Overview of 1,5-Selective Click Reaction of Azides with Alkynes or Their Synthetic Equivalents

Yaqi Zhao, Zhengqi Chai, Qingrui Zeng, and Wen-Xiong Zhang*

Molecules 2023, 28, 1400. https://doi.org/10.3390/molecules28031400.

Nowadays click reaction of azides with alkynes has evolved rapidly and become one of the most efficient methods to synthesize 1,2,3-triazoles, which are an important class of N-containing heterocycles. While 1,4-selective click reaction of azides with alkynes is well established to synthesize 1,4-substituted 1,2,3-triazoles, the corresponding 1,5-selective click reaction for the generation of 1,5-substituted-1,2,3-triazoles is much less explored and there is no systematic review for 1,5-selective click reaction. This timely review summarizes the discovery and development of 1,5-selective click reaction of azides with alkynes for the synthesis of the 1,5-substituted 1,2,3-triazoles. The 1,5-selective click reactions will be divided into three types according to the critical reactive intermediates: metallacyclic intermediates, acetylide intermediate and formal 1,5-selective azide-alkyne cycloaddition. The related mechanistic studies will also be involved in this review.