Enantioselective construction of dispirotriheterocycles featuring a 4-aminopyrazolone motif through a cascade Michael/cyclization process

Abstract

A highly efficient and asymmetric process to achieve spirocyclic 4-aminopyrazolone derivatives through a cascade Michael addition/cyclization reaction of 4-isothiocyanato pyrazolones with 3-ylideneoxindoles was developed. This reaction forged multicyclic dispiro[pyrazolone-pyrrolidinethione-oxindole] core structures bearing three contiguous stereogenic centers, including two spiro-quaternary stereocenters with excellent diastereo- and enantioselectivities (up to 99% ee, >20 : 1 dr). The product can be readily diversified to expand the chemical space of spiropyrazolone species. A plausible mechanism to account for the stereochemical course of the cascade process was proposed.