發(fā)布時間：2018-03-14 23:16

  本文選題：碳氫鍵活化　切入點：VA唑啉　出處：《浙江大學》2017年博士論文　論文類型：學位論文

【摘要】：由于無需對反應(yīng)底物進行預官能團化,反應(yīng)步驟減少、策略簡便,碳氫鍵直接官能團化反應(yīng)為天然產(chǎn)物以及藥物分子的合成提供了高效且原子經(jīng)濟的途徑。近年來對碳氫鍵直接官能團化反應(yīng)的研究已經(jīng)成為有機化學中的熱門領(lǐng)域。但是克服碳氫鍵的高鍵能并且實現(xiàn)區(qū)域選擇性碳氫鍵活化反應(yīng)具有很大的挑戰(zhàn)。本論文基于導向策略分別研究了過渡金屬鈀,銅,釕催化的碳氫鍵官能團化反應(yīng),發(fā)展了構(gòu)筑碳氧鍵,碳鹵鍵和碳碳鍵的新策略,主要內(nèi)容介紹如下:1.鈀催化酰胺β-C(sp~3)-H鍵活化制備多取代VA唑啉該研究以脂肪族酰胺為底物,以吡啶為單齒導向基團,通過串聯(lián)惰性C(sp~3)-H鍵活化/C-O鍵環(huán)化反應(yīng)實現(xiàn)了VA唑啉衍生物的高效合成。該策略不僅能夠以高產(chǎn)率制備甲基活化后的VA唑啉產(chǎn)物,普通亞甲基C(sp~3)-H鍵也能很好的轉(zhuǎn)化為相應(yīng)的VA唑啉結(jié)構(gòu)。生成的VA唑啉結(jié)構(gòu)可以水解為相應(yīng)的β-氨基醇。初步的機理研究表明,反應(yīng)可能是經(jīng)過先氯代再親核環(huán)化的過程進行的。2.銅催化鄰位碳氫鍵活化合成(雜)芳基鹵代物該研究以2-(2-吡啶基)異丙基胺(PIPNH_2)作為雙齒導向基團,以N-鹵代丁二酰亞胺作為鹵素來源,發(fā)展了銅催化的鄰位C(sp~2)-H鍵的鹵代反應(yīng)。該反應(yīng)具有良好的官能團容忍性且底物普適性廣,為合成芳基鹵代物和雜芳基鹵代物提供了新的有效方法。反應(yīng)可以放大至克級規(guī)模,而且導向基團可以脫除,充分說明了此方法在有機合成中的應(yīng)用價值。3.釕催化間位選擇性C-H鍵芐基化反應(yīng)該研究以吡啶作為導向基團,通過結(jié)合釕催化鄰位C-H活化與芳烴特定位置的C(sp~2)-H和甲苯衍生物C(sp~3)-H的脫氫偶聯(lián)反應(yīng),實現(xiàn)了芳烴間位選擇性C-H芐基化反應(yīng)。該反應(yīng)的區(qū)域選擇性高,官能團容忍性較好,為合成二芳基甲烷骨架提供了 一種新的有效策略。初步研究表明,反應(yīng)可能通過自由基機理進行。
[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.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O621.25
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本文編號：1613384