Addition Reaction of Thiols to Carbohydrate Vinyl Azides: Synthesis of Unusual Sugar Derivatives Containing Thioaminal‐Like Motifs

Carbohydrate‐derived vinyl azides showed a unique reactivity with thiols as they readily led to addition products. In this way, 2‐azido‐2,3‐dideoxy‐β‐ D ‐ erythro ‐hex‐2‐enopyranose derivatives led to a new class of modified carbohydrates, having the azido group and the thioalkyl residue attached to the same carbon (C‐2). The configuration of the new stereogenic centers formed at C‐2 were determined on the basis of spectroscopic data and molecular modeling calculations applying the DP4+ method and confirmation by X‐ray crystallography. The addition reactions occurred with high diastereomeric excess in favor of the products having the thiol residue opposite the anomeric substituent. Thus, whereas β‐vinyl azide led to products having R configuration at C‐2 with the thiol equatorially disposed toward the α‐face, the α‐vinyl azide produced 2 S ‐configured products with the thiol in axial disposition. Additionally, unexpected hexopyranosid‐2‐ulose thioximes were also obtained when the sterically hindered 1‐adamantanethiol was used. These findings demonstrate the versatility of carbohydrate vinyl azides as building blocks for the synthesis of modified carbohydrates and derivatives of unique structures. Also, these results can contribute to the access to new glycomimetics with potential activity as inhibitors of enzymes or suitable as tools for studies in the glycobiology field.