A Streamlined Regenerative Glycosylation Reaction: Direct, Acid-Free Activation of Thioglycosides

Our group has previously reported that 3,3-difluoroxindole (HOFox) is able to mediate glycosylations via intermediacy of OFox imidates. Thioglycoside precursors were first converted into the corresponding glycosyl bromides that were then converted into the OFox imidates in the presence of Ag2O followed by the activation with catalytic Lewis acid in a regenerative fashion. Reported herein is a direct conversion of thioglycosides via the regenerative approach that bypasses the intermediacy of bromides and eliminates the need for heavy-metal-based promoters. The direct regenerative activation of thioglycosides is achieved under neutral reaction conditions using only 1 equiv. NIS and catalytic HOFox without the acidic additives.

Automated summary

This research describes a direct conversion of thioglycosides using a regenerative approach, bypassing the need for bromide intermediates and heavy-metal-based promoters. The reaction conditions are mild, with only 1 equiv. NIS and catalytic HOFox needed under neutral conditions.