臺灣博碩士論文加值系統

本論文以樟腦衍生物之γ-胺基硫醇(-)-MITH (2)、β-氨基醇(+)-MINBOL (3)為主要概念，開發新型的掌性配位基：γ-醯胺基硫醇(10)以及β-氨基醇 (11)。更進一步使用β-氨基醇 (11)為掌性配位基，應用於二乙基鋅以及芳香基鋅試劑對醛類的不對稱加成反應。
在二乙基鋅(1.1 M in toluene)加成反應中僅需0.5 mol % 添加量、在常溫下反應就可得到最高99 %之產率以及最高98 % ee之鏡像選擇性的R組態二級醇產物；在芳香基鋅加成反應中僅需 2.5 mol % 添加量就可得到最高99 % 之產率以及最高90 % ee之鏡像選擇性的雙芳香基甲醇產物。

This thesis dealt with the development of new chiral ligands, γ-amido thiol (10) and β-amino alcohol (11), based on γ-amino thiol(-)-MITH (2) and β- amino alcohol (+)-MINBOL (3), respectively. Furthermore, this thesis also dealt with the application of β-amino alcohol (11) in catalytic asymmetric addition reactions of diethylzinc and arylzinc to aldehydes to construct chiral secondary alcohols.
Asymmetric ethylation using a stock solution of diethylzinc (1.1 M in toluene) was carried out in the presence of 0.5 mol % of β-amino alcohol (11) at room temperature and the (R)-secondary alcohols with high yields (up to 99 %) and ee values (up to 98 %) were obtained. On the other hand, asymmetric arylation was carried out in the presence of 2.5 mol % of β-amino alcohol (11) and the chiral diarylmethanols with high yields (up to 99 %) and ee values (up to 90 %) were obtained.

第一章 緒論 ...............................................1
第二章 不對稱二乙基鋅及芳香基鋅加成反應 ..................... 6
2.1 文獻回顧
2.1.1不對稱二乙基鋅加成反應 ................................6
2.1.2不對稱芳香基鋅加成反應................................15
2.2 研究動機 ............................................28
2.3 結果與討論...........................................29
2.4 結論 ................................................48
第三章 實驗部分...........................................49
3.1 一般實驗方法..........................................49
3.2製備掌性配位基(10)之實驗步驟.............................51
3.3製備掌性配位基(11)之實驗步驟.............................57
3.4二乙基鋅加成至醛類的標準步驟.............................66
3.5芳香基鋅加成至醛類的標準步驟.............................73

參考文獻 .................................................78
附錄一 化合物之核磁共振光譜 ................................83
附錄二 HPLC 分析之圖譜 ...................................120

1. McFadden, R. G.; Fraher, L. J.; Thompson, J. M. CHEST 1989, 96, 216-218.
2. Stinson, S. C. Chem Eng News 1992, 70, 46-79.
3. (a) Knowles, W. S.; Sabacky, M. J. Chem. Commun. 1968, 1445-1446. (b) Noyori, R. Science 1990, 248, 1194-1199. (c) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765-5780.
4. Oguni, N.; Omi, T. Tetrahedron Lett. 1984, 25, 2823-2824.
5. Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833-856.
6. Pu, L.; Yu, H. B. Chem. Rev. 2001, 101, 757-824.
7. Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071-6072.
8. Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1989, 111, 4028-4036.
9. Yamakawa, M.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 6327-6335.
10. Oppolzer, W.; Radinov, R. N. Tetrahedron Lett. 1988, 29, 5645-5648.
11. 吳學亮, 博士論文, 國立清華大學化學系, 2003.
12. 鄭楹霓, 碩士論文, 國立清華大學化學系, 2008.
13. (a) Wu, Z. L.; Wu, H. L.; Wu, P. Y.; Uang, B. J. Tetrahedron: Asymmetry 2009, 20, 1556-1560. (b) 吳志龍, 碩士論文, 國立清華大學化學系, 2005.
14. (a) Casy, A. F.; Drake, A. F.; Ganellin, C. R.; Mercer, A. D.; Upton, C. Chirality 1992, 4, 356-366. (b) Shafiee, A.; Hite, G. J. Med. Chem. 1969, 12, 266. (c) Kim, J. G.; Walsh, P. J. Angew. Chem. Int. Ed. 2006, 45, 4175-4178. (d) Meguro, K.; Aizawa, M.; Sohda, T.; Kawamatsu, Y.; Nagaoka, A. Chem. Pharm. Bull. 1985, 33, 3787-3797. (e) Stanchev, S.; Rakovska, R.; Berova, N.; Snatzke, G. Tetrahedron: Asymmetry 1995, 6, 183-198. (f) Toda, F.; Tanaka, K.; Koshiro, K. Tetrahedron: Asymmetry 1991, 2, 873-874. (g) Kim, J. G.; Walsh, P. J. Angew.Chem. Int. Ed. 2006, 45, 4175-4178.
15. Boyd, E. C.; Eaton, M. A. W.; Warrellow, G. J. W. 94/10118 1994
16. McCalmont, W. F.; Heady, T. N.; Patterson, J. R.; Lindenmuth, M. A.; Haverstick, D. M.; Gray, L. S.; Macdonald, T. L. Bioorg. Med. Chem. Lett. 2004, 14, 3691-3695.
17. Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006, 35, 454-470.
18. (a) Bolm, C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem. Int. Ed. 2001, 40, 3285-3308. (b) Corey, E. J.; Helal, C. J. Angew. Chem. Int. Ed. 1998, 37, 1987-2012. (c) Noyori, R.; Ohkuma, T. Angew. Chem. Int. Ed. 2001, 40, 40-73.
19. Soai, K.; Kawase, Y.; Oshio, A. J. Chem. Soc. Perkin. Tran. 1 1991, 1613-1615.
20. Dosa, P. I.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1997, 62, 444-445.
21. Huang, W. S.; Pu, L. J. Org. Chem. 1999, 64, 4222-4223.
22. Ko, D. H.; Kim, K. H.; Ha, D. C. Org. Lett. 2002, 4, 3759-3762.
23. Bolm, C.; Hermanns, N.; Hildebrand, J. P.; Muniz, K. Angew. Chem. Int. Ed. 2000, 39, 3465.
24. Bolm, C.; Rudolph, J. J. Am. Chem. Soc. 2002, 124, 14850-14851.
25. Liu, X. Y.; Wu, X. Y.; Chai, Z.; Wu, Y. Y.; Zhao, G.; Zhu, S. Z. J. Org. Chem. 2005, 70, 7432-7435.
26. Liu, C.; Guo, Z. L.; Weng, J.; Lu, G.; Chan, A. S. C. Chirality 2010, 22, 159-164.
27. Glynn, D.; Shannon, J.; Woodward, S. Chem. Eur. J. 2010, 16, 1053-1060.
28. Karthikeyan, J.; Jeganmohan, M.; Cheng, C. H. Chem. Eur. J. 2010, 16, 8989-8992.
29. Muramatsu, Y.; Kanehira, S.; Tanigawa, M.; Miyawaki, Y.; Harada, T. Bull. Chem. Soc. Jpn. 2010, 83, 19-32.
30. Wu, K. H.; Zhou, S.; Chen, C. A.; Yang, M. C.; Chiang, R. T.; Chen, C. R.; Gau, H. M. Chem. Commun. 2011, 47, 11668-11670.
31. (a) Wu, P. Y.; Wu, H. L.; Uang, B. J. J. Org. Chem. 2006, 71, 833-835. (b) 吳平宇, 博士論文, 國立清華大學化學系, 2008.
32. 許家榕, 碩士論文, 國立清華大學化學系, 2011.
33. 楊博堯, 碩士論文, 國立清華大學化學系, 2010.
34. (a) Wu, H. L.; Wu, P. Y.; Shen, Y. Y.; Uang, B. J. J. Org. Chem. 2008, 73, 6445-6447. (b) Wu, P. Y.; Wu, H. L.; Shen, Y. Y.; Uang, B. J. Tetrahedron: Asymmetry 2009, 20, 1837-1841. (c) Wu, Z. L.; Wu, H. L.; Wu, P. Y.; Uang, B. J. Tetrahedron: Asymmetry 2009, 20, 1556-1560. (d) Tseng, C. H.; Hung, Y. M.; Uang, B. J. Tetrahedron: Asymmetry 2012, 23, 130-135. (e) 黃偉銘, 碩士論文, 國立清華大學化學系, 2010. (f) 曾志豪, 博士論文, 國立清華大學化學系, 2011.
35. Martínez, A. G.; Vilar, E. T.; Fraile, A. G.; Cerero, S. M.; Ruiz, P. M.; Subramanian, L. R. Tetrahedron: Asymmetry 1996, 7, 1257-1260.
36. Martínez, A. G.; Vilar, E. T.; Barcina, J. O.; Herrero, M. E. R.; Cerero, S. M.; Hanack, M.; Subramanian, L. R. Tetrahedron: Asymmetry 1993, 4, 2333-2334.
37. Martínez, A. G.; Vilar, E. T.; A., G. F.; Cerero, S. M.; Oliva, C. D.; Subramanian, L. R.; Maichle, C. Tetrahedron: Asymmetry 1994, 5, 949-954.