Photocatalyzed hydrogen atom transfer enables multicomponent olefin oxo-amidomethylation under aerobic conditions

Abstract

The direct functionalization of abundant and readily available feedstock chemicals has emerged as a powerful strategy to rapidly increase molecular complexity and access valuable scaffolds. Herein, we report a novel photocatalyzed three-component oxo-amidomethylation of aromatic olefins under aerobic conditions, enabling the synthesis of N-(γ-oxopropyl)amides via simultaneous incorporation of two orthogonal functional groups across the alkene CC bond in a single step. Mechanistic features include the photocatalyzed hydrogen atom transfer (HAT)-mediated engagement of the α-N-alkyl C(sp³)–H bond in inexpensive, unfunctionalized amide feedstocks and the trapping of a key olefin-derived carbon-centered radical intermediate by molecular oxygen to afford the oxo-functionalized homologated products. This cascade protocol demonstrates compatibility with a broad range of aryl olefins and amides, as well as efficient scalability. The method provides streamlined access to high-value molecular architectures of synthetic and pharmaceutical relevance without the need for pre-functionalized radical precursors.