Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

Dedicated to Professor Herbert Mayr on the occasion of his 70^th birthday

Abstract

There have been significant developments in the area of perfluoroalkyl group transfer using silicon reagents, specifically in nucleo­philic trifluoromethylation. The mild and versatile activation conditions bestow significant synthetic prowess to the silicon reagents in the area of fluoroalkylations. Owing to the importance of difluoromethylene (CF₂) containing compounds in pharmaceuticals, materials, and agrochemicals, several CF₂ group transfer methods using related silicon reagents have been developed and studied in detail. This review summarizes the recent developments and trends in this area.

1 Introduction

2 Trimethyl(trifluoromethyl)silane (Me₃SiCF₃)

3 (Difluoromethyl)trimethylsilane (Me₃SiCF₂H)

3.1 Nucleophilic Addition

3.2 Nucleophilic Substitution

3.3 Nucleophilic Difluoromethylation of Electron-Deficient Hetero­cycles

3.4 Metal-Mediated Cross Coupling

3.5 Oxidative Coupling of Terminal Alkynes

4 Post-functionalizable Difluoromethyl Transfer Reagents

4.1 (Chlorodifluoromethyl)trimethylsilane (Me₃SiCF₂Cl)

4.2 (Bromodifluoromethyl)trimethylsilane (Me₃SiCF₂Br)

4.3 [Difluoro(iodo)methyl]trimethylsilane (Me₃SiCF₂I)

4.4 [Difluoro(phenylthio)methyl]trimethylsilane (Me₃SiCF₂SPh)

4.5 [Difluoro(phenylsulfonyl)methyl]trimethylsilane (Me₃SiCF₂SO₂Ph)

4.6 Diethyl [Difluoro(trimethylsilyl)methyl]phosphonate [Me₃SiCF₂P(O)(OEt)₂]

4.7 Ethyl Difluoro(trimethylsilyl)acetate (Me₃SiCF₂CO₂Et)

4.8 Difluoro(trimethylsilyl)acetamides (Me₃SiCF₂CONR₂)

4.9 Difluoro(trimethylsilyl)acetonitrile (Me₃SiCF₂CN)

5 Others

6 Conclusions

Key words

difluoromethylation - difluoromethylenation - silicon reagents - fluoroalkylation

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