导　　师： 周海兵

学科专业： 071010

授予学位： 博士

作　　者： ;

机构地区： 武汉大学

摘　　要： 手性方酰胺作为一类结构特殊并具有良好催化活性的氢键供体催化剂,其设计合成及在不对称催化反应中的应用已经成为不对称催化领域备受关注的研究热点之一。手性方酰胺在不对称催化反应中得到了广泛的应用,目前已经被成功的应用于不对称Michael加成反应、不对称Friedel-Crafts反应、不对称Morita-Baylis-Hillman反应、不对称Aldol反应等不对称催化反应中,并取得了很好的研究进展。我们在前期的研究基础上,设计并合成了两类结构新颖的手性方酰胺催化剂,一类是具有多氢键供体的双功能联二萘酚-金鸡纳碱手性方酰胺有机催化剂；另一类是二氧化硅包裹四氧化三铁/(Fe3O4@SiO2/)磁性纳米颗粒负载的金鸡纳碱手性方酰胺催化剂。然后分别将其应用于不对称催化反应中来考察催化活性及对映选择性。本论文主要包括以下五个部分： 第一部分,根据催化反应的类型,我们分别对近十几年来手性方酰胺类催化剂和Fe3O4@SiO2磁性纳米颗粒负载手性催化剂的研究及应用进展进行了综述。 第二部分,我们设计并合成了两类新颖结构的手性方酰胺类有机催化剂,类是以金鸡纳碱和BINOL为骨架衍生的具有多氢键供体的双功能手性方酰胺催化剂,希望通过各个官能团之间的协同催化作用来实现高活性和高对映选择性。另一类是Fe3O4@SiO2磁性纳米颗粒负载的金鸡纳碱手性方酰胺催化剂,我们希望在保持手性方酰胺催化剂优异的催化性能的前提下,成功实现催化剂的可循环利用性。 第三部分,我们对多氢键手性方酰胺催化剂催化的不对称1,3-二羰基化合物与β-硝基烯的Michael加成反应进行研究。结果表明,以/(S/)-BINOL和奎宁衍生的手性方酰胺催化剂Cat-la,在催化剂用量仅为0.5mmo1/%的条件下,对含有不同取代基的硝基烯及1,3-二羰基化合物均呈现出了很好的催化活性和选择性,对映选择性高达>99/%,非对映选择性高达>99：1。通过这一方法合成了一系列具有高光学活性的硝基异噁唑衍生物和β-氨基酸酯衍生物,从而为开发具有潜在生物活性的手性异嗯唑类药物提供了一条全新途径。 第四部分,设计合成的手性方酰胺催化剂Cat-la也被成功应用于不对称2-羟基-1,4-萘醌对β-硝基烯的加成反应。结果表明,当Cat-la用量仅为0.5mo1/%时,在这一催化体系中仍然表现出了优异的催化活性和选择性/(up to99/%yieldand93/%ee/),进一步研究发现,该有机催化剂在反复使用3次后,依然能保持较高的活性和选择性。加成产物可以进一步衍生化得到手性苯并吲哚衍生物/(upto91/%ee/)。 第五部分,我们将Fe3O4@SiO2磁性纳米颗粒负载的手性方酰胺催化剂Cat-5b应用于不对称1,3-二羰基化合物与β-硝基烯的Michael加成反应中,取得了较好的实验结果/(up to69/%yield,up to93/%ee/),在外加磁场的存在下,催化剂可以迅速的与反应液分离,方便回收利用,该催化剂可以反复回收利用4次而活性和对映选择性没有明显降低。 In recent years, much attention has been paid to hydrogen bonding donor chiral squaramide catalysts owing to their unique structure and excellent catalytic properties. These organocatalysts have been successfully applied into lots of asymmetric reactions, such as Michael addition reaction, Friedel-Crafts reaction, Morita-Baylis-Hillman reaction, Aldol reaction and so on, and made a great progress. Preparation and application of the chiral squaramide catalysts now is a hot topic in field of asymmetric catalysis research. Two kinds of novel chiral squaramide catalysts were designed and developed by our group based on our early researches, which including a series of multiple hydrogen bonding donor BINOL-quinine-squaramide catalysts and Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalysts. Their application in different asymmetric reactions has been investigated, and excellent yields and enantioselectivities as well diastereoselectivities have been obtained. The contents of the thesis were as following: Prat1:The progress of research and application of chiral squaramid catalysts and Fe3O4@SiO2megnetic nanoparticles supported chiral organocatalysts in asymmetric catalysis was introduced according to the asymmetric catalytic reaction types. Prat2:Two kinds of chiral squaramide catalysts were successfully preparaed. One is chiral bifunctional squaramide catalysts derived from BINOL and quinine with multiple hydrogen bonding donors, high yield and excellent enantioselectivity and diastereoselectivity of these catalysts will be realized through the concerted catalysis of all the active groups. Another is the Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalysts, these immobilized catalysts proved to be highly effective in asymmetric Michael addition and could be recycled easily without loss of the activity and enantioselectity. Part3:A set of BINOL-quinine-squaramides bearing multiple hydrogen bonding donors catalysts were used to promote the catalytic enantioselective Michael addition reaction of of β-nitroalkenes to pentane-2,4-dione, in which Cat-la was found to be the best catalyst. After screening the reaction condition, the substrate scope was next investigated. The reaction was catalyzed by Cat-la and the products were obtained with excellent ees and drs /(up to>99/%ee, up to>99:1dr/) at low catalyst loading /(0.5mol/%/). Further more, the methodology was applied successfully to the synthesis of enantiomerically pure isoxazole derivatives and β-amino acid esters. Part4:A chiral BINOL-quinine-squaramide bearing multiple hydrogen bonding donors Cat-la has been identified as the best catalyst for the asymmetric Michael addition of2-hydroxy-1,4-naphthoquinone to β-nitroalkenes, the Cat-la give the products with excellent yields and ees /(up to99/%yield and93/%ee/) at low catalyst loading /(0.5mol/%/). Moreover, the catalyst also could be recycled, after3cycles, it's also with high activity and enantioselectivty. To further illustrate the synthetic potential of this methodology, the synthesis of /(S/)-3-phenyl-2,3-dihydro-1H-benzoindole-4,9-dione was performed with high ee value /(up to91/%ee/). Part5:The Fe3O4@SiO2megnetic nanoparticles supported chiral squaramide catalyst Cat-5b was successfully applied to asymmetric Michael addition of pentane-2,4-dione to β-nitroalkenes to give the products in moderate yields and good ee values /(up to69/%yield, up to93/%ee/). Furthermore, the catalyst can be easily and quickly recycled in the presence of external magnetic field and can be reused for4times without loss of the activity and enantioselectivity.

关 键 词： 手性方酰胺 金鸡纳碱 联二萘酚 多氢键供体 加成反应 磁性纳米颗粒

分 类 号： [O643.36]

领　　域： [理学] [理学]