銀介導溶劑控制下從5-溴-1,2,3-三嗪選擇性合成呋喃以及吡咯

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陳湘文(Hsiang-Wen Chen) 查詢紙本館藏

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化學學系

論文名稱

銀介導溶劑控制下從5-溴-1,2,3-三嗪選擇性合成呋喃以及吡咯
(Silver-Mediated Divergent Synthesis of Furans and Pyrroles from 5-Bromo-1,2,3-Triazine by Solvent Control)

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★ 選擇性標記含胍基化合物的化學探針分子

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摘要(中)

烯炔類分子的環化異構化反應是一種經常用來合成五員雜環化合物的途徑之一，該途徑符合原子經濟的要求。我們旨在開發藉由單一起始物選擇性合成呋喃以及吡咯的方法。傳統合成方法在進行此類反應時，需要過渡金屬催化對多重鍵進行活化，合成特定含有酮基或胺基的前驅物，從中促使酮基或胺基攻打多重鍵進行環化異構化反應，建構呋喃或吡咯骨架。本論文中，我們則是藉由5-炔基取代-1,2,3-三嗪作為起始物，選擇適當的溶劑及親核試劑，藉由銀介導親核性開環反應形成含烯炔官能基的中間體，有效控制合環反應的選擇性，同時得到相對應的產物。研究結果顯示，當反應溶劑四氫呋喃中含水時，5-取代呋喃-3-醛則是主要的產物；而當反應溶劑僅使用四氫呋喃，並以二乙胺作為親核試劑時，則有效促使反應趨向產生5-取代吡咯-3-醛。該反應不需要使用昂貴的試劑，只需使用硝酸銀或醋酸銀來促進反應，使得兩種產物均可分別得到良好到優異的產率及化學選擇性。該方法同時展示反應物的多樣性、簡易的實驗操作和原子經濟性等優點。

摘要(英)

The cycloisomerization reaction of enynes is a commonly employed synthetic route for the synthesis of five-membered heterocycles that meets the requirements of atom economy. Herein, we aim to develop a method to selectively synthesize furans and pyrroles from a single starting material. Traditional synthetic methods for such cycloisomerization reactions often use a specific starting material containing ketone or amine groups as precursors, which promotes the attack of multiple bonds by ketone or amine groups to undergo transition metal-catalyzed cyclization isomerization reactions, resulting in the construction of furan or pyrrole skeletons, respectively. In this thesis, we employed 5-substituted-1,2,3-triazine as the starting material and chose a suitable solvent and nucleophilic reagent, forming an intermediate with an alkyne functional group through silver-mediated nucleophilic ring-opening reactions. The selectivity of the cyclization reaction was effectively controlled, and the corresponding furan and pyrrole products were obtained. Our findings show that when the reaction is in aqueous tetrahydrofuran, 5-substituted furan-3-aldehyde is the major product, while using tetrahydrofuran as the reaction solvent and diethylamine as the nucleophilic reagent effectively promotes the production of 5-substituted pyrrole-3-aldehyde. This reaction does not require expensive reagents, only silver nitrate or silver acetate to promote the reaction, allowing both products to be obtained with good to excellent yields and chemoselectivity. This approach has advantages in terms of substrate scope, user-friendly procedures, and atom economy.

關鍵字(中)

★ 烯炔
★ 環化異構化反應
★ 三嗪
★ 呋喃
★ 吡咯

關鍵字(英)

★ Enynes
★ Cycloisomerization
★ Triazines
★ Furans
★ Pyrroles

論文目次

目次
摘要 vii
Abstract viii
誌謝 ix
目次 x
圖次 xi
表次 xii
簡稱用語對照表 xii
第一章緒論 1
1-1雜環化合物的種類及其應用 1
1-2 官能化五員芳香雜環化合物相關衍生物及其相關衍生物 2
1-3 傳統五員芳香雜環化合物的建構方法 3
1-3-1 帕爾–克諾爾合成 (Paal–Knorr synthesis) 4
1-3-2 克勞森-凱絲反應 (Clauson-Kass reaction) 5
1-3-3 Feist–Benary合成 (Feist–Benary synthesis) 5
1-4 在五員雜環化合物上引入不同官能基的方法 6
1-4-1 鈀催化偶聯反應 (Pallidium catalyzed coupling reaction) 6
1-4-2 維爾斯邁爾-哈克反應 (Vilsmeier–Haack reaction) 7
1-5近期研究建構五員雜環化合物的方法 8
1-6 建構五員芳香雜環化合物的文獻回顧 10
1-7 研究動機 14
第二章實驗結果與討論 16
2-1 5-溴-1,2,3-三嗪的合成及5-取代炔基-1,2,3-三嗪的合成 16
2-2 反應條件優化 17
2-3 底物範圍 21
2-4 反應機構 23
第三章結論 25
第四章實驗部分 25
參考文獻 66
圖次
圖1、雜環化合物的分類 1
圖2、雜環化合物的應用 2
圖3、常見的五員雜環化合物的骨架 3
圖4、合成五員雜環芳香化合物中間體的鍵結建構模式 4
圖5、合成五員雜環芳香化合物典型的斷片結構[1] 4
圖6、由Paal–Knorr Synthesis得到2,5-雙取代呋喃、吡咯以及噻吩 5
圖7、克勞森–凱絲反應得到N取代吡咯[2] 5
圖8、α-鹵代酮與β-二羰基化合物通過Feist–Benary synthesis 得到取代呋喃 6
圖9、雜環化合物可進行的鈀催化偶聯反應[4] 7
圖10、藉由不同立體障礙大小的甲醯胺在吡咯上不同位置引入醛基 8
圖11、由過渡金屬促進合成單一或多個雜原子雜環化合物的方法 9
圖12、合成呋喃的各種方法及其起始物的常見結構[22] 9
圖13、使用溴化連烯酮基化合物進行環化異構化反應[23] 10
圖14、連烯酮基進行環化異構化反應推測之反應路徑 10
圖15、利用金/銀催化劑進行環化異構化反應反應得到吡咯 11
圖16、利用金催化合成2,4-雙取代呋喃推測之反應路徑 12
圖17、利用一級胺取代烯醇透過碘化亞銅催化合成吡咯[26] 12
圖18、以水作為溶劑不需要加入催化劑合成呋喃 13
圖19、利用烯炔醯胺透過催化劑控制合成具稠環結構的呋喃和吡咯[28] 13
圖20、利用二乙基鋅促進α-溴羰基化合物合成多取代呋喃、吡咯[29] 14
圖21、使用二級胺對1,2,3-三嗪進行加成得到β-氨基烯醛[30] 14
圖22、從5-溴-1,2,3-三嗪合成1,5-雙取代吡咯-3-醛 15
圖23、利用二乙胺開環得到以吡咯為主的產物 15
圖24、化合物9的合成 16
圖25、化合物11a-11a’的合成路徑 17
圖26、推測之反應機構 24
表次
表1、使用四氯金酸進行條件篩選 18
表2、用銀催化劑反應條件的篩選 20
表3、5-取代呋喃-3-醛底物範圍 22
表4、5-取代吡咯-3-醛底物範圍 23

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指導教授

謝俊結侯敦仁(Juin-Jie Shie Duen-Ren Hou)

審核日期

2024-8-21

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