We have recently reported enantioselective Michael reac-
tion7 and fluorination8 using a catalytic amount of novel
chiral palladium complexes 1 and 2 (Scheme 1). In these
reactions proceeded in high yields, giving the products with
excellent enantioselectivities of up to 99% ee in the Michael
reaction and up to 94% ee in the fluorination. Since the
palladium complexes are not sensitive to water, both reac-
tions were carried out in protic solvents (alcohols, H2O9).
While the usage of environmentally friendly solvents is
advantageous, the recovery of the palladium complexes from
the reaction mixtures is not easy. To address this issue, we
planed to develop an efficient catalytic system using IL, in
which the palladium complexes can be repeatedly used. Thus,
we envisaged that the palladium complexes 1 and 2 might
be immobilized in IL due to their cationic property and that
the same level of enantioselectivity would be obtained
because the palladium enolate 4 may be configurationally
stable even in polar ionic liquid. Herein we wish to report a
successful example of the reuse of palladium complexes and
its applications to two catalytic asymmetric reactions.
Catalysts could be reused at least 10 times in fluorination
and 5 times in the Michael reaction.
Scheme 1. Asymmetric Reactions Catalyzed by Cationic
Palladium Complexes
At the outset, we examined the catalytic enantioselective
fluorination of the â-ketoester 3a using three ionic liquids
7-9 (Table 1).10, 11 Thus, to a solution of Pd complex 1a in
Table 1. Catalytic Asymmetric Fluorination in Ionic Liquid
reactions, â-ketoesters were directly activated to form a chiral
palladium enolate 4,7 which reacted with electrophiles such
as enones and N-fluorobenzenesulfonimide (NFSI). Both
(5) Recent selected examples: Kim, D. W.; Song, C. E.; Chi, D. Y. J.
Org. Chem. 2003, 68, 4281-4285. (b) Gmouh, S.; Yang, H.; Vaultier, M.
Org. Lett. 2003, 5, 2219-2222. (c) Kabalka, G. W.; Dong, G.; Venkataiah,
B. Org. Lett. 2003, 5, 893-895. (d) Zerth, H. M.; Leonard, N, M.; Mohan,
R. S. Org. Lett. 2003, 5, 55-57. (e) Boxwell, C. V.; Dyson, P. J.; Ellis, D.
J.; Welton, T. J. Am. Chem. Soc. 2002, 124, 9334-9335. (f) Dupont, J.;
Fonseca, G. S.; Umpierre, A. P.; Fichtner, P. F. P.; Teixeira, S. R. J. Am.
Chem. Soc. 2002, 124, 4228-4229. (g) Yao, Q. Org. Lett. 2002, 4, 2197-
2199. (h) Mehnert, C. P.; Dispenziere, N. C.; Cook, R. A. Chem. Commun.
2002, 1610-1611. (i) Mathews, C. J.; Smith, P. J.; Welton, T. Chem.
Commun. 2002 1249-1250. See also ref 4.
entry ketoester ionic liquid time (h) yielda (%) eeb (%)
1
2
3
4
5
3a
3a
3a
3b
3c
7
8
9
7
9
60
60
60
12
6
68
88
93
80
94
91
92
92
85
91
(6) Hydrogenation: (a) Chauvin, Y.; Mussmann, L.; Olivier, H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2698-2700. (b) Monteiro, A. L.; Zinn, F.
K.; de Souza, R. F.; Dupont, J. Tetrahedron: Asymmetry 1997, 2, 177-
179. (c) Brown, R. A.; Pollet, P.; McKoon, E.; Eckert, C. A.; Liotta, C. L.;
Jessop, P. G. J. Am. Chem. Soc. 2001, 123, 1254-1255. (d) Guernik, S.;
Wolfson, A.; Herskowitz, M.; Greenspoon, N.; Geresh, S. Chem. Commun.
2001, 2314-2315. Epoxidation: (e) Song, C. E.; Roh, E. J. Chem. Commun.
2000, 837-838. Dihydroxylation: (f) Branco, L. C.; Afonso, C. A. M.
Chem. Commun. 2002, 3036-3037. (g) Song, C. E.; Jung, D.; Roh, E. J.;
Lee, S.; Chi, D. Y. Chem. Commun. 2002, 3038-3039. Aldol reaction:
(h) Loh, T.-P.; Feng, L.-C.; Yang, H.-Y.; Yang, J.-Y. Tetrahedron Lett.
2002, 43, 8741-8743. (i) Kotrusz, P.; Kmentova´, I.; Gotov, B.; Toma, S.;
Solca´niova´, E. Chem. Commun. 2002, 2510-2511. Cyclopropanation: (j)
Fraile, J. M.; Garc´ıa, J. I.; Herrer´ıas, C. I.; Mayoral, J. A.; Carrie´, D.;
Vaultier, M. Tetrahedron: Asymmetry 2001, 12, 1891-1894. Epoxide
opening reaction: (k) Song, C. E.; Oh, C. R.; Roh, E. J.; Choo, D. J. Chem.
Commun. 2000, 1743-1744. (l) Oh, C. R.; Choo, D. J.; Shim, W. H.; Lee,
D. H.; Roh, E. J.; Lee, S.; Song, C. E. Chem. Commun. 2003, 1100-1101.
(7) Hamashima, Y.; Hotta, D.; Sodeoka, M. J. Am. Chem. Soc. 2002,
124, 11240-11241.
a Isolated yield after ether extraction. b Ee’s and the absolute configuration
of the products were determined by chiral HPLC analysis using the
conditions reported previously.8
IL were added 3a and N-fluorobenzenesulfonimide (1.5
equiv). The reaction mixture was stirred at ambient temper-
ature. While the length of the side chain and the counteranion
of IL seemed to have some influence on the reaction rate,
excellent enantioselectivities (91-92% ee) were obtained in
all three cases (entries 1-3). Using IL 9, the desired product
was obtained in 93% yield and 92% ee. Although the
(8) Hamashima, Y.; Yagi, K.; Takano, H.; Tama´s, L.; Sodeoka, M. J.
Am. Chem. Soc. 2002, 124, 14530-14531.
3226
Org. Lett., Vol. 5, No. 18, 2003