【作者】 龙艳；

【导师】 曾佑林； 蔡倩；

【作者基本信息】 湖南师范大学 ， 有机化学， 2014， 硕士

【摘要】 铜催化芳基卤代物与胺类化合物的偶联反应是构建C-N键实现N-芳基化的有力手段。由于Ullmann类C-N偶联反应的反应位点不直接涉及手性中心的形成,因此实现不对称铜催化Ullmann类偶联反应仍然是一个挑战。通过实验室前期工作的积累,我们发展了铜催化的不对称Ullmann构建C-N键的偶联反应。本文的主要内容为：利用Cu催化Ullmann反应,通过不对称去对称化以及动力学拆分两种手段分别构建了含C-N键的手性含氮杂环化合物。第一部分：去对称化的Ullmann C-N偶联反应以含有潜手性中心的氰基伯胺类对称分子为反应底物,在碘化亚铜和手性配体(R)-BINOL衍生物的共同作用下,通过分子内的UllmannC-N偶联反应,高选择性的合成了含有手性季碳中心的四氢喹啉类化合物,其产物的ee值最高可以达到94%,收率90%。第二部分：动力学拆分的Ullmann C-N偶联反应动力学拆分在不对称催化研究中是一种有效的获得单一手性化合物的手段。基于前期去对称化中所需对称分子的限制,本部分以氰基伯胺类化合物为原料在碘化亚铜和手性配体(R)-BINOL衍生物的作用下,通过动力学拆分的手段,实现分子内的Ullmann不对称C-N偶联反应,对映选择性的合成了含有手性季碳中心的四氢喹啉类化合物。拆分后反应残余底物的ee值最高可以达到85%,C-N偶联反应产物的ee值可以达到75%。本文通过不对称去对称化和动力学拆分两种手段,详细研究了铜催化的不对称Ullmann偶联反应,成功的实现了带有手性中心的C-N键偶联反应。更多还原

【Abstract】 Copper-catalyzed coupling reactions of aryl halides with amines may be the most powerful methods for theformation of N-arylation products.Achieving enantioselectivity in Ullmann-type reactions still remains as a significant challenge, since the copper-catalyzed aryl carbon-heteroatom coupling didn’t involve with the direct formation of a chiral centers. The main content of this paper focuses on:Copper-catalyzed Ullmann coupling reaction for building the chiral N-Heterocycles through asymmetric desymmetrizations and kinetic resolutionsPart I Desymmetric Intramolecular Ullmann C-N CouplingEnantioselective desymmetrization is an efficient method in asymmetric synthesis. In this paper,we are developing copper-catalyzed asymmetric Ullmann coupling reaction to build C-N bound. Starting from3-amino-2,2-bis(2-iodobenzyl) propanenitrile, under the Cul and (R)-BINOL-derived ligands, we synthesied the1,2,3,4-tetrahydroquinolines in highly enantioselectively through intramolecular Ullmann coupling.The product enantiomeric excesse could up to94%,yiled90%.Part II Intramolecular Ullmann C-N coupling via kinetic resolutionThe kinetic resolution is an efficient method to obtain highly enantioselective products in the studies of asymmetric catalysis. Based on the asymmetric desymmetrization strategy, the products bear two aryl rings with similar substitutes, To overcome these problems and increases variations in copper-catalyzed intramolecualr N-arylation.This work started from3-amino-2-benzyl-2-(2-iodobenzyl)propanenitrile, under the CuI and (R)-BINOL-derived ligands,1,2,3,4-tetrahydroquinolines were sythesied though intramolecular Ullmann coupling. The residue substrate could up to85%and pruduct to75%.In summary,this work studied copper-catalyzed Ullmann-type reactions through asymmetric desymmetrizations and kinetic resolutions in detail.We successful developed C-N coupling reaction bearing a chiral quaternary carbon center更多还原