Manganese-Catalyzed α-Alkylation of Ketones with Unactivated Secondary Alcohols: A Sustainable Route to β-Branched Ketones.

Herein, we report a series of phosphine-free, bench-stable, and cost-effective Mn(II)-salen complexes (Mn-ph, Mn-di-F, and Mn-di-Me) as precatalysts for the α-alkylation of aromatic ketones with unactivated secondary alcohols via a hydrogen autotransfer (HA) strategy. Among the synthesized catalysts, the simple phenyl-bridged complex Mn-ph exhibited excellent catalytic activity, while electronic modifications on the phenyl diimine bridge (di-F and di-Me) failed to enhance the efficiency, indicating an insignificant role of further electronic tuning at the phenyl diimine bridge of salen complexes in this reaction. The Mn-ph-catalyzed protocol enables the efficient synthesis of β-branched carbonyl compounds in moderate to excellent yields under base-assisted conditions. A broad scope of secondary alcohols, including cyclic, acyclic, benzylic, and heterocyclic variants, has been successfully employed as alkylating agents to produce the β-disubstituted ketones. The steric bulk on the aryl moiety of the ketone was found to play a decisive role in suppressing self-condensation and minimizing undesired in situ carbonyl reduction. Control experiments and preliminary mechanistic studies provided evidence supporting the operation of an HA mechanism. Notably, the reaction proceeds with good selectivity and generates water as the byproduct, rendering the protocol environmentally benign.