利用烯丙基金屬化合物（allylmetal）與醛基化合物進行不對稱烯丙基加
成反應（allylation），乃是有機合成中相當重要的合成方式。反應所得到之產
物─烯丙醇，於有機合成上之應用亦相當廣泛，藉由各種不同的反應條件，
可以製備醛基、酮基、環氧化合物、γ-內酯、δ-內酯……等不同的官能基化
合物；再者，烯丙醇在許多天然物的分子（如：Laulimide（21）、LY426965
（22）……等）結構中亦為重要的一種官能基。因此，若能有效掌握產物─
烯丙醇的「立體化學中心」，必更能增進烯丙基加成反應的應用。
本研究以對掌輔助劑camphorpyrazolidinone（112）為主架構，利用其衍
生物125 與126，進行不對稱烯丙基加成反應，並探討其立體化學中心的控
制，均獲致不錯的結果。
首先，利用N-glyoxyloyl camphorpyrazolidinone（125）進行之不對稱烯
丙基加成反應，篩選出以一當量的路易士酸Eu(OTf)3 進行催化的最佳反應條
件，亦探討溶劑的影響情況。本實驗的最高產率可達90 %，雖然立體選擇性
方面不甚理想，以非鏡像超越值為48 % de 最高。
接著，再利用-keto amide（126）之不同官能基取代化合物進行不對稱
烯丙基加成反應，更成功地篩選出以一當量路易士酸Sn(OTf)2 進行催化的最
佳反應條件，且發現不同的路易士酸會使產物的立體化學中心反轉，並就反
應機構加以推測及探討；其最高產率達95 %，非鏡像超越值更可高達95 % de
以上。

Asymmetric carbonyl allylation represents one of the most useful tools for the
construction of regio- and stereodefined carbon framework. The alkene
functionality is readily available for further functional group transformation to
give epoxides, γ-lactam, δ-lactam, ect. The Lewis acid-mediated allylation of
aldehydes is a highly useful synthetic operation to form chiral secondary
homoallyl alcohols and has been studied extensively.
Diastereoselective allylation of camphorpyrazolidinone derived N-glyoxylate
(125) and α-keto amides (126) was examined by using allyltributyltin in the
presence of various Lewis acids. The chiral camphor pyrazolidinone (112) can be
easiliy prepared from the known (S)-ketopinic acid (118) in three steps in total 80
% yield.
This research is to study the asymmetric allylation by using
camphorpyrazolidinone derived N-glyoxylate (125) as a substrate. Treatment of
compound 125 with various of Lewis acids gave good chemical yield (up to 90 %)
in presence of allyltributyltin but unsatisfied diastereoselectivity. On the other
hand, Then camphorpyrazolidinone phenylate (126c) was used as a substrate, to
our surprise, a high stereoselectivity was achieved (up to 95 % de). The absolute
stereochemistry of the newly generated steregenic center was assigned as
R-configuration by single crystal X-ray analysis of 126c. Therefore, the effect
between diastereoselectivity and reaction rate of various α-keto amides (126a-d)
were studied. A reasonable mechanism was proposed.

51
1. Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
2. Buse, C. T.; Heathcock, C. H. Tetrahedron Lett. 1978, 19, 1685.
3. Hoffmann, R. W.; Zeiss, H.–J. Angew. Chem., Int. Ed. Engl. 1979, 18, 306.
4. Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K. J. Am. Chem. Soc. 1980,
102, 7107.
5. Yamamoto, Y.; Yatagai, H.; Maruyama, J. Org. Chem. 1980, 45, 195.
6. Collum, D. B.; McDonald, J. H.; Still, W. C. J. Am. Chem. Soc. 1980, 102,
2118.
7. Yatagai, H.; Yamamoto, Y.; Maruyama, K. J. Am. Chem. Soc. 1980, 102, 4548.
8. Mukaiyama, T., cited by N. Andersen et al. Tetrahedron Lett. 1981, 22, 4069.
9. Yamamoto, Y.; Maruyama, K. Tetrahedron Lett. 1981, 22, 2895.
10. Sato, F.; Iida, K.; Iijima, S. Moriya, H.; Sato, M. J. Chem. Soc. Chem.
Commum. 1980, 1140.
11.Wuts, P. G..; Obrzut, M. L.; Thompson, P. A. Tetrahedron Lett. 1984, 25, 4051.
12. Brown, H. C.; Kulkarni, S. V.; Racherla, U. S. J. Org. Chem. 1994, 59, 365.
13. Enev, V. S.; Kaehlig, H.; Mulzer, J. J. Am. Chem. Soc. 2001, 123, 10764.
14. Denmark, S. E.; Fu, J. Org. Lett. 2002, 4, 1951.
15. Germay, O.; Kumar, N.; Thomas, E. J. Tetrahedron Lett. 2001, 42, 4969.
16. Kondo, S. Yasui, K. Natsume, M. Katayama, M. Marumo, S. J. Antibiot
(Tokyo). 1988, 41(9), 1196.
17. Yamamoto, Y.; Maruyama, K. Tetrahedron Lett. 1981, 22, 2895.
18.Mishima, K.; Yasuda, H.; Asami, T.; Nakamura, A. Chem. Lett. 1983, 219.
52
19. Lewis, M. D. ;Kisi, Y. Tetrahedron Lett. 1982, 23, 2343.
20. Denmark, S. E.; Coe, D. M.; Pratt, N. E.;Griedel, B. D. J. Org. Chem. 1994, 59,
6161.
21. Denmark, S. ; Fu, J. J. Am. Chem. Soc. 2000, 122, 12021.
22. Denmark, S.; Wynn, T.; J. Am. Chem. Soc. 2001, 123, 6199.
23. Denmark, S.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488.
24. Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron Lett. 1999, 40,
2767.
25. Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron 1999, 55, 977
26. Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998,
120, 6419.
27. Gennari, C.; Chataigner, I.; Piarulli, U. Tetrahedron Lett. 1999, 40, 3633
28. Chan, T. H.; Wang, D. Chem. Rev. 1992, 92, 995.
29.Wang, D.; Yang, Y.; Wang, M. Chem. Commum. 1997, 1651.
30. Leighton, L.; Kinnaird, J.; W. A.; Ng, P. Y.; Kubota, K.; Wang, X. J. Am. Chem.
Soc. 2002, 124, 7920.
31.Wang, D.; Wang, Z. G.; Wang, M. W.; Chen, Y. J.; Liu, L.; Zhu, Y. Tetrahedron:
Asymmetry, 1999, 10, 327.
32. Heathcock, C. H.; Kiyooka, S.; Blumenkopf, T. A. J. Org. Chem. 1984, 49,
4214.
33. Soai, C.; Ishizaki, M. J. Org. Chem. 1986, 51, 3290.
34. Soai, K.; Ishizaki, M.; Yokoyama, S. Chem. Lett. 1987, 341.
35. Kawanami, Y.; Katayama, K. Chem. Lett. 1990, 1749.53
36. Kim, Y. H.; Kim, S. H. Tetrahedron Lett. 1995, 36, 6895.
37. Gewald, R.; Kira, M.; Sakurai, H. Synthesis, 1996, 9, 111.
38.McCluskey, A.; Garner, J.; Young, D. J. Caballero, S. Tetrahedron Lett. 2000,
41, 8147.
39. Fukuzawa, S.; Miura, M.; Matsuzawa, H. Tetrahedron Lett. 2001, 42, 4167.
40. Jurczak, J.; Bauer, T.; Jezewski, A.; Chapuis, C. Tetrahedron: Asymmetry. 1996,
7, 1385.
41. Jurczak, J.; Bauer, T.; Chapuis, C.; Kiegiel, J.; Krajewski, J. W.; Piechota, K.
Urbanczyk-Lipkowska, Z. Helv. Chem. Acta. 1996, 79, 1059.
42. Jurczak, J.; Kielgiel, K.; Prokopowicz, P. Syn. Commun. 1999, 29, 3999.
43. Jurczak, J.; Kielgiel, K. Tetrahedron Lett. 1999, 40, 1009.
44. Oppolzer, W.; Chapuis, C.; Bernardinelli, G. Helv. Chem. Acta. 1984, 67, 1397.
45. Chen, K.; Pan, J. F.; Lee, W. D. Tetrahedron Lett. 2004, 45, 2541.
46. 楊孔碩，國立台灣師範大學化研所（民91）
47. 藍錦全，國立台灣師範大學化研所（民90）
48. 潘佳甫，國立台灣師範大學化研所(unpublished results)