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研究生: 王文洋
Wang, Wen-Yang
論文名稱: N-保護-3-硝基吲哚和2-氨基苯扎丙酮的不對稱有機催化形式 [4+2] 環加成反應
Asymmetric Organocatalytic Formal [4+2] Cycloaddition of N-protected-3-Nitroindoles and 2-Aminobenzalacetones
指導教授: 陳焜銘
Chen, Kwunmin
口試委員: 李文山
Li, Wen-Shan
葉怡均
Yeh, Yi-Chun
陳焜銘
Chen, Kwunmin
口試日期: 2022/07/26
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 109
中文關鍵詞: 有機催化不對稱合成[4+2]環加成3-硝基吲哚四氫-5H-吲哚并[2,3-b]喹啉
英文關鍵詞: Organocatalysis, Asymmetric synthesis, [4+2] cycloaddition, 3-nitroindole, tetrahydro-5H-indolo[2,3-b]quinoline
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202201094
論文種類: 學術論文
相關次數: 點閱:135下載:6
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  • 近年來,發現一些具有生物活性的天然物,都有著四氫-5H-吲哚并[2,3-b]喹啉的核心骨架。過去的文獻中,對於此類架構合成必須透過金屬催化劑控制立體選擇性,直接使用3-硝基吲哚搭配不對稱有機催化方法尚未被發表。本研究首次展示透過不對稱有機催化形式[4+2]環加成反應,構建四氫-5H-吲哚并[2,3-b]喹啉衍生物。
    使用雙功能金雞納生物鹼方醯胺催化劑,對3-硝基吲哚和甲基-2-(甲苯磺酰氨基)苯基α,β-不飽和酮,在溫和的反應條件下,進行鏡像選擇性有機催化反應,合成一系列含有三個連續立體中心的四氫-5H-吲哚并[2,3-b]喹啉衍生物,得到良好的產率(高達60%)和高度立體選擇性(高達15:1 dr和98% ee)。

    In recent years, some biologically active natural products have been found to have the core skeleton of tetrahydro-5H-indolo[2,3-b]quinoline. In the past literature, the stereoselectivity must be controlled by metal catalysts for this type of architecture synthesis, and the direct use of 3-nitroindole with asymmetric organocatalysis methods has not been published. This study features the first asymmetric organocatalytic formal for constructed tetrahydro-5H-indolo[2,3-b]quinolines derivatives.
    An organocatalytic enantioselective synthesis of tetrahydro-5H-indolo[2,3-b]quinolines derivatives was demonstrated using 3-nitroindoles and methyl 2-(tosylamino)phenyl α,β-unsaturated ketones in the presence of the bifunctional cinchona alkaloids squaramide catalyst. A series of tetrahydro-5H-indolo[2,3-b]quinolines derivatives containing three continuous stereogenic centers were obtained in good yields (up to 60%) and with high stereoselectivities (up to 15:1 dr and up to 98% ee).

    簡歷 i 謝誌 ii 摘要 iii Abstract iv 目錄 v 第一章 緒論 1 1-1 前言 1 1-2 有機不對稱催化 3 1-2-1 有機共價催化─烯胺與亞胺離子催化 4 1-2-2 有機非共價催化─氫鍵催化 6 1-2-3 有機非共價催化─陰陽離子對催化 8 1-2-4 自由基催化─SOMO催化 9 1-3 不對稱有機催化連鎖反應 10 1-3-1 不對稱有機催化Cascade反應 10 1-3-2 不對稱有機催化Domino反應 11 1-3-3 不對稱有機催化Tandem反應 12 1-4 3-硝基吲哚與多電子物質的反應性 13 1-4-1 (3+2)形式環加成 14 1-4-2 (4+2)形式環加成 16 1-5 四氫-5H-吲哚并[2,3-b]喹啉衍生物之合成 19 1-6 研究動機 21 第二章 結果與討論 22 2-1 起始物的製備 22 2-1-1 3-硝基吲哚衍生物之製備 22 2-1-2 (E)-4-(2-氨基苯基)丁-3-烯-2-酮衍生物之製備 22 2-2 實驗結果 23 2-2-1 掌性催化劑篩選 23 2-2-2 溶劑效應 25 2-2-3 最佳化條件篩選 27 2-2-4 取代基效應 28 2-3 產物之結構解析 31 2-4 反應機構探討 37 2-5 結論 38 第三章 實驗部分 39 3-1 分析儀器及基本實驗操作 39 3-2 實驗步驟 41 3-2-1 General procedure for the preparation of N-protected-3-nitroindole derivatives 43 41 3-2-2 General procedure for the preparation of (E)-4-methyl-N-(2-(3-oxobut-1-en-1-yl)phenyl)benzenesulfonamide derivatives 69 42 3-2-3 General experimental procedure for the synthesis of tetrahydro-5H-indolo[2,3-b]quinolines derivatives 74 43 3-3 光譜數據 45 參考資料 54 附錄一 1H及13C-NMR光譜 58 附錄二 2D-光譜圖 77 附錄三 X-ray單晶繞射結構解析與數據 87

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