Influence of Functional Groups towards the β‐Selective Glycosylation of 2‐Azido‐2‐deoxy Glycosyl Thioglycosides

The influence of the functional groups present in the glycosyl donor on the stereoselective glycosylation of 2-azido-2-deoxy sugar thioglycosides under the N-iodosuccinimide (NIS) and triflic acid (TfOH) mediated glycosylation conditions has been studied in detail. It was observed that beta glycosides of 2-azido-2-deoxy sugar are formed mainly via a stable alpha-glycosyl triflate intermediate followed by S(N)2 substitution of the triflate group by the acceptor. The presence of an electron withdrawing functional group such as O-picoloyl (Pico) in the glycosyl donor facilitates the formation of stable alpha-glycosyl triflate to furnish beta-glycosides, whereas the presence of an electron donating hydrogen bond mediating functional group such as p-methoxybenzyl (PMB) in the glycosyl donor directs the formation of 1,2-cis glycosides via the glycosyl oxycarbenium ion intermediate with B-2,B-5 and H-4(3) conformation. Excellent yields of the beta-glycosides were obtained in case of 2-azido-2-deoxy-d-mannose and 2-azido-2-deoxy-d-galactose thioglycosides, and 2-azido-2-deoxy-d-glucose thioglycosides furnish moderate yields of the beta-glycosides.