本文選題：Nazarov反應(yīng) + 芳基烯基酮　； 參考：《西南大學(xué)》2017年碩士論文

【摘要】：茚滿酮類(lèi)化合物的核心結(jié)構(gòu)為芳基并五元環(huán)結(jié)構(gòu),因其存在于大量天然產(chǎn)物和一些藥物分子當(dāng)中,該類(lèi)結(jié)構(gòu)的合成近年來(lái)受到廣泛的關(guān)注。合成茚滿酮類(lèi)化合物方法有很多,其結(jié)構(gòu)中的五元環(huán)往往是合成重點(diǎn),而Nazarov反應(yīng)是一類(lèi)非常重要的構(gòu)建五元環(huán)的方法。該方法利用二烯酮結(jié)構(gòu)化合物通過(guò)Lewis酸或Bronst酸作用發(fā)生分子內(nèi)4π電環(huán)化過(guò)程,順旋關(guān)環(huán)得到環(huán)戊烯酮結(jié)構(gòu)。在I.N.Nazarov首次報(bào)道了這個(gè)反應(yīng)后,該反應(yīng)被廣泛的用于構(gòu)建五元環(huán)狀化合物并取得了很大進(jìn)展,期間發(fā)展了較多類(lèi)型的反應(yīng)底物以及催化劑。Trauner小組在2003年首次報(bào)道了該反應(yīng)的不對(duì)稱(chēng)催化,使傳統(tǒng)的Nazarov反應(yīng)的研究更加多元化。但將芳基烯基酮作為二烯酮類(lèi)似物做Nazarov反應(yīng)的研究目前發(fā)展較少且反應(yīng)催化結(jié)構(gòu)相對(duì)單一,反應(yīng)底物活性較高。本文針對(duì)文獻(xiàn)中存在的問(wèn)題進(jìn)行了深入研究,將文獻(xiàn)中芳基烯基酮的1,3-二羰基結(jié)構(gòu)替換為甲基,在低活性反應(yīng)物條件下對(duì)催化劑進(jìn)行了三方面工作的研究。1、混合路易斯酸本文設(shè)計(jì)催化劑時(shí)受到了Pd催化工作的啟發(fā),擬設(shè)計(jì)一種具有雙活化模式的催化體系,在經(jīng)過(guò)篩選后發(fā)現(xiàn)鐵鹽和硼酸的組合能夠有效的提高反應(yīng)效率,并且經(jīng)過(guò)一系列的實(shí)驗(yàn)研究發(fā)現(xiàn)用3,5-二三氟甲基苯硼酸與Fe(OTf)3的比例為1:2時(shí)反應(yīng)效率最高。在該條件下進(jìn)行了底物擴(kuò)展,發(fā)現(xiàn)該條件下低活性的芳基烯基酮特別是含有吸電子取代基的芳基烯基酮均能很好的發(fā)生Nazarov反應(yīng),得到了大于80%的產(chǎn)率和較好的非對(duì)映選擇性。并利用該催化模式成功的合成了天然產(chǎn)物片段。通過(guò)對(duì)反應(yīng)產(chǎn)物的結(jié)構(gòu)鑒定發(fā)現(xiàn)該條件下的反應(yīng)產(chǎn)物為熱力學(xué)穩(wěn)定產(chǎn)物,隨后對(duì)該反應(yīng)的機(jī)理進(jìn)行了探究,在實(shí)驗(yàn)基礎(chǔ)上推測(cè)出可能的反應(yīng)機(jī)理。2、不對(duì)稱(chēng)研究的嘗試在上述氯化亞鐵離子交換法催化芳基烯基酮的Nazarov反應(yīng)取得一定成果后,本文擬利用手性Salan配體代替聯(lián)吡啶配體,初步嘗試該反應(yīng)的不對(duì)稱(chēng)研究工作。但在配體合成過(guò)程中我們發(fā)現(xiàn)傳統(tǒng)的配體合成路線較為復(fù)雜,因此我們嘗試對(duì)傳統(tǒng)的配體合成路線進(jìn)行改進(jìn),最終優(yōu)化了Salen配體的合成路線,并利用該合成路線制得了一系列的Salen配體。最后用這些配體對(duì)芳基烯基酮的Nazarov反應(yīng)進(jìn)行了不對(duì)稱(chēng)的嘗試。
[Abstract]:The core structure of ninemanone compounds is aryl pentacrone structure. Because of its existence in a large number of natural products and some drug molecules, the synthesis of this kind of structure has received extensive attention in recent years. There are many methods for synthesizing ninemanone compounds, and the five-member ring in its structure is often the focus of synthesis, while Nazarov reaction is a very important method to construct five-member ring. In this method, the structure of cyclopentenone was obtained by the intramolecular electrocyclization of 4 蟺 by the interaction of Lewis acid or Bronst acid. After I.N. Nazarov first reported the reaction, the reaction was widely used to construct a five-member ring compound and a lot of progress was made. More types of substrates and catalyst. Trauner group first reported the asymmetric catalysis of the reaction in 2003, which made the traditional Nazarov reaction more diversified. However, the research on the Nazarov reaction of arylenyl ketone as a dienone analogue is less developed, the catalytic structure of the reaction is relatively single, and the substrate activity is relatively high. In this paper, the existing problems in the literature have been studied in depth, and the structure of aryl alkenyl ketones has been replaced by methyl group, and the structure of 1'3 'dicarbonyl group has been replaced by methyl group. The catalyst was studied in three aspects under the condition of low activity reactants. 1. The mixed Lewis acid catalyst was inspired by PD catalytic work, and a catalytic system with double activation mode was designed. After screening, it was found that the combination of iron salt and boric acid could effectively improve the reaction efficiency, and through a series of experimental studies, it was found that the reaction efficiency was the highest when the ratio of 3o 5- difluoromethylphenyl boric acid to Fe (OTF) 3 was 1:2. It was found that the low activity aryl alkenyl ketones, especially the aryl alkenyl ketones containing electron absorbent substituents, could react well with Nazarov reaction under this condition, and the yield was more than 80% and the enantioselectivity was better than 80%. The natural product fragments were successfully synthesized by this catalytic model. It was found that the reaction product under this condition was thermodynamically stable, and the mechanism of the reaction was studied. On the basis of experiments, the possible mechanism of reaction. 2. An asymmetric study attempt was made. After the above results were achieved in the Nazarov reaction of aryl alkenyl ketones catalyzed by the iron-exchange method mentioned above, the chiral Salan ligand was proposed to replace the bipyridine ligand, and the chiral Salan ligand was used to replace the bipyridine ligand. A preliminary attempt was made to study the asymmetry of the reaction. However, in the process of ligand synthesis, we found that the traditional ligand synthesis route is more complex, so we try to improve the traditional ligand synthesis route, and finally optimize the Salen ligand synthesis route. A series of Salen ligands were prepared by this synthetic route. Finally, these ligands were used to asymmetric Nazarov reaction of aryl alkenyl ketones.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：O625.42

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 IBARA Chie;FUJIWARA Masamune;HAYASE Shuichi;KAWATSURA Motoi;ITOH Toshiyuki;;Development of sequential type iron salt-catalyzed Nazarov/Michael reaction in an ionic liquid solvent system[J];Science China(Chemistry);2012年08期

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本文編號(hào)：2093738