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Author: 吳榮軒
Wu, Rong-Xuan
Thesis Title: 路易斯酸輔佐環型2,3-環氧基炔醯胺、六環炔‒炔醯胺及呋喃炔醯胺化合物的環化反應:雙環㗁唑啶、螺旋γ-內醯胺與吡咯衍生物的合成
Lewis Acid-Promoted Cyclization Reactions of Cyclic 2,3-Epoxy-1-ynamides, Six-Membered Ring Yne-Ynamides, and Ynamide-Tethered Furans: Synthesis of Bicyclic Oxazolidines, Spiro γ-Lactams, and Pyrrole Derivatives.
Advisor: 葉名倉
Yeh, Ming-Chang
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2018
Academic Year: 106
Language: 中文
Number of pages: 355
Keywords (in Chinese): 路易斯酸氯化鋅雙環㗁唑啶炔‒炔醯胺氯化亞鐵螺旋γ-內醯胺三氯化金吡咯
Keywords (in English): Lewis acid, zinc chloride, bicyclic oxazolidine, yne-ynaminde, iron(II) chloride, spiro γ-lactam, gold(III) chloride, pyrrole
DOI URL: http://doi.org/10.6345/THE.NTNU.DC.045.2018.B05
Thesis Type: Academic thesis/ dissertation
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  • 本文分為三個主題,依序探討路易斯酸輔佐環型2,3-環氧基-1-炔醯胺化合物、六環炔‒炔醯胺化合物與呋喃炔醯胺化合物,分別合成雙環㗁唑啶、螺旋 γ-內醯胺與吡咯衍生物。

    (1) 利用環型2,3-環氧基-1-炔醯胺化合物作為起始物,在氯化鋅輔佐下,密封管中進行分子內環化反應,得到具三個立體中心、單一(Z)構型的雙環㗁唑啶骨架化合物。此反應優點為操作簡單、產率高且得到唯一的立體異構物。

    (2) 利用六環炔‒炔醯胺化合物作為起始物,在乾燥空氣及氯化亞鐵輔佐下進行分子內環化反應,得到氯取代的螺旋 γ-內醯胺化合物。此反應經由開環‒E2 消去反應‒aza-Prins-cyclization 系列形成氯取代的螺旋 γ-內醯胺化合物,優點為起始物製備容易與條件溫和。

    (3) 利用金(III)催化呋喃炔醯胺化合物進行分子內環化反應,得到順式-3-(3-側氧基-3-芳香基-1-丙烯基)-4-苯基吡咯衍生物。此反應優點為條件溫和及反應時間短。

    Three topics are discussed in this thesis. The Lewis acid-promoted cyclization reactions of cyclic 2,3-epoxy-1-ynamides, six-membered ring 1-yne-ynamides and ynamide-tethered furans afforded bicyclic oxazolidines, spiro γ-lactams and pyrrole derivatives, respectively.

    (1) The ZnCl2-promoted intramolecular cyclization reactions of aryl-substituted cyclic 2,3-epoxy-1-ynamides in a sealed tube yielded bicyclic oxazolidines containing three contiguous stereocenters with Z configuration. This methodology benefits from simple procedures, excellent yields, and a single stereoisomer of desired products.

    (2) The FeCl2-promoted intramolecular cyclization of alkyl or aryl-substituted six-membered 1-yne-ynamides under dry air afforded chlorinated spiro γ-lactams. The reaction mechanism was suggested to proceed via a ring-opening‒E2-elimination‒aza-prins-cyclization sequence, generating chlorinated spiro γ-lactams. The advantages of this reaction are mild reaction conditions and easily available of starting materials.

    (3) Gold(III)-catalyzed intramolecular cyclization reaction of ynamide-tethered furans afforded 3-((Z)-(3-aryl-3-oxopropen-1-yl) -4-phenyl-pyrrole derivatives. The advantages of this reaction are mild reaction conditions and short reaction times.

    目錄 i 圖目錄 v 表目錄 vii 式目錄 viii 流程目錄 x 縮寫列表 xiii 摘要 xv Abstract xvii 第一章 緒論 1 第二章 雙環㗁唑啶的合成 7 2.1 文獻回顧 7 2.1.1 雙環㗁唑啶的合成方法學 7 2.1.2 具環氧基分子之環化反應 11 2.1.3 氯化鋅分子內環化反應 13 2.2 實驗設計 17 2.3 實驗結果與討論 20 2.3.1 合環前起始物製備 20 2.3.2 環氧基炔醯胺化合物環化條件測試 25 2.3.3 反應機構探討 32 2.4 結論 32 第三章 螺旋 γ-內醯胺的合成 33 3.1 文獻回顧 33 3.1.1 螺旋 γ-內醯胺的合成方法學 33 3.1.2 炔‒炔醯胺分子環化反應 38 3.1.3 氯化亞鐵環化反應 41 3.2 實驗設計 44 3.3 實驗結果與討論 47 3.3.1 合環前起始物製備 47 3.3.2 炔‒炔醯胺化合物環化反應及結構證明 50 3.3.3 反應機構探討 66 3.4 結論 69 第四章 吡咯衍生物合成 71 4.1 文獻回顧 71 4.1.1 吡咯的合成方法學 71 4.1.2 呋喃炔醯胺分子的環化反應 74 4.1.3 三氯化金催化分子內合環反應 75 4.2 實驗設計 79 4.3 實驗結果與討論 81 4.3.1 合環前起始物製備 81 4.3.2 呋喃炔醯胺化合物環化條件測試及結構證明 84 4.3.3 反應機構探討 89 4.4 結論 92 第五章 實驗部分 93 5.1 分析儀器及基本實驗操作 93 5.2 Zinc(II) Chloride-Promoted Synthesis of Bicyclic Oxazolidines. 95 5.2.1 Experiments 95 5.3 Iron(II) Chloride-Promoted Synthesis of Halogenated Spiro γ-Lactams. 99 5.3.1 Experiments 99 5.4 Gold(III) Chloride-Catalyzed Synthesis of Pyrrole Derivatives. 102 5.4.1 Experiments 102 5.5 Synthesis of Six-Membered Ring 2,3-Epoxy-1-ynamide II-24. 107 5.6 Synthesis of Bicyclic Oxazolidines II-36. 113 5.7 Synthesis of Six-Membered Ring 1-(Arylethynyl)cyclohexan-1-amine III-30. 119 5.8 Synthesis of Six-Membered Ring Yne-Ynamide III-28. 136 5.9 Synthesis of Sprio γ-Lactam III-34 and III-35. 165 5.10 Synthesis of N-((5-(Aryl)furan-2-yl)methyl)-4-methylbenzenesulfonamide IV-25. 195 5.11 Synthesis of Ynamide-Tethered Furan IV-24. 197 5.12 Synthesis of Pyrrole IV-31. 200 參考文獻 203 附錄 209 1H、13C與19F的NMR光譜 211 X-ray ORTEP 解析圖譜及checkCIF/PLATON report 323

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