Application of immobilized rhodium catalyst precursors in enantio- and chemoselective hydrogenation reactions

Article abstract of DOI:10.1021/op034004a

Two different homogeneous catalyst precursor complexes, i.e. [Rh(COD)₂]BF₄ and [Rh(COD)Cl]₂, were immobilized on phosphotungstic acid-modified alumina to form γ-Al₂O₃/PTA/Rh(COD)₂BF₄ (1b) and γ-Al₂O₃PTA/[Rh(COD)Cl]₂ (2b), respectively. These immobilized complexes have been modified with (R,R)-MeDuPHOS to form the immobilized chiral catalysts γ-Al₂O₃/PTA/Rh((R,R)-MeDuPHOS)(COD)BF₄ (1c) and γ-Al₂O₃/PTA/Rh((R,R)-MeDuPHOS)(COD)Cl (2c). It is shown that immobilization and subsequent modification by ligand exchange reactions of general precursor complexes is a powerful method to prepare chiral and achiral anchored rhodium catalysts. Enantioselective hydrogenation reactions show that the activity and selectivity differences between the homogeneous catalysts [((R,R)-MeDuPHOS)Rh(COD)]BF₄ (1a) and the in situ prepared [((R,R)-MeDuPHOS)Rh(COD)]Cl (2a) are larger than the differences between the immobilized analogues (1c, 2c). At elevated temperature and H₂ pressure the activity and selectivity of 1c are comparable to those of its homogeneous analogue. Complex 1b was also used to prepare γ-Al₂O₃/PTA/Rh(DiPFc)-(COD)BF₄ (1d) via a ligand exchange reaction with 1,1′-bis(diisopropylphosphino)ferrocene (DiPFc). This complex was used as a selective and heterogeneous hydrogenation catalyst with special chemoselective hydrogenation properties. The described immobilized rhodium catalysts prepared from the general precursor complexes 1b and 2b display hydrogenation activity and selectivity comparable to those of their homogeneous analogues. Moreover, it is demonstrated that these catalysts can be reused multiple times with neither activity nor selectivity loss and that leaching can be minimized by using optimized reaction parameters.

Full text of DOI:10.1021/op034004a

Organic Process Research & Development 2003, 7, 393−398
Application of Immobilized Rhodium Catalyst Precursors in Enantio- and
Chemoselective Hydrogenation Reactions
Jim A. M. Brandts* and Peter H. Berben
Engelhard de Meern B.V., StrijkViertel 67, P.O. Box 19, 3454 ZG De Meern, The Netherlands
Abstract:
Although heterogeneous precious metal catalysts can be very
effective in hydrogenations, the chemo-, regio-, and espe-
cially enantioselectivity are more difficult to control. On the
contrary, the properties of homogeneous catalysts can be
tuned by changing both the electronic and steric influences
on the catalytic center by modification of the ligands
attached.3,5 Optimization of homogeneous catalysts allows
the generation of more active and selective catalysts. Despite
the higher activity and selectivity, homogeneous catalysts
have not widely replaced heterogeneous catalysts on indus-
trial scale, partly due to the difficult product-from-catalyst
separation.
One possible option to circumvent the problems of catalyst
separation in homogeneously catalyzed reactions is im-
mobilization of the catalyst to a support.4 The obvious
advantages would be the easy separation of the catalyst from
the product (downstream product purification is simplified),
the possibility for performing the reactions in a continuous
mode, and higher turn-over numbers (TON) by reusing the
catalyst.
In homogeneous catalysis [Rh(COD)Cl]2 and [Rh(COD)2]-
BF4 (COD ) 1,5-cyclooctadiene) are important general
precursor complexes to prepare a number of symmetric and
asymmetric Rh-based hydrogenation catalysts.5 A simple
ligand exchange reaction, in which one COD ligand is
replaced by, for example, a chiral diphosphine ligand, gives
the wanted, ligand-modified homogeneous catalyst. Im-
mobilization of the Rh-precursor complexes would create
the possibility to prepare a large number of different
immobilized Rh catalysts by similar ligand exchange reac-
tions. One of the most promising techniques for immobiliza-
tion of these type of catalysts was reported by Augustine.6
Both the precursor complexes as well as the ligand-modified
homogeneous Rh-based catalysts can be anchored on a
heteropoly acid-modified support (Scheme 1). Phosphotung-
stic acid (PTA) is especially suitable for this purpose.
Interestingly, the immobilized catalysts prepared according
Two different homogeneous catalyst precursor complexes, i.e.
[Rh(COD)2]BF4 and [Rh(COD)Cl]2, were immobilized on phos-
photungstic acid-modified alumina to form γ-Al2O3/PTA/
Rh(COD)2BF4 (1b) and γ-Al2O3/PTA/[Rh(COD)Cl]2 (2b), re-
spectively. These immobilized complexes have been modified
with (R,R)-MeDuPHOS to form the immobilized chiral catalysts
γ-Al2O3/PTA/Rh((R,R)-MeDuPHOS)(COD)BF4 (1c) and γ-Al2O3/
PTA/Rh((R,R)-MeDuPHOS)(COD)Cl (2c). It is shown that
immobilization and subsequent modification by ligand exchange
reactions of general precursor complexes is a powerful method
to prepare chiral and achiral anchored rhodium catalysts.
Enantioselective hydrogenation reactions show that the activity
and selectivity differences between the homogeneous catalysts
[((R,R)-MeDuPHOS)Rh(COD)]BF4 (1a) and the in situ prepared
[((R,R)-MeDuPHOS)Rh(COD)]Cl (2a) are larger than the
differences between the immobilized analogues (1c, 2c). At
elevated temperature and H2 pressure the activity and selectivity
of 1c are comparable to those of its homogeneous analogue.
Complex 1b was also used to prepare γ-Al2O3/PTA/Rh(DiPFc)-
(COD)BF4 (1d) via a ligand exchange reaction with 1,1′-bis-
(diisopropylphosphino)ferrocene (DiPFc). This complex was
used as a selective and heterogeneous hydrogenation catalyst
with special chemoselective hydrogenation properties. The
described immobilized rhodium catalysts prepared from the
general precursor complexes 1b and 2b display hydrogenation
activity and selectivity comparable to those of their homoge-
neous analogues. Moreover, it is demonstrated that these
catalysts can be reused multiple times with neither activity nor
selectivity loss and that leaching can be minimized by using
optimized reaction parameters.
Introduction
Reduction of unwanted side-product formation in CdC,
CdO, and CdN double bond reductions is attractive both
from an economic and environmental point of view. These
reduction reactions can effectively be performed with sto-
ichiometric amounts of hydride complexes, but equimolar
amounts of salts have to be discarded as waste. Catalytic
reduction with hydrogen is a more attractive alternative in
terms of waste, selectivity, and ease.1
(2) (a) Augustine, R. L. Heterogeneous Catalysis for the Synthetic Chemist;
Marcel Dekker: New York, 1996. (b) Nishimura, S. Handbook of
Heterogeneous Catalytic Hydrogenation for Organic Synthesis; John Wiley
& Sons: New York, 2001.
(3) (a) Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2024. (b) Noyori, R.
Angew. Chem., Int. Ed. 2002, 41, 2008. (c) Knowles, W. S. Angew. Chem.,
Int. Ed. 2002, 41, 1998.
Both homogeneous and heterogeneous precious metal
catalysts can perform these catalytic reduction reactions very
effectively with the use of hydrogen as the only reagent.2
(4) (a) Pugin, B. J. Mol. Catal. 1996, 107, 273. (b) Chiral Catalyst Immobiliza-
tion and Recycling; Vos, D. E., Vankelecom, I. F. J., Jacobs, P. A., Eds.;
Wiley-VCH: New York, 2000.
(5) Ojima, I. Catalytic Asymmetric Synthesis, 2nd ed.; Wiley-VCH: New York,
2000.
* Author for correspondence. E-mail: jim.brandts@engelhard.com.
(1) (a) Hudlicky, M. Reductions in Organic Chemistry; Halsted Press: New
York, 1984. (b) Blaser, H.-U.; Studer, M. Appl. Catal., A 1999, 189, 191.
(6) (a) Tanielyan, S. K.; Augustine, R. L. (Seton Hall University). U.S. Patent
6,025,295, 2000. (b) Augustine, R. L.; Tanielyan, S. K.; Anderson, S.; Yang,
H. Chem. Commun. 1999, 1257.
10.1021/op034004a CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/15/2003
Vol. 7, No. 3, 2003 / Organic Process Research & Development
•
393

Scheme 1
to Augustine’s method maintain a high degree of activity
and selectivity and show minimum leaching.
equimolar amounts of AgBF4 and excess 1,5-cyclooctadiene.
Chiral GC was measured with the use of a Chiraldex,
â-cyclodextrin trifluoroacetyl, 30 m × 0.25 mm column; GC
analysis was done with the use of a HP-1 methyl siloxane
capillary 30 m × 320 µm × 0.25 µm column; ICP
(inductively coupled plasma) analyses were determined on
a ThermoJarrell Ash, Atom Scan 16; and XRF analyses were
determined on a Philips Uniquant Analyzer.
Procedures. γ-Al2O3/PTA. The preparation method was
used as described in the literature6 using 100 g of γ-Al2O3
and 20 g of phosphotungstic acid. The final product (yield
120 g) contains 11.4 wt % W by ICP and was stored in air.
γ-Al2O3/PTA/Rh(COD)2BF4 (1b). Preparation method
was used as described in the literature6 using 100 g of
γ-Al2O3/PTA and 0.82 g of [Rh(COD)2]BF4 (2.02 mmol).
The final orange-colored product contains 0.20 wt % Rh and
10.2 wt % W by ICP.
It is known that the characteristics of the anion of the
homogeneous catalysts (Cl, BF4, PF6, etc.) greatly influence
the catalytic properties. Large differences between the
different anions have been observed.7 Interestingly, the anion
effect in the immobilized analogues has not yet been
addressed. One of the objectives of this study was to
determine if such anion effects also exist for the immobilized
catalysts prepared from different cationic rhodium complexes
and PTA-modified alumina.
In this contribution, we present the immobilization and
application of two different homogeneous catalyst precursor
complexes, i.e., [Rh(COD)2]BF4 and [Rh(COD)Cl]2 to form
γ-Al2O3/PTA/Rh(COD)2BF4 (1b) and γ-Al2O3/PTA/[Rh-
(COD)Cl]2 (2b), respectively. These complexes have been
modified with (R,R)-MeDuPHOS to form the immobilized
chiral catalysts γ-Al2O3/PTA/Rh((R,R)-MeDuPHOS)(COD)-
BF4 (1c) and γ-Al2O3/PTA/Rh((R,R)-MeDuPHOS)(COD)-
Cl (2c). Complexes 1c and 2c and their homogeneous
analogues were tested in chiral hydrogenation reactions, and
the results were compared in terms of activity and selectivity.
Moreover, the influence of experimental conditions on the
stability towards leaching of the immobilized catalysts is
demonstrated.
γ-Al2O3/PTA/[Rh(COD)Cl]2 (2b). A preparation method
similar to that for 1b was used with 100 g of γ-Al2O3/PTA
and 0.50 g of [Rh(COD)Cl]2 (1.01 mmol). The final yellow-
to-orange-colored product contains 0.21 wt % Rh and 10.6
wt % W by ICP.
In Situ Prepared [((R,R)-MeDuPHOS)Rh(COD)]Cl
(2a). To a 2-mL MeOH solution containing 0.0010 g of
[Rh(COD)Cl]2 (2.0 µmol) was added a 1-mL MeOH solution
of (R,R)-MeDuPHOS (0.0013 g, 4.3 µmol). The yellow-
colored solution was stirred for 2 h and was used as such.
γ-Al2O3/PTA/Rh((R,R)-MeDuPHOS)(COD)BF4 (1c). In
a 20-mL Schlenk vessel were placed 1.00 g of 1b (20 µmol
Rh) and 0.0076 g of (R,R)-MeDuPHOS (25 µmol). The air
in the Schlenk was replaced by N2 by three vacuum (10 min,
oil pump)-N2 cycles. To the solids 10 mL of MeOH was
added, and the Schlenk vessel was shaken several times
during 1 h. The color of the solid material changed from
orange to yellow. After 1 h the upper layer was removed by
decantation. The remaining solids were washed with MeOH
(two times 10 mL). The solids were dried in vacuo and stored
in inert atmosphere. The yellow solids (yield 0.99 g,
quantitative) contained 0.20 wt % Rh, 10.3 wt % W by ICP
analysis.
Complex 1b was also used to prepare γ-Al2O3/PTA/Rh-
(DiPFc)(COD)BF4 (1d) via a ligand exchange reaction with
1,1′-bis(diisopropylphosphino)ferrocene (DiPFc). This com-
plex can be used as a very selective and heterogeneous
hydrogenation catalyst with special chemoselective hydro-
genation properties and exemplifies the advantages of this
immobilization technique.
Experimental Section
Materials. All reactions were carried out using standard
Schlenk techniques under inert nitrogen atmosphere unless
stated otherwise. The phosphotungstic acid (Acros), dimethyl
itaconate (Acros), 1,5-cyclooctadiene (Acros), γ-Al2O3 (Al-
drich, activated, neutral, 150 mesh, SA 155 m2/g), [Rh-
(COD)Cl]2 (Engelhard), (R,R)-MeDuPHOS (Strem), [((R,R)-
MeDuPHOS)Rh(COD)]BF4 (Strem), 1,1′-bis(diisopropyl-
phosphino)ferrocene (ChiroTech) were used without purifi-
cations. MeOH, EtOH, isopropyl alcohol, cyclohexane, CH2-
Cl2 (LabScan) were flushed with N2 for several hours before
use. [Rh(COD)2]BF4 was prepared from [Rh(COD)Cl]2 and
γ-Al2O3/PTA/Rh(( R,R)-MeDuPHOS)(COD)Cl (2c). A
method similar to that for the preparation of 1c was used
starting with 1.00 g of 2b. The resulting yellow solid (yield
0.99 g, quantitative) contains 0.19 wt % Rh, 10.1 wt % W
by ICP analysis.
(7) (a) Blankenstein, J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001, 23, 4445. (b)
Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Angew.
Chem., Int. Ed. 2002, 41, 2348. (c) For Alder ene reactions, see: Lei, A.;
He, M.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 8198
γ-Al2O3/PTA/Rh(DiPFc)(COD)BF4 (1d). A similar
method was used as for the preparation of 1c using 1.00 g
of 1b and 0.0096 g of 1,1′-bis(diisopropylphosphino)-
394
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Vol. 7, No. 3, 2003 / Organic Process Research & Development

Table 1. Hydrogenation of dimethyl itaconate using different catalystsa
conversion (%) at
H2 pressure
(bar)
timeb
98% (min)
TOF
(h-1 c
entry
catalyst
solvent
MeOH
T (°C)
0.5 (min)
5 (min)
10 (min)
)
ee (%)d
1
1a
1a
1a
2a
1c
1c
1c
1c
2c
2c
3.3
3.3
3.3
3.3
3.3
6.6
6.6
6.6
3.3
6.6
20
20
20
20
20
20
50
50
20
50
20.7
-
91.4
-
>99
-
<10
80
<10
>60
120
40
30000
24000
32000
1200
2000
5500
17000
19000
1400
96
95
95
92
97
96
96
96
97
97
2e
3
MeOH
isopropyl alcoholf
MeOH
26.7
-
94.6
14.3
19.4
43.1
82.2
-
>99
23.2
34.5
68.4
96.5
-
4
5
6
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
-
7.1
16.9
-
7
12
8e
9
100
>60
15
-
15.2
14.3
74.8
28.1
93.7
10
13000
a Standard reaction conditions: 2-4 µmol Rh catalyst, 3.54 mmol dimethyl itaconate, 20 mL of solvent, 1000 rpm. b Time to reach 98% conversion. c Approximate
turnover frequencies calculated at 20% conversion. d ee’s determined at 98% conversion. e [dimethyl itaconate] ) 1 M, 0.01 mol % catalyst. f Reaction mixture contains
10 vol % MeOH.
ferrocene (23 µmol). The resulting yellow solid (quantitative
yield) contains 0.21 wt % Rh, 10.8 wt % W by ICP analysis.
Hydrogenation Tests. Standard hydrogenation reactions
were carried out in a 50-mL stirred stainless steel Parr
autoclave with a mechanic stirrer (1000 rpm). Reaction
temperatures applied were between 20 and 60 °C. H2
Figure 1. Hydrogenation of dimethyl itaconate as model
reaction to test the different catalysts.
pressures between 0.7 and 6.6 bar were applied. Substrates
were used as such without purifications. Solvents were
(R,R)-MeDuPHOS-Modified Precursor Complexes.
Complex 1c and 2c were prepared by modification of 1b
and 2b with (R,R)-MeDuPHOS, respectively. The im-
mobilized catalysts 1c and 2c were tested in the hydrogena-
tion of the prochiral substrate dimethyl itaconate (see Figure
1). For comparison reasons the homogeneous analogues
[((R,R)-MeDuPHOS)Rh(COD)]BF4 (1a) and the in situ
prepared [((R,R)-MeDuPHOS)Rh(COD)]Cl (2a) were tested
under similar reaction conditions. The data are collected in
Table 1.
flushed with N2 for several hours before use. The reactor
was loaded with the appropriate amount of catalyst (2-4
µmol Rh-based), purged with nitrogen, and a 20-mL solution
(0.1-1.0 M in isopropyl alchol) containing the appropriate
amount of substrate was added via a cannula. While stirring,
the reaction was started by putting the reactor under H2
pressure. The reaction progress was followed in time by
taking samples at predetermined time intervals. Products were
analyzed by (chiral) GC and ICP. After the reaction was
completed, the stirring was stopped, the catalyst was allowed
to settle, and the upper layer was removed. In reuse
experiments a fresh batch of the dissolved substrate was
added, and the procedure was repeated.
The rate of the catalyzed enantioselective hydrogenations
showed a first-order dependency in substrate concentration
(except 1b). No evidence for catalyst activation times was
found in the hydrogenation of dimethyl itaconate, similar to
what was found by Cobley et al. for this substrate,10 although
it is known that the cyclooctadiene complexes of the rhodium
catalysts can give rise to such phenomena at low s:c ratios.11
A significant difference in activity and selectivity was
found between the homogeneous catalysts 1a and 2a under
comparable reaction conditions (entries 1 and 4). Complex
2a was approximately 20 times less active compared to 1a
and the enantioselectivety was lower as well (96% vs 92%).
Moreover, slow deactivation of 2a was observed during the
reaction. It is known that these differences can be ascribed
to the influence of the anion and that the (R,R)-MeDuPHOS-
based rhodium catalysts work best with noncoordinating
Results and Discussion
Anchoring of homogeneous Rh catalysts on phospho-
tungstic acid (PTA)-modified supports using Augustine’s
immobilization technology can be achieved by following two
different routes.8 The first method is the reaction between a
solution of a metal-ligand complex [M(L)n]+[X]- (where
X ) Cl, BF4, OTf or another suitable counterion) and the
PTA-modified alumina. In a second method the immobilized
catalyst is formed by reaction of a cationic metal-precursor,
e.g., [Rh(COD)Cl]2 or [Rh(COD)2]BF4, on a support fol-
lowed by modification with a ligand of choice. This latter
method is preferable in case of having to screen many
different ligands. This method also tends to give better
reproducible results in terms of activity and leaching stability.
A similar immobilization concept was reported by Hems et
al.9 Although [Rh(COD)Cl]2 is a dimeric species, it is unclear
at this moment if the immobilized form is monomeric or
dimeric in character.
-
-
anions such as OTf-, BF4 , or PF6 .
At room temperature and standard H2 pressure the
immobilized catalyst 1c displayed a somewhat higher ee
(97% vs 95%) but a lower activity compared to 1a (entries
(10) Cobley, C. J.; Lennon, I. C.; McCague, R.; Ramsden, J. A.; Zanotti-Gerosa,
A. Tetrahedron Lett. 2001, 42, 7481.
(11) (a) Drexler, H.-J.; Baumann, W.; Spannenberg, A.; Fischer, C.; Heller, D.
J. Organomet. Chem. 2001, 621, 89. (b) Bo¨rner, A.; Heller, D. Tetrahedron
Lett. 2001, 42, 223.
(8) Presented by R. L. Augustine at ChiraSource 2001, Philadelphia, PA, 2001.
(9) Hems, W. P.; Hutchings, G. J. Patent WO 02/36261, 2002
Vol. 7, No. 3, 2003 / Organic Process Research & Development
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395

3 and 5). Catalyst 1c is approximately 16 times less active,
a phenomenon which can be explained in terms of transport
limitation differences.4b The catalyst activity can be improved
by increase of H2 pressure (entry 6) or temperature (entry
7). The reaction parameter changes had no significant effect
on the enantioselectivity.
Catalyst 2c is somewhat less active compared to the BF4
equivalent 1c (entries 5 and 9, entries 7 and 10), but the
differences between the immobilized complexes and the
homogeneous analogues are less distinct, both in terms of
activity and selectivity. The difference in activity between
the immobilized complexes 2c and 1c is less than a factor
of 2, whereas this same difference between 1a and 2a is 25.
At low substrate-to-catalyst ratios (s:c ) 100-300)
catalyst 1c could be reused more than 10 times with constant
activity and enantioselectivity (ee ) 96-97%). Neither Rh
nor W leaching was observed. At higher substrate-to-catalyst
ratios (s:c ) 10000) the activity of the immobilized catalyst
decreased upon reuse. Small amounts of Rh and W leaching
could be detected, but no proof was found that this leached
material contributed to the activity. Since the observed ee’s
remained unchanged, deactivation of the catalyst could be
caused by substrate impurities. Although the phosphotungstic
acid is able to catalyze the formation of i-propyl esters from
methyl esters in the isopropyl alcholic solvent, only very
small traces (<0.5%) of i-propyl esters were found in the
products.
Figure 2. Catalyst 1d is reused three times in hydrogenation
of 4-bromostyrene.
Table 2. Selective hydrogenation using 1d and 10 % Pd/Ca
The results obtained by using the immobilized catalyst
1c at high substrate-to-catalyst ratios are very comparable
to those from the homogeneously catalyzed hydrogenation
of dimethyl itaconate (entries 2 and 8) in terms of activity
(reaction time to > 98% conversion: 1c ) 100 min, 1a )
80 min) and selectivity (1c ee ) 96%, 1a ee ) 95%) under
the conditions that were used. Although the results of the
two catalysts are comparable, different reaction conditions
(increased temperature, increased H2 pressure) had to be
applied. Comparison between 1c and its homogeneous
derivative 1a is delicate because the two catalysts are
intrinsically different.
a Standard reaction conditions: 4 µmol Rh catalyst, 4 mmol substrate, 20
mL of isopropyl alcohol, 1000 rpm, 6.6 bar H2 pressure, 50 °C. b Approximately
10% was ethylbenzene. c >96% ) 4-carboxaldehyde aniline.
neous catalysts give more overhydrogenated side products
or have only limited activity due to the poisoning effect of
the sulfur. To demonstrate its practicability catalyst 1d was
used in the reduction 4-bromostyrene to bromo-4-ethylben-
zene. At relatively mild reaction conditions (50 °C, 6.6 bar
H2, isopropyl alcohol, 0.1 mol % catalyst, [4-bromo-styrene]
) 0.19 mol/L) the catalyst could be reused three times after
full conversion (total TON ) 4000) (see Figure 2).
Neither deactivation nor leaching of the catalyst (Rh, W
leaching determined by ICP) was observed. The bromide-
aromatic bond remained unaffected. A 10% Pd/C catalyst
under similar reaction conditions gave 10% ethylbenzene as
a result of dehalogenation (see Table 2).
Complex 1b Modified with (DiPFc). Complex γ-Al2O3/
PTA/Rh(DiPFc)(COD)BF4 (1d) was prepared via a ligand
exchange reaction with 1,1′-bis(diisopropylphosphino)fer-
rocene (DiPFc) and 1b and was jointly developed by
Chirotech Technology Limited and Engelhard Corporation.
Complex 1d is the immobilized equivalent of the homoge-
12
neous catalyst [Rh(DiPFc)(COD)]BF4 and has similar
activity and selectivity properties.13 Catalyst 1d is particularly
useful for chemoselective hydrogenations of (sulfur-contain-
ing) alkenes, alkynes, and aldehydes.
However, 1d can be separated from the product mixture
by simple filtration techniques. Moreover, it can be reused
several times, without loss of (chemo)selectivity or activity.
Of particular interest is the observation that the chemo-
selectivity of this catalyst allows reduction of alkenes,
alkynes, and aldehydes in the presence of aromatic bromides,
aromatic nitro groups, and sulfur. Conventional heteroge-
Catalyst 1d can also be used for the hydrogenation of
other functionilized alkenes and alkynes in alcoholic solvents.
Substrates such as 3-nitrostyrene, phenyl vinyl sulfone,
1-phenyl-1-hexyne, and 1-dodecyne could be converted
to their corresponding hydrogenated products.13 No over-
hydrogenation was observed when 1d was used, but other
products were found when 10% Pd/C was used as a catalyst.
Conventional heterogeneous catalysts do not give these types
of chemoselectivity as shown by the data in Table 2.
(12) Burk, M. J.; Harper, T. P. G.; Lee, J. R.; Kalberg, C. Tetrahedron Lett.
1994, 35, 4963.
(13) Burk, M. J.; Gerlach, A.; Semmeril, D. J. Org. Chem. 2000, 65, 8933.
396
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Vol. 7, No. 3, 2003 / Organic Process Research & Development

Table 3. Leaching data obtained from 1c-catalyzed reaction mixturesa
reaction time
Rh leach
W leach
entry
solvent
MeOH
EtOH
isopropyl alcohol
cyclohexane
[substrate] (M)
(min)
T (°C)
(% total Rh)
(% total W)
1
2
3
4
5
6
7
8
9c
0.1
0.1
0.1
0.1
1.0
1.0
1.0
0.1
0.1
20
20
20
20
20
20
20
1020
20
50
50
50
50
50
50
20
50
50
2.3
1.5
0.05
0.05
<1b
<1
<1
1.2
<0.002b
<0.002
<0.002
0.008
cyclohexane
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
isopropyl alcohol
<1
2.0
7.3
<0.002
0.03
0.06
a Standard reaction conditions: 0.1 mol % 1c, substrate ) dimethyl itaconate, 20 mL solvent, 1000 rpm, 6.6 bar H2. b Below detection limits of ICP. c Addition of
0.1 mol % Et3NHCl.
The activity of 1d is very comparable to the homogeneous
catalyst [Rh(DiPFc)(COD)]BF4 in the case of alkene and
alkyne hydrogenations. In aldehyde reductions the activity
of [Rh(DiPFc)(COD)]BF4 is usually significantly higher.
Depending on the substrate, the reaction conditions (higher
temperature, H2 pressure) could be optimized to compensate
for this difference.
similar to those of BF4, could explain why the differences
between the homogeneous (1a, 2a) are larger than the
differences between the immobilized complexes (1c, 2c).
However, more evidence is needed to verify this hypothesis.
The bond between the rhodium complex and heteropoly
acid-modified support (ionic interaction) is fairly strong but
is still susceptible towards leaching. This susceptibility,
however, strongly depends on the nature (i.e., ligands) of
the immobilized complex. An immobilized Rh catalyst
prepared from 1b and ligand X might leach in MeOH under
standard reaction conditions, while another catalyst prepared
from 1b and ligand Y is stable. This leaching stability is
influenced by the polarity of the reaction environment, and
a correlation between leaching and solvent polarity was
found. Using alcoholic solvents leaching of the Rh complexes
decreased from MeOH > EtOH > isopropyl alcohol. In
MeOH some leaching was detected in dimethyl itaconate
hydrogenations using 1c and 2c as catalysts. In isopropyl
alcohol the leaching was reduced below the detection limits
of ICP. In cyclohexane no leaching was ever observed (see
Table 3, entries 1-5). Parameters such as substrate concen-
tration, addition of ammonium salts, temperature, and
reaction time were investigated for their influence on the
catalyst stability towards leaching (Table 3).
An increase in the dimethyl itaconate concentration
(entries 3 and 6), prolonged reaction or stirring times (entries
3 and 8) and the addition of Et3NHCl (entries 3 and 9)
resulted in more leaching of rhodium. A decrease in reaction
temperature (entries 6 and 7) decreased the amount of
rhodium in the reaction mixture. These results show how
parameters such as reaction media, reaction temperature,
substrate concentration, and purity influence the catalyst
leaching stability. The ratio between the amounts of Rh and
W found in the reaction mixtures indicates that the interaction
between the PTA and the support is fairly strong under the
reaction conditions used. The interaction between the rho-
dium and PTA, or between the rhodium and other heteropoly
acids,15 is the more leaching-sensitive interaction. All this
knowledge can be used to optimize the leaching stability of
the immobilized hydrogenation catalysts.
Some acetal formation was observed in the aldehyde
hydrogenations in alcoholic solvents, probably due to acid-
catalyzed reaction between the alcohol and the aldehyde.
Catalyst Stability to Leaching. Although the reaction
mechanism of the bonding between the homogeneous
catalysts and the heteropoly acid-modified support remains
unclear, some evidence suggests that the bond is mainly ionic
in character. Addition of ionic components such as am-
monium and potasium salts, causes leaching of at least a
part of the immobilized complexes. However, the addition
of, for example, LiBF4 hardly causes leaching.8 A weak
covalent coordinating interaction between the Rh atom and
the phosphotungstic acid oxygen atom(s) is also conceivable
as was found for comparable Ir and Rh complexes by Finke
et al.14 No evidence was found that the counterion in the Rh
complex is removed from the catalyst during the reaction
between the PTA-modified alumina and the rhodium-
precursor complexes. We were unable to detect Cl by ICP
analysis in the removed liquids after the reaction between
the modified alumina and [Rh(COD)Cl]2. However, XRF
analysis of 2b could not confirm the presence of Cl. The
relatively small amount of Cl in the final product 2b (0.07
wt %) is very close to the detection limit of the XRF analysis
technique. Experiments resulting in immobilized [Rh(COD)-
Cl]2 products with higher Cl content should provide more
clarity.
One possible explanation for the experimental results is
to assume that the heteropoly acid not only binds the anion
but also influences the anion-cation interaction of the
rhodium complex. This will have an effect on the reactivity
and selectivity of the bonded Rh complex. Immobilization
of [Rh(COD)Cl]2 on the heteropoly acid-modified support
will thus influence the Rh-Cl bond. These interactions could
effect the coordinating ability of the Cl anion to the rhodium
cation. A shift towards more noncoordinating characteristics,
(15) Brandts, J. A. M.; Donkervoort, J. G.; Ansems, C.; Berben, P. H.; Gerlach,
A.; Burk, M. J. Tethering Technology: Anchored Homogeneous Catalysts.
In Catalysis of Organic Reactions; Ford, M. E., Ed.; Marcel Dekker: New
York, 2001; p 573.
(14) Pohl, M. P.; Lyon, D. K.; Mizuno, N.; Nomiya, K.; Finke, R. G. Inorg.
Chem. 1995, 34, 1413.
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397

Conclusions
is very suitable to prepare a library of ligand-modified
immobilized Rh catalysts. Parameters such as solvent (polar-
ity), substrate, substrate concentration, substrate purity,
temperature, and reaction time can be tuned to optimize
leaching stability. It has been demonstrated that leaching can
be minimized, provided that the reaction parameters used
are optimized. Due to its leaching stability under optimized
conditions, the catalysts can be reused several times without
losses in activity and selectivity.
The immobilization and subsequent modification by
ligand exchange reactions of the general precursor complexes
[Rh(COD)Cl]2 and [Rh(COD)2]BF4, is a powerful method
to prepare a number of chiral and achiral anchored rhodium
complexes. At elevated temperature and H2 pressure the Rh
catalysts immobilized on PTA-modified alumina have activ-
ity and selectivity properties comparable to those of the
homogeneous analogues. Chiral hydrogenation reactions
show that the activity and selectivity differences between
the homogeneous catalysts bearing different anions (BF4: 1a,
Cl: 2a) are larger than the differences between the im-
mobilized analogues (1c, 2c). This immobilization technology
Received for review January 7, 2003.
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