本文選題：含氮雜環(huán) + 可見光催化　； 參考：《華中師范大學(xué)》2017年博士論文

【摘要】：含氮雜環(huán)廣泛存在于天然產(chǎn)物、功能材料以及一些具有重要生理活性的藥物分子中。氮自由基由于其活潑的化學(xué)性質(zhì)和獨(dú)特的反應(yīng)特性,為碳-氮鍵的高效、高選擇性構(gòu)建提供一條有效方法。然而,和碳自由基相比,氮自由基一般較難產(chǎn)生,這極大的限制了它在有機(jī)合成中的廣泛應(yīng)用。近年來,可見光誘導(dǎo)的光氧化還原催化為氮自由基的溫和產(chǎn)生提供了一條新的思路。本論文詳細(xì)概述了該領(lǐng)域的最新研究進(jìn)展,并圍繞可見光誘導(dǎo)的氮自由基反應(yīng)開展了相關(guān)研究工作。具體內(nèi)容如下:首先,我們發(fā)展了可見光誘導(dǎo)的氧化脫質(zhì)子電子轉(zhuǎn)移催化模式(ODET),實(shí)現(xiàn)了可見光誘導(dǎo)腙的N-H鍵直接轉(zhuǎn)化為氮中心自由基,并將該策略成功應(yīng)用于β,γ-不飽和腙的氫胺化反應(yīng),溫和高效地合成了一系列具有重要生物活性的二氫吡唑類化合物。通過熒光淬滅實(shí)驗(yàn)和相關(guān)的控制實(shí)驗(yàn),我們提出了可能的反應(yīng)機(jī)理。與此同時(shí),我們通過底物的合理調(diào)控和催化體系的篩選,成功實(shí)現(xiàn)了可見光誘導(dǎo)的氮自由基6-endo串聯(lián)環(huán)化反應(yīng),并將該反應(yīng)策略應(yīng)用于一類具有良好生物活性的二氫噠嗪類化合物的構(gòu)建。值得一提的是,通過兩步簡單的合成轉(zhuǎn)換,我們可以得到一類具有良好抗菌活性的噠嗪鹽類化合物。此外,通過DFT理論計(jì)算和相關(guān)的控制實(shí)驗(yàn),我們提出了可見光誘導(dǎo)的氧化脫質(zhì)子電子轉(zhuǎn)移(ODET)以及四甲基哌啶氮氧化物(TEMPO)輔助的氫原子轉(zhuǎn)移反應(yīng)機(jī)理。另外,我們通過將可見光催化和氧氣氧化相結(jié)合,實(shí)現(xiàn)了溫和條件下烯基腙的胺氧化反應(yīng)。在該反應(yīng)體系里需要加入催化量的TEMPO(10 mol%)作為有機(jī)共催化劑,以提高氮自由基的產(chǎn)生效率。通過合理的條件篩選,我們最終以氧氣作為綠色氧化劑,有機(jī)染料作為廉價(jià)的光敏劑,在室溫條件下以中等到較好的收率得到了烯烴胺氧化的產(chǎn)物。此外,我們使用當(dāng)量的二乙酸碘苯PhI(OAc)2作為氧化劑,以及1,4-二氮雜二環(huán)[2.2.2]辛烷作為有機(jī)堿,成功實(shí)現(xiàn)了無金屬參與條件下烯烴的氫胺化和氧胺化反應(yīng)。機(jī)理研究表明該反應(yīng)是通過氮自由基中間體進(jìn)行的。值得一提的是,該反應(yīng)可以成功拓展到烯基肟的氫氧化反應(yīng)和雙氧化反應(yīng)之中,簡單高效的合成了一系列異VA唑啉類化合物。最后,基于我們?cè)陔昊瘜W(xué)方面的工作基礎(chǔ),我們使用α-鹵代腙作為缺電子氮雜二烯前體,發(fā)展了其與甲亞胺葉立德實(shí)現(xiàn)了[4+3]偶極環(huán)加成反應(yīng),以中等到較好的收率得到目標(biāo)Tetrazepine類衍生物。此外,通過合理的調(diào)控腙上的保護(hù)基,我們可以以較好的區(qū)域選擇性得到[3+3]環(huán)加成的產(chǎn)物,這也極大地拓展了該反應(yīng)的實(shí)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, 緯 -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 偽 -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.
【學(xué)位授予單位】：華中師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O626

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 余曉葉;周帆;陳加榮;肖文精;;可見光促進(jìn)的酰胺氮自由基參與的分子內(nèi)氫胺化反應(yīng)[J];化學(xué)學(xué)報(bào);2017年01期

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本文編號(hào)：1774593