The Study Of The Construction Of Pyran Derivatives Through Asymmetrical [3+3] Cascade Reaction Catalyzed By Thiourea And Squaramide Catalysts

Chiral compounds are widely found in all kinds of life forms in nature and play an important role in the process of drug development.The asymmetric reaction can be catalyzed by enzyme catalysts,metal catalysts and organic catalysts.Organic catalysis is an environmentally friendly and universal catalytic method.Asymmetry synthesis could be catalyzed by various catalysts,which include thiourea catalysts,squaramide catalysts,phosphoric acid catalysts,carbene catalysts,proline catalysts and so on.Thiourea catalysts and squaramide catalysts embrace some advantages which include easily accessible starting material,good universality and effect.Pyrans are often used as precursors of a variety of drugs.[3+3] cascade reaction is an important method to construct pyrans.However,when enynes are used as the substrate of [3+3] domino reaction,products of double bond outside the ring are obtained.To obtain isomerized pyran derivatives,we proceeded the [3+3] cascade reaction between pyrazolone and enynes catalyzed by thiourea and squaramide catalysts.The squaramide catalysts were better than the thiourea catalysts for the [3+3] cascade reaction between pyrazolone and enynes,which delivered 70% yield and 76% ee vaule.Next,solvents,catalyst dosage,material ratio and reaction temperature were screened.Finally,the yield increased to 86% and the ee value increased to 79%.After obtained the optimal reaction conditions,the study of pyrans synthesizing by various substracts was performed,which delivered 53-88% yield and 68-84% ee vaule.To obtain the absolute configuration of the product,the crystal of product 3ac was detected by XRD ray diffraction.Finally,this thesis also deduced reaction mechanism.