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

alpha-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 beta-monofluorinated alcohols using alpha-trimethylsilyl-alpha-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. (C) 2011 Elsevier B.V. All rights reserved.