基于α-氨基酮α-位氧化碳?xì)涔倌芑磻?yīng)研究
發(fā)布時(shí)間：2018-11-26 07:31
【摘要】：隨著自然資源的日益短缺和環(huán)境的不斷惡化,可持續(xù)發(fā)展戰(zhàn)略的實(shí)施已刻不容緩。因此,發(fā)展高效的合成策略,從源頭上消除或減少?gòu)U物排放及節(jié)約能源是有機(jī)化學(xué)家所面臨的嚴(yán)峻挑戰(zhàn)。交叉脫氫偶聯(lián)(CDC)反應(yīng)是近年來(lái)發(fā)展起來(lái)的一種新型偶聯(lián)反應(yīng),該類反應(yīng)原子經(jīng)濟(jì)性高,操作簡(jiǎn)潔,反應(yīng)底物無(wú)需預(yù)先官能化,副產(chǎn)物只是氫氣或水或醇,既節(jié)約能源,又綠色環(huán)保,符合綠色化學(xué)發(fā)展要求。因此,對(duì)各種交叉脫氫偶聯(lián)反應(yīng)的研究成已經(jīng)成為有機(jī)化學(xué)一個(gè)研究熱點(diǎn)領(lǐng)域。在該研究領(lǐng)域中,考慮到α-氨基酮類衍生物在有機(jī)化學(xué)、藥物化學(xué)以及天然產(chǎn)物化學(xué)等領(lǐng)域中的重要作用,α-氨基酮類化合物的交叉脫氫偶聯(lián)反應(yīng)已經(jīng)得到人們廣泛研究。然而,對(duì)α-氨基酮與各種1,3-偶極子和sp~3雜化的芐基碳親核體的脫氫偶聯(lián)環(huán)加成反應(yīng)研究卻很少。本論文以簡(jiǎn)單易得的α-氨基酮類化合物或者其前體為起始原料,以交叉脫氫偶聯(lián)反應(yīng)為策略,重點(diǎn)研究其與1,3-偶極子、sp~3雜化芐基碳和sp2芳基碳之間的偶聯(lián)反應(yīng)。具體研究?jī)?nèi)容如下:首先,以α-氨基酮類化合物為起始原料,在DBU存在的條件下,用氧氣作為氧化劑,首次實(shí)現(xiàn)了CuBr2催化的α-氨基酮與α-重氮化合物連續(xù)的氧化/[3+2]環(huán)加成/氧化芳構(gòu)化過(guò)程,制備了一系列多取代的1,2,3-三氮唑類化合物。在此基礎(chǔ)上,以異氰基乙酸乙酯為1,3-偶極子,在CuBr2和AgOAc共同催化下,實(shí)現(xiàn)了α-氨基酮與其連續(xù)氧化/[3+2]環(huán)加成反應(yīng),合成了多種咪唑類化合物。上述反應(yīng)不僅具有具有底物簡(jiǎn)單易得、條件溫和以及原子經(jīng)濟(jì)性很高等優(yōu)點(diǎn),而且創(chuàng)建了一種由α-氨基酮一步直接制備1,2,3-三氮唑和咪唑類衍生物簡(jiǎn)單、高效的新方法。其次,在無(wú)過(guò)渡金屬催化的條件下,只用過(guò)氧化苯甲酸叔丁酯為氧化劑,成功的實(shí)現(xiàn)了α-氨基酮類化合物與芐位sp~3C H鍵的交叉脫氫偶聯(lián)反應(yīng)。該反應(yīng)具有原料簡(jiǎn)單易得、無(wú)需過(guò)渡金屬以及原子經(jīng)濟(jì)性高等優(yōu)點(diǎn)。在此基礎(chǔ)上,通過(guò)官能團(tuán)引入和轉(zhuǎn)化策略,對(duì)該類反應(yīng)在合成3,4-二氫喹啉-2-酮類化合物的應(yīng)用進(jìn)行了研究。最后,我們從簡(jiǎn)單的2-炔基苯胺類化合物出發(fā),以現(xiàn)場(chǎng)生成的環(huán)狀α-氨基酮氧化脫氫偶聯(lián)反應(yīng)為核心步驟,在Au(I)和Cu(II)共同催化下,首次實(shí)現(xiàn)了2-炔基苯胺與TBHP連續(xù)的分子間親核加成、分子內(nèi)的環(huán)化、氧化和交叉脫氫偶串聯(lián)反應(yīng),合成了一系列2-(3’-吲哚基)二氫吲哚-3-酮類化合物。該方法不僅底物適用范圍廣,官能團(tuán)容忍度高,反應(yīng)簡(jiǎn)單高效,一步建立四個(gè)化學(xué)鍵和兩個(gè)吲哚環(huán),而且創(chuàng)建了由鏈狀化合物一步合成2-(3’-吲哚基)二氫吲哚-3-酮類化合物簡(jiǎn)單、高效新方法。
[Abstract]:With the shortage of natural resources and the deterioration of environment, the implementation of sustainable development strategy is urgent. Therefore, it is a serious challenge for organic chemists to develop efficient synthesis strategies to eliminate or reduce waste emissions and save energy at the source. Cross dehydrogenation coupling (CDC) reaction is a new type of coupling reaction developed in recent years. It is characterized by high atomic economy, simple operation, no need for pre-functionalization of the substrate, and the by-product is only hydrogen or water or alcohol, which saves energy. Green and environmental protection, in line with the requirements of green chemistry development. Therefore, the study of cross-dehydrogenation coupling reactions has become a hot research field in organic chemistry. In this field, the cross-dehydrogenation of 偽 -aminoketones has been widely studied, considering the important role of 偽 -amino ketones in organic chemistry, pharmaceutical chemistry and natural product chemistry. However, few studies have been carried out on the dehydro-coupling cycloaddition reaction of 偽 -aminone with various 1-, 3-dipole and sp~3 hybrid benzyl carbon nucleophiles. In this paper, the simple and easily available 偽 -aminoketones or their precursors were used as the starting materials, and the cross-dehydrogenation coupling reaction was used as the strategy. The coupling reaction between 偽 -aminoketones and 1-dipole, sp~3 hybrid benzyl carbon and sp2 aryl carbon was studied emphatically. The specific research contents are as follows: firstly, using 偽 -amino ketones as starting material, oxygen is used as oxidant in the presence of DBU. The continuous oxidation / [32] cycloaddition / oxidative aromatization of 偽 -aminoketone and 偽 -diazo compounds catalyzed by CuBr2 was first realized. A series of polysubstituted 1o _ 2N _ 3-triazole compounds were prepared. On this basis, several imidazoles were synthesized by continuous oxidation / [32] cycloaddition reaction of 偽 -aminone with ethyl isocyanate as 1 ~ 3- dipole under the catalysis of CuBr2 and AgOAc. The above reactions not only have the advantages of simple and easy to obtain substrates, mild conditions and high atomic economy, but also create a simple and efficient method for the direct preparation of 1o 2N 3 triazole and imidazole derivatives from 偽 -amino ketones in one step. Secondly, under the condition of no transition metal catalysis, the cross-dehydrogenation of 偽 -amino ketones with benzyl sp~3C H bond was successfully realized by using tert-butyl peroxide as oxidant. The reaction has the advantages of simple raw material, no transition metal and high atom economy. On the basis of this, the application of this kind of reaction in the synthesis of 3o 4-dihydroquinoline-2-one compounds was studied through the introduction and transformation strategy of functional groups. Finally, starting from the simple 2-alkynyl aniline compounds and taking the in-situ oxidative dehydrogenation of cyclic 偽 -amino ketones as the core step, we co-catalyzed by Au (I) and Cu (II). For the first time, a series of 2- (3-) dihydroindole-3-one compounds were synthesized by the continuous intermolecular nucleophilic addition, intramolecular cyclization, oxidation and cross-dehydrogenation of 2-acetylaniline with TBHP. The method not only has wide application range, high functional tolerance, simple and efficient reaction, but also has four chemical bonds and two indole rings in one step. Furthermore, a simple and efficient method for the synthesis of 2- (3-indolyl) dihydroindole-3-ketones from chain compounds was established.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.25
本文編號(hào)：2357797
[Abstract]:With the shortage of natural resources and the deterioration of environment, the implementation of sustainable development strategy is urgent. Therefore, it is a serious challenge for organic chemists to develop efficient synthesis strategies to eliminate or reduce waste emissions and save energy at the source. Cross dehydrogenation coupling (CDC) reaction is a new type of coupling reaction developed in recent years. It is characterized by high atomic economy, simple operation, no need for pre-functionalization of the substrate, and the by-product is only hydrogen or water or alcohol, which saves energy. Green and environmental protection, in line with the requirements of green chemistry development. Therefore, the study of cross-dehydrogenation coupling reactions has become a hot research field in organic chemistry. In this field, the cross-dehydrogenation of 偽 -aminoketones has been widely studied, considering the important role of 偽 -amino ketones in organic chemistry, pharmaceutical chemistry and natural product chemistry. However, few studies have been carried out on the dehydro-coupling cycloaddition reaction of 偽 -aminone with various 1-, 3-dipole and sp~3 hybrid benzyl carbon nucleophiles. In this paper, the simple and easily available 偽 -aminoketones or their precursors were used as the starting materials, and the cross-dehydrogenation coupling reaction was used as the strategy. The coupling reaction between 偽 -aminoketones and 1-dipole, sp~3 hybrid benzyl carbon and sp2 aryl carbon was studied emphatically. The specific research contents are as follows: firstly, using 偽 -amino ketones as starting material, oxygen is used as oxidant in the presence of DBU. The continuous oxidation / [32] cycloaddition / oxidative aromatization of 偽 -aminoketone and 偽 -diazo compounds catalyzed by CuBr2 was first realized. A series of polysubstituted 1o _ 2N _ 3-triazole compounds were prepared. On this basis, several imidazoles were synthesized by continuous oxidation / [32] cycloaddition reaction of 偽 -aminone with ethyl isocyanate as 1 ~ 3- dipole under the catalysis of CuBr2 and AgOAc. The above reactions not only have the advantages of simple and easy to obtain substrates, mild conditions and high atomic economy, but also create a simple and efficient method for the direct preparation of 1o 2N 3 triazole and imidazole derivatives from 偽 -amino ketones in one step. Secondly, under the condition of no transition metal catalysis, the cross-dehydrogenation of 偽 -amino ketones with benzyl sp~3C H bond was successfully realized by using tert-butyl peroxide as oxidant. The reaction has the advantages of simple raw material, no transition metal and high atom economy. On the basis of this, the application of this kind of reaction in the synthesis of 3o 4-dihydroquinoline-2-one compounds was studied through the introduction and transformation strategy of functional groups. Finally, starting from the simple 2-alkynyl aniline compounds and taking the in-situ oxidative dehydrogenation of cyclic 偽 -amino ketones as the core step, we co-catalyzed by Au (I) and Cu (II). For the first time, a series of 2- (3-) dihydroindole-3-one compounds were synthesized by the continuous intermolecular nucleophilic addition, intramolecular cyclization, oxidation and cross-dehydrogenation of 2-acetylaniline with TBHP. The method not only has wide application range, high functional tolerance, simple and efficient reaction, but also has four chemical bonds and two indole rings in one step. Furthermore, a simple and efficient method for the synthesis of 2- (3-indolyl) dihydroindole-3-ketones from chain compounds was established.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.25
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