【作者】 张晶；

【导师】 陈立功；

【作者基本信息】 天津大学 ， 应用化学， 2019， 博士

【摘要】 含有氮、氧、硫等元素的手性化合物在医药、染料、香料、农药、电子材料等精细化工领域均有重要应用。开发新型高效的合成方法,获取这些化合物依然是近年来的研究热点。发展一系列环境友好、经济、高效的手性杂环化合物合成方法,无疑对我国精细化工行业的发展具有重要意义。近年来,有机催化作为一种环境友好的催化方法发展迅速,在催化不对称串联反应中得到了广泛应用。其中膦、胺等有机催化剂在催化Morita–Baylis–Hillman(MBH)酯化物形成环状化合物方面取得了重要进展。MBH酯化物能够在膦、胺作用下生成烯丙基叶立德中间体,作为C1、C2、C3合成子发生串联环化反应,构造形式多样的杂环结构。基于此,本文设计了几种在手性膦、胺催化剂作用下MBH酯化物参与的3+3、3+2环化反应,手性合成巴比妥酸稠合的四氢吡喃化合物、香豆素骈吡喃化合物、双螺环氧化吲哚化合物。主要研究工作如下:1)设计合成了5种仲胺硫脲类催化剂,用于催化?-硝基苯乙烯衍生的MBH醋酸酯与1,3-二甲基巴比妥酸的3+3环化反应。在温和反应条件下,以高产率、高对映选择性和非对映选择性获得了巴比妥酸稠合的四氢吡喃化合物。建立了一种绿色、高效合成手性巴比妥酸衍生物的方法。2)在上述工作基础上,将建立的催化方法用于合成手性香豆素骈吡喃化合物。在温和反应条件下,以高产率、高对映选择性及非对映选择性获得了香豆素骈吡喃化合物。反应机理研究表明:催化剂结构中的氮氢参与形成氢键网络,对反应的立体选择性控制有十分重要的作用。3)发展了螺环膦(S)-SITCP催化MBH碳酸酯与吡唑酮基、吲哚基乙烯的3+2串联环化反应。实现了在温和反应条件下,以高产率、高对映选择性及非对映选择性合成含有两个连续季碳中心的双螺环氧化吲哚化合物。发展了一种绿色、高效合成双螺环氧化吲哚的方法。更多还原

【Abstract】 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.更多还原