Difluoromethylation and trifluoromethylation reagents derived from tetrafluoroethane β-sultone: Synthesis, reactivity and applications

Tetrafluoroethane beta-sultone (TFES) has hundreds of useful fluorinating derivatives as reagents. The reactions of TFES with nucleophiles provide a variety of interesting fluoroalkylsulfonic acids and their derivatives, as well as omega-halo-perfluoropentanesulfonyl fluorides. Fluorosulfonyldifluoroacetic acid derivatives such as FSO2CF2COOH, FSO2CF2COOMe, FSO2CF2COOTMS, HCF2SO2R (R=F, OH, OCF2H, OC6H5), ICF2SO2F, and RCF2OCF2CF2SO2F (R=CF2I, CO2Me, CO2Na) are versatile difluoromethylation and/or trifluoromethylation reagents. FSO2CF2COOH, FSO2CF2COOMe, FSO2CF2COOTMS, HCF2SO2R, and ICF2SO2F can effectively incorporate a CF2 group into O-H, N-H, S-H, C=C, and C C bonds. HCF2SO2R (R=OH, OCF2H, OC6F5) and FSO2CF2CO2H generate difluorocarbene under acidic conditions, which significantly expanded the scope of the carbene-based difluoromethylation reactions. FSO2CF2CO2Me, FSO2CF2I, and RCF2OCF2CF2SO2F (R=CF2I, CO2Me, CO2Na) are powerful trifluoromethylation reagents, with FSO2CF2CO2Me being world-renowned and widely used in the design of drug candidates and synthesis of novel functional materials. FSO2CF2CO2Me, FSO2CF2I, and RCF2OCF2CF2SO2F are generally produced by nucleophilic substitution, thermal decomposition, or single-electron transfer mechanism in trifluoromethylation reactions under mild conditions. FSO2CF2CF2OCF2CO2Me can successfully trifluoromethylate unactivated aryl chlorides with CuI, and FSO2CF2CF2OCF2CO2 K/CuI can smoothly transform aryl halides at very low temperature. For more than half a century's development, the chemistry of TFES and its derivatives has been extensively studied. This review recounts the recent progress of TFES and reports on TFES-derived difluoromethylation and trifluoromethylation reagents. The syntheses and reactivities of these interesting reagents, as well as their applications in medicinal chemistry and materials science, are briefly summarized. (C) 2013 Elsevier B.V. All rights reserved.