Boronic Acid Catalysis for Diol Activation under Lewis Base Promotion: Site-Selective Propargylation of Carbohydrates

A catalytic method for the site-selective installation of a terminal propargyl group onto carbohydrate scaffolds was developed. This transformation hinges on identifying the optimal pairing of an electron-deficient boronic acid with a base, a combination that promotes the formation of a tetracoordinate boron intermediate and substantially enhances the nucleophilicity of carbohydrate hydroxyl groups. The method enables efficient propargylation across a wide variety of carbohydrate substrates, affording propargylated products with high to complete site-selectivity. Mechanistic and control studies clarified the indispensable roles of both the boronic acid and the base in driving the reaction, while the method itself demonstrates notable selectivity among different carbohydrates. By employing readily available catalysts and achieving predictable site-selectivity, this strategy establishes a practical and versatile platform for installing a terminal propargyl group as a functional handle for click chemistry. Its broad applicability was further demonstrated through postpropargylation click reactions, which facilitated the synthesis of glycosylated bioactive natural products and pharmaceuticals, construction of pseudoglycan conjugates, and development of molecular probes for fluorescent labeling and photoaffinity labeling.