Electrochemical C(sp3)–C(sp3) cross-coupling of alcohols

Abstract

The preparation of C(sp3)–C(sp3) bonds is of great importance for the construction of molecular frameworks found in pharmaceuticals and natural products. Alkyl alcohols, which are commercially available and naturally abundant alkylation precursors, offer direct conversion into C(sp3)-rich molecules by C(sp3)–C(sp3) cross-coupling, however, such transformations remain challenging in synthesis due to the inertness of the C(sp3)–O bond. Here we report a modular, versatile and selective electrochemical strategy that achieves C(sp3)–C(sp3) cross-coupling of alkyl alcohols by means of a doubly dehydroxylative cross-coupling process under nickel catalysis. The highly selective cross-coupling strategy eliminates the need for prefunctionalization of alcohols, providing a general platform for the modification of hydroxyl-containing bioactive molecules. This protocol demonstrates good functional group compatibility and is well-suited for late-stage functionalization, with the potential to streamline the synthesis of pharmaceuticals and drug analogues that would typically necessitate multi-step processes.