On the Gluco/Manno Paradox: Practical [alpha]-Glucosylations by NIS/TfOH Activation of 4,6-O-Tethered Thioglucoside Donors

A practical protocol for obtaining [alpha]-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 [alpha]-selective glucosylation under conditions of N-iodosuccinimide (NIS)/triflic acid (TfOH) activation. The [alpha]-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.