'Click' Preparation of Carbohydrate 1-Benzotriazoles, 1,4-Disubstituted, and 1,4,5-Trisubstituted Triazoles and their Utility as Glycosyl Donors

Abstract

Glycosyl triazoles can be prepared from readily available anomeric azides through various ‘click’ methodologies: thermal Huisgen cycloaddition with alkynes, strain-promoted Huisgen cycloaddition of benzynes, and CuI-catalyzed azide-alkyne cycloaddition of terminal alkynes (CuAAC reaction). Here we investigate the formation of glycosyl 1-benzotriazoles from anomeric and non-anomeric carbohydrate azides using benzynes derived from substituted anthranilic acids. The reactivity of the resulting anomeric 1-benzotriazoles as glycosyl donors was investigated and compared with 1,4-disubstituted glycosyl triazoles (from the CuAAC reaction) and 1,4,5-trisubstituted glycosyl triazoles (prepared by Huisgen cycloaddition of glycosyl azides and dimethyl acetylene dicarboxylate). The 1,4,5-trisubstituted glycosyl triazoles were activated by Lewis acids and could be converted to O-glycosides, S-glycosides, glycosyl chlorides, and glycosyl azides. By contrast, under all conditions investigated, the 1,4-disubstituted glycosyl triazoles were unreactive as glycosyl donors. Glycosyl 1-benzotriazoles were generally inert as glycosyl donors; however, a tetrafluorobenzotriazole derivative, which bears electron-withdrawing substituents on the benzotriazole group, was a moderate glycosyl donor and could be converted to an S-glycoside by treatment with thiocresol and tin(iv) chloride.