Stereodivergent Organocatalytic Glycosylation of 2-Deoxyglycosides

The stereocontrolled construction of glycosidic linkages from 2-deoxyglycoside donors remains a major challenge in the synthesis of complex oligosaccharides. Herein, we report catalyst-controlled glycosylation protocols that deliver either anomer on demand from the same glycosyl donor, across a broad range of acceptors through simple variation of the chiral Brønsted acid catalyst. Systematic evaluation of a library of readily accessible chiral Brønsted acids reveals how catalyst, donor, and acceptor jointly govern reactivity and stereoselectivity. Mechanistic studies reveal that the stereodivergence originates from distinct reaction pathways promoted by seemingly similar chiral Brønsted acids. This work establishes a general platform for catalyst-controlled anomeric selectivity and expands the synthetic toolbox for stereoselective complex carbohydrate assembly.