Facile synthesis of α-monofluoromethyl alcohols: Nucleophilic monofluoromethylation of aldehydes using TMSCF(SO2Ph)2

α-Fluoromethyl phenyl sulfone derivatives have been extensively employed in various reactions as versatile fluoromethylating reagents. While nucleophilic monofluoromethylations of aldehydes have been achieved using fluoromethyl phenyl sulfone or fluorobis(sulfonyl)methanes, a facile protocol under mild reaction conditions remains an ardently sought goal. We now report a feasible synthetic approach toward β-monofluorinated alcohols using α-trimethylsilyl-α-fluorobis(phenylsulfonyl)methane [TMSCF(SO2Ph)2, TFBSM] as a novel monofluoromethylating reagent. Initiated by a catalytic amount of fluoride, the reagent can be readily added to a variety of aldehydes providing the desired products in high yields. Computational and kinetic studies have revealed the exceptional lability of the Si–C bond in TFBSM compared with other fluoromethylsilane counterparts.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► α-Trimethylsilyl-α-fluorobis(phenylsulfonyl)methane (TFBSM) is prepared. ► The reagent can be added to various aldehydes. ► Mechanistic studies have rationalized the exceptional lability of the Si–CF bond in TFBSM. ► Natures of Si–CF bonds in a series of fluoromethyl silyl reagents have been investigated.