【作者】 申国栋；

【导师】 包伟良；

【作者基本信息】 浙江大学 ， 有机化学， 2011， 博士

【摘要】 有效构建碳-杂(N, O, S, Se等)或碳-碳键是有机合成的核心任务之一。过渡金属催化下的交叉偶联反应是一种高效构建碳-碳和碳-杂骨架的重要方法。这就要求我们选择一些绿色、经济、高效和广适的金属催化体系。常用金属Pd和Ni可以很好的催化反应,但自身却存在某些缺点(如：毒性较大、价格较高、通常需要不稳定且剧毒的有机膦作配体等),这大大阻碍了它们在有机合成中的工业化应用。近年来,铜催化偶联反应研究取得了令人瞩目的成就,由于其廉价、低毒等优点,使得铜催化偶联反应显示出广阔的应用前景。基于铜催化反应的一系列优点及应用前景,我们课题组对亚铜催化的偶联反应进行了研究。本论文共分为五章,第一章综述了铜催化偶联反应的发展、研究现状以及发展趋势；第二章主要研究了改进条件下的亚铜盐催化的C-N键的偶联反应；第三章主要研究了亚铜盐偶联在无配体、“一锅法”串联反应中合成杂环化合物中的应用。第四章主要研究了亚铜盐偶联与C-C键氧化断裂/形成反应在合成香豆素类衍生物中的应用。第五章主要研究了优化条件下铁催化的“一锅法”串联反应在合成苯并呋喃衍生物中的应用。第二章主要包括两部分,第一部分研究了CuI/联二萘胺盐酸盐催化的芳基咪唑衍生物的合成。我们以碘代芳烃和咪唑为反应原料,发现了一种高效的CuI/联二萘胺盐酸盐的催化体系,各种取代的卤代芳烃都可以很好的与咪唑偶联。第二部分研究了Cu2O催化的溴代烯烃和咪唑、苯并咪唑的偶联反应合成N-烯基咪唑类化合物。在金属Cu2O和新型配体β-环已酮酸乙酯的催化下,我们建立了一条合成N-烯基咪唑类化合物的方法,该催化体系金属与配体用量较少,反应条件更温和、产率高、且立体选择性好、污染小,有较大的工业化应用前景。随着铜催化偶联反应的发展,利用铜催化偶联反应参与的一锅法串联反应有效构建各种有用的杂环,也是当前铜催化偶联的发展趋势。第三章主要包括三部分,这三部分(第1-3节)主要研究了在无配体条件下CuI催化的一锅法串联反应在合成杂环化合物中的应用。我们发现：在无配体条件下,利用分子间加成-分子内偶联的方法,可通过一锅法从易得原料便捷、有效地合成苯并噻唑、苯并噁唑、苯并咪唑、噁嗪类衍生物。第四章主要研究了铜催化的C-O偶联反应与C-C键氧化断裂/形成反应,通过这两种方法,我们合成了一系列含有杂环的香豆素衍生物。第五章主要研究了优化条件下铁催化的以邻碘苯酚和取代苯乙炔、苯基三甲基硅乙炔为原料的一锅法合成苯并呋喃衍生物反应。该催化体系下FeCl3/邻啡咯啉作为催化剂的用量较少、产率高,各种取代的苯并呋喃衍生物都可以很好的合成。更多还原

【Abstract】 The efficient C-X (X=N,O,S,Se,etc.) or C-C bond formation is one of the most important tasks in organic synthesis. Transition metal-catalyzed cross coupling reaction is a powerful protocol for the formation of C (sp, sp2 or sp3)-C and C-X (N, O, S, Se, etc.) bonds. This requires us to seek for some green, economic, efficient and versatile catalytic systems. The metals Pd and Ni catalyzed reactions usually proceeded well, but it have some intrinsic shortcomings (for example:toxic, higher prices, usually need unstable and highly toxic organic phosphine ligands, etc.), this has greatly impeded their large-scale application in organic synthesis. In recent years, copper catalyzed coupling reaction has made remarkable achievements, because of its low-cost, low toxicity, etc., the copper catalyzed coupling reaction has showed broad application prospects.In view of the advantages and application prospects, the copper catalyzed coupling reaction and optimization of the reaction condition were studied by our group. The dissertation includes five parts. The research development, current progress and trend of copper catalyzed coupling reactions were summarized in chapter one. In the second chapter, we studied the C-N bonds formation of copper (I)-catalyzed reaction under improved condition. In the third chapter, copper-catalyzed coupling reactions have been successfully applied to the assembly of various heterocyclic compounds via ligand-free one-pot strategies. In the forth chapter, we synthesis various of coumarin derivatives by the copper (Ⅰ)-catalyzed coupling reaction and the transition-metal-catalyzed C-C bond oxidative cleavage/re-formed reaction. The last chapter reported the iron-catalyzed "one pot" reaction in the synthesis of benzofuran derivatives under improved condition.The second chapter contains two sections. The first section is the synthesis of N-arylimidazole derivates by the catalyst of CuI/1,1’-binaphthyl-2,2’-diamine dihydrochloride (BINAM). Employing 1,1’-binaphthyl-2,2’-diamine (BINAM) dihydrochloride as an efficient and commercially available ligand, relatively mild and highly efficient copper-catalyzed coupling reaction of imidazole with aryl and heteroaryl halides have been developed. Various functional groups on the aryl halide could be tolerated. The second section is mainly in Cu2O-catalyzed Ullmann-Type reaction of vinyl bromides with imidazole and benzimidazole. We synthesized a series of N-vinylimidazoles under the mild CuI/β-keto ester catalyst system. The catalyst system needs less the amount of the catalyst, the reaction condition is mild, high yields and good stereoselectivity was also got. It has showed large industrial application prospects.Recently, copper-catalyzed coupling reactions have been successfully applied to the efficient assembly of various heterocyclic compounds via one-pot strategies. The third chapter contains three sections. These sections (part 1-3) are the application of copper-catalyzed coupling reactions in synthesis heterocyclic compounds via ligand-free one-pot protocols. We found that some useful heterocyclic compounds such as benzothiazole, benzoxazole, benzimidazole, benzoxazine derivatives could be facilely and efficiently synthesized from readily available materials.In the forth chapter, we studied the copper (Ⅰ)-catalyzed coupling reaction and the transition-metal-catalyzed C-C bond oxidative cleavage/re-formed reaction, various of heterocyclic coumarin derivatives were synthesized.In the fifth chapter, an iron-catalyzed procedure was employed to achieve both the Sonogashira cross-coupling and intramolecular O-arylation of o-iodophenols and aryl acetylenes or 1-aryl substituted-2-trimethylsilyl acetylenes. A variety of benzofurans were synthesized under the catalyst of FeCl3/1,10-phenanthroline. The catalyst system needs less the amount of FeCl3/1,10-phenanthroline and the yield is good.更多还原