Highly effective soluble polymer-supported catalysts for asymmetric hydrogenation [2]

Full text of DOI:10.1021/ja9837497

J. Am. Chem. Soc. 1999, 121, 7407-7408
7407
Highly Effective Soluble Polymer-Supported
Catalysts for Asymmetric Hydrogenation
Qing-hua Fan, Chang-yu Ren, Chi-hung Yeung,
Wen-hao Hu, and Albert S. C. Chan*
Union Laboratory of Asymmetric Synthesis and
Department of Applied Biology and
Chemical Technology
Figure 1. The synthesis of chiral polyester-supported BINAP ligands.
The Hong Kong Polytechnic UniVersity
Hong Kong, China
mixture through the manipulation of several different solvents
including diethyl ether was still inconvenient. A disadvantage of
the use of poly(ethylene glycol) support was that it limited the
binding site of the ligand to the terminals of the polymer and
consequently limited the possible interactions of the polymer
support with the catalyst. In this study, we developed a new type
of polymer-supported catalysts which offered better rate of
reaction than the corresponding monomeric homogeneous catalyst
while retaining the high stereoselectivity. This new approach also
offered opportunities for the study of polymer-catalyst interaction
in the supported chiral phosphine-containing catalysts.9
In choosing a model ligand for this study, we noticed that
among all the known chiral phosphine ligands which had been
studied for asymmetric catalysis, BINAP was probably the most
versatile and effective.10 Both rhodium and ruthenium BINAP
complexes have been extensively studied and several commercial
processes based on these catalysts have been developed.11 An
innovative attempt to immobilize this class of catalysts was the
use of “supported aqueous-phase catalysis” in which the sul-
fonated form of the complex was dissolved in a thin ethylene
glycol film that was adhered to a high-surface-area hydrophilic
support.12 However, the system was restricted in the choice of
possible substrates and solvents, and the supported catalyst showed
lower catalytic activity in comparison to the corresponding “free”
catalyst. Recently, Vankelecom and co-workers13 reported another
approach to immobilized BINAP complexes via the occlusion of
the catalyst in a poly(dimethylsiloxane) membrane. The system,
however, was also restricted in the choice of possible substrates
and showed lower enantioselectivity and activity. In this paper,
we report the first example of the soluble polymer-supported chiral
phosphine-containing catalyst, which showed higher activity
than the corresponding “free” catalyst while retaining the high
stereoselectivity.
ReceiVed October 27, 1998
Homogeneous asymmetric catalysis is one of the most impor-
tant developments in modern chemistry over the past three
decades. Many chiral catalysts are known to exhibit high activities
and enantioselectivities.1 However, a major problem associated
with most homogeneous catalyst systems is the separation and
recycling of the expensive chiral catalyst. A possible solution to
this problem is to “heterogenize” a homogeneous catalyst, either
by anchoring the catalyst on a solid support or by using a liquid-
liquid two-phase system. Over the past two decades, the studies
of insoluble polymer-supported catalysts have attracted much
attention.2,3 Unfortunately, despite the advantage of easy separa-
tion, the use of insoluble polymer-supported catalysts suffered
from lowered catalytic activity and stereoselectivity due to the
restriction of the polymer matrix which resulted in limited mobility
and accessibility of the active sites. The leaching of the noble
metal catalyst from the polymer support was also a significant
problem. Recently, some progress on using polymer-supported
heterogeneous catalysts has been made in the areas such as
asymmetric dihydroxylation,4 epoxidation,5 and hydrogenation.6
However, the significant decline of catalytic activity and/or
enantioselectivity of the catalysts was still the major obstacle of
this approach. Thus the development of a novel polymeric catalyst
with high activity and enantioselectivity without leaching of
catalytic species is highly desirable. For this purpose, we have
designed and developed a highly effective polymer-supported
chiral catalyst by using the concept of “one-phase catalysis and
two-phase separation”. This class of catalysts combines the
advantages of homogeneous and heterogeneous catalysis: high
catalytic activity and stereoselectivity with easy separation and
convenient recycle of the polymer-supported catalyst from the
reaction mixture. Because of the possible positive influence of
the polymer support on the rate and/or stereoselectivity of the
catalyst, the successful use of soluble polymer as chiral catalyst
support may open up a new area for active research. Recently,
cinchona alkaloid-type ligands were anchored on soluble poly-
(ethylene glycol) and showed similar catalytic activity and
selectivity as compared to the corresponding free catalysts in the
osmium-catalyzed asymmetric dihydroxylation of unfunctional
olefins.7,8 This finding was highly interesting, even though the
separation of the polymer-supported ligands from the reaction
Since BINAP itself cannot be easily attached to a polymer
support, 5,5′-diamino-BINAP (1)14 was used for this study.
Polymer-supported BINAP ligands (2 or 3) were synthesized by
the polycondesation of (S)-1 or (R)-1, terephthaloyl chloride, and
(2S,4S)-pentanediol in the presence of pyridine in 1,2-dichloro-
ethane (Figure 1). A model compound of small molecule 4 (5,5′-
dibenzamido-BINAP) was also synthesized by reacting (S)-1 with
benzoyl chloride in the presence of pyridine in dichloromethane
for the purpose of comparison. The chiral polyester-supported
BINAP ligands (2 or 3) were soluble in common nonprotic organic
solvents such as toluene, THF, and dichrolomethane, but quan-
titatively precipitated upon the addition of methanol. The ligands
(1) Parshall, G. W.; Ittel S. D. Homogeneous catalysis, 2nd ed.; Wiley:
New York, 1992.
(2) Hartley, F. R. Supported metal complexes,; Ugo, R., James, B. R., Eds.;
Reidel: New York, 1985.
1
were characterized by H and 31P NMR. The molecular weights
(3) Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K. Synthesis 1997, 1217-
of the polyester-supported ligands (2 or 3) were determined by
1239.
(4) Song, C. E.; Yang, J. W.; Ha, H. J.; Lee, S.-G. Tetrahedron: Asymmetry
1996, 7, 645-648.
(5) (a) Minutolo, F.; Pini, D.; Petri, A.; Salvadori, P. Tetrahedron:
Asymmetry 1996, 7, 2293-2302. (b) Minutolo, F.; Pini, D.; Salvadori, P.
Tetrahedron Lett. 1996, 37, 3375-3378.
(9) Fan, Q. H.; Yeung, C. H.; Li, Y. C.; Chan, A. S. C. Abst. Pap. Am.
Chem. Soc. 1997, 213, 219-Inor.
(10) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345-350.
(11) Noyori, R. Chemtech 1992, 360-367.
(6) Bayston, D. J.; Fraser, J. L.; Ashton, M. R.; Baxter, A. D.; Polywka,
M. E. C.; Moses, E. J. Org. Chem. 1998, 63, 3137-3140.
(7) Han, H.; Janda, K. D. J. Am. Chem. Soc. 1996, 118, 7632-7633.
(8) Bolm, C.; Gerlach, A. Angew Chem., Int. Ed. Engl. 1997, 36, 741-
743.
(12) Wan, K. T.; Davis, M. E. Nature 1994, 370, 449-450.
(13) Vankelecom, Ivo. F. J.; Tas, D.; Parton, R. F.; Van de Vyver, V.;
Jacobs, P. A. Angew. Chem., Int. Ed. Engl. 1996, 35, 1346-1348.
(14) Okano, T.; Kumobayashi, H.; Akutagawa, S.; Kiji, J.; Konishi, H.;
Fukuyama, K.; Shimano, Y. U.S. Patent 4 705 895, 1987
10.1021/ja9837497 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/30/1999

7408 J. Am. Chem. Soc., Vol. 121, No. 32, 1999
Communications to the Editor
Figure 2. A plot of conversion and ee values vs the number of recycles
in the asymmetric hydrogenation of 5 catalyzed by polyester-supported
Ru(BINAP).
Figure 3. The comparison of the rates of hydrogenation catalyzed by
Ru-(2), Ru-(4), and Ru-(S)-BINAP.
gel permeation chromatography (GPC). The detailed experimental
data are summarized in the Supporting Information. BINAP
attached to polymer support by copolymerization provided several
key advantages: (1) facile control of the incorporation of BINAP
in the polymer chains and (2) easy adjustment of the nature of
the polymer matrix (configuration of chiral center on the polymer
chain, rigidity, polarity, etc.) by using suitable comonomers, which
offered an opportunity to study the “polymer effect” and to fine-
tune the catalyst.
Table 1. Studies of the Polymer Effect on the Asymmetric
Hydrogenation of 5a
entry
catalyst (prepared in situ)
time, h conv, %b ee, %b
1
2
3 + [Ru(cymene)Cl2]2
2 + [Ru(cymene)Cl2]2
18
12
12
36
48
4
100
97.4
100
99.8
94.7
95.4
64.2
56.5
92.9 (R)
93.6 (S)
93.3 (S)
93.5 (S)
93.5 (S)
87.7 (S)
89.2 (S)
88.7 (S)
3c 2 + [Ru(cymene)Cl2]2
4
5
6
7
8
4 + [Ru(cymene)Cl2]2
(S)-BINAP + [Ru(cymene)Cl2]2
2 + [Ru(cymene)Cl2]2
We chose the asymmetric hydrogenation of 2-(6′-methoxy-2′-
naphthyl)acrylic acid (5) as the model reaction. This choice was
4 + [Ru(cymene)Cl2]2
4
4
(S)-BINAP + [Ru(cymene)Cl2]2
a The hydrogenation was carried out in 0.026 M 5 in methanol-
toluene (2:3, v/v) solution (except for entry 3) under the following
conditions: Sub./Cat. ) 200 (mol/mol); NEt3/Sub. ) 1:1 (mol/mol);
H2 ) 110 kg/cm2 except for entries 6-8 (69 kg/cm2). reaction
temperature ) 1-2 °C except for entries 6-8 (room temperature).
b Determined by HPLC analysis using a SUMICHIRAL OA-2500
column. c Methanol/toluene ) 1:3, v/v; other conditions were identical
to those listed in footnote a.
based on the fact that Ru(BINAP)-type catalysts were effective
in the asymmetric hydrogenation of 2-arylacrylic acids and the
reduced products represented an important class of antiinflam-
matory drugs. The product (naproxen) in this particular reaction
is a high-value antiinflammatory drug with annual sales of $600
million. The catalyst, which was conveniently prepared in situ
from polyester-supported BINAP ligand (1) and [Ru(cymene)-
Cl2]2 in a methanol-toluene (2:3, v/v) mixed solvent system, was
completely homogeneous. The hydrogenation of 5 with a substrate/
catalyst molar ratio of 200 and under 69.0 kg cm-2 H2 pressure
at room temperature gave 95.5% conversion and 87.7% ee in 4
h. When the methanol-toluene (9:1, v/v) solvent system was used,
the same reaction under otherwise identical conditions gave only
37.5% conversion and 80.5% ee in 60 h. The profound solvent
effect was due to the insolubility of the polyester-supported
catalysts in the solvent system with a high level of methanol.
These results are consistent with the rationale of designing soluble
polymer-supported chiral catalysts.
The different solubility of the chiral polyester-supported BINAP
ligands in different types of solvents provided a convenient and
reliable method for the separation and recovery of the polymeric
catalysts. Upon completion of the catalytic hydrogenation, meth-
anol was added to the reaction mixture and the catalyst was
quantitatively precipitated, filtered, and reused. The filtrate con-
tained the hydrogenation product, and the Ru content in the filtrate
was found to be below 16 ppb according to atomic absorption
measurement (detection limit). In repeated experiments, the poly-
ester-supported catalyst was found to maintain the same activity
and enantioselectivity after more than 10 recycles (Figure 2).
The positive influence of the polymer support on the catalyst
is another potential advantage of the soluble polymer-supported
catalyst and is of high scientific and practical interest. For
comparison, ligand 4 was synthesized as a homogeneous mon-
omeric analogue of the polymer-supported ligand. The results of
the comparison study are shown in Figure 3, which clearly
revealed the positive influence of the support on catalytic activity.
The polyester-supported catalyst was found to be substantially
more active as compared to the corresponding monomeric catalyst.
This effect was probably due to the cooperation of the polyester
backbone and the BINAP ligand, in which the polyester chains
serve as large substituents on the BINAP ligand. The steric effect
of these large substituents affected the dihedral angle of the
binaphthyl rings in the Ru(BINAP) complex, which consequently
gave faster rate of reaction. Similar acceleration effects have been
observed in the asymmetric hydrogenation of unsaturated car-
boxylic acids catalyzed by Ru(II) catalysts containing H8-BINAP15
or bis-steroidal phosphine,16 which possessed a larger steric
hindrance than that of BINAP. It was also observed that while
the rate of hydrogenation was faster with the polymer-supported
catalyst the high ee of the product was maintained (Table 1).
In conclusion, we have developed a new, highly efficient
polymer-supported chiral catalyst that showed higher catalytic
activity as compared to the free corresponding catalysts. This
study opens up a new frontier for the development of highly
effective and easily separated chiral catalysts. We believe this
new technique will have the potential not only for laboratory-
scale research but also for industrial applications.
Acknowledgment. We thank The Hong Kong Polytechnic University
and The Hong Kong Research Grant Council (Project No. HKP 24/95P)
for financial support of this study.
Supporting Information Available: Experimental details for the
characterization of the modified BINAP ligands, the synthesis of polyester-
supported ligands 2 and 3, and procedures for the hydrogenation and
recycling of catalysts (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
JA9837497
(15) Uemura, T.; Zhang, X.; Matsumura, K.; Sayo, N.; Kumobayashi, H.;
Ohta, T.; Nozaki, K.; Takaya, H. J. Org. Chem. 1996, 61, 5510-5516.
(16) Enev, V.; Ewers, C. L. J.; Harre, M.; Nickisch, K.; Mohr, J. T. J.
Org. Chem. 1997, 62, 7092-7093.