Diastereoselective Radical Cascade via Dowd–Beckwith-Type Ring Expansion: Modular Assembly of Fused Carbocycles

Abstract We report an unprecedented radical-promoted cascade reaction of vinyl cycloalkanone carboxylates with aromatic aldehydes, featuring a benzoylation/ring-expansion/oxa-cyclization cascade that enables rapid access to functionalized cis-fused carbocycles with high diastereoselectivity. This transformation proceeds through the formation of two C–C bonds and one C–O bond, generating quaternary and tertiary stereocenters as a single diastereomer in good to excellent yields. The strategy represents a novel dimension of the Dowd–Beckwith-type reaction by incorporating a benzoyl group that not only facilitates ring expansion but also actively participates in the subsequent intramolecular cyclization with the β-keto radical. Mechanistic investigations, supported by DFT calculations, are consistent with a radical-mediated pathway and provide insight into the origin of the observed diastereoselectivity. Further, this method offers a versatile platform for the synthesis of complex fused carbocyclic scaffolds.