Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous aluminosilicate: Application and solvent effects

Article abstract of DOI:10.1002/chem.200400528

A new Bronsted acidic aluminosilicate, AlTUD-1, with ideal characteristics for catalyst immobilisation (mesoporous structure, high surface area, and high Al_tetrahedral/Si ratio), was used successfully for the noncovalent anchoring of two well-established asymmetric hydrogenation catalysts: [Rh^I(cod){(R,R)-MeDuPHOS}]BF₄ (1) and [Rh ^I(cod){(S,S)-DiPAMP}]BF₄ (2). The new heterogeneous catalysts, 1-AlTUD-1 and 2-AlTUD-1, prepared by a straightforward ion-exchange procedure, were highly active and selective in the asymmetric reduction of dimethyl itaconate (3) and methyl 2-acetamidoacrylate (4), giving enantiomeric excesses of up to >98%. The catalysts showed similar behaviour to their homogeneous counterparts. Catalyst 2-AlTUD-1 could be re-used multiple times without loss of enantioselectivity or activity. Leaching of Rh showed a significant dependence on the polarity of the solvent in which the catalysis was performed. By applying tert-butylmethyl ether (MTBE) as solvent, the loss of Rh could be reduced to <0.1%. The solvent also had a noteworthy effect on the enantioselectivity in the hydrogenation of 4 (an effect not seen with 3 as substrate), that is, in MeOH the ee was 92%, in MTBE it dropped to 26% when using 2-AlTUD-1 as catalyst.

Full text of DOI:10.1002/chem.200400528

FULL PAPER
Noncovalent Anchoring of Asymmetric Hydrogenation Catalysts on a New
Mesoporous Aluminosilicate: Application and Solvent Effects
ChrØtien Simons,[a, b] Ulf Hanefeld,[b] Isabel W. C. E. Arends,[a] Roger A. Sheldon,*[a] and
Thomas Maschmeyer*[b, +]
Abstract: A new Brønsted acidic alu-
minosilicate, AlTUD-1, with ideal char-
acteristics for catalyst immobilisation
(mesoporous structure, high surface
area, and high Altetrahedral/Si ratio), was
used successfully for the noncovalent
anchoring of two well-established
asymmetric hydrogenation catalysts:
[RhI(cod){(R,R)-MeDuPHOS}]BF4 (1)
and [RhI(cod){(S,S)-DiPAMP}]BF4 (2).
The new heterogeneous catalysts, 1-
AlTUD-1 and 2-AlTUD-1, prepared
by a straightforward ion-exchange pro-
cedure, were highly active and selective
in the asymmetric reduction of dimeth-
yl itaconate (3) and methyl 2-acetami-
doacrylate (4), giving enantiomeric ex-
cesses of up to >98%. The catalysts
showed similar behaviour to their ho-
mogeneous counterparts. Catalyst 2-
AlTUD-1 could be re-used multiple
times without loss of enantioselectivity
or activity. Leaching of Rh showed a
significant dependence on the polarity
of the solvent in which the catalysis
was performed. By applying tert-butyl-
methyl ether (MTBE) as solvent, the
loss of Rh could be reduced to
<0.1%. The solvent also had a note-
worthy effect on the enantioselectivity
in the hydrogenation of 4 (an effect
not seen with 3 as substrate), that is, in
MeOH the ee was 92%, in MTBE it
dropped to 26% when using 2-
AlTUD-1 as catalyst.
Keywords: asymmetric catalysis
·
hydrogenation
materials
·
mesoporous
·
solvent effects
·
supported catalysts
Introduction
In recent years highly enantioselective catalysts for a broad
range of substrates such as olefins, ketones and imines[2]
have been developed. However, large-scale applications of
this mature methodology are often hampered by the difficult
removal of the homogeneous catalysts. Heterogenisation of
the metal complexes provides a way to greatly ease this sep-
aration and to improve the recycling of the expensive cata-
lyst. A commonly applied technique is the covalent binding
of the complex to a solid support.[3] Serious drawbacks of
this approach are the time-consuming and difficult ligand
modification as well as the not always predictable effects on
activity and selectivity. Augustine et al. reported a very ele-
gant method for the heterogenisation of ionic transition-
metal complexes, which did not require any modification of
the complexes and additionally, in some cases, improved
their catalytic activity and selectivity.[4] This method utilised
the cationic character of the complex to bind it noncovalent-
ly to an inorganic support, employing heteropoly acids as
the anchors. Variations of this approach using different sur-
face modification strategies to anchor by electrostatic bind-
ing have been reported by Hçlderich et al.,[5] Hems and
Hutchings,[6] and Broene et al.[7]
Transition-metal-catalysed asymmetric hydrogenation is be-
coming increasingly important for the production of enan-
tiopure pharmaceuticals and agrochemicals. The Monsanto
l-DOPA process[1] represents one of the most prominent ex-
amples of the successful implementation of this technology.
[a] Drs. C. Simons, Dr. I. W. C. E. Arends, Prof. Dr. R. A. Sheldon
Laboratory of Biocatalysis and Organic Chemistry
Delft University of Technology
Julianalaan 136
2628 BL Delft (The Netherlands)
Fax : (+31)15-278-1415
E-mail: R.A.Sheldon@tnw.tudelft.nl
[b] Drs. C. Simons, Dr. U. Hanefeld, Prof. Dr. T. Maschmeyer+
Laboratory for Applied Organic Chemistry and Catalysis
Delft University of Technology
Julianalaan 136
2628 BL Delft (The Netherlands)
E-mail: Th.Maschmeyer@chem.usyd.edu.au
[+] Current address: School of Chemistry
Inspired by these new anchoring techniques, we set out to
utilise the new mesoporous aluminosilicate, AlTUD-1, as a
support for chiral rhodium complexes. Here, we describe the
preparation of this new aluminosilicate and its use in the im-
University of Sydney
NSW 2006 (Australia)
Fax : (+61)2-9351-3329
Chem. Eur. J. 2004, 10, 5829 – 5835
DOI: 10.1002/chem.200400528
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FULL PAPER
mobilisation of two established, asymmetric hydrogenation
catalysts, [RhI(cod)((R,R)-MeDuPHOS)]BF4 (1)[8] and
[RhI(cod)((S,S)-DiPAMP)]BF4 (2),[9] wherein cod is 1,5-cy-
clooctadiene. The application of these new heterogeneous
catalysts in asymmetric hydrogenation and the striking influ-
ence of the solvent, a factor often ignored, were investigat-
ed.
Results and Discussion
The starting point for the development of the mesoporous
aluminosilicate (AlTUD-1, pore diameter 20–500 Š) was
the recent discovery of a new templating method for meso-
porous networks.[10] This novel approach uses inexpensive,
nonsurfactant chemicals to produce mesoporous materials
with high surface areas (up to ca. 1000 m2 gÀ1) and three-di-
mensional (3D) connectivities. The 3D pores should allow
better accessibility of the catalyst compared with one-di-
mensional pore systems as found in materials such as MCM-
41.[11]
For the purpose of immobilising cationic complexes on
the material, an unusually low Si/Al ratio of about 4 is desir-
able. Preferably, to ensure a high Brønsted acidity, the alu-
minium center should display tetrahedral coordination. The
templates described have the ability to stabilise metal alkox-
ides by complexation,[12] and thus seemed ideally suited for
production of the desired aluminosilicate.
Figure 1. a) Powder XRD (CuKa) pattern of AlTUD-1; b) nitrogen sorp-
tion isotherms of AlTUD-1. Inset: corresponding pore-size distribution.
Initial experiments with the most frequently reported
template triethanolamine, did not give satisfactory results.
However, with tetraethyleneglycol (TEG)[13] as a template, a
white solid, denoted as AlTUD-1, was obtained. The com-
plete removal of the template was confirmed by IR spectro-
scopy, and the structural properties of AlTUD-1 were inves-
tigated with X-ray powder diffraction and N2 physisorption.
The XRD pattern in Figure 1a shows one dominant
signal, an intense peak around 0.658 q, indicating that
AlTUD-1 is a mesostructured material. The N2 sorption iso-
therms (Figure 1b) show the mesoporous texture in what is
a typical Type IV isotherm with a type H1 hysteresis loop,
characteristic for mesoporous materials. Additional data, de-
rived from the isotherm, illustrate that AlTUD-1 has a large
surface area of about 600 m2 gÀ1 and a total pore volume of
1.1 cm3 gÀ1. The pore size distribution is fairly broad and
shows a maximum at 150 Š (inset). In the synthesis of the
purely siliceous mesoporous silica (TUD-1) by this templat-
ing method, the pore-size distribution could be tuned by var-
iation of the hydrothermal treatment time: a longer duration
increased the pore diameter. For AlTUD-1, variation in the
hydrothermal treatment time had little to no effect on the
pore-size distribution. This is, to a large degree, due to the
faster formation of Al-O-Si bonds compared with Si-O-Si
bonds, which renders the overall system less dynamic and,
therefore, less sensitive towards changes in pore size with
temperature. Increasing the time over a range of 3 to 24 h
gave a pore diameter of 150–250 Š, all with the same broad
distribution (see Figure 1b inset). Similarly, the surface area
increased only marginally when prolonging the hydrother-
mal treatment from 3 to 24 h (~500–625 m2 gÀ1). It can rea-
sonably be assumed that AlTUD-1 exhibits a three-dimen-
sional structure owing to the synthesis method used. Fur-
thermore, all analyses of AlTUD-1 indicate that it is consis-
tent with a TUD-1-like structure.
The nature of Al in AlTUD-1 was investigated by using
27Al NMR spectroscopy (Figure 2). The spectrum exhibits a
strong resonance at d = 55 ppm, which can be assigned to
the desired Brønsted acidic, tetrahedrally coordinated Al
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Anchored Asymmetric Hydrogenation Catalysts
5829 – 5835
catalyst (entry 1, Table 1) and 1-AlTUD-1 (entry 2, Table 1)
under identical conditions reveals that there is no decrease
in either selectivity or activity upon anchoring 1 on AlTUD-
1. However, significant leaching of Rh was observed, casting
doubt on the heterogeneity of the reaction. We therefore
screened other solvents using the Avantium Quick Catalyst
Screen platform (entries 4–9, Table 1) to reduce this prob-
lem. When switching from the mechanically stirred auto-
clave to the magnetically stirred Quick Catalyst Screen plat-
form, a significant drop in activity was observed (entry 3
versus entry 5, Table 1), whereas the enantioselectivity was
hardly affected by the change of reaction vessel and stirring
mode. The reduction in activity is principally due to a re-
Figure 2. 27Al NMR spectrum of AlTUD-1.
Table 1. Asymmetric hydrogenation of 3 in various solvents.[a]
(Altetrahedral) center. The signals
at d = 31 and 0 ppm can be as-
cribed to pentacoordinate Al
and hexacoordinate Al centers,
respectively. It follows from the
integration that approximately
43% of the Al is coordinated
tetrahedrally. Although the ad-
dition of TEG did not com-
pletely suppress the formation
of hexacoordinate Al centers, it
did allow the formation of a
Entry
Catalyst
Solvent
Conv.
[%]
3/Rh
ratio
TOF
ee
[%]
Rh loss
[molmolÀ1 hÀ1
]
[mgLÀ1] (%)[c]
1[b]
2[b]
3[b]
4
5
6
7
8
9
1
MeOH
MeOH
2-PrOH
MeOH
2-PrOH
CH2Cl2
EtOAc
MTBE
toluene
100
100
100
22
32
26
11
10
0
1250
1250
200
250
325
250
175
250
250
>1000
>1000
>1000
51
96
98
96
97
96
98
98
96
n.d.
–
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
2.00 (23)
0.35 (1.4)
4.5 (15)
0.78 (2.5)
0.29 (0.7)
0.29 (0.5)
0.04 (0.1)
n.d.
105
62
19
mesoporous
aluminosilicate
with a high surface area and a
Si/Altetrahedral ratio of 9:1 (overall
Si/Al = 4:1). This new material
(AlTUD-1) with its large sur-
face area, mesoporous struc-
ture, and high proportion of
Brønsted acidic Al combines all
the desired properties for an
anionic carrier.
25
0
[a] Reaction was performed using the Avantium Quick Catalyst Screen platform; conditions: ~6 mg supported
catalyst, pinitial(H2) = 5 bar, volume 1.5 mL, [substrate] = 0.1m, time = 60 min, S major enantiomer with
(R,R)-MeDuPHOS as ligand. [b] Reaction was performed in a Parr hastelloy C autoclave; conditions: 100 mg
supported catalyst, 50 mL solvent, p(H2) = 5 bar, [substrate] = 0.1m, time = 30 min, S major enantiomer
with (R,R)-MeDuPHOS) as ligand. [c] Percentage of total amount Rh.
Complexes 1 and 2 were immobilised by straightforward
ion exchange, using the three-dimensional mesoporous alu-
minosilicate (AlTUD-1). A high Altetrahedral/Rh ratio of ap-
proximately 10:1 was chosen, so that any cationic complex
that is inadvertently mobilised during the hydrogenation re-
action is surrounded by many vacant acidic sites, increasing
the chances to be immobilised again. Both, pre-formed com-
plexes and those prepared in situ, can be immobilised. The
resulting immobilised catalysts are expected to have a virtu-
ally unmodified, and possibly even improved, catalytic be-
haviour. The immobilised catalysts, denoted as 1-AlTUD-1
and 2-AlTUD-1, respectively, were washed with ethanol or
2-propanol to remove any unanchored catalyst. Typically, a
loading of 1 wt% Rh was obtained.
For a direct comparison of the immobilised and homoge-
neous catalysts, the catalytic behaviour of 1-AlTUD-1 was
studied in the asymmetric hydrogenation of dimethyl itaco-
nate (3) (Table 1). No difference was found between chiral
catalysts that were immobilised as synthesised and those
that were prepared by addition of a solution of bis(1,5-cyclo-
octadiene)rhodium tetrafluoroborate and the chiral ligand
to AlTUD-1. The comparison between the homogeneous
duced mass-transfer of hydrogen from the gas to the liquid
phase, caused by the different reaction vessel design. The re-
duction in hydrogen uptake slows down the reaction, since
hydrogen is involved in the rate-determining step.[14a] Never-
theless, this system is suited to finding trends in the leaching
of Rh. The lack of activity in toluene is not surprising, since
aromatic compounds tend to form stable h6-arene complexes
with RhI.[15]
The screening revealed a similar loss of Rh with methanol
as solvent, when compared with the original experiment. As
expected, the Rh loss could largely be overcome by switch-
ing to less polar solvents. With the less polar, but still protic,
2-propanol as solvent, leaching of Rh could already be re-
duced by a factor of 6. When we used dichloromethane or
ethyl acetate, both regarded as polar aprotic solvents, the
Rh in solution could be reduced to 0.29 mgLÀ1, correspond-
ing to 0.5–0.7% of the total amount of Rh. Minimal leach-
ing (0.04 mgLÀ1, 0.1% of the original Rh) was obtained
with the much less polar and aprotic tert-butylmethyl ether
(MTBE). By simply switching the polarity of the solvent,
the leaching of the catalyst could be reduced by a factor of
150.
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R. A. Sheldon, T. Maschmeyer et al.
FULL PAPER
A good measure for solvent polarity is the normalised
lyst is poorly soluble in this solvent, but when using the im-
mobilised catalyst, reasonable TOFs with moderate ee were
obtained (entry 9, Table 2). Thus, immobilisation on
AlTUD-1 also broadens the range of solvents for asymmet-
ric hydrogenation.
N [16]
empirical parameter ET
,
which is based on the transition
energy for the longest wavelength solvatochromic absorp-
tion band of a pyridinium N-phenolate betaine dye. This pa-
rameter also takes into account specific solute–solvent inter-
actions, like hydrogen bonding and electron pair donation
and electron pair acceptance interactions. The correlation
between this parameter and loss of Rh is given in Figure 3.
Once more, significant leaching was observed with MeOH
as the solvent. Analogous to the experiments with 3, this
leaching could be reduced by a change of solvent. The
leaching could even be suppressed to <0.1%. Loss of Rh is
slightly higher for 2-AlTUD-1, especially when 2-propanol
is used as solvent. Surprisingly, the amount of Rh leached in
water is considerably lower than with methanol (entries 7
N
and 9, Table 2), although its ET value is higher (1.00). This
is due to the hydrophobic character of the cation.
The results with 2-AlTUD-1 clearly show that the solvent
also has an influence on the activity of the catalyst, where
the TOF drops from >200 for methanol and ethanol (en-
tries 7 and 8, Table 2) to 69 for 2-propanol (entry 10,
Table 2). An obvious explanation could be the different sol-
ubility of H2 in the various solvents. However, there is no
correlation between the hydrogen solubility and the TOF
(Table 3).
Figure 3. The correlation between the polarity of the solvent (ETN) and
the loss of Rh (in percentage of total amount of Rh).
This exponential correlation
Table 2. Asymmetric hydrogenation of 4 in various solvents.[a]
can be rationalised by the in-
creasing ability to stabilise
charged species with increasing
polarity. Whereas MTBE has
almost no possibility to stabilise
charges, ethyl acetate has the
ability to stabilise positive
charges by lone pair donation
and its dipolar moment. How-
ever, ethyl acetate is far less ef-
ficient in the stabilisation of
negative charges. Methanol on
the other hand has the capabili-
ty to stabilise both cations and
anions, explaining the large
amounts of Rh in solution.
The screening of various sol-
vents also shows that the enan-
tioselectivity in the hydrogena-
tion of 3 with 1-AlTUD-1 is in-
dependent of the solvent. The
catalyst 1-AlTUD-1 exhibits ex-
cellent enantioselectivities of
Entry
Catalyst
p(H2)[b]
[bar]
Solvent
Conv.
[%]
TOF
ee
[%]
Rh loss
[molmolÀ1 hÀ1
]
[mgLÀ1] (%)[c]
1
2
3
4
5
6
7
8
1
1
1
1
1
1
3
3
3
3
3
3
3
MeOH
MeOH
MTBE
EtOAc
2-PrOH
MeOH
MeOH
EtOH
100
100
100
100
100
100
100
100
81
>350
>350
>350
>350
>350
>200
>200
>200
159
>98
>98
90
–
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
1-AlTUD-1
2
2-AlTUD-1
2-AlTUD-1
2-AlTUD-1
2-AlTUD-1
2-AlTUD-1
2-AlTUD-1
4.9 (17)
0.01 (0.05)
0.01 (0.05)
0.4 (1.6)
–
4.6 (20)
0.9 (4)
1.2 (5.6)
1.3 (7.5)
0.02 (0.09)
0.09 (0.45)
84
75
92
92
79
64
44
26
9
water
10
11
12
2-PrOH
MTBE
EtOAc
26
54
35
69
103
75
30
[a] Reaction was performed in a Parr hastelloy C autoclave, conditions: 50 mL solvent, [4] = 0.025m, 0.1 g cat-
alyst, 4/Rh ratio = 100, R major enantiomer with (R,R)-MeDuPHOS) or (S,S)-DiPAMP) as ligand, reaction
time: 20 min for 1 and 30 min for 2. [b] Initial pressure. [c] Percentage of total amount Rh.
Table 3. The mole fraction solubilities xH of hydrogen and the TOF in
the asymmetric hydrogenation of 4 using 2-AlTUD-1 as catalyst in vari-
ous solvents.
up to 98% in all solvents. The enantioselectivity fluctuated
only within 1 to 2% between different solvents.
2
The encouraging results with 3 as substrate motivated us
to investigate the asymmetric hydrogenation of the more
highly functionalised substrate methyl 2-acetamidoacrylate
(4) (Table 2, the reaction times are close to the shortest re-
action times in which 100% conversion could be obtained
for the best solvent/catalyst combination; all reactions gave
quantitative yields when the reaction time was extended).
Again, 1-AlTUD-1 in methanol gave results similar to the
homogeneous catalyst, as was the case for 2-AlTUD-1. In-
terestingly, the asymmetric hydrogenation of 4 with 2-
AlTUD-1 proceeded even in water. The homogeneous cata-
[a]
Solvent
xH (10À4
)
TOF [molmolÀ1 hÀ1
]
2
methanol
ethyl acetate
2-propanol
ethanol
15
3.5
2.7
>200
75
69
>200
159
2.1
water
0.14[b]
[a] xH at 10 bar H2 and 258C.[17] [b] xH at 1 bar H2 and 258C.[17b]
2
2
Unexpectedly, the solvent also had a significant influence
on the enantioselectivity of 1-AlTUD-1 and 2-AlTUD-1 in
the hydrogenation of 4. Whereas 3 was hydrogenated with
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Anchored Asymmetric Hydrogenation Catalysts
5829 – 5835
excellent enantioselectivity using 1-AlTUD-1 in all solvents
screened, the ee in the reduction of 4 varied between
>98% for methanol and 75% for 2-propanol. Burk et al.
reported essentially identical enantiomeric excesses in the
solvents methanol, THF, dichloromethane, ethanol, 2-propa-
nol, and ethyl acetate for the homogeneous hydrogenation
of 4.[8] The interaction between the support and the catalyst,
which varies for different solvents, seems to influence the
enantioselectivity in the hydrogenation of 4. From these re-
sults, MTBE appears to be the ideal solvent when using 1-
AlTUD-1, since it combines high ee with virtually no loss of
Rh for either substrate.
ures 5 and 6. In all solvents, with the exception of methanol,
the activity of 1-AlTUD-1 drops in the second run and in
the third run. But with prolongation of the reaction time,
100% conversion could again be achieved in the fourth run,
stressing the importance of short reaction times when com-
With regard to leaching, MTBE is also the first choice for
2-AlTUD-1, but the enantioselectivity of 2-AlTUD-1 drops
dramatically (entry 11, Table 2). It appears that for this cata-
lyst the solvent dependence of the enantioselectivity is even
greater, ranging from 92 to 26 ee%. Once again the homo-
geneous complex shows different behaviour. Whereas
Knowles reports a marginally better efficiency in higher al-
cohols,[1] here the enantiomeric excess decreases with higher
alcohols. As for 1-AlTUD-1, the interaction between sup-
port and catalyst seemingly plays a significant role. Howev-
er, the relation between solvent and enantiomeric excess is
not identical for both catalysts, which becomes particularly
apparent for MTBE, ethyl acetate, and 2-propanol. For 1-
AlTUD-1, 2-propanol is the least suitable solvent, and
MTBE is the second best. For 2-AlTUD-1 MTBE is by far
the poorest solvent, whereas it performs reasonably well in
2-propanol.
Figure 5. Recycling of 1-AlTUD-1 in the asymmetric hydrogenation of 4
using conditions described in Table 2. Different bars represent consecu-
tive runs. For run 4 modified conditions were used: pinitial(H2) = 5 bar,
time 120 min.
This dependence of the enantioselectivity on the solvent
is unexpected. It is, however, not entirely surprising, since
the energy difference responsible for an enantiomeric excess
of 99.9% is only about 4 kcalmolÀ1.[14] This energy differ-
ence is similar to that between solvated species, making the
ee quite dependent on the solvent.
To confirm that the catalytic hydrogenation is indeed het-
erogeneous, the residual activity of the filtrate was measured
in a filtration test.[18] A few minutes after the start of a
normal hydrogenation procedure, 2-AlTUD-1 was removed
and the reaction was continued with the filtrate only. There
is no additional conversion after the removal of the catalyst,
(Figure 4), which clearly demonstrates that it is the hetero-
geneous catalyst that catalyses the reaction and that any Rh
leached is inactive. This was also confirmed for 1-AlTUD-1.
The recyclability of 1-AlTUD-1 and 2-AlTUD-1 was stud-
ied for all experiments described; results are depicted in Fig-
Figure 6. Recycling of 2-AlTUD-1 in the asymmetric hydrogenation of 4
using conditions described in Table 2. Different bars represent consecu-
tive runs.
paring activities in consecutive runs. The enantioselectivity
remains almost constant upon re-use and decreases only
slightly in run 4, which can partially be explained by the al-
tered reaction conditions. In MeOH the catalyst retains its
activity in run 2, but is almost inactive in runs 3 and 4. The
different behaviour in MeOH can be ascribed to the consid-
erable leaching in this solvent. However, 2-AlTUD-1 could
be recycled without loss of activity or selectivity, even in
MeOH.1 In some cases the activity increased after run 1,
which could be rationalised by the induction period needed
to form the active species.[19]
The deactivation of 1-AlTUD-1 cannot only be ascribed
to the decreasing amount of Rh in successive runs, since this
effect should be equal for 1-AlTUD-1 and 2-AlTUD-1. An-
other reason why this cannot be the only explanation is that
the magnitude of deactivation is almost independent of the
solvent. Even in MTBE, in which leaching is <0.1%, the
same decrease of activity is observed. The dissimilarity in re-
cyclability between the two catalysts should most likely be
Figure 4. Determination of the heterogeneity of the AlTUD-1 supported
~
catalysts by a filtration test. Lines: ( ) conversion of 4 in MeOH, with 2-
AlTUD-1 as catalyst (entry 7, Table 2); (”) conversion of 4 in methanol,
where the catalyst, 2-AlTUD-1, was removed after 5 min.
1
Mass transfer limitations were investigated, but did not seem to occur.
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R. A. Sheldon, T. Maschmeyer et al.
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nuclear reactor, with a neutronflux of 1017 neutrons sÀ1 cmÀ2, was used as
a source of neutrons, and the gammaspectrometer was equipped with a
germanium semiconductor as detector. Rhodium leaching was deter-
mined by analysing the reaction filtrates with graphite AAS on a Perkin
Elmer 4100ZL. N2 desorption isotherms were measured on a Quantach-
rome Autosorb-6B at 77 K and X-ray powder diffraction patterns were
recorded by using CuKa radiation on a Philips PW 1840 diffractometer
equipped with a graphite monochromator. Conversions of the hydrogena-
tion reactions were determined by 1H NMR and GC analysis, using a
Varian Star 3400 CX GC with a CP wax 52 CB column (50 m”0.70 mm,
df = 2.0 mm), on column injection, FID at 2508C and nitrogen as carrier
attributed to their different stabilities. The instability of Rh-
DuPHOS complexes has been described earlier.[20] The cata-
lyst probably decomposes at the end of the reaction or
during the recycling procedure.
Conclusion
The ability to readily separate and recycle homogeneous
catalysts was achieved by noncovalently anchoring this type
of catalyst on a new aluminosilicate. These new catalysts
showed a virtually identical behaviour to their homogeneous
counterparts. Upon recycling, the immobilised catalyst 2-
AlTUD-1 displayed neither loss of activity nor of selectivity.
1-AlTUD-1 was not fully recyclable, which is in line with
the known instability of the homogeneous catalyst. The ad-
vantage of not having to modify the complex for the immo-
bilisation and the absence of a negative influence of the im-
mobilisation make this methodology fast and reliable for
positively charged, proven homogeneous systems.
The choice of solvent is extremely important when apply-
ing this methodology. This factor not only influences the ac-
tivity, but also the enantioselectivity of the catalyst and the
leaching of Rh. The remobilisation of the Rh complex from
the support shows an exponential increase with increasing
polarity of the solvent. To minimise leaching, apolar solvents
are recommended, but solvents like ethyl acetate and di-
chloromethane already give satisfactory results. Further-
more, this new immobilisation of the catalysts makes it pos-
sibile to combine catalysts and substrates that are normally
incompatible owing to different solubilities. Thus, a new car-
rier material allows the straightforward immobilisation of
transition-metal catalysts, while simultaneously broadening
their applicability.
gas (10 psi). Oven program for
3 and its products: 608C (2 min),
58CminÀ1 to 1858C (3 min). Oven program for 4 and its products: 608C
(2 min), 108CminÀ1 to 2008C (6 min). Enantiomeric excesses in the hy-
drogenation of 3 were determined by chiral HPLC using a Chiralcel OD
column (250”4.6 mm) with 2-propanol/hexane (2:98) as eluent, a flow of
0.8 mLminÀ1, and UV detection at 215 nm. Retention times (min): (R)-
dimethyl 2-methylsuccinate (10), dimethyl itaconate (15), and (S)-dimeth-
yl 2-methylsuccinate (19). Enantiomeric excesses in the hydrogenation of
4 were determined by chiral GC using a Shimadzu GC-17A, equipped
with a Chiralsil DEX CB column (25 m”0.32 mm, df = 0.25 mm), He as
carrier gas, split injector (36/100) at 2208C and FID at 2208C. Retention
times (min) at 958C isotherm: 2-acetamidoacrylate (5.4), (S)-methyl 2-
acetamidopropanoate (7.5), and (R)-methyl 2-acetamidopropanoate.
Synthesis of [RhI(cod){(R,R)-MeDuPHOS}]BF4 (1): [Rh(cod){(R,R)-Me-
DuPHOS}]BF4 was prepared by a slightly modified literature proce-
dure.[8] [Rh(cod)2]BF4 (0.12 g, 0.29 mmol) and (R,R)-MeDuPHOS (0.09 g,
0.29 mmol) were dissolved in CH2Cl2 (8 mL) and stirred for 30 min.
Slowly diethyl ether (28 mL) was added, yielding an orange precipitate,
which was collected by filtration. Yield 0.10 g (59%). 1H NMR (CDCl3):
d = 1.03 (dd, 3J(H,H) = 6.6 Hz Hz, 3J(P,H) = 15.0 Hz, 6H; CH3), 1.46
(dd, 3J(H,H)
= = 18.3, 6H; CH3), 1.63 (m, 4H;
7.2 Hz Hz, 3J(P,H)
CH2), 1.93 (m, 2H; CH, CH2), 2.30–2.80 (m, 12H; CH2, CH), 2.61 (m,
2H; CH, CH2), 2.71 (m; CH, CH2), 5.07 (br, 2H; CH=C), 5.63 (br, 2H;
CH=C), 7.70 ppm (m, 4H; Ph); 31P NMR (CDCl3): d = 77.15 ppm (d,
1J(Rh,P) = 148.1 Hz).
Synthesis of [RhI(cod){(S,S)-DiPAMP}]BF4 (2): [Rh(cod){(S,S)-Di-
PAMP}]BF4 was synthesised according to the procedure of Knowles
et al.[9] [{Rh(cod)Cl}2] (0.27 g, 0.55 mmol) was added to (S,S)-DiPAMP
(0.50 g, 1.1 mmol) in 90% MeOH. The slurry became orange and after
1 h stirring gave a red-orange solution. The complex was precipitated by
the slow addition of NaBF4 (0.18 g) in water (1.37 mL). After 1 h of addi-
tional stirring a red-orange solid was obtained by filtration. The solid was
washed with water and recrystallised from ethanol, yielding 0.69 g
(84%). 1H NMR (CDCl3): d = 2.32–2.39 (m, CH2; 12H), 3.62 (s, 6H;
OCH3), 4.64 (br, 2H; CH=C), 5.30 (br, 2H; CH=C), 6.93–7.04 (m, 6H;
Ar), 7.50 (m, 2H; Ar), 7.66 (m, 6H; Ar), 7.97 ppm (m, 4H; Ar); 31P
NMR (CDCl3): d = 48.5 ppm (dd, J(Rh,P) = 151 Hz, 2J(P,P) = 38 Hz).
Experimental Section
General: Reactions and manipulations involving air-sensitive compounds
were performed under an atmosphere of dry nitrogen using standard
Schlenk techniques. Dry solvents were purchased from Aldrich and flush-
ed with nitrogen for an hour before use. Dimethyl itaconate (DMI) from
Acros was purified by crystallisation from methanol by cooling to
À788C. Bis(1,5-cyclooctadiene)rhodium tetrafluoroborate was prepared
according to a literature procedure.[21] Chloro(1,5-cyclooctadiene)rhodi-
um dimer was purchased from Strem. All other reagents were purchased
from Aldrich, Acros, or Fluka and used without further purification. Hy-
drogenations were performed in a 100-mL Parr hastelloy C autoclave
(A1128HC) or using the Avantium Quick Catalyst Screen platform:
96 small scale pressure reactors with a volume of 8 mL in parallel. These
reactors are equipped with a Teflon insert and utilise magnetic stirring.
IR spectra were recorded on a Perkin Elmer Spectrum One FT-IR spec-
Synthesis of methyl 2-acetamidoacrylate (4): The procedure of Gladiali
et al. was used to methylate 2-acetamidoacrylic acid.[22] The 2-acetamido-
acrylic acid (6.45 g, 50 mmol) was added to acetone (300 mL), followed
by K2CO3 (13.82 g, 100 mmol). The mixture was stirred mechanically and
heated to 60–658C. Iodomethane (10.64 g, 75 mmol) was added slowly
and the suspension was stirred overnight at the same temperature. The
precipitate was removed by filtration and the acetone was removed by
evaporation. The residue was dissolved in a small amount of ethyl ace-
tate/petroleum ether (7:3) and filtered over silica. The volatiles were re-
moved by evaporation and the residue was crystallised from n-hexane,
yielding 5.86 g (82%) of a colourless solid. M.p. 50–518C; 1H NMR
(CDCl3): d
= 2.14 (s, 3H; CH3CO), 3.85 (s, 3H; OCH3), 5.88 (d,
2J(H,H)
=
1.2 Hz, 1H; HCH), 6.60 ppm (d, 2J(H,H)
= 1.2 Hz, 1H;
trometer in KBr from 4000–450 cmÀ1 1H and 13C NMR spectra were ob-
.
HCH); 13C NMR (CDCl3): d = 24.7 (CH3(CO)), 53.0 (CH3O), 108.7
(CH2), 130.9 (CCH2), 164.6 (COOCH3), 168.9 ppm ((CO)N).
tained on a Varian Inova 300 MHz or a Varian VXR-400S spectrometer,
relative to TMS. 31P NMR spectra were recorded on a Varian Inova
300 MHz relative to 1% H3PO4 and were 1H decoupled. 27Al MAS ex-
periments were performed at 9.4 T on a Varian VXR-400 S spectrometer
operating at 104.2 MHz with pulse width of 1 ms. We used 4-mm zirconia
rotors with a spinning speed set to 6 kHz. The chemical shifts are report-
ed with respect to Al(NO3)3 as external standard at d = 0 ppm. The rho-
dium content of the immobilised catalysts was measured using instrumen-
tal neutron activation analysis (INAA), which was performed at the In-
terfaculty Reactor Institute (IRI), Delft. The “Hoger Onderwijs Reactor”
Preparation of AlTUD-1: Aluminium isopropoxide (6.12 g, 0.03 mol) was
added to a mixture of absolute ethanol (27.6 g, 0.60 mol), anhydrous 2-
propanol (27.05 g, 0.45 mol) and tetraethyl orthosilicate (25.0 g, 0.12 mol)
under stirring at 458C. This was followed by the addition of tetraethylene
glycol (29.1 g, 0.15 mol). Finally a solution of absolute ethanol (27.6 g,
0.60 mol), anhydrous 2-propanol (27.05 g, 0.45 mol) and H2O (5.41 g,
0.30 mol) was added dropwise to this mixture. The resulting mixture was
stirred for 0.5 h at room temperature, followed by aging without stirring
5834
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 5829 – 5835

Anchored Asymmetric Hydrogenation Catalysts
5829 – 5835
for 6 h, also at room temperature. The resulting wet gel was dried at
708C for 21 h and at 988C for 2 h; it was then hydrothermally treated at
1608C for 3–21 h in an autoclave with Teflon insert. Finally the solids
were calcined (with 18CminÀ1 to 5508C, 4 h at 5508C, with 18CminÀ1 to
600, 10 h at 6008C). Elemental analysis gave a Si/Al ratio of 3.8–4:1. An
Altetrahedral/Si ratio of 0.11:1 was determined by 27Al MAS (see Figure 2).
For other analyses see Figure 1 in Results and Discussion.
the Royal Netherlands Academy of Arts and Sciences (KNAW) for a fel-
lowship. Avantium is gratefully acknowledged for the Quick Catalyst
Screening Platform, Prof. Dr. J.C. Jansen for fruitful discussions and sug-
gestions, Delia van Rij for the INAA analysis, Joop Padmos for AAS
analysis, and Sander Brouwer for N2 adsorption measurements.
Immobilisation procedure for 1: AlTUD-1 (1.1 g) was dried at 2008C
under vacuum for 2 h. Some 2-propanol (45 mL) was added to the dried
support. After 30 min stirring, 1 (88.4 mg, 0.146 mmol) in 2-propanol
(20 mL) was added and the resulting suspension was stirred for 3 h. The
solid was collected by filtration and washed thoroughly with portions of
2-propanol (30 mL) until the washings were colourless (approx. 5 times).
Finally the catalyst was dried at 558C under vacuum for 2 h. Rh loading
was determined by INAA: 11.5 mgRhgÀ1 support, which corresponds to
an Altetrahedral/Rh ratio of approximately 10:1.
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Immobilisation procedure for 2: AlTUD-1 (1.1 g) was dried at 2008C
under vacuum for 2 h. Absolute ethanol (45 mL) was added to the dried
support. After 30 min stirring, 2 (166.0 mg, 0.219 mmol) in absolute etha-
nol (20 mL) was added and the resulting suspension was stirred for 3 h.
The solid was collected by filtration and Soxhlet extracted with absolute
ethanol overnight. Finally the catalyst was dried at 558C under vacuum
for 2 h. Rh loading was determined by INAA: 12.2 mgRhgÀ1 support,
which corresponds to an Altetrahedral/Rh ratio of approximately 10:1.
Typical hydrogenation reaction: All hydrogenation experiments were
performed with 0.1 g of immobilised catalyst (~1 wt% Rh). The catalyst
was transferred to the autoclave under a nitrogen atmosphere, followed
by 50 mL of substrate solution (concentrations and solvents given in
Tables 1 and 2). The sealed autoclave was purged with hydrogen by pres-
surising to 7 bar while stirring at 300 rpm, followed by release of pres-
sure. This cycle was repeated five times and finally the desired pressure
was applied and the stirring speed was increased to 1000 rpm. At the end
of the reaction the remaining hydrogen pressure was released and the au-
toclave was purged three times with nitrogen, pressurizing to 5 bar while
stirring at 300 rpm, followed by release. Under a nitrogen atmosphere
the solution was separated from the catalyst by a syringe equipped with
an Acrodisc GF syringe filter (1.0 mm pore size). After removal of the so-
lution, fresh substrate solution was added to the used catalyst and the hy-
drogenation procedure was repeated. All catalysts were reused in this
way several times.
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Hydrogenation using the Avantium Quick Catalyst screen: The small-
scale pressure reactors were charged with 1-AlTUD-1 (6 mg), followed
by 1.5 mL of a 0.1m solution of 3. The following solvents were screened
in parallel: methanol, ethyl acetate, dichloromethane, 2-propanol,
MTBE, and toluene. The reactors were simultaneously pressurised to
5 bar, followed by release of pressure to purge the system with hydrogen.
This cycle was repeated five times, after which the reactors were again
pressurized to 5 bars and stirred at 1500 rpm for 1 h.
Filtration test: To determine the heterogeneity of the reaction, the activi-
ty of the filtrate was measured using a filtration test. A hydrogenation re-
action was carried out according to the typical hydrogenation procedure
described above. After 5 min (17–25% of normal reaction time) the hy-
drogenation reaction was stopped by releasing the hydrogen pressure and
purging with nitrogen. The solution was withdrawn from the autoclave
with a syringe equipped with an Acrodisc GF syringe filter (1.0 mm pore
size) and the solution was stored under nitrogen. The catalyst was re-
moved from the autoclave and the stored solution was transferred back
into the autoclave under a nitrogen atmosphere. The hydrogenation reac-
tion was then continued using the typical hydrogenation procedure. After
filtration no additional conversion was observed.
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Acknowledgements
C.S. gratefully acknowledges the Dutch National Research School Com-
bination Catalysis (NRSC-Catalysis) for financial support. U.H. thanks
Received: May 27, 2004
Published online: October 7, 2004
Chem. Eur. J. 2004, 10, 5829 – 5835
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5835