Basic Search / Detailed Display

Author: 劉芳年
Liu, Fang-Nian
Thesis Title: 經由不對稱連鎖1,6-加成/1,4-氧麥可加成反應合成四取代4H-吡喃化合物
Asymmetric Synthesis of 2,4,5,6-Tetrasubstituted Tetrahydropyrans via Domino 1,6-Addition /1,4-Oxa Michael Addition Sequence
Advisor: 陳焜銘
Chen, Kwun-Min
Committee: 林文偉 劉維民
Approval Date: 2021/07/21
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2021
Academic Year: 109
Language: 中文
Number of pages: 122
Keywords (in Chinese): 不對稱連鎖反應1,6-加成反應4H-吡喃
Keywords (in English): Asymmetric domino reaction, 1,6-addition, 4H-pyran
DOI URL: http://doi.org/10.6345/NTNU202100843
Thesis Type: Academic thesis/ dissertation
Reference times: Clicks: 119Downloads: 8
Share:
School Collection Retrieve National Library Collection Retrieve Error Report

有機催化不對稱連鎖反應,具簡單操作及符合綠色化學的特色,已成為目前研究的趨勢。透過氧-麥可加成反應可以合成許多具有生物活性的化合物,結合1,6-加成反應與1,4-氧麥可加成反應,進行不對稱合成反應有其挑戰性。
本研究使用4-羥基香豆素與1,3-茚二酮雙烯化合物作為起始物,在20 mol%三乙胺的催化下,於60 oC下反應一天,進行1,6-加成/1,4-氧麥可加成鹼催化連鎖反應,得到具有四取代4H-吡喃架構的產物,並測試此反應之官能基容忍度,得到中等產率及優異非鏡像選擇性(> 20:1 d.r.)。

The use of organic catalyzed asymmetric domino reaction has become the current research trend, which characteristics are simple operation and corresponding to the principle of green chemistry. Many biologically active compounds can be synthesized through oxa-Michael reaction. Combining with the 1,6-addition reaction and 1,4-oxa Michael reaction to carry out asymmetric synthesis has its challenges.
In this study, the reactions were carried out with 4-hydroxycoumarin and 1,3-indenedione compounds as starting materials, under 20 mol% triethylamine to react at 60 oC for one day. Through 1,6-addition and 1,4-oxa Michael reaction base catalyzed domino reaction to obtain a product with tetra-substituted 4H-pyran structure and tested the tolerance of functional group, which obtained moderate yield and excellent diastereoselectivity (> 20 :1 d.r.).

第一章 緒論1 1-1 前言1 1-2 有機不對稱催化2 1-2-1 共價催化3 1-2-2 非共價催化5 1-3 有機不對稱連鎖反應6 1-3-1 一鍋化反應之domino reaction7 1-4 1,4-加成反應12 1-4-1 Oza-麥可反應14 1-5 1,6-加成反應19 1-6 香豆素的合成與應用23 1-7 研究動機26 第二章 結果與討論27 2-1 1,3-茚二酮雙烯化合物之製備27 2-2 不對稱連鎖反應合成4H-吡喃化合物27 2-2-1 有機溶劑的篩選28 2-2-2 酸性及鹼性添加劑的篩選29 2-2-3 溫度的篩選30 2-2-4 時間的篩選31 2-2-5 最佳化條件的篩選32 2-2-6 取代基效應33 2-3 4H-吡喃產物分析36 2-3-1 X-ray單晶繞射結構分析36 2-3-2 NMR光譜分析37 2-4 反應機構之探討43 2-5 結論44 第三章 實驗流程與數據45 3-1 分析儀器及基本實驗操作45 3-2 實驗部分47 3-2-1 雙烯化合物之製備47 3-2-2 4H-吡喃產物之合成53 第四章 參考文獻65 附錄一 1H-NMR、13C-NMR光譜圖67 附錄二 X-ray單晶繞射結構解析與數據 112

1. Guidotti, M.; Palumbo, C. ScienceOpen Research., 2015.
2. Kasprzyk, H. B. Chem Soc Rev., 2010, 39, 4466.
3. Iorio, D. N. In New Organocatalytic Strategies for the Selective Synthesis of
Centrally and Axially Chiral Molecules., 2018.
4. Jurberg, I. D.; Chatterjee, I.; Tannert, R.; Melchiorre, P. Chem Commun., 2013,
49, 4869.
5. Kateri, A. A.; Christopher, J. B.; MacMillan, D. W. C. J. Am. Chem. Soc., 2000, 122,
4243.
6. Doyle, A. G.; Jacobsen, E. N. Chem. Rev., 2007, 107, 5713.
7. Reisman, S. E.; Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc., 2008, 130, 7198.
8. Tietze, L. F. Chem. Rev., 1996, 96, 115.
9. Enders, D.; Huttl, M. R.; Grondal, C.; Raabe, G. Nature., 2006, 441, 861.
10. Szőllősi, G. Catal. Sci. Technol., 2018, 8, 389.
11. Fish, P.V.; Johnson, W. S. J. Org. Chem., 1994, 59, 2324.
12. Rodriguez, J. Synlett., 1999, 5, 505.
13. Tomida, S.; Doi, T.; Takahashi, T. Tetrahedron Lett., 1999, 40, 2363.
14. Sauer, E. L. O.; Barriault, L. Org. Lett., 2004, 6, 3329.
15. Deschamp, J.; Hermant, T.; Riant, O. Tetrahedron., 2012, 68, 3457.
16. Michael, A. J. Prakt. Chem., 1887, 35, 349.
17. Halland, N.; Hansen, T.; Jørgensen, K. A. Angew. Chem., 2003, 115, 5105.
18. Ye, J.; Dixon, D. J.; Hynes, P. S. Chem Commun., 2005, 4481.
19. Wang, W.; Wang, J.; Li, H. Angew. Chem., 2005, 117, 1393.
20. Nising, C. F.; Brase, S. Chem Soc Rev., 2012, 41, 988.
21. Nising, C. F.; Brase, S. Chem Soc Rev., 2008, 37, 1218.
22. Wang, L.; Liu, X.; Dong, Z.; Fu, X.; Feng, X. Angew. Chem. Int. Ed., 2008, 47, 8670.
23. Noto, K.; Sasaki, M.; Fuwa, H. Org. Lett., 2010, 12, 1636.
24. Wang, H.; Luo, J.; Han, X.; Lu, Y. Adv. Synth. Catal., 2011, 353, 2971.
25. Mao, H.; Lin, A.; Tang, Y.; Shi, Y.; Hu, H.; Cheng, Y.; Zhu C. Org. Lett., 2013, 15,
4062.
26. Lee, H. J.; Eun, B.; Sung, E.; Hwang, G. T.; Ko, Y. K.; Cho, C. W. Org. Biomol.
Chem., 2018, 16, 657.
27. Tokunaga, N.; Inoue, K.; Hayashi, T. Org. Lett., 2004, 6, 305.
28. Silva, A.; Silva, E. Synthesis., 2012, 44, 3109.
29. Yasuhara, Y.; Sawano, T.; Nishimura, T.; Hayashi, T. J. Am. Chem. Soc., 2010, 132,
7872.
30. Bernardi, L.; Cantarero, J. L.; Niess, B.; Jørgensen K. A. J. Am. Chem. Soc., 2007,
129, 5772.
31. Tian, X.; Melchiorre, P. Angew. Chem. Int. Ed., 2013, 52, 5360.
32. Roy, S.; Pradhan, S.; Kumar, K.; Chatterjee, I. Org. Chem. Front., 2020, 7, 1388.
33. Stefanachi, A.; Leonetti, F.; Pisani, L.; Catto, M.; Carotti, A. Molecules., 2018, 23,
250.
34. Vekariya, R. H.; Patel, H. D. Synth. Commun., 2014, 44, 2756.
35. Heravi, M. M.; Khaghaninejad, S.; Mostofi, M. Adv. Heterocycl. Chem., 2014,
112, 1.
36. Salem, M. A.; Helal, M. H.; Gouda, M. A.; Ammar, Y. A. Synth. Commun., 2018,
48, 1534.
37. Christiansen, G. E.; Watson, B.T. Tetrahedron Lett., 1998, 39, 6087.
38. Mamoto, K.; Shibata, T.; Hirose, T.; Inayama, S. J. Med. Chem., 1976, 19, 433.

下載圖示
QR CODE