Asymmetric transfer hydrogenation of imines catalyzed by a polymer-immobilized chiral catalyst

Article abstract of DOI:10.1039/b815407b

The asymmetric transfer hydrogenation of imines was performed with the use of a polymer-immobilized chiral catalyst. The chiral catalyst, prepared from crosslinked polystyrene-immobilized chiral 1,2-diamine monosulfonamide, was effective in the asymmetric transfer hydrogenation of N-benzyl imines in CH ₂Cl₂ to give a chiral amine in high yield and good enantioselectivity. Furthermore, an amphiphilic polymeric catalyst prepared from crosslinked polystyrene containing sulfonated groups successfully catalyzed the asymmetric transfer hydrogenation of cyclic imines in water. Enantioenriched secondary amines with up to 94% ee were obtained by using a polymeric catalyst.

Full text of DOI:10.1039/b815407b

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Asymmetric transfer hydrogenation of imines catalyzed by a
polymer-immobilized chiral catalyst†
Naoki Haraguchi,* Keiichi Tsuru, Yukihiro Arakawa and Shinichi Itsuno
Received 3rd September 2008, Accepted 6th October 2008
First published as an Advance Article on the web 6th November 2008
DOI: 10.1039/b815407b
The asymmetric transfer hydrogenation of imines was performed with the use of a polymer-immobilized
chiral catalyst. The chiral catalyst, prepared from crosslinked polystyrene-immobilized chiral
1,2-diamine monosulfonamide, was effective in the asymmetric transfer hydrogenation of N-benzyl
imines in CH2Cl2 to give a chiral amine in high yield and good enantioselectivity. Furthermore, an
amphiphilic polymeric catalyst prepared from crosslinked polystyrene containing sulfonated groups
successfully catalyzed the asymmetric transfer hydrogenation of cyclic imines in water. Enantioenriched
secondary amines with up to 94% ee were obtained by using a polymeric catalyst.
meric ruthenium(II) complex prepared from polymer-immobilized
Introduction
chiral TsDPEN and [RuCl2(p-cymene)] was applied to asymmetric
transfer hydrogenation of ketones in water.7 Interestingly, both
reactivity and enantioselectivity in the reaction by using the
polymeric chiralcatalyst was somewhat higher than thoseobtained
by using Ikariya’s original catalyst in homogeneous solution.
We found that a chiral polymeric ligand having a quaternary
ammonium salt structure at the polymer side chains was highly
suitable for use in water.
Although prochiral imines are subject to hydrogenation by
Ikariya catalyst, asymmetric transfer hydrogenation of prochiral
imines with the use of a supported version of the catalyst
has been much less investigated than that of the ketones. Very
recently, Ying et al. reported the successful preparation of siliceous
mesocellular foam-immobilized chiral TsDPEN.8 The ruthenium
complex showed high catalytic activity and recyclability in organic
solvent, but the reaction in water is not investigated. In this article,
we demonstrate asymmetric transfer hydrogenation of imines
catalyzed by a polymer-immobilized chiral catalyst. The influence
of polymer structure on the reaction was mainly investigated.
Enantiomerically pure amines are highly important intermediates
or building blocks for biologically active molecules in medical,
pharmaceutical, and agricultural science. Numerous completely
different methods have emerged for the preparation of enan-
tiomerically pure amines in the past few years.1 One of the
popular methods for preparation of chiral amines is asymmetric
transfer hydrogenation of imines. Among the various chiral
catalysts reported for asymmetric transfer hydrogenation, the most
significant to date is the ruthenium(II) complex with optically
active N-toluenesulfonyl-1,2-diphenylethylenediamine (TsDPEN)
developed by Ikariya and Noyori’s group.2 As the catalytic
system, chiral TsDPEN/RuCl2(p-cymene) complex is well known
as a highly effective and enantioselective catalyst for asymmetric
transfer hydrogenation of various kinds of ketones and imines.
On the other hand, the use of a polymer-support technique is
now going to be recognized as one of the standard techniques
in modern organic synthesis.3 The advantage of immobilization
of a chiral catalyst to a polymer is not only easy separation
of the chiral catalyst from the reaction mixture and its reuse
but the easy modification of the characters (e.g. contents of
chiral catalyst, degree of crosslinking, hydrophilic–hydrophobic
balance, and so on). The first study on polymer-immobilization
Results and discussion
Preparation of polymer-immobilized ruthenium(II) complex
of Ikariya and Noyori’s catalyst was reported by Lemaire.4
A
similar polystyrene-immobilized chiral TsDPEN was utilized for
the synthesis of (S)-fluoxtine.5 Since this catalyst is known to
be tolerant in asymmetric transfer hydrogenation in aqueous
media,6 a polymeric chiral catalyst suitable for aqueous conditions
was developed. Poly(ethylene glycol)-supported chiral TsDPEN
developed by Xiao7 was highly effective in asymmetric transfer
hydrogenation of simple ketones by sodium formate in neat water.
Recently, we have successfully synthesized novel crosslinked
polymer-immobilized chiral TsDPENs containing hydrophilic
functional groups such as carboxylate and sulfonate. The poly-
Three types of polymer-immobilized chiral TsDPENs were pre-
pared by radical polymerization of enantiopure 1,2-diamine
monosulfonamide monomer,9 styrene derivative, and divinylben-
zene in DMF (Fig. 1). (R,R)-1, (R,R)-2, and (R,R)-3 were
obtained in 92, 94, and 86% yields, respectively. The styrene-
based polymer (R,R)-1 was well swollen in a good solvent for
crosslinked polystyrene such as DMF, THF and toluene, but
completely shrunk in water due to the hydrophobic character. In
contrast, polymers bearing sulfonate groups (R,R)-2, and (R,R)-3
were found to be swollen in dimethylsulfoxide and water.
Polymer-immobilized ruthenium(II) complex was prepared ac-
cording to Ikariya’s procedure. The polymer-supported chiral
TsDPEN was treated with [RuCl2(p-cymene)]2 in an organic
solvent such as CH2Cl2 and CH3CN at 80 ◦C for 1 h. The
obtained polymer-immobilized complex showed an orange color,
Department of Materials Science, Toyohashi University of Technology, 1-1
Hibarigaoka, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan. E-mail:
haraguchi@tutms.tut.ac.jp; Fax: +81 532 48 5833; Tel: +81 532 44 6812
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra of compounds. See DOI: 10.1039/b815407b
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Fig. 1 Polymer-immobilized chiral ligands.
which is typical of the ruthenium(II) complex. Although the
polymer complex is insoluble due to its crosslinked structure, we
measured the gel-phase 1H NMR of the polymers. The 1H NMR
spectrum of the crosslinked polymeric complex showed that methyl
and aromatic proton signals assigned to p-cymene were clearly
observed after the complexation (Fig. 2). The result indicated that
the ruthenium(II) complex was formed on the polymer.
in CH2Cl2. The ruthenium(II) complex derived from chiral
TsDPEN catalyzed the asymmetric transfer hydrogenation of 4
and the enantioenriched secondary amine (R)-5 was obtained
in quantitative conversion with 78% ee (Table 1, entry 12).10 We
have examined three types of polymer-immobilized ruthenium(II)
complex for the same reaction in CH2Cl2. Hydrophobic polymeric
ruthenium(II) complex prepared from (R,R)-1 (x–y–z = 0.1 :
0.8 : 0.1) successfully catalyzed the reaction at room temperature
to afford (R)-5 in 95% conversion with 84% ee after 48 h
(entry 1). In contrast to the results, the reactions with the use
of polymeric ruthenium(II) complexes prepared from amphiphilic
polymer (R,R)-2 and hydrophilic polymer (R,R)-3 resulted in very
low conversions (3%) (entries 2 and 3). The catalyst moiety in the
hydrophilic polymer chain would not have sufficient interaction
with the substrate and hydrogen source. These results indicate
that the effect of the hydrophobic and/or hydrophilic segment is
significant in the reaction.
Asymmetric transfer hydrogenation of N-benzylimine 4 using
polymer-immobilized chiral catalyst in organic solvent
At first, asymmetric transfer hydrogenation of N-benzyl imine
4 with the use of polymer-immobilized ruthenium(II) complex
was carried out to investigate the catalytic activity in CH2Cl2.
The results are summarized in Table 1. The asymmetric transfer
hydrogenation of N-benzyl imine 4 was performed by using
Et3N–HCO2H (5 : 2, v/v, 5 equiv. to 4) as a hydrogen source
Fig. 2 Gel-phase 1H NMR spectra of polymer-immobilized chiral TsDPEN (a) and ruthenium(II) complex (b).
70 | Org. Biomol. Chem., 2009, 7, 69–75
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a,b,c
Table 1 Asymmetric transfer hydrogenation of 4 catalyzed by polymer-immobilized ruthenium(II) complex in CH2Cl2
(R)-5
Entry
Ligandc
Metal precursor
Temp/◦C
Time/h
Conv (%)d
Ee (%)e
1
2
3
(R,R)-1
(R,R)-2
(R,R)-3
(R,R)-1
(R,R)-1
(R,R)-1
(R,R)-1
(R,R)-1
(R,R)-1
(R,R)-1
(R,R)-1
TsDPEN
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RhCl2Cp*]
rt
rt
rt
rt
rt
rt
40
0
rt
rt
rt
rt
48
120
24
3
36
24
48
48
48
48
24
3
95
3
3
92
96
99
87
80
0
84
ND
ND
88
86
63
69
93
ND
29
77
4
5f
6g
7
8
9h
10
11
12
> 99
> 99
> 99
[IrCl2Cp*]
[RuCl2(p-cymene)]2
78
a Unless otherwise stated, the reaction was carried out with Et3N–HCO2H (5 : 2, v/v, 5 equiv. to 4). b S/C = 100. c The ratio of x–y–z was 0.1 : 0.8 : 0.1.
d The conversion was determined by 1H NMR. e The ee was determined by HPLC analysis with a Daicel Chiralcel OD-H column. f In CH3CN. g In DMF.
h HCO2Na was used instead of Et3N–HCO2H.
reaction. The reuse examination was carried out under conditions
similar to those of entry 1 in Table 1. From the catalyst derived
from (R,R)-1, we obtained 5 in >90% yield with 84, 77, 78% ees
for three recycling experiments. Reuse of the polymeric catalyst
was possible with keeping the catalytic activity.
Scheme 1 Asymmetric transfer hydrogenation of 4 using polymer-immo-
bilized chiral catalyst in CH2Cl2.
Asymmetric transfer hydrogenation of various imines in CH2Cl2
Encouraged by the results mentioned above, asymmetric trans-
Since the hydrophobic polymeric ruthenium(II) complex derived
fer hydrogenation of various imines by using the polymer-
from (R,R)-1 was found to be suitable for asymmetric transfer
immobilized chiral catalyst prepared from (R,R)-1 was investi-
hydrogenation of imine 4, a further investigation into the reaction
gated in CH2Cl2 (Table 2). Acyclic N-benzyl imine prepared from
conditions was performed. The conversion of (R)-5 was 92% even
4¢-bromoacetophenone 6a was converted into the corresponding
after 3 h, which indicated that 4 was smoothly hydrogenated by the
optically active secondary amine with 64% ee (entry 2). The
polymer-immobilized chiral catalyst (entry 4). Enantioselectivity
transfer hydrogenation of 6b resulted in the decomposition of
obtained in CH3CN (86%) was similar to the value obtained in
the substrate (entry 3). Cyclic imines such as 10 and 12 could
CH2Cl2 (entries 1, 4, and 5). These enantioselectivities obtained
be subjected to asymmetric transfer hydrogenation, which yielded
from the polymeric chiral catalysts was apparently higher than that
(S)-11 and (S)-13 with higher enantioselectivities (92% ee and
obtained from TsDPEN and [RuCl2(p-cymene)]2. The use of DMF
95% ee, respectively) (entries 5 and 6). Unfortunately, no or trace
gave the higher conversion of 99% but lowered the enantioselec-
reaction was observed when N-aryl imine 14, 15, and 16 were
tivity (entry 6). The temperature effect on the enantioselectivity
employed as substrates.
was examined in CH2Cl2. A significant enhancement in ee value
was observed when the reaction temperature was decreased to
0 ◦C (entry 8). No conversion was observed when sodium formate
Table 2 Asymmetric transfer hydrogenation of various imines catalyzed
a,b,c
by polymer-immobilized chiral catalyst in CH2Cl2
was used instead of a 5 : 2 triethylamine–formic acid azeotropic
mixture11 as a hydrogen source (entry 9). Although both rhodium
and iridium complex could be used as a metal precursor in the
reaction, these ee values were inferior to that of ruthenium (entries
10 and 11). The effect of polymer segment on the reactivity and
enantioselectivity is still obscure, but one possible explanation
is that the steric hindrance of the polymer chain and network
might affect the enantioselectivity if the polymer chain leads to
the suitable conformation of chiral catalyst and substrate. The
other possibility is due to the structural difference of the chiral
ligand. The structure we employed is N-isopropylbenzenesulfonyl-
1,2-diphenylethylenediamine rather than N-toluenesulfonyl-1,2-
diphenylethylenediamine.
Entry Imine Temp/◦C Time/h Amine Conv (%)d Ee (%)e Config.
1
2
3
4
5
6
7
8
9
4
rt
rt
rt
rt
rt
rt
rt
rt
rt
48
24
24
144
24
24
168
24
24
5
95
>99
Degrad.
86
>99
91
0
0
<5
84
64
—
49
92
95
—
—
ND
R
6a
6b
8
7a
7b
9
R
—
R
S
S
—
—
—
10
12
14
15
16
11
13
—
—
—
a Unless otherwise stated, the reaction was carried out with Et3N–HCO2H
(5 : 2, v/v, 5 equiv. to substrate). b S/C = 100. c The ratio of x–y–z was
0.1 : 0.8 : 0.1. d The conversion was determined by 1H NMR. e The ee was
determined by HPLC analysis with a Daicel Chiralcel OD-H column.
The polymeric chiral catalyst could be easily separated from the
reaction mixture due to its insolubility and reused for the following
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Fig. 3 Imines and corresponding chiral amines.
Asymmetric transfer hydrogenation of cyclic imine 10 using
polymer-immobilized chiral catalyst in H2O
reaction occurred in water and longer reaction time and higher
temperature caused the hydrolysis of the substrate. Cyclic imine
10, which was stable in water for an even longer reaction time
and at a higher temperature, was then employed as a substrate of
transfer hydrogenation in water. The reaction was carried out in
water with 5 equivalents of HCO2Na to substrate 10. The results
are summarized in Table 3.
Since this type of catalyst is known to be tolerant in water,
we used the polymer-immobilized catalyst in water (Scheme 2).
Despite the progress made in the asymmetric transfer hydrogena-
tion of ketones in water,12 little work on asymmetric transfer
hydrogenation of imines13 in water has been reported. Zhu
and Deng have recently reported the first asymmetric transfer
hydrogenation of imines and iminiums in aqueous media.14 They
utilized a water soluble ruthenium(II) complex of a designed Ts-
DPEN bearing two sulfonated groups as a chiral catalyst and
cetyltrimethylammonium chloride as an additive. They concluded
that the formation of micelles and the electrical charge on a
micelle are important to achieve high enantioselectivity. They also
reported a water-soluble rhodium(III) catalyst bearing two amino
groups to enhance the hydrophilicity.15 These catalysts were found
to be suitable in asymmetric transfer hydrogenation of imines in
neat water. New water-soluble arene ruthenium catalysts were
also designed by Su¨ss-Fink et al.16 They examined the catalytic
potential for asymmetric transfer hydrogenation of imines in
aqueous solution.
Polystyrene-immobilized chiral catalyst derived from (R,R)-1,
which consists of a hydrophobic polymer chain, was not suitable
for the reaction due to the shrinkage in water (Table 3, entry 1).
Even though the reaction in water is slower than in organic
solvent, the polymer-immobilized chiral catalysts prepared from
(R,R)-2 and (R,R)-3 showed good catalytic activities in neat water
(entries 2, 3 and 4). The reaction could be accelerated when
polymeric catalyst with 2 mol% crosslinking was used (entry
5). The enantioselectivities of (S)-11 obtained at 40 ◦C were
slightly higher than those obtained at room temperature (entries 6
and 7). Addition of benzyltributylammonium chloride resulted
in lowering the enantioselectivity (entry 8). However, interest-
ingly, cetyltrimethylammonium chloride and bromide, possessing
longer alkyl chains, as additives were effective in obtaining the
enantioenriched amine (entries 9 and 10). Only a trace amount
of product was obtained by employing Et3N–HCO2H as the
hydrogen donor (entry 11). Rhodium and iridium complexes were
also found to be effective metal precursors in the asymmetric
transfer hydrogenation of 10 in water. Both the conversions
and enantioselectivities were similar to the values obtained with
ruthenium(II) complex (entries 12 and 13). These results clearly
indicate that the polymeric chiral catalysts prepared from (R,R)-
2 and (R,R)-3 are one of the most effective chiral catalysts of
asymmetric transfer hydrogenation of imines in water.
Scheme 2 Asymmetric transfer hydrogenation of 10 using polymer-im-
mobilized chiral catalyst in H2O.
In our system, the use of a polymer-immobilized chiral catalyst
enabled us to change the hydrophilic–hydrophobic balance as
well as the electrical effect easily because the various functional
groups could be introduced at the pendant position of the polymer
main chain. We expected that the polymeric effect would lead to
successful asymmetric transfer hydrogenation of imines in water.
We attempted transfer hydrogenation of 4 in water with the
use of a polymeric chiral catalyst in the beginning. However, no
Conclusions
In conclusion, we have developed the catalytic asymmetric
transfer hydrogenation of imines with the use of a polymer-
immobilized chiral catalyst both in organic solvent and in water.
Polystyrene-immobilized ruthenium(II) complex prepared from
(R,R)-1 was effective for the asymmetric transfer hydrogenation
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Table 3 Asymmetric transfer hydrogenation of 10 catalyzed by polymer-immobilized ruthenium(II) complex in H2Oa,b
(S)-11
Entry
Ligand
Monomer ratio x–y–z
Temp/◦C
Time/h
Conv (%)c
Ee (%)d
1
2
3
4
5
(R,R)-1
(R,R)-2
(R,R)-3
(R,R)-3
(R,R)-3
(R,R)-2
(R,R)-3
(R,R)-3
(R,R)-3
(R,R)-3
(R,R)-3
(R,R)-3
(R,R)-3
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.88 : 0.02
0.1 : 0.8 : 0.1
0.1 : 0.88 : 0.02
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
0.1 : 0.8 : 0.1
rt
rt
rt
rt
rt
40
40
rt
rt
rt
rt
rt
rt
24
24
6
<1
50
24
75
88
82
95
66
69
61
6
ND
89
ND
89
88
91
90
86
94
93
24
24
48
48
24
24
24
24
24
24
6
7
8e
9f
10g
11h
12i
13j
ND
89
86
72
79
a Unless otherwise stated, the reaction was carried out with [RuCl2(p-cymene)]2 and HCO2Na (5 equiv. to 10). b S/C = 100. c The conversion was
1
determined by H NMR. d The ee was determined by HPLC analysis with a Daicel Chiralcel OD-H column. e Benzyltributylammonium chloride was
added. f Cetyltributylammonium chloride was added. g Cetyltributylammonium chloride was added. h Et3N–HCO2H was used instead of HCO2Na.
i [RhCl2Cp*] was used instead of [RuCl2(p-cymene)]2. j [IrCl2Cp*] was used instead of [RuCl2(p-cymene)]2.
of N-benzyl imines in organic solvent such as CH2Cl2 and
CH3CN. The corresponding amines were obtained in good yields
with good enantioselectivities. In contrast, polymer-immobilized
ruthenium(II) complexes prepared from amphiphilic (R,R)-2 and
hydrophilic (R,R)-3 were found to be effective for the asymmetric
transfer hydrogenation of cyclic imines in water. We concluded that
the hydrophilic–hydrophobic balance in a polymer-immobilized
chiral catalyst on the asymmetric reaction was an important factor
in controlling the catalytic activity. To our knowledge, this is the
first successful report on the asymmetric transfer hydrogenation
of imines by utilizing a polymer-supported chiral catalyst in water.
b-DEX 325, 30 m x 0.25 mm). HPLC analyses were performed with
a JASCO HPLC system composed of a 3-line degasser DG-980–
50, HPLC pump PV-980, column oven CO-965, equipped with a
chiral column (CHIRALCEL OD or AD, Daicel) using hexane/2-
propanol as eluent. A UV detector (JASCO UV-975 for JASCO
HPLC system) was used for the peak detection. Optical rotations
were taken on a JASCO DIP-149 digital polarimeter using a 10 cm
thermostatted microcell. Size exclusion chromatography (SEC) for
the characterization of molecular weight and its distribution of
linear polymers was conducted at 40 ◦C with a JASCO PU-980 as
a pump, JASCO UVIDEC- 100-III as a UV detector, and Shodex
˚
column A-802 (pore size: 20 A) ¥ 2 as columns. The eluent was
THF, and the flow rate was 1.0 mL min-1. A molecular weight
calibration curve was obtained by using a series of polystyrene
standards (Tosoh Co., Japan).
Experimental
General
Materials. Unless otherwise stated, all solvents and styrene,
ketone, and amine derivatives were distilled from calcium hy-
dride (CaH2) under reduced pressure or ambient pressure.
Sodium 4-vinylbenzenesulfonate, benzyltributylammonium chlo-
ride, cetyltrimethylammonium chloride, cetyltrimethylammonium
bromide, and sodium formate were used as received. (R,R)-
1,2-Diphenylethylenediamine ((R,R)-DPEN) was purchased from
Fujimoto Molecular Planning. Co. and used without purification.
Preparation of polymer-immobilized chiral catalyst
Synthesis of (1R,2R)-N1-(4-vinylbenzenesulfonyl)-1,2-diphenyl-
ethane-1,2-diamine9. A 50 mL round-bottomed flask equipped
with a magnetic stirring bar was charged with (1R,2R)-1,2-
diphenylethane-1,2-diamine (0.997 g, 4.70 mmol), triethylamine
(0.950 g, 9.39 mmol) and 7 mL of dry CH2Cl2 under dry nitrogen.
4-Vinylbenzene-1-sulfonyl chloride1 (0.865 g, 4.27 mmol) and
3 mL of dry CH2Cl2 were then added to the mixture at 0 ◦C and the
mixture was stirred under an atmosphere of dry nitrogen. After
the mixture was stirred for 24 h, the solvent was removed with
a pump and the residual solid was purified by silica gel column
chromatography (with 1 : 1 ethyl acetate–hexane as an eluent).
Removal of the solvents under reduced pressure gave (1R,2R)-N1-
(4-vinylbenzenesulfonyl)-1,2-diphenylethane-1,2-diamine (1.37 g,
3.62 mmol) as a white powder. Yield 85%; [a]D = -36.7 (c =
Measurements. Reactions were monitored by TLC using
Merck precoated silica gel plates (Merck 5554, 60F254). Column
chromatography was performed with a silica gel column (Wakogel
C-200, 100–200 mesh). Melting points were taken on a Yanaco
micro melting apparatus and are uncorrected. 1H (300 MHz)
and 13C (75 MHz) spectra were measured on a Varian Mercury
300 spectrometer using tetramethylsilane as an internal standard,
and J values are reported in Hertz. 31P (162 MHz) spectra were
measured on a Varian Inova 400 spectrometer. IR spectra were
recorded with a JEOL JIR-7000 FT-IR spectrometer and are
reported in reciprocal centimetres (cm-1). Elemental analyses were
performed at the Microanalytical Center of Kyoto University.
GC analyses were performed with a Shimadzu Capillary Gas
Chromatograph 14B equipped with a capillary column (SPERCO
1
1.00 g/dL in CHCl3); H NMR (300 MHz, DMSO-d6, d = 0
((CH3)4Si)): d = 3.96 (d, J = 7.3 Hz, 1H, CH), 4.34 (d, J =
7.4 Hz, 1H, CH), 5.36 (d, J = 10.9 Hz, 1H, vinyl), 5.88 (d, J =
17.6 Hz, 1H, vinyl), 6.69 (dd, J = 10.9, 11.2 Hz, 1H, vinyl), 6.91–
7.42 ppm (m, 14H, Ar-H); 13C NMR (75 MHz, DMSO-d6, d =
0 ((CH3)4Si)): d = 60.64, 64.86, 117.05, 126.06, 126.38, 126.51,
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126.57, 127.27, 127.34, 127.40, 127.59, 135.44, 139.77, 140.10,
(br, CH2Ph), 3.1 (br, CH2N), 1.6 (br, CH2), 1.1 (br, CH2), 0.8 ppm
(br, CH3); 13C NMR (100 MHz, DMSO-d6, d = 0 ((CH3)4Si)):
d = 134–125, 62–56, 24–22, 20–18, 13.4 ppm; FT-IR (KBr): n =
1333 cm-1 (SO2 of sulfonamide); Elem. Anal.: calcd C 71.2; H 8.67;
N 3.35; S 6.89%, found C 71.1; H 8.61; N 3.29; S 6.86%.
140.28, 142.50 ppm; FT-IR (KBr): n = 3350, 3294 (NH2), 3160
-1
=
(NH), 3086, 3026 (CH CH2), 2861 (CH), 1323, 1152 cm (SO2);
Elem. Anal. for C22H22N2O2S: calcd. C 69.8, H 5.86, N 7.40, S
8.47%, found: C 69.6, H 5.83, N 7.36, S 8.57%.
Synthesis of 4-vinylbenzenesulfonic acid benzyltributylammo-
nium salt. A 50 mL round-bottomed flask equipped with
a magnetic stirring bar was charged with sodium 4-vinyl-
benzenesulfonate (0.680 g, 3.30 mmol) and 10 mL of H2O. Ben-
zyltributylammonium chloride (0.686 g, 2.20 mmol) and 10 mL of
CH2Cl2 were then added to the mixture at room temperature and
the mixture was stirred vigorously for 30 min. The aqueous layer
was extracted with 10 mL of Et2O three times and the combined
organic layer was dried with anhydrous MgSO4. Removal of
MgSO4 by filtration and removal of solvent under high vacuum
gave 4-vinylbenzenesulfonic acid benzyltributylammonium salt
(1.01 g, 2.20 mmol) as a colorless viscous liquid. Yield >99%;
1H NMR (300 MHz, CDCl3, d = 0 ((CH3)4Si)): d = 0.99 (t, J =
7.3 Hz, 9H, CH3), 1.37–1.45 (q, J = 7.4 Hz, 6H, CH2), 1.76 (m, 6H,
CH2), 3.24 (t, J = 10.9 Hz, 2H, CH2), 4.74 (s, 2H, Ph-CH2), 5.21–
5.25 (d, J = 17.6 Hz, 1H, vinyl), 5.71–5.77 (d, J = 11.2 Hz, 1H,
vinyl), 6.65–6.74 (dd, J = 10.9, 11.2 Hz, 1H, CH), 7.34–7.52, 7.86–
7.89 ppm (m, 14H, Ar-H); 13C NMR (75 MHz, DMSO-d6, d = 0
((CH3)4Si)): d = 13.38, 19.13, 23.26, 57.40, 61.27, 114.52, 125.34,
Poly(sodium 4-vinylbenzenesulfonate)-based chiral ligand ((R,R)-
3). (1R,2R)-N1-(4-Vinylbenzenesulfonyl)-1,2-diphenylethane-1,
2-diamine (75.7 mg, 0.20 mmol), divinylbenzene (26.0 mg,
0.20 mmol), sodium 4-vinylbenzenesulfonic acid (0.323 g,
1.60 mmol), AIBN (6.6 mg, 0.04 mmol), and 1.2 mL of DMSO
gave 0.371 g of (R,R)-2 as a white solid. Yield = 86%; The
measurements of Gel phase 1H NMR and 13C NMR in DMSO-d6
and D2O were found to be difficult. FT-IR (KBr): n = 1341 cm-1
(SO2 of sulfonamide); Elem. Anal.: calcd C 52.3; H 4.02; N 1.27%,
found C 52.0; H 3.98; N 1.23%.
General procedure for the preparation of polymer-immobilized
chiral catalyst
General procedure for the preparation of polymer-immobilized
chiral catalyst in organic solvent. A 10 mL round-bottom flask
equipped with a magnetic stirring bar was charged with polymer-
immobilized chiral ligand (diamine: 0.015 mmol), [RuCl2(p-
cymene)]2 (0.0050 mmol), and 1 mL of organic solvent under
argon. After three cycles of freeze–thaw under liquid nitrogen,
the mixture was heated to 80 ◦C. After 1 h, removal of the solvent
under high vacuum gave polymer-immobilized chiral catalyst as
a reddish solid. The resulting chiral catalyst was directly used for
the next asymmetric transfer hydrogenation of imines.
125.77, 127.99, 128.90, 130.19, 132.54, 136.14, 137.06, 147.87 ppm;
-1
=
FT-IR (KBr): n = 3089, 3040 (CH CH2), 1380, 1199 cm (SO3);
Elem. Anal. for C27H41NO3S: calcd. C 70.6; H 8.99; N 3.05; S,
6.98%, found: C 70.5, H 8.96, N 2.99, S 6.94%.
General procedure for the preparation of polymer-immobilized
chiral ligand. A 10 mL glass ampoule equipped with a mag-
netic stirring bar was charged with (1R,2R)-N1-(4-vinylbenzene-
sulfonyl)-1,2-diphenylethane-1,2-diamine, divinylbenzene, styrene
derivative, AIBN, and solvent under nitrogen. After three cycles
of freeze–thaw under liquid nitrogen, the ampoule was sealed and
then heated to 60 ◦C. After 24 h, the ampoule was opened and
the mixture was filtrated by glass filter. The resulting polymer was
washed with THF, methanol, and water and dried at 40 ◦C under
high vacuum.
General procedure for the preparation of polymer-immobilized
chiral catalyst in water. A 10 mL round-bottom flask equipped
with a magnetic stirring bar was charged with polymer-
immobilized chiral ligand (diamine: 0.015 mmol), [RuCl2(p-
cymene)]2 (0.0050 mmol), and 1 mL of degassed water under
argon. After three cycles of freeze–thaw under liquid nitrogen,
the mixture was heated to 40 ◦C. After 1 h, removal of the solvent
under high vacuum gave polymer-immobilized chiral catalyst as a
reddish solid. The resulting chiral catalyst was used for asymmetric
transfer hydrogenation without further purification.
Polystyrene-based chiral ligand ((R,R)-1). ((1R,2R)-N1-(4-
Vinylbenzenesulfonyl)-1,2-diphenylethane-1,2-diamine (75.7 mg,
0.20 mmol), divinylbenzene (26.0 mg, 0.20 mmol), styrene (0.167 g,
1.60 mmol), AIBN (6.6 mg, 0.04 mmol), and 1 mL of DMF gave
Asymmetric transfer hydrogenation of imines
Representative asymmetric transfer hydrogenation of imine 4
in CH2Cl2 (Table 1, entry 8). A 10 mL round-bottom flask
equipped with a magnetic stirring bar was charged with 4
(0.209 g, 1.00 mmol), polymer-immobilized chiral catalyst (Ru:
0.010 mmol), a 5 : 2 HCO2H–Et3N azeotropic mixture (HCO2H:
5.0 mmol), and 2.0 mL of CH2Cl2 under argon. After three cycles
of◦freeze–thaw under liquid nitrogen, the mixture was stirred at
0 C for 24 h. After adding saturated Na2CO3, the mixture was
filtrated by glass filter. The solvent of the filtrate was removed
with a vacuum pump and the residual solid was purified by silica
gel column chromatography (with 1 : 4 ethyl acetate–hexanes
as an eluent). N-Benzyl-1-phenylethanamine 5 was obtained as
1
0.247 g of (R,R)-1 as a white solid. Yield = 92%; Gel phase H
NMR (300 MHz, CDCl3, d = 0 ((CH3)4Si)): d = 0.6–2.5 (br, CH
and CH2 of styrene), 4.0–4.5 (br, CH of DPEN), 6.0–6.7, 6.7–7.0,
and 8.0–8,1 ppm (br, Ar-H); 13C NMR (100 MHz, CDCl3, TMS):
20–56, 57–75, 120–135 ppm; FT-IR (KBr): n = 3383, 3299 (NH2),
1333 cm-1 (SO2 of sulfonamide); Elem. Anal.: calcd C 85.9; H 7.21;
N 2.09; S 2.39%, found C 85.9; H 7.18; N 2.03, S 2.33%.
Poly(4-vinylbenzenesulfonate benzyltributylammonium salt)-
based chiral ligand ((R,R)-2). (1R,2R)-N1-(4-Vinylbenzenesul-
fonyl)-1,2-diphenylethane-1,2-diamine (75.7 mg, 0.20 mmol),
divinylbenzene (26.0 mg, 0.20 mmol), 4-vinylbenzenesulfonic
acid benzyltributylammonium salt (0.735 g, 1.60 mmol), AIBN
(6.6 mg, 0.04 mmol), and 1 mL of DMF gave 0.793 g of (R,R)-3
1
a colorless liquid. Yield: 80% by H NMR in CDCl3; 93% ee
by HPLC analysis (Chiralcel OD-H, hexanes–2-propanol = 99 :
1 (v/v), 0.4 mL min-1, rt, 254 nm, t(S) isomer (minor) = 39.2 min,
t(R) isomer (major) = 41.2 min).
1
as a white solid. Yield = 94%; Gel phase H NMR (300 MHz,
CDCl3, d = 0 ((CH3)4Si)): d = 7.9–7.1 and 7.1–6.4 (m, Ar-H), 4.5
74 | Org. Biomol. Chem., 2009, 7, 69–75
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Representative asymmetric transfer hydrogenation of imine 10
in H2O (Table 3, entry 7). A 10 mL round-bottom flask
equipped with a magnetic stirring bar was charged with 10
(0.205 g, 1.00 mmol), polymer-immobilized chiral catalyst (Ru:
0.010 mmol), HCO2Na (74 mg, 5.0 mmol), cetyltrimethylam-
monium chloride (0.16 g, 0.50 mmol) and 2.0 mL of degassed
water under argon. After three cycles of freeze–thaw under
liquid nitrogen, the mixture was stirred at room temperature for
24 h. After adding saturated Na2CO3, the mixture was filtrated
by glass filter. The solvent of the filtrate was removed with a
vacuum pump and the residual solid was purified by silica gel
column chromatography (with 92 : 5 : 3 ethyl acetate–methanol–
triethylamine as an eluent). 1,2,3,4-Tetrahydro-6,7-dimethoxy-1-
methylisoquinoline 11 was obtained as a colorless liquid. Yield:
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1
69% by H NMR in CDCl3; 94% ee by HPLC analysis (Chi-
ralcel OD-H, hexanes–2-propanol–Et2NH = 90 : 10 : 0.1 (v/v),
0.4 mL min-1, rt, 254 nm, t(S) isomer (major) = 36.4 min, t(R) isomer
(minor) = 52.6 min).
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