Nickel-Catalyzed O-Alkylisourea-Enabled Electrochemical Radical C(sp³)-C(sp²) Cross-Coupling

The development of efficient methods to employ naturally abundant alcohol derivatives as C(sp³) precursors for deoxygenative carbon-carbon (C-C) cross-coupling holds significant value for expanding sp³-enriched chemical space. While progress has been made in this area, the field lacks readily accessible, bench-stable alkylation reagents capable of undergoing reductive activation to generate alkyl radicals. Herein, we report an electroreductive nickel-catalyzed system for efficient C(sp³)-C(sp²) radical cross-coupling between aryl electrophiles (halides, triflates, tosylates, and boronic acids) and O-alkylisoureas as radical progenitors. This protocol demonstrates broad substrate scope with good functional group compatibility. Its synthetic utility is highlighted through the preparation of beclobrate analogs and bifonazole, as well as late-stage functionalization of bioactive compounds. Mechanistic investigations support a radical cross-coupling pathway for this transformation.