可见光驱动的腙类氮自由基产生及其环化反应研究

发布时间：2018-04-19 20:26

本文选题：含氮杂环 + 可见光催化　；参考：《华中师范大学》2017年博士论文

【摘要】：含氮杂环广泛存在于天然产物、功能材料以及一些具有重要生理活性的药物分子中。氮自由基由于其活泼的化学性质和独特的反应特性,为碳-氮键的高效、高选择性构建提供一条有效方法。然而,和碳自由基相比,氮自由基一般较难产生,这极大的限制了它在有机合成中的广泛应用。近年来,可见光诱导的光氧化还原催化为氮自由基的温和产生提供了一条新的思路。本论文详细概述了该领域的最新研究进展,并围绕可见光诱导的氮自由基反应开展了相关研究工作。具体内容如下:首先,我们发展了可见光诱导的氧化脱质子电子转移催化模式(ODET),实现了可见光诱导腙的N-H键直接转化为氮中心自由基,并将该策略成功应用于β,γ-不饱和腙的氢胺化反应,温和高效地合成了一系列具有重要生物活性的二氢吡唑类化合物。通过荧光淬灭实验和相关的控制实验,我们提出了可能的反应机理。与此同时,我们通过底物的合理调控和催化体系的筛选,成功实现了可见光诱导的氮自由基6-endo串联环化反应,并将该反应策略应用于一类具有良好生物活性的二氢哒嗪类化合物的构建。值得一提的是,通过两步简单的合成转换,我们可以得到一类具有良好抗菌活性的哒嗪盐类化合物。此外,通过DFT理论计算和相关的控制实验,我们提出了可见光诱导的氧化脱质子电子转移(ODET)以及四甲基哌啶氮氧化物(TEMPO)辅助的氢原子转移反应机理。另外,我们通过将可见光催化和氧气氧化相结合,实现了温和条件下烯基腙的胺氧化反应。在该反应体系里需要加入催化量的TEMPO(10 mol%)作为有机共催化剂,以提高氮自由基的产生效率。通过合理的条件筛选,我们最终以氧气作为绿色氧化剂,有机染料作为廉价的光敏剂,在室温条件下以中等到较好的收率得到了烯烃胺氧化的产物。此外,我们使用当量的二乙酸碘苯PhI(OAc)2作为氧化剂,以及1,4-二氮杂二环[2.2.2]辛烷作为有机碱,成功实现了无金属参与条件下烯烃的氢胺化和氧胺化反应。机理研究表明该反应是通过氮自由基中间体进行的。值得一提的是,该反应可以成功拓展到烯基肟的氢氧化反应和双氧化反应之中,简单高效的合成了一系列异VA唑啉类化合物。最后,基于我们在腙化学方面的工作基础,我们使用α-卤代腙作为缺电子氮杂二烯前体,发展了其与甲亚胺叶立德实现了[4+3]偶极环加成反应,以中等到较好的收率得到目标Tetrazepine类衍生物。此外,通过合理的调控腙上的保护基,我们可以以较好的区域选择性得到[3+3]环加成的产物,这也极大地拓展了该反应的实用性。
[Abstract]:Nitrogen-containing heterocycles are widely found in natural products, functional materials and some pharmaceutical molecules with important physiological activities. Because of its active chemical properties and unique reaction characteristics, nitrogen radical provides an effective method for the efficient and highly selective construction of carbon-nitrogen bonds. However, compared with carbon radical, nitrogen radical is generally difficult to produce, which greatly limits its wide application in organic synthesis. In recent years, visible light induced photoredox catalysis has provided a new idea for the mild production of nitrogen free radicals. In this paper, the latest research progress in this field is reviewed in detail, and the related research work is carried out around the visible light induced nitrogen radical reaction. The main contents are as follows: firstly, we developed the visible light-induced oxidative deprotonation electron transfer catalytic mode (ODETT), and realized the direct conversion of N-H bond of Hydrazone to nitrogen-centered free radical induced by visible light. The strategy was successfully applied to the hydrogenation of 尾, 纬 -unsaturated Hydrazone, and a series of dihydropyrazole compounds with important biological activities were synthesized mildly and efficiently. The possible reaction mechanism was proposed by fluorescence quenching experiment and related control experiment. At the same time, we successfully realized the series cyclization of nitrogen radical 6-endo induced by visible light through the reasonable control of substrate and the screening of catalytic system. The reaction strategy was applied to the construction of a class of dihydropyridazines with good biological activity. It is worth mentioning that a class of pyridazine salts with good antibacterial activity can be obtained by two simple synthesis transformation. In addition, the mechanism of hydrogen atom transfer reaction assisted by visible light induced oxidative deproton electron transfer (ODET) and tetramethyl piperidine nitrogen oxide (TEMPO) was proposed by DFT theoretical calculation and related control experiments. In addition, by combining visible light catalysis with oxygen oxidation, the amines oxidation reaction of allyl hydrazone was realized under mild conditions. In order to improve the production efficiency of nitrogen radical, the amount of catalyst TEMPO(10 mol should be added to the reaction system as organic co-catalyst. Through reasonable screening, we finally take oxygen as green oxidant, organic dye as cheap Guang Min, and obtain the product of olefin amine oxidation at room temperature with moderate to better yield. In addition, the iso-iodobenzene diacetate (PhI(OAc)2) was used as the oxidant, and the 1,4-diaza-dicyclo [2.2.2] octane was used as the organic base to successfully realize the hydroamination and oxyamination of olefins without metal participation. The mechanism study showed that the reaction was carried out by nitrogen radical intermediate. It is worth mentioning that this reaction can be successfully extended to the hydroxidation and double oxidation of alkyl oxime and a series of isovazoline compounds have been synthesized in a simple and efficient way. Finally, based on our work in Hydrazone chemistry, we developed the [43] dipolar cycloaddition reaction with imine ylide by using 伪 -halohydrazone as the precursor of electron-deficient azadiene. The target Tetrazepine derivatives were obtained in medium to better yield. In addition, the product of [33] cycloaddition can be obtained by reasonably regulating the protective group on Hydrazone, which greatly expands the practicability of the reaction.
【学位授予单位】：华中师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O626

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