Stereoselective glycosylations using (R)- or (S)-(ethoxycarbonyl)benzyl chiral auxiliaries at C-2 of glycopyranosyl donors

The stereoselective introduction of a glycosidic bond presents the greatest challenge to complex oligosaccharide synthesis. Important developments such as automated polymer-supported oligosaccharide synthesis will not realize their full potential until this problem is addressed. In this paper, a novel approach for stereoselective glycosylations is described whereby a chiral auxiliary at C-2 of a glycosyl donor controls the anomeric outcome of a glycosylation. It was found that participation of an (S)-ethoxycarbonylbenzyl auxiliary led to the formation of 1,2-cis glycosides, probably through a trans-fused dioxolenium ion intermediate. On the other hand, the use of an auxiliary with (R) configuration gave 1,2-trans glycosides, and this glycosylation proceeds through a cis-fused dioxolenium ion intermediate. The auxiliary could conveniently be removed by Birch reduction. Computational studies support the formation of the proposed ethoxy-carbonium ion intermediate with all pseudo-equatorial substituents.