Leveraging B(C6F5)3-catalyzed hydroxyl protection for unlocking O-glycosylation

Here, we report a mild, metal-free, and highly efficient catalytic strategy using B(C6F5)3 for both hydroxyl protection and direct O-glycosylation. This method enables the facile installation of tetrahydropyranyl (THP) protecting groups under exceptionally mild conditions (30°C) and, in a key advancement, directly facilitates O-glycosylation with high efficiency. The protocol exhibits broad functional-group tolerance and substrate generality across a wide range of aliphatic alcohols, phenols, and complex molecular scaffolds, including serine derivatives and natural products such as cholesterol. Its synthetic utility is further demonstrated through a concise, gram-scale preparation of salidroside. By operating under mild and metal-free conditions, this B(C6F5)3-catalyzed approach provides a powerful and sustainable tool for glycosyl-conjugate synthesis, bridging protective group chemistry with glycosidic bond formation.