發(fā)布時間：2018-03-03 00:09

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

【摘要】：近年來,過渡金屬催化的碳氫鍵官能團化反應(yīng)為天然產(chǎn)物以及藥物分子的合成提供了一種高效且原子經(jīng)濟的方法。由于脂肪族化合物的C(sp~3)-H鍵鍵能高、反應(yīng)活性低,因此實現(xiàn)脂肪族化合物的C(sp~3)-H鍵活化,特別是惰性亞甲基C(sp~3)-H鍵活化仍然面臨著巨大的挑戰(zhàn)。另外,芳香族化合物中含有多個C(sp2)-H鍵,如何將反應(yīng)發(fā)生在特定的碳氫鍵上即實現(xiàn)芳烴區(qū)域選擇性碳氫鍵活化同樣是一個關(guān)鍵而又亟待解決的問題。本論文圍繞鈀催化惰性C(sp~3)-H鍵官能團化以及跨環(huán)間位選擇性碳氫鍵芳基化兩個方面展開,具體包括以下內(nèi)容：1.鈀催化丙氨酸β-C(sp~3)-H鍵單芳基化／內(nèi)酰胺化串聯(lián)反應(yīng)制備手性α-氨基-β-內(nèi)酰胺該研究從天然L-丙氨酸底物出發(fā),以5-甲氧基-8-氨基喹啉作為雙齒導向基團,實現(xiàn)了鈀催化β-C(sp~3)-H鍵單芳基化／內(nèi)酰胺化串聯(lián)反應(yīng)。該方法的底物普適性廣且具有良好的官能團容忍性,導向基團可以在溫和的條件下得到脫除,為合成手性α-氨基-β-內(nèi)酰胺衍生物提供了一種有效的途徑。另外,該方法可進一步應(yīng)用到正交保護手性α,β-二胺的合成。2.鈀催化鏈狀脂肪胺γ,-位亞甲基C(sp~3)-H鍵以及δ-位C-H鍵芳基化反應(yīng)該研究以新發(fā)展的雙齒配位2-嗯唑啉甲酰胺為導向基團,實現(xiàn)了鈀催化鏈狀脂肪胺產(chǎn)位惰性亞甲基C(sp~3)-H鍵芳基化以及遠程δ-位C-H鍵芳基化反應(yīng)。在嗯唑啉導向基團上引入手性中心,對γ-位亞甲基C(sp~3)-H鍵不對稱芳基化反應(yīng)進行了初步探究。3.鈀催化跨環(huán)間位C-H鍵芳基化反應(yīng)該研究以降冰片烯作為瞬態(tài)介質(zhì),實現(xiàn)了鈀催化2-氨基聯(lián)苯衍生物跨環(huán)間位選擇性C-H鍵芳基化反應(yīng)。三氟乙�；鳛榘被Ｗo基在實現(xiàn)區(qū)域選擇性碳氫鍵活化過程中起著關(guān)鍵作用。實驗中分離得到跨環(huán)鄰位環(huán)鈀中間體并通過X-射線單晶衍射進行結(jié)構(gòu)表征,中間體當量以及催化量轉(zhuǎn)化實驗表明該中間體是活性環(huán)鈀中間體。此外,跨環(huán)間位芳基化產(chǎn)物可通過氨基原位炔基化反應(yīng)以及導向同環(huán)鄰位碳氫鍵官能團化反應(yīng)為合成一系列不同官能團化的2-氨基聯(lián)苯衍生物提供了有效的方法。
[Abstract]:In recent years, transition metal-catalyzed carbon-hydrogen bond functionalization has provided a highly efficient and atomic economical method for the synthesis of natural products and drug molecules. Because of the high bond energy and low reactivity of aliphatic compounds, Therefore, it is still a great challenge to realize the activation of C ~ (sp ~ (3)) -H bond of aliphatic compounds, especially the activation of inert methylene carboxylic acid ~ (3 +) -H bond. In addition, the aromatic compounds contain many Cnsp _ (2) ~ (-H) bonds. It is also a key and urgent problem to realize the activation of aromatics region-selective hydrocarbon bonds on a specific hydrocarbon bond. In this thesis, the functionalization of palladium catalyzed inert CSPN _ 3H bond and the transring separation of aromatics are discussed. Selective arylation of hydrocarbon bonds, The main contents are as follows: 1. Palladium catalyzed single arylation / lactamination of 尾 -Csp-3H bond of alanine to produce chiral 偽 -amino- 尾 -lactam. The study started from the natural L- alanine substrate and used 5-methoxy-8-aminoquinoline as the didentate guiding group. The palladium catalyzed single arylation / lactam reaction of 尾 -Cn SSP 3H bond in series was realized. The substrate of this method is universal and has good functional group tolerance. The guided group can be removed under mild conditions. It provides an effective way for the synthesis of chiral 偽-amino-尾-lactam derivatives. This method can be further applied to the synthesis of chiral 偽, 尾 -diamine. Palladium catalyzed chain fatty amine 緯 -methylene-methylenediamine 3H bond and 未 -site C-H bond arylation reaction. The study is based on the newly developed didentate coordination 2-hmazolinamide as the leading group. The palladium catalyzed arylation of inert methylene methylidene 3H bond at the production site of chain aliphatic amine and the arylation of the long range 未 -site C-H bond have been achieved. Chiral centers have been introduced into the mizoline-guided group. In this paper, the asymmetric arylation of 緯 -methylene-methylene-C ~ (sp) _ (3) -H bond was studied. Palladium catalyzed arylation of C-H bond across rings was studied. Norbornene was used as a transient medium. Palladium catalyzed arylation of transcyclic selective C-H bond of 2-aminobiphenyl derivatives was achieved. Trifluoroacetyl plays a key role in the activation of regioselective hydrocarbon bonds. To the intermediate of trans-ring orthocyclic palladium and characterized by X-ray single crystal diffraction, The intermediate equivalent and catalytic conversion experiments show that the intermediate is an active cyclic palladium intermediate. The transcyclic arylation products can be synthesized by in situ amino-alkynylation reaction and homocyclic ortho-hydrocarbon bond functionalization reaction, which provides an effective method for the synthesis of a series of 2-aminobiphenyl derivatives with different functional groups.
【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：1558687