Excited-State Palladium-Catalyzed α-Selective -Ketonylation.

-Glycosides are important carbohydrate mimetics found in natural products, bioactive compounds, and marketed drugs. However, stereoselective preparation of this class of glycomimetics remains a significant challenge in organic synthesis. Herein, we report an excited-state palladium-catalyzed α-selective -ketonylation strategy using readily available 1-bromosugars to access a range of -glycosides. The reaction features excellent -selectivity and mild conditions that tolerate a wide range of functional groups and complex molecular architectures. The resulting α-ketonylsugars can serve as versatile precursors for their β-isomers and other -glycosides. Preliminary experimental and computational studies of the mechanism suggest a radical pathway involving the formation of palladoradical and glycosyl radical that undergoes polarity-mismatched coupling with silyl enol ether, affording the desired α-ketonylsugars. Insight into the reactivity and mechanism will inspire new reaction development and provide straightforward access to both α- and β--glycosides, greatly expanding the chemical and patent spaces of glycomimetics.