Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

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 Introduction2 Trimethyl(trifluoromethyl)silane (Me3SiCF3)3 (Difluoromethyl)trimethylsilane (Me3SiCF2H)3.1 Nucleophilic Addition3.2 Nucleophilic Substitution3.3 Nucleophilic Difluoromethylation of Electron-Deficient Hetero­cycles3.4 Metal-Mediated Cross Coupling3.5 Oxidative Coupling of Terminal Alkynes4 Post-functionalizable Difluoromethyl Transfer Reagents4.1 (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 Others6 Conclusions