Cu-catalyzed oxidative imino Diels–Alder cyclization: synthesis of dihydrofuroquinolines

Abstract

Quinolines, dihydrofuroquinolines, and quinoline-fused lactones are privileged scaffolds found in numerous natural products and bioactive molecules. We report a novel and efficient Cu-catalyzed intermolecular oxidative imino Diels–Alder (Povarov-type) cyclization of (2-propargyloxy)acetaldehydes with aromatic amines for the synthesis of dihydrofuro[3,4-b]quinolines. This method employs inexpensive and readily available substrates and proceeds through sequential imine formation, intramolecular [4 + 2] cycloaddition, and oxidative aromatization, while tolerating a broad range of functional groups. Oxone acts as a green and cost-effective oxidant, affording the desired products in high yields. Furthermore, subsequent benzylic oxidation enables efficient conversion of dihydrofuroquinolines into quinoline-fused lactones, which are valuable intermediates in natural product synthesis.