Thermomorphic system with non-fluorous phase-tagged Ru(BINAP) catalyst: Facile liquid/solid catalyst separation and application in asymmetric hydrogenation

Article abstract of DOI:10.1021/jo052092m

The thermomorphic BINAP derivative 1 tagged with long alkyl chains was prepared from (S)-5,5′-diamino BINAP and applied to Ru-catalyzed asymmetric hydrogenation of β-ketoesters under homogeneous conditions in 3:1 (v/v) ethanol/ 1,4-dioxane at 60 °C with high enantioselectivity (up to 98% ee). Results indicated that the Ru(1) catalyst was easily recovered by simple cooling and precipitation and could be used for at least four cycles without any loss of enantioselectivity.

Full text of DOI:10.1021/jo052092m

neous chiral catalysts have recently been reviewed.3 These
included the immobilization of homogeneous chiral catalysts
either by anchoring the catalyst onto organic or inorganic
supports via covalent or noncovalent attachment or by using a
liquid/liquid two-phase system. In most cases, however, the
activity and enantioselectivity of the immobilized catalysts are
usually lower than those of the parent homogeneous system as
a result of mass transfer limitations.
Thermomorphic System with Non-Fluorous
Phase-Tagged Ru(BINAP) Catalyst: Facile
Liquid/Solid Catalyst Separation and Application
in Asymmetric Hydrogenation
Yi-Yong Huang,†,‡ Yan-Mei He,† Hai-Feng Zhou,† Lei Wu,†
Bao-Lin Li,† and Qing-Hua Fan*,†
Fluorous biphasic catalysis (FBC), since the pioneering work
of Horva´th was reported, has provided an elegant solution to
the separation of the catalysts from the products and their
reuse.3i,4,5 One of the unique features of this strategy is that the
thermomorphic two phases become homogeneous during the
reaction when being heated and then could be readily separated
by cooling the reaction mixtures. Although FBC combines the
advantages of homogeneous catalysis and heterogeneous ca-
talysis, the large-scale use of perfluorocarbon solvents has some
drawbacks: high cost and environmental persistence. In response
to these limitations, several research groups have introduced
some new methodologies. Recently, Gladysz’s group6 and
Yamamoto’s group7 independently introduced the solubility-
based thermomorphic properties of heavy fluorous catalysts in
nonpolar organic solvent as a new strategy to perform homo-
geneous fluorous catalysis without fluorous solvent. Jessop and
co-workers described a new method for FBC, in which the
fluorous solvent was replaced by fluorinated silica, and the
fluorous catalyst was dissolved in organic solvent by the
presence of CO2 pressure and could be recovered after the
reaction by release of the CO2 pressure.8 In addition, Bergbreiter
and others developed some novel thermomorphic systems
consisting of nonfluorous polymer-supported catalysts via
Laboratory of Chemical Biology, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, P. R. China,
and Graduate School of Chinese Academy of Sciences,
Beijing 100080, P. R. China
fanqh@iccas.ac.cn
ReceiVed October 5, 2005
The thermomorphic BINAP derivative 1 tagged with long
alkyl chains was prepared from (S)-5,5′-diamino BINAP and
applied to Ru-catalyzed asymmetric hydrogenation of â-ke-
toesters under homogeneous conditions in 3:1 (v/v) ethanol/
1,4-dioxane at 60 °C with high enantioselectivity (up to 98%
ee). Results indicated that the Ru(1) catalyst was easily
recovered by simple cooling and precipitation and could be
used for at least four cycles without any loss of enantiose-
lectivity.
(2) (a) Special Issue on Recoverable Catalysts and Reagents. Gladysz,
J. A., Ed. Chem. ReV. 2002, 102, 3215-3892. (b) Chiral Catalyst
Immobilization and Recycling; de Vos, D. E., Vankelekom, I. F. J., Jacobs,
P. A., Eds.; Wiley-VCH: Weinheim, Germany, 2000. (c) Cole-Hamilton,
D. J. Science 2003, 299, 1702.
(3) For recent reviews, see: (a) Fan, Q. H.; Li, Y. M.; Chan, A. S. C.
Chem. ReV. 2002, 102, 3385. (b) Song, C. E.; Lee, S. G. Chem. ReV. 2002,
102, 3495. (c) Vankelekom, I. F. J. Chem. ReV. 2002, 102, 3779. (d)
Kobayashi, S.; Akiyama, R. Chem. Commun. 2003, 449. (e) Saluzzo, C.;
Lemaire, M. AdV. Synth. Catal. 2002, 344, 915. (f) Ngo, H. L.; Lin, W.
Top. Catal. 2005, 34, 85. (g) Sinou, D. AdV. Synth. Catal. 2002, 344, 221.
(h) Song, C. E. Chem. Commun. 2004, 1033. (i) Pozzi, G.; Shepperson, I.
Coord. Chem. ReV. 2003, 242, 115. (j) Yoshida, J.; Itami, K. Chem. ReV.
2002, 102, 3693.
Homogeneous asymmetric catalysis is one of the most
important developments in modern synthetic and pharmaceutical
chemistry over the past several decades. Many chiral catalysts
are known to exhibit high activity and enantioselectivity.1
However, the high cost of both these chiral ligands and transition
metals as well as the regulatory issues associated with trace
metal contaminants in the products have restricted their industrial
applications. The heterogenization of homogeneous catalysts
provides a possible approach to catalyst separation and recy-
cling.2 Different approaches to the immobilization of homoge-
(4) (a) Horva´th, I. T. Acc. Chem. ReV. 1998, 31, 641. (b) Barthel-Rosa,
L. P.; Gladysz, J. A. Coord. Chem. ReV. 1999, 192, 587.
(5) Selected recent examples of fluorous chiral catalysts for FBC, see:
(a) Pozzi, G.; Cinato, F. Montanari, F.; Quici, S. Chem. Commun. 1998,
877. (b) Francio`, G.; Leitner, W. Chem. Commun. 1999, 1663. (c) Kleijn,
H.; Rijnberg, E.; Jastrzebski, J. T. B. H.; van Koten, G. Org. Lett. 1999, 1,
853. (d) Nakamura, Y.; Takeuchi, Y.; Ohgo, Y.; Curran, D. P. Tetrahedron
Lett. 2000, 41, 57. (e) Chen, W.; Xu, L.; Xiao, J. Tetrahedron Lett. 2001,
42, 4275. (f) Adams, D. J.; Chen, W.; Hope, E. G.; Lange, S.; Stuart, A.
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D. J. Org. Chem. 2004, 69, 3121. (h) Shirakawa, S.; Tanaka, Y.; Maruoka,
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† Chinese Academy of Sciences.
‡ Graduate School of Chinese Academy of Sciences.
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R. In Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994.
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E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999. (d) Lin, G.
Q.; Li, Y. M.; Chan, A. S. C. In Principles and Applications of Asymmetric
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10.1021/jo052092m CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/01/2006
2874
J. Org. Chem. 2006, 71, 2874-2877

properly choosing of organic solvent mixtures.9 These thermo-
morphic catalysts performed homogeneous catalytic reactions
and could be easily recovered by simple cooling or heating.
However, all these new approaches, to the best of our know-
ledge, have not been applied for asymmetric catalysis.
SCHEME 1. Synthesis of the Alkyl Chain-Tagged BINAP
Liganda
In this paper, we report the first example of a thermomorphic
system for asymmetric hydrogenation and liquid/solid separation
of the chiral catalyst.10 Our strategy employed alkyl “ponytails”
instead of the expensive fluorous ones as the “phase-tags” of
the immobilized chiral catalyst. This nonfluorous phase tagged
Ru(BINAP) catalyst shows temperature-dependent solubility in
1,4-dioxane/ethanol mixtures. This new system was applied for
the asymmetric catalytic hydrogenation of â-ketoesters and
exhibited both the advantages of very simple catalyst recycling
by liquid/solid-phase separation and high enantioselectivity due
to its homogeneous manner at high temperature.
a Reagents and conditions: (a) (PhO)3P, pyridine, CaCl2, NMP, 120 °C,
BINAP [2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] was
chosen as a model ligand for this study because it has proven
to be an excellent ligand for homogeneous catalysis in vari-
ous asymmetric hydrogenation reactions.1a,11 Considering that
BINAP itself could not be easily attached onto an organic
support via covalent chemical bond, 5,5′-diamino-BINAP 3 was
first synthesized according to a literature procedure.12 The
method used to prepare the alkyl chain-tagged BINAP ligand 1
was similar to that of dendritic BINAP described in our previous
reports.13 Condensation reaction of 3,4,5-trioctadecyloxybenzoic
acid 214 with 3 in the presence of triphenyl phosphite, pyridine,
and calcium chloride in N-methyl-2-pyrrolidone (NMP) at 120
°C gave 1 in 70% yield (Scheme 1). The ligand was purified
by flash chromatography under N2 atmosphere and characterized
6 h.
example, 100 mg of 1 was dissolved in 8 mL of 1,4-dioxane at
60 °C, while more than 96% of 1 was precipitated when the
mixture was cooled to 0 °C. Most importantly, in the solvent
mixture of 1,4-dioxane and ethanol (1:3, v/v), which was chosen
as the reaction solvent for the thermomorphic catalytic system
studied below, much lower solubility was observed at low
temperature (in this case, 98% of 1 could be precipitated after
being cooled). This significantly large temperature-dependent
solubility of ligand 1 in ethanol and 1,4-dioxane should allow
the efficient recycling of the catalyst by simple cooling.
We chose asymmetric hydrogenation of â-ketoesters as a
model reaction for evaluation of this thermomorphic catalytic
system.15,16 This is due to the following facts: (a) the re-
duced products are useful building blocks for the synthesis
of biologically active compounds and natural products; (b)
Ru(BINAP)-type complexes have proved to be excellent
catalysts for this asymmetric transformation; (c) such reactions
are usually carried out at high temperature.
The alkyl chain-tagged Ru(BINAP) catalyst Ru(II) was
prepared in situ by the reaction of ligand 1 with [RuCl2-
(benzene)]2 in DMF at 100 °C for 20 min.17 To choose the
proper solvent system, which meets the requirements of the
thermomorphic biphase catalysis, we first studied the solubility
of the Ru complex in the mixture of ethanol and 1,4-dioxane.
Ru[(S)-1] complex (3.6 mg) was dissolved in 0.5 mL of 1,4-
dioxane at 60 °C, and then the poor solvent, ethanol, was added
dropwise into the solution. The complex was dissolved until
the volume of the ethanol was up to 2 mL. Thus, a homogeneous
catalysis could be achieved over a range of 20-100% (v/v) of
1,4-dioxane in the mixture solvent at this temperature. Upon
1
by H, 13C, and 31P NMR, MALDI TOF mass spectrometry,
and element analysis. All results were in full agreement with
the designed structure.
The solubility of the alkyl chain-tagged BINAP was inves-
tigated by screening of several commonly used organic solvents.
It was found that ligand 1 was soluble in solvents of low to
moderate polarity such as hexane, dichloromethane, chloroform,
toluene, and THF at room temperature. In contrast, much lower
solubility was observed in higher polar solvents such as
methanol, ethanol, DMF, and 1,4-dioxane at ambient temper-
ature. It is noteworthy that a significant increase of solubility
in DMF or 1,4-dioxane at high temperature was observed. For
(9) (a) Bergbreiter, D. E.; Liu, Y. S.; Osburn, P. L. J. Am. Chem. Soc.
1998, 120, 4251. (b) Bergbreiter, D. E.; Osburn, P. L.; Wilson, A.; Sink,
E. M. J. Am. Chem. Soc. 2000, 122, 9058. (c) Bergbreiter, D. E.; Osburn,
P. L.; Frels, J. D. J. Am. Chem. Soc. 2001, 123, 11105. (d) Ko¨llhofer, A.;
Plenio, H. Chem. Eur. J. 2003, 9, 1416. (e) Mizugaki, T.; Murata, M.; Ooe,
M.; Ebitani, K.; Kaneda, K. Chem. Commun. 2002, 52. (f) Ooe, M.; Murata,
M.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126,
1604.
(10) Selected examples of thermomorphic system (liquid/solid) with
achiral catalysts, see: (a) Bergbreiter, D. E.; Chandran, R. J. Am. Chem.
Soc. 1987, 109, 174. (b) Bergbreiter, D. E.; Zhang, L.; Mariagnanam, V.
M. J. Am. Chem. Soc. 1993, 115, 9295. (c) Bergbreiter, D. E.; Case, B. L.;
Liu, Y. S.; Caraway, J. W. Macromolecules 1998, 31, 6053. (d) Barre, G.;
Taton, D.; Lastecoueres, D.; Vincent, J. M. J. Am. Chem. Soc. 2004, 126,
7764.
(15) (a) Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.;
Kumobayashi, H.; Akutagawa, S. J. Am. Chem. Soc. 1987, 109, 5856. (b)
Ager, D. J.; Laneman, S. A. Tetrahedron: Asymmetry 1997, 8, 3327. (c)
Wolfson, A.; Vankelecom, I. F. J.; Geresh, S.; Jacobs, P. A. J. Mol. Catal.
A: Chem. 2003, 198, 39. (d) Ratovelomanana-Vidal, V.; Girard, C.; Touati,
R.; Tranchier, J. P.; Hassine, B. B.; Genet, J. P. AdV. Synth. Catal. 2003,
345, 261. (e) Hu, A.; Ngo, H. L.; Lin, W. Angew. Chem., Int. Ed. 2004,
43, 2501.
(16) Selected recent examples of immobilized chiral catalysts for
asymmetric hydrogenation of â-ketoesters, see: (a) ter Halle, R.; Colasson,
B.; Schulz, E.; Spagnol, M.; Lemaire, M. Tetrahedron Lett. 2000, 41, 643.
(b) Guerreiro, P.; Ratovelomanana-Vidal, V.; Genet, J. P.; Dellis, P.
Tetrahedron Lett. 2001, 42, 3423. (c) Ngo, H. L.; Hu, A.; Lin, W. Chem.
Commun. 2003, 1912. (d) Berthod, M.; Saluzzo, C.; Mignani, G.; Lemaire
M. Tetrahedron: Asymmetry 2004, 15, 639.
(11) (a) Noyori, R. Acc. Chem. Res. 1990, 23, 345. (b) Tang, W. J.;
Zhang, X. M. Chem. ReV. 2003, 103, 3029.
(12) (a) Okano, T.; Kumobayashi, H.; Akutagawa, S.; Kiji, J.; Konishi,
H.; Fukuyama, K.; Shimano, Y. U.S. 4 705 895, 1987. (b) Huang, Y. Y.;
Deng, G. J.; Wang, X. Y.; Fan, Q. H. Chin. J. Chem. 2004, 22, 891.
(13) (a) Fan, Q. H.; Chen, Y. M.; Chen, X. M.; Jiang, D. Z.; Xi F.;
Chan, A. S. C. Chem. Commun. 2000, 789. (b) Deng, G. J.; Fan, Q. H.;
Chen, X. M.; Liu, D. S.; Chan, A. S. C. Chem. Commun. 2002, 1570.
(14) Percec, V.; Tomazos, D.; Heck, J.; Blackwell, H.; Ungar, G. J. Chem.
Soc., Perkin Trans. 2 1994, 34.
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J. Org. Chem, Vol. 71, No. 7, 2006 2875

SCHEME 2. Illustration of Sequenced Asymmetric
Hydrogenation of â-Ketoesters 4b and 4a by the
Thermomorphic System with Ru(1) in Solvent Mixture of
Ethanol/1,4-Dioxane and Catalyst Recycling via Liquid/
Solid-Phase Separation Showing the Complete Separation of
the Product in the First Run
FIGURE 1. Photographs of the alkyl phase-tagged Ru(BINAP) catalyst
in ethanol/1,4-dioxane (3:1) solvent at different temperatures: (A)
catalyst suspension (before heating); (B) homogeneous solution when
heating at 60 °C; and (C) catalyst precipitation after cooling to 0 °C
and centrifuging.
TABLE 1. Solvent Effect on Asymmetric Hydrogenation of
â-Ketoester 4a Catalyzed by Ru(1)a
entry
solvent
convb (%)
eeb (%)
1
2
3
4
5
6
7
8d
CH2Cl2
toluene
THF
1,4-dioxane
ethanol
ethanol/1,4-dioxane (1:1, v/v)
ethanol/1,4-dioxane (3:1, v/v)
ethanol
100 (>98)c
0
12
93.5
0
33.0
57.0
96.0
96.5
97.0
96.9
22
93 (81)c
100 (>98)c
100 (>98)c
100 (>98)c
lectivity and 100% conversion (entry 7). The ratio of two
solvents showed almost no effects on the catalyst performance
(entries 6 and 7). Therefore, we chose 3:1 ethanol and 1,4-di-
oxane as the optimizing solvent system for the later experiments.
We then turned our attention to investigating the facile
recovery of the alkyl chain-tagged Ru(BINAP) catalyst from
the reaction mixtures. As illustrated in Scheme 2, the unique
feature of this strategy was that the catalytic reaction was carried
out in a homogeneous manner, and the reaction mixture would
be separated into two phases (liquid/solid) by simple cooling
after the reaction. In the presence of 0.1 mol % of Ru(1), the
hydrogenation of 4b was first carried out under 40 atm H2
pressure at 60 °C for 24 h. Upon cooling to 0 °C and release of
H2, the catalyst was precipitated and isolated by centrifugation
or filtration as in the usual solid-supported catalytic reaction.
The first run reaction gave 5b with 100% conversion and 97%
ee, which was significantly higher that that of Ru catalyst
derived from fluorous phase-tagged BINAP derivative (up to
80% ee).5k The recovered catalyst was then used for the
hydrogenation of 4a under otherwise identical reaction condi-
tions. In the second run reaction, 100% conversion and 98% ee
were achieved without detecting any 5b (Scheme 2). It was thus
demonstrated that the reaction product could be completely
separated from the solid catalyst phase. In contrast, in the case
of liquid/liquid biphasic catalysis, a few products from the
previous run did remain in the catalyst-containing phase of the
next run.9,13b
a All reactions were carried out with a substrate concentration of 0.12
M (V ) 2 mL) under 40 atm of H2 at 60 °C for 24 h with 0.5 mol %
catalyst loading. b ee values and conversions were determined by GC on a
Chirasil-Dex CP 7502 (30 m × 0.25 mm) column. c Selectivity for 5a based
on GC analysis is shown in parentheses. d Catalyst Ru(BINAP) was used
instead of Ru(1).
cooling to 0 °C, it was found that ruthenium complex stayed
mainly in the solid phase of this thermomorphic system (Fig-
ure 1). The amount of the metal catalyst dissolved in the sol-
vent mixtures with different ratios was determined by using
ICP-MS. It was found that the ruthenium concentrations in
solvent of 1:1, 2:1, and 3:1 ethanol/1,4-dioxane (2 mL volume
in total) are 2.28 (96.2% recovery), 1.96 (96.7 recoevery), and
0.87 (98.6% recoevery) ppm, respectively. In the case of
increasing the amount of ethanol in the solvent mixture, slightly
lower catalyst solubility was observed.
To investigate the solvent effect, tert-butyl acetoacetate 4a
was chosen as the standard substrate for the asymmetric
hydrogenation. As shown in Table 1, the reaction proceeded
smoothly in dichloromethane with high enantioselectivity and
100% conversion (entry 1). In contrast, no activity was observed
in toluene. When the moderate polarity solvents such as THF
and 1,4-dioxane were used, low activities and low to moderate
enantioselectivities were obtained (entries 3 and 4). These results
are similar to those obtained by Ru(BINAP) reported by
Vankelecom.15c Performing the reaction in ethanol, which has
proven to be a good solvent for this type reaction, resulted in
high enantioselectivity and 93% conversion, albeit much lower
selectivity as compared to the Ru(BINAP) catalyst (81% vs >
98% as shown in entry 5 and entry 8). The insolubility of the
catalyst in ethanol leaded to low activity, and the acetal
formation as the byproduct was observed.15c It is noteworthy
that the thermomorphic catalytic system consisting of solvent
mixture of ethanol and 1,4-dioxane gave the highest enantiose-
Next, the recycling of catalyst Ru(1) was studied in the
asymmetric hydrogenation of 4a and 4b, respectively. As shown
in Table 2, catalyst Ru(1) could be used for at least four cycles
in both cases without any loss of enantioselectivity. To study
the activity of the recycled catalyst, we measured the TOF of
each catalytic run at 1 h reaction time. The results (Table 2)
indicated that the activity decreased slightly for the first three
runs but began to drop sharply at the fourth run. This loss of
2876 J. Org. Chem., Vol. 71, No. 7, 2006

TABLE 2. Recycle of the Catalyst for Asymmetric Hydrogenation
conversions except for 4g (60% conversion) by using 0.5 mol
% of Ru catalyst derived from ligand 1 at 60 °C. It should be
emphasized that the level of enantiocontrol for all â-aryl keto-
esters was higher than those obtained from the parent homo-
geneous Ru(BINAP) catalyst. For example, 4c was reduced to
5c with 92.9% ee by Ru(1) but 87.3% ee by Ru(BINAP) (entry
1). This enantioselectivity enhancement was probably due to
the steric effect of the 5,5′-substituents on BINAP, and a similar
but much more remarkable substituent effect was observed in
the case of 4,4′-substited BINAP derivatives.15e
In summary, a new BINAP derivative bearing alkyl ponytails
was synthesized and proven to be a highly effective ligand for
Ru-catalyzed hydrogenation of â-ketoesters in the mixture of
ethanol/1,4-dioxane. This nonfluorous phase-tagged catalyst
could be easily recovered by simple cooling and reused without
any loss of enantioselectivity. Since light alcohols have been
found to be the best solvents for most asymmetric hydrogenation
reactions, this system can be extended to other chiral phosphine-
containing catalysts. Thus, this strategy will lead to a general
method for separating products from homogeneous catalysts and
recovering the chiral catalysts by simple liquid/solid-phase
separation.
of â-Ketoesters 4a and 4ba
4a
4b
run
convb,c (%)
eeb (%)
convb (%)
eeb (%)
1
2
3
4
100 (92)
100 (85)
100 (70)
93 (25)
96.9
96.5
94.9
96.0
100
100
100
83
97.8
98.6
98.2
97.3
a All reactions were carried out with substrate concentration of 0.06 M
(1.5 mL of ethanol and 0.5 mL of 1,4-dioxane) under 40 atm of H2 at 60
°C for 10 h with 1 mol % catalyst loading. b ee values and conversions
were determined by GC on a Chirasil-Dex CP 7502 (30 m × 0.25 mm)
column. c Average TOF at lower than 100% conversion (after 1 h reaction)
is shown in parentheses.
TABLE 3. Asymmetric Hydrogenation of Various â-Aryl
Ketoesters Catalyzed by Ru(1)a
entry
substrate (R1/R2)
ee (%)
1
2
3
4
5
4c (H/Me)
4d (H/Et)
4e (Cl/Me)
4f (F/Me)
92.9 (87.3)b,d
91.1 (86.3)c,d
89.6 (86.6)c,d
87.3 (85.7)c,d
83.7 (82.5)c,d
Experimental Section
General Procedure for the Asymmetric Hydrogenation of
â-Ketoesters and the Catalyst Recycling. In a glovebox, to a
mixture of [RuCl2(benzene)]2 (3.0 mg, 0.006 mmol) in 2 mL of
freshly distilled and degassed DMF was added ligand (S)-1 (33.0
mg, 0.0135 mmol). The mixture was stirred at 100 °C for 20 min,
and DMF was removed under vacuum to give the Ru catalyst. Then
an autoclave containing a glass tube was charged with Ru(1) (3.6
mg, 1.2 × 10-3 mmol), â-ketoester (0.24 mmol) and 2 mL of
ethanol/1,4-dioxane (3:1, v/v) under N2 atmosphere. The autoclave
was closed and finally pressurized with hydrogen to 40 atm. After
being stirred at 60 °C for a certain time, the autoclave was cooled
to room temperature and the H2 was carefully released. The tube
in the autoclave was taken out in the glovebox and sealed. The
reaction mixtures were further cooled to 0 °C, and the precipitated
catalyst was isolated by centrifuging and washed with ethanol one
time. The solution was sucked out with a syringe and used for
product analysis. The recovered catalyst could be reused just as in
the first run. The enantiomeric purity of the product was determined
by GC on a Chirasil-Dex CP 7502 column.
4g (MeO/Me)
a All reactions were carried out with a substrate concentration of 0.12
M (1.5 mL of ethanol and 0.5 mL of 1,4-dioxane) under 40 atm of H2 at
60 °C for 24 h with 0.5 mol % catalyst loading. All reactions have >99%
conversion except for entry 5 (60% conversion). b The ee value was
determined by GC on a Chiraldex G-TA CA 73035 (50 m × 0.25 mm)
column. c The ee values were determined by GC on a Chirasil-Dex CP 7502
(30 m × 0.25 mm) column. d Data in parentheses was obtained from
Ru(BINAP) catalyst.
activity may not reflect the intrinsic instability of the thermo-
morphic Ru(1) catalyst. The catalyst recycling and reused
experiments were conducted without rigorous exclusion of air.
Thus, a few of the oxygen-sensitive ruthenium hydride species
could be oxidized, which may contribute to the loss of activity
of the recycled catalyst. On the other hand, after isolation of
the catalyst, the filtrate of 5a in 2 mL of ethanol/1,4-dioxane
was further employed for the catalytic hydrogenation of 4b
under the same experimental conditions. In this case, no product
of 5b was observed at all. In addition, the ICP-MS spectroscopic
analysis of the filtrate indicated that about 1.78% of Ru catalyst
has leached into the organic product. These results indicated
that the catalytically active ruthenium species could be ef-
fectively recovered under this biphasic condition.
Acknowledgment. We are grateful to the National Natural
Science Foundation of China, the Major State Basic Research
Development Program of China (2005CCA06600), the Chinese
Academy of Sciences (CAS), and Institute of Chemistry, CAS,
for financial support of this study.
Supporting Information Available: General experimental
information, BINAP ligand synthesis details, and characterization
data of the ligand and the reduced products. This material is
available free of charge via the Internet at http://pubs.acs.org.
Having established the facile catalyst recycling of this
thermomorphic catalytic system, we next examined a variety
of â-aryl ketoesters. As shown in Table 3, all substrates were
successfully hydrogenated with high ee values and complete
JO052092M
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