簡易檢索 / 詳目顯示
| 研究生： |
顏莉庭 Yen, Li-Ting |
|---|---|
| 論文名稱： |
有機催化不對稱Aza-麥可/麥可環化加成連鎖反應：控制三個立體中心合成螺環噻唑酮2-四氫吡咯酮衍生物 Organocatalytic Asymmetric Aza-Michael/Michael Cyclization Cascade Reaction: Control of Three Stereocenters Synthesis of Spiro-thiazolone Pyrrolidin-2-one Derivatives |
| 指導教授： |
陳焜銘
Chen, Kwun-Min |
| 口試委員： | 楊德芳 杜玲嫻 |
| 口試日期： | 2021/07/23 |
| 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： | 122 |
| 中文關鍵詞： | 有機催化 、不對稱合成 、麥可加成 、有機連鎖反應 、噻唑酮 |
| 英文關鍵詞： | Organocatalysis, Asymmetric synthesis, Cascade reaction, Michael Addition, Thiazolone |
| 研究方法: | 實驗設計法 |
| DOI URL： | http://doi.org/10.6345/NTNU202100840 |
| 論文種類： | 學術論文 |
| 相關次數： | 點閱：209 下載：8 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
本文使用(Z)-5-亞苄基-2-苯基-4(5H)噻唑酮以及(E)-4-(甲氧基氨基)-4-氧代丁-2-烯酸乙酯作為起始物，利用具有方醯胺架構的奎寧衍生物之掌性催化劑提供氫鍵，以活化此有機催化不對稱合成連鎖反應，進行兩次的麥可加成，反應得到螺環化合物。經過一系列條件的篩選，以甲苯作為溶劑，於-20 oC回復至室溫的條件下，添加5 mol%的催化劑進行反應，獲得具有三個手性中心的螺環噻唑酮衍生物，其產率為63%，鏡像選擇性達87% ee。此為一方便且溫和的反應策略，期望未來能為有機不對稱催化合成發展有所貢獻。
A simple asymmetric synthesis of spiro-thiazolone pyrrolidin-2-one was achieved. Uses (Z)-5-benzylidene-2-phenylthiazol-4(5H)-one and ethyl (E)-4-(methoxyamino)-4-oxobut-2-enoate as the starting material. A quinine derivative with a squaramide structure as the catalyst to activate the organocatalytic asymmetric aza-Michael/Michael cyclization Cascade reaction. After a series of screening conitions, toluene was used as the solvent and 5 mol% of the catalyst was added under -20 oC then return to room temperature. The reaction obtained a spiro-thiazolone pyrrolidin-2-one derivative with three chiral centers, the yield was 63% and the enantioselectivity get 87% ee. This is a convenient reaction under mild conditions, and it is expected that it will contribute to the development of organocatalytic asymmetric synthesis in the future.
1.Ca ̂rcu-Dobrin, M.; Buda ̌u, M.; Hancu, G.; Gagyi, L.; Rusu, A.; Kelemen, H. Saudi Pharmaceutical Journal 2017, 25, 397.
2.Lepola, U.; Wade, A.; Andersen, H.F. Int. Clin. Psychopharmacol. 2004, 19, 149.
3.Jacobsen, E.N.; Sigman, M. S. J. Am. Chem. Soc. 1998, 120, 4901.
4.List, B.; Lerner, R.A.; Barbas, C.F., III. J. Am. Chem. Soc. 2000, 122, 2395.
5.MacMillan, D.W.C.; Ahrendt, K.A.; Borths, C.J. J. Am. Chem. Soc. 2000, 122, 4243.
6.Jurberg, I.D.; Chatterjee, I.; Tannert, R.; Melchiorre, P. Chem. Commun. 2013, 49, 4869.
7.Enders, D.; Hu ̈ttl, M.R.M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861.
8.Pihko, P.M. Angew. Chem. Int. Ed. 2004, 43, 2062.
9.Li, K.; Jin, Z.; Chan, W.-L.; Lu, Y. ACS Catal. 2018, 8, 8810.
10.Sakai, T.; Hirashima, S.; Yamashita, Y.; Arai, R.; Nakashima, K.; Yoshida, A.; Koseki, Y.; Miura, T. J. Org. Chem. 2017, 82, 4661.
11.Liu, Y.; Wang, J.; Wei, Z.; Cao, J.; Liang, D.; Lin, Y.; Duan, H. Org. Lett. 2019, 21, 5719.
12.MacMillan, D.W.C.; Beeson, T.D.; Mastracchio, A.; Hong, J.-B.; Ashton, K. Science 2007, 316, 582.
13.Kanger, T.; Trubitsõn, D.; Martõnova, J.; Kudrjašova, M.; Erkman, K.; Järving, I. Org. Lett. 2021, 23, 1820.
14.MacMillan, D.W.C.; Chen, Y.K.; Yoshida, M. J. Am. Chem. Soc. 2006, 128, 9328.
15.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. J. Org. Chem. 2019, 84, 4381.
16.Wang, W.; Liu, C.; Zhang, X.; Wang, R. Org. Lett. 2010, 12, 4948.
17.Couve-Bonnaire, S.; Huang, X.; David, E.; Jubault, P.; Besset, T. J. Org. Chem. 2020, 85, 14055.
18.Wang, Y.; Zhang, J.; Xu, Y.; Wang, Z.; Zhong, R. J. Org. Chem. 2021, 86, 4262.
19.Sheldrick, G.M.; Tietze, L.F.; Brand, S.; Pfeiffer, T.; Antel, J.; Harms, K. J. Am. Chem. Soc. 1987, 109, 921.
20.Kraus, G.A.; Taschner, M.J. J. Am. Chem. Soc. 1980, 102, 1974.
21.Du, D.-M.; Song, Y.-X. Journal Name 2020, 00, 1.
Li, W.; Lib, P.; Guo, X.; Huang, A. Adv. Synth. Catal. 2020, 362, 3542.
22.Li, J.-L.; Han, B.; Feng, X.; Li, Q.-Z.; Yang, J.; Li, M.-H.; Yang, K.-C.; Zhang, X.; Dai, Q.-S. Adv. Synth. Catal. 2018, 360, 4435.
23.Jiang, Z.; Lee, R.; Coote, M.L.; Li, J.; Qiu, S.; Zhu, B. Chem. Sci. 2016, 7, 6060.
24.Yan, W.; Wang, K.; Chen, H.; Deng, Y.; Wen, D.; Zhou, Y.; Guo, Y.; Sun, M.; Gao, F.; Liu, J.; Li, B. Org. Biomol. Chem. 2019, 17, 2892
