Stereoselective <i>O</i> ‐ and <i>N</i> ‐Glycosylation Catalyzed by Simple Pyridinium Tetrafluoroborate Using Trichloroacetimidate Donors

The sustainable development of efficient and stereocontrolled catalytic strategies for the synthesis of biologically relevant glycosides is of paramount importance in modern glycoscience. Herein, we report an operationally simple and scalable catalytic system employing an easily accessible, highly stable, and inexpensive pyridinium tetrafluoroborate salt as an effective organocatalyst for the stereoselective synthesis of β-O- and N-glycosides. The protocol utilizes readily available glycosyl trichloroacetimidates (TCAs) as donors and accommodates a broad range of aliphatic alcohols (including sugar and non-sugar derivatives) as well as challenging arylamines as acceptors, delivering the corresponding O- and N-glycosides in good to excellent yields with high to exclusive β-anomeric selectivity under mild reaction conditions. Mechanistic investigations suggest that the catalyst facilitates selective glycosylation through non-covalent interactions (NCIs) between catalyst and acceptor, which contribute to both donor activation and stereochemical control. The utility and robustness of the methodology are further demonstrated through gram-scale synthesis and the construction of trisaccharide.