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

Abstract

The radical relay provides an effective paradigm for intermolecular assembly to achieve functionalization across remote chemical bonds. Herein, we report the first radical relay 1,3carbocarbonylation of α-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 1,3carbocarbonylation products. The plausible mechanism is investigated through a series of control experiments, including radical trapping, radical clock experiments, critical intermediate trapping, and 18 O labeling experiment.