Asymmetric Michael Addition And Synthesis Of Polycyclic Pyrrole Compounds Based On Nitroene Compounds

Nitroolefins compounds are important nitrogen-containing organic compounds and organic reaction building blocks for synthesis.They can be used as Michael addition reaction receptors and key intermediates for preparing polycyclic pyrrole compounds.Asymmetric Michael additions are one of the most effective organic synthesis methods to construct C-C bond,and the asymmetric Michael addition products of aldehydes and nitroenes are important materials for synthesizing many kinds of chiral drugs and natural product molecules.L-prolinamides are one of the important chiral catalysts for the catalytic asymmetric Michael addition reaction.The development of new methods for the asymmetric Michael addition reaction of aldehydes and nitroenes catalyzed by L-prolinamides,and construction of polycyclic pyrrole compounds library based on nitroene polycyclic pyrrole skeleton have important research significance.In this paper,the synthesis of nitroene compounds,asymmetric Michael addition reaction and the advance of synthesis polycyclic pyrrole compounds have been reviewed.Six novel prolylamine chiral catalysts were designed,synthesized,and used successfullyas organic catalysts in the asymmetric Michael addition reaction of aldehydes and nitroenes.In addition,a series of polycyclic pyrrole compounds were synthesized based on multi-component "one-pot" reaction of nitroolefins in this paper.Via the reactions of amidation and de-Boc protecting groups,six novel L-Prolinamides catalysts were synthesized by using N-Boc-amino acid,N-Boc-L-proline and diphenylmethylamine or triphenylmethylamine as smaterials tarting material and reagents.A methodological study on the catalytic application of chiral catalysts in the asymmetric Michael addition of aldehydes with nitroenes was carried out.Under the optimum reaction conditions,the catalyst 160 exhibits the desired catalytic activity and stereoselectivity in the asymmetric Michael addition reaction of the aldehyde with the nitroene.17 asymmetric Michael addition products were synthesized in high yield(82%-94%),excellent diastereomeric selectivity(60:40-99:1,dr)and practical selectivity(85%-99%,ee)(Fig.1).This study may provide some theoretical guidance for the discovery and application of novel chiral catalysts and the development of some chiral drugs.Fig.1 Asymmetric Michael addition reaction of aldehydes and nitroenes catalyzed by 160A highly efficient multi-component "one-pot" synthesis method for preparing novel polycyclic pyrrole compounds was established basing on the reactions of nitroenes,chiral amino acids and acenaphthene quinones.Under the optimum reaction conditions,22 novel polycyclic pyrrole derivatives were synthesized in excellent yield(81%-91%)(Fig.2).All compounds were characterized by 1H-NMR spectroscopy(nuclear magnetic resonance(NMR)),13C-NMR(nuclear magnetic resonance(NMR)),high resolution mass spectrometry,infrared spectroscopy and melting point.The experimental results shown that the electron-withdrawing groups of nitroene compounds(172)such as Cl,Br and CF3 is advantageous for the reaction to proceed(Yield 84%-89%).The reaction is equally applicable to multicomponent reactions involving nitroene compounds having electron donating substituents(CH3,OCH3).The synthetic method has excellent universality for amino acid(62)compounds of different structures.When X is CH2(S or(CH2)2),the corresponding polycyclic pyrrole derivative is synthesized in the ideal yield.This study can lay the foundation for the establishment of novel polycyclic pyrrole compounds and the discovery of novel drug molecules.Fig.2 Synthesis of Novel Polycyclic Pyrrole Compounds...