Research Report Based On Asymmetric Michael Addition Reaction And Asymmetric Michael Cyclization Tandem Reaction

The asymmetric Michael addition of 1,3-dicarbonyl compounds and nitroalkenes is an important method for the preparation of chiral γ-nitrocarbonyl compounds.Chiral γ-nitrocarbonyl compounds can be further cyclized and converted into chair dihydrofuranone derivatives.Chiral dihydrofuranone derivatives are important structure of many biologically active natural products and drugs.The asymmetric Michael/C yclization Tandem reaction is one of the important research methods for the synthesis of chiral dihydrofuranone compounds.Therefore,the study of obtaining chiral dihydrofuranone derivatives by asymmetric Michael/C yclization reaction is of great significance.Due to its rigid structure,4-hydroxycoumarin is often used as a special 1,3-dicarbonyl compound in asymmetric Michael addition reactions.At present,the literature about the asymmetric Michael addition/C yclization Tandem reaction of 4-hydroxycoumarin and nitroolefin is very limited,with only two literatures.Furthermore,the limitation of catalyst types,low stereoselectivity and generality need to be improved.Therefore,we hope to expand the catalyst types,the scope of substrates and obtain better stereoselectivity through the study of the asymmetric Michael/C yclization Tandem reaction of 4-hydroxycoumarin and nitroalkenes,which will provide a theoretical basis for the development of chiral4-hydroxycoumarin drugs.The large number of applications of optically active nitrogen-containing heterocyclic compounds in the fields of organic synthesis,medicinal chemistry and material science.As special nitrogen-containing heterocyclic compounds,azole compounds have been widely used in asymmetric Michael addition reactions.At present,through the Scifinder database search,there is no relevant literature report on the asymmetric Michael addition reactio n between chalcone and benzimidazole.In order to explore the types of chiral catalysts suitable for this reaction,obtain better stereoselectivity,expand the scope of substrate application,and provide a theoretical basis for the development of chiral nitrogen-containing heterocyclic drugs,this article has studied the asymmetric Michael addition reaction between chalcone and benzimidazole.1.In the research report on the asymmetric Michael/C yclization Tandem reaction of nitroalkenes and 4-hydroxycoumarin organocatalyzed by cinchona alkaloid derivatives 1a-l,the catalytic system selected by optimizing the conditions was: 10mol% quinidine derived catalyst [(1S)-((2R)-5-(2-((2-((tert-butyldimethylsilyl)oxy)ethyl)thio)ethyl)quinuclidin-2-yl)(6-methoxyquinolin-4-yl)methanol] 1l,chloroform as solvent,3(?) molecular sieve as additive,and react at room temperature.By applying the optimal condition in the asymmetric Michael/C yclization Tandem reaction of 4-hydroxycoumarin with 10 nitroalkenes,the desired products were obtained in moderate yields(40%-87%),with low to excellent stereoselectivities(11%-92% ee).2.In the research report on the asymmetric Michael/C yclization Tandem reaction of nitroalkenes and 4-hydroxycoumarin organocatalyzed by chiral Takemoto’s thiourea derivatives 2a-i,the catalytic system selected by optimizing the conditions was: 10 mol% cyclohexanediamine-derived chiral thiourea catalyst [1-(3,5-bis--(trifluoromethyl)phenyl)-3-((1R,2R)-2-(dimethylamino)cyclohexyl)] 2d,chloroform as solvent,and react at room temperature.By applying the optimal condition in the asymmetric Michael/C yclization Tandem reaction of 4-hydroxycoumarin with 10 nitroalkenes,the desired products were obtained in moderate yields(45%-68%),with low to excellent stereoselectivities(11%-94% ee).3.In a research report that used cinchona alkaloid derivatives 1h-i,1l and chiral Takemoto’s thiourea derivatives 2a-d,2f,2g as organic catalysts to catalyze the asymmetric Michael addition reaction between benzimidazole and chalcone,the catalytic system selected by optimizing the conditions was: 10 mol% chiral urea catalyst[1-(3,5-bis(trifluoromethyl)phenyl)-3-((1S,2S)-2-(dimethylamino)cyclohe--xyl)urea] 2a,0.5 m L dichloromethane as the solvent,and react at room temperature.By applying the optimal condition in the asymmetric Michael addition reaction of benzimidazole with 10 chalcones,the desired products were obtained in moderate yield(40%-65%),with up to 80% stereoselectivity.The cinchona alkaloid derivatives 1a-l have been first applied in the asymmetric Michael/C yclization Tandem reaction of nitroolefins and 4-hydroxycoumarin,which can catalyze the reaction smoothly and obtain good results.The types of catalysts for this asymmetric reaction have been expanded,but the generality of the reaction needs to be improved.The asymmetric Michael addition reaction of benzimidazole and chalcone has not yet been reported in the literature.We studied this reaction for the first time and obtained a stereoselectivity of up to 80% ee.Due to the epidemic,further research on the determination of configuration of the main product of the asymmetric Michael addition reaction between benzimidazole and chalcones,the improvement of stereoselectivity,and the catalytic mechanism are still deepening.