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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:98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

    1. Chirality (chemistry). https://en.wikipedia.org/wiki/Chirality_(chemistry).
    2. Stereoisomerism. https://en.wikipedia.org/wiki/Stereoisomerism.
    3. Leitereg, T. J.; Guadagni, D. G.; Harris, J.; Mon, T. R.; Teranishi, R. Chemical and Sensory Data Supporting the Difference between the Odors of the Enantiomeric Carvones. J. Agr. Food. Chem. 1971, 19 (4), 785-787.
    4. Friedman, L.; Miller, J. G. Odor Incongruity and Chirality. Science 1971, 172 (3987), 1044-1046.
    5. Enantiopure Drug. https://en.wikipedia.org/wiki/Enantiopure_drug.
    6. Vargesson, N. Thalidomide-Induced Teratogenesis: History and Mechanisms. Birth Defects Res. C Embryo Today 2015, 105 (2), 140-156.
    7. MacMillan, D. W. The Advent and Development of Organocatalysis. Nature 2008, 455 (7211), 304-308.
    8. The Nobel Prize in Chemistry. https://www.nobelprize.org/prizes/chemistry/.
    9. Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Asymmetric Enamine Catalysis. Chem. Rev. 2007, 107 (12), 5471-5569.
    10. List, B.; Lerner, R. A.; Barbas, C. F. Proline-Catalyzed Direct Asymmetric Aldol Reactions. J. Am. Chem. Soc. 2000, 122 (10), 2395-2396.
    11. Erkkila, A.; Majander, I.; Pihko, P. M. Iminium Catalysis. Chem. Rev. 2007, 107 (12), 5416-5470.
    12. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. New Strategies for Organic Catalysis:  The First Highly Enantioselective Organocatalytic Diels−Alder Reaction. J. Am. Chem. Soc. 2000, 122 (17), 4243-4244.
    13. Doyle, A. G.; Jacobsen, E. N. Small-Molecule H-bond Donors in Asymmetric Catalysis. Chem. Rev. 2007, 107 (12), 5713-5743.
    14. Zhou, X. J.; Zhao, J. Q.; Chen, X. M.; Zhuo, J. R.; Zhang, Y. P.; Chen, Y. Z.; Zhang, X. M.; Xu, X. Y.; Yuan, W. C. Organocatalyzed Asymmetric Dearomative Aza-Michael/Michael Addition Cascade of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes with 2-Aminochalcones. J. Org. Chem. 2019, 84 (7), 4381-4391.
    15. Yoshida, K.; Inoue, H.; Oji, Y.; Suzuki, H.; Takao, K. I. Enantioselective Organocatalytic Construction of Spirochroman Derivatives. J. Org. Chem. 2020, 85 (15), 10189-10197.
    16. Akiyama, T. Stronger Bronsted Acids. Chem. Rev. 2007, 107 (12), 5744-5758.
    17. Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Enantioselective Mannich-Type Reaction Catalyzed by a Chiral Bronsted Acid. Angew. Chem. Int. Ed. 2004, 43 (12), 1566-1568.
    18. Connon, S. J. Chiral Phosphoric Acids: Powerful Organocatalysts for Asymmetric Addition Reactions to Imines. Angew. Chem. Int. Ed. 2006, 45 (24), 3909-3912.
    19. Beeson, T. D.; Mastracchio, A.; Hong, J. B.; Ashton, K.; Macmillan, D. W. Enantioselective Organocatalysis Using SOMO Activation. Science 2007, 316 (5824), 582-585.
    20. Huang, Y.; Walji, A. M.; Larsen, C. H.; MacMillan, D. W. Enantioselective Organo-Cascade Catalysis. J. Am. Chem. Soc. 2005, 127 (43), 15051-15053.
    21. Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Cascade Reactions in Total Synthesis. Angew. Chem. Int. Ed. 2006, 45 (43), 7134-7186.
    22. Liu, Y.; Izzo, J. A.; McLeod, D.; Ricko, S.; Svenningsen, E. B.; Poulsen, T. B.; Jorgensen, K. A. Organocatalytic Asymmetric Multicomponent Cascade Reaction for the Synthesis of Contiguously Substituted Tetrahydronaphthols. J. Am. Chem. Soc. 2021, 143 (21), 8208-8220.
    23. Tietze, L. F. Domino Reactions in Organic Synthesis. Chem. Rev. 1996, 96 (1), 115-136.
    24. Kaya, U.; Chauhan, P.; Mahajan, S.; Deckers, K.; Valkonen, A.; Rissanen, K.; Enders, D. Squaramide-Catalyzed Asymmetric aza-Friedel-Crafts/N,O-Acetalization Domino Reactions Between 2-Naphthols and Pyrazolinone Ketimines. Angew. Chem. Int. Ed. 2017, 56 (48), 15358-15362.
    25. Denmark, S. E.; Thorarensen, A. Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes. Chem. Rev. 1996, 96 (1), 137-166.
    26. Lai, Y. T.; Nagaraju, K.; Gurubrahamam, R.; Chen, K. Enantioselective Organocatalytic Synthesis of δ‐Lactone‐Fused 4‐Chromanones. Adv. Synth. Catal. 2020, 362 (18), 3846-3850.
    27. Rkein, B.; Bigot, A.; Birbaum, L.; Manneveau, M.; De Paolis, M.; Legros, J.; Chataigner, I. Reactivity of 3-Nitroindoles with Electron-Rich Species. Chem. Commun. 2021, 57 (1), 27-44.
    28. Pelkey, E. T.; Gribble, G. W. One-Step Syntheses of the Pyrrolo[3,4-b]indole and Pyrrolo[2,3-b]indole Ring Systems from 3-Nitroindoles. Chem. Commun. 1997, 1873-1874.
    29. Zhao, J. Q.; Zhou, M. Q.; Wu, Z. J.; Wang, Z. H.; Yue, D. F.; Xu, X. Y.; Zhang, X. M.; Yuan, W. C. Asymmetric Michael/Cyclization Cascade Reaction of 3-Isothiocyanato Oxindoles and 3-Nitroindoles with Amino-Thiocarbamate Catalysts: Enantioselective Synthesis of Polycyclic Spirooxindoles. Org. Lett. 2015, 17 (9), 2238-2241.
    30. Chen, X. M.; Lei, C. W.; Yue, D. F.; Zhao, J. Q.; Wang, Z. H.; Zhang, X. M.; Xu, X. Y.; Yuan, W. C. Organocatalytic Asymmetric Dearomatization of 3-Nitroindoles and 3-Nitrobenzothiophenes via Thiol-Triggered Diastereo- and Enantioselective Double Michael Addition Reaction. Org. Lett. 2019, 21 (14), 5452-5456.
    31. Andreini, M.; De Paolis, M.; Chataigner, I. Thiourea-Catalyzed Dearomatizing [4+2] Cycloadditions of 3-Nitroindole. Catal. Commun. 2015, 63, 15-20.
    32. Li, Y.; Tur, F.; Nielsen, R. P.; Jiang, H.; Jensen, F.; Jorgensen, K. A. Enantioselective Formal [4+2] Cycloadditions to 3-Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles. Angew. Chem. Int. Ed. 2016, 55 (3), 1020-1024.
    33. Yue, D. F.; Zhao, J. Q.; Chen, X. Z.; Zhou, Y.; Zhang, X. M.; Xu, X. Y.; Yuan, W. C. Multiple Hydrogen-Bonding Bifunctional Thiourea-Catalyzed Asymmetric Dearomative [4+2] Annulation of 3-Nitroindoles: Highly Enantioselective Access to Hydrocarbazole Skeletons. Org. Lett. 2017, 19 (17), 4508-4511.
    34. Cao, D.; Ying, A.; Mo, H.; Chen, D.; Chen, G.; Wang, Z.; Yang, J. [4+2] Annulation of 3-Nitroindoles with Alkylidene Malononitriles: Entry to Substituted Carbazol-4-amine Derivatives. J. Org. Chem. 2018, 83 (20), 12568-12574.
    35. May, J. A.; Zeidan, R. K.; Stoltz, B. M. Biomimetic Approach to Communesin B (a.k.a. nomofungin). Tetrahedron Lett. 2003, 44 (6), 1203-1205.
    36. May, J. A.; Stoltz, B. The Structural and Synthetic Implications of the Biosynthesis of the Calycanthaceous Alkaloids, the Communesins, and Nomofungin. Tetrahedron 2006, 62 (22), 5262-5271.
    37. Shao, W.; You, S. L. Highly Diastereo- and Enantioselective Synthesis of Tetrahydro-5H-Indolo[2,3-b]quinolines through Copper-Catalyzed Propargylic Dearomatization of Indoles. Chem. Eur. J. 2017, 23 (51), 12489-12493.
    38. Suo, J.-J.; Du, J.; Jiang, Y.-J.; Chen, D.; Ding, C.-H.; Hou, X.-L. Diastereo- and Enantioselective Palladium-Catalyzed Dearomative [4+2] Cycloaddition of 3-Nitroindoles. Chin. Chem. Lett. 2019, 30 (8), 1512-1514.
    39. Shao, W.; Xu-Xu, Q. F.; You, S. L. Highly Diastereoselective Synthesis of Polycyclic Indolines through Formal [4+2] Propargylic Cycloaddition of Indoles with Ethynyl Benzoxazinanones. Chem. Asian. J. 2020, 15 (16), 2462-2466.
    40. Yang, W.; He, H. X.; Gao, Y.; Du, D. M. Organocatalytic Enantioselective Cascade Aza‐Michael/Michael Addition for the Synthesis of Highly Functionalized Tetrahydroquinolines and Tetrahydrochromanoquinolines. Adv. Synth. Catal. 2013, 355 (18), 3670-3678.
    41. Liu, K.; Wang, G.; Cheng, S.-J.; Jiang, W.-F.; He, C.; Ye, Z.-S. Phosphine-Catalyzed Dearomative [3+2] Annulation of 3-Nitroindoles and Allenoates. Tetrahedron Lett. 2019, 60 (29), 1885-1890.
    42. Vinoth, P.; Karuppasamy, M.; Vachan, B. S.; Muthukrishnan, I.; Maheswari, C. U.; Nagarajan, S.; Pace, V.; Roller, A.; Bhuvanesh, N.; Sridharan, V. Palladium-Catalyzed Regioselective Syn-Chloropalladation-Olefin Insertion-Oxidative Chlorination Cascade: Synthesis of Dichlorinated Tetrahydroquinolines. Org. Lett. 2019, 21 (9), 3465-3469.
    43. Sahoo, M. K.; Jaiswal, G.; Rana, J.; Balaraman, E. Organo-Photoredox Catalyzed Oxidative Dehydrogenation of N-Heterocycles. Chem. Eur. J. 2017, 23 (57), 14167-14172.

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