Ligand-Controlled Zinc Catalysis for Selective Transformations of Alcohols

The direct functionalization of readily available biomass-derived alcohols offers an sustainable route in modern synthetic chemistry to access value-added compounds, yet achieving precise product selectivity through catalyst or reaction condition control remains a formidable challenge. To address this, a ligand-controlled Zn-amide catalytic system is reported that enables effective and mild chemodivergent transformations of alcohols to distinct molecular scaffolds, either ketone or ester, via discrete radical pathways, for the first time to the best of our knowledge. In this design, the tetrahedral zinc center templates two amide ligands for facile intramolecular electron transfer, enabling a radical-mediated catalytic process. Notably, the present protocol enables the formation of α-alkylated ketones via homocoupling of primary benzyl alcohols and further extends to the one-pot synthesis of unsymmetrical α-alkylated or α-branched ketones through cross-coupling between different alcohols, a transformation not achieved directly from alcohol. The developed protocols feature mild reaction conditions, broad substrate scope, high chemoselectivity, and tolerance toward various functional groups, and the synthetic utility is further highlighted by the late-stage diversification of heterocyclic frameworks and pharmaceutically relevant drug derivatives. Finally, thorough mechanistic investigations including intermediate trapping, control experiments, and DFT studies provided key insights into the underlying reaction pathways that underpin the observed chemodivergence.