On the Gluco/Manno Paradox: Practical α‐Glucosylations by NIS/TfOH Activation of 4,6‐O‐Tethered Thioglucoside Donors

A practical protocol for obtaining α‐glucosides was established. It was found that 4,6‐O‐benzylidene or 4,6‐O‐(di‐tert‐butylsilylene) tethering of glucosyl donors of the thioglycoside type enables highly α‐selective glucosylation under conditions of N‐iodosuccinimide (NIS)/triflic acid (TfOH) activation. The α‐glucosylations were further found to be largely independent of promoter system, temperature, leaving group and anomeric configuration. The results are discussed in the context of the Glucose/Mannose paradox in glycosylation chemistry.