Synthesis of chiral azides from C-2 substituted glycals and their transformation to C3-glycoconjugates and & alpha;-triazolo-naphthalene polyol

A Lewis-acid-mediated highly regio- and stereoselective chiral azidation of C2-substituted glycals is reported. This strategy provides excellent, scalable, and mild reaction conditions for the stereoselective introduction of the azido group at the C3-position of various C2-substituted glycals. The reactivity of the various glycals reveals that the electron-withdrawing behavior of the C2-group is crucial for C3-selectivity. The newly installed azido group was used as a handle for the synthesis of various C3-glycoconjugates and & alpha;-chiral azido naphthalene polyols.

Automated summary

A Lewis-acid-mediated azidation of C2-substituted glycals with high regio- and stereoselectivity is described. This method offers excellent, scalable, and mild reaction conditions for introducing the azido group at the C3-position of various C2-substituted glycals. The electron-withdrawing nature of the C2-substituent is found to be crucial for the C3-selectivity. The installed azido group can be used for the synthesis of various C3-glycoconjugates and α-chiral azido naphthalene polyols.