可回收的l-脯氨酸催化剂在水相中直接催化不对称aldol反应的方法研究-study on the method of directly catalyzing asymmetric aldol reaction with recoverable l - proline catalyst in aqueous phase.docxVIP

摘要可回收的L．脯氨酸催化剂在水相中直接催化不对称Aldol反应 的方法研究摘要手性化合物普遍存在，但是在生物医药领域，大多数手性化合物的两 个对映体有着不同甚至是相反的生物活性和作用。因此人们力求得到有价 值的单一构型的对映体，不对称合成解决了这一问题。L．脯氨酸是合成 C．C键的有机小分子催化剂，由于其在水和空气中稳定，便宜容易制备， 应用简单，无毒无害，在不对称催化合成领域备受关注。从经济环保的角 度出发，人们希望有机反应能够在水等绿色溶剂中进行并且催化剂可以回 收使用。本论文对L．脯氨酸进行衍生，通过引入p．环糊精功能化磁性纳 米粒子，制备了两种能在水相中直接催化不对称Aldol反应的L．脯氨酸催 化剂。在本研究中，成功合成了N4．叔丁基．苯磺L．脯氨酰胺，通过衍生提 高了催化剂的催化活性和立体选择性。它能够在过量酮存在的条件下催化 水相中不对称Aldol反应。相比有机溶剂DMSO和过量环己酮，催化剂 在水相中催化性能最好。还研究了催化剂的普适性，分析了不同芳香醛取 代基电子效应对反应的影响。研究表明，该催化剂虽然有疏水基团，但是 也具有强极性，相比于有机溶剂更倾向于溶于水相，因此用简单的萃取法 可实现催化剂的回收和重复使用，该催化剂能重复使用至少5次。此外，本研究还设计引入p一环糊精功能化Fe304@Si02磁球，万方数据万方数据摘要RECYCLABLE L．PROLINE CATALYSIS SYSTEMSCATALYZE DIRECT ALOLD REACTIoN INⅥ硝汀ERABSTRACTChiral compounds are ubiquity,but in the field of pharmaceutical synthesis．Most of the two enantiomers of chiral compounds have different or even opposite biological activity and function．A single configuration of enantiomers was needed．Asymmetric synthesis solved this problem．L-proline is small organic molecules catalyst for the C—C bond forming．It attracts more attention in the field of asymmetric catalytic synthesis due to its stability in thewater and air,easy preparation and application，non—toxic harmless properties．In the view of economic and environmental protection，it is desired that organic reactions can carry out in green solvent and the catalysts can be repeated and recycled．In this papeL L—proline was derived and 13-cyclodextrin functionalized magnetic nanoparticles were introduced to design tworecyclable catalytic systems which can catalyze direct asymmetric Alold reaction in water．First，anovelN一4-tert—butylbenzenesulfonyl—L—prolineamideorganocatalyst was successfully prepared and its catalytic performance was万方数据北京化工大学硕士学位论文evaluated in the direct aldol addition of cyclohexanone and p-nitrobenzaldehyde．Significantly improved reactivity and stereoselectivity were achieved in various solvents especially in water．Furthermore，substituenteffect on direct aldol addition of cyclohexanone and benzalde