Synthesis Of Novel Organocatalysts And Their Applications In Asymmetric Michael Additions

Objective:In organic synthesis,Michael addition is a powerful tool to form the C-C bonds.In recent years,more and more attention has been attract to the development of environment-friendly organocatalysis.In this article,several types of benzoyl thiourea and pyrrolidine-based imides catalysts were designed and synthesized.Therefore apply organocatalysis in Michael addition of pyrazolin-5-ones to nitroolefins and Michael addition of cyclohexanone to nitroolefins in water.Methods:?1?In this article,using S-2-aminomethylpyrrolidine,9-amino-9-deoxyepicinchona alkaloids,trans N,N-dimethylaminocyclohexanediamine as starting materials,react with benzoyl isothiocyanate or anhydride to afford target catalyst.?2?The target catalyst was used in the asymmetric Michael addition of pyrazolone to nitroalkene.The optimal reaction conditions were obtained through the conditions screening and to afford the single enantiomers.?3?The target catalyst was used for the asymmetric Michael addition of cyclohexanone and nitroalkene in the aqueous phase.The optimal reaction conditions were obtained through the conditions screening and afford the single enantiomers.Results:?1?Eight benzoyl thioureas and pyrrolidine-based imide catalysts were designed and synthesized and identified by HR-MS,¹HNMR,¹³CNMR and IR.Five of them were not reported.?2?A single S or R enantiomers can be selectively obtained in the reaction of pyrazolones with a series of substituted nitroolefins.Among them,S enantiomers can obtained 85%-96%yield,37%-92%ee value.R enantiomers obtained 85%-96%yield,ee values of 36%-89%.?3?The addition reaction of cyclohexanone with a series of substituted nitroalkenes in water obtain 30%.-92%yield 93%-99%ee value and96:4-99:1 dr valueConclusion:Eight benzoyl thiourea and imide catalysts were designed and synthesized.The reaction of pyrazolones with nitroolefins catalyzed by organocatalysis can afford S or R-type optical isomers with higher yields and higher ee values.Catalytic reaction of cyclohexanone with nitroolefin in the aqueous phase gives higher yields,excellent ee values and excellent dr values.