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.

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.