Photoredox-Catalyzed Trifunctionalization of β,γ-Unsaturated Ketones Enabled by Four-Component 1,2-Carbonyl Migration/Radical-Polar Crossover Cascade.

We report an unprecedented photoredox-catalyzed four-component cascade reaction of β,γ-unsaturated ketones with bromodifluoroalkyl compounds, nitriles and water. Merging 1,2-carbonyl migration and radical-polar crossover, this protocol delivers a variety of valuable fluorine-containing acetamides and features broad substrate compatibility, including natural product and pharmaceutical skeletons. Gram-scale synthesis, product derivatization and AIE properties are demonstrated. Mechanistic control experiments including radical trapping, deuterium labeling, and luminescence quenching studies collectively support a catalytic cycle involving photoinduced single-electron transfer, intramolecular 1,2-carbonyl migration, and subsequent ionic nucleophilic capture through radical-polar crossover.