Photoredox/Nickel Dual Catalysis for C(sp2)-C(sp3) Cross-Electrophile Coupling Reaction of Mesylates of Phenols and Primary Alcohols

Introducing alkyl groups, particularly through innovative C(sp(2))-C(sp(3)) bond-forming methods utilizing abundant feedstocks, holds promise for expanding chemical space, especially in drug discovery programs. Herein, we employed biomass-derived abundant phenols and unactivated aliphatic alcohols as the coupling partners for C(sp(2))-C(sp(3)) cross-electrophile coupling reactions. Our innovation involved activating both the coupling partner via the same activator and designing a catalytic system that activates stronger bonds while ensuring cross-selectivity. The visible-light photoredox/nickel dual catalytic systems accommodate a large substrate scope tolerating diverse functional groups. Besides, both the activation and cross-coupling reactions could be performed in one pot, and the reaction could be scaled up. The method was also executed for iterative cross-coupling and applied for the late-stage functionalization of drug molecules, highlighting their synthetic applicability. Preliminary mechanistic studies involving luminescence quenching, cyclic voltammetry, radical quenching, and radical clock studies elucidated the proposed reaction mechanism.