DMAP-Catalyzed Efficient Diastereo- and Regioselective Synthesis of Isoxazolone-Based Bisspiroheterocyclic Oxindoles

A strategic approach to incorporate CF₃ group into oxindoles, pyrrolidines, and isoxazolones to construct spiro heterocyclic skeletons with quaternary carbon stereocenters was developed. Using a DMAP catalyst under mild conditions, the controllable synthesis of spiro oxindole-pyrrolidine-isoxazoline derivatives was achieved via concerted 1,3-dipolar cycloaddition reactions of arylidene isoxazolones with N-(2,2,2-trifluoroethyl)isatin ketimines. This method exhibits robust regioselectivity and provides a series of isoxazolone-based bispiro heterocycles in good to high yields (72 %–99 %) with excellent diastereoselectivity (in all cases >20 : 1 dr), offering new candidate compounds for drug screen.