【摘要】：吲哚及其衍生物是天然產(chǎn)物及藥物活性分子的重要骨架,吲哚環(huán)的官能團(tuán)化一直都是有機(jī)合成領(lǐng)域的熱門研究方向。由于吲哚當(dāng)中吡咯環(huán)上電子云密度較高,較易進(jìn)行反應(yīng),近年來已經(jīng)有大量關(guān)于吲哚C2和C3位官能團(tuán)化的工作見諸報道。然而關(guān)于吲哚苯環(huán)區(qū)域官能團(tuán)化反應(yīng)的研究,在有機(jī)合成界尚屬少見。有鑒于此,本論文發(fā)展了一系列過渡金屬催化體系,通過不同反應(yīng)條件與導(dǎo)向基團(tuán)的調(diào)控,高區(qū)域選擇性地得到了吲哚苯環(huán)區(qū)域各位置官能團(tuán)化產(chǎn)物。本論文具體的研究內(nèi)容包括如下幾部分:第一部分:我們從過渡金屬催化的角度出發(fā),以一類大位阻二叔丁基磷氧作為導(dǎo)向基團(tuán),利用Pd(OAc)_2作為催化劑,芳基硼酸作為芳基源,2-氯吡啶作為配體,銀鹽和銅鹽作為氧化劑,完美地克服了 2,3號位的優(yōu)先順序問題,首次成功實(shí)現(xiàn)了吲哚7號位高選擇性的直接芳基化。該反應(yīng)體系底物范圍廣,區(qū)域選擇性高,極有望拓展到其他吲哚C7位C-H官能團(tuán)化反應(yīng)體系,為接下來的課題研究打下了基礎(chǔ)。第二部分:利用之前開發(fā)的二叔丁基磷氧作為導(dǎo)向基團(tuán),以CuO作為催化劑,二芳基高碘化物作為芳基源,在不加任何配體和添加劑的作用下,高區(qū)域選擇性地實(shí)現(xiàn)了吲哚6號位的直接芳基化。該反應(yīng)底物對不同官能團(tuán)耐受性好,區(qū)域選擇性高,產(chǎn)率普遍優(yōu)異。我們設(shè)計了一個連續(xù)合成反應(yīng),其高產(chǎn)率和高區(qū)域選擇性說明了該反應(yīng)體系的應(yīng)用價值。第三部分:通過在吲哚C3位引入特戊�；鳛閷�(dǎo)向基團(tuán),以Pd(PPh_3)_2C1_2為催化劑,芳基碘化物為芳基源,Ag_2O為氧化劑,DBU為堿,在溶劑HFIP當(dāng)中高區(qū)域選擇性地實(shí)現(xiàn)了吲哚4號位的直接芳基化。該反應(yīng)區(qū)域選擇性高,底物范圍廣,同時導(dǎo)向基團(tuán)易脫除。在克級反應(yīng)實(shí)驗(yàn)當(dāng)中,反應(yīng)仍然具有很好的區(qū)域選擇性和產(chǎn)率。通過一個天然產(chǎn)物分子的合成示例,證明了該反應(yīng)策略在分子合成中的應(yīng)用價值。第四部分:利用之前開發(fā)的二叔丁基磷氧官能團(tuán)化的吲哚作為底物,以P(p-CF_3C_6H_4)_3AuNTf_2作為催化劑,α-苯基酯重氮化合物為卡賓前體,HNTf_2為添加劑,高區(qū)域選擇性地實(shí)現(xiàn)了吲哚苯環(huán)區(qū)域的直接烷基化。底物拓展表明該反應(yīng)體系具有良好的區(qū)域選擇性。
[Abstract]:Indole and its derivatives are important skeletons of natural products and drug active molecules. The functionalization of indole ring has always been a hot research direction in organic synthesis. Due to the high electron cloud density of pyrrole ring in indole, there have been a lot of reports on indole-C2 and C3 functionalization in recent years. However, studies on the regional functionalization of indole ring are rare in organic synthesis. In view of this, a series of transition metal catalytic systems were developed in this paper. Through the regulation of different reaction conditions and guided groups, the functionalized products of various positions in the indole ring region were obtained selectively in the high region. The specific research contents of this thesis are as follows: the first part: from the point of view of transition metal catalysis, we use Pd (OAc) _ 2 as the catalyst with a large hindrance of tert-Ding Ji as the guiding group. Aryl boric acid as aryl source, 2-chloropyridine as ligand, silver salt and copper salt as oxidant, which perfectly overcome the priority of 2,3 sites, and successfully realized the highly selective direct arylation of indole 7 site for the first time. This reaction system has a wide range of substrates and high regioselectivity, which is expected to be extended to other C-H functionalized reaction systems at indole C _ 7 position, which will lay a foundation for further research. The second part: using the second tert-Ding Ji as the guiding group, CuO as the catalyst and the diaryl polyiodide as the aryl source, without any ligands and additives. The direct arylation of indole 6 site is realized selectively in high region. The substrate has good tolerance to different functional groups, high regional selectivity and excellent yield. A continuous synthetic reaction was designed, and its high yield and high region selectivity showed the application value of the reaction system. The third part: by introducing tervalyl group as the guiding group at indole-C3 site, using Pd (PPh_3) _ 2C1_2 as catalyst, aryl iodide as aryl source, Ag_2O as oxidant, DBU as base, The direct arylation of indole 4 site was achieved in high region selectivity in solvent HFIP. The region selectivity of the reaction is high, the substrate range is wide, and the guided group is easy to be removed. The reaction still has good regioselectivity and yield. The application value of this reaction strategy in molecular synthesis is proved by an example of the synthesis of natural product molecules. The fourth part: using indoles as substrate, using P (p-CF_3C_6H_4) _ 3AuNTf_2 as catalyst, 偽 -phenyl ester diazo compound as carbene precursor and HNTf_2 as additive. The direct alkylation of indole ring was realized selectively in high region. The substrate expansion shows that the reaction system has good regioselectivity.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：O621.251

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 汪焱鋼;有機(jī)合成中的化學(xué)選擇性與區(qū)域選擇性[J];高等函授學(xué)報(自然科學(xué)版);1994年03期

2 陸洋;;區(qū)域選擇性芳環(huán)親電溴化反應(yīng)[J];中國醫(yī)藥工業(yè)雜志;2008年10期

3 王磊;;區(qū)域選擇性和酮的活潑亞甲基反應(yīng)[J];淮北煤師院學(xué)報(自然科學(xué)版);1990年03期

4 劉大嶺,李苗盛,王植才;控制區(qū)域選擇性的間接途徑新進(jìn)展(一)——Diels-Alder反應(yīng)中控制區(qū)域選擇性的間接途徑[J];化學(xué)研究與應(yīng)用;1998年04期

5 樓鑫;侯金松;Seamas Cassidy;;錫類絡(luò)合物在糖衍生物合成中的區(qū)域選擇性[J];化學(xué)通報;2010年04期

6 呂澤光;周其忠;;銅催化的2,x-二溴吡啶與硫酚的高度區(qū)域選擇性偶聯(lián)反應(yīng)[J];浙江大學(xué)學(xué)報(理學(xué)版);2013年05期

7 姜淑芳;侯淑芳;郭成福;;不對稱D—A反應(yīng)區(qū)域選擇性及其理論解析[J];哈爾濱師范大學(xué)自然科學(xué)學(xué)報;1991年01期

8 彭新華,呂春緒;皂土催化劑上芳烴的硝酸酯硝化反應(yīng)的區(qū)域選擇性研究[J];有機(jī)化學(xué);2000年04期

9 彭新華,呂春緒;酸性皂土催化劑作用下硝酸硝化鹵苯的區(qū)域選擇性[J];火炸藥學(xué)報;2000年03期

10 章本禮;卓金聰;高振衡;;不對稱β-二酮與苯胺反應(yīng)的區(qū)域選擇性研究[J];有機(jī)化學(xué);1989年06期

相關(guān)會議論文 前10條

1 崔建國;曾隴梅;蘇鏡娛;林翠梧;;多羰基甾酮的區(qū)域選擇性還原反應(yīng)研究[A];新世紀(jì) 新機(jī)遇 新挑戰(zhàn)——知識創(chuàng)新和高新技術(shù)產(chǎn)業(yè)發(fā)展（下冊）[C];2001年

2 梁建華;姚國偉;曹志凌;;2',4"-O-雙(三甲基硅)紅霉素9-肟衍生物的區(qū)域選擇性[A];中國化學(xué)會第四屆有機(jī)化學(xué)學(xué)術(shù)會議論文集（上冊）[C];2005年

3 唐守萬;李曉芳;金召磊;田利利;王芳;劉貴花;潘富友;;區(qū)域選擇性修飾淀粉衍生物的制備及其在液相色譜分離對映體中的應(yīng)用[A];全國生物醫(yī)藥色譜及相關(guān)技術(shù)學(xué)術(shù)交流會（2012）會議手冊[C];2012年

4 王文峰;傅南雁;李俊{，

本文編號：2314223