Chiral auxiliaries for 1,2-cis stereoselective glycosylations
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A novel strategy for the stereoselective introduction of 1,2-cis-glycosides is described here. The new glycosylation approach is based on neighboring group participation of a (S)-(phenylthiomethyl)benzyl chiral auxiliary at the C-2 of a glycosyl donor which can form a quasi-stable anomeric sulfonium ion. The formation of trans-decalin is expected due to steric and electronic factors. Displacement of the equatorial anomeric sulfonium ion by glycosyl acceptors leads to the stereoselective formation of -glycosides. NMR experiments were employed to show convincingly the presence of the -linked sulfonium ion intermediate. This methodology has been applied to the synthesis of Galili trisaccharide, an epitope that can trigger acute rejections in xeno-transplantations. To explore the possibility of the remote participation of the chiral auxiliary, a series of 2-deoxy glycosyl donors containing a chiral auxiliary at C-6 were synthesized. This methodology proved to be very useful for the synthesis of 2-deoxy glycosides for -selective glycosylations. In situ formation of sulfonium ions by addition of thioethers to the reaction mixture was also investigated. We have observed that glycosylations of 2-azido-2-deoxy-glucosyl donors performed in the presence of a thioether such as PhSEt provide glycosides with excellent -selectivity. Traditional glycosylations with trichloroacetimidates give products within a short period of time. However, the addition of PhSEt led to a different reaction profile. The glycosylation products were formed over a period of several hours. Thus it is reasonable to assume that the intermediate sulfonium-ion had been formed. NMR and computational studies have indicated that steric factors determine the selective formation of the -anomeric sulfonium ion.