Minimally Protected and Stereoselective O-Glycosylation of Carboxylic Acid Allows Rapid Access to α-1-O- and 2-O-Acyl Glycosides

We herein reported a catalytic, minimally protected, and highly α-stereoselective glycosylation protocol using carboxylic acid as an acceptor and glycosyl 8-alkynyl-1-naphthoate as a donor, enabling efficient access to unprotected α-1-O- and 2-O-acyl glycosides. This method demonstrates excellent functional compatibility and scope generality, allowing for the glycosylation of a wide range of complex carboxylic acids. Notably, we successfully synthesized two natural products, α-penta-O-galloyl-d-glucopyranose and nyctanthesin A, using this protocol. Mechanistic studies highlighted the crucial role of the 1-O ester functionality in ensuring chemoselectivity and the important contribution of the 2-O functionality in facilitating the reaction.