Direct Evidence of a Dinuclear Copper Intermediate in Cu(I)-Catalyzed Azide-Alkyne Cycloadditions

How Copper Clicks The copper-catalyzed coupling of azides and alkynes has been termed a “click” reaction on account of its efficiency and versatility, but despite its widespread use, the mechanism remains somewhat unclear. Through a series of kinetic and isotopic labeling studies, Worrell et al. (p. 457 , published online 4 April) show that, in the case of terminal alkynes (capped at one end by an H atom), two equivalents of copper participate in activating each molecule's reactivity toward azide. Surprisingly, the reaction also appears to proceed through an intermediate in which the two copper centers become equivalent and functionally exchangeable, despite initially coordinating to distinct sites on the alkyne.