Abstract
Bimolecular homolytic substitution (S(H)2) is an open-shell mechanism that is implicated across a host of biochemical alkylation pathways. Surprisingly, however, this radical substitution manifold has not been generally deployed as a design element in synthetic C–C bond formation. We found that the S(H)2 mechanism can be leveraged to enable a biomimetic sp(3)-sp(3) cross-coupling platform that furnishes quaternary sp(3)-carbon centers, a long-standing challenge in organic molecule construction. This heteroselective radical-radical coupling uses the capacity of iron porphyrin to readily distinguish between the S(H)2 bond-forming roles of open-shell primary and tertiary carbons, combined with photocatalysis to generate both radical classes simultaneously from widely abundant functional groups. Mechanistic studies confirm the intermediacy of a primary alkyl–Fe(III) species prior to coupling and provide evidence for the S(H)2 displacement pathway in the critical quaternary sp(3)-carbon bond formation step.