Visible-Light-Driven Dehydrogenative Ketone Synthesis from Unprotected Primary Alcohols and Aryl Bromides

Abstract Owing to their widespread natural abundance, alcohols are regarded as highly attractive coupling partners in organic synthesis. Although O–H or C–O activating cross-couplings of alcohols have been well-established in distinct contexts, the direct C–H oxidative coupling of alcohols to form ketones remains rare. Herein, we disclose a visible-light-driven, bromine-radical-mediated hydrogen-atom-transfer/nickel relay that enables the direct conversion of unprotected primary alcohols and aryl bromides to aryl alkyl ketones under ambient conditions. The transformation merges selective α-C–H arylation of alcohols with in situ dehydrogenation of the resulting secondary alcohol intermediates, thereby accomplishing C–C bond formation and ketone formation in one catalytic manifold without an exogenous stoichiometric oxidant or hydrogen acceptor. The protocol is compatible with simple and functionalized primary alcohols, aryl and heteroaryl bromides, as well as complex fragments relevant to late-stage diversification, delivering 80 ketone products in up to 91% yield. Combined mechanistic experiments and density functional theory calculations support a pathway initiated by bromine-radical-mediated hydrogen-atom transfer to generate ketyl radicals, followed by nickel-catalyzed arylation and dehydrogenation of the resulting secondary alcohol intermediates to furnish the ketone products. This work establishes native primary alcohols as practical ketone-building partners in metallaphotoredox catalysis and offers a mild and efficient cross-coupling strategy for the direct transformation of alcohols to ketones.