Enantioselective Radical Cascade Cyclization to Axially Chiral Medium‐Sized Lactones

We report a synergistic photoredox/copper‐catalyzed radical cascade cyclization for the enantioselective synthesis of axially chiral medium‐sized lactones. Compared with conventional ionic pathways that require stringent polarity matching and substrate prefunctionalization, the present strategy employs alkyl halides as radical precursors, wherein photoredox mediated single electron transfer (SET) generates radicals that undergo radical addition to non‐polarized alkenes followed by C–O bond formation. High stereocontrol and efficiency are achieved through a carboxylate‐coordinated chiral copper complex (up to 83% yield, up to 96% e.e., >20:1 d.r.). The synthetic utility is demonstrated by the late‐stage diversification of bioactive molecules. Theoretical calculations reveal that the stereodetermining step occurs during C–O bond formation, and that thermodynamic stability facilitates a central‐to‐axial chirality relay, thereby governing axial stability in the flexible seven‐membered scaffolds.