2 Nucleophilic Aromatic Substitution
13.19.3 Intramolecular Claisen Ring Closure
13.20 Pyrimidines and Pyrimidones
13.20.1 Condensation of Amidines with 1,3-Dicarbonyl Derivatives
13.20.2 Condensation of Amidines with Michael Acceptors
13.20.3 Cyclization of Cyano Amides
13.21 Quinazolines and Quinazolinones
13.21.1 Derivatization of Anthranilic Acids
13.21.2 Reaction of Benzonitriles
13.21.3 Intramolecular Condensations
13.21.4 Electrophilic Aromatic Substitution
13.22 Pyrazines and Quinoxalines
13.22.1 Condensation of Dianilines
13.22.2 Condensation of Dicarbonyl Derivatives with Ammonia
13.23 Pyridazines, Phtalazines, and Cinnolines
13.23.1 Addition of Hydrazine to Dicarbonyl Derivatives
13.23.2 Addition to a Diazo Derivative
13.23.3 Electrophilic Aromatic Substitution
13.24 1,2,4-Triazines
13.24.1 Reaction of Amidrazones with Glyoxal Derivatives
13.24.2 Reaction of Nitroanilines with Cyanamide
13.24.3 Reaction of Aminopyrroles
13.25 Furans and Benzofurans
13.25.1 Condensation of 1,3-Dicarbonyls with an &rmalpha
-Halocarbonyl
13.25.2 Cyclodehydration of a 1,4-Dicarbonyl Compound
13.25.3 Dehydration
13.25.4 Metal-Mediated Cyclization
13.26 Benzopyran-4-One (Chromen-4-One, Flavone) and Xanthone
13.26.1 Condensation of ortho-Phenoxy-1,3-dicarbonyl Derivatives
13.26.2 Condensation of ortho-Acylcarbonyl Derivatives
13.26.3 Electrophilic Cyclization
13.26.4 Nucleophilic Aromatic Substitution
13.27 Coumarins
13.27.1 Condensation of ortho-Acylcarbonyl Derivatives
13.27.2 Arylation of Bromobenzoic Acid Derivatives
13.28 Thiophenes and Benzothiophenes
13.28.1 Aldol Condensation
13.28.2 Knoevenagel Condensation
13.28.3 Cyclodehydration of 1,4-Dicarbonyl Derivatives
13.28.4 Nucleophilic Addition to Sulfur Followed by Cyclocondensation
13.29 Isoxazoles and Benzisoxazoles
13.29.1 Hydroxylamine Addition to 1,3-Dicarbonyl Derivatives/Enaminoketones
13.29.2 Alkylation of Dihalides
13.29.3 Dipolar Cycloaddition
13.29.4 Nucleophilic Aromatic Substitution
13.30 Oxazoles and Benzoxazoles
13.30.1 Cyclization on an Activated Carbonyl Derivative
13.30.2 Dipolar Cycloaddition
13.31 Isothiazoles and Benzisothiazoles
13.31.1 Intramolecular Cyclization
13.31.2 Addition to ortho-Thiobenzonitriles
13.32 Thiazoles and Benzothiazoles
13.32.1 Condensation of Thioamides with Haloketones
13.32.2 Condensation of Carboxylic Acid Derivatives with 2-Aminothiols
13.32.3 Nucleophilic Aromatic Substitution
13.33 1,2,4-Oxadiazoles
13.33.1 Condensation of Hydroxyurea with Carboxylic Acids
13.33.2 Condensation of Hydroxyurea with Carboxylic Acid Derivatives
13.34 1,3,4-Oxadiazoles
13.34.1 Cyclodehydration of Hydrazide
13.34.2 Nitrogen Extrusion
Chapter 14 Access to Chirality
14.1 Introduction
14.2 Using the Chiral Pool
14.3 Classical Resolutions
14.3.1 The Family Approach (the Dutch Resolution)
14.3.2 Separation of Covalent Diastereomers
14.3.3 Kinetic Resolutions
14.3.3.1 Resolution of Alcohols
14.3.3.2 Resolution of Amines
14.3.3.3 Resolution of Epoxides
14.4 Dynamic Kinetic Resolutions
14.4.1 Dynamic Kinetic Resolutions via Chemical Reactions
14.4.2 Dynamic Kinetic Resolutions via Crystallization
14.5 Desymmetrization of Meso Compounds
14.6 Chiral Chromatography
Chapter 15 Biocatalysis
15.1 Introduction
15.2 Group Transfer Reactions
15.2.1 Amine Synthesis Catalyzed by Transaminases
15.2.2 Reactions Catalyzed by Hydrolases
15.2.2.1 Chiral Carboxylic Acids and Amides from Esters
15.2.2.2 Acylation of Racemic and Prochiral Alcohols and Amines in Organic Solvents
15.2.2.3 Miscellaneous Hydrolases
15.3 Reductions
15.3.1 Reduction of C=C Bonds
15.3.2 Reductive Amination of &rmalpha
-Ketoacids to &rmalpha
-Amino Acids
15.3.3 Reduction of C=O Bonds
15.3.3.1 Reduction of Ketones and Aldehydes
15.4 Oxidations
15.4.1 Baeyer-Villiger Monoxygenase (BVMO) Oxidations
15.4.2 C-H Oxidations
15.4.3 C=C Oxidations
15.4.4 Alcohol Oxidations
15.4.4.1 Cofactor-Dependent Alcohol Oxidations
15.4.4.2 Cofactor-Independent Alcohol Oxidations
15.4.5 C-N Oxidations
15.5 C-C Bond Forming Reactions
15.5.1 Aldol Reaction
15.5.1.1 Acetaldehyde Aldolases
15.5.1.2 Pyruvate-Dependent Aldolases
15.5.1.3 DHAP Aldolases
15.5.1.4 Threonine Aldolase
15.5.2 Cyanohydrin Formation
15.5.3 Acyloin Condensation
15.6 Future Developments
Chapter 16 Green Chemistry
16.1 Introduction
16.2 Green Chemistry Metrics
16.2.1 Atom Economy (AE)
16.2.2 Reaction Mass Efficiency (RME)
16.2.3 E Factor
16.2.4 Process Mass Intensity (PMI)
16.2.5 Life Cycle Assessment (LCA)
16.2.6 Innovation Green Aspiration Level (iGAL) Methodology
16.3 Solvent and Reagent Selection
16.3.1 Organic Solvent Selection
16.3.2 Aqueous Systems
16.3.3 Classic Reactions in Aqueous Systems
16.4 Green Reactions/Reagents
16.5 Examples of Green Methods and Reagents for Common Reaction Types
16.5.1 Formation of Aryl Amines and Aryl Amides
16.5.2 Carbon-Carbon Bond Formation
16.5.3 Oxidation
16.5.4 Nonprecious Metals Catalysis
16.6 Predictive Tools to Design for Green Chemistry
16.7 Green Chemistry Improvements in Process Development
16.7.1 Pregabalin
16.7.2 Sitagliptin
Chapter 17 Continuous Chemistry
17.1 Introduction
17.2 Aliphatic Nucleophilic Substitutions
17.2.1 Aliphatic Nucleophilic Substitutions at sp3 Carbons
17.2.2 Amidations
17.2.3 Esterification with Diazomethane
17.3 Additions to C-Het Multiple Bonds
17.3.1 Reductive Aminations
17.4 Addition to C-C Multiple Bonds
17.4.1 Cyclopropanation
17.4.2 Hydroformylation
17.4.3 Hydroboration/Oxidation of Olefins
17.5 Nucleophilic Aromatic Substitutions
17.6 Electrophilic Aromatic Substitution
17.6.1 Nitration
17.7 Catalysis
17.8 Rearrangements
17.8.1 Curtius Rearrangement
17.8.2 Claisen Rearrangement
17.8.3 Newman-Kwart Rearrangement
17.8.4 Overman Rearrangement
17.9 Eliminations
17.9.1 Thermal Deprotection of tert-Butyloxycarbonyl (Boc) Amines
17.9.2 Deprotection of t-Butyl Esters
17.10 Reductions
17.10.1 Hydrogenation of Olefins
17.10.2 Hydrogenation of Nitroarenes
17.10.3 Hydrogenolysis
17.11 Oxidations
17.11.1 Aerobic Oxidations
17.11.2 Nonaerobic Oxidation
17.11.3 Dehydrogenation
17.12 Free Radical Reactions
17.12.1 Chemical Initiated Free Radical Reactions
17.12.2 Photochemical Reactions
17.13 Syntheses of Organometallic Reagents
17.13.1 Organolithium
17.13.2 Organomagnesium
17.13.3 Organozinc
17.14 Synthesis of Aromatic Heterocycles
17.14.1 Synthesis of Aromatic Hyterocycles under Superheated Conditions
17.14.2 Heterocycles from Azido or Hydrazine Compounds
17.15 Access to Chirality
17.15.1 Access to Chirality via Asymmetric Hydrogenations
17.16 Biotransformations
Chapter 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
Chapter 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
19.2.1 Heat Transfer
19.2.2 Heat Profiles
19.2.3 Stirring
19.2.4 Homogeneous vs. Heterogeneous Reactions
19.2.5 Electrophilic vs. Nucleophilic Substitution Reactions
19.2.6 Gas Generation
19.2.7 Execution of Energetic Reactions
19.3 Solvents and Reagents
19.3.1 Solvent Selection
19.3.2 Removal of Water from Solvents or Reactions
19.3.3 Solvent Contamination
19.3.4 Reagent Selection and Compatibility
19.3.4.1 Replacements for NaH
19.3.4.2 Use of Hydrides
19.3.4.3 Metal Catalysts
19.3.4.4 Generation of HCl
19.3.4.5 HF
19.3.4.6 NBS
19.3.4.7 Use of POCl3
19.3.4.8 KOH Contamination
19.3.4.9 Material Compatibility
19.4 Isolation
19.4.1 Reaction Workups
19.4.1.1 Extractions
19.4.1.2 Emulsions
19.4.1.3 Workup of Hydrides
19.4.1.4 Workup of POCl3
19.4.1.5 Reduction of Iodine
19.4.1.6 Removal of Ph3PO
19.4.1.7 Removal of Triethylamine
19.4.2 Purification
19.4.2.1 Crystallization
19.4.2.2 Reslurries or Repulping
19.4.2.3 Formation of Salts or Adducts
19.4.2.4 Purging Heavy Metals
19.4.2.5 Silica Gel Purification
19.5 Analysis
19.5.1 Thin Layer Chromatography
19.5.2 High or Ultra High Performance Liquid Chromatography
19.5.3 Supercritical Fluid Chromatography
19.5.4 Gas Chromatography
19.5.5 Nuclear Magnetic Resonance Spectroscopy
Subject Index
Combo Index
EULA

Systemvoraussetzungen

Als PDF speichern Als Link merken