Asymmetric transfer hydrogenation of aromatic ketones catalyzed by SBA-15 supported Ir(I) complex under mild conditions

Article abstract of DOI:10.1007/s10562-010-0341-0

A heterogeneous catalyst of Ir(I)-9-amino epi-cinchonine complex immobilized on the surface of mesoporous SBA-15 was firstly synthesized and used in the asymmetric transfer hydrogenation of aromatic ketones. Enhanced enantioselectivity compared with homog

Full text of DOI:10.1007/s10562-010-0341-0

Catal Lett (2010) 137:104–109
DOI 10.1007/s10562-010-0341-0
Asymmetric Transfer Hydrogenation of Aromatic Ketones
Catalyzed by SBA-15 Supported Ir(I) Complex Under Mild
Conditions
•
Yanbin Shen Qiu Chen Lan-Lan Lou Kai Yu
•
•
•
•
Fei Ding Shuangxi Liu
Received: 19 January 2010 / Accepted: 3 April 2010 / Published online: 15 April 2010
Ó Springer Science+Business Media, LLC 2010
Abstract A heterogeneous catalyst of Ir(I)-9-amino epi-
cinchonine complex immobilized on the surface of meso-
porous SBA-15 was firstly synthesized and used in the
asymmetric transfer hydrogenation of aromatic ketones.
Enhanced enantioselectivity compared with homogeneous
catalyst was obtained at room temperature. Furthermore,
the heterogeneous system with very low leaching of irid-
ium can be easily regenerated.
cases, always suffer from lower catalytic activity and
enantioselectivity compared to their homogeneous coun-
terparts [12–14].
Cinchona alkaloids have a long and proud history in the
field of asymmetric synthesis. Nowadays, cinchona alka-
loids and their synthetic derivatives have been widely used
in the asymmetric reaction. In particular, an osmium cat-
alyst bearing cinchona alkaloid-type ligand has been well
studied for asymmetric dihydroxylation of olefins [15–21].
In 2006, a catalyst with 9-amino cinchona alkaloids as
ligand has been found to be effective in the asymmetric
transfer hydrogenation of ketones, the catalyst could be
recycled under homogeneous conditions, but it could not be
recovered totally, and high iridium leaching was observed
in the recycling process [22, 23].
Keywords 9-Amino epi-cinchonine Á Immobilization Á
Asymmetric transfer hydrogenation
1 Introduction
Chiral secondary aromatic alcohols constitute one of the
most important classes of building blocks in organic syn-
thesis [1–7]. Asymmetric transfer hydrogenation of ketones
is an attractive method to prepare chiral alcohols. Although
a variety of homogeneous chiral Ir, Rh and Ru catalysts
have been proved to be highly enantioselective in the
asymmetric transfer hydrogenation of prochiral ketones
[8–11], most of them have not been industrialized due to
the high cost of noble metals and chiral ligands as well as
the difficulties in removing trace amounts of toxic metals
from organic products. To overcome these problems,
homogeneous chiral catalysts can be immobilized on var-
ious supports such as organic polymers and inorganic
supports. However, the heterogenized catalysts, in most
Recently, the mesoporous materials as supports for
chiral catalysts have drawn much more attention. The large
surface area and ordered mesopore channels of mesoporous
materials can help avoid the aggregation of catalytic active
species and maintain excellent stereocontrol performance.
The commercial availability of cinchona alkaloids and the
virtues of mesoporous materials as supports encouraged us
to investigate the heterogeneous catalysts’ utility in
asymmetric transfer hydrogenation. More importantly, they
can be easily recycled via simple filtration.
In this paper, we report a highly ordered mesoporous
SBA-15 anchored 9-amino epi-cinchonine-[Ir(COD)Cl]2
complex for asymmetric transfer hydrogenation of aro-
matic ketones at room temperature. Enhancement of
enantioselectivity was expected to be obtained from the
heterogeneous catalyst due to the confinement effects of
SBA-15 channel. The metal leaching during the reaction
will be another concern. To the best of our knowledge, this
is the first report on immobilization of 9-amino epi-cin-
chonine onto mesoporous materials.
Y. Shen Á Q. Chen Á L.-L. Lou Á K. Yu Á F. Ding Á S. Liu (&)
Institute of New Catalytic Materials Science, College of
Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
e-mail: sxliu@nankai.edu.cn
123

Asymmetric Transfer Hydrogenation
2 Experimental
105
(ICP-AES) on an ICP-9000 (N ? M) spectrometer (TJA
Co.). To accomplish this measurement, the solution was
vapourized and then the sample was calcined. The
remaining residue was dissolved in hydrogen fluoride and
2.1 Preparation of 9-Amino epi-Cinchonine
1
9-Amino epi-cinchonine was synthesized following the
method in literature [24]. 9-Amino epi-cinchonine 1
(slightly yellow oil, yield 65.2%). 1H NMR (CDCl3,
300 MHz) 0.85–0.99 (m, 1H), 1.08–1.15 (m, 1H), 1.48–
1.60 (m, 3H), 2.05(s, 2H), 2.24–2.26 (m, 1H), 2.90–3.10
(m, 5H), 4.79 (d, J = 8.1 Hz, 1H), 5.01–5.04 (m, 2H), 5.87
(m, 1H), 7.54–8.36 (m, 5H), 8.91 (d, J = 4.5 Hz, 1H); IR
(CH2Cl2) m 3392, 3308, 3056, 2952, 2868, 1663, 1637,
then dissolved by 5% hydrogen chloride. H NMR spectra
were recorded at 300 MHz using a Varian Mercury Vx-300
spectrometer. FT-IR spectra were recorded on a Bruker
Vector 22 spectrometer using self-supporting wafers.
Powder XRD patterns of the samples were obtained using a
R/max-2500 diffractometer with Cu Ka source and a step
size of 0.02°. Elemental analysis was conducted with a
Perkin–Elmer 240C analyzer. N2 adsorption–desorption
analysis was carried out at 77 K on a Micromeritics TriStar
3000 apparatus. The analytical data were processed by the
BET equation for surface areas and by the BJH model for
pore size distributions. Enantiomeric excess (ee) values
were determined by GC with b-DEX 325 chiral column,
using a GC-7800 chromatograph equipped with a flame
ionization detector.
1590, 1569, 1506, 1459, 1260 cm-1
.
2.2 Preparation of Catalyst
The synthesis procedure towards the catalyst is shown in
Scheme 1. The parent silica SBA-15 was prepared fol-
lowing the reported procedure [25]. The template was
removed by calcination at 823 K in air for 6 h. Calcined
SBA-15 (0.60 g) was treated with 0.90 mL of (3-merca-
ptopropyl)trimethoxysilane in refluxing anhydrous toluene
for 24 h. The solid was washed with toluene followed by
Soxhlet extraction with dichloromethane and dried under
vacuum for 1 h, resulting in 1.73 mmol of S element per g
of modified SBA-15 calculated from TG result. The sample
is denoted as SH-SBA-15. Then 0.60 g of SH-SBA-15 was
suspended in chloroform and refluxed with 0.22 g of
9-amino epi-cinchonine 1 and 0.06 g of AIBN as radical
initiator for 24 h [26]. The sample was filtered followed by
washing with chloroform, Soxhlet extraction and drying
under vacuum for 1 h to yield 2 (1.74 wt% of N). The
resulting catalyst was prepared in situ by mixing the solid 2
with [Ir(COD)Cl]2 in i-propanol at room temperature for
4 h under N2.
2.4 Typical Procedure for the Asymmetric Transfer
Hydrogenation
A general reaction run was as follows: [Ir(COD)Cl]2
(8.4 mg) and the solid 2 (60.3 mg) were added to 5 mL of
dry degassed i-propanol and stirred at room temperature for
4 h under N2. Then KOH (2.8 mg) was added and the
reaction mixture was stirred for another 10 min. The ketone
was then added in portion (0.25 mmol) and the reaction was
conducted at room temperature for two days. The reaction
mixture was filtered and the reaction products were ana-
lyzed by GC. The homogeneous reaction was carried out
with 9-amino epi-cinchonine (7.3 mg), [Ir(COD)Cl]2
(8.4 mg), KOH (2.8 mg) and substrate (0.25 mmol) in
5 mL of i-propanol, at room temperature for 2 days.
After completion of the asymmetric transfer hydroge-
nation reaction, the heterogeneous catalyst was separated
by filtration and then subjected to the next run with a new
batch of KOH and the substrate, without the addition of any
[Ir(COD)Cl]2 or ligand.
2.3 Characterization
Ir loading in the reaction solution was determined by
inductively coupled plasma-atomic emission spectrometry
Scheme 1 Depiction of the
epi-cinchonine bound inside the
hexagonal pores of SBA-15
OCH3
H
H2N
S
O
O
N
O
Si
SH
Si
N
NH2
O
OCH3
AIBN, CHCl3
N
N
1
2
123

106
Y. Shen et al.
(100)
3 Results and Discussion
3.1 Characterization of the Catalyst
SBA-15 possesses good thermal and hydrothermal stabil-
ity, large surface area, well-ordered pore arrays and uni-
form pore size distribution. In this work, calcined SBA-15
is applied as the support for 9-amino epi-cinchonine 1. The
SH-SBA-15, sample 2 and catalyst of Ir(I)-9-amino epi-
cinchonine complex were characterized by FT-IR spec-
troscopy, element analysis, N2 adsorption-desorption
experiments, powder XRD and ICP-AES. The FT-IR
spectrum of SH-SBA-15 showed a vibration band at
2575 cm-1 assigned to SH group (Fig. 1a). The spectrum
of 2 showed a absorption band at 1595 cm-1 assigned to
the –C=N– stretchings of the quinoline ring, bands at 1511
and 1459 cm-1 which are presented in the spectrum of
9-amino epi-cinchonine can also be observed. These
observations, together with the absence of the band
attributed to SH group at 2575 cm-1, demonstrated the
successful immobilization of chiral 9-amino epi-cincho-
nine onto the SBA-15. The element analysis of 2 confirmed
immobilization of 0.41 mmol/g of 9-amino epi-cinchonine
1. The leaching of Ir from catalyst into the solution was
determined by ICP, only 5.9 9 10-2% Ir was detected in
the liquid phase after the first run, which indicates that the
Ir(I) complex is strongly bonded on the support.
(110)
(200)
a
b
2
4
6
8
10
2Theta(degree)
Fig. 2 Powder XRD patterns of a calcined SBA-15 and b 2
0.30
a
1000
0.25
0.20
c
800
0.15
0.10
b
0.05
600
0.00
0
5
10
15
20
25
Pore Diameter (nm)
400
200
0
a
b
c
The powder XRD pattern of 2 is showed in Fig. 2. Similar
to calcined pure SBA-15, sample 2 showed one intense peak
and two weak peaks indexable as (100), (110), and (200)
reflections, respectively, suggesting that the hexagonal
mesoporous structure (p6mm) could be well preserved. The
decrease in the XRD peak intensity indicated that the
modification and immobilization might disturb the ordered
mesoporous structure to a certain degree. The N2
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure(P/P0)
Fig. 3 N2 adsorption-desorption isotherms and pore size distributions
of a SBA-15, b SH-SBA-15 and c 2
adsorption–desorption isotherms and pore size distributions
in Fig. 3 revealed that all of the SBA-15, SH-SBA-15 and 2
exhibited an isotherm typical of type IV with a steep increase
in adsorption at P/P0 = 0.6–0.8. A narrow and well-ordered
mesopores can be observed in the pore size distribution.
Some structural parameters are listed in Table 1. It’s found
Table 1 Pore structural parameters of various materials
b
a
Sample
Mesopore volume Surface area Pore diameter
(cm3/g)
(m2/g)
(nm)
Calcined SBA-15 1.37
859
499
382
227
193
8.8
7.5
7.4
5.0
4.4
SH-SBA-15
0.73
0.63
0.34
0.27
2
4000
3500
3000
2500
2000
1500
1000
500
Fresh catalyst
Used catalysta
a
ν/cm-1
Fig. 1 FT-IR spectra of a SH-SBA-15 and b 2
The catalyst used for three runs
123

Asymmetric Transfer Hydrogenation
107
that incorporation of mercaptopropyl groups and ligands
onto SBA-15 resulted in a gradual decrease in BET surface
area, pore volume and pore size. This could be attributed to
the coverage of pore surface of the calcined SBA-15 with
mercaptopropyl groups and 9-amino epi-cinchonine, lead-
ing to an increase in the wall thickness.
effects originating from the regular and adjustable pores of
the support, which can give rise to significant effects on the
microenvironment of the active sites [27–29]. On the basis
of the excellent result, a series of aromatic ketones were
examined as substrates in this work, in order to investigate
the effects of the electronic property and position of sub-
stituent in the acetophenone. In general, substituted ace-
tophenone was less effective than acetophenone under
similar conditions. Electron donating substituent in the
ortho-position, gave the product in higher ee value but with
lower conversion compared with electron-withdrawing
substituent (Table 2, entry 5 vs 3 and 7). Aromatic ketone
incorporating chlorine group in the ortho-position afforded
higher catalytic activity and enantioselectivity than that
with the same group in the para-position (entry 7 vs 9).
These results indicate that, unlike the reported results [30,
31], the catalytic activity and enantioselectivity of the
reaction were affected by the electronic property and
position of substituent. In view of the low catalytic activity
of substituted acetophenones over heterogeneous catalyst,
3.2 Catalytic Studies
The catalytic activity of catalyst was explored in the
asymmetric transfer hydrogenation of aromatic ketones.
i-Propanol serving as H-donor was applied in the Ir-cata-
lyzed asymmetric reaction. The initial heterogeneous
experiments were carried out using the acetophenone as a
model substrate, as shown in Table 2, the asymmetric
transfer hydrogenation reaction at room temperature pro-
vided (S)-1-phenylethanol in 94.0% conversion and 66.0%
ee. This ee value is higher than the corresponding homo-
geneous catalyst (60.1%, entry 2 in Table 2). The increase
in ee value may be mainly attributed to the confinement
Table 2 Asymmetric transfer hydrogenation of aromatic ketonesa
OH
O
CH3
[Ir(COD)Cl]2/2
CH3
R
R
KOH
3b-7b
3a-7a
O
O
O
O
O
CH3
CH3
CH3
CH3
CH3
CH3
F
Cl
Cl
3a
4a
5a
6a
7a
Entry
Substrate
Temp (K)
Conv. (%)b
ee (%)c
1
2d
3a
3a
4a
4a
5a
5a
6a
6a
7a
7a
5a
298
298
298
298
298
298
298
298
298
298
313
94.0
97.6
64.1
[99
32.8
99.3
80.0
98.3
74.8
97.8
53.5
66.0
60.1
59.2
54.5
78.3
74.7
64.6
63.9
47.6
45.3
69.8
3
4d
5
6d
7
8d
9
10d
11
a
Reactions were performed in isopropanol for 2 days with ketone-Ir-ligand-KOH = 1:0.05:0.1:0.2
b
c
d
Conversion % determined by GC with chiral column
ee % determined by GC with BETA-DEX 325 chiral column. The absolute configuration was S
Reaction performed using the homogeneous catalyst
123

108
Y. Shen et al.
periodicity after three runs. The used catalyst was found to
have a surface area of 193 m2/g and a narrow distribution
of pore size with a maximum at 4.4 nm as shown in
Table 1, which is smaller than that of the fresh catalyst.
Therefore, after the fourth run the catalyst was washed
thoroughly with solvents. Excitingly, 95.7% conversion
and 64.6% ee were observed in the fifth run, which is quite
comparable to the conversion and ee of the first run. Thus
the reason for the drop in activity and enatioselectivity
is possibly that the catalytic active sites are covered by
the adsorbed reactant, product, or impurities during the
reaction. Iridium leaching from each recycle is also
presented in Table 3, the amount of Ir leaching in the
Table 3 Recycle studies of the heterogeneous catalyst in the asym-
metric transfer hydrogenation of acetophenonea
Entry
Conv. (%)
ee (%)
Leaching of Metal (%)
0
1
2
3
4b
a
94.0
97.8
98.1
53.3
95.7
66.0
67.0
65.0
58.4
64.6
5.9 9 10-2
1.4 9 10-2
7.4 9 10-3
6.3 9 10-3
–
Reactions were performed in isopropanol at 298 K for 2 days
b
The catalyst was washed thoroughly with isopropanol, acetone,
ether and hexane
four runs was 5.9 9 10-2%, 1.4 9 10-2%, 7.4 9 10-3
%
we just investigated the effects of temperature by using
2-methylacetophenone as a substrate. As the temperature
was increased to 313 K, the catalytic activity increased
from 32.8 to 53.5% for conversion (entries 5 and 11) but
the enantioselectivity decreased slightly. It revealed that
the enhancement of reaction temperature had a favourable
effect on the catalytic activity. Next, the further investi-
gation is necessary to give a detailed understanding of the
factors that influenced the reaction.
and 6.3 9 10-3%, respectively. Total Ir leaching for four
runs was less than 0.1%, which is lower than previous
reports [23, 32, 33]. This noticeably low Iridium leaching
might be resulted from the stable coordination of Ir-N
complex, and also be owing to the formation of a strong
bond between Ir(I) complexes and mesoporous SBA-15.
Moreover, no further increase in the conversion occurred
while fresh reactant was added to the filtrate after each
reaction.
Recovery and reusability of the catalytic system was
evaluated by carrying out consecutive cycles for aceto-
phenone. The catalyst was carefully separated from the
reaction mixture by simple filtration and dried in a vacuum
without any other treatment. It was found that the catalyst
run 3 times still afforded almost the same conversion and
ee value as the first run (Table 3, entries 0–2). But for the
fourth run, both the ee value and conversion were observed
to fall. To make clear what is responsible for the drop in the
activity and enantioselectivity, the catalyst after three runs
was characterized by TEM and N2 adsorption-desorption
experiments. The well-ordered array of channels can be
clearly observed by TEM as shown in Fig. 4, indicating
that the mesoporous structure of the catalyst retained good
4 Conclusion
In summary, for the first time, 9-amino epi-cinchonine
ligand was immobilized on mesoporous silica SBA-15 to
produce an effective heterogeneous catalyst for the asym-
metric transfer hydrogenation of aromatic ketones. This
heterogeneous catalyst showed enhanced enantioselectivity
compared to the corresponding homogeneous analogue.
Moreover, total Ir leaching during four runs of the catalyst
was less than 0.1%. The catalyst could be easily regener-
ated by solvent washing.
Fig. 4 TEM micrograph of the
catalyst after three runs
123

Asymmetric Transfer Hydrogenation
109
Acknowledgements The authors are grateful to the National
Natural Science Foundation of China (20773069) and the Research
Fund for the Doctoral Program of Higher Education of China
(200800551017) for financial support.
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