研究生: |
王崧年 Wang, Sung-Nien |
---|---|
論文名稱: |
有機連鎖反應:鹼催化多環香豆素衍生物的非鏡像選擇性合成 Organcascade Reaction:Diastereoseletive Synthesis of Polycyclic Chromenone Derivatives Catalyzed by Base |
指導教授: |
陳焜銘
Chen, Kwun-Min |
口試委員: | 林文偉 劉維民 |
口試日期: | 2021/07/21 |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2021 |
畢業學年度: | 109 |
語文別: | 中文 |
論文頁數: | 116 |
中文關鍵詞: | 有機連鎖反應 、麥可加成 、去芳香化反應 、香豆素 、2-硝基苯並呋喃 |
英文關鍵詞: | coumarin, Michael addition, dearomatization |
DOI URL: | http://doi.org/10.6345/NTNU202100841 |
論文種類: | 學術論文 |
相關次數: | 點閱:106 下載:5 |
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近年來,香豆素及其衍生物表現出多樣生物學活性,最常作為抗凝血劑使用,故西豆素衍生物的製備與應用成為許多人研究合成的目標。本文利用3-高醯基香豆素與2-硝基苯並呋喃進行反應,透過碳酸銫活化下,經由Michael/Michael去芳香化連鎖反應,建立多環多取代香豆素衍生物,此產物具有四個連續得立體中心,產率(52-72%)、非鏡像選擇性比例(11:1~>20:1)。不對稱合成具有高光學純度產物仍須後續探討。
In recent year, coumarin and its heterocyclic derivatives exhibit diverse biological activities, It is most commonly used as an anticoagulant,therefore, the preparation and application of coumarin derivatives has become the goal of many group’s research and synthesis. In this study, 3-homocoumarin and 2-nitrobenzofuran are used to be starting material, activated by cesium carbonate, and through a Michael/Michael dearomatization reaction to establish a polycyclic polysubstituted coumarin derivative bearing continuous four stereogenic center in moderate yield. (52-72%) , diastereoselectivities reaches (11:1~>20:1).Asymmetric synthesis of products with high enantioselectivity are still in study.
1. 李尚仁. 沙利竇邁藥害事件的兩位醫學英雄. 2017; https://scitechvista.nat.gov.tw/Article/C000003/detail?ID=00839caf-aa57-4ab5-ac4a-23bdc0e38910.
2. Tietze, L.F., Domino reactions in organic synthesis. Chemical reviews, 1996. 96. 115-136.
3. Johnson, W.S., M.B. Gravestock, and B.E. McCarry, Acetylenic bond participation in biogenetic-like olefinic cyclizations. II. Synthesis of dl-progesterone. Journal of the American Chemical Society, 1971. 93 p. 4332-4334.
4. H. Pellissier. Adv. Synth. Catal, 2012. 354,237.
5. Li, H, Organocatalytic Asymmetric Domino Aza-Michael–Mannich Reaction: Synthesis of Tetrahydroimidazopyrimidine Derivatives. The Journal of organic chemistry, 2011. 76,p. 8064-8069.
6. Kraus, G.A. and J. Kim, Tandem diels− alder/ene reactions. Organic letters, 2004. 6,p. 3115-3117.
7. BIRCH, A., The Birch Reduction. J. Chem. Soc, 1944. 430: p. 436.
8. B.A.TrofimovN.A.Nedolya, Pyrroles and their Benzo Derivatives: Reactivity. 2008.
9. Thomas, T.J.D.R.E., The partial reduction of electron-deficient pyrroles:
procedures describing both Birch (Li/NH3) and ammonia-free (Li/DBB). conditions. 2007.
10. Murphy, W.S. and S. Wattanasin, Anionic cyclization of phenols. Chemical Society Reviews, 1983. 12,213-250.
11. Lovchik, M.A., A. Goeke, and G. Fráter, Stereoselective synthesis of cyclohexa-2, 4-dien-1-ones and cyclohex-2-en-1-ones from phenols. Tetrahedron: Asymmetry, 2006. 17,1693-1699.
12. Raikar, S.B., et al., Synthesis of polyprenylated benzoylphloroglucinols by regioselective prenylation of phloroglucinol in an aqueous medium. 2008, Wiley Online Library.
13. Kloetzel, M.C., The D iels‐A lder Reaction with Maleic Anhydride. Organic Reactions, 2004. 4,1-59.
14. Huang, J. and R.P. Hsung, Chiral Lewis acid-catalyzed highly enantioselective [4+ 3] cycloaddition reactions of nitrogen-stabilized oxyallyl cations derived from allenamides. Journal of the American Chemical Society, 2005. 127,50-51.
15. Pettus, T.R., et al., A fully synthetic route to the neurotrophic illicinones: syntheses of tricycloillicinone and bicycloillicinone aldehyde. Journal of the American Chemical Society, 2000. 122,6160-6168.
16. Tisdale, E.J., I. Slobodov, and E.A. Theodorakis, Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels–Alder/Claisen rearrangement. Proceedings of the National Academy of Sciences, 2004. 101,12030-12035.
17. Lam, J.K., Y. Schmidt, and C.D. Vanderwal, Complex polycyclic scaffolds by metathesis rearrangement of Himbert arene/allene cycloadducts. Organic letters, 2012. 14, 5566-5569.
18. Vo, N.T., et al., An enantioselective organocatalytic oxidative dearomatization strategy. Journal of the American Chemical Society, 2008. 130, 404-405.
19. Liu, Q. and T. Rovis, Asymmetric synthesis of hydrobenzofuranones via desymmetrization of cyclohexadienones using the intramolecular Stetter reaction. Journal of the American Chemical Society, 2006. 128, 2552-2553.
20. Zhuo, C.X., W. Zhang, and S.L. You, Catalytic asymmetric dearomatization reactions. Angewandte Chemie International Edition, 2012. 51,12662-12686.
21. Chandrasekhar, S., et al., Palladium− triethylborane-triggered direct and regioselective conversion of allylic alcohols to allyl phenyl sulfones. The Journal of organic chemistry, 2005. 70, 6506-6507.
22. Bandini, M., et al., Highly enantioselective synthesis of tetrahydro-β-carbolines and tetrahydro-γ-carbolines via Pd-catalyzed intramolecular allylic alkylation. Journal of the American Chemical Society, 2006. 128,1424-1425.
23. Austin, J.F., et al., Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (–)-flustramine B. Proceedings of the National Academy of Sciences, 2004. 101,5482-5487.
24. Michael, A., Ueber die Addition von Natriumacetessig‐und Natriummalonsäureäthern zu den Aethern ungesättigter Säuren. Journal für Praktische Chemie, 1887. 35,349-356.
25. Ghorai, P., Enantioselective, Organocatalytic, Dissymmetric 1,4- and 1,2-Addition of Malononitrile to a Keto-bisenone Followed by an Oxa-Michael Addition Cascade. 2019.
26. Su, Z., H.W. Lee, and C.K. Kim, Asymmetric 1, 4‐Michael Addition Reactions Catalyzed by a Cinchona Alkaloid Derived Primary Amine: A Theoretical Investigation of the Reaction Mechanism and Enantioselectivity. European Journal of Organic Chemistry, 2013. 1706-1715.
27. Zhao, K., et al., Asymmetric organocatalytic synthesis of 3-diarylmethine-substituted oxindoles bearing a quaternary stereocenter via 1, 6-conjugate addition to para-quinone methides. ACS Catalysis, 2016. 6, 657-660.
28. Bae, J.-Y., et al., Organocatalytic Asymmetric Synthesis of Chiral Pyrrolizines by Cascade Conjugate Addition− Aldol Reactions. Organic letters, 2010. 12, 4352-4355.
29. Kotame, P., B.-C. Hong, and J.-H. Liao, Enantioselective synthesis of the tetrahydro-6H-benzo [c] chromenes via Domino Michael–Aldol condensation: control of five stereocenters in a quadruple-cascade organocatalytic multi-component reaction. Tetrahedron Letters, 2009. 50, 704-707.
30. 香豆素的合成. 2012; https://wenku.baidu.com/view/2e085506bed5b9f3f90f1c1d.
31. Chen, Y.-R., et al., 3-Homoacyl coumarin: an all carbon 1, 3-dipole for enantioselective concerted (3+ 2) cycloaddition. Chemical Communications, 2018. 54, 12702-12705.
32. Ku, Y., Reaction of Salicylaldehydes with Bromonitrometnane. Chem. Pharm. Bull., 1984.
33. Cheng, B., et al., Synthesis and Anti‐neuroinflammatory Activity of Lactone Benzoyl Hydrazine and 2‐nitro‐1‐phenyl‐1H‐Indole Derivatives as p38α MAPK Inhibitors. Chemical biology & drug design, 2015. 86, 1121-1130