利用天然物左旋醋酸冰片酯49合成高穩定性的掌性雙環[2.2.1]雙烯配體，並結合銠（I）催化芳香基硼酸對反丁烯二酸酯進行不對稱1,4-加成反應。在這個催化系統中，銠(I) (1mol% of Rh)催化量和掌性雙烯配體進行不對稱1,4-加成反應，產物具有高產率和高立體選擇性（高達>99.5％ ee值）。並將其應用在合成掌性3-(2-甲氧基)苯基吡咯啶（α2 -腎上腺素受體拮抗劑）和合成掌性氮-苄基-3-苯基吡咯啶。

A new set of stable chiral bicyclo[2.2.1] diene ligands were prepared from (-)-bornyl acetate 49, and were employed in the rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to fumarates. In this catalytic system, rhodium-diene complex (1.0 mol%) generated in situ from chiral diene 53a and [RhCl(C2H4)2]2 successfully yielded the corresponding adducts with good to excellent chemical yields and excellent levels of enantioselectivities (up to >99.5% ee). This methodology was demonstrated by its utilization in the enantioselective total synthesis of 3-(2-methoxyphenyl)pyrrolidine (an α2-adrenoceptor antagonist) and asymmetric synthesis of N-benzyl-3-phenylpyrrolidine.

1. Calne, D. B.; Sandler, M., Nature 1970, 226, 21-24.
2. Seyden-Penne, J., Chiral auxiliaries and ligands in asymmetric synthesis. Wiley
New York: 1995.
3. Triem, G., Chem. Ber. 1938, 71, 1522.
4. (a) Betti, M. M., M., Chem. Ber. 1908, 41, 2071; (b) Wheeler, G. P.; Ingersoll, A.
W., J. Am. Chem. Soc. 1951, 73, 4604-4606.
5. Kawasaki, T.; Jo, K.; Igarashi, H.; Sato, I.; Nagano, M.; Koshima, H.; Soai, K.,
Angew. Chem. Int. Ed. 2005, 44, 2774-2777.
6. Blaser, H. U., Chem. Rev. 1992, 92, 935-952.
7. (a) Ojima, I., Catalytic asymmetric synthesis. Wiley: 2010; (b) Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Comprehensive asymmetric catalysis: Supplement.
Springer Verlag: 2004; (c) Lin, G. Q.; Li, Y. M.; Chan, A. S. C., Principles and
applications of asymmetric synthesis. Wiley Online Library: 2001.
8. Sakai, M.; Hayashi, H.; Miyaura, N., Organometallics 1997, 16, 4229-4231.
9. Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N., J. Am. Chem.
Soc. 1998, 120, 5579-5580.
10. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K., J. Am. Chem. Soc. 2003,
125, 11508-11509.
11. (a) Stone, F. G. A.; Wilkinson, G., Comprehensive Organometallic Chemistry II;
Pergamon: Oxford 1995, Vols.1-14; (b) Paiaro, G.; Panunzi, A.; De Henzi, A.,
Tetrahedron Lett. 1966, 7, 3905-3908; (c) Panunzi, A.; De Renzi, A.; Paiaro, G.,
Inorg. Chim. Acta 1967, 1, 475-478.
12. Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T., Org. Lett. 2004, 6,
3425-3427.
13. Sibi, M. P.; Liu, P.; Ji, J.; Hajra, S.; Chen, J.-X., J. Org. Chem. 2002, 67,
1738-1745.
14. (a) Fagnou, K.; Lautens, M., Chem. Rev. 2002, 103, 169-196; (b) Hayashi, T.;
Yamasaki, K., Chem. Rev. 2003, 103, 2829-2844.
15. Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.;
Akutagawa, S.; Noyori, R., J. Org. Chem. 1986, 51, 629-635.
16. Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.;
Kumobayashi, H., Adv. Synth. Catal. 2001, 343, 264-267.
17. Shi, Q.; Xu, L.; Li, X.; Jia, X.; Wang, R.; Au-Yeung, T. T. L.; Chan, A. S. C.;
Hayashi, T.; Cao, R.; Hong, M., Tetrahedron Lett. 2003, 44, 6505-6508.
18. Boiteau, J.-G.; Minnaard, A. J.; Feringa, B. L., J. Org. Chem. 2003, 68,
9481-9484. 94

19. Curtin, M. L.; Garland, R. B.; Heyman, H. R.; Frey, R. R.; Michaelides, M. R.;
Li, J.; Pease, L. J.; Glaser, K. B.; Marcotte, P. A.; Davidsen, S. K., Bioorg. Med.
Chem. Lett. 2002, 12, 2919-2923.
20. Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T.,
J. Am. Chem. Soc. 2004, 126, 13584-13585.
21. Paquin, J.-F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M., Org. Lett. 2005,
7, 3821-3824.
22. Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M., Org. Lett. 2004, 6,
3873-3876.
23. (a) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q., J. Am. Chem. Soc. 2007,
129, 5336-5337; (b) Li, Q.; Yu, Z.-X., Angew. Chem. Int. Ed. 2011, 50,
2144-2147; (c) Okamoto, K.; Hayashi, T.; Rawal, V. H., Chem. Commun. 2009,
4815-4817; (d) Shintani, R.; Takeda, M.; Nishimura, T.; Hayashi, T., Angew.
Chem. Int. Ed. 2010, 49, 3969-3971; (e) Li, Q.; Dong, Z.; Yu, Z.-X., Org. Lett.
2011, 13, 1122-1125.
24. Uozumi, Y.; Sang-Yong, L.; Hayashi, T., Tetrahedron Lett. 1992, 33, 7185-7188.
25. Leonard, N. J.; Boyer, J. H., J. Org. Chem. 1950, 15, 42-45.
26. (a) Lemke, K.; Ballschuh, S.; Kunath, A.; Theil, F., Tetrahedron: Asymmetry
1997, 8, 2051-2055; (b) Zhong, Y.-w.; Lei, X.-s.; Lin, G.-q., Tetrahedron:
Asymmetry 2002, 13, 2251-2255; (c) Feng, C.-G.; Wang, Z.-Q.; Tian, P.; Xu,
M.-H.; Lin, G.-Q., Chem. Asian J. 2008, 3, 1511-1516.
27. Allen, M. S.; Darby, N.; Salisbury, P.; Sigurdson, E. R.; Money, T., Can. J. Chem.
1979, 57, 733-741.
28. Comins, D. L.; Dehghani, A., Tetrahedron Lett. 1992, 33, 6299-6302.
29. Brock, S.; Hose, D. R. J.; Moseley, J. D.; Parker, A. J.; Patel, I.; Williams, A. J.,
Org. Process Res. Dev. 2008, 12, 496-502.
30. Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S., Angew. Chem.
Int. Ed. 2008, 47, 7669-7672.
31. Brown, M. K.; Corey, E. J., Org. Lett. 2009, 12 (1), 172-175.
32. (a) Blobel, C. P., Nat Rev Mol Cell Biol 2005, 6, 32-43; (b) Janes, P. W.; Saha, N.;
Barton, W. A.; Kolev, M. V.; Wimmer-Kleikamp, S. H.; Nievergall, E.; Blobel, C.
P.; Himanen, J.-P.; Lackmann, M.; Nikolov, D. B., Cell 2005, 123, 291-304; (c)
Wolfsberg, T. G.; Primakoff, P.; Myles, D. G.; White, J. M., The Journal of Cell
Biology 1995, 131, 275-278; (d) Yamamoto, S.; Higuchi, Y.; Yoshiyama, K.;
Shimizu, E.; Kataoka, M.; Hijiya, N.; Matsuura, K., Immunology Today 1999, 20,
278-284; (e) White, J. M., Current Opinion in Cell Biology 2003, 15, 598-606;
(f)Klein, T.; Bischoff, R., Journal of Proteome Research 2010, 10, 17-33.
33. (a) Roy A. Black, Charles T. Rauch, Carl J. Kozlosky, Jacques J. Peschon, 95

Jennifer L. Slack, Martin F. Wolfson, Beverly J. Castner, Kim L. Stocking,
Pranitha Reddy, Subhashini Srinivasan, Nicole Nelson, Norman Boiani, Kenneth
A. Schooley, Mary Gerhart, Raymond Davis, Jeffrey N. Fitzner, Richard
S. Johnson, Raymond J. Paxton, Carl J. March , Douglas Pat Cerretti, Nature
1997, 385, 729-733; (b) Marcia L. Moss, S.-L. Catherine Jin, Marcos E. Milla,
William Burkhart, H. Luke Carter, Wen-Ji Chen, William C. Clay, John
R. Didsbury, Daniel Hassler, Christine R. Hoffman, Thomas A. Kost, Millard
H. Lambert, M. Anthony Leesnitzer, Philip McCauley, Gerard McGeehan,
Justin Mitchell, Mary Moyer, Gregory Pahel, Warren Rocque, Laurie K. Overton,
Frank Schoenen, Theresa Seaton, Jui-Lan Su, Janet Warner, Derril Willard & J.
David Becherer, Nature 1997, 385, 733-736.
34. (a) Hurtado, A.; Holmes, K. A.; Geistlinger, T. R.; Hutcheson, I. R.; Nicholson, R.
I.; Brown, M.; Jiang, J.; Howat, W. J.; Ali, S.; Carroll, J. S., Nature 2008, 456,
663-666; (b) Olayioye, M., Breast Cancer Res 2001, 3, 385 - 389.
35. Purves, D.; Augustine, G. J.; Fitzpatrick, D.; Katz, L. C.; Katz, L.; Coquery, J.
M.; LaMantia, A. S.; McNamara, J. O.; Williams, M. S., Neurosciences: Avec
CD-Rom Sylvius. Le systeme nerveux humain. De Boeck Universite: 2004.
36. Yao, W.; Zhuo, J.; Burns, D. M.; Xu, M.; Zhang, C.; Li, Y.-L.; Qian, D.-Q.; He,
C.; Weng, L.; Shi, E.; Lin, Q.; Agrios, C.; Burn, T. C.; Caulder, E.; Covington, M.
B.; Fridman, J. S.; Friedman, S.; Katiyar, K.; Hollis, G.; Li, Y.; Liu, C.; Liu, X.;
Marando, A.; Newton, R.; Pan, M.; Scherle, P.; Taylor, N.; Vaddi, K.; Wasserman,
Z. R.; Wynn, R.; Yeleswaram, S.; Jalluri, R.; Bower, M.; Zhou, B.-B.; Metcalf,
B., J. Med. Chem. 2007, 50, 603-606.
37. Jincong Zhuo, David M. Burns, Colin Zhang, Meizhong Xu, Lingkai Weng,
Ding-Quan Qian, Chunhong He, Qiyan Lin, Yun-Long Li, Eric Shi, Costas
Agrios, Brian Metcalf, Wenqing Yao, Synlett 2007, 460-464
38. M. P. Seiler; J. Nozulak, WO 2001055132.
39. Shintani, R.; Duan, W.-L.; Nagano, T.; Okada, A.; Hayashi, T., Angew. Chem. Int.
Ed. 2005, 44, 4611-4614.
40. Guzikowski, A. P.; Tamiz, A. P.; Acosta-Burruel, M.; Hong-Bae, S.; Cai, S. X.;
Hawkinson, J. E.; Keana, J. F. W.; Kesten, S. R.; Shipp, C. T.; Tran, M.;
Whittemore, E. R.; Woodward, R. M.; Wright, J. L.; Zhou, Z.-L., J. Med. Chem.
2000, 43, 984-994.
41. Dingemans, T. J.; Murthy, N. S.; Samulski, E. T., The Journal of Physical
Chemistry B 2001, 105, 8845-8860.
42. Geny, A.; Agenet, N.; Iannazzo, L.; Malacria, M.; Aubert, C.; Gandon, V., Angew.
Chem. Int. Ed. 2009, 48, 1810-1813.
43. Agami,C.; Couty, F.; Evano, G., Eur. J. Org. Chem. 2002, 29-38.
44. Roussi, G.; Zhang, J., Tetrahedron, 1991, 47, 5161-5172.