NaOH-Mediated Intermolecular Cascade Cyclization Reaction of Conjugated Dieneimines with α-Halomalonates to Access Functionalized Cyclopentene Cores

Abstract

An efficient intermolecular cascade cyclization of conjugated dieneimines with α-halomalonates in the presence of a NaOH base was developed. This method facilitates the synthesis of a diverse range of functionalized cyclopentenes featuring two adjacent stereocenters, including a quaternary carbon center, in high yields with excellent diastereoselectivities and perfect regioselectivities. The reaction proceeds through a sequence of Michael addition, cyclopropanation, isomerization, ring opening of the cyclopropane intermediate, isomerization, and intramolecular cyclization. Furthermore, the practical utility of this methodology is demonstrated through its application in subsequent synthetic transformations and late-stage functionalization of drug molecules. Additionally, a molecular docking study was conducted to investigate the potential biological activity of the products.