Copper-Mediated Oxidative Chloro- and Bromodifluoromethylation of Aliphatic Alcohols

The synthesis of chloro- and bromodifluoromethyl alkyl ethers remained a fundamental challenge in synthetic chemistry. Herein we report the efficient and direct synthesis of chloro- and bromodifluoromethyl alkyl ethers through copper-mediated oxidative chrolo- and bromodifluoromethylation of aliphatic alcohols with difluorocarbene-reagents. This difluorocarbene-involved oxidative coupling protocol exhibited broad functional group compatibility and was applicable to a wide range of primary and secondary alcohols.