A copper-catalyzed annulation reaction of diazo esters with propargyl amines for the synthesis of 2,5-dihydropyrroles

Abstract

2,5-Dihydropyrrole derivatives are considered privileged structures as reflected by their presence in many biologically active molecules and therapeutic agents. Herein, we develop a concise and efficient method utilizing a commercially available copper salt as a catalyst to facilitate the formation of 2,5-dihydropyrroles from propargyl amines and diazo esters. This reaction proceeds via the formation of an N-ylide, followed by bond cleavage/recombination. Control experiments and density functional theory (DFT) calculations provide a detailed analysis of the reaction pathway. The key features of this protocol include simple operation, readily available starting materials, mild conditions, and high atom economy. In addition, the gram-scale preparation experiment and the transformations of 2,5-dihydropyrroles demonstrate the potential applicability of our synthetic method.