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| 研究生： |
張芸毓 Chang, Yun-Yu |
|---|---|
| 論文名稱： |
有機催化連鎖反應合成全取代2,3,4,5-四氫-1H-茚[1,2-b]吡啶-5-酮化合物 Organocatalytic Synthesis of Fully-Substituted 2,3,4,5-Tetrahydro-1H-Indeno[1,2-b]Pyridine-5-One |
| 指導教授： |
陳焜銘
Chen, Kwun-Min |
| 學位類別： |
碩士 Master |
| 系所名稱： |
化學系 Department of Chemistry |
| 論文出版年： | 2015 |
| 畢業學年度： | 103 |
| 語文別： | 中文 |
| 論文頁數： | 130 |
| 中文關鍵詞： | Michael/aza-環化反應 、2,3,4,5-四氫-1H-茚[1,2-b]吡啶-5-酮化合物 、外消旋硝基烯丙胺 |
| 英文關鍵詞： | 2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridin-5-one, Michael/aza-cyclization, racemic nitroallylic amine |
| 論文種類： | 學術論文 |
| 相關次數： | 點閱：126 下載：1 |
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近年來，已有許多針對茚[1,2-b]吡啶-5-酮單元分子的相關合成方法陸續被發表，因其芳香結構之組成，不具有鏡像性質，在天然物合成及衍生藥物的製備上，欠缺應用價值；因此，合成具有高立體選擇性的全取代2,3,4,5-四氫-1H-茚[1,2-b]吡啶-5-酮化合物為重要的研究目標之一。本實驗使用新開發的外消旋硝基烯丙胺及1,3-氫茚二酮作為起始物，依序添加20 mol%的1,4-二氮雜二環[2.2.2]辛烷與50 mol%對甲苯磺酸，作為布忍斯特酸鹼進行共催化，四氫呋喃為溶劑，於0 oC的條件下，進行連鎖Michael/aza-環化反應，得到具有優異非鏡像選擇性（up to 96:4 d.r.）之全取代2,3,4,5-四氫-1H-茚[1,2-b]吡啶-5-酮化合物，產率方面亦有良好的表現（38-73%）；此外，在此化合物分子中具有多重官能基，透過後續反應之修飾，期望此合成路徑得以應用在往後的相關天然物合成中。
In the recent years, various methods regarding the synthesis of indeno[1,2-b]pyridin-5-one motif have been developed. Achiral character caused by the aromaticity within the structural constitution accounts for the lack of applicability in total synthesis of natural products as well as preparation of medicinal derivatives. Therefore, efficient and environmentally-friendly synthetic route toward fully- substituted 2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridin-5-one with excellent stereoselectivity is highly desired. The Michael/aza-cyclization sequence was performed using novel racemic nitroallylic amine and 1,3-indandione as starting materials, which were dissolved in 0.5 mL of THF at 0 oC in the presence of 20 mol% DABCO combined with 50 mol% p-TsOH. Fully-substituted 2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridin-5-one, were obtained in good chemical yields (38-73%) and with high diastereoselectivity (up to 96:4 d.r.). In addition, the title compounds with multi-functionalities can be modified through subsequent reactions, and the synthetic applicability for the synthesis of relating natural products is under investigated in our lab.
1.Brønsted, J. N. Chem. Rev. 1928, 5(3), 231.
2.Akiyama, T. Chem. Rev. 2007, 107, 5744.
3.Akiyama, T.; Ishida, Y.; Kagoshima, H. Tetrahedron Lett. 1999, 40, 4219.
4.Matsui, K.; Takizawa, S.; Sasai, H. J. Am. Chem. Soc. 2005, 127,3680.
5.Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 84.
6.Kampen, D.; List, B. Synlett. 2006, 2589.
7.Gao, X.; Zhang, F.; Deng, G.; Yang, L. Org. Lett. 2014, 16, 3664.
8.Dobish, M. C.; Johnston, J. N. Org. Lett. 2010, 12, 5744.
9.Kondoh, A.; Terada, M. Org. Lett. 2013, 15, 4568.
10.Hatano, M.; Maki, T.; Moriyama, K.; Arinobe, M.; Ishihara, K. J. Am. Chem. Soc. 2008, 130, 16858.
11.Michael, A. J. Prakt. Chem. 1887, 35, 349.
12.Mao, Z.; Jia, Y.; Li, W.; Wang, R. J. Org. Chem. 2010, 75, 7428.
13.Blümel, M.; Chauhan, P.; Hahn, R.; Raabe, G.; Enders, D. Org. Lett. 2014, 16, 6012.
14.Halland, N.; Hansen, T.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2003, 42, 4955.
15.Yao, H.; Song, L.; Liu, Y.; Tong, R. J. Org. Chem. 2014, 79, 8774.
16.Wu, F.; Li, H.; Hong, R.; Deng, L. Angew. Chem. Int. Ed. 2006, 45, 947.
17.Zhang, Z. H.; Dong, X. Q.; Chen, D.; Wang, C. J. Chem. Eur. J. 2008, 14, 8780.
18.Wang, X. F.; An, J.; Zhang, X. X.; Tan, F.; Chen, J. R.; Xiao, W. J. Org. Lett. 2011, 13, 808.
19.De Almeida, M. E. I.; Braz, F. R.; von Bulow, M. V.; Gottleib, O. R.; Maia, J. G. S. Phytochemistry 1976, 15, 1186.
20.Cushman, M.; Cheng, L. J. Org. Chem. 1978, 43, 3781.
21.Goulart, M. O. F.; Sant’ana, A. E. G.; de Oliveira, A. B.; de Oliveira, G. G.; Maia, J. G. S. Phytochemistry 1986, 25, 1691.
22.Padwa, A.; Heidelbaugh, T. M.; Kuethe, J. T. J. Org. Chem. 2000, 65, 2368.
23.Nagarajan, M.; Morrell, A.; Fort, B. C.; Meckley, M. R.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. J. Med. Chem. 2004, 47, 5651.
24.Moustafa, A. H.; E1-Abbady, S. A.; Gado, S. H.; E1-Borai, M. A. Pharmazie 1983, 38, 221.
25.(a) Tadic, D.; Cassels, B. K.; Cave, A.; Goulart, M. P. F.; de Oliveira, A. B. Phytochemistry 1987, 26, 1551.
(b) Prostakov, N. S.; Vasil’ev, G. A.; Zvolinskii, V. P.; Varlamov, A. V.; Savina, A. A.; Sorokin, O. I.; Lopatina, N. D. Chem. Heterocycl. Compd. (Engl. Transl.) 1975, 971.
26.Prostakov, N. S.; Soldatenkov, A. T.; Radzhan, P. K.; Fedorov, V. O.; Fomichev, A. A.; Rezakov, V. A. Chem. Heterocycl. Compd. (Engl. Transl.) 1982, 390.
27.Zhang, J.; el-Shabrawy, O.; el-Shabrawy, M. A.; Schiff, P. L., Jr.; Slatkin, D. J. J. Nat. Prod. 1987, 50, 800.
28.Padwa, A.; Heidelbaugh, T. M.; Kuethe, J. T. J. Org. Chem. 2000, 65, 2368.
29.Alves, T.; de Oliveira, A. B.; Snieckus, V. Tetrahedron Lett. 1988, 29, 2135.
30.Tu, S.; Jiang, B.; Jia, R.; Zhang, J.; Zhang, Y. Tetrahedron Lett. 2007, 48, 1369.
31.Mukhopadhyay, C.; Tapaswi, P. K.; Butcher, R. J. Tetrahedron Lett. 2010, 51, 1797.
32.Tapaswi, P. K.; Mukhopadhyay, C. Arkivoc 2011, 287.
33.Deb, I.; Dadwal, M.; Mobin, S. M.; Namboothiri, I. N. N. Org. Lett. 2006, 8, 1201.
