A novel system consisting of easily recyclable dendritic Ru-BINAP catalyst for asymmetric hydrogenation

Article abstract of DOI:10.1039/b203117e

Dendritic Ru-BINAP catalysts functionalized with alkyl chain at the periphery together with organic binary solvent system that exhibited phase separation induced by addition of a little water have been employed for asymmetric hydrogenation, leading to high catalytic activity and en-antioselectivity as well as facile catalyst recycling.

Full text of DOI:10.1039/b203117e

A novel system consisting of easily recyclable dendritic Ru-BINAP
catalyst for asymmetric hydrogenation†
Guo-Jun Deng,a Qing-Hua Fan,*a Xiao-Min Chen,a Dong-Sheng Liua and Albert S. C. Chan*b
a Center for Molecular Science, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100080,
P.R. China. E-mail: fanqh@infoc3.icas.ac.cn; Fax: 86-10-62559373
b Open Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology, The
Hong Kong Polytechnic University, Hong Kong, P.R. China
Received (in Cambridge, UK) 28th March 2002, Accepted 6th June 2002
First published as an Advance Article on the web 20th June 2002
Dendritic Ru-BINAP catalysts functionalized with alkyl
chain at the periphery together with organic binary solvent
system that exhibited phase separation induced by addition
of a little water have been employed for asymmetric
hydrogenation, leading to high catalytic activity and en-
antioselectivity as well as facile catalyst recycling.
unique properties and well-defined nanostructures of den-
drimer,10,11 we modified BINAP by incorporating it onto the
Fréchet-type dendrimer functionalized with alkyl chains at the
periphery so as to make its metal complexes exclusively soluble
in hydrocarbons at room temperature. To the best of our
knowledge, such a liquid–liquid phase separating system
including a dendrimer-bound chiral metal catalyst has not been
previously reported.
Homogeneous asymmetric catalysis is one of the most im-
portant developments in modern chemistry over the past several
decades.1 Transition metal complexes with diphosphine li-
gands, such as BINAP [2,2A-bis(diphenylphosphino)-1,1A-bina-
phthyl], have proved to be excellent homogeneous catalysts in
various asymmetric hydrogenation reactions.2 As these chiral
catalysts are often expensive, attempts have been made to
heterogenize these catalysts so as to reuse them as often as
possible. Different approaches to the heterogenization of chiral
catalysts have recently been reviewed.3 These included im-
mobilization of chiral metal complexes by anchoring the
catalyst on a solid support4 or by using a liquid–liquid two-
phase system.5 In most cases, however, the activity and
enantioselectivity of the immobilized catalysts were lower than
those of the parent homogeneous system as a result of mass
transfer limitations. Recently, two new strategies—soluble
polymer-supported catalyst systems6 and thermomorphic cata-
lyst systems7—have been highlighted as new options for
catalyst heterogenization so as to combine the advantages of
homogeneous catalysis and heterogeneous catalysis. The
unique feature of both strategies is that the catalytic reactions
were carried out in homogeneous manner (one phase) under
proper reaction conditions.8 The recovering of the thermo-
morphic catalyst could be realized via phase separation by
cooling the reaction mixture (two-phase). This strategy, how-
ever, was limited to high reaction temperature and, to our
knowledge, has not been applied for asymmetric catalysis.
Here, we reported a novel system for highly effective
asymmetric hydrogenation and liquid–liquid separation of the
catalyst (Scheme 1). Our strategy9 relies on the following two
ideas: (1) Some solvent pairs of non-polar hydrocarbons and
polar light alcohols, such as hexane and pure ethanol, are
completely miscible, but exhibit phase separation with the
addition of a little water. (2) The chiral catalyst should have a
strong phase preference under biphasic conditions. In this study,
we chose BINAP as a model ligand. Taking advantage of the
This system provided several key advantages: (a) Unlike the
thermomorphic system, this binary solvent system provided
complete miscibility of the phase over a broad range of reaction
temperature. (b) The organic binary solvent system avoided the
use of water which has often shown detrimental effect on the
enantioselectivity in the asymmetric hydrogenation. (c) Upon
completion of the reaction, the addition of very small amount of
water (only 2.5%) could induce phase separation and provided
facile catalyst recovery. (d) As compared to soluble polymer-
supported asymmetric catalysis, this strategy avoided the use of
large amounts of other solvents for catalyst precipitation.
Consequently, this system combines the advantages of homoge-
neous asymmetric catalysis and the traditional two-phase
catalysis: high catalytic activity and enantioselectivity, tailor-
made catalyst, facile phase separation and reuse of the
catalyst.
The preparation of new dendritic chiral BINAP ligands
(Scheme 2) was conducted according to our recently reported
procedure.11f Condensation reaction of 5,5A-diamino-BINAP
with the peripherally alkyl-functionalized polyether dendritic
wedges with carboxy group located at the focal point in the
presence of triphenylphosphite, pyridine, and calcium chloride
in N-methyl-2-pyrrolidone at 100 °C gave the chiral dendrimer
ligands in moderate reaction yield. These ligands were purified
1
by fast column chromatography and characterized by H and
31P NMR spectroscopy and MALDI-TOF mass spectrometry.
All results are in full agreement with the compounds synthe-
sized.
The dendritic Ru-BINAP catalysts were prepared in situ by
the reaction of dendritic BINAP ligand with [RuCl2(benzene)]2
Scheme 1 Illustration of the effective and recyclable catalyst system.
† Electronic supplementary information (ESI) available: synthesis details,
partition coefficients of dendritic BINAP ligands and their Ru complexes,
hydrogenation and recycling procedure. See http://www.rsc.org/suppdata/
cc/b2/b203117e/
Scheme 2
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This journal is © The Royal Society of Chemistry 2002

in DMF at 100 °C for 20 min. Their catalytic efficiency was
evaluated by choosing asymmetric hydrogenation of 2-ar-
ylacrylic acids, 2-phenylacryclic acid 1 and 2-[p-(2-methylpro-
pyl)phenyl]acrylic acid 2, as the model reactions. All dendritic
Ru-BINAP complexes were tested, and complete conversions
of 1 or 2 were obtained with high enantioselectivities in 4 h. The
preliminary results are summarized in Table 1. The dendritic
catalysts showed similar enantio-selectivity to Ru-BINAP. The
high catalytic activity and enantioselectivity were probably due
to the homogeneous nature of the reaction. The number of the
alkyl end groups of the dendritic wedges slightly influenced the
reaction performance and the results depended on the solubility
of the dendrimer in hexane.
As shown in Table 1, similar enantioselectivities were
obtained by using a mixture of ethanol/hexane in a different
ratio as solvent (entries 3–5). However, when using a mixture of
ethanol/hexane/H2O (1+1+0.05) as solvent, much lower conver-
sion and enantioselectivity were obtained in the hydrogenation
of 2 (entries 13 vs 14). This profound solvent effect was mainly
due to phase separation upon the addition of a little water, which
thus resulted in mass transfer limitations.
Another unique feature of this system was the facile catalyst
recycling via liquid–liquid biphasic separation technique. It was
found that these dendrimers with an alkyl-functionalized
periphery preferred to dissolve in a non-polar solvent system. In
the case of the second-generation dendrimer ligands AB2-G2
and AB3-G2, more than 99% of their Ru complexes could be
extracted to the non-polar hexane phase in a n-hexane/ethanol
(2.5% H2O) biphasic system. For example, upon completion of
the catalytic hydrogenation of 2, a small amount of water (2.5%)
was added to the reaction mixture to induce phase separation.
The hexane layer, which contained the catalyst AB2-G2-Ru
(about 99.3% of catalyst was recovered), was separated and
reused in the next round of reaction. The recovered catalyst gave
similar conversions in 2 h reaction times under 50 or 80 atm H2
with only slight loss of enantioselectivity over at least three
cycles (entries 15–18). In order to further demonstrate the
recovery of the catalyst, the colorless ethanol layer which
contained the reduced product was further used to catalyse the
hydrogenation of 1 under the same reaction conditions, but did
not, however, give any hydrogenated product.
In conclusion, peripherally alkyl-functionalized dendritic
Ru-BINAP catalysts have been synthesized and employed for
asymmetric hydrogenation using a mixture of ethanol/hexane as
reaction medium. The combination of chiral dendritic catalyst
and organic biphasic system provided high catalytic activity and
enantioselectivity as well as efficient and easy catalyst re-
cycling. Since light alcohols (e.g. ethanol and methanol) 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 of separating products from homoge-
neous catalysts and recovering the chiral catalysts by simple
liquid–liquid biphasic separation. The investigation of other
hydrogenation reactions and the extension of this strategy to
other chiral diphosphine systems are in progress.
We thank National Natural Science Foundation of China
(projects 20132010 and 29904009), CMS, Chinese Academy of
Sciences, and The Hong Kong Polytechnic University ASD
Fund for financial support of this study.
Notes and references
1 G. Q. Lin, Y. M. Li and A. S. C. Chan, Principles and Applications of
Asymmetric Synthesis, Wiley-Interscience, New York, 2001.
2 R. Noyori, Acc. Chem. Res., 1990, 23, 345.
3 Chiral Catalyst Immobilization and Recycling, ed.D. E. De Vos, I. F. J.
Vankelecom and P. A. Jacobs, Wiley-VCH, Weinheim, 2000.
4 Insoluble polymer-supported BINAP ligands, see: (a) D. J. Bayston, J.
L. Fraser, M. R. Ashton, A. D. Baxter, M. E. C. Polywka and E. Moses,
J. Org. Chem., 1998, 63, 3137; (b) R. ter Halle, B. Colasson, E. Schulz
and M. Lemaire, Tetrahedron Lett., 2000, 41, 643.
Table 1 Dendritic Ru-BINAP catalysed asymmetric hydrogenation and
catalyst recyclinga
5 Immobilized Ru-BINAP catalysts for biphasic hydrogenation, see: (a)
K. T. Wan and M. E. Davis, Nature, 1994, 370, 449; (b) Q. H. Fan, G.
J. Deng, X. M. Chen, W. C. Xie, D. Z. Jiang, D. S. Liu and A. S. C.
Chan, J. Mol. Catal. A: Chem., 2000, 159, 37; (c) R. A. Brown, P. Pollet,
E. McKoon, C. A. Eckert, C. L. Liotta and P. G. Jessop, J. Am. Chem.
Soc., 2001, 123, 1254.
6 Soluble polymer-supported BINAP ligands, see: (a) Q. H. Fan, C. Y.
Ren, C. H. Yeung, W. H. Hu and A. S. C. Chan, J. Am. Chem. Soc.,
1999, 121, 7407; (b) Q. H. Fan, G. J. Deng, C. C. Lin and A. S. C. Chan,
Tetrahedron: Asymmetry, 2001, 12, 1241; (c) H. B. Yu, Q. S. Hu and L.
Pu, J. Am. Chem. Soc., 2000, 122, 6500; (d) Q. H. Fan, G. H. Liu, G. J.
Deng, X. M. Chen and A. S. C. Chan, Tetrahedron Lett., 2001, 42,
9047.
7 For later examples of thermomorphic catalysts, see: (a) I. Horvath and
J. Rabai, Science, 1994, 266, 72; (b) D. E. Bergbreiter, P. L. Osburn, A.
Wilson and E. M. Sink, J. Am. Chem. Soc., 2000, 122, 9058; (c) D. E.
Bergbreiter, P. L. Osburn and J. D. Frels, J. Am. Chem. Soc., 2001, 123,
11105; (d) T. Mizugaki, M. Murata, M. Ooe, K. Ebitani and K. Kaneda,
Chem. Commun., 2002, 52.
bConv.
H2 (atm) Time (h) (%)
Entry Sub. Ligand
bE.e. (%)
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
(R)-BINAP
AB2-G1
AB2-G2
AB2-G2
AB2-G2
AB3-G1
AB3-G2
(R)-BINAP
AB2-G1
AB2-G2
AB3-G1
AB3-G2
AB3-G1
AB3-G1
80
80
80
80
80
80
80
80
80
80
80
80
80
80
4
4
4
4
4
4
4
4
4
4
4
4
2.5
2.5
2
2
2
100
100
100
100
100
100
100
100
100
100
100
100
95
87
88
87
86
85
88
84
89
90
90
90
89
91
80
2
3
4c
5d
6
7
8
9
10
8 R. T. Baker and W. Tumas, Science, 1999, 284, 1477.
9 Similar strategy has been applied to hydroformylation of higher olefins,
see: A. G. Abatjoglou, R. R. Peterson and D. R. Bryant, Chem. Ind.,
1996, 68, 133.
10 For comprehensive reviews on dendritic organometallic catalysts, see:
(a) G. E. Oosterom, J. N. H. Reek, P. C. J. Kamer and P. W. N. M. van
Leeuwen, Angew. Chem., Int. Ed., 2001, 40, 1828; (b) D. Astruc and F.
Chardac, Chem. Rev., 2001, 101, 2991.
11 For later examples of chiral dendritic catalysts, see: (a) Q. S. Hu, V.
Pugh, M. Sabat and L. Pu, J. Org. Chem., 1999, 64, 7528; (b) H. Seller,
C. Faber, P. B. Rheiner and D. Seebach, Chem. Eur. J., 1999, 5, 3692;
(c) C. Köllner, B. Pugin and A. Togni, J. Am. Chem. Soc., 1998, 120,
10274; (d) R. Breinbauer and E. N. Jacobsen, Angew. Chem., Int. Ed.,
2000, 39, 3604; (e) Y. C. Chen, T. F. Wu, J. G. Deng, H. Liu, Y. Z. Jiang,
M. C. K. Choi and A. S. C. Chan, Chem. Commun., 2001, 1488; (f) Q.
H. Fan, Y. M. Chen, X. M. Chen, D. Z. Jiang, F. Xi and A. S. C. Chan,
Chem. Commun., 2000, 789; (g) Q. H. Fan, G. H. Liu, X. M. Chen, G.
J. Deng and A. S. C. Chan, Tetrahedron: Asymmetry, 2001, 12, 1559.
11
12
13
14e
15
16
17
18
38
AB2-G2 (run 1)f 50 (80)
AB2-G2 (run 2)f 50 (80)
AB2-G2 (run 3)f 50 (80)
AB2-G2 (run 4)f 50 (80)
72 (94) 84 (90)
70 (93) 84 (90)
69 (93) 81 (89)
68 (91) 82 (89)
2
a Reaction conditions: sub./cat. = 100 (mol/mol); NEt3/sub. = 3+2 (mol/
mol); rt. b Based on GC analysis. The absolute configuration of product is
(R). c A mixture of hexane/ethanol = 2+3 (v/v) was used as solvent. d A
mixture of hexane/ethanol = 3+2 (v/v) was used as solvent. e Hydrogen-
ation was carried out under two-phase condition by using a mixture of
hexane/ethanol/H2O = 1+1+0.05 (v/v) as solvent. f Hydrogenation was
carried out under 50 and 80 atm H2 using recovered catalyst.
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