Unified Photocatalytic Strategy for the Cross-Coupling of Alcohols with Aryl Halides Enabled by Synergistic Nickel and Iron LMCT Catalysis

The use of alcohol feedstock as a coupling partner in cross-coupling reactions offers an extraordinary potential for the efficient synthesis of Csp3-rich complex molecular scaffolds. This prominent strategy relies on the generation of alkoxy radicals, which can react via various radical pathways to give carbon-centered radicals that can be engaged in C–C bond formation reactions. However, cross-coupling reactions involving catalytic generation of alkoxy radicals directly from native alcohols are highly challenging and the scope of existing catalytic methods remains particularly limited. Moreover, a unified strategy that can incorporate a broad range of alcohols in catalytic cross-coupling with aryl halides is currently unavailable. Herein, we report a general photocatalytic platform that combines nickel and iron ligand-to-metal charge transfer (LMCT) catalysis for the selective deconstructive Csp3–Csp3 bond cleavage and arylation of various unactivated alcohols. This protocol leverages the ability of photoinduced iron LMCT catalysis to generate radicals from diversely substituted alcohols, enabling implementation of various C–C bond-forming manifolds. These include dehydroxymethylative arylation of aliphatic alcohols, remote arylation of cyclic alcohols to yield alkyl ketones, and the methylation of aryl halides using tertiary alcohols as the methyl radical source. This methodology offers a practical and unified strategy for engaging a large variety of commercially available alcohols in cross-coupling reactions under mild conditions, using abundant nickel and iron catalysts. Mechanistic studies, including stoichiometric organometallic chemistry and cyclic voltammetry, provide insights into the crucial role of the ancillary ligand surrounding the iron catalyst in stabilizing both low- and high-valent iron catalytic intermediates.