【作者】 陆居有；

【导师】 付华；

【作者基本信息】 清华大学 ， 化学， 2013， 博士

【摘要】 氮杂环化合物广泛存在于天然产物和生物活性分子中，在医药和农药化学领域具有重要用途。在过去几十年里，过渡金属催化交叉偶联反应合成杂环化合物一直是研究的热门领域。近年来，C-H键直接功能化取得了很大的进步，普遍应用于氮杂环化合物的合成中。本博士论文主要围绕过渡金属催化含氮稠杂环化合物的新合成方法展开研究，取得了如下重要研究成果。发展了一种简单、高效铜催化“一锅法”制备苯并咪唑[1,2-b]异喹啉-11-酮衍生物的新方法。反应使用廉价的CuCl作催化剂，易得的2-卤代-N-（2-卤苯基）苯甲酰胺衍生物和烷基2-氰基乙酸酯或者丙二腈为起始原料，无需任何配体或者添加剂。该方法具有原子经济、高效、底物易得以及条件温和等优点，为苯并咪唑并异喹啉酮类化合物的合成提供了一种新的途径。发展了一种铜催化串联反应合成烷基6-氨基苯并咪唑[2,1-a]异喹啉-5-羧酸酯衍生物的新方法。该方法以廉价、低毒的CuI作为催化剂，以易得的2-（2-卤苯基）苯并咪唑衍生物和烷基2-氰基乙酸酯作为起始原料，制备的产物中包含氨基和酯基，为目标分子的进一步修饰奠定了良好的基础。该方法底物官能基容忍性较好，为制备苯并咪唑并异喹啉类化合物提供了新的路径。发展了一种钯催化选择性芳烃C-H键酰化合成芳基酮和异吲哚并苯并咪唑衍生物的新方法。该方法以Pd（OAc）₂作催化剂，易得的羧酸为酰化试剂，三氟乙酸酐为羧酸活化试剂，目标产物收率较高。该方法底物官能基容忍性较好，无需配体参与，具有较高的选择性，为制备芳基酮和异吲哚并苯并咪唑类化合物提供了新的途径。发展了一种高效铜催化需氧氧化分子内烯烃C-H键胺化构建氮杂环的新方法。该方法使用廉价、易得的三氟乙酸铜作催化剂，取代的3-苯亚甲基-2-吡啶-2-甲基-1,3-二氢-异吲哚-1-酮为起始原料，特戊酸作添加剂，采用经济实惠、环境友好的空气作为氧化剂。该方法首次实现了异喹啉酮并1,4-二氢吡嗪衍生物的人工合成，为含氮稠杂环化合物的合成提供了新的途径。更多还原

【Abstract】 N-Heterocycles are ubiquitous in a variety of natural products and biologicallyactive molecules, and they play important roles in the pharmaceutical and agrochemicalindustries. The development of transition metal-catalyzed cross-coupling reactions forthe formation of heterocycles continues to be an active area of research. Recently, thedirect functionalization of C-H bonds has made great progress. Their application on theconstruction of N-heterocycles has been reported. In this dissertation, new transitionmetal-catalyzed methods have been developed for synthesis of N-fused heterocycles,and some important results were obtained.A simple and efficient copper-catalyzed one-pot tandem method has beendeveloped for synthesis of benzimidazo[1,2-b]isoquinolin-11-one derivatives. Theprotocol used cheap CuCl as the catalyst, readily available substituted2-halo-N-（2-halophenyl）benzamides and alkyl2-cyanoacetates or malononitrile as thestarting materials. The couplings of substituted2-halo-N-（2-halophenyl）benzamideswith alkyl2-cyanoacetates or malononitrile were performed well under mild conditionswithout addition of any ligand or additive, and the correspondingbenzimidazo[1,2-b]isoquinolin-11-ones were obtained in good to excellent yields. Thepresent method shows economical, practical and starting material readily availableadvantages over the previous methods, so it will provide a new strategy for constructionof diverse and useful N-fused heterocyclic compounds for organic chemistry andmedicinal chemistry.A convenient and efficient copper-catalyzed cascade method has been developedfor synthesis of benzimidazoisoquinoline derivatives. The protocol used inexpensiveCuI as the catalyst, readily available substituted2-（2-halophenyl）benzoimidazoles andalkyl cyanoacetates as the starting materials, and the corresponding alkyl6-aminobenzimidazo[2,1-a]isoquinoline-5-carboxylates were obtained in good toexcellent yields. The novel method provides diverse and useful N-fused heterocycles forcombinatorial chemistry and medicinal chemistry.A convenient and efficient palladium-catalyzed synthesis of aromatic ketones andisoindolobenzimidazoles has been developed via selective aromatic C-H bond acylation. The protocol used Pd（OAc）₂as the catalyst, readily available carboxylic acids as theacylating reagents,（CF₃CO）₂O as the activated agent of the acids, and thecorresponding aromatic ketones and isoindolobenzimidazoles were obtained in good toexcellent yields. The novel and practical method provides a new and useful strategy forsynthesis of aromatic ketones and isoindolobenzimidazoles.An efficient copper-catalyzed aerobic oxidative intramolecular alkene C-Hamination leading to N-heterocycles has been developed. The protocol used cheap andreadily available Cu（O₂CCF₃）₂as the catalyst, substituted3-benzylidene-2-pyridin-2-ylmethyl-2,3-dihydro-isoindol-1-ones as the startingmaterials, economical and environment friendly air as the oxidant, and thecorresponding N-heterocycles were obtained in good to excellent yields. This methodshould provide a new and useful strategy for constructing N-fused heterocycles.更多还原