Dearomatization [4+2] cycloaddition for constructing bridged polycyclic lactams

Abstract

This article presents a metal-free catalytic system for the [4+2] cycloaddition of isoquinoline and maleimide derivatives, enabling the one-step construction of structurally complex bridged polycyclic lactams. This three-component tandem cyclization reaction generates C–N, CO, and C–C bonds, achieving functionalization at the C1, N2, C3, and C4 positions of 3-halogenated isoquinolines. This dearomatization strategy exhibits exceptional chemoselectivity and regioselectivity, operates without transition metals, and offers a high atom and step economy.