發(fā)布時間：2018-02-07 13:06

  本文關鍵詞： 多組分反應 串級環(huán)化反應 自分類串級反應 芳基酮醛 鄰氨基芐胺 色胺 硝基烯烴 肉桂醛 丁炔二酸二甲酯 丙二腈 芳乙酮 4-羥基香豆素 硫脲 二氫吡咯并[2 1-b]喹唑啉 二氫中氮茚并[8 7-b]吲哚 吡喃酮并[3 2-c]香豆素 吡　出處：《華中師范大學》2017年博士論文　論文類型：學位論文

【摘要】：雜環(huán)化合物是一類廣泛存在于各種天然產物、農藥、醫(yī)藥以及功能材料分子中的重要核心骨架。在合成化學領域與醫(yī)藥行業(yè)中,對于雜環(huán)化合物的合成已成為當前研究的熱點。然而從簡單易得的起始原料出發(fā)直接合成具有多樣性與復雜性的雜環(huán)化合物是一項十分具有挑戰(zhàn)性的研究課題。目前,最具發(fā)展前景的合成方法之一是基于多組分串級環(huán)化反應來直接構建雜環(huán)化合物。多組分反應由于其反應效率高、原子利用率高、操作簡便、步驟經濟性、匯聚性、產物結構復雜性和多樣性等優(yōu)點廣泛應用于有機合成與生物醫(yī)藥合成等領域之中。而串級環(huán)化反應是基于一鍋中連續(xù)發(fā)生多個化學鍵的形成并成環(huán)的過程,不僅避免了分步反應的繁瑣操作,而且節(jié)約了溶劑和試劑的消耗,具有綠色高效、經濟環(huán)保的優(yōu)點,因而作為一種最直觀有效的合成雜環(huán)化合物的方法受到有機合成化學家們的廣泛關注。本論文采用芳基酮醛參與的多組分反應作為合成策略,以串級環(huán)化反應作為媒介,通過多個單元反應的自組織集成,設計合成一系列具有潛在生物活性和藥理活性的含氮、含氧以及含硫雜環(huán)化合物。主要包括以下幾個部分:第一章,首先概述了多組分串級環(huán)化反應的理論,然后總結了近年來國內外多組分串級環(huán)化反應在合成雜環(huán)化合物方面的研究進展,包括基于人名反應、過渡金屬催化、酸/堿介導、小分子催化以及其他條件下的多組分串級環(huán)化反應的研究,并對芳基酮醛參與的多組分串級環(huán)化反應合成多元雜環(huán)或稠環(huán)化合物進行了詳細的論述。最后,提出了本論文的研究目標和研究思路。第二章,以芳基酮醛、鄰氨基芐胺、硝基烯烴三組分作為反應底物,通過縮合、親核加成、Michael加成、Henry環(huán)化、氧化芳構化等有機單元反應的集成,在酸的催化下發(fā)生串級雙環(huán)化反應直接合成了 4,9-二氫吡咯并[2,1-b]喹唑啉衍生物,并且實現(xiàn)了一鍋一步連續(xù)構建兩個環(huán),合成四個鍵的成鍵方式。該方法與前期的文獻相比,具有反應高效、原料簡單易得、條件溫和、操作簡便等優(yōu)點。第三章,以芳基酮醛、色胺、硝基烯烴三組分作為反應底物,通過Pictet-Spengler環(huán)化、Michael加成、Henry環(huán)化、氧化芳構化等有機單元反應的集成,在無金屬催化的條件下直接合成了二氫中氮茚并[8,7-b]吲哚衍生物,通過對活潑中間體1-芳甲�；臍�-β-咔啉的原位捕獲首次實現(xiàn)了生物堿類似物的一鍋一步直接合成。第四章,在第三章的基礎上,以芳基酮醛、色胺作為基本反應底物,生成活潑中間體1-芳甲�；臍�-β-咔啉后,分別利用肉桂醛、丁炔二酸二甲酯、丙二腈進行原位捕獲,通過多樣性導向合成的策略,合成一系列不同取代基的二氫中氮茚并[8,7-b]吲哚衍生物,進一步揭示了含有α-氨基酮片段的化合物在合成雜環(huán)方面具有十分廣泛的應用。第五章,基于sp3 C-H雙官能團化反應的迅猛發(fā)展,我們設計以芳乙酮作為底物,對甲基sp3C-H進行碘代和Kornblum氧化生成芳基酮醛,并用兩分子4-羥基香豆素進行原位捕獲,形成雙官能團取代的芳乙酮,進而通過酯交換、氧化芳構化等反應直接構建吡喃酮并[3,2-c]香豆素衍生物。相比傳統(tǒng)的金屬催化sp3 C-H活化并雙官能團化的反應而言,此合成方法不需要使用金屬催化劑、配體以及其他添加劑,具有反應條件溫和、底物適用范圍廣泛、經濟環(huán)保等優(yōu)點。第六章,基于自組織反應網(wǎng)絡的研究,我們設計將多組分串級環(huán)化反應與自分類反應有機地結合起來,形成一種新穎的多組分自分類串級環(huán)化反應,利用芳基酮醛、腈類化合物、硫脲三組分作為反應底物,通過溶劑的調控,使其化學選擇性地合成四氫吡咯并[1,2-c]咪唑和四氫吡咯并[1,2-c]噻唑衍生物。第七章,對本博士論文的全部工作進行了總結,并對后期利用多組分串級環(huán)化反應策略合成雜環(huán)化合物進行了展望。
[Abstract]:Heterocyclic compounds are widely distributed in a variety of natural products, pesticide, medicine and functional materials important core molecules. In synthetic chemistry and pharmaceutical industry, for the synthesis of heterocyclic compounds has become a research hotspot. However, from readily available starting materials of direct synthesis of heterocyclic compounds with diversity and the complexity is a very challenging research topic. At present, one of the most promising synthesis method is a multicomponent cascade cyclization to directly construct heterocyclic compounds based on multicomponent reactions due to its high reaction efficiency, high atom utilization, simple operation steps, economy, convergence. The advantages of product structure complexity and diversity are widely used in organic synthesis and biological medicine synthesis field. The cascade cyclization is a continuous occurrence of multiple chemical bonds based on The formation and loop process, not only to avoid the tedious operation step, but also save solvent and reagent consumption, with a green and efficient, economical and environmental advantages, as a kind of method of the most intuitive and effective synthesis of heterocyclic compounds has attracted wide attention of synthetic organic chemists. This paper uses aryl ketone aldehyde in the multicomponent reaction as a synthetic strategy to cascade cyclization reaction as a medium, through self organization integrated multiple unit responses, design and synthesis of a series of potential biological activity and pharmacological activity of nitrogen, oxygen and sulfur heterocyclic compounds. Mainly includes the following parts: the first chapter firstly summarizes the multicomponent cascade cyclization reaction theory, then summarized the multi-component cascade ring research progress in synthesis of heterocyclic compounds on chemical reactions, including the name should be based on the transition of gold A catalytic, acid / base mediated multicomponent cascade cyclization of small molecular catalysis and other conditions, and the aryl ketone aldehyde in multi-component cascade cyclization to synthesize multiple heterocycles or fused ring compounds are discussed in detail. Finally, this paper puts forward the research objectives and research ideas. In the second chapter, with aryl ketone aldehyde, o-amino benzylamine, nitroalkene three components as substrates, through condensation, nucleophilic addition, Michael addition, Henry cyclization, integrated oxidation aromatization reaction of organic unit, occurrence of cascade double loop reaction in acid under the catalysis of the direct synthesis of 4,9- two pyrrolidine and [2,1-b] quinazoline derivatives, and the realization of the two step continuous construction of a key ring, into synthesis of four key. Compared with the previous methods of the literature, has high efficiency, easily available raw materials, mild conditions, simple operation and other advantages. No. In chapter three, aryl ketone aldehyde, amine, nitro olefin of three components as substrates, the Pictet-Spengler ring, Michael addition, Henry cyclization, integrated oxidation aromatization reaction in organic unit, metal free catalytic conditions for direct synthesis of two hydrogen indolizine and [8,7-b] indole derivatives by in situ 1- of active intermediates arylformyl four hydrogen - carboline alkaloids capture is realized for the first time a similar step direct synthesis. The fourth chapter, on the basis of the third chapter, with aryl ketone aldehyde, tryptamine as the basic substrate, generating active intermediate aroyl 1- four hydrogen acyl beta carboline, respectively using cinnamaldehyde, acetylenedicarboxylate two methyl propylene nitrile, two in situ capture, through the strategy of diversity oriented synthesis, the synthesis of a series of different substituted two hydrogen indolizine and [8,7-b] indole derivatives, further reveals the fragment containing alpha amino ketone The compounds are widely used in the synthesis of heterocycles. The fifth chapter, the rapid development of SP3 C-H bifunctional reaction based on our design based on aromatic acetophenone as substrate of iodine and Kornblum oxidation of aryl ketone aldehyde to methyl sp3C-H, with two molecules of 4- hydroxy coumarin in situ capture, formation bifunctional substituted aryl methyl ketone, then through ester exchange, oxidative aromatization reaction and direct construction of pyrone derivatives. Compared with the traditional [3,2-c] coumarin metal catalyzed SP3 activation of C-H and double functionalization reaction, this method does not require the use of metal catalysts, ligands and other additives, with mild reaction conditions, substrate for a wide range of economic, environmental protection and other advantages. In the sixth chapter, the study of self organization reaction based on network, we design the multi-component cascade cyclization reaction and self classification combination machine Together, the formation of a novel multi component self sorting tandem cyclization reaction with aryl ketone aldehyde, nitriles, thiourea three components as substrates, through the solvent control, the chemical selective synthesis of pyrrolidine and four [1,2-c] imidazole and four hydrogen pyrrolo [1,2-c] thiophene derivatives seventh. Chapter, all the works of this dissertation are summarized, and the later use of multi-component cascade cyclization strategy for synthesis of heterocyclic compounds is prospected.

【學位授予單位】：華中師范大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O626

【參考文獻】

相關期刊論文 前1條

1 JING YuFeng;LIU RuiTing;LIN YangHui;ZHOU XiGeng;;Lanthanide-catalyzed cyclocarbonylation and cyclothiocarbonylation: a facile synthesis of benzannulated 1,3-diheteroatom five- and six-membered heterocycles[J];Science China(Chemistry);2014年08期

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本文編號：1494443