Regio- and stereoselective [3 + 2] cycloaddition reaction: access to isoxazole-dispirobisoxindoles featuring three contiguous stereocenters

Abstract

A novel methodology toward the diversity-oriented asymmetric construction of densely functionalized isoxazole-dispirobisoxindoles was developed. This approach is distinguished by an organocatalytic stereo- and appealing β-regioselective [3 + 2] cycloaddition reaction of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles and 3-isothiocyanato oxindoles. Complex polycyclic oxindoles 3 featuring two different oxindole moieties and three contiguous stereocenters were smoothly afforded in up to 96% yield, 96% ee, and >20 : 1 dr. The described method, which is different from our previous work of α-regioselective asymmetric annulation of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles, is the first β-regioselective asymmetric annulation.