Rapid synthesis of hexahydropyrrolo[3,4-b]pyrrole-fused quinolines via a consecutive [3 + 2] cycloaddition and reduction/intramolecular lactamization cascade

Abstract

An unprecedented synthesis of novel hexahydropyrrolo[3,4-b]pyrrole-fused quinolines is achieved through the sequential [3 + 2] cycloaddition reaction of azomethine ylides with maleimides followed by intramolecular lactamization. Condensation of the α-amino acid methyl ester with 2-nitrobenzaldehyde leads to an ester stabilized azomethine ylide which further reacts with maleimide to form hexahydropyrrolo[3,4-c]pyrrole. After the reduction of a nitro group, an unusual transamidation reaction is observed, furnishing the novel hexahydropyrrolo[3,4-b]pyrrole-fused quinolines. Isolation of the hexahydropyrrolo[3,4-c]pyrrole amide intermediate revealed the pathway of the reaction mechanism.