Reductive Couplings Via Nucleophilic Photoactivation of Carbonyls

The umpolung reaction of carbonyls and unsaturated systems is a powerful strategy for the synthesis of aliphatic alcohols. Despite significant advances in the field, the coupling of aliphatic carbonyls with unsaturated molecules remains a critical challenge. Herein, we present how a novel catalytic activation mode for aliphatic carbonyl compounds enables the development of a mild and general platform for reductive couplings. Central to this process is the formation of a hemiaminal intermediate with a nucleophilic phenothiazine catalyst, which releases alkyl ketyl radicals via photolysis upon absorption of visible light. Our protocol is distinguished by its mild reaction conditions, wide substrate scope and broad applicability, including unprecedented transformations such as on-DNA couplings, synthesis of Z-allylic alcohols using aromatic alkynes and the challenging reaction between ketones and unactivated alkynes.