The stereoselective synthesis of sialosides is still one of the major challenges in carbohydrate chemistry. The synthesis and glycosidation of novel sialyl donors bearing a picoloyl substituent at C-4 are reported. High stereoselectivities and faster reactions were observed in the presence of an excess of triflic acid. The acid excess does not have the same effect on conventional sialyl donors, which suggests a possible synergistic effect of the picoloyl substituent and the triflic acid.

Examples include all common hexoses, aminosugars, sialic acids, and disaccharides.

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 Ag 2 Of ollowedb yt he activation withc atalytic Lewis acid in ar egenerative 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 activationo ft hioglycosides is achieved under neutral reactionc onditions using only 1equiv.N IS and catalytic HOFox withoutthe acidic additives. Scheme1.Regenerative glycosylation approach.

Thioglycosides are among the most common glycosyl donors that find broad application in the synthesis of glycans and glycoconjugates. However, the requirement for toxic and/or large access of activators needed for common glycosylations with thioglycosides remains a notable draw-back. Due to the increased awareness of the chemical waste impact on the environment, synthetic studies have been driven by the goal of finding non-toxic reagents. The main focus of this review is to highlight recent methods for thioglycoside activation that rely on transition metal catalysis.