Dimethylformamide: An Unusual Glycosylation Modulator

摘要

The key steps in oligosaccharide synthesis are protecting-group manipulation and stereoselective glycosylation. Various strategies have emerged to expedite glycosylation, and some of these strategies have been elaborated for automated solid-phase synthesis and one-pot cascade glycosylation. Most glycosylation strategies rely on traditional methods for stereochemical control over glycosidic-bond formation. Although such tactics work well for the formation of 1,2-trans β-glycosidic bonds, there is no straightforward solution for the formation of a 1,2-cis a-glycosidic bond. Existing methods often require extensive optimization of the reaction conditions, including the selection of an ethereal solvent, a transition-metal-complex promoting system, a remote participating group, a silylidene protecting group, and a chiral or achiral accessory group at the C2 position, or the installation of a fluoride substituent at the C2 position. However, most of these methods require additional steps for the installation of a specific functionality and are therefore less convenient for routine synthesis. Herein, we report a simple and general α-glycosylation method in which N,N-dimethylformamide (DMF) is used as a modulating molecule to direct the stereochemical course of glycosylation. Further elaboration of this approach led to a practical α-selective procedure based on preactivation that is useful for the glycosylaton of both O-glycoside and thioglycoside acceptors.