Photoredox/Nickel Dual Catalysis for C(sp<sup>2</sup>)–C(sp<sup>3</sup>) Cross-Electrophile Coupling Reaction of Mesylates of Phenols and Primary Alcohols
Sayan K. Jana, R. N. Bhattacharya, Purusattam Dey, Sunit Chakraborty, Biplab Maji
Abstract
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.