Synthesis of α-hydroxy-β,β-difluoro-γ-ketoesters via [3,3]sigmatropic rearrangements

Abstract

Readily available γ,γ-difluorinated allylic alcohols obtained from trifluoroethanol were esterified efficiently. Exposure to strong base (LDA) afforded the ester enolates, in which chelation both controlled configuration and stabilised against fragmentation, which were trapped as their silyl ketene acetals. Rearrangement occurred to afford base-sensitive acid products. Esterification under mild conditions afforded the purifiable methyl esters in which the masked ketone had been released. Educts with either a benzyloxy or an allyloxy group at the α-position could be deprotected releasing the alcohols.