F<sup>–</sup>-Free Deoxyhydrotrifluoromethylation of α-Keto Esters with Ph<sub>3</sub>P<sup>+</sup>CF<sub>2</sub>CO<sub>2</sub><sup>–</sup>: Synthesis of α–CF<sub>3</sub>-Substituted Esters
Ying Zheng, Yimin Jia, Yuan Yuan, Zhong‐Xing Jiang, Zhigang Yang
Abstract
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 α-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 α-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.