Desymmetrization of Prochiral <i>N</i>-Pyrazolyl Maleimides via Organocatalyzed Asymmetric Michael Addition with Pyrazolones: Construction of Tri-<i>N</i>-Heterocyclic Scaffolds Bearing Both Central and Axial Chirality
Jianqi Geng,
Xingfu Wei,
Biru He,
Yuting Hao,
Jingping Qu,
Baomin Wang
Affiliations
Jianqi Geng
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
Xingfu Wei
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
Biru He
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
Yuting Hao
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
Jingping Qu
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
Baomin Wang
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China
The desymmetrization of N-pyrazolyl maleimides was realized through an asymmetric Michael addition by using pyrazolones under mild conditions, leading to the formation of a tri-N-heterocyclic pyrazole–succinimide–pyrazolone assembly in high yields with excellent enantioselectivities (up to 99% yield, up to 99% ee). The use of a quinine-derived thiourea catalyst was essential for achieving stereocontrol of the vicinal quaternary–tertiary stereocenters together with the C–N chiral axis. Salient features of this protocol included a broad substrate scope, atom economy, mild conditions and simple operation. Moreover, a gram-scale experiment and derivatization of the product further illustrated the practicability and potential application value of this methodology.
