Direct, Stereoselective Thioglycosylation Enabled by an Organophotoredox Radical Strategy

While strategies involved 2e- transfer pathway have dictated glycosylation development, direct glycosylation of readily accessible glycosyl donors as radical precursors is particularly appealing because of high radical anomeric selectivity and atom- and step-economy. However, the development of the radical process has been challenging owning to notorious competing reduction, elimination and/or SN side reactions of commonly used, labile glycosyl donors. Here we introduce an organophotocatalytic strategy that glycosyl bromides can be efficiently converted into corresponding anomeric radicals by a photoredox mediated HAT catalysis without a transition metal or a directing group and achieve highly anomeric selectivity. The power of this platform has been demonstrated by the mild reaction conditions enabling synthesis of challenging α-1,2-cis-thioglycosides, the tolerance of various functional groups and the broad substrate scope for both common pentoses and hexoses. Furthermore, this general approach is compatible to both sp2 and sp3 sulfur electrophiles and late-stage glycodiversification for total 48 substrates probed.