![60. Determining the Origin of Rate-Independent Chemoselectivity in CuAAC Reactions: An Alkyne-Specific Shift in Rate-Determining Step](https://cdn.prod.website-files.com/6380be6ed1140b78394d35e6/64809d7f7b284df36933b68d_anie201612288-toc-0001-m.jpeg)
We report a kinetic and spectroscopic analysis of alkyne-dependent chemoselectivity in the copper-catalyzed azide–alkyne click (CuAAC) reaction. Studies of six alkyne subtypes reveal that the rate-determining step (RDS) of an aromatic ynamine class is shifted from acetylide formation to the azide ligation/migratory insertion event allowing chemoselectivity independent of overall rate.