The radical-radical cross-coupling of alkyl carboxylic acids and organoborons

Abstract

Carbon–carbon bond-forming reactions are fundamental in organic synthesis. Radical–radical cross-coupling stands out as a key strategy for carbon–carbon bond formation, especially for C(sp3)–C(sp3) bonds, to construct complex, three-dimensional, value-added molecules. Existing approaches for direct radical–radical cross-coupling involve a persistent radical and a transient radical to leverage the persistent radical effect. Kolbe electrolysis is one of the few methods that directly cross-couples two transient radicals via electro-oxidative activation of carboxylic acids. However, the direct cross-coupling of transient radicals from two distinct radical precursors, such as carboxylic acids and boronic acids, remains challenging. Here we integrate redox-matched alternating-polarity electrolysis with controlled activation of redox-active species to enable the cross-coupling of alkyl carboxylic acids with alkyl boronic acids. In addition, we demonstrate the synthetic utility and versatility of this transformation by showcasing homocoupling reactions and net carboxylic acid–alkene cross-coupling via in situ alkene hydroboration, as well as tandem processes with Suzuki coupling and Buchwald–Hartwig amination.