Palladium-Catalyzed Synthesis of S-Glycosides Via Stereoretentive Cross-Coupling.

S-Glycosides represent a valuable class of biomolecules owing to their exceptional hydrolytic stability, diverse biological activities, and broad applications in natural product synthesis and glycomimetic design. Here, we present a novel and efficient method for the stereospecific synthesis of S-glycosides via cross-coupling, introducing for the first time a sugar aryl thioether as an electrophilic coupling partner. Our strategy focuses on developing an easily accessible, odorless, and bench-stable S-linked tetrazole glycosyl donor via a one-pot synthesis from free sugar, which subsequently serves as a strong electrophilic coupling partner with boronic acid. The reactivity and versatility of this reaction are demonstrated in over 30 examples, including different monosaccharides and disaccharides. Furthermore, the synthetic utility was highlighted by the synthesis of thiosugar analogues of ipragliflozin and dapagliflozin.