Stereoselective synthesis of 2-deoxy-β-glycosides from glycal precursors. 2. Stereochemistry of glycosidation reactions of 2-thiophenyl- and 2-selenophenyl-α-D-gluco-pyranosyl donors

Article abstract of DOI:10.1016/S0040-4020(97)90395-1

We have demonstrated that 4-O-acetyl-6-bromo-3-O-(tert- butyldimethylsilyl)-2-deoxy-2-thiophenyl-1-trichloroacetimido-α-D- glucopyranose 11b is the most efficient and selective donor for use in the synthesis of 2-deoxy-β-glycosides of the series of glycosyl donors examined. Unlike the 2-selenophenyl substituted donors 8 which proved to be configurationally unstable under standard TMS-OTf promoted glycosylation conditions, giving rise to α-manno glycosides 14, 17 and 20 from β-gluco donors 8, the 2-thiophenyl substituted donors 9 and 11 appeared to be completely configurationally stable (at C(2)). The main problem with imidates 11 is that the stereoselectivity of their reactions with alcohols is substrate dependent, with best selectivity for the desired β-glycosides 35 and 42 being obtained with the least sterically hindered alcohols. The fact that the α-glycosides 36 and 43 comprise up to 20-50% of the product in glycosidation reactions of hindered secondary alcohols supports the thesis that the reaction stereoselectivity is not governed by the intermediacy of episulfonium ions (47 and 47'), but rather that substitution reactions of oxonium ions 46 and its conformationally inverted isomer 46' play a dominant role.