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

ABSTRACT 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.