Desymmetrization of Prochiral N-Pyrazolyl Maleimides via Organocatalyzed Asymmetric Michael Addition with Pyrazolones: Construction of Tri-N-Heterocyclic Scaffolds Bearing Both Central and Axial Chirality.

Content Provider	Europe PMC
Author	Geng, Jianqi Wei, Xingfu He, Biru Hao, Yuting Qu, Jingping Wang, Baomin
Editor	Silverberg, Lee J.
Copyright Year	2023
Abstract	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.
Journal	Molecules
Volume Number	28
DOI	10.3390/molecules28114279
PubMed Central reference number	PMC10254726
Issue Number	11
PubMed reference number	37298754
e-ISSN	14203049
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-05-23
Access Restriction	Open
Subject Keyword	desymmetrization tri-N-heterocycle C–N chiral axis asymmetric Michael addition
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry