基于α-氨基酮α-位氧化碳氢官能化反应研究
发布时间：2018-11-26 07:31
【摘要】：随着自然资源的日益短缺和环境的不断恶化,可持续发展战略的实施已刻不容缓。因此,发展高效的合成策略,从源头上消除或减少废物排放及节约能源是有机化学家所面临的严峻挑战。交叉脱氢偶联(CDC)反应是近年来发展起来的一种新型偶联反应,该类反应原子经济性高,操作简洁,反应底物无需预先官能化,副产物只是氢气或水或醇,既节约能源,又绿色环保,符合绿色化学发展要求。因此,对各种交叉脱氢偶联反应的研究成已经成为有机化学一个研究热点领域。在该研究领域中,考虑到α-氨基酮类衍生物在有机化学、药物化学以及天然产物化学等领域中的重要作用,α-氨基酮类化合物的交叉脱氢偶联反应已经得到人们广泛研究。然而,对α-氨基酮与各种1,3-偶极子和sp~3杂化的苄基碳亲核体的脱氢偶联环加成反应研究却很少。本论文以简单易得的α-氨基酮类化合物或者其前体为起始原料,以交叉脱氢偶联反应为策略,重点研究其与1,3-偶极子、sp~3杂化苄基碳和sp2芳基碳之间的偶联反应。具体研究内容如下:首先,以α-氨基酮类化合物为起始原料,在DBU存在的条件下,用氧气作为氧化剂,首次实现了CuBr2催化的α-氨基酮与α-重氮化合物连续的氧化/[3+2]环加成/氧化芳构化过程,制备了一系列多取代的1,2,3-三氮唑类化合物。在此基础上,以异氰基乙酸乙酯为1,3-偶极子,在CuBr2和AgOAc共同催化下,实现了α-氨基酮与其连续氧化/[3+2]环加成反应,合成了多种咪唑类化合物。上述反应不仅具有具有底物简单易得、条件温和以及原子经济性很高等优点,而且创建了一种由α-氨基酮一步直接制备1,2,3-三氮唑和咪唑类衍生物简单、高效的新方法。其次,在无过渡金属催化的条件下,只用过氧化苯甲酸叔丁酯为氧化剂,成功的实现了α-氨基酮类化合物与苄位sp~3C H键的交叉脱氢偶联反应。该反应具有原料简单易得、无需过渡金属以及原子经济性高等优点。在此基础上,通过官能团引入和转化策略,对该类反应在合成3,4-二氢喹啉-2-酮类化合物的应用进行了研究。最后,我们从简单的2-炔基苯胺类化合物出发,以现场生成的环状α-氨基酮氧化脱氢偶联反应为核心步骤,在Au(I)和Cu(II)共同催化下,首次实现了2-炔基苯胺与TBHP连续的分子间亲核加成、分子内的环化、氧化和交叉脱氢偶串联反应,合成了一系列2-(3’-吲哚基)二氢吲哚-3-酮类化合物。该方法不仅底物适用范围广,官能团容忍度高,反应简单高效,一步建立四个化学键和两个吲哚环,而且创建了由链状化合物一步合成2-(3’-吲哚基)二氢吲哚-3-酮类化合物简单、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 伪 -aminoketones has been widely studied, considering the important role of 伪 -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 伪 -aminone with various 1-, 3-dipole and sp~3 hybrid benzyl carbon nucleophiles. In this paper, the simple and easily available 伪 -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 伪 -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 伪 -amino ketones as starting material, oxygen is used as oxidant in the presence of DBU. The continuous oxidation / [32] cycloaddition / oxidative aromatization of 伪 -aminoketone and 伪 -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 伪 -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 伪 -amino ketones in one step. Secondly, under the condition of no transition metal catalysis, the cross-dehydrogenation of 伪 -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 伪 -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.
【学位授予单位】：东北师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25
本文编号：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 伪 -aminoketones has been widely studied, considering the important role of 伪 -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 伪 -aminone with various 1-, 3-dipole and sp~3 hybrid benzyl carbon nucleophiles. In this paper, the simple and easily available 伪 -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 伪 -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 伪 -amino ketones as starting material, oxygen is used as oxidant in the presence of DBU. The continuous oxidation / [32] cycloaddition / oxidative aromatization of 伪 -aminoketone and 伪 -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 伪 -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 伪 -amino ketones in one step. Secondly, under the condition of no transition metal catalysis, the cross-dehydrogenation of 伪 -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 伪 -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.
【学位授予单位】：东北师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25
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2 蒋宗林,鄢家明,谢如刚;咪唑环合成方法的新进展[J];合成化学;1998年01期
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