Strained Ion Pair Interactions-Driven Anion-Assisted Concerted Addition of Ketoximes/Aldoximes and Hydroxamic Acids to Glycals

Oximes and hydroxylamides are notable for their role as coupling partners in organic synthesis. However, their direct application as acceptors in O-glycosylation with glycal donors remains largely unexplored. Herein, we introduce a novel 2-deoxy glycosylation method for synthesizing N–O linked glycosides facilitated by sterically strained 2,4,6-tri-tert-butylpyridinium salts. This approach offers a broad substrate range, high tolerance for functional groups, and easy scalability, resulting in glycosyl oximes and glycosyloxyamines with exclusive α-selectivity and excellent yields. The effectiveness of this method is showcased through functionalization of glycosylated products, late-stage modification of bioactive drug molecules, and disaccharide synthesis. This innovative strategy offers an alternative route and holds promise for wide-ranging applications in the construction of bioactive N–O-linked glycosides in the future. The unique catalytic mechanism by the sterically hindered pyridinium salt has been studied via 1H NMR, IR, UV–vis, and fluorescence studies.