A Reagent-Controlled SN2-Glycosylation for the Direct Synthesis of β-Linked 2-Deoxy-Sugars

The efficient and stereoselective construction of linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as beta-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce beta-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an alpha-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an S(N)2-pathway.