Rhodium-catalyzed synthesis of N-substituted 3-acylpyrroles from enaminones and vinylene carbonate

Abstract

Herein, we present a protocol for constructing N-substituted 3-carbonylpyrroles (NSCPRs) through the reaction of vinylene carbonate with enaminone building blocks, facilitated by Rh(III)-catalyzed [3 + 2] annulation. This reaction enabled the straightforward and efficient construction of NSCPRs and their drug analogs. Specifically, we developed a cascade Rh(III)-catalyzed C–H activation/[3 + 2] annulation reaction for enaminones and internal vinylene carbonate, catalyzed by [Cp*RhCl₂]₂ and oxidized with Cu(OAc)₂, AgSbF₆ and air. This method allowed for the efficient synthesis of highly functionalized NSCPRs with good yields. The reaction proceeded through C–H activation, alkene insertion, decarboxylation and reductive elimination, ketone-enol tautomerization, 1,2-addition, and dehydration. This protocol demonstrates excellent functional group tolerance, a broad substrate scope, and scalability for gram-scale synthesis, showcasing its applicability to drug molecules and highlighting its utility in organic synthesis and pharmaceutical chemistry.