Sugar Silanes: Versatile Reagents for Stereocontrolled Glycosylation via Intramolecular Delivery.

Abstract

Carbohydrates play many roles in the complex biological systems found within Nature. An important goal in carbohydrate chemistry is the development of diastereoselective glycosylation methods to incorporate carbohydrates in an expedient and high yielding fashion. Intramolecular glycosylation is an approach whereby a glycosyl donor and acceptor are tethered together and subsequent activation of the donor results in diastereoselective transfer of the aglycone to the anomeric position. Previous work in the Montgomery group has focused on the development of carbohydrate-bearing silane reducing agents termed “sugar silanes.” Using these reagents, the direct reductive glycosylation of carbonyl substrates and the three-component assembly of glycosylated products via the catalytic union of aldehydes, alkynes, and sugar silanes is possible. We now describe a new method for the dehydrogenative silylation of alcohols using sugar silanes followed by intramolecular glycosylation. Appropriate combinations of silane position and protecting group allow highly selective access to beta-manno, alpha-gluco, or beta-gluco stereochemical relationships as well as beta-2-azido and beta-2-deoxyglycosides. Expanding upon the more traditional tethering at the C2 hydroxyl of the donor, the C6 hydroxyl is utilized for tethering to give the first general method to obtain 1,2-trans-glycosides via intramolecular aglycone delivery.