Science of Synthesis

Science of Synthesis is the authoritative and comprehensive reference work for the entire field of organic and organometallic synthesis.

Science of Synthesis presents the important synthetic methods for all classes of compounds and includes:

Methods critically evaluated by leading scientists

Background information and detailed experimental procedures

Schemes and tables which illustrate the reaction scope

Preface

As our understanding of the natural world increases, we begin to understand complex phenomena at molecular levels. This level of understanding allows for the design of molecular entities for functions ranging from material science to biology. Such design requires synthesis and, as the structures increase in complexity as a necessity for specificity, puts increasing demands on the level of sophistication of the synthetic methods. Such needs stimulate the improvement of existing methods and, more importantly, the development of new methods. As scientists confront the synthetic problems posed by the molecular targets, they require access to a source of reliable synthetic information. Thus, the need for a new, comprehensive, and critical treatment of synthetic chemistry has become apparent. To meet this challenge, an entirely new edition of the esteemed reference work Houben–Weyl Methods of Organic Chemistry will be published starting in the year 2000.

To reflect the new broader need and focus, this new edition has a new title, Science of Synthesis, Houben–Weyl Methods of Molecular Transformations. Science of Synthesis will benefit from more than 90 years of experience and will continue the tradition of excellence in publishing synthetic chemistry reference works. Science of Synthesis will be a balanced and critical reference work produced by the collaborative efforts of chemists, from both industry and academia, selected by the editorial board. All published results from journals, books, and patent literature from the early 1800s until the year of publication will be considered by our authors, who are among the leading experts in their field. The 48 volumes of Science of Synthesis will provide chemists with the most reliable methods to solve their synthesis problems. Science of Synthesis will be updated periodically and will become a prime source of information for chemists in the 21st century.

Science of Synthesis will be organized in a logical hierarchical system based on the target molecule to be synthesized. The critical coverage of methods will be supported by information intended to help the user choose the most suitable method for their application, thus providing a strong foundation from which to develop a successful synthetic route. Within each category of product, illuminating background information such as history, nomenclature, structure, stability, reactivity, properties, safety, and environmental aspects will be discussed along with a detailed selection of reliable methods. Each method and variation will be accompanied by reaction schemes, tables of examples, experimental procedures, and a background discussion of the scope and limitations of the reaction described.

The policy of the editorial board is to make Science of Synthesis the ultimate tool for the synthetic chemist in the 21st century.

We would like to thank all of our authors for submitting contributions of such outstanding quality, and, also for the dedication and commitment they have shown throughout the entire editorial process.

The Editorial Board

October 2000

D. Bellus (Basel, Switzerland)

E. N. Jacobsen (Cambridge, USA)

S. V. Ley (Cambridge, UK)

R. Noyori (Nagoya, Japan)

M. Regitz (Kaiserslautern, Germany)

P. J. Reider (New Jersey, USA)

E. Schaumann (Clausthal-Zellerfeld, Germany)

I. Shinkai (Tsukuba, Japan)

E. J. Thomas (Manchester, UK)

B. M. Trost (Stanford, USA)

Volume 19: Three Carbon–Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives

Preface

Table of Contents

Introduction

S.-I. Murahashi

19.1 Product Class 1: Nitrile Oxides, Sulfides, and Selenides

S. Kanemasa

19.2 Product Class 2: Nitrile Imines

S. Kanemasa

19.3 Product Class 3: Nitrilium Salts

S. Kanemasa

19.4 Product Class 4: Nitrile Ylides

S. Kanemasa

19.5 Product Class 5: Nitriles

L. R. Subramanian

19.5.1 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Free Starting Material

L. R. Subramanian

19.5.2 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Containing Starting Material

L. R. Subramanian

19.5.3 Introduction of the Cyano Group by Substitution of Hydrogen

A. Schmidt

19.5.4 Introduction of the Cyano Group by Substitution of Metals

L. R. Subramanian

19.5.5 Introduction of the Cyano Group by Substitution of a Halogen

L. R. Subramanian

19.5.6 Introduction of the Cyano Group by Substitution of Oxygen Functions

L. R. Subramanian

19.5.7 Introduction of the Cyano Group by Substitution of Sulfur Functions

L. R. Subramanian

19.5.8 Introduction of the Cyano Group by Substitution of Nitrogen Functions

L. R. Subramanian

19.5.9 Introduction of the Cyano Group by Addition to a Carbonyl Group

M. North

19.5.10 Introduction of the Cyano Group by Addition to an Imino Group

M. North

19.5.11 Introduction of the Cyano Group by Conjugate Addition

J. Podlech

19.5.12 Introduction of the Cyano Group by Addition to Alkynes

J. Podlech

19.5.13 Introduction of the Cyano Group by Addition to Alkenes

J. Podlech

19.5.14 Synthesis from Nitriles with Retention of the Cyano Group

S.-I. Murahashi

19.5.15 Applications of Nitriles as Reagents for Organic Synthesis with Loss of the Nitrile Functionality (Including Cycloaddition Reactions)

S. J. Collier and P. Langer

19.6 Product Class 6: Phosphaalkynes (Alkylidynephosphines)

U. BergstralSer

19.7 Product Class 7: Isocyanides and Related Compounds

M. Suginome and Y. Ito

Keyword Index

Author Index

Abbreviations

Table of Contents

Introduction

S.-I. Murahashi

Introduction

19.1 Product Class 1: Nitrile Oxides, Sulfides, and Selenides

S. Kanemasa

19.1 Product Class 1: Nitrile Oxides, Sulfides, and Selenides

19.1.1 Product Subclass 1: Nitrile Oxides

19.1.1.1 Synthesis of Product Subclass 1

19.1.1.1.1 Method 1: Dehydrohalogenation of Hydroximoyl Halides

19.1.1.1.2 Method 2: Dehydration of Activated Nitroalkanes and Nitroalkenes

19.1.1.1.3 Method 3: Halogenation/Dehydrohalogenation of Aldoximes

19.1.1.1.4 Method 4: Dehydration of Nitroalkanes (The Mukaiyama Reaction)

19.1.1.1.5 Method 5: Oxidation of Aldoximes

19.1.1.1.6 Method 6: Thermolysis of 1,2,5-Oxadiazole 2-Oxides (Furoxans)

19.1.1.1.7 Methods 7: Miscellaneous Methods

19.1.2 Product Subclass 2: Nitrile Sulfides

19.1.2.1 Synthesis of Product Subclass 2

19.1.2.1.1 Method 1: Thermolysis of 1,3,4-Oxathiazol-2-ones

19.1.2.1.1.1 Variation 1: Thermolysis of 1,3,4-Oxathiazoles

19.1.3 Product Subclass 3: Nitrile Selenides

19.2 Product Class 2: Nitrile Imines

S. Kanemasa

19.2 Product Class 2: Nitrile Imines

19.2.1 Synthesis of Product Class 2

19.2.1.1 Method 1: Dehydrohalogenation of Hydrazonoyl Halides

19.2.1.2 Method 2: Oxidation of Hydrazones

19.2.1.3 Methods 3: Miscellaneous Methods

19.2.1.3.1 Variation 1: From a Lithiated Diazomethane

19.2.1.3.2 Variation 2: Thermolysis or Photolysis of Heterocycles

19.3 Product Class 3: Nitrilium Salts

S. Kanemasa

19.3 Product Class 3: Nitrilium Salts

19.3.1 Synthesis of Product Class 3

19.3.1.1 Method 1: Dehydration of Oximes

19.3.1.2 Method 2: N-Alkylation of Nitriles

19.3.1.3 Method 3: Generation of Nitrilium Salts in Ring-Closure and Rearrangement Reactions Leading to Heterocycles

19.3.1.4 Method 4: Synthesis from Triazenyl Chlorides and Dialkylcyanamides

19.4 Product Class 4: Nitrile Ylides

S. Kanemasa

19.4 Product Class 4: Nitrile Ylides

19.4.1 Synthesis of Product Class 4

19.4.1.1 Method 1: Dehydrochlorination of Imidoyl Chlorides

19.4.1.2 Method 2: Preparation of Nitrile Ylide Equivalents

19.4.1.3 Method 3: Reaction of Nitriles with Carbenes

19.4.1.4 Method 4: Photolysis of Azirines

19.4.1.5 Methods 5: Miscellaneous Methods

19.5 Product Class 5: Nitriles

L. R. Subramanian

19.5 Product Class 5: Nitriles

19.5.1 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Free Starting Material

L. R. Subramanian

19.5.1 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Free Starting Material

19.5.1.1 Transformation of an Aldehyde Group

19.5.1.1.1 Method 1: One-Pot Reactions Involving Intermediate Aldimines

19.5.1.1.1.1 Variation 1: By Copper-Catalyzed Oxidation

19.5.1.1.1.2 Variation 2: By Nickel-Catalyzed Oxidation

19.5.1.1.1.3 Variation 3: By Oxidation with Manganese(IV) Oxide

19.5.1.1.1.4 Variation 4: By Oxidation with Ammonium Cerium(IV) Nitrate

19.5.1.1.1.5 Variation 5: By Oxidation with Iodine

19.5.1.1.1.6 Variation 6: By Oxidation with Hydrogen Peroxide

19.5.1.1.2 Method 2: Reactions Involving Intermediate Oximes

19.5.1.1.2.1 Variation 1: Using Boron Trifluoride–Diethyl Ether Complex

19.5.1.1.2.2 Variation 2: Using 4-Toluenesulfonic Acid

19.5.1.1.2.3 Variation 3: Using Acetic Anhydride

19.5.1.1.2.4 Variation 4: Using Phthalic Anhydride

19.5.1.1.2.5 Variation 5: Using 1-Methylpyrrolidin-2-one

19.5.1.1.2.6 Variation 6: Using Pyridine/Formamide

19.5.1.1.2.7 Variation 7: Using Sodium Iodide

19.5.1.1.2.8 Variation 8: By Dehydration with Triphosgene

19.5.1.1.2.9 Variation 9: By Treatment with Iron(II) Chloride Modified Montmorillonite K 10

19.5.1.1.2.10 Variation 10: Using Dry Alumina

19.5.1.1.2.11 Variation 11: By Using Microwaves

19.5.1.1.3 Methods 3: Miscellaneous Methods

19.5.1.1.3.1 Variation 1: Using S, S-Dimethylsulfurdiimide as Iminating Agent

19.5.1.1.3.2 Variation 2: Using Sodium Azide/Aluminum Trichloride

19.5.1.2 Transformation of a Carboxylic Acid or Derivatives

19.5.1.2.1 Method 1: Transformation of Carboxy Groups

19.5.1.2.2 Method 2: Transformation of Carboxylic Ester Groups

19.5.1.2.3 Method 3: Transformation of Carboxylic Acid Halides

19.5.2 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Containing Starting Material

L. R. Subramanian

19.5.2 Construction of the Cyano Group by Functional-Group Transformation from a Nitrogen-Containing Starting Material

19.5.2.1 Method 1: Synthesis from Hydrazones

19.5.2.1.1 Variation 1: By Alkylation Followed by Basic Cleavage

19.5.2.1.2 Variation 2: By Oxidation Reactions

19.5.2.1.3 Variation 3: By Microwave-Assisted Oxidation with Oxone

19.5.2.2 Method 2: Synthesis from Aldoximes

19.5.2.2.1 Variation 1: By Microbial Dehydration of Aldoximes

19.5.2.2.2 Variation 2: By Chemical Dehydration at Room Temperature

19.5.2.2.3 Variation 3: By Thermal Dehydration with Suitable Reagents

19.5.2.2.4 Variation 4: By Microwave Irradiation

19.5.2.3 Method 3: Synthesis from O-Substituted Aldoximes

19.5.2.4 Method 4: Synthesis from Primary Carboxamides and Thioamides

19.5.2.5 Method 5: From Miscellaneous Nitrogen-Containing Carbonyl and Carboxy Derivatives

19.5.3 Introduction of the Cyano Group by Substitution of Hydrogen

A. Schmidt

19.5.3 Introduction of the Cyano Group by Substitution of Hydrogen

19.5.3.1 Synthesis of Heteroaromatic and Aromatic Cyanides

19.5.3.1.1 Method 1: Using Cyanogen Bromide

19.5.3.1.2 Method 2: Using Tosyl Cyanide

19.5.3.1.2.1 Variation 1: By Modified Reissert Reactions

19.5.3.1.3 Method 3: Using Trimethylsilyl Cyanide

19.5.3.1.3.1 Variation 1: By Modified Reissert–Henze Reaction

19.5.3.1.3.2 Variation 2: By Catalytic Asymmetric Reissert-Type Reactions

19.5.3.1.4 Method 4: Using Trichloroacetonitrile

19.5.3.1.5 Method 5: Using Chlorosulfonyl Isocyanate

19.5.3.1.6 Method 6: Using Ethyl (Triphenylphosphoranylidene)carbamate/Boron Trifluoride

19.5.3.1.7 Method 7: Using Triphenylphosphine/Thiocyanogen

19.5.3.1.8 Method 8: Using Acetone Cyanohydrin

19.5.3.1.9 Method 9: Using Diethyl Cyanophosphonate

19.5.3.1.10 Method 10: Using Tetranitromethane

19.5.3.1.11 Method 11: Using Viehe’s Reagent

19.5.3.1.12 Method 12: By Anodic Substitution

19.5.3.1.13 Method 13: By Modified Vilsmeier–Haack Reactions

19.5.3.1.14 Method 14: Oxidative Cyanation of Quinoline 1-Oxides with Potassium Cyanide in the Presence of Potassium Hexacyanoferrate(III)

19.5.3.1.15 Method 15: By Nucleophilic Aromatic Substitution of Hydrogen with Cyanides

19.5.3.2 Synthesis of Acetylenic Nitriles

19.5.3.2.1 Method 1: Using Copper(I) Cyanide

19.5.3.2.1.1 Variation 1: In the Presence of Chlorotrimethylsilane

19.5.3.2.1.2 Variation 2: In the Presence of Bis(trimethylsilyl) Peroxide

19.5.3.2.2 Method 2: Using Tosyl Cyanide and Zinc(II) Iodide

19.5.3.2.3 Method 3: Using Phenyl Cyanate

19.5.3.2.4 Method 4: Using 1H-Imidazole-1-carbonitrile

19.5.3.3 Synthesis of Vinyl Nitriles

19.5.3.3.1 Method 1: Using Cyanogen Bromide and Cyanogen Chloride

19.5.3.3.2 Method 2: Using Tosyl Cyanide

19.5.3.3.3 Method 3: Using Phenyl Cyanates

19.5.3.3.4 Method 4: Using Triphenylphosphine/Thiocyanogen

19.5.3.4 Synthesis of Aliphatic Nitriles

19.5.3.4.1 Method 1: Using 2,3-Dichloro-5,6-dicyanobenzo-1,4-quinone and Trimethylsilyl Cyanide

19.5.3.4.2 Method 2: By Aerobic Ruthenium-Catalyzed Oxidative Cyanation with Sodium Cyanide

19.5.3.4.3 Method 3: Using Chlorine Dioxide and Sodium Cyanide

19.5.3.4.4 Method 4: By Anodic Cyanation

19.5.3.4.5 Method 5: Using 2-Chlorobenzyl Thiocyanate

19.5.3.4.6 Method 6: Using Sulfonyl Cyanides

19.5.3.4.7 Method 7: Using 1,2-Benziodoxole-1-carbonitriles

19.5.3.4.8 Method 8: Using Phenyl Cyanate

19.5.3.4.9 Method 9: Starting from N-Oxides of Tertiary Amines with Trifluoroacetic Acid Anhydride and Cyanide

19.5.4 Introduction of the Cyano Group by Substitution of Metals

L. R. Subramanian

19.5.4 Introduction of the Cyano Group by Substitution of Metals

19.5.4.1 Method 1: From Organozinc Compounds

19.5.4.2 Method 2: From Organocopper Compounds

19.5.4.3 Method 3: From Organomagnesium Compounds

19.5.4.4 Method 4: From Organolithium Compounds

19.5.4.5 Method 5: From Other Organometallic Compounds

19.5.5 Introduction of the Cyano Group by Substitution of a Halogen

L. R. Subramanian

19.5.5 Introduction of the Cyano Group by Substitution of a Halogen

19.5.5.1 Method 1: From Aliphatic and Alicyclic Halides

19.5.5.2 Method 2: From Vinyl and Alkynyl Halides

19.5.5.3 Method 3: From Aryl Halides

19.5.5.3.1 Variation 1: Using Copper(I) Cyanide

19.5.5.3.2 Variation 2: Using Alkali Metal Cyanides

19.5.5.3.3 Variation 3: By Palladium- and Nickel-Catalyzed Substitutions

19.5.5.3.4 Variation 4: By Microwave-Assisted Cyanations

19.5.5.3.5 Variation 5: By Electrophilic Cyanation

19.5.5.4 Method 4: From Heterocyclic Halides

19.5.6 Introduction of the Cyano Group by Substitution of Oxygen Functions

L. R. Subramanian

19.5.6 Introduction of the Cyano Group by Substitution of Oxygen Functions

19.5.6.1 Method 1: Substitution of a Hydroxy Group in a One-Pot Procedure

19.5.6.2 Method 2: Substitution of Hydroxy Derivatives

19.5.6.2.1 Variation 1: Displacement of Alkyl Sulfonates

19.5.6.2.2 Variation 2: Displacement of Alkenyl Sulfonates

19.5.6.2.3 Variation 3: Displacement of Aryl Sulfonates

19.5.6.3 Method 3: Substitution of a Carbonyl Group by Direct Displacement

19.5.7 Introduction of the Cyano Group by Substitution of Sulfur Functions

L. R. Subramanian

19.5.7 Introduction of the Cyano Group by Substitution of Sulfur Functions

19.5.7.1 Method 1: Displacement of a Sulfanyl Group

19.5.7.2 Method 2: Displacement of a Sulfonyl Group

19.5.8 Introduction of the Cyano Group by Substitution of Nitrogen Functions

L. R. Subramanian

19.5.8 Introduction of the Cyano Group by Substitution of Nitrogen Functions

19.5.8.1 Method 1: By Replacement of Amines

19.5.8.1.1 Variation 1: From Aliphatic and Alicyclic Amines

19.5.8.1.2 Variation 2: From Aromatic Amines

19.5.8.2 Method 2: By Replacement of a Nitro Group

19.5.8.3 Method 3: By Fragmentation and Rearrangement Reactions

19.5.8.3.1 Variation 1: From Beckmann Fragmentation of Oximes and Derivatives

19.5.8.3.2 Variation 2: Miscellaneous Reactions

19.5.9 Introduction of the Cyano Group by Addition to a Carbonyl Group

M. North

19.5.9 Introduction of the Cyano Group by Addition to a Carbonyl Group

19.5.9.1 Cyanohydrins Derived from Aldehydes

19.5.9.1.1 Method 1: Addition without External Stereocontrol

19.5.9.1.2 Method 2: Addition to Achiral Substrates in the Presence of a Chiral Catalyst

19.5.9.1.2.1 Variation 1: Use of (R)-Oxynitrilase Enzymes

19.5.9.1.2.2 Variation 2: Use of (S)-Oxynitrilase Enzymes

19.5.9.1.2.3 Variation 3: Use of Cyclic Dipeptides as Catalysts

19.5.9.1.2.4 Variation 4: Use of Chiral Titanium Complexes as Catalysts

19.5.9.1.2.5 Variation 5: Use of Chiral Aluminum Complexes as Catalysts

19.5.9.1.2.6 Variation 6: Use of Other Chiral Metal Complexes as Catalysts

19.5.9.2 Cyanohydrins Derived from Ketones

19.5.9.2.1 Method 1: Addition without External Stereocontrol

19.5.9.2.2 Method 2: Addition to Achiral Substrates in the Presence of a Chiral Catalyst

19.5.9.2.2.1 Variation 1: Use of Oxynitrilase Enzymes

19.5.9.2.2.2 Variation 2: Use of Metal-Based Catalysts

19.5.9.2.2.3 Variation 3: Use of Chiral Lewis Bases

19.5.10 Introduction of the Cyano Group by Addition to an Imino Group

M. North

19.5.10 Introduction of the Cyano Group by Addition to an Imino Group

19.5.10.1 ±-Aminonitriles Derived from Aldimines

19.5.10.1.1 Method 1: Addition without Stereocontrol

19.5.10.1.1.1 Variation 1: Strecker Reactions under Aqueous Conditions

19.5.10.1.1.2 Variation 2: Strecker Reactions under Nonaqueous Conditions

19.5.10.1.1.3 Variation 3: Using Trimethylsilyl Cyanide

19.5.10.1.1.4 Variation 4: Addition of Cyanide to Aldimines Derived from Chiral Aldehydes

19.5.10.1.2 Method 2: Addition to Substrates Containing a Chiral Auxiliary on the Nitrogen Atom

19.5.10.1.2.1 Variation 1: Use of (1-Phenylethyl)amine

19.5.10.1.2.2 Variation 2: Use of 2-Phenylglycinol

19.5.10.1.2.3 Variation 3: Use of Phenylglycinamide

19.5.10.1.2.4 Variation 4: Use of Sugar-Derived Auxiliaries

19.5.10.1.2.5 Variation 5: Use of an ±-Aminonitrile as a Chiral Auxiliary

19.5.10.1.3 Method 3: Addition to Achiral Substrates in the Presence of a Chiral Catalyst

19.5.10.1.3.1 Variation 1: Use of Nonmetallic Catalysts

19.5.10.1.3.2 Variation 2: Catalysis by Aluminum Complexes

19.5.10.1.3.3 Variation 3: Catalysis by First-Row Transition-Metal Complexes

19.5.10.1.3.4 Variation 4: Catalysis by Zirconium Complexes

19.5.10.2 ±-Aminonitriles Derived from Ketimines

19.5.10.2.1 Method 1: Addition without Stereocontrol

19.5.10.2.1.1 Variation 1: Use of Ultrasound

19.5.10.2.1.2 Variation 2: Using Trimethylsilyl Cyanide

19.5.10.2.1.3 Variation 3: Other Addition Reactions

19.5.10.2.2 Method 2: Addition to Substrates Containing a Chiral Auxiliary on the Nitrogen Atom

19.5.10.3 Products Derived from Other Compounds Containing a C=N Bond

19.5.10.3.1 Method 1: Products Derived from Hydrazones

19.5.10.3.1.1 Variation 1: Processes Using Trimethylsilyl Cyanide

19.5.10.3.1.2 Variation 2: Reaction under Phase-Transfer Conditions

19.5.10.3.2 Method 2: Products Derived from Nitrones

19.5.10.3.3 Method 3: Products Derived from Sulfinimines

19.5.10.3.4 Method 4: Products Derived from Oximes

19.5.11 Introduction of the Cyano Group by Conjugate Addition

J. Podlech

19.5.11 Introduction of the Cyano Group by Conjugate Addition

19.5.11.1 Method 1: Hydrocyanation of ±,²-Unsaturated Carbonyl Compounds

19.5.11.1.1 Variation 1: Using Alkali Metal Cyanides

19.5.11.1.2 Variation 2: Using Acetone Cyanohydrin

19.5.11.1.3 Variation 3: Using Trimethylsilyl Cyanide

19.5.11.1.4 Variation 4: Using Dialkylaluminum Cyanide or Hydrogen Cyanide/ Trialkylaluminum Compounds

19.5.11.1.5 Variation 5: Using Organic Isocyanides

19.5.12 Introduction of the Cyano Group by Addition to Alkynes

J. Podlech

19.5.12 Introduction of the Cyano Group by Addition to Alkynes

19.5.12.1 Method 1: Hydrocyanation of Alkynes

19.5.12.2 Method 2: Addition of Trimethylsilyl Cyanide or Tributylstannanecarbonitrile to Alkynes

19.5.12.2.1 Variation 1: Addition to Terminal Arylalkynes

19.5.12.2.2 Variation 2: Addition to Ynamines

19.5.13 Introduction of the Cyano Group by Addition to Alkenes

J. Podlech

19.5.13 Introduction of the Cyano Group by Addition to Alkenes

19.5.13.1 Method 1: Hydrocyanation of Alkenes and Arylalkenes

19.5.13.1.1 Variation 1: Hydrocyanation of Alkenes

19.5.13.1.2 Variation 2: Hydrocyanation of Arylalkenes

19.5.13.2 Method 2: Hydrocyanation of Conjugated and Isolated Dienes

19.5.13.3 Method 3: Enantioselective Hydrocyanation of Alkenes

19.5.14 Synthesis from Nitriles with Retention of the Cyano Group

S.-I. Murahashi

19.5.14 Synthesis from Nitriles with Retention of the Cyano Group

19.5.14.1 Method 1: Reaction of ±-Cyano Carbanions with Electrophiles

19.5.14.1.1 Variation 1: Alkylation by Alkyl Halides

19.5.14.1.2 Variation 2: Alkylation by Alcohols

19.5.14.1.3 Variation 3: Alkylation by Organoboranes

19.5.14.1.4 Variation 4: Reaction with Epoxides

19.5.14.1.5 Variation 5: Reaction with Carboxylic Acid Derivatives

19.5.14.1.6 Variation 6: Reaction with Carbonyl Compounds (Aldol Reaction)

19.5.14.1.7 Variation 7: Reaction of Active Methylene Compounds Bearing a Cyano Group with Carbonyl Compounds (Knoevenagel Reaction)

19.5.14.1.8 Variation 8: Reaction with Alkenes and Alkynes Bearing Electron-Withdrawing Groups (Michael Addition)

19.5.14.1.9 Variation 9: Reaction with Nitriles (Thorpe–Ziegler Reaction)

19.5.14.2 Method 2: Wittig Reaction

19.5.14.3 Method 3: Reaction of Organozinc Compounds Bearing Cyano Groups with Electrophiles

19.5.14.4 Method 4: Reaction of Organocopper Compounds Bearing Cyano Groups with Electrophiles

19.5.14.5 Method 5: Addition of Radicals Bearing Cyano Groups by Reductive Coupling

19.5.14.6 Method 6: Friedel–Crafts Reaction

19.5.14.7 Method 7: Addition of Carbenes Bearing Cyano Groups

19.5.14.8 Method 8: Addition to Alkenenitriles

19.5.14.8.1 Variation 1: Conjugate Addition of Ketone and Ester Enolates to Alkenenitriles (Cyanoethylation)

19.5.14.8.2 Variation 2: Conjugate Addition of Enamines to Alkenenitriles (Cyanoethylation)

19.5.14.8.3 Variation 3: Conjugate Addition of Metalated Nitriles to Alkenenitriles

19.5.14.8.4 Variation 4: Conjugate Addition of Metalated Nitroalkanes and Metalated Sulfones and Sulfoxides to Alkenenitriles

19.5.14.8.5 Variation 5: Addition of Diazonium Salts to Alkenenitriles (Meerwein Reaction)

19.5.14.8.6 Variation 6: Conjugate Addition of Grignard Reagents to Alkenenitriles

19.5.14.8.7 Variation 7: Conjugate Addition with Organocopper Reagents

19.5.14.8.8 Variation 8: Conjugate Addition with Organozinc Reagents

19.5.14.8.9 Variation 9: Nickel-Catalyzed Addition to Alkenenitriles

19.5.14.8.10 Variation 10: Palladium-Catalyzed Addition to Benzylidenemalononitrile

19.5.14.8.11 Variation 11: Conjugate Addition of Allylsilanes to Alkenenitriles

19.5.14.8.12 Variation 12: Conjugate Addition of Thiols to Alkenenitriles

19.5.14.8.13 Variation 13: Conjugate Addition of Amines to Alkenenitriles

19.5.14.8.14 Variation 14: Cyanoselenation of Alkenes

19.5.14.8.15 Variation 15: [2+2] Cycloadditions of Alkenenitriles

19.5.14.8.16 Variation 16: 1,3-Dipolar Cycloadditions

19.5.14.8.17 Variation 17: The Diels–Alder Reaction

19.5.14.8.18 Variation 18: Dimerization and Condensation of Nitriles

19.5.14.9 Method 9: Metal-Catalyzed Reaction of Alkenes Bearing Cyano Groups.

19.5.14.9.1 Variation 1: The Heck–Mizoroki Reaction

19.5.14.9.2 Variation 2: Palladium-Catalyzed Allylation of Nitriles

19.5.14.9.3 Variation 3: Catalytic Dimerization of Propenenitrile

19.5.14.9.4 Variation 4: Metathesis Reaction of Alkenenitriles

19.5.14.9.5 Variation 5: Ruthenium-Catalyzed Addition of Alcohols to Alkenenitriles

19.5.14.10 Method 10: Addition to Alkynenitriles

19.5.14.11 Method 11: Metal-Catalyzed Cross-Coupling Reactions

19.5.14.11.1 Variation 1: Cross Coupling Using Organozinc Compounds Bearing Cyano Groups

19.5.14.11.2 Variation 2: Cross Coupling of Organoboranes with Organic Halides

19.5.14.11.3 Variation 3: Cross Coupling Using Organotin Compounds

19.5.14.11.4 Variation 4: Cross Coupling Using Organosilicon Compounds

19.5.14.11.5 Variation 5: Direct Catalytic Arylation of Cyanoesters

19.5.14.12 Method 12: Reduction of Alkenenitriles

19.5.14.13 Method 13: Oxidation of Nitrile Compounds

19.5.14.14 Method 14: Synthesis of Polycyano Compounds

19.5.15 Applications of Nitriles as Reagents for Organic Synthesis with Loss of the Nitrile Functionality (Including Cycloaddition Reactions)

S. J. Collier and P. Langer

19.5.15 Applications of Nitriles as Reagents for Organic Synthesis with Loss of the Nitrile Functionality (Including Cycloaddition Reactions)

19.5.15.1 Method 1: Base-Mediated One-Pot Reactions of Nitriles

19.5.15.2 Method 2: Nitriles as Reagents in Reactions of Three or More Components

19.5.15.2.1 Variation 1: Reactions with One Nitrile Molecule

19.5.15.2.2 Variation 2: Reactions with Two Nitrile Molecules

19.5.15.2.3 Variation 3: Reactions with Three or More Nitrile Molecules

19.5.15.3 Method 3: Cycloaddition Reactions

19.5.15.3.1 Variation 1: [2+2+2]-Self-Cyclotrimerization Reactions

19.5.15.3.2 Variation 2: [2+2+2]-Cyclotrimerization Reactions of Nitriles and Alkynes

19.5.15.3.3 Variation 3: [4+2]-Cycloaddition Reactions

19.5.15.3.4 Variation 4: [3 +2]-Cycloaddition Reactions

19.5.15.3.5 Variation 5: [2 +2]-Cycloaddition Reactions

19.6 Product Class 6: Phosphaalkynes (Alkylidynephosphines)

U. BergstralSer

19.6 Product Class 6: Phosphaalkynes (Alkylidynephosphines)

19.6.1 Synthesis of Product Class 6

19.6.1.1 Method 1: Elimination of Hydrogen Halides

19.6.1.1.1 Variation 1: From Alkyldichlorophosphines

19.6.1.1.2 Variation 2: From Substituted (Dihalomethyl)phosphines

19.6.1.2 Method 2: Elimination of Organometallic Compounds

19.6.1.2.1 Variation 1: Of Chlorotrimethylsilane

19.6.1.2.2 Variation 2: Of Hexamethyldisiloxane

19.6.1.2.3 Variation 3: Of Lithium Trimethylsilanolate

19.6.1.3 Method 3: Rearrangement of Halophosphaalkenes

19.6.1.4 Method 4: Rearrangement of Alkynylphosphines

19.6.1.5 Method 5: Rearrangement of Phosphiranes or Allylphosphines by Flash-Vacuum Pyrolysis

19.6.1.6 Method 6: Rearrangement of 1-Aza-3-phosphaallenes

19.6.1.7 Methods 7: Other Methods

19.6.2 Applications of Product Class 6 in Organic Synthesis

19.6.2.1 Method 1: Cycloaddition Reactions of Phosphaalkynes

19.6.2.1.1 Variation 1: [2+1] Cycloadditions

19.6.2.1.2 Variation 2: [3+2] Cycloadditions

19.6.2.1.3 Variation 3: [4+2] Cycloadditions

19.6.2.2 Method 2: 1,2-Addition Reactions of Phosphaalkynes

19.6.2.2.1 Variation 1: Addition of Enophiles

19.6.2.2.2 Variation 2: Addition of Organometallic Groups

19.6.2.3 Method 3: Phosphaalkynes as Ligands in Transition-Metal Complexes

19.6.2.4 Method 4: Cyclooligomerization Reactions of Phosphaalkynes

19.7 Product Class 7: Isocyanides and Related Compounds

M. Suginome and Y. Ito

19.7 Product Class 7: Isocyanides and Related Compounds

19.7.1 Product Subclass 1: Carbon-Bound Isocyanides

19.7.1.1 Synthesis of Product Subclass 1

19.7.1.1.1 Method 1: Nucleophilic Substitution of Halides with Metal Cyanides

19.7.1.1.1.1 Variation 1: From Halides and Equivalents

19.7.1.1.1.2 Variation 2: From Epoxides and Oxetanes

19.7.1.1.2 Method 2: Reduction of Isocyanates and Related Compounds

19.7.1.1.3 Method 3: Reduction of Carbamates

19.7.1.1.4 Method 4: Dehalogenation of Isocyanide Dihalides

19.7.1.1.5 Method 5: Dehydration of Formamides

19.7.1.1.5.1 Variation 1: With Phosgene

19.7.1.1.5.2 Variation 2: With Trichloromethyl Chloroformate (Diphosgene)

19.7.1.1.5.3 Variation 3: With Bis(trichloromethyl) Carbonate (Triphosgene)

19.7.1.1.5.4 Variation 4: With Thionyl Chloride/Dimethylformamide (Vilsmeier Reagent)

19.7.1.1.5.5 Variation 5: With Phosphoryl Chloride

19.7.1.1.5.6 Variation 6: With Arenesulfonyl Chlorides

19.7.1.1.5.7 Variation 7: With Other Reagents

19.7.1.1.6 Method 6: By ±-Elimination Reactions Involving Fragmentation of Heterocyclic Compounds

19.7.1.1.7 Method 7: Addition of Cyanides to Alkenes

19.7.1.1.8 Method 8: Reaction of Dihalocarbenes with Primary Amines

19.7.1.1.9 Method 9: From Other Isocyanides through Their ±-Anions

19.7.1.1.9.1 Variation 1: Reaction with Alkyl Halides and Epoxides

19.7.1.1.9.2 Variation 2: Reaction with Carbonyl Compounds and Michael Acceptors

19.7.1.1.9.3 Variation 3: Elimination and C=C Transposition Reactions

19.7.1.2 Applications of Product Subclass 1 in Organic Synthesis

19.7.1.2.1 Method 1: Simple ±-Additions

19.7.1.2.1.1 Variation 1: Addition of Brønsted Acids

19.7.1.2.1.2 Variation 2: Addition of Hydrogen-Heteroatom Bonds and Heteroatom-Heteroatom Bonds

19.7.1.2.1.3 Variation 3: Addition of Metal Hydrides and Bimetals

19.7.1.2.1.4 Variation 4: Addition of Organometallic Compounds

19.7.1.2.1.5 Variation 5: Oxidative ±-Additions Including the Addition of Halogen-Containing Reagents

19.7.1.2.1.6 Variation 6: Addition of Acid Chlorides and Related Compounds

19.7.1.2.1.7 Variation 7: Synthesis of Heteroaromatic Compounds by Intramolecular ±-Addition Reactions of ortho-Functionalized Aryl Isocyanides

19.7.1.2.1.8 Variation 8: Addition to π-Systems (Including Aromatic Compounds)

19.7.1.2.2 Method 2: Cyclizations Utilizing Isocyanides as One-Carbon Donors

19.7.1.2.3 Method 3: The Passerini Reaction and Ugi Reaction: Multicomponent Couplings by an ±-Addition Reaction

19.7.1.2.3.1 Variation 1: The Passerini Reaction: Synthesis of ±-Acyloxycarboxamides by the Three-Component Coupling of an Isocyanide, a Carbonyl Compound, and a Carboxylic Acid

19.7.1.2.3.2 Variation 2: The Ugi Reaction: Synthesis of ±-Acylaminocarboxamides by the Four-Component Coupling of an Isocyanide, a Carbonyl Compound, an Amine, and a Carboxylic Acid

19.7.1.2.4 Method 4: Cycloadditions via ±-Isocyanomethyl Anions

19.7.1.2.5 Method 5: Transition-Metal Catalysis Involving Activation of C-H Bonds ± to the Isocyano Group

19.7.1.2.6 Method 6: Oligomerization and Polymerization

19.7.1.2.6.1 Variation 1: Of Monoisocyanides

19.7.1.2.6.2 Variation 2: Of Diisocyanides

19.7.1.2.7 Method 7: Reactions Accompanied by Cleavage of the C-NC Linkage: Isomerization to Nitriles and Removal of the Isocyano Group

19.7.1.2.8 Method 8: Use of Transition-Metal Complexes of Isocyanide as Catalysts

19.7.2 Product Subclass 2: Oxygen-, Sulfur-, Nitrogen-, and Phosphorus-Bound Isocyanides

19.7.2.1 Synthesis of Product Subclass 2

19.7.2.1.1 Method 1: Dehydration

19.7.2.1.2 Method 2: Fragmentation of Heterocyclic Compounds

19.7.2.1.3 Methods 3: Miscellaneous Methods

Keyword Index

Author Index

Abbreviations

Introduction

S.-I. Murahashi

This volume covers the synthesis of compounds with three carbon–heteroatom bonds which include nitrile oxides, nitrile sulfides, nitrile imines, nitrilium salts, nitrile ylides, nitriles, phosphaalkynes, and carbon- and heteroatom-bound isocyanides. These are shown in ▶ Table 1, together with the sections in which they appear.

▶ Table 1 Structures and Nomenclature for the Three Carbon-Heteroatom Bond Containing Compounds Covered in Volume 19

Product Class | Structural Formula | Section
nitrile oxides | R¹C≡N⁺–O⁻ | 19.1.1
nitrile sulfides | R¹C≡N⁺–S⁻ | 19.1.2
nitrile imines | R²C≡N⁺–N⁻R¹ | 19.2
nitrilium salts | R²C≡N⁺–R¹ | 19.3
nitrile ylides | r²C≡N⁺–C⁻R¹ | 19.4
nitriles | R¹ C≡N | 19.5
phosphaalkynes | R¹C≡P | 19.6
isocyanides | R¹N=C | 19.7.1
heteroatom-bound isocyanides | YN=C(Y = N, s, O, P) | 19.7.2

References to reviews on these specific functional groups are given in each section. Discussion of each specific group is generally subdivided into methods that have been selected as the most useful for the preparation of the product class or subclass in question. Each method is presented separately as follows:

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!