Chiral Phosphine And Amine Catalyzed Asymmetric Annulations Of Morita–Baylis–Hillman Esters

Chiral compounds containing nitrogen,oxygen and sulfur atoms have been found multi-pronged applications in the manufactures of fine chemicals,such as medicine,dyes,spices,pesticides and electronic materials.The development of highly efficient synthesis methods for the preparation of these compounds is still hot research topic in recent years.Thus,developing environmental-friendly,economical and efficient methods to access these compounds is of significant important for the development of fine chemical industry.Organocatalysis,as an environmental-friendly catalytic method,has been rapidly developed in the past decades,and has displayed important applications in the catalytic asymmetric cascade reaction.Great progress has been made by phosphines and amines in catalyzing the formation of cyclic compounds from Morita–Baylis–Hillman(MBH)esters.Under the activation of nucleophilic catalysts,the MBH adducts are transformed to the corresponding phosphonium enolate zwitterions intermediates,often works as C1,C2 and C3 synthons,leading to diverse annulations.In this paper,we designed several annulation reactions involving MBH adducts to construct diverse cyclic compounds.Under the activation of chiral phosphine and amine catalysts,the MBH esters proceeded [3 + 3],[3 + 2] cyclization to yields chiral barbiturate fused dihydropyrans,pyran coumarins and bispiro-oxindoles.The main achievements are as follows:1)Secondary amine thiourea catalysts were designed and synthesized,and employed to promote the [3 + 3] cyclization of MBH acetates with 1,3-dimethylbarbituric acid.Under mild conditions,the chiral barbiturate fused dihydropyrans were obtained in high yields with high enantioselectivities and diasteroselectivities.An efficient and environmental-friendly method for the achievement of barbiturates was successfully established.2)On the basis of above work,the developed method was applied for the preparation of chiral pyran-coumarins.Under mild conditions,chiral pyran-coumarins were obtained in high yields with high enantioselectivities and diasteroselectivities.The mechanism studies indicated that the N-H group participated in the formation of hydrogen bond network,which plays an important role in the chirality-controlled procedures.3)Phosphine(S)-SITCP for the enantioselective [3 + 2] annulation of Morita-Baylis-Hillman(MBH)carbonates and pyrazoloneyldiene oxindoles was developed.A series of chiral bispiro[pyrazolone-3,3'-oxindoles],which possess two contiguous quaternary spiro stereocenters,can be obtained in high yields with excellent enantioselectivities and diastereoselectivities under mild conditions.An efficient and environmental-friendly method for the synthesis of bis spiro-oxindoles has been developed.