Metal Salts Catalyzed Stereoselective O-Glycosylation with an Armed Glycosyl Trichloroacetimidates Donor

Abstract

The majority of carbohydrates prevail as O-glycosides, often found in the form of glycoconjugates or polysaccharides. Hence, O-glycosylation, commonly termed as glycosylation reactions that stitch together two carbohydrate moieties (acceptor and donor), is a very important reaction in the area of glycol-chemistry to synthesize structurally complex oligo- or polysaccharide structures. Among various glycosyl donors, O-glycosyl trichloroacetimidates are one of the most preferred options due to several advantages. One such advantage is that the stereoselectivity of the formed glycosidic bond can be guided as required by varying solvents, reagents, or other reaction conditions. Traditional catalysts (TMSOTf, BF3·OEt2) were employed for the activation of glycosyl trichloroacetimidate derivatives, which were utilized at the nitrogen of the O-glycosyl trichloroacetimidates, proceeding via an SN1-type mechanism. The stereoselectivity of the newly formed glycosidic bond is conventionally directed by the neighboring group participation of the C-2 functionality of the donor molecule. The synthesis of 1,2-trans-glycosides, carried out without the involvement of neighboring group participation, has long been a source of fascination for glycochemists due to the significant obstacles it poses. Over the last two decades, several new methods have been developed to synthesize 1,2-trans-glycosides by activating armed glycosyl trichloroacetimidate derivatives using various commercially available metal salts.