Aqueous enantioselective hydrogenation of methyl 2-acetamidoacrylate with Rh-MeduPHOS occluded in PDMS

Article abstract of DOI:10.1039/b109234k

A new chiral heterogeneous catalytic system obtained by occlusion of the Rh - MeDuPHOS complex in a polydimethylsiloxane film was tested in the asymmetric hydrogenation of methyl 2-acetamidoacrylate in aqueous medium.

Full text of DOI:10.1039/b109234k

Aqueous enantioselective hydrogenation of methyl 2-acetamidoacrylate
with Rh–MeDuPHOS occluded in PDMS
Adi Wolfson,a Sofie Janssens,b Ivo Vankelecom,b Shimona Geresh,*c Moshe Gottlieba and Moti
Herskowitza
a Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
b Center for Surface Chemistry and Catalysis, Faculty of Agricultural and Applied Biological Sciences,
Catholic University, Leuven, Belgium
c
Institute for Applied Biosciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
E-mail: geresh@bgumail.bgu.ac.il
Received (in Cambridge, UK) 10th October 2001, Accepted 21st November 2001
First published as an Advance Article on the web 7th February 2002
A new chiral heterogeneous catalytic system obtained by
occlusion of the Rh–MeDuPHOS complex in a poly-
dimethylsiloxane film was tested in the asymmetric hydro-
genation of methyl 2-acetamidoacrylate in aqueous me-
dium.
The chiral complex was heterogenized by occlusion in a
PDMS film as previously reported.15,16 Before curing, a
weighed amount of silica (Hi-sil 233, Cabot, predried at 120 °C)
was stirred into a mixture of PDMS and cross-linker in
dichloromethane, followed by the addition of Pt catalyst (for
cross-linking). Approximately 10 mmol of Rh–MeDuPHOS in a
small volume of dichloromethane ( ~ 2 mL) was added
dropwise to the PDMS solution. After 20 to 30 min, the
homogeneous solution obtained was poured into a Petri dish to
allow slow evaporation of the solvent and subsequent curing.
Curing time of 5–6 h resulted in a ~ 1000 mm thick membrane.
Leaching of the complex and solvent sorption were evaluated
by immersing 2 g of the catalyst-entrapped PDMS film in 20 mL
of various solvents. The extent of leaching of the metal complex
from the polymer matrix was measured by analyzing the liquid
phase on a PQ3/VG ICP-MS system with an accuracy of ~ 1
ppt. The sorption of the solvents was determined by weighing
the film pieces before and after immersion in the solvent.
The asymmetric hydrogenation of methyl 2-acetamidoacry-
late, a precursor of an alanine derivative, was selected as a test
reaction (Scheme 1). A 25 mL reactor with a magnetic stirrer
was used for both the homogeneous and the heterogeneous
reactions. In heterogeneously catalyzed reactions, the film was
added as pieces to the reaction medium under nitrogen
atmosphere. Samples were withdrawn periodically to determine
the reaction rate, and the enantiomeric excess as a function of
time. The samples were analyzed by a Hewlet Packard GC on a
chiral 7503 WCOT fused silica column (CP-Chiracil-Dex CB).
Reuse of the catalyst was tested by replacing the liquid phase
reaction and washing the PDMS film with the reaction solvent
before addition of new substrate.
Over the past 30 years,1 economic incentives2 and scientific
challenges have led to significant progress in the R&D of
enantioselective homogeneous and heterogeneous catalysts for
the production of pure enantiomers from prochiral substrates.
Transition metal complexes with biphosphine ligands, such as
BINAP [2,2-bis(diphenylphosphino)-1,1A-binaphthyl]3–5 and
DuPHOS [1,2-bis(phospholano)benzene],6–8 have proved to be
excellent homogeneous catalysts in various asymmetric hydro-
genation reactions. Attempts have been made to heterogenize
these complexes so as to combine advantages of heterogeneous
catalysts (high stability, facile catalyst recycling, and the
possibility for continuous operation) with the inherent advan-
tages of homogeneous catalysis (high activity and enantiose-
lectivity).
Different approaches to the heterogenization of chiral metal
complexes have recently been reviewed.9,10 These include
immobilization of chiral transition metal complexes via cova-
lent bonding to organic11 and inorganic12 supports or via ionic
interactions.13 Potential alternatives to these methods are
entrapment of metal complexes in silica matrices by sol–gel
methods14 or occlusion of the complexes in polydimethylsilox-
ane (PDMS) films.15,16 A disadvantage of the methods
described above for heterogenization of the catalysts is that
recyling is impeded by leaching of the metal complex and/or
loss of activity and enantioselectivity.9,10
Most organic chemical reactions take place in organic
solvents, but the advantages of being able to use water as the
solvent are self-evident: water is cheap, environmentally benign
and non-hazardous. To the best of our knowledge, this paper
reports the first successful asymmetric hydrogenation in an
aqueous medium by means of the Rh–MeDuPHOS complex
(Fig. 1) occluded in a PDMS matrix. The entrapped catalyst is
well dispersed in the polymer matrix, and the strongly
hydrophobic polymer selectively sorbs the organic substrate
from the reaction mixture to facilitate the reaction.
Selection of the solvent is a key element in the development
of the heterogeneous catalytic system. In our previous study,16
we focused on the preparation of the optimal polymer film with
respect to catalytic activity. In this work, we dealt with the
problem of catalyst leaching by choosing the type of solvent for
the reaction so as to minimize leaching while preserving the
activity and enantioselectivity of the catalyst. However, addi-
Table 1 Leaching of Rh–MeDuPHOS from PDMS films with 20 wt% silica
and sorption of solvents in the polymer film (Conditions: 10 mmol of Rh–
MeDuPHOS, 20 mL solvent, 25 °C, 24 h)
Sorption of
Solubility of the solvent
complex
in solvent
in PDMS
(g/g)
%
Solvent
Leaching
Methanol
Dichloromethane
Xylene
Heptane
Water
Xylene + methanol (10+1, v/v)
Water + methanol (10+1, v/v)
High
High
Low
Low
Low
—
0.049
1.152
1.177
1.456
0.065
0.954
0.063
31
52
2.9
0.7
0.9
65
1
—
Fig. 1 Rh–MeDuPHOS complex.
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CHEM. COMMUN., 2002, 388–389
This journal is © The Royal Society of Chemistry 2002

Table 2 Enantioselective hydrogenation of methyl 2-acetamidoacrylate with Rh–MeDuPHOS complex occluded in a PDMS film (Reaction conditions:
25 °C, 2 bars, 0.1 g methyl 2-acetamidoacrylate, 10 mmol catalyst, 15 mL solvent)
Sorption of the
solvent in
PDMS (g/g)
Catalyst
Solvent
TOF (h21 a
)
Ee (%)
Homogeneous RhMeDuPhos
Homogeneous RhMeDuPhos
Methanol
Methanol/waterb
Water
Water
Water
—
—
320
210
9.9
10.6
12.6
12.6
99.1
99.0
93.1
92.8
96.9
91.1
0
RhMeDuPhos/PDMS (10 wt% Si)
RhMeDuPhos/PDMS (15 wt% Si)
RhMeDuPhos/PDMS (20 wt% Si)
RhMeDuPhos/PDMS (20 wt% Si) (Reuse)c
Pt catalyst/PDMS (10 wt% Si)d
0.035
0.037
0.049
0.049
0.035
Water
Water
100
a After 3 h. b 9 mL methanol and 9 mL water. c Reuse of the catalysts from previous entry. d 0.4 mmol extra platinum crosslinking catalyst instead of Rh–
MeDuPhOS.
was replaced with additional Pt catalyst, leading to a complete
loss of enantioselectivity in the film. The low activity of the
PDMS occluded catalysts is probably a result of mass-transfer
limitations in the 1 mm thick film.
Scheme 1 Asymmetric hydrogenation of methyl 2-acetamidoacrylate
catalyzed by Rh–MeDuPHOS complex in PDMS.
The catalytic activity could be increased by increasing the
content of silica in the film. The presence of silica probably
attracted water, leading to a higher amount of substrate into the
tional considerations were taken into account, since in some
film. Increasing the silica content up to 20 wt% substantially
cases the solvent acts as a temporary ligand in the catalytic
increased the water sorption. With a content of silica above
cycle.3 We found that leaching occurred with all the solvents
20 wt%, a brittle film was obtained. A slight decrease in
that dissolved the catalyst, even when the degree of sorption of
enantioselectivity was observed in the reuse of the heteroge-
the solvent by the polymer film was very low (e.g. methanol), as
neous catalyst, but without loss of activity. Dissolved oxygen
shown in Table 1. Poor solvents for the complex like water,
may be the reason for the reduction in enantiometric excess
heptane or xylene yielded negligible leaching. However, when
between runs. The possibility of a homogeneous-catalyzed
methanol was added to xylene, leaching was very high,
reaction due to the low leaching in water was excluded since by
probably due to the good solubility of the complex in methanol
adding fresh substrate to a filtrate from a reaction at low
and high degree of swelling of the PDMS film in xylene. The
conversion no asymmetric hydrogenation of the enamide was
results of sequential replacement of methanol or water every 24
detected.
h (typical reaction time) are shown in Fig. 2. The potential
In conclusion, the ability to heterogenize a transition metal
advantage of water as solvent in this reaction is evident.
complex by occlusion in a polymer film, with a non-dissolving
solvent as the reaction medium, is reported for the first time and
is demonstrated for the water/Rh–MeDuPHOS/PDMS system.
Due to the insolubility of the transition metal complex in water,
the reported catalytic system is truly recyclable and thus
represents an excellent example of ‘green’ chemistry.
Notes and references
1 R. A. Sheldon, Chirotechnology, Marcel Dekker Inc., New York,
1993.
2 S. C. Stinson, Chem. Eng. News, 2000, 23, 55.
3 R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley,
New York, 1994.
4 K. Mashima, K. Kusano, N. Sato, Y. Matsumura, K. Nozaki, H.
Kumobayashi, N. Sayo, Y. Hori, T. Ishizaki, S. Akutagawa and H.
Takaya, J. Org. Chem., 1994, 59, 3064.
5 S. Akutagawa, ‘Asymmetric Synthesis by Metal BINAP Catalysts’,
Appl. Catal., 1995, 128, 171.
Fig. 2 Cumulative leaching of the complex in (-) methanol and (5) water.
(10 mmol of Rh–MeDuPHOS occluded in 1 g of PDMS films with 20 wt.%
silica.)
6 M. J. Burk, ChemTracts-Org. Chem., 1998, 11, 787.
7 M. J. Burk, J. Am. Chem. Soc., 1991, 113, 8518.
8 M. J. Burk, J. Am. Chem. Soc., 1995, 117, 4423.
9 K. Fodor, S. G. A. Kolmschot and R. A. Sheldon, Enantiomer, 1999, 4,
497.
10 P. A. Jacobs, I. F. J. Vankelecom and D. De Vos, Chiral Catalyst
Immobilisation and Recycling, Wiley-VCH, Weinheim, Germany,
2000.
11 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.
12 B. F. G. Johnson, S. A. Raynor, D. S. Shephard, T. Machmeyer, J. M.
Sanker, S. G. Bromley, R. Oldroyd, L. Gladden and M. D. Mantle,
Chem. Commun., 1999, 1167.
13 D. Tas, D. Jeanmart, R. F. Parton and P. Jacobs, Stud. Surf. Sci. Catal.,
1997, 108, 493.
A series of catalytic experiments were thus carried out in an
aqueous medium (Table 2). A blank reaction was carried out
with pure catalyst in water. No reaction took place. Although
addition of water to methanol in a homogeneous reaction (entry
2) decreased the reaction rate, the enantioselectivity of the
reaction was not affected. The data shown in Table 2 indicate
that reactions carried out in aqueous systems with the PDMS
occluded RhMeDuPhos catalysts yielded excellent results in
terms of enantioselectivity of the catalyst. A comparison cannot
be made with the analogous homogeneous system, since the
complex does not dissolve in water. However, the activity and,
to a lesser extent, the enantioselectivity are lower for the
heterogeneous system. A possible reason for the small decrease
in the enantiomeric excess is the symmetric reduction of methyl
2-acetamidoacrylate by the platinum catalyst used to catalyze
the crosslinking reaction of the PDMS film. Evidence for this
was provided by an experiment in which the Rh–MeDuPHos
14 F. Gelman, D. Avnir, H. Schumann and J. Blum., J. Mol. Catal., 1999,
146, 123.
15 I. F. J. Vankelecom and P. A. Jacobs, Catal. Today, 1999, 1, 1905.
16 I. Vankelecom, A. Wolfson, S. Geresh, M. Landau, M. Gottlieb and M.
Herskowitz, Chem. Commun., 1999, 2407.
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