手性联萘胺类化合物的合成

发布时间：2018-04-13 08:15

本文选题：轴手性联芳烃类 + BINAM　；参考：《第四军医大学》2014年硕士论文

【摘要】：1,1’-binaphthyl-2,2,-diamine(BINAM)衍生物是非常有用的手性联芳烃类化合物，和几个以BINAM为基础的催化剂已经用于不对称催化。然而，缺少合适的合成方法阻碍了它们的发展。立体选择性的合成BINAM的方法很少，BINAM的合成主要依赖于传统的合成方法，虽然有些立体选择的氧化耦合的报道。与BINOL不同，氧化耦合方法并不十分有效。酸催化二芳基肼[3,3]-重排可能是一个合成外消旋或光学活性的BINAM衍生物的有效的和通用的方法。最近，Kürti和List小组使用手性磷酸酸催化二芳基肼[3,3]-重排合成光活性的联萘胺。不幸的是，这种方法从实际来看，二芳基肼和手性磷酸酸的合成十分困难。立体选择,方便和有效的合成结构多样化BINAM衍生物将对于发现新的联芳烃类手性配体和催化剂有深远的影响。本论文研究工作描述一个有效和实用的合成光活性BINAM衍生物的[3,3]-重排的方法。 1.使用金属催化卤代芳烃与胺类化合物的交叉偶联，用于合成薄荷氧羰基保护的二芳基肼，筛选了不同配体和金属的组合，反应温度，反应时间和溶剂等，来得到最佳的反应条件，使得产率最高。 2.在N,N'-双(2-萘基)-肼基甲酸-(-)-薄荷酯等发生分子内重排反应的反应中，我们筛选了不同的酸、溶剂、反应温度和反应时间等，确定了最佳的反应条件，使得杂质最少，，产率最高。 3.探索了52a等化合物酰胺键的水解条件，分别使用酸水解和碱水解两种方式可以得到产物联萘胺及其衍生物，酸水解得到的产物中有杂质生成，而碱水解基本定量反应，产率很高。使用HPLC检测所得产物ee值都在99%以上。本论文设计合成了光学活性的联萘胺及其衍生物，为手性联萘胺及其衍生物的合成提供了一条可行有效的合成途径，为手性联萘胺的进一步应用打下了基础。
[Abstract]:However, their development is hampered by the lack of suitable synthetic methods.The synthesis of BINAM by stereoselectivity is rare. The synthesis of binam mainly depends on the traditional synthesis methods, although some stereoselective oxidative coupling reports have been reported.Unlike BINOL, the oxidative coupling method is not very effective.Acid catalyzed diarylhydrazine [3o 3]-rearrangement may be an effective and universal method for the synthesis of racemic or optically active BINAM derivatives.Recently, the K 眉 rti and List groups used chiral phosphoric acid to catalyze the synthesis of photoactive binaphthylamine from diarylhydrazine [3o 3]-rearrangement.Unfortunately, in practice, the synthesis of diarylhydrazine and chiral phosphoric acid is very difficult.Stereoselective, convenient and effective synthesis of diversified BINAM derivatives will have a profound impact on the discovery of new chiral biarene ligands and catalysts.This paper describes an effective and practical method for [3H3]-rearrangement of photoactive BINAM derivatives.1.Metal catalyzed cross-coupling of halogenated aromatics with amine compounds was used to synthesize menthoxy carbonyl protected diaryl hydrazine. Different ligand and metal combinations, reaction temperature, reaction time and solvent were screened.To obtain the best reaction conditions, making the highest yield.2.3.The hydrolysis conditions of amide bond of 52a and other compounds were explored. Binaphthylamine and its derivatives were obtained by acid hydrolysis and alkaline hydrolysis, respectively.The yield is very high.The ee value of the products detected by HPLC was above 99%.In this paper, the optically active binaphthylamine and its derivatives are designed and synthesized, which provides a feasible and effective way for the synthesis of chiral binaphthylamine and its derivatives, and lays a foundation for the further application of chiral binaphthylamine.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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