Mechanism of Copper(I)-Catalyzed 5-Iodo-1,2,3-triazole Formation from Azide and Terminal Alkyne.

5-Iodo-1,2,3-triazole (iodotriazole) can be prepared from a copper(I)-catalyzed reaction between azide and terminal alkyne in the presence of an iodinating agent, with 5-protio-1,2,3-triazole (protiotriazole) as the side product. The increasing utilities of iodotriazoles in synthetic and supramolecular chemistry drive the efforts in improving their selective syntheses based on a sound mechanistic understanding. A routinely proposed mechanism takes the cue from the copper(I)-catalyzed azide-alkyne cycloaddition, which includes copper(I) acetylide and triazolide as the early and the late intermediates, respectively. Instead of being protonated to afford protiotriazole, an iodinating agent presumably intercepts the copper(I) triazolide to give iodotriazole. The current work shows that copper(I) triazolide can be iodinated to afford iodotriazoles. However, when the reaction starts from a terminal alkyne as under the practical circumstances, 1-iodoalkyne (iodoalkyne) is an intermediate while copper(I) triazolide is bypassed on the reaction coordinate. The production of protiotriazole commences after almost all of the iodoalkyne is consumed. Using (1)H NMR to follow a homogeneous iodotriazole forming reaction, the rapid formation of an iodoalkyne is shown to dictate the selectivity of an iodotriazole over a protiotriazole. To ensure the exclusive production of iodotriazole, the complete conversion of an alkyne to an iodoalkyne has to, and can be, achieved at the early stage of the reaction.