1254
J. Am. Chem. Soc. 2001, 123, 1254-1255
Table 1. The Asymmetric Hydrogenation of Tiglic Acid in
[bmim]PF6/H2O Followed by Extraction with scCO2
(Enantioselectivity and Conversion as a Function of the Number of
Cycles)a
Asymmetric Hydrogenation and Catalyst Recycling
Using Ionic Liquid and Supercritical Carbon Dioxide
Richard A. Brown,† Pamela Pollet,‡ Erin McKoon,†
run no.
catalyst solution
% ee
% conversion
Charles A. Eckert,§ Charles L. Liotta,‡ and Philip G. Jessop*,†
1
2
3
4
5
fresh
85
90
88
87
91
99
98
97
98
97
recycled from run 1b
recycled from run 2b
recycled from run 3b
recycled from run 4b,c
Department of Chemistry, UniVersity of California
DaVis, California 95616-5295
Schools of Chemistry and Chemical Engineering
Georgia Institute of Technology, Atlanta, Georgia 30332-0100
a Reaction conditions as described in ref 9. b Before each subsequent
run, 1.1 mmol of tiglic acid was added to the catalyst/IL solution in
the vessel. c The last reaction cycle was not stirred.
ReceiVed October 20, 2000
Asymmetric hydrogenation of tiglic acid catalyzed by
Ru(O2CMe)2((R)-tolBINAP) in wet ionic liquid ([bmim]PF6 with
added water, bmim ) 1-n-butyl-3-methylimidazolium) gave
2-methylbutanoic acid with high enantioselectivity and conversion.
The product was extracted with supercritical CO2 (scCO2) giving
a clean separation of product and catalyst. The catalyst/ionic liquid
solution was then reused repeatedly without significant loss of
enantioselectivity or conversion.
suggested by Blanchard et al.8 It is our aim to demonstrate that
the combination of ionic liquids and scCO2 for catalysis can have
substantial advantages over the use of either type of solvent alone.
Biphasic solvent systems for homogeneous catalysis typically
consist of a lower phase solvent that dissolves the catalyst and
an upper phase solvent that carries the substrate into the reaction
vessel and the products out. The ideal biphasic solvent system
would consist of a lower solvent that is able to dissolve both the
homogeneous catalyst and the substrate (for optimum rates) and
an upper solvent that is environmentally friendly, can dissolve
the substrate and products, can be easily removed from the
products, and has negligible ability to extract the lower solvent
or the catalyst. Aqueous/organic1 or fluorous/organic2 biphasic
systems do not meet the environmentally benign requirements,
fluorous/organic systems also have problems with partial solubility
of the catalyst in the organic phase, and H2O/scCO2 systems3 can
have problems with pH.3b Finally, all of these systems when used
for asymmetric catalysis employ sulfonated or fluorinated chiral
ligands, which can be synthetically challenging. We have found
that an ionic liquid/scCO2 biphasic system, which meets all of
these requirements without the need for a sulfonated or fluorinated
ligand, can be used for asymmetric catalysis followed by facile
product/catalyst separation and catalyst recycling.
We found that the hydrogenation of tiglic acid using
Ru(O2CMe)2((R)-tolBINAP) proceeds with good selectivity and
excellent yield in [bmim]PF6 (hereafter referred to as ionic liquid
or IL) with some water added (eq 1, Table 1). The product was
extracted from the IL by scCO2.9 Fortunately, the ionic liquid
has no solubility whatsoever in scCO2.8 Equally fortunately, the
tolBINAP complex is far more soluble in the IL than it is in the
scCO2, so that there is no tendency of the scCO2 to extract the
complex. One then obtains essentially pure product from the CO2
effluent, contaminated with no ionic liquid or catalyst, and
containing only some H2O. The catalyst solution left behind in
the vessel can be reused for at least four more runs. The ee
(enantiomeric excess) of the product using recycled catalyst was
higher than that obtained using fresh catalyst, and the ee and
conversion remained high through the total of five cycles.
We further tested the hydrogenation of tiglic acid in [bmim]-
PF6 to explore the parameters which influence the enantioselec-
tivity (Table 2). These tests were performed on a smaller scale
than those in Table 1, and were not followed by scCO2 extraction
Supercritical carbon dioxide4,5 has been used as an alternative
medium for a number of asymmetric hydrogenations,6 although
catalyst solubility, especially with the complexes of the highly
aromatic ligand BINAP, has been a problem.6a Ionic liquids have
not received as much attention until recently, but there has been
an initial report by Monteiro et al. of their use as a solvent for
enantioselective hydrogenation.7 The possibility of combining
ionic liquids and scCO2 for chemical separations was first
* To whom correspondence should be addressed. Tel. (530) 754-9426.
† University of California, Davis.
‡ Georgia Institute of Technology, School of Chemistry.
§ Georgia Institute of Technology, School of Chemical Engineering.
(1) Cornils, B.; Herrmann, W. A., Eds. Aqueous-Phase Organometallic
Catalysis; Wiley-VCH: Weinheim, 1998.
(2) Horva´th, I. T.; Ra´bai, J. Science 1994, 266, 72
(3) (a) Bhanage, B. M.; Ikushima, Y.; Shirai, M.; Arai, M. Chem. Commun.
1999, 1277-1278. (b) Bonilla, R. J.; James, B. R.; Jessop, P. G. Chem.
Commun. 2000, 941-942.
(8) Blanchard, L. A.; Hancu, D.; Beckman, E. J.; Brennecke, J. F. Nature
1999, 399, 28-29.
(9) Method for hydrogenation and extraction: The [bmim]PF6 (30 g,
degassed, density 1.36 g/mL), water (10 mL), Ru(O2CMe)2(R-tolBINAP) (22
µmol), tiglic acid (1.1 mmol), and a stir bar were combined in a 160 mL steel
vessel under nitrogen atmosphere. The reaction was performed over 18 h under
5 bar of H2 at 25 °C. The vessel was then warmed to 35 °C and scCO2 (175
bar, 1 mL/min) was bubbled through the solution and vented through a JASCO
back-pressure regulator into a cold trap (approximately 18 h). Yields were
(4) Jessop, P. G.; Leitner, W., Eds. Chemical Synthesis using Supercritical
Fluids; VCH/Wiley: Weinheim, 1999.
(5) Jessop, P. G.; Ikariya, T.; Noyori, R. Chem. ReV. 1999, 99, 475-493.
(6) (a) Xiao, J.; Nefkens, S. C. A.; Jessop, P. G.; Ikariya, T.; Noyori, R.
Tetrahedron Lett. 1996, 37, 2813-2816. (b) Burk, M. J.; Feng, S.; Gross, M.
F.; Tumas, W. J. Am. Chem. Soc. 1995, 117, 8277-8278. (c) Kainz, S.;
Brinkmann, A.; Leitner, W.; Pfaltz, A. J. Am. Chem. Soc. 1999, 121, 6421-
6429. (d) Lange, S.; Brinkmann, A.; Trautner, P.; Woelk, K.; Bargon, J.;
Leitner, W. Chirality 2000, 12, 450-457.
i
higher (90% recovery) if the trap contained cold PrOH. After several hours
of extraction, the CO2 flow was stopped, and the gas was vented from the
vessel. The contents of the trap were analyzed by chiral capillary GC. More
tiglic acid (1.1 mmol) was added to the ionic liquid solution remaining in the
vessel, followed by H2 gas. This was the start of the second reaction cycle.
(7) Monteiro, A. L.; Zinn, F. K.; DeSouza, R. F.; Dupont, J. Tetrahedron-
Asymmetry 1997, 8, 177-179.
10.1021/ja005718t CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/17/2001