Pd/Rh-Catalyzed Asymmetric Dearomatization Annulation of 4-Nitroisoxazoles with Vinylcyclopropanes

Abstract

A synergistic Pd/Rh-catalyzed asymmetric dearomatization cyclization reaction between vinylcyclopropanes and 4-nitroisoxazoles has been established, enabling the facile construction of structurally diverse and polyfunctionalized chiral cyclopentane-fused isoxazoline frameworks. In bimetallic Pd/Rh synergistic catalysis, a broad range of cyclic and acyclic vinylcyclopropanes serve as versatile 1,3-dipole precursors to couple with various 3-aryl-4-nitroisoxazoles. This transformation delivers a series of densely functionalized cyclopentane-fused isoxazoline derivatives with excellent yields and high diastereo- and enantioselectivities. Notably, this protocol features a broad substrate scope and versatile downstream derivatization of obtained products. DFT calculations further elucidate the stereochemical origin and formation mechanism of the major diastereomeric products, providing fundamental insights into the stereocontrol of this asymmetric transformation.