DMAP-Promoted Cascade Synthesis of Bispirooxindole–Cyclopentene–Isoxazolones

A DMAP-catalyzed Michael addition/cyclization cascade reaction has been developed for the efficient construction of a bispirooxindole–cyclopentene–isoxazolone framework. Under the optimized conditions (10 mol% DMAP, CH2Cl2, room temperature), the desired product was obtained in 92% yield with >20:1 diastereoselectivity. The reaction exhibited broad substrate scope, tolerating various substituents on both the isoxazolone and oxindole rings, and affording the corresponding products in 72–96% yields. The relative configuration of a representative product was determined as rel-(2’S,3R,3’R) by X-ray single-crystal diffraction. The utility of this method was further demonstrated by a gram-scale experiment (82% yield). This cascade reaction provides a concise and efficient route to structurally novel spiroisoxazolone derivatives bearing a cyano group and multiple spiro chiral centers.