A highly stereoselective construction of 1,2- trans-β-glycosidic linkages capitalizing on 2-azido-2-deoxy- d-glycosyl diphenyl phosphates as glycosyl donors

Abstract

The scope of TMSOTf-promoted glycosidation of 2-azido-2-deoxyglycopyranosyl diphenyl phosphates is investigated. The 3,4,6-tri- O-benzyl-protected glucosyl and galactosyl donors and the 4,6- O-benzylidene-protected galactosyl donor each react with a range of acceptor alcohols in the presence of a stoichiometric amount of TMSOTf in propionitrile at −78 °C to afford 1,2- trans-β-linked disaccharides in high yields with α: β ratios ranging from 9:91 to 1:>99, regardless of the anomeric composition of the donor used. The use of propionitrile as a solvent at −78 °C has proven to be among the best choice for the highest levels of β-selectivity reported to date for this type of glycosidation. A plausible reaction mechanism, which features a large equilibrium preference for α-glycosyl-nitrilium ions over β-nitrilium ions, is proposed based on byproducts formed through their intermediacy and accounts for the observed excellent β-selectivities.