过渡金属卡宾参与膦氧基吲哚衍生物的立体选择性合成
发布时间：2018-08-19 16:30
【摘要】：近年来,大量的研究发现含膦的有机化合物表现出了特别的生物活性和化学性质,这使其在药物化学、材料化学和有机合成中得到广泛的应用。此外,吲哚是许多具有显著的药物疗效以及生物活性的天然产物的基本骨架。因此,3-膦氧基吲哚衍生物在药物疗效中起着至关重要的角色。重氮化合物是一种能够高效构建碳-杂(C-X)键的化合物,相比于有着显著研究的杂-氢(X-H)键的插入反应,对于P-H插入反应,由于膦元素自身的高配位性,金属催化剂通常易被有机磷化合物毒化,以及有机膦化合物难以控制参与反应的立体选择性,导致P-H插入反应的进展缓慢。本论文的研究工作分为两个部分:一是发展由α-亚胺基吲哚重氮化合物以及膦氢化合物合成3-膦氧基吲哚衍生物的合成方法;二是采用光学纯的(1S,2S,5R)-苯基膦酸薄荷酯做为手性辅基参与的立体选择性合成。在论文研究的第一部分,我们通过金属铜催化α-亚胺基吲哚重氮化合物形成α-亚胺基铜卡宾,优化和筛选反应条件,以48%-88%的收率一步反应直接合成3-膦氧基吲哚衍生物。有效的构建了 C(sp2)-P键。在论文的第二部分,我们以(1S,2S,5R)-苯基膦酸薄荷酯做为P-H插入反应的对象,首次尝试对α-亚胺基金属卡宾进行P-H插入反应的立体选择性合成研究。采用了31P NMR方法,确定了一系列合成产物的dr值,从中验证了该合成方法具有高效的立体选择性,也为含有手性膦中心的有机化合物提供新的合成策略。
[Abstract]:In recent years, a large number of studies have found that phosphine-containing organic compounds exhibit special biological activity and chemical properties, which makes them widely used in pharmaceutical chemistry, material chemistry and organic synthesis. In addition, indole is the basic skeleton of many natural products with significant drug efficacy and biological activity. Therefore, 3-phosphonyl indole derivatives play a crucial role in drug efficacy. Diazo compounds are a kind of compounds which can efficiently construct carbon-hetero (C-X) bonds. Compared with the insertion reactions of hetero-hydrogen (X-H) bonds which have been studied significantly, for P-H insertion reactions, due to the high coordination of phosphine elements themselves, Metal catalysts are usually easily poisoned by organophosphorus compounds and the stereoselectivity of organic phosphine compounds is difficult to control which leads to the slow progress of P-H insertion reactions. The research work of this thesis is divided into two parts: one is to develop the synthesis methods of 3-phosphonoxy indole derivatives from 伪 -imindolediazo compounds and phosphine compounds; The second is the stereoselective synthesis of (1Sch _ 2S _ 5R) -Phenylphosphonic acid menthyl ester as the chiral auxiliary group. In the first part of the thesis, we synthesized 3-phosphinoxy indole derivatives directly with 48 ~ 88% yield by metal copper catalyzed 伪 -imino indole-diazo compound to form 伪 -imino copper carbene. C (sp2) -P bond was constructed effectively. In the second part of the thesis, we first try to study the stereoselective synthesis of 伪 -iminodium metal carbene by using (1Sn2Sn5R) -phenylphosphonate as the object of P-H insertion reaction. The 31P NMR method was used to determine the dr values of a series of synthetic products, which proved that the synthesis method had high stereoselectivity and provided a new synthesis strategy for organic compounds with chiral phosphine centers.
【学位授予单位】：广西大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.13
本文编号：2192205
[Abstract]:In recent years, a large number of studies have found that phosphine-containing organic compounds exhibit special biological activity and chemical properties, which makes them widely used in pharmaceutical chemistry, material chemistry and organic synthesis. In addition, indole is the basic skeleton of many natural products with significant drug efficacy and biological activity. Therefore, 3-phosphonyl indole derivatives play a crucial role in drug efficacy. Diazo compounds are a kind of compounds which can efficiently construct carbon-hetero (C-X) bonds. Compared with the insertion reactions of hetero-hydrogen (X-H) bonds which have been studied significantly, for P-H insertion reactions, due to the high coordination of phosphine elements themselves, Metal catalysts are usually easily poisoned by organophosphorus compounds and the stereoselectivity of organic phosphine compounds is difficult to control which leads to the slow progress of P-H insertion reactions. The research work of this thesis is divided into two parts: one is to develop the synthesis methods of 3-phosphonoxy indole derivatives from 伪 -imindolediazo compounds and phosphine compounds; The second is the stereoselective synthesis of (1Sch _ 2S _ 5R) -Phenylphosphonic acid menthyl ester as the chiral auxiliary group. In the first part of the thesis, we synthesized 3-phosphinoxy indole derivatives directly with 48 ~ 88% yield by metal copper catalyzed 伪 -imino indole-diazo compound to form 伪 -imino copper carbene. C (sp2) -P bond was constructed effectively. In the second part of the thesis, we first try to study the stereoselective synthesis of 伪 -iminodium metal carbene by using (1Sn2Sn5R) -phenylphosphonate as the object of P-H insertion reaction. The 31P NMR method was used to determine the dr values of a series of synthetic products, which proved that the synthesis method had high stereoselectivity and provided a new synthesis strategy for organic compounds with chiral phosphine centers.
【学位授予单位】：广西大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.13
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