Chiral vanadyl Schiff base complex anchored on silicas as solid enantioselective catalysts for formation of cyanohydrins: Optimization of the asymmetric induction by support modification

Article abstract of DOI:10.1016/S0021-9517(03)00007-1

A series of vanadyl Schiff base complexes having a terminal carbon-carbon double bond pending alkyl chains of various lengths attached to the para position of the salen ligand were prepared and anchored on three large surface area silicas, i.e., amorphous

Full text of DOI:10.1016/S0021-9517(03)00007-1

Journal of Catalysis 215 (2003) 199–207
www.elsevier.com/locate/jcat
Chiral vanadyl Schiff base complex anchored on silicas as solid
enantioselective catalysts for formation of cyanohydrins: optimization
of the asymmetric induction by support modification
Carlos Baleizão,a,b Bárbara Gigante,a,∗ Hermenegildo Garcia,b,∗ and Avelino Corma b,∗
a
INETI-Departamento de Tecnologia das Industrias Químicas, Estrada do Paço do Lumiar, 22, 1649-038 Lisboa, Portugal
b
Instituto de Tecnología Química/CSIC-Av. de los Naranjos, s/n, 46022 Valencia, Spain
Received 5 August 2002; revised 22 November 2002; accepted 2 December 2002
Abstract
A series of vanadyl Schiff base complexes having a terminal carbon–carbon double bond pending alkyl chains of various lengths attached
to the para position of the salen ligand have been prepared and anchored on three large surface area silicas, namely amorphous silica,
ITQ-2, and MCM-41 through mercaptopropysilyl groups. The resulting solids having vanadium content around 0.04 mmol/g were tested
as enantioselective catalysts for the reaction of aldehyde with trimethylsilyl cyanide and low ee values compared to solution were found.
To optimize the enantioselectivity of the solid catalysts, silylation of the free silanol groups, variation of the linker length, and screening of
the solvent were studied. The optimized enantioselective catalyst was found to be that in which the vanadyl salen complex is anchored to
amorphous silica with the longest alkyl chain of the series (11 C) and in which the residual silanol groups were masked with trimethylsilyl
◦
groups. It was found that under optimal conditions (CHCl as solvent and 0 C) the activity of these solid catalysts is very close to that of
3
the analogous complex in solution. Thus, for the reaction of benzaldehyde (1.64 mmol) with trimethylsilyl cyanide (3 mmol) in the presence
◦
of vanadium salen complex anchored on silica (100 mg) using chloroform as solvent at 0 C the enantiomeric excess was 85% as compared
to the 90% measured for the homogeneous catalyst. The solid catalyst can be reused by simple filtration up to three times, retaining a large
part of the activity of the fresh catalyst.
2003 Elsevier Science (USA). All rights reserved.
Keywords: Asymmetric catalysis; Heterogeneous enantioselective catalysis; Vanadium salen complexes; Chiral cyanohydrins; ITQ-2 as support; MCM-41 as
support
1. Introduction
a significant loss of its activity and asymmetric induction
capability with respect to that of the homogeneous phase.
However, considerable progress showing that high enan-
tiomeric excesses, sometimes very close to those obtained
for the analogous soluble complexes, can be obtained by an-
choring pure complexes has been made recently [5,6].
Herein, we describe that covalent anchoring of pure
vanadyl salen complexes on the surface of silicas is not
enough to achieve high enantiomeric excesses for the cyano-
hydrin formation from aldehydes as is observed in solution.
It is necessary to protect free surface silanol groups, to have
a linker of sufficient length, and to choose the appropriate
solvent. In this way, the complex behaves like that in
homogeneous phase, but still anchored to the solid surface.
In this way, the catalysts are truly heterogeneous and
retain a significant percentage of their initial activity and
enantioselectivity.
Anchoring a soluble catalyst onto a solid surface is
a general methodology to convert a homogeneous into
a heterogeneous catalyst [1–4]. The main advantages of
heterogeneization are the easy separation of the catalyst
from the reaction mixture, allowing the possibility to recover
and reuse the catalyst, and the possibility of continuous-flow
operation.
The most challenging heterogeneization processes are
those related to the transformation of homogeneous enan-
tioselective catalytic reactions. Until quite recently, covalent
anchoring of a highly enantioselective catalyst resulted in
*
Corresponding authors.
E-mail addresses: barbara.gigante@ineti.pt (B. Gigante),
hgarcia@qim.upv.es (H. Garcia), acorma@itq.upv.es (A. Corma).
0021-9517/03/$ – see front matter
doi:10.1016/S0021-9517(03)00007-1
2003 Elsevier Science (USA). All rights reserved.

200
C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
2. Experimental
2.3. Diffuse reflectance (DR) UV–vis spectra
Transmission UV–vis spectra of transparent solutions
were recorded in a Shimadzu UV–vis spectrophotometer.
DR spectra of the opaque powders were recorded in a Varian
Cary 5G UV–vis NIR spectrophotometer adapted with a
praying mantis attachment and using BaSO4 as reference.
The reflectance data were converted to the Kubelka–Munk
function F(R) that correlates with the absorbance of the
complex [13].
2.1. Compounds and materials
Starting reagents (trans-R,R-1,2-cyclohexanediamine,
3-tert-butyl-salicylaldehyde, 3,5-di-tert-butyl-salicylalde-
hyde), vanadyl sulfate, azoisobutyrylnitrile, 10-undecen-
1-ol, allyl alcohol, 5-hexen-1-ol, trimethylsilyl cyanide
(TMSCN), aldehydes, and anhydrous solvents were pur-
chased from Aldrich. The reagent-grade solvents were ob-
tained from Scharlau and used without further purifica-
tion. Homogeneous vanadyl (IV) complexes 1a [7] and 5-
chloromethyl-3-tert-butylsalicylaldehyde intermediate 4 [8]
and the asymmetric ligand 7a–c [9] and complex 1a–c [7]
were prepared according to the procedures reported in the
literature. Silica was purchased from Aldrich; MCM-41
was prepared by hydrothermal crystallization at 100 ◦C us-
ing cetyltrimetyl ammonium bromide as structure direct-
ing agent and Aerosil as silica source following the pro-
cedure described in detail elsewhere [10,11]. ITQ-2 was
synthesized by ultrasound delamination of a MCM-22 pre-
cursor previously submitted to swelling by ion exchanging
the initial hexamethyleneimine template agent by hexade-
cyltrimethyl ammonium as reported [12]. The particle size,
surface area, and pore volume of these solids were mea-
sured by scanning electron microscopy and isothermal ni-
trogen adsorption, respectively. The values are summarized
in Table 1.
2.4. Elemental analysis and atomic absorption
Combustion chemical analyses (C, H, N) of the silicates
containing organic material were carried out in a Perkin–
Elmer analyzer. Vanadium analyses of the solids were
carried out by quantitative atomic absorption spectroscopy
after attacking a given amount of the solid with concentrated
hydrofluoric acid at 60 ◦C for 2 days.
2.5. General procedure for the preparation of
mercaptopropyl-functionalized solid supports
After dehydration of the solids (1 g at 200 ◦C under
10−2 Torr for 2 h), the required amount of 3-mercaptopropyl-
trimethoxysilane (3.12 ml, 0.0166 mol) in dry toluene
(3.5 ml) was added and the suspension stirred at reflux
temperature under nitrogen atmosphere for 48 h. The solid
was filtered and Soxhlet-extracted with dichloromethane for
24 h. After drying the solids (at 45 ◦C under 10−1 Torr for
2 h), the density of the 3-mercaptopropyl groups anchored in
the solid was estimated from combustion chemical analysis.
2.2. IR spectra
FT-IR spectra of unsupported asymmetric ligand and
complex 1a were recorded in KBr disks at room temperature
in a Nicolet 710 FT spectrophotometer. FT-IR spectra of
supported complexes were recorded at room temperature
under vacuum using a sealed greaseless quartz cell fitted
with CaF2 windows in a Nicolet 710 FT spectrophotometer.
Self-supported wafers (∼ 10 mg) were prepared by pressing
the silicate powder at 1 Ton cm−2 for 3 min. The samples
were outgassed at 100 ◦C under 10−2 Pa at 1 h before
recording the IR spectra.
2.6. General procedure for the protection of the solid
supports
When desired to protect residual silanol groups, solids
modified by mercaptopropyl silyl groups were degassed
at 50 ◦C under 10−2 Pa for 1 h. Then, an excess of
ethoxytrimethylsilane (7.8 ml, 0.033 mol) in dry toluene
(5.3 ml) was added and the suspension stirred at reflux
temperature under nitrogen atmosphere for 24 h. The solid
was filtered, Soxhlet-extracted with dichloromethane for
24 h, and dried (at 45 ◦C under 10−1 Torr for 2 h). The
amount of trimethylsilyl groups anchored was estimated
from the difference in the C content of the solid before
and after silylation. The residual population of unprotected
silanol groups was determined by IR spectroscopy.
Table 1
Structural, textural, and analytical data for the solids used as supports
SiO
ITQ-2
MCM-41
2
Structure
Amorphous Layers
Hexagonal
channels (38 Å)
0.1–0.3
800
2.7. Preparation of the metal salen complexes having
ω-C=C double bonds
Particle size (µm)
Surface area (m g
Micropore volume (cm g
Degree of silylation
–
350
–
< 0.5
700
0.009
90%
0.04
2
−1
)
3
−1
)
0.61
70%
0.04
a
> 95%
0.04
The corresponding ω-unsaturated alcohol (2 mmol) was
added to a xylene solution (10 ml) of the mixture of
complexes 1a–c in the statistical proportion indicated in
Scheme 2 (600 mg). The solution was stirred at reflux
−1
Vanadium content (mmol g
a
)
Estimated by the decrease in the intensity of the OH groups in the IR
spectrum of the solids before and after silylation.

C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
201
temperature for 24 h. After this time, the solvent was
evaporated under vacuum and the crude containing the
complex 1d was used to anchor onto the solid without further
purification.
conversion, half the volume was filtered and the resulting
clear solution let to react. The percentage of leaching was
estimated by comparing the time-conversion plot of the twin
reactions with and without solid.
2.8. General procedure for anchoring the vanadyl Schiff
base complex on the surface of the modified solids
3. Results and discussion
The reaction under study is shown in Eq. (1) and consists
of the catalytic addition of trimethylsilyl cyanide to the
carbonyl group of an aldehyde, whereby the trimethylsilyl
derivative of the corresponding cyanohydrin is formed.
This reaction has been reported to occur with high
enantioselectivity in the presence of chiral vanadyl salen
complexes having bulky tert-butyl groups in the ortho–para
positions of the phenolic moiety (structure 1a) [14,15]. The
substrate to catalyst molar ratio was 1000 and dichloro-
methane was the solvent of choice for this reaction.
To the crude of metal salen complexes containing 1d
prepared previously, modified solids (350 mg) and AIBN
(100 mg) were added in nitrogen atmosphere. Then, de-
gassed chloroform (10 ml) was added and the suspension
stirred magnetically at 80 ◦C under nitrogen atmosphere
for 20 h. The solid was filtered and Soxhlet-extracted with
dichloromethane for 24 h. After drying the solids (45 ◦C un-
der 10−1 Torr for 2 h), the quantity of vanadium was deter-
mined by quantitative atomic absorption spectroscopy after
desegregation of the solid. The data are contained in Table 1.
The target of our research is to anchor a chiral vanadyl
salen complex having a structure close to that of 1a on the
surface of different silica types. We [18] and others [3] have
previously reported the anchoring of metal salen complexes
on zeolites and other structured or amorphous silicates, with
only limited success with regard to asymmetric induction.
In some cases, leaching of the catalyst from the solid to
the solution has been observed [16]. In other cases, the e.e.
using the immobilized catalyst was much lower than that
of the soluble complex due to the presence of undesirable
adventitious acid sites on the solid [19] or to the need of
a cooperative contribution of two complexes, rendering the
process bimolecular from the point of view of the catalyst
as for the enantioselective epoxide ring opening with Cr
salen complexes [20]. In those cases, immobilization of
the catalyst has a considerable negative influence on the
obtained e.e. [18].
2.9. General procedure for the asymmetric addition of
cyanide to aldehydes
For the control reactions with the homogeneous catalyst
1a, the experimental procedure described by Belokon et al.
[14,15] was followed. Thus, a Schlenk tube was charged
with the homogeneous catalyst (0.1 mmol%) and 1.9 ml of
dry chloroform. The aldehyde (1.64 mmol) and nitroben-
zene (1.64 mmol; internal standard) were also added. The
mixture was stirred for 5 min and then TMSCN was added
(1.1 eq; 1.8 mmol). The resulting mixture was stirred at
room temperature or 0 ◦C under nitrogen atmosphere and
the course of the reaction followed by GC (ChiralDex G-
TA chiral column, 30 m, 0.25 mm). For the heterogenized
catalysts a similar procedure was followed: 100 mg of het-
erogeneous catalyst (0.04 mmol/g of V) was suspended in
dry chloroform (1.9 ml) followed by the addition of the alde-
hyde (1.64 mmol) and the nitrobenzene as internal standard
(1.64 mmol). The suspension was stirred for 5 min and then
TMSCN (4.92 mmol) was added. The heterogeneous reac-
tion mixture was stirred at the corresponding temperature
and the course of the reaction followed by analyzing the or-
ganic phase by GC (with the same column as before). The
physical and analytical data of the trimethylsilyl ethers of
corresponding cyanohydrins were consistent with those re-
ported in the literature [16,17]. In all cases, the (R,R)-isomer
of the catalyst gave an excess of the (S)-enantiomer of the
cyanohydrin derivative by analogy with the literature reports
[14,15].
However, in the reaction under consideration here
(Eq. (1)), the catalytic process has been demonstrated [15]
to be unimolecular with respect to the catalyst concentra-
tion and requires a low catalyst/substrate ratio. Therefore
this reaction seems more suitable to being performed with
covalently anchored metal salen complexes.
To address the influence of the solid support on the enan-
tioselectivity of the anchored vanadyl complex, three solids
2.10. Leaching tests
The percentage of activity due to the complex or vana-
dium species leached from the solid and present in the so-
lution was determined by performing the reactions at the
corresponding temperature under the reaction conditions de-
scribed above until the conversion was about 30%. At this
Equation 1.

202
C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
Scheme 1.
having large surface area were selected in the present study.
Table 1 contains the main textural and physicochemical pa-
rameters of the solid used.
The strategy to obtain chiral vanadyl salen complexes
covalently anchored to the silica surface was the same for
the three solids and is illustrated in Scheme 1.
We selected amorphous silica since it is the most easily
available solid, but we also include in the study all silica-
ITQ-2 and all silica-MCM-41. ITQ-2 is a relatively novel
delaminated zeolite [11], whose structure is formed by
crystalline zeolite layers (25 Å depth). The main advantage
of ITQ-2 is the large accessible surface area (see Table 1)
and the presence of a significant population of OH groups
located on the ring cups where anchoring can occur. In
contrast to the ITQ-2 structure having a large external area
and a reduced microporosity, the structure of MCM-41
encompasses a series of parallel hexagonal channels (38 Å
diameter) and most of the total area corresponds to the
internal mesopores [10,11]. The interior of the mesoporous
channels of MCM-41 is available to substrates and products
and is full of silanol groups that can be used to anchor the
catalytic active complex.
Basically the methodology consists in anchoring on the
solid surface the 3-mercaptopropylsilyl groups followed
by exhaustive silylation of the rest of the silanol groups.
For the sake of comparison, one of the silica catalysts
[VO/SiO2(OH)] was prepared omitting the silylation step.
This provides a valid comparison to establish the influence
of the presence of residual silanol groups on the product
enantioselectivity. The degree of silylation was determined
by comparing the area of the OH stretching band in the IR
for each solid before and after silylation. The results are also
included in Table 1. To avoid the interference of coadsorbed
water in the measurement of the silanol group population,
before recording the IR, the solids were degassed at 100 ◦C
under reduced pressure for 1 h. From these measurements it
can be concluded that in the cases of ITQ-2 and MCM-41
part of the initial population of the silanol groups remains

C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
203
still unaltered after the silylation procedure. The residual
silanol groups that have not been silylated could correspond
to the fraction of OH groups located in nests or pockets
where spatial restrictions preclude silylation. This residual
population of OH groups was minimum for silica, but for
this solid a catalyst [VO–SiO2(OH)] containing OH was also
studied. These data will become relevant when rationalizing
the enantiomeric excesses obtained for each solid.
A major strength of our anchoring methodology is the
independent preparation of vanadyl salen complex 1a–c
before anchoring to the solid surface. This allows the
complete characterization of the complexes to be anchored
onto the solid, thus ensuring the identity and purity of the
catalytic active complex. To prepare the vanadyl complex
we have followed a previous report in the literature [9] in
which a statistical distribution of a mixture of salen ligands
differing in the nature of the groups at the para position was
obtained in a one-pot reaction (Scheme 2).
covalent anchoring onto the mercapto groups of the solid
after appropriate transformation into ω-terminated C=C
double bond.
After preparation of the ligand, the vanadyl complex
was formed by reacting 7a–c with vanadyl sulfate us-
ing ethanol/water as solvent [7]. The last step before at-
taching the mixture of complexes to the support was the
nuchleophilic substitution of benzylic chlorine by an ω-
unsaturated linear long-chain alcohol [21]. The leading idea
is to bind the complex to the solid surface by means of flex-
ible tethers with different lengths, so to address the possible
influence of the degree of freedom of the complex with re-
spect to the solid surface. By varying the length of the chain
it may be possible to address whether the proximity of the
solid surface and the metallic center of the complex has a
negative influence, restricting or making difficult the coordi-
nation of the substrate to the vanadium metal. This potential
negative factor should be minimized by increasing the length
of the tether anchoring the complex to the surface. The ob-
jective is to permit the complex to adopt conformations sim-
ilar to those in the homogeneous phase, wherein large e.e.
have been already achieved for this type of complex.
The actual anchoring of the vanadyl Schiff base complex
to the modified solids was accomplished through a radical
chain addition of a thiol to the terminal carbon–carbon dou-
As is indicated in Scheme 2, preparation of the ligand
was carried out by reacting R,R-1,2-cyclohexanediamine (5)
with a mixture of unequivalent amounts of salicylaldehydes,
4 and 6. This results in a distribution of three salen ligands
in which the one having two tert-butyl groups at the para
position (7a) cannot be anchored while ligands 7b and 7c
having a chloromethyl functionality makes them suitable for
Scheme 2.

204
C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
ble bond using AIBN as radical initiator [8]. After the an-
choring procedure the solid was thoroughly extracted to re-
move it from any adsorbed complex not properly anchored
and, particularly, adventitious 1a that is present predomi-
nantly in the complex mixture used for the preparation of
the solid catalyst (see Scheme 2 for proportions). The actual
loading of vanadyl complex is controlled by the density of
mercaptopropylsilyl groups and the efficiency of the radical-
promoted addition. This loading is independent of the den-
sity of silanol groups. It was maintained purposely low since
the reaction under study works at a high substrate/vanadium
ratio.
The solids were characterized by analytical and spec-
troscopy techniques. The loading of the complex was deter-
mined by vanadium analysis after the disaggregation of the
solid. The data are contained in Table 1. The most salient
feature from the analytical data is that the vanadium con-
tent of the three solids per weight is very similar, although
obviously the loading differs considerably if the vanadium
content per surface area is is the parameter considered. The
density of complexes per surface area is more than double
for VO/silica compared to the other two solids, which in
turn have similar values of vanadyl complex considered ei-
ther per weight or per surface area.
Fig. 2. IR spectra of the ligand mixture 7a–c (a), the corresponding vanadyl
complexes 1a–c (b), catalyst VO/SiO (c), catalyst VO/ITQ-2 (d), and
2
catalyst VO/MCM-41 (e). The characteristic band of the metal salen
The presence of vanadium Schiff base complex anchored
on the solids can be assessed spectroscopically. Thus, in the
diffuse reflectance UV–visible spectra of the solids (Fig. 1)
the characteristic metal–ligand band appearing at 360 nm
is observed although with lower resolution than that for
the transmission spectrum of the vanadium complex 1a in
solution. In the IR spectra of the solids (Fig. 2) the most
characteristic band from the point of view of the structural
identification is the presence of the metal salen complexes
characteristic band appearing at 1536 cm−1, which is absent
for the ligand but can be clearly observed for the vanadium
complexes either free or anchored on the solids. This band
together with the optical spectra indicates that the complex
1d has survived the anchoring procedure based on the
complexes has been labeled with arrows. Spectra c, d, and e were recorded
◦
at room temperature in sealed cell after outgassing the water at 100 C under
−2
10 Pa for 1 h.
radical addition under mild conditions of thiol groups to the
terminated carbon–carbon double bond of the alkyl chain at
the para position of the complex.
The solids were screened as enantioselective catalyst for
the reaction of benzaldehyde with TMSCN using dichloro-
methane as solvent under the experimental conditions re-
ported in the literature [14] and complex/substrate ratio of
0.24 mol%, somewhat higher than the ratio reported in the
literature for this reaction (0.1 mol%) [14]. The results are
summarized in Tables 2 and 3. A blank control using the
modified solid (SiO2/SHp) lacking vanadyl complex indi-
cated that at even much longer reaction times this support
exhibits a very low activity (Table 2), thus demonstrating
that the activity of the solid catalyst is really due to the pres-
Table 2
Influence of the chain length linking the complex and the solid on the results
of the catalytic addition of TMSCN to benzaldehyde in dichloromethane in
a
the presence of vanadyl salen complex supported on silylated silica
Catalyst
SiO /SHp
Chain length
Conversion (%)
e.e. (%)
–
3
6
8
68
66
70
0
52
56
63
2
VO–SiO
VO–SiO
VO–SiO
2
2
2
11
a
Reactions were run at room temperature under N atmosphere for
2
Fig. 1. Transmission UV–vis spectrum of homogeneous catalysts 1a (a) and
72 h: benzaldehyde (1.64 mmol), TMSCN (1.1 eq), heterogeneous catalyst
diffuse reflectance UV–vis spectra (plotted as the Kubelka–Munk function
(100 mg, 0.24 mol%), nitrobenzene (1.64 mmol), and CH Cl (1.9 ml). No
2 2
of reflectance; R) of VO/ITQ-2 (b), VO/MCM-41 (c), and VO/SiO (d).
leaching was detected.
2

C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
205
Table 3
the solid in which the population of free silanol groups is
higher, thus lowering the e.e. value. On the other hand, silica
is the support with less residual OH groups and this may ex-
plain the higher e.e. value achieved for this solid. To support
this assumption a vanadyl salen sample anchored on SiO2
that was not submitted to silylation of the silanol groups was
also used as catalyst (Table 3). The lower e.e. obtained for
this unsilylated VO–SiO2(OH) sample strongly supports our
claim of a negative influence of the free silanol groups on the
asymmetric induction ability of the solid catalyst. Concern-
ing the unfavorable presence of free silanol groups, an alter-
native that could diminish the need of silylation would be to
optimize the calcination procedure and synthesis conditions
to reduce to the minimum possible level the population of
free silanols.
Results of the catalytic addition of TMSCN to benzaldehyde in dichloro-
methane in the presence of vanadyl salen complex anchored to different
supports
a
b
c
Catalyst
Time (h)
Conversion (%)
e.e. (%)
c
VO/(1a)
VO/SiO
VO/SiO (OH)
VO/ITQ-2
24
72
72
72
144
90
70
70
53
40
90
63
48
58
49
2
d
2
VO/MCM-41
a
Reactions were run at room temperature under N atmosphere:
2
benzaldehyde (1.64 mmol), TMSCN (1.1 eq), heterogeneous catalyst
(100 mg, 0.24 mol%), nitrobenzene (1.64 mmol), and CH Cl (1.9 ml).
No leaching was detected.
2
2
b
Carbon chain n = 9, in Scheme 1.
c
0.1 mol% used.
d
Support without surface silylation. Carbon chain, n = 9.
In an attempt to increase the e.e. values for the reaction
of benzaldehyde, we screened the activity of VO–SiO2 for
the same process and conditions using different solvents.
The rationale behind this is that a variation of the polarity
and hydrophilicity of the solvent could modify the activity
of the complex by electrostatic interactions and by changes
in the location of the complex at the solid–liquid interface.
As a matter of fact, Table 4 shows that there is a large
influence of the nature of the solvent on the e.e. values of
the cyanohydrin derivative. Although there is not an obvious
correlation between the polarity of the solvent and the e.e.
achieved in the reaction product, it is clear from Table 4
that the solvent can dramatically vary the outcome of the
reaction. The best solvent of the series was chloroform
and when the reaction is carried out at low temperatures
the e.e. is similar to that attained in solution with the
homogeneous catalyst. Table 4 indicates that there probably
are several factors influencing concurrently the reaction and
that the interaction between the complex, solvent, and solid
surface is not simple to understand. In addition, the lower
asymmetric induction of the VO–ITQ-2 as compared to VO–
SiO2 was also reconfirmed under the optimum conditions.
ence of the anchored complex. No catalytically significant
leaching of vanadium from the solid to the solution (which
could catalyze the reaction in the homogeneous phase) was
observed for any of the three supported catalysts. Thus, if
some vanadium metal goes from the solid to the solution
it has to be catalytically silent and below the analytic de-
tection limits (nevertheless see deactivation of solids be-
low). The most important data from Tables 2 and 3 are
the e.e., which are significantly lower (maximum 63% e.e.)
than that reported for the homogeneous reaction in solution
(94%) [14]. In our hands, we repeated the reported reaction
in dichloromethane using complex 1a as catalyst and ob-
tained an e.e. value of 90%, very close although somewhat
lower than that reported. Therefore it can be concluded that
anchoring of the complex on the solid surface has a nega-
tive influence on the asymmetric induction of the solid cat-
alyst, even though the support has no significant activity in
promoting the nonasymmetric product formation. To over-
come this problem encountered also in related studies, we
attempted to minimize as much as possible the solid surface–
complex interaction by varying the linker length, protecting
free silanol groups, and varying the nature of the solvent.
The influence of the chain length on the e.e. values
of the product for the vanadyl salen complex anchored
on silica is shown in Table 2. As can be seen there, the
e.e. value increases progressively with the length of the
tether linking the complex to the silica solid. These data
demonstrate the beneficial influence of designing a complex
with sufficiently large flexibility to allow the substrate–
complex adduct to adopt a spatial disposition similar to that
in the homogeneous phase. Molecular modeling indicates
that the stretched conformation for the C11 linker should
allow the complex to be as far as 46 Å from the solid surface.
Also we noted that there is an influence of the nature
of the support in which the complex is anchored (Table 3).
A likely explanation for this observation stems from corre-
lating the decrease of the asymmetric induction ability of
the complex with the presence of the free silanol groups on
the support. As indicated in Table 1, the VO–MCM-41 is
Table 4
Results of the reaction of TMSCN with benzaldehyde using VO–SiO as
2
a
catalyst in the presence of different solvents
b
Solvent
CH Cl
Hexane
Toluene
Ether
Electric dipole (debye) Time (h) Conversion (%) e.e. (%)
1.60
0
72
24
72
96
96
72
72
48
48
120
70
71
71
74
43
67
79
67
73
78
62
32
2
2
0.37
1.15
1.75
3.92
0
31
28
22
26
THF
CH CN
3
CCl
4
36
CCl CH
1.76
1.04
1.04
31
72
85 (90)
3
3
CHCl
CHCl
3
3
c
a
Reactions were run at room temperature under N atmosphere: ben-
2
zaldehyde (1.64 mmol), TMSCN (1.1 eq), VO/SiO (100 mg, 0.24 mol%),
2
nitrobenzene (1.64 mmol), and solvent (1.9 ml).
b
Data taken from [22].
c
◦
TMSCN (3 eq), temperature 0 C; mass balance 94%. The value in
parentheses corresponds to the e.e. with homogeneous catalyst.

206
C. Baleizão et al. / Journal of Catalysis 215 (2003) 199–207
Table 5
concluded that the vanadyl complex anchored through an 11-
carbon tether on silylated silica is a general enantioselective
catalyst for the cyanohydrin formation from aldehydes and
promotes an enantioselectivity very similar (although lower)
than the analogous complex in homogeneous catalysis under
the same conditions.
Results of the recycling of the catalyst VO–SiO in the reaction of TMSCN
with benzaldehyde
2
a
Used
Conversion (%)
Mass balance (%)
e.e. (%)
1
2
3
4
5
78
80
75
50
23
94
> 95
> 95
> 95
> 95
85
84
85
82
63
4. Conclusions
a
◦
Reactions were run at 0 C under N atmosphere for 120 h: benzalde-
2
hyde (1.64 mmol), TMSCN (3 eq), VO–SiO (100 mg, 0.24 mol%), ni-
trobenzene (1.64 mmol), and CHCl (1.9 ml).
3
2
Anchoring of a highly enantioselective complex on a
solid surface, even if it is pure, may reduce its asymmetric
induction capability, due to its interaction with the solid
surface, but it is possible to increase the enantioselectivity
of the anchored complex to the values obtained in solution.
To achieve this goal, the tether linking the complex and the
solid should be long enough to permit the complex to have a
large conformational freedom and the solid surface has to be
modified to reduce the presence of residual silanol groups.
Finally the importance of the solvent on the asymmetric
induction is consistent with variations in the location of the
complex with respect to the solid–liquid interface and has
to be considered when reporting the enantioselectivity of a
heterogeneous catalyst.
With the optimum conditions from Table 4 (0 ◦C and
CHCl3 as solvent) we proceeded to study the reusability of
the catalyst. The results are summarized in Table 5. After
having used the solid catalyst in a reaction, the solid was
recovered by simple filtration and used for a new batch with
fresh reagents. As can be seen in Table 5, large changes
in the activity and enantioselectivity are observed in the
fourth use of the catalyst. The reason for the deactivation
of the vanadium complex could be poisoning of the solid,
loss of the vanadium metal, degradation of the ligand, or a
combination of these possibilities. From the analytical data
and the diffuse reflectance and IR spectra of the deactivated
catalyst it can be concluded that some depletion in the
vanadium content occurs upon repetitive use. Chemical
analysis of the deactivated VO/SiO2 catalyst after the fifth
use indicates vanadium content of 0.02 mmol g−1, which is
significantly lower than that of the fresh catalyst. However
it has to be remembered that the vanadium leached out of
the solid is below the detection limit and thus does not
contribute to the catalytic activity (see above and Table 3
for the leaching test).
Acknowledgments
Financial support to C. Baleizão from Fundação para a
Ciência e Tecnologia, Portugal (PRAXIS XXI/BD/21375/99)
is gratefully acknowledged. Part of this work has been fi-
nanced by the Spanish DGES (MAT2000-1768-CO2-01).
Once the studies on the activity and recycling of the VO–
SiO2 were complete for the reaction with the benzaldehyde,
we expanded the study to other aldehydes. The substrates,
the conditions, and the results obtain are collected in Ta-
ble 6. For the sake of comparison, the e.e. values achieved in
chloroform solution using soluble 1a as homogeneous cata-
lyst are also included in Table 6. From these results it can be
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4-Fluorbenzaldehyde
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88
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