Stereoselective Synthesis of N–O-Linked α-<i>N</i>-Acetylgalactosaminoglycosides via Oxime <i>O</i>-Glycosylation with 2-Nitrogalactals

GalNAc-type <i>O</i>-glycosylation is an essential post-translational modification that plays fundamental roles in various biological processes. N-O-linked glycosidic linkages are desirable and practical mimetics of native <i>O</i>-glycosidic bonds. However, efficient construction of α-aminooxy GalNAc linkages remains challenging. Herein, we present a highly stereoselective oxime <i>O</i>-glycosylation of 2-nitroglycal promoted by a substoichiometric amount of <i>t</i>-BuOLi, enabling efficient access to a broad spectrum of N-O-linked α-GalNAc glycosides. This approach features an excellent yield and α-selectivity, broad substrate scope, and easy scalability. The synthetic applications of this method are illustrated by the late-stage glycosylation of structurally complex drug molecules and diverse precise synthetic transformations.