Determining the Origin of Rate‐Independent Chemoselectivity in CuAAC Reactions: An Alkyne‐Specific Shift in Rate‐Determining Step

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. The old switcheroo: A kinetic and spectroscopic analysis of alkyne‐dependent chemoselectivity in the copper‐catalyzed azide–alkyne click (CuAAC) reaction is reported. 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.