Heterogenization of Rh-MeDuPHOS by occlusion in polyvinyl alcohol films

Article abstract of DOI:10.1016/S0957-4166(02)00083-6

A new recyclable chiral heterogeneous catalytic system was obtained by the occlusion of Rh-MeDuPHOS in polyvinyl alcohol film. Enantiomeric excess of up to 96% was achieved in the asymmetric hydrogenation of methyl 2-acetamidoacrylate in aqueous medium.

Full text of DOI:10.1016/S0957-4166(02)00083-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 465–468
Heterogenization of Rh-MeDuPHOS by occlusion in polyvinyl
alcohol films
Adi Wolfson,a Shimona Geresh,a,c,* Moshe Gottliebb and Moti Herskowitza
aBlechner Center for Industrial Catalysis and Process Development, Department of Chemical Engineering,
Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
bStadler Minerva Center for Mesoscopic Macromolecule Engineering, Department of Chemical Engineering,
Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
cInstitute for Applied Biosciences, Department of Biotechnology Engineering, Ben-Gurion University of the Negev,
Beer-Sheva 84105, Israel
Received 9 December 2001; accepted 15 February 2002
Abstract—A new recyclable chiral heterogeneous catalytic system was obtained by the occlusion of Rh-MeDuPHOS in polyvinyl
alcohol film. Enantiomeric excess of up to 96% was achieved in the asymmetric hydrogenation of methyl 2-acetamidoacrylate in
aqueous medium. © 2002 Elsevier Science Ltd. All rights reserved.
resides in a different phase from the substrate and/or
1. Introduction
product.6,7
The use of immobilized homogeneous catalysts is of
The Rh-MeDuPHOS complex (Fig. 1) has been found
continuing interest. Polymer-supported chiral catalysts
to be a very active and a most efficient enantioselective
for high throughput synthesis such as dihydroxylation
complex in the homogeneous asymmetric reduction of
of olefins with microencapsulated osmium tetroxide,1
enamides to chiral amino acid derivatives.8,9 In our
allylic substitution and Suzuki coupling using microen-
ongoing study of the heterogenization of homogeneous
capsulated palladium catalysts2 have recently been
chiral catalysts, we recently demonstrated that occluded
developed. Efficient chiral heterogeneous catalysts were
Rh-MeDuPHOS in PDMS films could be used in the
obtained by immobilization of transition-metal com-
asymmetric hydrogenation of methyl 2-acetamidoacry-
plexes through attachment to organic or inorganic sup-
late in aqueous medium. In this case, the metal complex
ports or by entrapment in various polymer matrixes.3–5
could be recycled without leaching.10 The enantioselec-
An alternative approach involved recycling of metal
tivity was found to be comparable to that of the
complexes using biphasic systems where the complex
analogous homogeneous system.
We report herein on a new chiral heterogeneous cata-
lytic system obtained by occlusion of Rh-MeDuPHOS
in a polyvinyl alcohol (PVA) film as a representative
hydrophilic film. The performance of the new hetero-
geneous system was compared with that of Rh-
MeDuPHOS occluded in a hydrophobic PDMS film in
the asymmetric hydrogenation of methyl 2-acetamido-
acrylate to N-acetyl alanine methyl ester (Scheme 1) in
aqueous medium.
Figure 1. Rh-MeDuPHOS complex.
Scheme 1. Asymmetric hydrogenation of methyl 2-acetamido-
acrylate catalyzed by Rh-MeDuPHOS complex.
* Corresponding author. Tel.: 972-6461903; fax: 972-6479074; e-mail:
geresh@bgumail.bgu.ac.il
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00083-6

466
A. Wolfson et al. / Tetrahedron: Asymmetry 13 (2002) 465–468
Preparation of the film and incorporation of the metal
complexes are straightforward processes and are
described in Section 2. Since PVA crosslinks by itself in
hydrophilic solvents such as water or ethylene glycol,
by dissolving PVA in either solvent and then evaporat-
ing the solvent, PVA films physically crosslinked by
hydrogen bonding are readily obtained.11 However,
PVA was dissolved in water rather than in ethylene
glycol, since the latter demands the use of higher tem-
peratures, which could harm the chiral complex. Addi-
tion of dialdehydes or dicarboxylic acids such as malic
acid as crosslinker in the presence of an additional acid
as catalyst yields covalently crosslinked PVA films.12,13
Thus, the PVA films containing Rh-MeDuPHOS com-
plex were successfully crosslinked both physically and
chemically. We then proceeded to examine the degree
of leaching of complex from the films in different
solvents (Table 2). For comparison, leaching of the
complex from a hydrophobic PDMS film was also
tested in the same solvents. ICP-MS was employed to
detect very low metal concentrations (ppb).
As expected, high sorption of hydrophilic solvents was
observed in the PVA films while the same solvents were
poorly absorbed by the hydrophobic PDMS (Table 2).
Chemically crosslinked PVA produced denser films
than physically crosslinked PVA, with the swollen films
displaying poorer sorption of all solvents, even good
PVA solvents such as water. Leaching was only affected
by the solubility of the metal complex in the solvent
used and was not influenced by the degree of swelling
of the film. In methanol, which dissolved the complex,
high leaching of the complex was observed (entries
1–3). In xylene (entries 4–6) or water (entries 8–10),
which are poor solvents for the complex, only limited
complex leaching was observed. Addition of a small
amount of methanol to xylene (entry 7) increased the
degree of leaching as compared with xylene alone due
to the higher solubility of the metal complex in the
solvent mixture. In all solvents, use of the chemically
crosslinked instead of physically crosslinked PVA film
led to lower leaching, probably due to the increase in
crosslinking density. A similar effect of crosslinking
density on leaching was found for Rh-MeDuPHOS
occluded in PDMS films.10
Homogeneous reactions were performed in the presence
of various components used in the preparation of PVA
films, such as water, acetic acid and malic acid (Table 1,
entries 2–4). To help determine whether any of these
components affect the activity and enantioselectivity of
the chiral complex, a homogeneous reaction was also
performed (entry 1). Water did not affect the enantiose-
lectivity of the asymmetric hydrogenation of methyl
2-acetamidoacrylate (MAC) with Rh-MeDuPHOS but
decreased the reaction rate. Likewise, addition of the
crosslinker, malic acid, and addition of acetic acid,
failed to alter either the activity or the
enantioselectivity.
Table 1. Effect of additives on the performance of Rh-
MeDuPHOS in the homogeneous asymmetric hydrogena-
tion of methyl 2-acetamidoacrylatea
Entry
Additive
TOF (h−1 b
)
E.e. (%)
1
2
3
4
–
65
42
63
65
99
98
97
97
Examination of the behavior of PVA and PDMS films
in different solvents revealed that leaching of the metal
complex was higher when the solvent caused swelling of
the polymer. In water, for example, leaching of Rh-
MeDuPHOS from the hydrophilic PVA film (entries 8
and 9) was substantially higher than that from the
hydrophobic PDMS film (entry 10). In xylene, the
opposite pattern was observed (entries 4–6). The pro-
cess of sorption seems to consist of two time-dependent
Waterc
Acetic acidd
Malic acidd
a Reaction conditions: 25°C, H2 (2 atm.), methanol (9 mL), MAC
(0.1 g), S/C=150.
b After 10 min.
c Water (3 mL) and methanol (6 mL).
d Acid (16 mmol).
Table 2. Sorption of solvents and leaching experiments of Rh-MeDuPHOS occluded in PVA and PDMS filmsa
Entry
Solvent
Solubility of complex
in the solvent
Polymer
Sorption of solvent
in polymer (g/g)
Leaching of
complex (%)
1
2
3
4
5
6
7
8
Methanol
Methanol
Methanol
Xylene
Xylene
Xylene
Xylene/methanol (10:1 v/v)
Water
Water
High
High
High
Low
Low
Low
High
Low
Low
Low
PVAb
PVAc
0.156
0.151
0.049
0.061
0.061
1.177
0.062
0.884
0.284
0.065
47
45
31
0.7
0.7
2.9
11
5.2
4.2
0.9
PDMSd
PVAb
PVAc
PDMSd
PVAc
PVAb
PVAc
9
10
Water
PDMSd
a Rh-MeDuPHOS (10 mmol), solvent (20 mL), 25°C, 1 atm, 24 h.
b Physical crosslinking.
c Chemical crosslinking with malic acid as crosslinker in the presence of acetic acid.
d PDMS dimethylvinyl terminated, average molecular weight of 5426 with 20 wt% silica.

A. Wolfson et al. / Tetrahedron: Asymmetry 13 (2002) 465–468
467
2. Experimental
2.1. Preparation of the catalyst
steps: first, sorption of a particular solvent into the
polymer takes place depending on the nature of both
polymer and solvent; this is followed by dissolution of
the chiral complex. Changing the nature of the film and
the solvent influences the permeability of the reactants
(substrate and hydrogen).
The Rh-salt [bis(1,5-cyclooctadiene) rhodium(l)trifluoro-
methanesulfonate, 99%] and methyl-DuPHOS ligand
[(−)-1,2-bis-(2R,5R)-2,5-dimethylphosphacyclopentyl)-
benzene, 98%] were purchased from Strem. The Rh-
MeDuPHOS catalyst was prepared in a glove box by
dissolving the rhodium salt and the DuPHOS ligand
separately in methanol (5 mmol salt in methanol (0.25
mL) and ligand (6 mmol) in methanol (0.2 mL), respec-
tively) and stirring for 40 min. The ligand solution (5%
excess) was added dropwise to the rhodium salt solution
under constant stirring. After 30 minutes, the methanol
was flushed out with nitrogen.
We tested the occluded complexes as catalysts in the
asymmetric hydrogenation of methyl 2-acetamidoacry-
late (MAC) in aqueous medium with Rh-MeDuPHOS
occluded in PVA films, as illustrated in Table 3. The
initial results obtained with Rh-MeDuPHOS occluded
in PVA films (Table 3) showed that it was possible to
perform the hydrogenation reaction in water and also
to recycle the heterogeneous catalyst (entries 3 and 4)
without any subsequent loss in activity or enantioselec-
tivity. The reaction rate when physically crosslinked
PVA film was used was slightly higher than that
observed for chemically crosslinked film, probably due
to the higher permeabilities of the physically
crosslinked support. The PVA films tested were much
denser than the PDMS film and the sorption of water
to PVA film was higher. Although no complete com-
parison can be made between PVA and PDMS films,
occlusion of the chiral metal complex in hydrophilic
and hydrophobic films demonstrates the feasibility of
working with different polymers and solvents.
2.2. Preparation of films
Polyvinyl alcohol films were prepared using two
crosslinking methods:10 (a) physical crosslinking in
water and (b) chemical crosslinking in water with the
addition of malic acid as crosslinker and acetic acid or
hydrochloric acid as catalyst. In both cases, an amount
of 0.5 g PVA (99% hydrolyzed, MW=50000, purchased
from Aldrich) was dissolved in distilled (5 g) water by
warming to 50°C for 5 min (in some cases ethylene
glycol was used instead of water, in which case the
mixture was warmed to 120°C). The chiral complex was
then dissolved in methanol (0.5 mL), added to the PVA
solution and poured into a Petri dish. Water was evap-
orated in a vacuum oven at 80°C for 3 h. Evaporation
was performed under a nitrogen atmosphere. After
evaporation the film was easily removed from the Petri
dish and added in pieces to the reaction mixture in the
reactor. For the chemically crosslinked PVA film, 3
wt% each of malic acid and acetic acid (both purchased
from Aldrich) were dissolved in water (5 mL) before the
addition of PVA (0.5 g).
In conclusion, for the first time a chiral transition-metal
complex was successfully incorporated into polyvinyl
alcohol films. The preparation of the heterogeneous
system was very easy and did not involve modification
of the metal complex. Leaching of Rh-MeDuPHOS
from the PVA film was studied and compared to that
from the PDMS system. It was found that using a poor
solvent for the chiral complex prevents leaching. The
heterogeneous catalytic system was successfully reused
without loss of activity and enantioselectivity. Other
substrates and complexes will have to be tested in order
to determine the scope and limitations of this new
catalytic system.
2.3. Leaching procedure
Leaching of the complex and solvent sorption were
tested in various solvents (20 mL) for 24 h. The extent
of leaching of the metal complex from the polymer
matrices was measured by analyzing the liquid phase
after separation with a PQ3/VG ICP-MS system. The
sorption of the solvents was measured by weighing the
polymer before and after sorption.
Table 3. Enantioselective hydrogenation of methyl 2-
acetamidoacrylate with Rh-MeDuPHOS occluded in PVA
and PDMS filmsa
Entry
Solvent
TOF (h−1 b
)
E.e. (%)
2.4. Typical hydrogenation procedure
1
2
3
4
Waterc
12.6
14.9
12.4
12.2
96.9
96.1
95.7
95.1
A 25 mL reactor with magnetic stirring was used for
both the homogeneous and the heterogeneous reac-
tions. In the homogeneous reactions, the complex was
dissolved in the reaction solvent. In the heterogeneous-
catalyzed reactions the film was added in pieces to the
reaction medium under a nitrogen atmosphere. A vol-
ume of solvent (18 mL) was added to the reactor
together with the substrate (0.1 g). The reaction was
performed at 25°C with high-purity hydrogen
(99.995%) at a pressure of 2 bar. Samples were with-
drawn periodically to determine the reaction rate and
Waterd
Watere (first cycle)
Watere (second cycle)
a Reaction conditions: 25°C, H2 (2 atm), MAC (0.1 g), solvent (19
mL), catalyst (10 mmol).
b After 6 h.
c PDMS dimethylvinyl terminated, average molecular weight of 5426,
with 20 wt% silica.
d Physically crosslinked PVA.
e Chemically crosslinked PVA.

468
A. Wolfson et al. / Tetrahedron: Asymmetry 13 (2002) 465–468
the enantiomeric excess as a function of time and were
analyzed on a GC with an Astec Chirasil-Val capillary
column. Reuse of the catalyst was tested by replacing
the reaction liquid phase and washing the PVA film
with the reaction solvent before addition of new reac-
tion mixture.
Catalyst Immobilisation and Recycling; Wiley-VCH:
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