A one carbon staple for orthogonal copper-catalyzed azide-alkyne cycloadditions

We describe herein the use of alpha-hydroxy-beta-azidotetrazoles, easily prepared in one step from alpha, beta-epoxynitriles, as new scaffolds for orthogonal CuAAC reactions performed on the same carbon atom. After a first ligation involving an alkyne with the beta-azido moiety, treatment with EDC smoothly releases an alkyne from the remaining alpha-hydroxytetrazole, ready for a second CuAAC reaction. This double click'' process can be performed iteratively, leading to triazolamers.