研究生: |
李佳蓉 Li, Jia-Rong |
---|---|
論文名稱: |
利用一價銠金屬催化芳基硼酸對環狀α,β-不飽和β-酮酯進行不對稱1,4-加成反應:合成三尖杉鹼天然物 Synthetic Studies Toward (−)-Cephalotaxine using Rh(I)-Catalyzed Enantioselective 1,4-Addition Reaction |
指導教授: | 吳學亮 |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2019 |
畢業學年度: | 107 |
語文別: | 中文 |
論文頁數: | 330 |
中文關鍵詞: | 銠金屬 、1,4-加成反應 、烷基化反應 、芳基硼酸 、雙烯配基 |
DOI URL: | http://doi.org/10.6345/NTNU201900232 |
論文種類: | 學術論文 |
相關次數: | 點閱:114 下載:0 |
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本研究利用掌性雙環[2.2.1]雙烯配基L1與一價銠金屬形成的催化劑催化芳基硼酸28對環狀α,β-不飽和β-酮酯27和環狀α,β-不飽和β-醯胺酯27進行不對稱1,4-加成反應。在3.0 mol %的銠金屬和3.6 mol %的掌性雙[2.2.1]雙烯配基L催化下,可以得到加成產物產率17−82%、鏡像超越值75 −>99.5%的加成產物,且此加成產物也可進行一鍋化的烷基化反應(C-alkylation),來建構出具有四級碳的產物,產物產率介於25−94%、鏡像超越值92−99%。此法可以應用在合成天然物(−)-Cephalotaxine以及抗憂鬱性質的藥物(−)-Paroxetine。
關鍵詞:銠金屬、1,4-加成反應、烷基化反應、芳基硼酸、雙烯配基
In this thesis, an enantioselective 1,4-addition of arylboronic acids 28 to cyclic α,β-unsaturated β-ketoesters 27 and cyclic α,β-unsaturated β-ketoamides 27 catalyzed by a Rh(I)-chiral diene catalyst is described.
In the presence of 3.0 mol % of the catalyst generated in situ from a Rh(I) salt and diene L1, the asymmetric reaction afforded the desired adducts 26 in up to 82% yield (17–82% yield) and with up to >99.5% ee (75– >99.5% ee). In addition, this method can be applied in the one-pot alkylation reaction to afford products with a quaternary carbon in up to 94% yield (25–94% yield for two steps) and with 99% ee (92–99% ee). The method was applied in the synthesis of (−)-Cephalotaxine and (−)-Paroxetine.
一.英文文獻
1. (a) Paudler, W. W.; McKay, J.; Kerley, G. I. J. Org. Chem. 1963, 28, 2194–2197. (b) Powell, R. G.; Weisleder, D.; Smith, C. R.; Wolff, I. A. Tetrahedron Lett. 1969, 10, 4081–4084.
2. Auerbach, J.; Weinreb, S. M. J. Am. Chem. Soc. 1972, 94, 7172–7173.
3. Isono, N.; Mori, M. J. Org. Chem. 1995, 60, 115-119.
4. Tietze, L. F.; Schirok, H. J. Am. Chem. Soc. 1999, 121, 10264–10269.
5. Liu, Q.; Ferreira, E. M.; Stoltz, B. M. J. Org. Chem. 2007, 72, 7352–7358.
6. Ikeda, M.; Bialy, S. A. A. E.; Hirose, K.-I.; Kotake, M.; Sato, T.; Bayomi, S. M. M.; Shehata, I. A.; Abdelal, A. M.; GAD, A. M,; Yakura. T. Chem Pharm Bull. 1999, 47, 983-987.
7. Taniguchi T.; Ishibashi. H. Org. Lett. 2008, 10, 4129–4131.
8. Takaya, Y.; Ogasawara, M,; Hayashi, T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579–5580.
9. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508–11509.
10. Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M. Org. Lett. 2004, 6, 3873–3876.
11. Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503–2508.
12. Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, Q.-G. J. Am. Chem. Soc. 2007, 129, 5336–5337.
13. Feng, C.-G.; Wang, Z.-Q.; Shao, C.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2008, 10, 4101–4104.
14. Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009, 24, 4815–4817.
15. Luo, Y.; Carnell, A. J.; Angew. Chem. Int. Ed. 2010, 49, 2750–2754.
16. Zhou, B.; So, C. M.; Lu, Y.; Hayashi, T. Org. Chem. Front. 2015, 2, 127–132.
17. Wei, W.-T.; Yeh, J.-Y.; Kuo, T.-S.; Wu, H.-L. Chem. Eur. J. 2011, 17, 11405–11409.
18. Liu, C.-C.; Janmanchi, D; Chen, C, C.; Wu, H.-L. Eur. J. Org. Chem. 2012, 23, 2503–2507.
19. Reeves, C. M.; Behenna, D. C.; Stoltz, B. M. Org. Lett. 2014, 16, 2314−2317.
20. Leskinen, M. V.; Yip, K.-T.; Valkonen, A.; Pihko, P. M. J. Am. Chem. Soc. 2012, 134, 5750−5753.
21. Cossy, J.; Mirguet, O.; Pardoa, D. G.; Desmurs, J. R. New J. Chem. 2003, 27, 475–482.
22. Liu, Y.-K.; Ma, C.; Jiang, K.; Liu, T.-Y.; Chen, Y.-C. Org. Lett. 2009, 11, 2848–2851.
23. Chiyoda, K.; Shimokawa, J.; Fukuyama, T. Angew. Chem. Int. Ed. 2012, 51, 2505–2508.
24. Ishikawa, H.; Suzuki, T.; Hayashi, Y. Angew. Chem. Int. Ed. 2009, 48, 1304–1307.
25. Alicia, R.-Ren.; Liu, Z.; Chen, Y.; Sin, N.; Sit, S.-Y.; Swidorski, J. J.; Chen, J.; Venables, B. L.; Zhu, J.; Nowicka-Sans, B.; Protack, T.; Lin, Z.; Terry, B.; Samanta, H.; Zhang, S.; Li, Z.; Beno, B. R.; Huang, X. S.; Rahematpura, S.; Parker, D. D.; Haskell,R.; Jenkins, S.; Santone, K. S.; Cockett, M. I.; Krystal, M.; Meanwell, N. A.; Hanumegowda, U.; Dicker, I. B. ACS Med. Chem. Lett. 2016, 7, 568−572.
26. Huang, K.-C.; Gopula, B.; Kuo, T.-S.; Chiang, C.-W.; Wu, P.-Y.; Julian, P. Henschke; Wu, H.-L. Org. Lett. 2013, 15, 5730−5733.
27. Brandst-tter, M.; Freis, M.; Huwyler, N.; Carreira, E. M. Angew. Chem. Int. Ed. 2019, 58, 2490–2494.
28. Pichlmair, S.; Ruiz, M. D. L.; Basu, K.; Paquette, L. A.; Tetrahedron. 2006, 62, 5178–5194.
29. Daele, I. V.; Munier-Lehmann, H.; Froeyen, M.; Balzarini, J.; Calenbergh, S. V. J. Med. Chem. 2007, 50, 5281−5292.
30. Padwa, A.; Kulkarni, Y. S.; Zhang, Z. J. Org. Chem. 1990, 55, 4144–4153.
31. Khapli, S.; Dey, S.; Mal, D. J. Indian Inst. Sci. 2001, 81, 461–476.
32. Nemoto, T.; Sakamoto, T.; Fukuyama T.; Hamada, Y. Tetrahedron Letters. 2007, 48, 4977–4981.
33. Johnson, T. A.; Curtis, M. D.; Beak, P. J. Am. Chem. Soc. 2001, 123, 1004–1005.
34. Bower, J. F.; Riis-Johannessen, T.; Szeto, P.; Whiteheadc, A. J.; Gallagher, T. Chem. Commun. 2007, 7, 728–730.
35. Krautwald, S.; Schafroth, M. A.; Sarlah, D.; Carreira, E. M. J. Am. Chem. Soc. 2014, 136, 3020−3023.
36. Quintero, Cruz-Gregorio, S.; Arenas, D. C.; Fuentes, L.; Hopfl, L. H.; Sartillo-Piscil, F. Eur. J. Org. Chem. 2017, 28,4104–4110.
37. Piovesana, S.; Schietroma, D. M. S.; Tulli, L. G.; Monaco M. M. R.; Bella, M. Chem. Commun. 2010, 46, 5160–5162.
二.中文文獻
1. 黃志浩(2016)。碩士論文,國立台灣師範大學化學研究所,臺北,臺灣。