F--Free Deoxyhydrotrifluoromethylation of alpha-Keto Esters with Ph3P+CF2CO2-: Synthesis of alpha-CF3-Substituted Esters

摘要

Trifluoromethylated compounds are usually obtained via trifluoromethylation reaction by the use of CF3SiMe3 and NaSO2CF3, Umemoto's and Togni's reagents. Here, an external fluorine anion-free direct deoxyhydrotrifluoromethylation of alpha-keto esters with a difluoromethylating reagent has been achieved, in which the employment of water can promote the dissociation of the CF2 group to form a CF3 moiety, which provides the successful transformation. The current protocol demonstrates one of the most practical approaches to generate alpha-trifluoromethyl esters with a broad substrate scope and high functional group compatibility, in which it is applicable to late-stage modification of biologically active compounds and can be readily scaled up. Mechanistic investigation reveals that an in situ-generated gem-difluoroalkene intermediate is decomposed by water, giving rise to acid fluoride and HF.