Copper-catalyzed azodicarboxylate–alkyne (3 + 2) cycloaddition

Abstract

A regioselective (3 + 2) cycloaddition between terminal alkynes and di-tert butyl azodicarboxylate under catalytic conditions is reported for the synthesis of novel N-aminooxazol-2-one scaffolds. The reaction employs an in situ-generated copper catalyst derived from inexpensive CuCl₂ and TMEDA, with a catalytic amount of DABCO serving as a base. The (3 + 2) annulation features broad functional group tolerance and a straightforward protocol. Mechanistic studies revealed that under these mild and practical conditions, the non-isolated ynehydrazide intermediate—formed via the catalytic addition of terminal alkynes to azodicarboxylate—undergoes a subsequent copper-catalyzed 5-endo-dig cyclization in situ, yielding the oxazol-2-one product. This transformation involves two consecutive steps within a single catalytic system, demonstrating high atom economy and step economy.