Synthesis of aryl α,α-difluoroethyl thioethers a novel structure motif in organic chemistry, and extending to aryl α,α-difluoro oxyethers

Abstract

A method for the preparation of aryl α,α-difluoroethyl thioethers (ArSCF₂CH₃) is reported and the synthesis approach is extended to aryl α,α-difluoroethyl oxygen ethers. Selected building blocks are further elaborated in cross-coupling reactions and are incorporated into analogues of established trifluoromethyl ether drugs. Conformations are explored and log P studies of these motifs indicate that they are significantly more polar than their trifluoromethyl ether analogues rendering them attractive for bioactives discovery.