节点文献
芳香醇化合物的绿色合成和不对称合成研究
【作者】 惠爱玲；
【导师】 汪志勇；
【作者基本信息】 中国科学技术大学 ， 有机化学， 2006， 博士
【摘要】 醛酮的烷基加成反应是合成C-C键的重要方法之一，同时合成的仲醇和叔醇是重要的有机合成的中间体，已被应用于许多含有仲醇和叔醇结构的复杂天然产物的合成中。通过简便有效的方法实现这一反应的绿色合成是有机化学的一项重要任务。同时，将这一反应发展成为具有高度对映选择性的不对称反应在合成含有手性芳香醇结构的药物或生物活性物质方面将具有更重要的意义。 本论文主要研究了烯丙醇化合物的绿色合成、醛的不对称烯丙基加成反应、烷基锌对醛酮的不对称加成反应。主要内容如下： 1．用双金属体系Zn／InCl3（cat．）在饱和NH4Cl溶液中，实现了水相中烯丙基氯与醛酮的高效加成。另外，对该反应的区域选择性也进行了研究。这一体系同以前单独用金属锌或金属铟促进的烯丙基化反应相比，可以使用活性低的烯丙基氯替代烯丙基溴来实现这一反应，而且反应速度加快，反应条件温和。此外，还发现烯丁基氯与醛酮的反应产率也非常高，并且给出了较好的区域选择性以及中等的非对映异构选择性。 2．利用天然的手性源樟脑、氨基酸、酒石酸衍生了一系列含羟基胺基的手性配体。这些配体的类型广泛，其中两齿配体有：羟基樟脑磺酰胺配体、氨基酸衍生的磺酰氨基醇配体以及酒石酸衍生的TADDOL类配体；三齿配体有氨基酸衍生的亚胺及还原产物；四齿配体如酒石酸衍生的C2-对称性的樟脑磺酰胺配体以及类SALEN配体。将这些手性配体依次用于金属锌、锡、铟促进的不对称的烯丙基的加成反应，但是没有获得可以接受的对映异构选择性。 3．在羟基樟脑磺酰胺配体的苯环上不同位置引入不同类型的取代基，研究了苯环上的取代模式及电子效应对二乙基锌与醛加成反应的产率及对映异构选择性的影响，从中筛选出配体3-16可以给出较好的结果（95％yield，72％ee），以此配体为模型，系统研究了该反应的溶剂效应、反应计量的影响、温度效应，从而确立了最合适的催化条件。在此条件下，研究了配体3-16对其它芳香醛底物的适应性，得到了高达83％ee。 4．利用酒石酸衍生出了一系列C2-对称轴的磺酰胺配体，并将这些配体应用于二乙基锌与醛的加成反应，从中优化出配体3-36可以给出较好的选择性。随后系统考察了反应溶剂、反应温度、时间、配体的用量及底物结构的影响，从而可以给出高达83％ee。
【Abstract】 The addition of alkyl group to aldehydes and ketones is one of the most important methods in forming C-C bond, which may also produce sec-alcohol or tert-alcohol as valuable intermediate compounds applied in the synthsis of natural products. Performing the reaction via green method is one of the imperative tasks in organic chemistrys. At the same time, expanding the addition into asymmetric one with high enantioselectivity may lead to its siginificant application in synthesizing medicaments and biologically active compounds.This thesis reported the research about the green synthesis of homoallylic alcohol, the asymmetric allylation of aldehydes, the asymmetric addition of dialkylzinc to aldehyde and ketones. The concreate content is as below:1. In saturated NH4CI solution, Zn/InCb （cat.）-mediated allylation of carbonyl compounds and allylic chloride could proceed smoothly to give the desired product in high yield. The regioselectivity and diastereoselectivity were also studied. Compared to the prior reports, the reaction can be carried out using allylic chloride instead of allylic bromide in the system, and it is a simple, efficient and environmentally benign synthesis method. Furthermore, crotyl chloride also gave excellent yields in this system. The reaction gave exclusively γ-adduct in most cases with medium diasteroselectivity.2. A series of chiral ligands containing hydroxyl and amido were derived from natural camphor, amino acid and tartaric acid, such as hydroxyl camphor sulfonylamide, sulfonamide alcohol, TADDOL, imine and its reductive product, C2-symmetric camphor sulfonylamide and SALEN analogue. Employing these ligands into the allylation mediated by zinc, tin, indium, no acceptable enantioselectivity was obtained.3. Different substituents were introduced in the phenyl ring of hydroxyl camphor sulfonamide. The influences of substitution patterns, electronic property were studied in the diethylzinc to aldehyde, chiral ligand 3-16 was choosed as the best one （95% yield, 72% ee）. Subsequently, varying the solvent, the temperature and the stoichiometry, the best condition was established and 83% ee was obtained in the system.