Photo-Induced Stereoselective Synthesis of C-Glycosides via Conformation-Locked Glycosyl Radical Coupling

<i>C</i>-glycosides are crucial scaffolds in the development of carbohydrate-based drugs, owing to their favorable pharmacological properties and metabolic stability. However, the stereoselective synthesis of specific anomers under mild conditions remains a significant challenge, particularly for the β-anomer. In this study, we developed a visible-light-mediated, photocatalyst- and metal-free strategy for the stereoselective synthesis of β-alkyl <i>C</i>-glycosides via radical coupling. The pivot of this methodology is the utilization of bulky silyl-protected 2,3,5,6-tetrafluoropyridin-4-ylthio (SPyf) glycosyl precursors, which induce a conformational flip to the ¹C₄-chair form, thereby overriding the inherent bias of the radical intermediates. This operationally simple method exhibits high stereoselectivity and functional group tolerance and is particularly efficient for the synthesis of β-configured <i>C</i>-xylopyranosides.