Fluoride-induced nucleophilic (phenylthio)difluoromethylation of carbonyl compounds with [difluoro(phenylthio)methyl]trimethylsilane (TMS–CF2SPh)

Abstract: A fluoride-induced nucleophilic (phenylthio)difluoromethylation method using TMS–CF2SPh has been achieved. This new methodology efficiently transfers “PhSCF2” group into both enolizable and non-enolizable aldehydes and ketones to give corresponding (phenylthio)difluoromethylated alcohols in good to excellent yields. Diphenyldisulfide can also be (phenylthio)difluoromethylated into PhSCF2SPh in high yield. The reaction with methyl benzoate, however, gives only low yield of (phenylthio)difluoromethyl phenyl ketone. The above-obtained PhSCF2-containing alcohols can be further transformed into difluoromethyl alcohols using an oxidation–desulfonylation procedure. This new type of nucleophilic (phenylthio)difluoromethylation methodology may have other potential applications in the medicinal and agrochemical fields. [Copyright &y& Elsevier]