Preparation and characterization of chiral oxazaborolidine complex immobilized SBA-15 and its application in the asymmetric reduction of prochiral ketones

Article abstract of DOI:10.1002/asia.200900412

The immobilization of chiral oxazaborolidine complex in the wellordered mesochannels of SBA-15 is demonstrated by a postsynthetic approach using 3-aminopropyltriethoxysilane as a reactive surface modifier. The immobilized catalysts are characterized by va

Full text of DOI:10.1002/asia.200900412

DOI: 10.1002/asia.200900412
Preparation and Characterization of Chiral Oxazaborolidine Complex
Immobilized SBA-15 and Its Application in the Asymmetric Reduction of
Prochiral Ketones
[
a, b]
[b]
[a]
Umesh Balakrishnan,
Nallamuthu Ananthi, Sakthivel Tamil Selvan,
[a] [a, b] [a]
[
a]
Ravindra Pal, Katsuhiko Ariga, Sivan Velmathi,*
and Ajayan Vinu*
Abstract: The immobilization of chiral
oxazaborolidine complex in the well-
ordered mesochannels of SBA-15 is
demonstrated by a postsynthetic ap-
proach using 3-aminopropyltriethoxysi-
lane as a reactive surface modifier. The
immobilized catalysts are characterized
by various techniques, such as XRD,
nitrogen adsorption, HRSEM, UV/Vis
diffuse reflectance spectroscopy, and
FTIR spectroscopy. The catalysts are
used for the enantioselective reduction
of aromatic prochiral ketones. The ac-
tivity of the chiral oxazaborolidine
complex immobilized SBA-15 catalysts
is also compared with that of the pure
chiral oxazaborolidine complex, which
is a homogeneous catalyst. It is found
that the activity of the chiral complex
immobilized SBA-15 heterogeneous
catalyst is comparable with that of the
homogeneous catalyst.
Keywords: asymmetric catalysis
·
ketones · mesoporous materials ·
reduction · silicates
Introduction
borane and homogeneous catalysts starting from chiral
amino alcohols. Several reports focus on the preparation of
chiral ligands with different functional moieties and their
Chiral secondary alcohols are important intermediates for
the synthesis of chiral natural products and biologically
[9,10]
catalytic activity under homogeneous conditions.
Howev-
[1]
active compounds. Among the various methods available
for the synthesis of secondary alcohols, the enantioselective
reduction of prochiral ketones with borane in the presence
of a chiral ligand is one of the efficient methods, and has re-
ceived considerable attention in recent years. The pioneer-
er, homogeneous catalysts have several drawbacks, such as
the difficulty in separation of products from the reaction
mixture, wastage of expensive chiral ligands, tedious
workup, and rigorous reaction conditions, which limit their
usage in industry. To avoid these problems, the conversion
of the homogeneous system into a heterogeneous phase by
immobilizing the chiral ligands in a solid matrix is highly
critical and interesting.
[2,3]
ing works of Itsuno and co-workers
and Corey and co-
[4–8]
workers
have inspired the research interest of chemists in
the asymmetric reduction of prochiral ketones to chiral sec-
ondary alcohols using chiral oxazaborolidines derived from
Yao et al. used organic polymers and silica materials as
the support for the immobilization of homogeneous asym-
[11]
metric catalysts and studied their chiral activity. Unfortu-
nately, these supports have poor textural parameters and
could not accommodate a huge quantity of the chiral li-
gands, which is critical for various applications. Recently,
mesoporous MCM-41 materials with various pore diameters,
which offers large surface areas and uniform pore size distri-
bution, were used as the supports for the immobilization of
amino alcohol derivatives and their catalytic properties were
[
a] U. Balakrishnan, S. T. Selvan, Dr. R. Pal, Dr. K. Ariga,
Dr. S. Velmathi, Dr. A. Vinu
International Center for Materials Nanoarchitectonics
World Premier International (WPI) Research Initiative
National Institute for Materials Science
Tsukuba, Ibaraki 305-0044 (Japan)
Fax : (+81)29-860-4706
E-mail: vinu.ajayan@nims.go.jp
[12–16]
investigated in the asymmetric reduction of ketones.
[
b] U. Balakrishnan, N. Ananthi, Dr. S. Velmathi
Organic and Polymer Synthesis Laboratory
Department of Chemistry
However, these materials suffer from poor thermal and
polar solvent stability. Thus, it is highly imperative to find
supports that are thermally and water stable. The highly or-
dered, large-pore mesoporous silica molecular sieve SBA-
National Institute of Technology
Tiruchirappalli-620 015 (India)
Chem. Asian J. 2010, 5, 897 – 903
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
897

FULL PAPERS
1
5, which has considerably thicker pore walls than MCM-41,
CAL was detected in the supernatant of the washing sol-
vent. It has been reported that the unreacted surface silanol
groups on the modified mesoporous catalyst significantly
was recently synthesized by using an amphiphilic triblock
copolymer as the structure-directing agent in highly acidic
media.
[17]
[20]
SBA-15 exhibits improved hydrothermal and
affect the enantioselectivity of a given chiral reaction.
[18,19]
water stability relative to MCM-41.
Thus, it is imperative to cap the unreacted surface silanol
groups with trimethyl silyl (TMS) groups after the encapsu-
lation of the CAL. As shown in Scheme 1, CAL-immobi-
lized SBA-15 was treated with hexamethyldisiloxane
(HMDS) to cap the free surface silanol groups with TMS
groups.
To understand the degree of CAL encapsulation and the
structure of the SBA-15 support after CAL immobilization,
the immobilized catalyst was characterized by XRD, nitro-
gen adsorption, and HRSEM studies. Figure 1 shows the
Herein we demonstrate for the first time the immobiliza-
tion of chiral oxazaborolidine complex on the porous matrix
of highly ordered, hexagonal-type, two-dimensional mesopo-
rous silica SBA-15 by a postsynthetic approach using 3-ami-
nopropyltriethoxysilane as a reactive surface modifier. The
immobilized catalyst was characterized by several physico-
chemical techniques to prove that the chiral complex is per-
fectly immobilized in the mesochannels of SBA-15. The cat-
alysts were tested for the enantioselective reduction of aro-
matic prochiral ketone. It was found that the immobilized
catalyst show similar activity as that of the homogeneous
catalysts in the above reaction. Further, it was found that
the chiral complex immobilized SBA-15 is more stable than
the pure chiral complex.
Results and Discussion
Synthesis and Characterization of (R,E)-Alkyl 2-(5-chloro-
2
-hydroxybenzylamino)-3-methyl butanoate (CAL)
Immobilized SBA-15
The first step in the preparation of (R,E)-alkyl 2-(5-chloro-
-hydroxybenzylamino)-3-methyl butanoate (CAL) immobi-
Figure 1. Powder XRD patterns of a) pure SBA-15, b) APTES-function-
alized SBA-15, and c) CAL-immobilized SBA-15.
2
lized SBA-15 is the covalent grafting of aminopropyltrie-
thoxysilane (APTES) groups on the surface of the pore wall
structure of SBA-15. This process introduces amine groups
on the surface of the pore walls, which is required for an-
choring the CAL (Scheme 1). Elemental analysis confirmed
that the APTES-modified SBA-15 contains a significant
amount of carbon and nitrogen, proving that the APTES
groups are covalently bound to the surface silanol groups of
SBA-15. The APTES-modified SBA-15 was further treated
with CAL to form CAL-immobilized SBA-15, a heterogene-
ous chiral catalyst. After the encapsulation, the catalyst was
washed several times with different solvents until no more
powder XRD patterns of pure SBA-15, APTES-functional-
ized SBA-15, and CAL-immobilized SBA-15. All the sam-
ples show a well resolved (100) reflection and several higher
order reflections at 2q angles between 1.5 and 38, indicating
excellent structural ordering with p6mm space group sym-
metry, and the XRD patterns are similar to that of the pre-
viously reported pure SBA-15 silica material. This result in-
dicates that all the materials, even after the modification
with amine or CAL, exhibit well ordered two-dimensional
hexagonal structures with linear arrays of pores arranged in
regular intervals. It is interest-
ing to note that the intensity of
the peaks at lower angle for the
amine-, and CAL-immobilized
SBA-15 is much lower than that
of the parent SBA-15 without
any modification. The reduction
in the intensity of the peaks
mainly arises from the encapsu-
lation of the CAL or APTES
groups on the surface, which
gives the large contrast in den-
sity between the silica walls and
the empty pores relative to that
between the silica walls and the
functional molecules, which are
Scheme 1. Preparation of CAL-immobilized SBA-15 end capped with TMS.
attached on the porous surface
898
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Chem. Asian J. 2010, 5, 897 – 903

Chiral Oxazaborolidine Complex Immobilized SBA-15
of SBA-15. These results also confirm that the CAL is im-
mobilized inside the mesochannels of SBA-15.
Figure 2 shows the nitrogen-adsorption isotherms of pure
SBA-15 as well as amine- and CAL-immobilized SBA-15,
and the results for those samples are given in Table 1. As ex-
Figure 3. Pore size distribution of pure SBA-15 (*), APTES-functional-
ized SBA-15 (
), CAL-immobilized SBA-15 (~), and CAL-immobilized
&
SBA-15 capped with TMS groups (!).
of CAL inside the mesoporous channels of SBA-15 support.
The results were also compared with the spectra of pure
SBA-15 and CAL. Figure 4 shows the FTIR spectra of pure
CAL and CAL-immobilized SBA-15 catalyst with and with-
out capping. As can be seen in Figure 4, the typical vibration
Figure 2. Nitrogen adsorption (filled)–desorption (empty) isotherms of
pure SBA-15 (*), APTES-functionalized SBA-15 (
SBA-15 (~), and CAL-immobilized SBA-15 capped with TMS groups
).
&
), CAL-immobilized
(!
ꢀ
1
modes of SBA-15 at 3328 cm
ꢀ
1
for OH, around 1076 cm for
SiꢀOꢀSi, and a sharp peak at
Table 1. Textural characterization of pure mesoporous silica SBA-15 and CAL-immobilized SBA-15.
Catalyst
BET surface area
Total pore volume
BJH pore diameter
[nm]
ꢀ1
9
45 cm for SiꢀOH were pres-
2
ꢀ1
ꢀ3 ꢀ1
A
H
U
G
R
N
U
G
]
ACHTUNGTRENNUNG[ cm g ]
ent in the case of both pure
SBA-15 (Figure 4b) and amine-
functionalized SBA-15 (Figur-
e 4c). In the case of amine-
functionalized SBA-15, a small
shoulder at 2934 cm , which is
ascribed to the CH stretching
frequency of the aminopropy-
SBA-15
895
304
176
108
1.20
0.64
0.32
0.20
9.0
6.9
6.7
5.7
APTES-functionalized SBA-15
CAL-immobilized SBA-15
CAL-immobilized SBA-15
end capped with TMS groups
ꢀ
1
pected, the modification of the SBA-15 support with amine
or CAL caused a significant change in the textural parame-
ters of the support. The amount of nitrogen adsorbed signifi-
cantly decreased after modification of the porous surface of
SBA-15 with amine or CAL, revealing that the specific sur-
face area and pore volume of the support are lower than
those of the parent SBA-15 (Table 1). It was found that the
capillary condensation step in the isotherms of amine and
CAL immobilized SBA-15 was shifted towards lower rela-
tive pressure, indicating that pore size of the support is also
significantly decreased after the modification. The decrease
in surface area, pore volume, and the pore diameter
ꢀ
1
late triethoxysilane, and a peak at 1515 cm , which is as-
signed to NH bending, were observed. It can also be seen
from Figure 4 that a number of sharp vibrational peaks ob-
ꢀ
1
ꢀ1
served in the ranges 3100–2900 cm and 1200–800 cm for
pure chiral ligand. Both the amine-functionalized and CAL-
immobilized SBA-15 (Figure 4c,d) show the bands in the
ꢀ
1
ꢀ1
range of 2900–3400 cm and 1200–800 cm . The shoulder
ꢀ
1
at 1735 cm is attributed to the ester carbonyl group of
chiral catalyst, confirming the presence of CAL groups,
which are perfectly anchored with the amine-modified SBA-
15, even after repeated washing with dichloromethane in the
(
Figure 3) of the immobilized sample is not related to the
collapse of the structural order of the materials during the
modification process but instead demonstrates that the CAL
molecules are immobilized inside the mesopore channels of
the SBA-15 support. In addition, the sharpness of the capil-
lary condensation step and the shape of the hysteresis loop
in the nitrogen adsorption isotherm are similar to those of
the pure SBA-15, further confirming that the order of the
mesopore structure of the support is retained even after
modification with CAL. These results are also in good
agreement with the data obtained from the XRD measure-
ments of the CAL immobilized SBA-15.
Figure 4. FTIR spectra of a) pure CAL, b) pure SBA-15, c) APTES-func-
tionalized SBA-15, d) CAL-immobilized SBA-15, and e) CAL-immobi-
lized SBA-15 capped with TMS groups.
The CAL-immobilized SBA-15 materials were character-
ized by FTIR spectroscopy to further prove the anchoring
Chem. Asian J. 2010, 5, 897 – 903
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899

S. Velmathi, A. Vinu et al.
FULL PAPERS
preparation process. However, most of the peaks related to
the pure chiral ligand were not observed for the chiral
ligand loaded SBA-15 support. This could be attributed to
the confinement or shielding effect of the mesoporous silica
framework of the SBA-15 support by the vibration of chiral
ligand 1 (see Scheme 2). This result confirms that the pure
chiral catalyst is anchored inside the pores and not simply
doped or physisorbed on the external surface of the SBA-15
support. It is interesting to note that the intensity of the OH
band significantly decreases after an end-capping process,
confirming that the free surface silanol groups present in the
pore walls of CAL immobilized SBA-15 are capped with
TMS groups (Figure 4).
The stability of the CAL groups inside the mesochannels
of SBA-15 was investigated by UV/Vis diffuse-reflectance
spectroscopy (DRS). Figure 5 shows the UV/Vis DRS spec-
Figure 6. HRSEM images of a) pure SBA-15 and b) CAL-immobilized
SBA-15 at low (left) and high (right) resolution.
of the materials were not affected by modification with
CAL. These results are also in agreement with the XRD
and nitrogen-adsorption data. From all these results, it can
be concluded that the SBA-15 support is highly robust
owing to its thick walls and is an excellent support for the
immobilization of different functionalities inside the meso-
channels.
Figure 5. UV/Vis DRS spectra of a) pure CAL, b) CAL-immobilized
SBA-15, and c) CAL-immobilized SBA-15 capped with TMS groups.
Catalytic Performance of Pure CAL
tra of pure SBA-15 and CAL-immobilized SBA-15. Pure
chiral ligand 1 exhibits two sharp bands in the UV spectrum
centered at 290 and 235 nm. The peak at 235 nm is attribut-
ed to a p–p* transition, whereas the peak at 290 nm is as-
signed to an n–p* transition. The intensity of the bands for
CAL-immobilized SBA-15 is much lower than that for pure
CAL. This is mainly on account of the low concentration of
ligand in the mesochannels of SBA-15. Also, there was a
slight shift in absorption frequency, which can be attributed
to the inducement interaction between NH group and cata-
lyst and the arrangement of the chiral ligands in the well-or-
dered mesopore channels of the SBA-15 support, confirming
that ligands are perfectly immobilized inside the mesochan-
nels and are highly stable even after immobilization.
The morphology of SBA-15 before and after CAL modifi-
cation was analyzed by HRSEM. Figure 6 shows the
HRSEM images of the SBA-15
We previously reported the synthesis of the amine ester of
salicylaldehyde with l-valine and studied the prochiral
ketone reduction reaction in stoichiometric quantity with an
[21–23]
enantioselectivity of 90% with a product yield of 95%.
Herein we demonstrate the use of CAL, the same ligand
with a halide substitution in amine esters of salicylaldehyde,
with the aim of linking the ligand on the surface of the mes-
oporous SBA-15 support and studying the borane reduction
in catalytic amounts under different reaction conditions
(Scheme 2).
The homogeneous reduction of acetophenone was carried
out as a model reaction to optimize the reaction conditions
(Scheme 3; Table 2). The enantioselectivity of borane reduc-
tion may be affected by reaction conditions such as solvent
[24,25]
and reaction temperature.
As it has been reported that
THF is the better solvent than toluene and dichlorome-
support before and after the
CAL encapsulation at low and
high resolution. Both samples
exhibit rodlike particles that
are uniform in size and shape
and aggregated as bundles. It is
important to note that the
structure and the morphology Scheme 2. Synthesis of chiral oxazaborolidine complex 1.
900
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Chem. Asian J. 2010, 5, 897 – 903

Chiral Oxazaborolidine Complex Immobilized SBA-15
Catalytic Performance of CAL-immobilized SBA-15 in the
Asymmetric Reduction of Prochiral Ketones
Reduction of acetophenone was carried out with CAL-im-
mobilized SBA-15 (30 mol%) dissolved in dry toluene.
Borane dimethylsulfide (0.12 mL, 1.5 mmol) was added
dropwise, and the mixture was
Scheme 3. Asymmetric reduction of prochiral ketones.
Table 2. Reduction of acetophenone with 30 mol% CAL.
heated at reflux for 30 min.
Acetophenone
1 mmol) was added dropwise,
and the mixture was heated at
(0.12 mL,
[
a]
Entry
Ligand
Catalyst
T [8C]
Yield [%]
ee [%]
Absolute
configuration
[
b]
concentration [mol%]
1
2
3
4
1
1
1
1
30
30
30
30
ꢀ77
0
35
65
100
98
99
0
0
10
92
racemic
racemic
S
S
reflux for
Table 3, entry 1). Subsequently,
the reaction mixture was cooled
a further 30 min
(
100
[
a] The enantiomeric excess was determined using a chiralcel OD-H column. [b] The absolute configuration to room temperature and fil-
was determined by the sign of the optical rotation.
tered. To the filtrate 2n HCl
[26]
thane, THF was used as the solvent in this study. As can
be seen in Table 2, the reaction temperature (ꢀ788C, 08C,
room temperature, refluxing conditions) has a profound
effect on the enantioselectivity of the product. As the reac-
tion temperature is increased from ꢀ77 to 658C, the enan-
tioselectivity to the chiral secondary alcohol increases from
Scheme 4. Reduction of acetophenone by chiral oxazaborolidines.
0
to 92% for the reduction of acetophenone with 30 mol%
of pure CAL. The product enantioselectivity is 0 at low tem-
perature, which is attributed to the formation of a dimer of
was added, and the product was extracted with dichlorome-
thane. The secondary alcohol was separated by column
chromatography with silica gel as adsorbent with 98:2
hexane/ethyl acetate as eluant. However, the alcohol ob-
tained was racemic, possibly because the free OH groups on
the silica surface could catalyze the reaction. Hence, the
acetophenone reduction was carried out with CAL-immobi-
lized SBA-15 end capped with TMS groups (Table 3,
entry 2). As expected, the enantioselectivity was increased
to 70%. Thus, the reduction of aromatic ketones was stud-
ied with CAL-immobilized SBA-15 end capped with a TMS
group (Table 3). p-Bromoacetophenone gave excellent enan-
tioselectivity of 98%, whereas other ketones, except for p-
methylacetophenone, gave moderate enantioselectivity (53–
86%).
[8]
oxazaborolidine. Another factor is that at low temperature
08C), the equilibrium could be shifted more towards the in-
(
tramolecular ester carbonyl coordination with boron, which
does not facilitate the selective reduction of ketone, leading
to a low enantioselectivity. In contrast, at reflux tempera-
ture, the equilibrium would be shifted more towards the
ketone carbonyl coordination with boron, which aids more
selective reduction of the ketone and is thus responsible for
a high enantioselectivity.
The instantaneous reduction indicates that the reduction
is effected by nitrogen-coordinated borane (NꢀBH ), which
3
is more nucleophilic. The predominant formation of the
S enantiomer may arise from the more selective transfer of
hydride from the reagent to the Si face of the ketone.
Hence, Coreyꢁs mechanism in-
volving the hydride transfer
from the reagent to the ketone
through the formation of a six- Entry Ketone
membered cyclic transition
state is expected for the reduc-
tion. However, the lower ob-
served ee value for the reduc-
tion may be a result of the
competition of the carbonyl
group of the ketone for coordi-
nation with boron from the
ester carbonyl of the reagent
Table 3. Reduction of aromatic ketones with CAL-encapsulated SBA-15 end capped with TMS groups.
[
a]
Catalyst
T [8C]
Yield [%]
ee [%]
Absolute
[
b]
concentration [mol%]
configuration
[
c]
1
2
3
4
5
6
7
8
9
1
acetophenone
acetophenone
30
30
30
30
30
30
30
30
30
30
105
105
105
105
105
105
105
105
105
105
30
90
38
76
40
35
35
80
44
40
0
racemic
70
60
86
98
53
4
45
28
25
S
S
S
S
S
S
S
S
S
p-OMe acetophenone
p-I-acetophenone
p-Br-acetophenone
2
-acetophenone
p-Me-acetophenone
p-NH
[
d]
1st recovery
2nd recovery
3rd recovery
0
(
Scheme 4).
[a] The enantiomeric excess was determined using a chiralcel OD-H column. [b] The absolute configuration
was determined by the sign of the optical rotation. [c] Reaction was performed with CAL-immobilized SBA-
15 without end capping. [d] Reduction with acetophenone.
Chem. Asian J. 2010, 5, 897 – 903
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901

S. Velmathi, A. Vinu et al.
FULL PAPERS
The catalyst was separated from the product mixture and
reused to study its recyclability. The recovered chiral cata-
lyst shows lower enantioselectivity and product yield than
those of fresh CAL-immobilized SBA-15 end capped with
TMS group (Table 3, entry 8–10). This decreased perfor-
mance could be as a result of the repeated washing of the
catalyst with methanol, which may change the active sites
from BꢀH to BꢀOMe. BꢀOMe is comparatively less reac-
tive than the BꢀH for reduction. In addition, this conversion
1H, -CH), 3.71–3.74 (d, 1H, -CH,), 3.76 (s, 3H, -OCH
H, Ar), 8.36 (s, 1H, -CH=N), 10.08 ppm (s, 1H, -OH); C NMR
CDCl ): d=18.13, 18.39, 30.94, 45.85, 52.23, 110.1, 119.9, 126.7, 133.8,
35.4, 160.2, 165.3, 171.3 ppm; MS: m/z 269, 254,226, 210, 166.
3
), 6.3–7.25 (m,
1
3
3
(
1
3
Synthesis of (R,E)-methyl 2-(5-chloro-2-hydroxybenzylamino)-3-methyl-
butanoate: The imine (2 g, 7.359 mmol) was dissolved in methanol,
cooled to 08C, and then sodium borohydride (1 g) was added. The reac-
tion mixture was stirred for 5 h and then quenched by adding 20 mL of
2
.5m HCl. The chiral amine (1.8 g, 80% yield) was obtained by extrac-
tion of the resultant mixture with diethyl ether, followed by the purifica-
tion by column chromatography using silica gel as an adsorbent with
process may also affect the number of actives sites available
for the reaction, which leads to low enantioselectivity and
product yield. It should be noted that removing the unreact-
ed reactant and product molecules adsorbed on the meso-
channels of the SBA-15 without affecting the active sites of
the CAL is a challenging task and encompasses a different
scope to that of this study. We are in the process of stabiliz-
ing the catalyst after the reaction with a different approach
that requires a lot of time, and the results will be reported
in the future.
9
0:10 hexane/ethyl acetate. Hereafter, (R,E)-alkyl 2-(5-chloro-2-hydroxy-
5
89
benzylamino)-3-methylbutanoate is denoted as CAL. ½aꢁ =ꢀ828 (c=
2
5
ꢀ
1
1
0
(
.4, methanol); IR: n˜ =3300, 2950, 1742, 1595, 1280, 1230 cm ; H NMR
CDCl ): d=0.89 (d, 6H, -(CH ), 2.01 (m, 1H, -CH), 3.1(d. 1H, -CH),
.67 (s, 3H, -OCH ), 3.93 (d, 1H, -CH), 5.22 (s, 1H, -CH), 6.67,6.74 (d,
3
3 2
)
3
1
3
H, aromatic), 6.74 (s, 1H, aromatic), 6.88–7.07 ppm (d, 1H, aromatic);
C NMR: d=18.21, 19.35, 31.36, 51.56, 51.81, 65.93, 116.43, 119.24,
1
3
122.26, 128.6, 129.03,157.8, 174.11 ppm; MS: m/z 270, 254, 239, 212, 185,
58.
Synthesis of SBA-15: Highly ordered mesoporous SBA-15 support was
1
[
14]
synthesized by the procedure previously reported by Zhao et al. under
hydrothermal conditions using a triblock organic copolymer as a tem-
plate. In a typical synthesis, triblock copolymer (4 g), poly(ethylene
oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO20-PO70-EO20
)
(
(
Pluronic P123, MW=5800) was dispersed in doubly distilled water
40 g) and 2m aqueous HCl (120 mL) was added with stirring at ambient
Conclusions
temperature (358C) for 3 h. Finally, tetraethylorthosilicate (4 g) was
added to the homogeneous solution with stirring at 408C for 24 h to form
a gel. The resultant gel was allowed to stand at 1008C for 48 h in a
Teflon Parr reactor, which led to crystallization under static hydrothermal
conditions. The white solid product was filtered off, washed with warm
distilled water several times, and dried at 1508C overnight. The as-syn-
thesized solid product was calcined at 5408C in air for 24 h to remove the
organic template.
The immobilization of chiral oxazaborolidine complex on
the porous matrix of highly ordered, hexagonal-type, two-di-
mensional mesoporous silica SBA-15 by a postsynthetic ap-
proach using 3-aminopropyltriethoxysilane as a reactive sur-
face modifier has been demonstrated. The immobilized cata-
lyst is perfectly anchored in the mesochannels of SBA-15.
Both the homogeneous and the heterogeneous catalytic ac-
tivity of the chiral oxazaborolidine ligand for the enantiose-
lective reduction of aromatic prochiral ketones were investi-
gated. It was found that the immobilized catalyst shows sim-
ilar activity to that of the homogeneous catalyst in the
above reaction. However, the enantioselectivity of the cata-
lyst decreases with repeated recycling experiments.
Preparation of 3-aminopropyltriethoxysilyl-functionalized SBA-15:
A
suspension of aminopropyltriethoxy silane (APTES) (0.45 g, 2 mmol) and
calcined SBA-15 (1 g) in toluene (20 mL) was heated at reflux with con-
tinuous stirring under an inert atmosphere for 24 h. The resulting mixture
was cooled to room temperature, filtered, washed with dry toluene and
diethyl ether, and then dried under vacuum at ambient temperature. The
dried material was further subjected to Soxhlet extraction with dry di-
chloromethane for 24 h to remove the unreacted APTES. Finally, the
functionalized SBA-15 solid product was dried at 708C under vacuum for
1
2 h.
Heterogenization of (R,E)-alkyl 2-(5-chloro-2-hydroxybenzylamino)-3-
methylbutanoate on aminopropyl-functionalized SBA-15: The immobili-
zation of CAL in the pore channels of APTES-functionalized SBA-15
was carried out by adding APTES-functionalized SBA-15 (1 g) and CAL
(0.2 g, 0.74 mmol) in dry toluene (20 mL). The resulting suspension was
heated at reflux for 48 h under inert atmosphere. The CAL-immobilized
supported catalyst was filtered, washed thoroughly with dry toluene and
diethyl ether, and extracted repeatedly with methanol and dichlorome-
thane in a Soxhlet extractor until the washings become colorless in order
to remove unreacted or physisorbed CAL from the pore surface of the
functionalized SBA-15. All washings were combined, the solvent was
evaporated, and the residue was dissolved in methanol (20 mL). The
degree of loading of CAL inside the pore channels of SBA-15 was calcu-
lated by subtracting the amount found by UV absorption in the final so-
lution after immobilization from the amount of CAL present before ad-
dition of the functionalized SBA-15 support.
Experimental Section
Chemicals were purchased from Aldrich and used without further purifi-
cation. Solvents were purchased from Merck and used after purification.
The chiral ligands were prepared under nitrogen atmosphere.
Synthesis of l-valine methyl ester hydrochloride: l-Valine (2 g,
7.1 mmol) was dissolved in methanol (20 mL). Thionyl chloride was
1
added dropwise with stirring at 08C, and stirring was continued over-
night. The final product (2.8 g, 100% yield) was obtained by removing
the excess thionyl chloride by rotary evaporation. M.p.: 171–1738C;
5
2
89
5
ꢀ1
½
aꢁ =+26.68 (c=5 in water); IR (cm ) 3340, 2900, 1736, and 1235;
1
H NMR (CDCl
H, -OCH ), 2.1–2,2 (s, 1H, -CH), 0.9 ppm (m, 6H, -(CH
CDCl ): d=17.68, 18.28, 28.97, 38.80, 40.06, 57.23, 170.06 ppm.
3 2
): d=8.4 (s, 2H, -NH ), 3.7–3.73 (d, 1H,-CH), 3.8 (s,
1
3
3
(
3
3
)
2
;
C NMR
3
Synthesis of (R,E)-methyl 2-(5-chloro-[2-hydroxybenzylidene]amino)-3-
methylbutanoate: l-Valine methyl ester hydrochloride (2 g, 12.075 mmol)
was dissolved in dry toluene, and triethylamine (2 mL) and 5-chlorosali-
cylaldehyde (1.89 g, 12.075 mmol) dissolved in dry toluene were added.
The reaction mixture was heated at reflux for 12 h. Finally, a yellow solid
product imine (3.15 g, 11.53 mmol) was obtained by removing the excess
Trimethylsilylation (TMS) of CAL-immobilized SBA-15: Under extreme-
ly dry conditions, a suspension of CAL-immobilized SBA-15 (1 g) and
hexamethyldisiloxane (HMDS) (0.1 mL) was heated at reflux overnight
with stirring under nitrogen atmosphere. The volatiles were stripped on a
rotary evaporator and the dry powder was washed two or three times
with dry ethanol (10 mL) by centrifugation and finally dried under
vacuum at 808C for 8 h. Greater than 98% of the material was recov-
5
2
89
5
solvent. M.p.: 71–728C, ½aꢁ =ꢀ96.68 (c=1 CHCl
3
); IR: n˜ =3432, 2923,
): d=0.84 (d, 6H, -(CH ), 2.23 (m,
ꢀ
1
1
1
737, 1630 cm
;
H NMR (CDCl
3
3 2
)
902
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 897 – 903

Chiral Oxazaborolidine Complex Immobilized SBA-15
ered. TMS capping of CAL-immobilized SBA-15 was confirmed by IR
spectroscopy.
tor, NITT) for constant encouragement, support, and research grants for
U.B. and N.A. This work was also supported in part by the Ministry of
Education, Culture, Sports, Science and Technology (MEXT) under the
Strategic Program for Building an Asian Science and Technology Com-
munity Scheme and World Premier International Research Center (WPI)
Initiative on Materials Nanoarchitectonics (MEXT, Japan).
Asymmetric borane reduction of prochiral ketone catalyzed by CAL:
CAL (82 mg, 7.34 mmol) was dissolved in dry tetrahydrofuran. Subse-
quently, borane dimethylsulfide (BMS) (0.15 mL, 2 mmol) was added by
syringe and heated at reflux for 30 min to give chiral oxazaborolidine
complex. Acetophenone (0.12 mL, 1 mmol) was added dropwise, and the
mixture was again heated at reflux for 30 min. After completion of the
reaction, the reaction mixture was quenched by the addition of 10 mL of
[1] V. K. Singh, Synthesis 1992, 7, 605.
2
n HCl. The organic phase was extracted with dichloromethane, and the
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chiral secondary alcohol was separated by column chromatography on
silica gel as adsorbent with 98:2 hexane/ethyl acetate as eluant.
[
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5] E. J. Corey, G. A. Reichard, Tetrahedron Lett. 1989, 30, 5207.
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Asymmetric borane reduction of prochiral ketone catalyzed by CAL-im-
mobilized SBA-15: CAL-immobilized SBA-15 (140 mg, 30 mol%) was
dissolved in dry toluene. BMS (0.12 mL, 1.5 mmol) was added by syringe
and heated at reflux for 30 min to give chiral oxazaborolidine complex
inside the mesoporous silica SBA-15. Subsequently, acetophenone
5
[
[
[
[
(
0.12 mL, 1 mmol) was added slowly. The reaction mixture was continu-
1
0938.
ously heated at reflux for 30 min, cooled to room temperature, and fil-
tered. To the filtrate was added 2n HCl, and the mixture was extracted
with dichloromethane. The chiral secondary alcohol was separated by
column chromatography on silica gel as adsorbent with 98:2 hexane/ethyl
acetate as an eluant.
[
9] B. Pugin, H. U. Blaser in Comprehensive Asymmetric Catalysis,
Vol. 3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, p. 367.
[
[
10] J. A. David, P. Indra, R. S. David, Chem. Rev. 1996, 96, 835.
11] X. Yao, H. Chen, W. Lu, G. Pan, X. Hu, Z. Zhen, Tetrahedron Lett.
Characterization of CAL-immobilized mesoporous SBA-15: The powder
X-ray diffraction (XRD) patterns of CAL-immobilized SBA-15 samples
were collected on a Rigaku diffractometer using CuKa (l=0.154 nm) ra-
diation. The diffractograms were recorded in the 2q range of 0.8 to 108
with a 2q step size of 0.018 and a step time of 10 s. Nitrogen adsorption
and desorption isotherms were measured at ꢀ1968C on a Quantachrome
Autosorb 1C sorption analyzer. All samples after the CAL immobiliza-
tion were outgassed at 408C for 48 h. The specific surface area was calcu-
lated using the Brunauer–Emmett–Teller (BET) method. The pore size
distributions were obtained from the adsorption branch of the nitrogen
2
000, 41, 10267.
[
[
12] G. J. Kim, J. H. Shin, Tetrahedron Lett. 1999, 40, 6827.
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997, 108, 485.
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16] M. S. Wang, Y. K. Kwon, G. J. Kim, J. Ind. Eng. Chem. 2002, 8, 262.
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Chem. Soc. 1998, 120, 6024.
1
13
isotherms by Barrett–Joyner–Halenda method. H and C NMR spectra
were recorded in CDCl on a BRUKER AMX-300 MHz instrument
3
[
[
18] P. Yang, D. Zhao, D. Margolese, B. F. Chmelka, G. D. Stucky, Nature
using tetramethylsilane as an internal standard. Specific rotations were
recorded with a Rudolph Autopol IV polarimeter. Enantiomeric excess
was determined with a Shimadzu 2010 A HPLC instrument (Chiral
column: Chiral Cel OD-H, mobile phase: hexane/isopropanol 98:2,
1
998, 396, 152.
19] D. Zhao, J. Feng, Q. Huo, N. Melosh, G. H. Fredrickson, B. F.
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cules 2001, 6, 988.
[
[
ꢀ
1
0
.5 mLmin , 254 nm. FTIR spectra were recorded on a Perkin–Elmer -
DXB spectrometer. Melting points of the chiral ligands were determined
with a Kherea digital melting point apparatus and are reported uncor-
rected. The morphology of the materials before and after the chiral
ligand immobilization was observed on a Hitachi S-4800 field emission
scanning electron microscope using an accelerating voltage of 5.0 to
[
[
2
0 kV. The samples were deposited on a sample holder with an adhesive
[
[
[
24] J. Xu, T. Wei, Q. J. Zhang, J. Org. Chem. 2003, 68, 10146.
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carbon foil and sputtered with platinum prior to imaging.
Received: September 1, 2009
Published online: January 15, 2010
Acknowledgements
We thank the DST for financial assistance (SR/FTP/CS-142-2006) in the
form of a fast track sponsored project and Dr. M. Chidambaram (Direc-
Chem. Asian J. 2010, 5, 897 – 903
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
903