Stereoselective Sulfenylative <i>N</i> ‐Glycosylation of Glycals Enabled by Hexafluoroisopropanol

The sulfenylative N-glycosylation of glycals, which exhibits high β-stereoselectivity, has been successfully developed for the first time under the facilitating effect of hexafluoroisopropanol (HFIP). This method is broadly applicable to four classes of nitrogen nucleophiles, including sulfamides, carbamates, ureas, and azoles. Furthermore, various glycal derivatives, such as D-galactal, D-arabinal, L-fucal, and D-glucal, can be effectively employed in this reaction system. A range of 2-phenylthio-N-glycosides were obtained in moderate to good yields with consistently high β-selectivity (β:α > 20:1). Density functional theory (DFT) calculations reveal the origin of the observed stereoselectivity and highlight the critical role of HFIP in promoting the glycosylation process.