Synthesis of chiral iridium complexes immobilized on amphiphilic polymers and their application to asymmetric catalysis

Article abstract of DOI:10.1002/pola.27351

This article details the enantioselective catalytic performance of crosslinked, polymer immobilized, Ir-based, chiral complexes for transfer hydrogenation of cyclic imines to chiral amines. Polymerization of the achiral vinyl monomer, divinylbenzene, and

Full text of DOI:10.1002/pola.27351

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Synthesis of Chiral Iridium Complexes Immobilized on Amphiphilic
Polymers and Their Application to Asymmetric Catalysis
Shinichi Itsuno, Yosuke Hashimoto, Naoki Haraguchi
Department of Environmental and Life Sciences, Toyohashi University of Technology, 441-8580, Japan
Correspondence to: S. Itsuno (E-mail: itsuno@ens.tut.ac.jp)
Received 10 June 2014; accepted 2 August 2014; published online 14 August 2014
DOI: 10.1002/pola.27351
ABSTRACT: This article details the enantioselective catalytic per-
formance of crosslinked, polymer immobilized, Ir-based, chiral
complexes for transfer hydrogenation of cyclic imines to chiral
amines. Polymerization of the achiral vinyl monomer, divinyl-
benzene, and a polymerizable chiral 1,2-diamine monosulfona-
mide ligand followed by complexation with [IrCl2Cp*]2 affords
the crosslinked polymeric chiral complex, which can be suc-
cessfully applied to asymmetric transfer hydrogenation of
cyclic imines. Polymeric catalysts prepared from amphiphilic
achiral monomers have high catalytic activity in the reaction
and can be used both in organic solvents and water to give
chiral cyclic amines with a high level of enantioselectivity (up
to 98% ee). The asymmetric reaction allows for reuse of the
heterogeneous catalyst without any loss in activity or enantio-
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2014 Wiley Periodicals, Inc. J.
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KEYWORDS: asymmetric transfer hydrogenation; catalysts; chiral
Ir complex; crosslinking; cyclic amine; cyclic imine; polymeric
catalyst; polystyrens
catalyst. In some cases, polymeric catalysts showed higher
enantioselectivities compared to monomeric catalysts.7 To
confirm the polymer effect on asymmetric catalysis, we syn-
thesized various kinds of polymer supports containing
hydrophobic, hydrophilic, and amphiphilic structures. We
focused on the polymer immobilization of a chiral iridium
catalyst for asymmetric transfer hydrogenation of cyclic
imines. To our knowledge, this is the first example of a poly-
meric iridium catalyst for chiral amine synthesis.
INTRODUCTION Polymer immobilization of chiral catalysts
has become an area of intense research over the decades.1
The dual ability to preferentially synthesize a particular
enantiomer and provide easy separation in a reaction makes
these catalysts highly practical for organic synthesis of opti-
cally active compounds. Crosslinked polystyrene supports
have been most widely used for immobilization.2 However,
heterogeneous reactions using polymer supported catalysts
sometime decrease the reactivity of the catalysts. In the case
of an asymmetric reaction, enantioselectivity was also
decreased with the use of a polystyrene supported catalyst.2
The hydrophobic microenvironment of the polystyrene sup-
port is not always optimal for reactions. Suitable polymer
structures should be chosen based on the reaction condi-
tions. Recently, some other solid supports for chiral catalysts
have been successfully developed for asymmetric reactions.3
In our previous study, a chiral ruthenium complex was
attached to a polystyrene support with ammonium salt
pendant groups, and this complex was efficiently used as a
polymeric catalyst for ketone reduction in aqueous solution.4
A polymeric catalyst prepared from chirally modified poly-
mer microspheres was used for the same reaction,5 and a
polymeric rhodium complex was efficiently used in the
asymmetric transfer hydrogenation of ketones.6
Since optically active amines and their derivatives are impor-
tant intermediates and building blocks for the synthesis of
biologically active molecules, asymmetric transfer hydrogena-
tion of imines has received significant attention.8 Although
numerous methods have emerged for the preparation of
enantiomerically pure amines in the past decades,9 catalytic
asymmetric transfer hydrogenation of imines offers the
advantages of a simple procedure and mild reaction condi-
tions for chiral amine synthesis.10 Various chiral catalysts
based on complexes of Ti, Ru, Rh, and Ir have been devel-
oped for transfer hydrogenation.11 Several examples of
polymer-immobilized versions of chiral transition metal cata-
lysts have also been reported.12 We found that the N-tolue-
nesulfonyl-1,2-diphenyl ethylenediamine (TsDPEN)-Ir-Cp*
complex showed high catalytic activity for the asymmetric
transfer hydrogenation of cyclic N-sulfonylimine, resulting in
the corresponding chiral sulfonamide. Within 10 min, the
The polymer conformation may change in different solvents,
and this can strongly influence the microenvironment of the
Additional Supporting Information may be found in the online version of this article.
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TABLE 1 Synthesis of Polymer-Immobilized TsDPEN Cross-
benzene, 2, as a crosslinking agent to give polymeric chiral
ligand 4. Complexation of the polymeric chiral ligand with
[IrCl2Cp*]2 afforded the polymeric chiral catalyst. The poly-
meric chiral Ir complex was then used as a catalyst for the
asymmetric transfer hydrogenation of cyclic imines to afford
the corresponding chiral sulfonamide. The catalytic activity
of the polymeric chiral Ir complexes strongly depended on
the structure of the achiral comonomers. We have synthe-
sized various polymeric chiral ligands, as shown in Table 1.
In this article, we describe the details of our study on the
asymmetric transfer hydrogenation of cyclic imines using a
polymer-immobilized chiral Ir catalyst.
linked with Divinylbenzenea
Entry Chiral polymer R1 in 3 R2 in 3
Yield (%)
1
2
4a
4b
CH3
H
CO2Me
88
88
3
4c
H
94
4
4d
4e
4f
H
CONHPri
CO2H
80
97
94
5
6b
CH3
H
7
8
9
4g
4h
4i
H
94
95
85
EXPERIMENTAL
Materials and General Considerations
H
(R,R)-1,2-Diphenylethylenediamine was purchased from Fuji
Molecular Planning and used without purification. Divinyl-
benzene 2 (96%) was supplied from Nippon Steel Chemical.
Methacrylic acid and methyl methacrylate were distilled
under reduced pressure. p-Styrenesulfonyl chloride was pre-
pared according to the method reported in the literature.14
Monomer 3i (2-methacryloyloxyethyl phosphorylcholine)
was supplied from NOF Corporation, Japan. All other com-
mercial reagents were purchased from Aldrich, Wako, or TCI
Chemicals and were used as received. Styrene and divinyl-
benzene were washed with aqueous sodium thiosulfate and
aqueous sodium hydroxide and distilled over calcium
hydride under a reduced pressure just before use. 2,20-Azobi-
s(isobutyronitrile) (AIBN) was purified by recrystallization
three times from anhydrous methanol. Water was purified
by a Millipore Milli-Q purification system. DMF was purified
by distillation over calcium hydride under a reduced pres-
sure. All other chemicals were used without purification.
CH3
10
4j
H
94
11
12
4k
4l
H
H
92
95
13b,c 4m
H
74
14
15
4n
4o
H
H
94
94
16
17
4p
4q
H
H
70
85
Reactions were monitored by thin layer chromatography
using Merck precoated silica gel plates (Merck 5554,
60F254). Column chromatography separations were per-
formed with a silica gel column (Wakogel C-200, 100–200
mesh). Melting points were taken on a Yanaco micro melting
apparatus and are uncorrected. Optical rotations were meas-
ured on a JASCO DIP-140 digital polarimeter with a 10-cm
thermostated microcell. NMR spectra were registered in Var-
ian Mercury 300 [300 MHz (1H)] or JEOL JNM-ECS400 spec-
trometers in CDCl3 or DMSO-d6 at room temperature
operating at 400 MHz (1H) and 100 MHz (13C{1H}). TMS was
used as internal standard for 1H-NMR and CDCl3 for 13C-
NMR. Chemical shifts were reported in ppm referred to TMS
and the J values were recorded in Hertz. IR spectra were
recorded with a JEOL JIR-7000 Fourier transform infrared
spectrometer and were reported in reciprocal centimeters
(cm21). Elemental analyses (carbon, hydrogen and nitrogen)
were performed on a Yanaco-CHN coder MT-6 analyzer. Ele-
mental analyses (sulfur) were performed at the Microanalyti-
cal Center of Kyoto University. GC analyses were performed
with a Shimadzu Capillary Gas Chromatograph GC-2014
equipped with a capillary column (SPERCO b-DEX 325, 30 m
a
Polymers crosslinked with 2% divinylbenzene (l:m:n 5 0.1:0.02:0.88)
were prepared unless otherwise noted.
b
10% crosslinked polymer.
c
4m was prepared from 4f and cetyltrimethylammonium chloride in
H2O at 60 ꢀC.
reaction was complete with quantitative conversion. This chi-
ral Ir complex was incorporated into crosslinked polymers
to evaluate the effect of polymer chains on the catalytic per-
formance of the polymeric Ir complex. The vinylphenyl group
is one of the most useful polymerizable functionalities for
polymer synthesis under the radical polymerization condi-
tion. The vinylphenyl group was easily introduced into the
chiral ligand, (R,R)-N1-(4-vinylbenzenesulfonyl)-1,2-diphenyl-
ethylene-1,2-diamine ((R,R)-1),13 which was copolymerized
with other achiral monomers, 3, in the presence of divinyl-
3
0.25 mm). High-performance liquid chromatography
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(HPLC) analyses were performed with a Jasco HPLC system
composed of a DG-980-50 three-line degasser, a PU 980
HPLC pump, and a CO-965 column oven equipped with a
chiral column (Chiralcell OD-H, Daicel) with hexane/2-propa-
nol as an eluent. A Jasco UV-975 UV detector was used for
the peak detection. Optical rotations were recorded with a
JASCO DIP-149 digital polarimeter, using a 10-cm thermo-
stated microcell.
yield. 1H NMR (300 MHz, DMSO-d6, d 5 0 ((CH3)4Si)): d5
3.96 (d, J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH),
5.36 (d, J 5 10.9 Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H;
vinyl), 6.69 (dd, J 5 10.9, 11.2 Hz, 1H; vinyl), 6.91-7.42 (m,
14H; Ar-H). Anal. calcd. for C27H41NO3S: C 70.55, H 8.99, N
3.05; found: C 70.62, H 8.83, N 3.06.
Monomer 3n
Solution of sodium p-toluenesulfonate (1.16 g, 6.0 mmol) in
Preparation of Achiral Monomers 3
Monomer 3h
H2O (15 mL) and
a solution of 4-vinylbenzyltrimethyl
ammonium chloride (0.844 g, 4.0 mmol) in CH2Cl2 (20 mL)
were placed in separatory funnel and shaking. Organic phase
was recovered and washed with brine. The solvent was
evaporated and dried in vacuo to give the white powder of
3n in 77% yield. 1H NMR (300 MHz, DMSO-d6, d 5 0
((CH3)4Si)): d5 3.96 (d, J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4
Hz, 1H; CH), 5.36 (d, J 5 10.9 Hz, 1H; vinyl), 5.88 (d, J
517.6 Hz, 1H; vinyl), 6.69 (dd, J 5 10.9, 11.2 Hz, 1H; vinyl),
6.91-7.42 (m, 14H; Ar-H). Anal. calcd. for C19H25NO3S: C
65.68, H 7.25, N 4.03; found: C 65.62, H 7.83 N 4.36.
A 50 mL round-bottomed flask with a magnetic stirring bar
was charged with CH2Cl2 (5 mL), 4-vinylbenzyl chloride
(0.775 g, 5.50 mL), tributylamine (0.926 g, 5.0 mmol). The
mixture was stirred for 48 h at room temperature. Solvent
was evaporated to give the white powder, which was washed
with ethyl acetate. After drying in vacuo, 3h was obtained in
1
85% yield. H NMR (400 MHz, CDCl3, d 5 0 ((CH3)4Si)): d5
3.96 (d, J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH),
5.36 (d, J 5 10.9 Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H;
vinyl), 6.69 (dd, J 5 10.9, 11.2 Hz, 1H; vinyl), 6.91–7.42 (m,
14H; Ar-H). Anal. calcd. for C21H36ClN: C 74.63, H 10.74, N
4.14; found: C 74.21, H 10.82, N 4.24.
Monomer 3o
A 50 mL of round-bottomed flask with a magnetic stirring
bar was charged with CH2Cl2 (5 mL), 4-vinylbenzyl chloride
(0.775 g, 5.5 mmol), triphenylphosphine (1.31 g, 5.0 mmol).
The mixture was stirred for 48 h at room temperature. Sol-
vent was evaporated to give the white powder, which was
washed with ethyl acetate. After drying in vacuo, 3o was
obtained in 84% yield. 1H NMR (300 MHz, CDCl3, d 5 0
((CH3)4Si)): d 5 5.50 (d, 2H, CH2), 5.22, 5.67 (d, 2H, CH2),
6.58 (q, 1H, CH), 7.07-7.77 (m, 19H, arom. CH)). Anal. calcd.
for C27H24ClP: C 78.16, H 5.83; found: C 78.01, H 5.80.
Monomer 3j
Solution of sodium p-styrenesulfonate (1.24 g, 6.0 mmol) in
H2O (15 mL) and a solution of tetrapropylammonium chlo-
ride (0.985 g, 4.0 mmol) in CH2Cl2 (20 mL) were placed in
separatory funnel and shaking. Organic phase was recovered
and washed with brine. The solvent was evaporated and
dried in vacuo to give the white powder of 3j in 81% yield.
1H NMR (400 MHz, DMSO-d6, d 5 0 ((CH3)4Si)): d5 3.96 (d,
J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH), 5.36 (d, J
5 10.9 Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H; vinyl), 6.69
(dd, J 5 10.9, 11.2 Hz, 1H; vinyl), 6.91–7.42 (m, 14H; Ar-H);
Elem. Anal. calcd. for C20H35NO3S: C 65.00, H 9.55, N 3.79, S
8.47; found: C 65.12, H 9.83 N 3.66, S 8.52.
Monomer 3p
Solution of sodium p-styrenesulfonate (1.24 g, 6.0 mmol) in
H2O (15 mL) and a solution of benzyltributylphosphonium
chloride (1.31 g, 4.0 mmol) in CH2Cl2 (20 mL) were placed
in separatory funnel and shaking. Organic phase was recov-
ered and washed with brine. The solvent was evaporated
and dried in vacuo to give the white powder of 3p in 95%
yield. 1H NMR (300 MHz, DMSO-d6, d 5 0 ((CH3)4Si)): d 5
3.96 (d, J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH),
5.36 (d, J 5 10.9 Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H;
vinyl), 6.69 (dd, J 5 10.9, 11.2 Hz, 1H; vinyl), 6.91-7.42 (m,
14H; Ar-H). Anal. calcd. for C27H41O3PS: C 68.03, H 8.67;
found: C 68.22, H 8.83.
Monomer 3k
Solution of sodium p-styrenesulfonate (1.24 g, 6.0 mmol) in
H2O (15 mL) and a solution of tetrabutylammonium chloride
(1.11 g, 4.0 mmol) in CH2Cl2 (20 mL) were placed in separa-
tory funnel and shaking. Organic phase was recovered and
washed with brine. The solvent was evaporated and dried in
1
vacuo to give the white powder of 3k in 90% yield. H NMR
(300 MHz, DMSO-d6, d 5 0 ((CH3)4Si)): d5 3.96 (d, J 5 7.3
Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH), 5.36 (d, J 5 10.9
Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H; vinyl), 6.69 (dd, J 5
10.9, 11.2 Hz, 1H; vinyl), 6.91–7.42 (m, 14H; Ar-H). Anal.
calcd. for C24H43NO3S: C 67.72, H 10.18, N 3.29, S 8.47;
found: C 67.62, H 10.03, N, 3.36, S 8.57.
Monomer 3q
Solution of sodium p-styrenesulfonate (1.24 g, 6.0 mmol) in
H2O (15 mL) and a solution of benzyltriphenylphosphonium
chloride (1.55 g, 4.0 mmol) in CH2Cl2 (20 mL) were placed
in separatory funnel and shaking. Organic phase was recov-
ered and washed with brine. The solvent was evaporated
and dried in vacuo to give the white powder of 3q in 98%
yield. 1H NMR (300 MHz, DMSO-d6, d 5 0 ((CH3)4Si)): d5
3.96 (d, J 5 7.3 Hz, 1H; CH), 4.34 (d, J 5 7.4 Hz, 1H; CH),
5.36 (d, J 5 10.9 Hz, 1H; vinyl), 5.88 (d, J 517.6 Hz, 1H;
vinyl), 6.69 (dd, J 5 10.9, 11.2 Hz, 1H; vinyl), 6.91-7.42 (m,
Monomer 3l
Solution of sodium p-styrenesulfonate (1.24 g, 6.0 mmol) in
H2O (15 mL) and a solution of benzyltributylammonium
chloride (1.24 g, 4.0 mmol) in CH2Cl2 (20 mL) were placed
in separatory funnel and shaking. Organic phase was recov-
ered and washed with brine. The solvent was evaporated
and dried in vacuo to give the white powder of 3l in 85%
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14H; Ar-H). Anal. calcd. for C33H29O3PS: C 73.86, H 5.45;
found: C 73.62, H 5.53.
General Procedure for the Preparation of Crosslinked
Polymer-Immobilized Chiral 1,2-Diamine
Monosulfonamide Ligand 4
A glass ampoule equipped with a magnetic stirring bar was
charged with DMF (0.78 g), (1R,2R)-1 (76 mg, 0.2 mmol),
divinylbenzene (5.3 mg, 0.04 mmol), vinyl monomer 3 (1.76
mmol), and AIBN (9.8 mg, 60 lmol). The ampoule was
sealed after three freeze-thaw cycles under liquid nitrogen.
Copolymerization was carried out at 60 ꢀC for 24 h. The
ampoule was opened and the resulting mixture was poured
into ether. The obtained polymer 4 was collected on a glass
filter and washed with THF, methanol and water and dried
under vacuum. The yields of the obtained polymers were
summarized in Table 1. The feed ratios of monomers (1, 2,
and 3), l:m:n 5 0.1:0.02:0.88, were in good agreement with
the monomer compositions of the polymers 4 determined by
the elemental analysis of the polymers.
General Procedure for Asymmetric Transfer
Hydrogenation in CH2Cl2
FIGURE 1 Synthesis of crosslinked polymer
4 containing
A 10 mL round-bottomed flask equipped with a magnetic
stirring bar was charged [IrCl2Cp*]2 (2.0 mg, 0.0025 mmol)
and the polymer-immobilized chiral 1,2-diamine monosulfo-
namide 4 (0.006 mmol) in CH2Cl2 (1 mL) under argon
atmosphere. After three cycles of freeze-thaw under liquid
TsDPEN structure.
tioselectivity were determined by GC and HPLC analysis,
respectively.
ꢀ
nitrogen, the mixture was heated to 40 C. After 1h, the mix-
ture was cooled to room temperature to give polymer-
iridium (III) complex. Cyclic sulfonimine 5a15 (90.6 mg, 0.50
mmol) and 5:2 HCO2H-Et3N azeotropic mixture (HCO2H 2.5
mmol) were then added and stirred at room temperature for
10 min. After the removal of the polymeric catalyst by filtra-
tion, the organic compounds were extracted twice with ether.
The conversion and enantioselectivity were determined by
GC and HPLC analysis, respectively.
RESULTS AND DISCUSSION
Synthesis of Polymer-Immobilized Chiral 1,2-Diamine
Monosulfonamide Ligand 4
We prepared the polymer-immobilized chiral N-sulfonyl 1,2-
diamine 4 with hydrophilic, hydrophobic, or amphiphilic
properties. These polymers (4) were prepared by radical
copolymerization of (R,R)-N1-(p-vinylbenzenesulfonyl)-1,2-
diphenylethylene-1,2-diamine ((R,R)-1),4(a) achiral monomer,
3, and divinylbenzene, 2 (Fig. 1). Achiral monomers, 3, used
in this study contain different properties based on their
hydrophilic, hydrophobic, or amphiphilic moieties. The struc-
tures of the chiral polymers, 4, are summarized in Table 1.
Radical polymerization of these monomers occurred
smoothly in DMF to give the chiral polymeric ligands 4 in
high yields. During polymerization, the viscosity of the solu-
tion increased and a gel-like polymer, 4, was obtained
because of the crosslinked structure formed with 2. The
In case of the reuse of the polymeric catalyst, the recovered
polymeric catalyst by filtration was transferred with CH2Cl2
(1 mL) into a 10 mL round-bottomed flask equipped with a
magnetic stirring bar. Cyclic sulfonimine 5a (0.50 mmol) and
5:2 HCO2H-Et3N azeotropic mixture (HCO2H 2.5 mmol) were
then added and stirred at room temperature for 10 min.
General Procedure for Asymmetric Transfer
Hydrogenation in Water
A 10 mL round-bottomed flask equipped with a magnetic
stirring bar was charged [IrCl2Cp*]2 (2.0 mg, 0.0025 mmol)
and the polymer-immobilized chiral 1,2-diamine sulphona-
mide 4 (0.006 mmol) in water (1 mL) under argon atmos-
phere. After the mixture had been degassed by three cycles
of freeze-thaw under liquid nitrogen, the mixture was stirred
at 40 ꢀC for 1 h under an argon atmosphere. Cyclic sulfoni-
mine 5a (0.50 mmol) and HCO2Na (2.5 mmol) were added
and stirred at room temperature for 24 h. After removal of
the polymeric catalyst by filtration, ether was added and
extracted the organic compounds. The conversion and enan-
FIGURE 2 Asymmetric transfer hydrogenation of cyclic sulfon-
amide 5.
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TABLE 2 Asymmetric Transfer Hydrogenation of Cyclic Imine
crosslinked polymers, 4, obtained in the polymerization were
insoluble in the solvent. All polymers, 4, were suspended in
ether and washed on a glass filter. Yields of the crosslinked
polymers, 4, are summarized in Table 1. Since the different
achiral monomers, 3, were incorporated in the chiral poly-
mers, 4, the polymeric chiral ligands contain different pend-
ant groups such as a hydrophobic moiety (4a, 4b, 4c),
hydrophilic moiety (4e, 4f) and amphiphilic moiety (4g–4p).
5a in CH2Cl2 at rta
Polymeric
Entry
Chiral Ligand
Time (min)
Yieldb (%)
Eec (%)
1
TsDPEN
4a
10
91
96
94
92
95
98
97
94
95
22
95
93
94
97
91
95
89
96
90
85
80
89
91
95
96
98
86
90
91
49
26
87
89
89
92
94
95
87
89
88
95
95
2
10
3d
4e
5f
4a
20
4a
2.5 h
19 h
30
Enantioselective Transfer Hydrogenation
with Polymeric Ir Complex
Ir-TsDPEN Catalyst
4a
6
4b
4c
To evaluate the catalytic activity of the resulting chiral poly-
meric complexes, enantioselective transfer hydrogenation of
cyclic sulfonimine, 5,16 was conducted in the presence of the
polymeric chiral Ir complex prepared from 4 (Fig. 2). First,
we used a low molecular weight Ir complex prepared
from (R,R)-N1-(p-toluenesulfonyl)-1,2-diphenylethylene-1,2-
diamine (TsDPEN). Based on the reaction conditions for the
Ru(II)-TsDPEN complex developed by Ikariya and
coworkers,17 we prepared the Ir-TsDPEN complex and used
it as a catalyst for the transfer hydrogenation of cyclic sulfo-
nimine, 5. With a S/C ratio of 100 at room temperature, the
catalyst was found to be very active in reducing the C@N of
5. Asymmetric transfer hydrogenation of cyclic imine 5a
occurred smoothly to give the product 6a as a quantitative
conversion in 10 min with an enantioselectivity of 89% ee
(Table 2, entry 1). The reduction proceeded at considerably
faster rates with the Ir complex than with Ru-based catalysts
for identical reactions.18 The corresponding Rh complex
showed lower enantioselectivity (68% ee) for the same
reaction.19
7
30
8
4d
10
9
4e
24 h
24 h
60
10
11
12
13
14
15
16
17
18
19
20
21
4fg
4g
4h
4i
30
90
4j
10
4k
10
4l
10
4mg
4n
4o
4p
4q
24 h
10
2 h
10
10
a
Reactions were carried out at room temperature with HCO2H-Et3N, S/C
5 100, l:m:n 5 0.1:0.02:0.88 unless otherwise noted.
b
Isolated yield.
c
ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
column.
Polymeric Catalyst
Effect of Temperature
d
Reaction was performed at 0 ꢀC.
e
Reaction was performed at 220 ꢀC.
f
Reaction was performed at 240 ꢀC.
We then used the polymeric Ir complex for the same reac-
tion. In general, the use of insoluble polymeric catalysts can
lower the reaction rate. However, by using the polymeric cat-
alyst derived from 4a, a surprisingly fast reaction occurred
to give the corresponding cyclic sulfonamine, 6a, in quantita-
tive yield with a high level of enantioselectivity (91% ee), as
shown in Table 2 (entry 2). The reaction rate observed for
the polymeric catalyst was almost the same as the rate for
monomeric TsDPEN. Although the chiral polymeric catalyst is
not soluble in organic solvents because of its crosslinked
structure, the reaction with 4a to give 6a was complete
within 10 min. We have also surveyed the effect of reaction
temperature on the asymmetric reaction with polymeric cat-
alyst 4a. Lowering the temperature gave higher enantioselec-
tivity with a decrease in the reaction rate as expected
(entries 2–5). The highest enantioselectivity (98% ee) was
g
l:m:n 5 0.1:0.1:0.8.
activity of the chiral Ir complex in the polymer (entries 9,
10). Polymers containing amphiphilic side chains (4g–4q)
had excellent performances in the asymmetric reaction,
except for 4m. The catalytic cites in the 4m polymer may be
buried in the long alkyl chain, which may disturb the sub-
strate accessibility, causing the lower catalytic activity (entry
17). The highest enantioselectivity (95% ee) with a high
yield of the product (95%) at room temperature was
obtained by using 4l, which contains quaternary ammonium
sulfonate side chain structures (entry 16). The same enantio-
selectivity was obtained by using 4p and 4q, which possess
quaternary phosphonium sulfonate pendant groups in the
side chains of the polymer support (entries 20, 21). With
these polymeric catalysts (4p, 4q), the isolated yields of the
product were slightly diminished because of their high vis-
cosity. The enantioselectivity obtained with these polymeric
catalysts prepared from 4l, 4p, and 4q is apparently higher
than that obtained with low molecular weight catalysts
ꢀ
obtained at 240 C (entry 5).
Effect of Polymer Structure
Other hydrophobic polymers such as 4b, 4c, and 4d showed
similar catalytic activities (entries 6–8). Hydrophilic poly-
mers (4e, 4f) containing carboxylic acid and sodium sulfo-
nate groups shrank in CH2Cl2 and suppressed the catalytic
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TABLE 4 Recycle Use of the Polymeric Catalyst 4l in Asymmet-
ric Transfer Hydrogenation of Cyclic Imine 5aa
Entry
Reaction cycle
Time (min)
Yieldb (%)
Eec (%)
1
2
3
4
5
1
2
3
4
5
10
10
20
20
20
95
95
97
94
98
95
95
96
96
95
a
All reactions were carried out at room temperature with HCO2H-Et3N,
S/C 5 100, l:m:n 5 0.1:0.02:0.88.
b
Isolated yield.
c
Ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
column.
FIGURE 3 Quaternary ammonium salts used as additives.
prepared from TsDPEN. The amphiphilic polymer chains
might form a suitable microenvironment that results in a
preferable catalyst conformation in the transition state of the
asymmetric reaction.
completed. The recovered polymeric catalysts were reused
for the same reaction. Table 4 shows the recycle results for
the use of polymeric catalyst 4l in the asymmetric transfer
hydrogenation of cyclic imine 5a. Over five recycle uses, no
significant loss in the catalytic activity was observed. Appli-
cation of such a robust polymeric catalyst to a continuous
flow system is expected.20
As shown in Table 2, we found that polymers containing
quaternary ammonium and phosphonium salt structures
exhibited efficient catalytic activity in the asymmetric trans-
fer hydrogenation of cyclic imines. To better understand the
effect of quaternary ammonium salts on the asymmetric
reaction, we used monomeric and polymeric quaternary
ammonium salts (7–9) as additives in the same reaction
(Fig. 3). Table 3 summarizes the effect of additives on the
asymmetric reaction. The quaternary ammonium salts had
no effect on the enantioselectivity of the catalyst (entries 2–
4). Only when quaternary ammonium sulfonate was incorpo-
rated into the polymer chain, the Ir complex on the same
polymer chain had high catalytic activity for the reaction
(entry 5). It is necessary to have quaternary ammonium sul-
fonate in the polymer chain for the formation of a suitable
microenvironment of the catalyst.
Effect of Monomer Composition
The microenvironment created in the polymer chain strongly
influenced the catalytic activity of the chiral transition metal
complex. The effect of monomer composition in polymer 4l
on the catalytic activity was investigated and is shown in
Table 5. An increase in the crosslinking degree caused a low-
ering of the catalytic activity (entries 2, 5–7). Linear
polymers showed slightly lower catalytic activity and enan-
tioselecitivity (entry 1). Higher loading of the catalyst
resulted in a lowering of the enantioselectivity (entry 4). A
suitable composition of monomers for 4l was 10% loading
of the chiral ligand, 2% crosslinkage, and 88% achiral qua-
ternary ammonium sulfonate (entry 2).
Recyclability of the Polymeric Catalyst
The polymeric catalysts prepared are insoluble because of
their crosslinked structures. They can be easily separated
from the reaction mixture after the asymmetric reaction
TABLE 5 Effect of Catalyst Loading of 4l on Asymmetric Trans-
fer Hydrogenation of 5aa
TABLE 3 Effect of Additives in Asymmetric Transfer Hydrogen-
ation of Cyclic Imine 5aa
Entry
l:m:n
Time (min)
Yieldb (%)
Eec (%)
1
2
3
4
5
6
7
0.1:0:0.9
30
10
10
30
20
30
60
92
95
92
90
91
90
90
93
95
95
92
94
93
94
Entry Chiral ligand Additive Time (min) Yieldb (%) Eec (%)
0.1:0.02:0.88
0.05:0.02:0.93
0.2:0.02:0.78
0.1:0.05:0.85
0.1:0.1:0.8
1
2
3
4
5
TsDPEN
TsDPEN
TsDPEN
TsDPEN
4l
-
10
20
60
20
10
91
84
75
91
95
89
89
89
89
95
7
8
9
-
0.1:0.2:0.7
a
a
All reactions were carried out at room temperature with HCO2H-Et3N,
All reactions were carried out at room temperature with HCO2H-Et3N,
S/C 5 100.
S/C 5 100, l:m:n 5 0.1:0.02:0.88.
b
b
Isolated yield.
Isolated yield.
c
c
Ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
Ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
column.
column.
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TABLE 7 Asymmetric Transfer Hydrogenation of Cyclic Imine
5a in Watera
Polymeric
chiral
Time
(h)
Yieldb
(%)
Eec
(%)
Entry
ligand
1
2
3
4
5
6
7
8
9
TsDPEN
24
24
20
20
20
20
20
20
20
–
–
4a
4f
–
–
70
92
95
93
96
95
90
80
72
78
80
81
86
80
FIGURE 4 Cyclic imines used in the asymmetric transfer
hydrogenation.
4h
4i
4j
4k
4l
Asymmetric Transfer Hydrogenation of Various Cyclic
Imines
4o
Some cyclic imines with different structures than 5a were
used in the transfer hydrogenation reaction under the same
reaction conditions using the polymeric Ir complex prepared
from 4l (Fig. 4). Table 6 summarizes the results for the
asymmetric transfer hydrogenation of imines 5b, 10, and 11.
Catalysts prepared from 4l demonstrated excellent activity in
the reaction to give the chiral product in 92% ee (entry 3),
which is higher than that obtained from the low molecular
weight soluble catalyst prepared from TsDPEN (entry 1). The
asymmetric transfer hydrogenation of the six membered ring
imine, 10, gave a lower enantioselectivity (entries 4, 5). Sur-
prisingly, the asymmetric transfer hydrogenation of 11 with
the Ir complex resulted in a racemic product (entries 6, 7).
However, when Ir was replaced with Rh, the enantioselectiv-
ity drastically increased to 95% ee (entries 8–10). Although
a similar tendency was observed in the dynamic kinetic reso-
lution of sulfoamidate,21 there is no rational explanation for
the dramatic change in the catalytic activity.
a
All reactions were carried out at room temperature with HCO2H-Et3N,
S/C 5 100, l:m:n 5 0.1:0.02:0.88.
b
Isolated yield.
c
Ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
column.
Asymmetric Transfer Hydrogenation in Water
With the idea of creating an environmentally friendly system,
organic reactions in aqueous phases have attracted signifi-
cant interest.22 Because of its hydrophobic character, the cat-
alyst prepared from TsDPEN showed no catalytic activity in
the asymmetric transfer hydrogenation of 5a (Table 7, entry
1). Zhu and Deng synthesized water soluble TsDPEN with
SO3Na substituents.23 A ruthenium complex was used as a
catalyst for the same reaction in water to afford the product
in a high conversion with 65% ee.23 As shown in Table 1,
many of the polymeric catalysts developed in this study con-
tain ionic structures in their side chains. Such polymers have
good affinities for aqueous solutions. These polymers can be
homogeneously suspended in water. For example, in the
presence of 4f, with SO3Na pendant groups on its polymer
side chain, the asymmetric transfer hydrogenation occurred
in water to give the corresponding chiral cyclic amine in a
70% yield with 80% ee (Table 7, entry 3). Other ionic poly-
mers 4h, 4i, 4j, 4k, 4l, and 4o showed high catalytic activity
in water to give the chiral product with a quantitative con-
version. The highest enantioselectivity (86% ee) was
obtained by using 4l.
TABLE 6 Asymmetric Transfer Hydrogenation of Other Cyclic
Iminesa
Chiral
ligand
Cyclic
Imine
Time
(min)
Yieldb
(%)
Eec
(%)
Entry
1
2
3
4
5
6
7
8
9
10
TsDPEN
5b
5b
5b
10
10
11
11
11
11
11
1
90
34
70
91
95
92
90
91
96
97
84
84
92
43
41
0
4a
12
1
4l
TsDPEN
1
4l
1
CONCLUSIONS
TsDPEN
1
Chiral ligand monomer, (R,R)-N1-(4-vinylbenzenesulfonyl)-
1,2-diphenylethylene-1,2-diamine, 1, was copolymerized with
divinylbenzene, 2, and various kinds of achiral monomers, 3,
to give polymer-immobilized chiral ligands, 4. Treatment of
4 with [IrCl2Cp*)]2 gave a polymeric chiral complex that was
used as a chiral catalyst for asymmetric transfer hydrogena-
tion of cyclic imines. Catalytic activity of the polymeric chiral
complex was strongly dependent on the polymer properties.
Polymeric catalysts prepared from polymer supports with
amphiphilic pendant groups on their side chains (4j, 4k, 4l,
4l
1
0
TsDPEN
24
24
24
95
95
95
4a
4l
a
All reactions were carried out at room temperature with HCO2H-Et3N,
S/C 5 100, l:m:n 5 0.1:0.02:0.88.
b
Isolated yield.
c
Ee was determined by HPLC analysis with a Daicel Chiralcel OD-H
column.
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7 (a) Z. Tang, H. Iida, H.–Y. Hu, E. Yashima, ACS Macro Lett.
2012, 1, 261–265; (b) M. M. Parvez, N. Haraguchi, S. Itsuno,
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4p, 4q) had high catalytic activity for asymmetric transfer
hydrogenation. Although they were crosslinked with divinyl-
benzene and insoluble in the solvent used, the reaction
occurred very quickly to give the product in a quantitative
conversion with a high level of enantioselectivity, up to 98%
ee at 240 ꢀC. For example, 4l, with quaternary ammonium
sulfonate pendant groups on the side chain of the polymer
support, had excellent catalytic activity for the reaction.
Enantioselectivities obtained using these amphiphilic poly-
meric catalysts were higher than that obtained from the cor-
responding low molecular weight catalyst prepared from
TsDPEN. Because of their insolubility, the polymeric catalysts
were easily separated from the reaction mixture and reused
several times without any loss of the catalytic activity. More-
over, the amphiphilic properties of the polymeric catalysts
enabled us to use them in aqueous systems. In contrast with
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occurred with 4l in water to give the chiral product in quan-
titative conversion. The polymeric catalysts with amphiphilic
properties developed in this research may be applied to vari-
ous kinds of polymer-immobilized catalysts in both organic
and aqueous systems.
8 N. Haraguchi, K. Tsuru., Y. Arakawa, S. Itsuno, Org. Biomol.
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ACKNOWLEDGMENTS
This work was partially supported by a Grant-in-Aid for Sci-
entific Research on Innovative Areas “New Polymeric Materi-
als Based on Element-Blocks” (No. 25102515) from the
Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan.
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