Reactions

The CuAAC processes through a stepwise mechanism, where the catalytic cycle is initiated by the 𝜋-coordination of the terminal alkyne to a first copper(I) complex, activating the terminal C-H bond (1). This is followed by deprotonation of the terminal alkyne, facilitated by a second copper(I) species (2), generating a dinuclear copper(I) acetylide intermediate in which one copper center is σ-bound to the carbon and the other remains 𝜋-coordinated to the triple bond. The counterion may act as the proton acceptor, releasing HX.
The alkyl azide then coordinates to the σ-bound copper center (3), activating the azide toward the cycloaddition (4). This sets off regioselective syn-addition of the two reactive ends, where the copper-bound carbon of the acetylide and the terminal nitrogen of the azide, form a strained six-membered dicopper(I) metallacycle. This key intermediate undergoes ring concentration to give a copper(I)-triazolide intermediate (5). Protodemetalation releases the 1,4-disubstituted 1,2,3-triazole as the final product and regenerates the initial copper complex (6).