Enantioselective construction of dispirotriheterocycles featuring a 4-aminopyrazolone motif through a cascade
Shiqiang Wei1, Xiaoze Bao, Wenyao Wang
1State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China. bmwang@dlut.edu.cn.
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.
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