Abstract

   Due to the importance of difluoromethylene unit incorporation in medicinal chemistry, increasing attention has been paying to the development of methodologies for the efficient and diversified syntheses of the molecules with this unit. Herein, we report a highly regioselective and stereoselective hydrocarboxylation of gem-difluoroallenes with carboxylic acids via the intermediacy of allylic palladium species. This reaction exhibits a broad substrate scope accommodating various synthetically versatile functional groups. By applying the protocol, we have achieved the late-stage modification of a series of drugs and bioactive molecules, and successfully developed a range of potential molecules with difluoromethylene units, providing a novel platform for future drug discovery.