Regioselective synthesis of multisubstituted 1,2,3-triazoles: moving beyond the copper-catalyzed azide–alkyne cycloaddition

Copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) is an essential "click chemistry" reaction that is widely used in chemical biology, medicinal chemistry and materials science. The CuAAC reaction of terminal alkynes provides a mild and efficient synthesis of 1,4-disubstituted 1,2,3-triazoles. However, the click reaction of internal alkynes with azides, giving trisubstituted triazoles, is very challenging. This feature article highlights the recent progress addressing this fundamental problem. Particular emphasis is on the current and emerging strategies to introduce functional groups to the C-5 position of triazoles in a regioselective manner.