Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

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