過渡金屬卡賓參與膦氧基吲哚衍生物的立體選擇性合成
發(fā)布時間：2018-08-19 16:30
【摘要】：近年來,大量的研究發(fā)現(xiàn)含膦的有機化合物表現(xiàn)出了特別的生物活性和化學(xué)性質(zhì),這使其在藥物化學(xué)、材料化學(xué)和有機合成中得到廣泛的應(yīng)用。此外,吲哚是許多具有顯著的藥物療效以及生物活性的天然產(chǎn)物的基本骨架。因此,3-膦氧基吲哚衍生物在藥物療效中起著至關(guān)重要的角色。重氮化合物是一種能夠高效構(gòu)建碳-雜(C-X)鍵的化合物,相比于有著顯著研究的雜-氫(X-H)鍵的插入反應(yīng),對于P-H插入反應(yīng),由于膦元素自身的高配位性,金屬催化劑通常易被有機磷化合物毒化,以及有機膦化合物難以控制參與反應(yīng)的立體選擇性,導(dǎo)致P-H插入反應(yīng)的進展緩慢。本論文的研究工作分為兩個部分:一是發(fā)展由α-亞胺基吲哚重氮化合物以及膦氫化合物合成3-膦氧基吲哚衍生物的合成方法;二是采用光學(xué)純的(1S,2S,5R)-苯基膦酸薄荷酯做為手性輔基參與的立體選擇性合成。在論文研究的第一部分,我們通過金屬銅催化α-亞胺基吲哚重氮化合物形成α-亞胺基銅卡賓,優(yōu)化和篩選反應(yīng)條件,以48%-88%的收率一步反應(yīng)直接合成3-膦氧基吲哚衍生物。有效的構(gòu)建了 C(sp2)-P鍵。在論文的第二部分,我們以(1S,2S,5R)-苯基膦酸薄荷酯做為P-H插入反應(yīng)的對象,首次嘗試對α-亞胺基金屬卡賓進行P-H插入反應(yīng)的立體選擇性合成研究。采用了31P NMR方法,確定了一系列合成產(chǎn)物的dr值,從中驗證了該合成方法具有高效的立體選擇性,也為含有手性膦中心的有機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 偽 -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 偽 -imino indole-diazo compound to form 偽 -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 偽 -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.
【學(xué)位授予單位】：廣西大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O626.13
本文編號：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 偽 -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 偽 -imino indole-diazo compound to form 偽 -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 偽 -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.
【學(xué)位授予單位】：廣西大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O626.13
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