Copper-Catalyzed One-Pot Three-Component Tandem Annulation: Streamlined Access to Functionalized 2-Pyrroline Carboxylates

Abstract Conventional synthetic methods for 2-pyrrolines suffer from tedious substrate preparation and reliance on noble metal catalysts, limiting their practical applications. Herein, we report a practical copper-catalyzed three-component tandem annulation to construct functionalized 2-pyrroline carboxylates from commercially available γ-aminobutyric acids, DMF-DMA/DMF-DME, and aryl iodides. This protocol features broad substrate scopes, good functional group tolerance, high step and atom economies, and scalable synthesis. The obtained products can be readily transformed into pyrrolines, pyrroles, and bioactive pyrroloquinolones. A plausible reaction mechanism is proposed based on the control experiments, providing a sustainable synthetic route for functionalized 2-pyrroline derivatives.