Solvent-less Dehydrogenative C–H Etherification with Alcohols Using Mechanochemistry

The aromatic C–H bond etherification with alcohols is one of the most atom-efficient ways to construct aryl ethers. However, it often requires a large excess of alcohols as etherification reagents, which limits the substrate scope (especially for the valuable alcohols). Herein, an alternative mechanochemical C–H bond etherification of oximes with diverse primary and secondary alcohols was developed for the first time. Given the solvent-less condition of ball milling technique, the amount of alcohols used in this chemistry has been significantly reduced (1.5–3.0 equiv to the substrates), thus enabling the incorporation of a wide range of alcohols in the C–H bond etherification for the first time. The present mechanochemical protocol enhances the application prospect of the cross dehydrogenative C–H etherification strategy in the late-stage synthesis of complex aromatic ethers.