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

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.

Keywords

• desymmetrization
• tri-<i>N</i>-heterocycle
• C–N chiral axis
• asymmetric Michael addition