Copper-Catalyzed Radical Relay 1,3-Carbocarbonylation across Two Distinct C=C Bonds

The radical relay provides an effective paradigm for intermolecular assembly to achieve functionalization across remote chemical bonds. Herein, we report the first radical relay 1,3-carbocarbonylation of alpha-carbonyl alkyl bromides across two separate C=C bonds. The reaction is highly chemo- and regioselective, with two C(sp(3))-C(sp(3)) bonds and one C=O bond formed in a single orchestrated operation. In addition, the synthesis method under mild conditions and using inexpensive copper as the catalyst allows facile access to structurally diverse 1,3-carbocarbonylation products. The plausible mechanism is investigated through a series of control experiments, including radical trapping, radical clock experiments, critical intermediate trapping, and O-18 labeling experiment.