康 · 学术 | Reaction of the Day No. 1769

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

Quansheng Mou,? Yun-Tao Ding,? Pei-Ting Li, Lixin Shan, and Mingxin Liu*

State Key Laboratory of Natural Product Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.

?Q.M. and Y.D. contributed equally to this work.

—ACS Catal. 2026, doi: org/10.1021/acscatal.6c04416

Recommended by Bingbing Chang_MC5

KEY WORDS: photo chemistry, Ni catalysis, C–H oxidative coupling, α-C–H arylation, dehydrogenation  (反应类型), C(sp2)–C(sp2) (成键类型), alcohols, aryl bromides (原料), ketones(产物), hydrogen-atom transfer (其他).

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, Prof. Mingxin Liu et al. 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.

Previous approaches to ketone synthesis (a, b) and this work (c)

Scope of alcohols

Scope of aryl and heteroaryl bromides

Proposed catalytic cycle for the bromine-radical/nickel-catalyzed cross-coupling reaction

Summary and Comments

Prof. Mingxin Liu et al. have developed a visible-light-driven dehydrogenative strategy for the synthesis of aryl alkyl ketones from unprotected primary alcohols and aryl bromides. This method combines bromine-radical HAT and nickel catalysis to merge α-C–H arylation with secondary-alcohol dehydrogenation in a single catalytic manifold, thereby avoiding preoxidation to aldehydes, stoichiometric oxidants, hydrogen acceptors, and preformed organometallic reagents. The reaction proceeds under ambient conditions and exhibits broad functional-group tolerance. Furthermore, late-stage functionalization of complex molecules and the expedited preparation of pharmacologically relevant compounds demonstrate the synthetic utility of this protocol. Mechanistic experiments and DFT calculations support a radical relay pathway involving selective formation of ketyl radicals and secondary alcohol intermediates, rather than a dominant aldehyde/acyl-radical route. By establishing primary alcohols as native ketone-building partners in metallaphotoredox catalysis, this work provides a mild and modular platform for aryl alkyl ketone synthesis and is expected to inspire further development of alcohol-based dehydrogenative cross-couplings.