含氮官能团导向的碳氢键活化反应研究

发布时间：2018-03-14 23:16

  本文选题：碳氢键活化　切入点：VA唑啉　出处：《浙江大学》2017年博士论文　论文类型：学位论文

【摘要】：由于无需对反应底物进行预官能团化,反应步骤减少、策略简便,碳氢键直接官能团化反应为天然产物以及药物分子的合成提供了高效且原子经济的途径。近年来对碳氢键直接官能团化反应的研究已经成为有机化学中的热门领域。但是克服碳氢键的高键能并且实现区域选择性碳氢键活化反应具有很大的挑战。本论文基于导向策略分别研究了过渡金属钯,铜,钌催化的碳氢键官能团化反应,发展了构筑碳氧键,碳卤键和碳碳键的新策略,主要内容介绍如下:1.钯催化酰胺β-C(sp~3)-H键活化制备多取代VA唑啉该研究以脂肪族酰胺为底物,以吡啶为单齿导向基团,通过串联惰性C(sp~3)-H键活化/C-O键环化反应实现了VA唑啉衍生物的高效合成。该策略不仅能够以高产率制备甲基活化后的VA唑啉产物,普通亚甲基C(sp~3)-H键也能很好的转化为相应的VA唑啉结构。生成的VA唑啉结构可以水解为相应的β-氨基醇。初步的机理研究表明,反应可能是经过先氯代再亲核环化的过程进行的。2.铜催化邻位碳氢键活化合成(杂)芳基卤代物该研究以2-(2-吡啶基)异丙基胺(PIPNH_2)作为双齿导向基团,以N-卤代丁二酰亚胺作为卤素来源,发展了铜催化的邻位C(sp~2)-H键的卤代反应。该反应具有良好的官能团容忍性且底物普适性广,为合成芳基卤代物和杂芳基卤代物提供了新的有效方法。反应可以放大至克级规模,而且导向基团可以脱除,充分说明了此方法在有机合成中的应用价值。3.钌催化间位选择性C-H键苄基化反应该研究以吡啶作为导向基团,通过结合钌催化邻位C-H活化与芳烃特定位置的C(sp~2)-H和甲苯衍生物C(sp~3)-H的脱氢偶联反应,实现了芳烃间位选择性C-H苄基化反应。该反应的区域选择性高,官能团容忍性较好,为合成二芳基甲烷骨架提供了 一种新的有效策略。初步研究表明,反应可能通过自由基机理进行。
[Abstract]:Since there is no need to prefunctionalize the substrate, the steps of the reaction are reduced, and the strategy is simple. The direct functionalization of hydrocarbon bonds provides an efficient and economical way for the synthesis of natural products and drug molecules. In recent years, the study of direct functionalization of hydrocarbon bonds has become a hot topic in organic chemistry. However, overcoming the high bond energy of hydrocarbon bond and realizing region-selective hydrocarbon bond activation have great challenges. In this paper, the transition metal palladium is studied based on the guidance strategy. A new strategy for the construction of carbon-oxygen bond, carbon-halogen bond and carbon-carbon bond was developed by the functionalization of carbon-hydrogen bond catalyzed by copper and ruthenium. The main contents are as follows: 1. Palladium catalyzed activation of amide 尾 -Cspspan 3H bond to prepare polysubstituted VA azoline. This study is based on aliphatic amide. Using pyridine as monodentate guide group, the high efficiency synthesis of VAZoline derivatives was realized by series inert Cnsp ~ (3 +) -H bond activation and cyclization reaction of C-O bond. This strategy can not only produce methyl activated VAZoline products with high yield, but also produce VAZoline derivatives with high yield. The common methylene spsph3- H bond can also be transformed into the corresponding VAZoline structure. The resulting VAZoline structure can be hydrolyzed to the corresponding 尾 -aminoalcohol. The preliminary mechanism study shows that the VAZoline structure can be hydrolyzed to 尾 -amino-alcohol. The synthesis of (hetero) aryl halides catalyzed by copper was carried out by chlorination and then nucleophilic cyclization. In this study, 2-PIPNH2) was used as the bidentate guiding group. Using N-halogenated succinimide as a halogen source, the copper-catalyzed halogenation reaction of ortho-Cnsp ~ (2 +) -H bond has been developed. The reaction has good functional tolerance and wide substrate universality. It provides a new and effective method for the synthesis of aryl halogenates and hetero aryl halides. The reaction can be scaled up to g scale and the leading groups can be removed. The application value of this method in organic synthesis is fully explained .3.The benzylation of m-site selective C-H bond catalyzed by ruthenium is studied with pyridine as the leading group. The selective C-H benzylation of aromatics was achieved by the dehydrogenation coupling reaction of 2-C-H activation catalyzed by ruthenium with the specific position of aromatics and the dehydrogenation of toluene derivative Cnsp ~ (3) O _ (3N) -H. The reaction was characterized by high regioselectivity and good functional group tolerance. It provides a new effective strategy for the synthesis of diarylmethane skeleton. The preliminary study shows that the reaction may be carried out by free radical mechanism.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25
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本文编号：1613384