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Author: 簡子強
Chien, Tzu-Chiang
Thesis Title: I. 路易斯酸輔佐六員環2‒烯‒, 2‒炔‒炔醯胺化合物的環化反應:稠雙環δ‒內醯胺化合物的合成 II. 三氯化金催化炔醯胺呋喃化合物的環化反應:吡咯化合物的合成
I. Lewis acid-Promoted Cyclization Reactions of Six-Membered Ring 2‒Ene‒ and 2-Yne-Ynamides:Synthesis of Fused Bicyclic δ-Lactams II. Gold(III) Chloride-Catalyzed Cyclization Reactions of Ynamide-Tethered Furans:Synthesis of pyrroles
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: 347
Keywords (in Chinese): 分子內環化反應炔醯胺分子三氟化硼乙醚稠雙環δ -內醯胺六氫異喹啉酮衍生物三氯化金
Keywords (in English): intramolecular cyclization, ynamide, BF3.OEt2, fused-bicyclic δ-lactam, gold(III) chloride
DOI URL: http://doi.org/10.6345/THE.NTNU.DC.051.2018.B05
Thesis Type: Academic thesis/ dissertation
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  • 本論文分成二個部分。第一部分是利用三氟化硼乙醚輔佐下第三丁基矽醚保護的2-(乙炔胺)-甲基環己烷-2-烯醇化合物進行分子內環化反應,可得到六氫異喹啉酮衍生物。利用氯化亞鐵輔佐六員環2-炔-炔醯胺化合物進行分子內環化反應,可得到稠雙環δ-內醯胺衍生物。第二部分為利用三氯化金催化5-甲基-2-(乙炔胺)呋喃化合物進行分子內環化反應,可得到吡咯衍生物。
    第一部分為三氟化硼乙醚輔佐第三丁基二甲基矽醚保護的2-(乙炔胺)甲基環己烷-2-烯醇化合物進行分子內環化反應,可以直接合成出六氫異喹啉酮衍生物,利用DBU可以將非鏡像異構物的六氫異喹啉酮混合物進行差向異構化(epimerization),得到單一非鏡像異構物。

    合成具三個立體中心含鹵素稠雙環δ-內醯胺衍生物,在乾燥空氣及四氫呋喃條件下,利用氯化亞鐵合成含鹵素稠雙環δ-內醯胺衍生物。此反應的優點為起始物合成步驟簡短、實驗操作簡單、不用加入額外的氧化劑且在溫和條件下進行反應。

    第二部分為在毒性較低的甲苯及室溫條件下,利用三氯化金催化使炔醯胺呋喃化合物轉變成吡咯衍生物,其優點為條件溫和、實驗操作簡單和不錯的產率。

    The thesis cantains two topics. The first part covers the synthesis of hexahydroisoquinolinone derivatives via BF3·OEt2-assisted intramolecular cyclization of alkyl- or aryl-substituted of TBS-protected 2-(ethynyl(tosyl)amino)-methylcyclohex-2-enols and the synthesis of fused-bicyclic δ-lactams via FeCl2-assisted intramolecular cyclization of six-membered yne-ynamide. The second part is the synthesis of pyrrole derivatives via gold(III) chloride-catalyzed intramolecular cyclization of 5-methyl-2-(ethynyl(tosyl)amino)methylfurans.
    The BF3·OEt2-assisted intramolecular cyclization of alkyl- or aryl-substituted of TBS-protected 2-(ethynyl(tosyl)amino)-methylcyclohex-2-enols enables a straightforward approach to hexahydroisoquinolinone derivatives. Upon epimerization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), the mixture of diastereomers lead to hexahydroisoquinolinone derivatives as a single isomer.

    A synthesis of halogenated fused-bicyclic δ-lactams with three stereogenic centers is developed. Treatment of iron(II) chloride with six-membered ring 2-yn-ynamides in THF under dry air afforded halogenated bicyclic δ-lactams in good yields. The reaction are procedurally simple, producing halogenated bicyclic δ-lactams under mild conditions without an additional oxidizing agent.

    Gold(III) chloride-catalyzed reaction of 5-methyl-2-(enthynyl(tosyl)amino)methylfuran occurred efficiently in toluene at room temperature, leading to a series of pyrrole derivatives
    The advantages of the reactions are mild reaction conditions、simple experimental operations and high yields.

    目錄 I 圖目錄 III 流程目錄 IV 表目錄 VI 式目錄 VII 縮寫列表 IX 摘要 XI Abstract XIII 第一章 緒論 1 第二章 路易斯酸輔佐烯炔醯胺合成六氫異喹啉酮衍生物 5 2-1 前言 5 2.1.1合成異喹啉酮衍生物架構的文獻探討 5 2.1.2 烯炔醯胺化合物分子之環化反應 9 2.1.3 利用路易斯酸進行環化反應 14 2.2 實驗設計與概念 18 2.3 實驗結果與討論 21 2.3.1 起始物製備 21 2.3.2 合成具有不同取代的六氫異喹啉酮衍生物 29 2.3.3 反應機構探討 31 2-4 結論 32 第三章 路易斯酸輔佐炔-炔醯胺化合物六氫喹啉酮衍生物 33 3.1 前言 33 3.1.1 合成喹啉酮衍生物架構的文獻探討 33 3.1.2 炔醯胺化合物分子之環化反應 40 3.1.3 以氯化亞鐵(ferrous chloride, FeCl2)進行合環反應 48 3.2 實驗設計 51 3.3 實驗結果與討論 53 3.3.1 起始物製備 53 3.3.2 六員環炔炔醯胺化合物環化反應及結構證明 59 3.4 反應機構探討 70 3.5結論 72 第四章 金(III)催化烯炔醯胺化合物化合物合成吡咯衍生物 73 4.1 前言 73 4.1.1 合成吡咯衍生物的方法 73 4.1.2 利用三氯化金(gold(III) chloride, AuCl3)催化進行合環反應 83 4.2 實驗設計 91 4.3 實驗結果與討論 93 4.3.1 起始物製備 93 4.3.2 炔醯胺呋喃化合物環化反應及結構證明 96 4.3.3 反應機制的探討 101 4.4 結論 101 第五章 實驗部分 102 5.1 分析儀器及基本實驗操作 102 5.2 BF3.OEt2-Promoted Synthesis of Hexahydroisoquinolinones. 104 5.2.1 Experiments 104 5.3 FeCl2-Promoted Synthesis of Hexahydroquinolinones. 113 5.3.1 Experments 113 5.4 Gold(III) chloride -Catalyzed Synthesis of 3,4-Disubsituted Pyrrole 117 5.4.1 Experiments 117 5.5 Synthesis of Alkyl- or Aryl-substituted TBS-Protected N-Tosyl-2-((arylethynyl)-amino)methyl)cyclohex-2-enols 121 5.6 Synthesis of Hexahydroisoqunolinones 129 5.7 Synthesis of six-membered ring of yne-ynamide compounds 136 5.8 Synthesis of Hexahydroqunolinones 149 5.9 Synthesis of 5-Methyl-N-Tosyl-2-ynamidomethylfurans 162 5.10 Synthesis of Pyrroles 173 參考文獻 184 附錄 189 1H、13C 與 19F 的NMR 光譜 191 X-ray ORTEP 解析圖譜、數據及checkCIF/PLATON report 319

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