Solvent‐Free Glycosylation from per‐O‐Acylated Donors Catalyzed by Methanesulfonic Acid

Abstract

The huge importance of carbohydrates and their derivatives in biomedical and industrial applications call for the development of streamlined and sustainable procedures for their synthetic elaboration. Here reported a novel glycosylation method based on direct activation of readily available per‐O‐acylated (acetylated or benzoylated) donors, promoted under air by methanesulfonic acid as a cheap and green catalyst in the absence of any solvent. Besides the beneficial avoidance of toxic and polluting organic solvents, these conditions were found critical for activating such poorly reactive donors with a very small catalyst loading (only 5 mol %), instead of stoichiometric Lewis acid promoters typically employed. Desired glycosides were quickly obtained, in most cases with high 1,2‐transstereoselectivity. Other main advantages over reported glycosylations with similar donors are the limited stoichiometric excess of the acceptor (or the donor), the easy applicability and low cost of the procedure and the wide target scope, also covering the synthesis of disaccharides and other non‐trivial glycosides with applicable potential.

Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds

“…Achiral thiourea, as a co-catalyst, exhibits a cooperative performance, having a strong effect on the reaction velocity, yield, and selectivity of glycosylation (Scheme 2). Solvent-free methodologies have been developed recently in stereoselective glycosylation reactions [32]; however, these procedures are uncommon in carbohydrate chemistry and have only directed very few applications to glycosylation reactions [33]. Solvent-free reactions avoid the use of polluting, high-boiling, toxic, and commonly used organic solvents; such approaches allowed a great simplification and improvement [34,35].…”