【作者】 邢延朋；

【导师】 吕萍； 王彦广；

【作者基本信息】 浙江大学 ， 有机化学， 2014， 博士

【摘要】 杂环化合物是最大的一类有机化合物,由于其独特的结构和性质,使得它们在许多领域中有着非常重要的用途。含氮杂环化合物作为杂环化合物家族中的重要成员,在生物、医药、材料等多个领域扮演着至关重要的角色。因此含氮杂环化合物的合成一直是有机合成化学领域研究的热点。发展简单的,安全的,高效的合成含氮杂环化合物的新方法,一直是有机合成化学家们努力的方向。本论文全面综述了烯酮亚胺的形成方法及其在杂环化合物合成中的重要应用。在此基础之上,发展了三类基于烯酮亚胺中间体合成含氮杂环化合的新反应和新方法。主要内容如下：1.发展了一种一价铜催化的磺酰叠氮,端基炔烃和氯代亚胺参与的四组分反应,高产率和高立体选择性地构筑了多功能化的2-亚胺氮杂环丁烷类化合物。原料易得,操作简便,反应条件温和,基团适应性广。我们成功地证明了该反应是按照一种新颖的平行催化的反应模式进行的,反应过程包含了两个相互平行的催化循环：CuAAC生成N-磺酰基烯酮亚胺的催化循环和铜催化的Csp2-Csp偶联反应循环。同时,所得到的产物只需经历一步简单的反应便可转化成一类结构更为新颖的四员环并七员环化合物,此种结构的化合物通过传统的合成方法是很难得到的。2.围绕4-取代丁二炔参与CuAAC反应生成的β-炔基烯酮亚胺中间体,我们发展了一种合成吡唑类和嘧啶磺酰亚胺类化合的新方法。在研究过程中,我们采取了由简入难,层层递进的研究策略。根据β-炔基烯酮亚胺与胺类化合物的亲核加成反应所得的实验结果,我们推测反应可能先后经历了两个具有高亲电反应活性位点的中间体：β-炔基烯酮亚胺中间体和联烯亚胺中间体。在此基础上,我们巧妙地选择了酰肼类化合物作为1,2-双亲核试剂来捕获β-炔基烯酮亚胺中间体及其后续产生的联烯亚胺中间体,成功地合成了一系列吡唑类化合物,这也证实了我们之前对反应机理的推测。接下来,我们进一步将此反应的应用范围扩展到了合成六员杂环化合物。应用具有1,3-双亲核反应位点的脒类化合物来捕获β-炔基烯酮亚胺中间体及其后续产生的联烯亚胺中间体,我们成功地合成了一系列嘧啶磺酰亚胺类化合物。3.发展了一类基于Staudinger反应和Wolff重排反应的串联反应,高效便捷地合成了一系列具有苯并[b]咔唑骨架的荧光化合物。该反应经历了关键的烯酮亚胺中间体及其参与的分子内双自由基环化的反应历程,操作简便,普适性好,为构筑苯并[b]咔唑类化合物提供了全新的思路。值得指出的是,通过该方法我们首次合成了具有全新骨架的线性杂并苯类化合物以及分子中同时具有苯并[b]咔唑结构和荧蒽结构的化合物。我们还进一步对所得化合物的光物理性质进行了测定,并结合理论计算,对其荧光性能进行了评估。实验结果表明我们合成的这一系列化合物具有比较宽的荧光发射波长,介于410-521nm之间,并且最高的荧光量子效率达到了62%。这就意味着我们合成的这一系列荧光分子将有可能在光电材料以及新型荧光传感器等研究领域得到比较好的应用。4.从分子内稳定三氮唑中间体的思路出发,发现并发展了一类基于CuAAC反应合成3-重氮吲哚亚胺类化合物的新方法。该方法原料易得,操作简便,反应条件温和,基团适应范围广。我们推测反应可能经历了吲哚并三氮唑中间体,由于磺酰基强的吸电子作用和并环结构环张力的存在,使得吲哚并三氮唑中间体中的三氮唑环容易发生环链异构化得到开环的3-重氮亚胺类化合物。我们进一步对3-重氮吲哚亚胺类化合物作为卡宾前体的化学进行了研究,合成了一系列结构新颖的吲哚衍生物。更多还原

【Abstract】 The heterocyclic compounds is the largest class of organic compounds. Given its unique structure and properties, they play an important role in many areas. As one of the most important heterocyclic compounds, nitrogen-containing heterocyclic compounds are widely used in biology, pharmaceutical chemistry and material. Synthesis of nitrogen-containing heterocyclic compounds has been a hot research field of organic synthetic chemistry. Development of simple, safe and efficient methods for the synthesis of new nitrogen-containing heterocyclic compounds is the mission of synthetic organic chemists. Based on the summary of reported synthetic methods of ketenimines and their utilizations in building heterocyclic compounds, three new methods were developed for the synthesis of nitrogen-containing heterocyclic compounds on the basis of ketenimines. The details are summarized as following:1. A novel Cu-catalyzed fourcomponent reaction of imidoly chlorides, sulfonyl azides, and two terminal alkynes was developed, which afforded polyfunctionalized azetidin-2-imines in good to excellent yield with high diastereoselectivity. Startingmaterials are easily accessible. This one-pot reaction proceeded smoothly at room temperature with easy operation. It occurred in a parallel catalysis manner, including a copper catalyzed Csp-Csp2coupling, a copper-catalyzed alkyne azide cycloaddition, and a [2+2] cycloaddition. All of these separate reactions represent the frontier of modern organic chemistry and fit the basic requirements of green chemistry with high atom economy. Moreover, the synthesized azetidin-2-imines could be conveniently converted into the structurally interesting dihydroazeto[1,2-a]benzo[e]azepin-2(4H)-immes.2. A concise and efficient method for the synthesis of polyfunctionalized pyrazoles and pyrimidine-imides was developed based on the CuAAC with the participation of4-substituted-1,3-butadiyne. Two key intermediates, β-alkynylketenimine and allenyl-imine, were included in this transformation and both of them were high nucleophilicity. Using hydrazides as1,2-dinucleophile, the β-alkynylketenimine and allenyl-imine intermediates were captured successively and a series of polyfunctionalized pyrazoles was successfully synthesized in high yields with good regioselectivity. Furthermore, we extended the application of this method to the synthesis of six-membered rings. Using amidine as1,3-dinucleophile, a series of pyrimidine-imides was synthesis in high yields with good regioselectivity. This methodology is concise, general, efficient, and atom-economic and could have a bright future in organic synthesis.3. Tandem reactions for the synthesis of benzo[b]carbazoles, benzo[b]benzo[5,6]indolo[3,2-h]carbazoles, fluoreno[9,1-ab]carbazoles, and fluoreno[9,1-ab]fluoreno[1’,9’:5,6,7]indolo[3,2-h]carbazoles have been developed. The one-pot reaction involved a tandem Wolff rearrangement/aza-Wittig reaction/biradical cyclization/1,5-H shift process. A variety of substrates were suitable for this reaction. The products have been demonstrated to emit lights at a range of410-521nm with quantum yields up to62%in dichloromethane solution. It is believed that the synthesized compounds might be fabricated in optoelectronics devices for material science study or applied as new fluorophores in the development of new fluorescent chemosensors in life science.4. From the thought of stabilizing1-copper-1,2,3-triazole intermediates through intramolecular coordination, a concise and efficient method for the synthesis of3-diazoindolinimines was developed from o-alkynylanilines and sulfonyl azides based on CuAAC. The reaction proceeded smoothly at room temperature with easy operation. Although the expected triazoloindoles were not obtained, we speculated that the final products3-diazoindolinimines were transformed from triazoloindoles through ring-chain isomerizations. Furthermore, the obtained3-diazoindolinimines could be utilized as a-imino carbene precursors for the constraction of a range of valuable indole molecules including pyrrolo[2,3-b]indoles, spirocyclopropyl iminoindoles,2,3-dihydropyrrolo[2,3-b]indoles,3,3’-biindoles, and2,3’-biindoles.更多还原