Nickel-Catalyzed Twofold Conjunctive Coupling via Philicity-Alternating Radical Relay

The formation of multiple and remote C-C bonds remains highly challenging owing to difficulties in reactivity and selectivity control. Herein, we report a nickel-catalyzed twofold conjunctive cross-electrophile coupling that employs an alkene and a 1,3-enyne as conjunctive platforms and alkyl and aryl halides as coupling partners. Through a philicity-alternating radical relay followed by selective radical capture, the reaction enables the formation of three or more C-C bonds. Combined experimental and theoretical investigations provide a rationale for the sequential radical additions to the π systems and the selective capture of a radical intermediate by the nickel catalyst. Furthermore, a five-component coupling showcases the sequential and controlled addition of alkyl and aryl moieties across three conjunctive units, demonstrating the synthetic versatility of the twofold conjunctive coupling.