Isoxazoles to Tetrasubstituted Pyrroles via a Copper-Mediated Aerobic Cyclizative Dimerization Reaction

Abstract

The regioselective synthesis of electron-deficient and highly substituted pyrroles from simple building blocks remains a considerable challenge. Herein, we report that isoxazoles can serve as effective precursors for the construction of tetrasubstituted pyrroles bearing diester groups via a copper-mediated aerobic cyclizative dimerization process. This protocol operates under mild conditions and exhibits a broad substrate scope along with good functional-group tolerance. Detailed mechanistic investigations, including control experiments and characterization of key intermediates, reveal an intermolecular aerobic cyclizative dimerization pathway. Furthermore, the synthetic utility is demonstrated through preparative-scale synthesis and subsequent diverse downstream transformations of the resulting tetrasubstituted pyrrole.