Reaction of Alkynes and Azides: Not Triazoles Through Copper-Acetylides but Oxazoles Through Copper-Nitrene Intermediates

Well‐defined copper(I) complexes of composition [Tpm*,BrCu(NCMe)]BF4 (Tpm*,Br=tris(3,5‐dimethyl‐4‐bromo‐pyrazolyl)methane) or [Tpa*Cu]PF6 (Tpa*=tris(3,5‐dimethyl‐pyrazolylmethyl)amine) catalyze the formation of 2,5‐disubstituted oxazoles from carbonyl azides and terminal alkynes in a direct manner. This process represents a novel procedure for the synthesis of this valuable heterocycle from readily available starting materials, leading exclusively to the 2,5‐isomer, attesting to a completely regioselective transformation. Experimental evidence and computational studies have allowed the proposal of a reaction mechanism based on the initial formation of a copper–acyl nitrene species, in contrast to the well‐known mechanism for the copper‐catalyzed alkyne and azide cycloaddition reactions (CuAAC) that is triggered by the formation of a copper–acetylide complex. Unexpected click: Oxazoles were formed in the reaction of alkynes and carbonyl azides, with copper(I) complexes as catalysts. The mechanism that governs this transformation does not involve the traditionally proposed copper–acetylides intermediates, but instead takes place through initial formation of a copper–nitrene species (see scheme).