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研究生: 林意蓉
Lin, Yi-Jung
論文名稱: 一、透過有機鏻鹽經由分子內Wittig反應合成雙取代異噁唑 二、透過亞胺葉立德及1,3-茚滿二酮亞芐基進行位向選擇性之 (3+2) 環加成反應合成具有高鏡像選擇性的chromeno[3,4-b]pyrrolidines
I. Phosphine-Mediated Synthesis of Di-substituted Isoxazoles via Intramolecular Wittig Reaction II. A highly enantioselective synthesis of chromeno[3,4-b]pyrrolidines via regioselective (3+2) cycloaddition of azomethine ylides and indandionebenzylidines
指導教授: 林文偉
Lin, Wen-Wei
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 319
中文關鍵詞: 有機鏻鹽異噁唑亞胺葉立德位向選擇性高鏡像選擇性
英文關鍵詞: chromeno[3,4-b]pyrrolidines
DOI URL: http://doi.org/10.6345/THE.NTNU.DC.012.2018.B05
論文種類: 學術論文
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  • 第一章、透過有機鏻鹽經由分子內 Wittig 反應合成雙取代異噁唑
      經由一連串反應條件優化,成功地透過本實驗室先前開發出製備呋喃、噁唑化合物之合成策略應用於合成具有生物活性之異噁唑衍生物,我們利用穩定、製備方法簡單的有機鏻鹽作為起始物,在溫和的反應條件下建立出一個高效率的氧醯化反應、分子內Wittig反應合成雙取代異噁唑,甚至透過一鍋化反應表現仍不遜色。

    第二章、透過亞胺葉立德及1,3-茚滿二酮亞芐基進行位向選擇性之 (3+2) 環加成反應合成具有高鏡像選擇性的chromeno[3,4-b]pyrrolidines
    藉由亞胺葉立德及1,3-茚滿二酮亞芐基合成出連續四個立體中心之chromeno[3,4-b]pyrrolidines,並透過金雞納鹼雙官能催化劑之氫鍵催化模式下進行 (3+2)環加成反應達到位向選擇性之目的以及合成出具有高立體選擇性之產物chromeno[3,4-b]pyrrolidines。並透過將產物進行衍生化解決了產物光譜判定之困難以及非鏡像異構物之判別不易的問題並建構出具有藥用的化合物。

    I. Phosphine-Mediated Synthesis of Di-substituted Isoxazoles via Intramolecular Wittig Reaction
    Motivated by the successful synthesis of the furans and oxazoles, we herein extend our intramolecular Wittig reaction strategy to construct potentially bio-active isoxazoles. To begin with, a series of stable isolable phosphonium salts were generated from α-halo ketoximes and the thus obtained phosphonium salts were subjected to a tandem O-acylation and intramolecular Wittig reaction to afford isoxazoles under mild conditions. Further, a one-pot protocol was also realized wherein the α-halo ketoximes were directly transformed into isoxazoles in moderate to good yields.

    II. A highly enantioselective synthesis of chromeno[3,4-b]pyrrolidines via regioselective (3+2) cycloaddition of azomethine ylides and indandionebenzylidines
    Scarcely reported chromeno[3,4-b]pyrrolidines bearing four contiguous stereocenters were synthesized starting from azomethine ylides and indandionebenzylidines. Cinchona alkaloid derived bifunctional hydrogen bonding catalyst was found to promote this regioselective (3+2) cycloaddition to generate the above products in good yields with high enantio and diastereoselectivities. Further derivatization of the adducts was not only helpful in determining the diasteromeric ratio of the adducts but also in demonstrating the synthetic utility of the protocol.

    Abstract IV 摘要 IV 第一章、透過有機鏻鹽經由分子內Wittig反應合成雙取代異噁唑 1 1-1 前言 1 1-1-1 雜環化合物 (Heterocyclic compounds) 與異噁唑 (Isoxazoles) 之生物活性 1 1-1-2 異噁唑之合成方法 2 1-1-2-1 (3+2) 環加成反應 2 1-1-2-2 縮合反應 3 1-1-2-3 環化異構化反應 4 1-1-2-4 其他方法 5 1-2 研究動機 9 1-2-1 有機膦試劑合成雜環化合物 9 1-2-2 鏻鹽合成雜環化合物 10 1-3 實驗結果與討論 12 1-3-1 3,5-雙取代異噁唑 (3.5-disubstituted isoxazole) 之反應條件優化 12 1-3-2 3,5-雙取代異噁唑化合物之取代基效應 18 1-3-3 3,5-雙取代異噁唑化合物之合成反應機構探討 20 1-3-4 一鍋化反應 21 1-4 結論及未來展望 22 1-5 實驗部分 24 1-5-1 分析儀器 24 1-5-2 實驗操作步驟 24 1-5-3 光譜數據 27 1-6 參考文獻 52 附件一、NMR光譜數據 54 附件二、X-ray 單晶繞射數據 107 第二章、透過亞胺葉立德及1,3-茚滿二酮亞芐基進行位向選擇性之 (3+2) 環加成反應合成具有高鏡像選擇性的chromeno[3,4-b]pyrrolidines 126 2-1 前言 126 2-1-1 (3+2) 環加成反應與 1,3-偶極化合物 126 2-1-2 亞胺葉立德 (Azomethine Ylide) 127 2-1-2-1 金屬與掌性配基 127 2-1-2-2 布忍斯特酸催化 128 2-1-2-3 二級胺催化 128 2-1-2-4 三級胺催化 129 2-2 研究動機 130 2-2-1 Pyrrolidine及Chromane架構化合物之生物活性 130 2-2-2 Chromenopyrrolidine之合成方法 131 2-2-2-1 Chromeno[4,3-b]pyrrolidines 132 2-2-2-2 Chromeno[3,4-c]pyrrolidines 133 2-2-2-3 Chromeno[3,4-b]pyrrolidines 134 2-2-2-4 亞胺葉立德之位向選擇性控制 135 2-3 實驗結果與討論 137 2-3-1 Chromeno[3,4-b]pyrrolidines 衍生物之反應條件優化 137 2-3-2 非鏡像異構物 (Diastereomer)及旋轉異構物 (Rotamer)之確認 141 2-3-3 Chromeno[3,4-b]pyrrolidines 之取代基效應 145 2-3-4 Chromeno[3,4-b]pyrrolidines之反應機構探討 148 2-3-5 產物之半胺縮醛化 148 2-4 結論及未來展望 151 2-5 實驗部分 152 2-5-1 分析儀器 152 2-5-2 實驗操作步驟 153 2-5-3 光譜數據 157 2-6 參考文獻 193 附件一、NMR光譜數據 196 附件二、HPLC層析圖 258 附件三、X-ray 單晶繞射數據 282

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