Glycosyl acceptor alcohol

After the formation of glycosyl triflate, addition of an acceptor alcohol, still at low temperature, results in the rapid formation of the desired glycosidic bond. 

When triflic anhydride is added to a preformed mixture of glycosyl sulfoxide and acceptor alcohol, it seems apparent that the first formed oxacarbenium ion is directly trapped by the alcohol, without the need for the implication of glycosyl triflates [75,280,323],... 

This method works very well for reactive glycosyl acceptors such as primary alcohols. It can be carried out without affecting other acid sensitive functionalities including acetonides and even orthoesters. Nishimura and co-workers successfully employed this method to prepare the ttisaccharide monomer 344 (Scheme 8.107). After deprotection, the product was copolymerized with acrylamide to give a biologically interesting glycoprotein model. 

In early attempts directed towards the solid-phase synthesis of oligosaccharides, glycosidic bonds were formed by treating pyranosyl bromides with partially protected carbohydrates (Figure 16.16). These syntheses could be performed with either the pyranosyl bromide (glycosyl donor) [184,185] or the alcohol (glycosyl acceptor) [186— 188] linked to the support. 

Starting with phosphite 59 stannous triflate catalyzes the formation of an oxenium ion 60, which is stabilized by the solvent (61). The complex 61 is more favored than 63, justified by the reverse anomeric effect until now. But as it is shown there is no possibility for 61 to react in an SN2 reaction to 62. The intermediate 63 can be attacked by the alcohol functionality of the glycosyl acceptor, and with MeCN as leaving group you get 64. Ultimately the equilibrium between 61 and 63 shifts completely to 63. This kind of stereocontrol during a glycosylation is known as the nitrile effect.28... 

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