Each Interruption is an Opportunity: Novel Synthetic Strategies Explored Through Interrupted Click Reactions

The particular and unique mechanism of the copper-catalyzed reaction between azides and alkynes (CuAAC) has not only allowed for the efficient synthesis of 1,2,3-trisubstituted 1,4-triazoles in excellent yields and under mild conditions, becoming the quintessential click reaction, but it has also enabled the straightforward formation of a metallocycle intermediate, the copper triazolyl. This, under suitable reaction conditions able to suppress its protonolysis, can be used either for the creation of new bicyclic triazolyl structures or for the generation of novel three or four-component reactions. The aim of this review is to rationalize and unify all these transformations, which are collectively referred to as "interrupted click reactions". The copper-catalyzed reaction between azides and alkynes, known as CuAAC, has allowed for the efficient synthesis of 1,2,3-trisubstituted 1,4-triazoles and the formation of a metallocycle intermediate. This intermediate can be used for creating new structures or generating multi-component reactions, collectively referred to as "interrupted click reactions" image