Synthesis of cinchona alkaloid sulfonamide polymers as sustainable catalysts for the enantioselective desymmetrization of cyclic anhydrides

Article abstract of DOI:10.1039/c6ra14535c

The Mizoroki-Heck polymerization of cinchona-based sulfonamide dimers and aromatic diiodides was investigated in the presence of a palladium catalyst, to obtain chiral polymers in high yields. An iodobenzenesulfonamide derivative of a cinchona alkaloid was also polymerized via self-polycondensation under the same reaction conditions. The catalytic activities of these chiral polymers were examined by using them as catalysts in the enantioselective desymmetrization of cyclic anhydrides.

Full text of DOI:10.1039/c6ra14535c

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ARTICLE
Synthesis of Cinchona Alkaloid Sulfonamide Polymers as
Sustainable Catalysts for the Enantioselective Desymmetrization
of Cyclic Anhydrides
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
DOI: 10.1039/x0xx00000x
S. Takata, Y. Endo, S. Ullah and S. Itsuno*
www.rsc.org/
The Mizoroki-Heck polymerization of cinchona-based sulfonamide dimers and aromatic diiodides was investigated in the
presence of a palladium catalyst, to obtain chiral polymers in high yields. An iodobenzenesulfonamide derivative of a
cinchona alkaloid was also polymerized via self-polycondensation under the same reaction conditions. The catalytic
activities of these chiral polymers were examined by using them as catalysts in the enantioselective desymmetrization of
cyclic anhydrides.
controlled by polymerization.
Introduction
Various kinds of polymer-immobilized cinchona alkaloid
catalysts have been synthesized via attachment onto the side
Cinchona alkaloids are extracted from the bark of the Cinchona
ledgeriana, which is an important medicinal plant of tropical
1
and sub-tropical regions. In addition to their medicinal use in
4
chain of synthetic polymers like crosslinked polystyrene.
Silica-supported cinchona alkaloids have also been prepared
5
-7
and used as catalysts in asymmetric reactions. Interestingly
however, chiral polymers containing a cinchona-based catalyst
as the repeating unit have rarely been synthesized. We have
developed several syntheses of polymeric cinchona-based
quaternary ammonium salts, with polymerization methods
as antimalarial and antiarrhythmic compounds, cinchona
alkaloids have also been employed as chiral organocatalysts in
2
asymmetric synthesis. Various efficient asymmetric catalysts
have been designed based on cinchona alkaloids, an important
class of which are their sulfonamide derivatives. Cinchona
alkaloids have various functionalities, including a quinuclidine
group, a secondary alcohol, a quinoline ring, and a vinylic unit.
The secondary alcohol can be easily converted into an amine,
which may be further modified to incorporate a sulfonamide
group. The acidic NH of a sulfonamide can act as a H-bond
donor, whereas the tertiary nitrogen of quinuclidine in
cinchona alkaloids may act as both a H-bond acceptor and a
base. By incorporating both acidic and basic sites into the
cinchona alkaloid sulfonamide derivatives, the combination of
acidic and basic sites allows the cinchona alkaloid sulfonamide
derivatives to hold substrates in a particular orientation,
therefore leading to a chiral environment. Several examples of
cinchona-based sulfonamide catalysts have been developed
for asymmetric reactions. For example, Chin et al. reported
that a sulfonamide derived from quinine showed excellent
catalytic activity in the enantioselective desymmetrization of
8
9
involving
a
Menshutkin reaction, ether formation,
a
1
Mizoroki-Heck coupling reaction, and an ion exchange
0
1
1,12
reaction.
In this paper, we present a new synthesis of chiral
polymers containing repeating cinchona-based sulfonamides in
their main chain structure. The well-established Mizoroki-Heck
reaction was chosen for the synthesis of the chiral sulfonamide
polymers, which usually provides the coupling product in high
yield. The chiral polymers were subsequently investigated as
catalysts for the asymmetric desymmetrization of cyclic
anhydrides.
Results and discussion
Synthesis of chiral polymers of cinchona sulfonamide
1
3
14
9
-Amino derivatives of cinchonidine and quinine
) were prepared by Mitsunobu-type azide formation,
followed by Staudinger reduction. Sulfonamides were easily
(1C,
1
Q
3
cyclic anhydrides. When cinchona-based sulfonamide
3
derivatives
are
incorporated
into
polymers,
the
microenvironment of the catalyst site is precisely modified and
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formed by the
Scheme 1 Preparation of cinchona alkaloid monomers 3.
Scheme 2 Synthesis of cinchona alkaloid polymers by Mizoroki-Heck
polymerization.
reaction of
1 and sulfonyl chloride 2 (Scheme 1). Sulfonamides
Scheme 3 Preparation of cinchona alkaloid dimers 5.
3CI and 3QI possess both aromatic iodide and vinyl groups.
Since Mizoroki-Heck (MH) coupling reactions occur between
aromatic iodides and olefins, repetitive MH reactions may
occur with these sulfonamides to give rise to polymers.
Indeed, under MH reaction conditions, both 3CI and 3QI
readily react intermolecularly to form chiral polymers P1C and
P1Q (Scheme 2). The polymers P1 were only soluble in high
polar solvents
such as DMF and DMSO. This efficient method of one
component, self-polycondensation of a chiral monomer
represents the first example of polymer synthesis using
cinchona alkaloid-derived sulfonamides. The polymerization
results are summarized in Table 1.
Table 1 Synthesis of chiral sulfonamide polymers P1, P2 using Mizoroki-Heck polymerization
Chiral sulfonamide
Entry
Y
H
R
-
Ar
-
Yield %
99
M
n
M
w
w n
M /M
polymer
1
2
P1C
8500
5800
11000
9400
1.4
1.6
P1Q
OMe
-
-
95
3
4
P2Caa
H
H
99
99
9500
3800
29000
4100
3.1
1.1
P2Cba
P2Cbb
5
6
H
H
97
99
11000
3100
18000
4400
1.7
1.4
P2Cca
7
9
P2Cda
P2Qba
H
98
99
6200
7400
21000
12000
3.5
1.6
OMe
a
b
-1
Polymerized in DMF at 100 °C for 24 h. Determined by SEC (polystyrene standards) using DMF as an eluent at a flow rate of 1.0 mL·min at 40 °C.
2
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Scheme 5 Enantioselective desymmetrization of cyclic anhydride 7.
Table 2 Solvent effect in enantioselective desymmetrization of cyclic anhydride 7 with
a
polymeric catalyst P1C
Temperature
b
c
Entry Catalyst
Solvent
hexane
Yield %
% ee
°C
1
2
3
4
P1C
P1C
P1C
P1C
25
25
25
25
99
91
39
93
10
49
51
37
CH
EtOAc
Et
Cl
2 2
2
O
Cyclopentyl
methyl ether
MTBE
Dioxane
THF
5
P1C
25
89
34
Scheme 4 Synthesis of cinchona alkaloid polymers P2 by two component
polycondensation.
6
7
P1C
P1C
P1C
P1C
P1C
P1Q
3CH
3CI
25
25
25
0
23
81
86
40
6
20
79
94
94
95
95
93
93
The successful synthesis of chiral polymers P1 by
repetitive MH polymerization prompted us to apply the same
method to a two-component polycondensation system. Two
8
9
THF
10
THF
-20
25
25
25
1
1
1
1
2
3
THF
97
99
99
equivalents of 9-amino cinchona alkaloid
react with disulfonyl dichloride to afford sulfonamide
dimers , as shown in Scheme 3. Polycondensation between
the dimer and aromatic diiodide under the previously
1 were allowed to
THF
4
THF
5
a
5
6
Unless otherwise indicated, reactions were carried out with 7 (0.1 mmol),
b
identified MH conditions gave the chiral polymer P2. In the
methanol (10 equiv, 1.0 mmol), and the polymeric catalyst (10 mol%). Isolated
c
yield. Determined by chiral HPLC (Chiralcel AD-H) after derivatization to 4-
case of the two-component polycondensation system,
bromophenyl ester of 8.
changing the structure of the disulfonyl dichloride
4 and
aromatic diiodide 6 allowed the synthesis of various
polymeric structures according to Scheme 4. The results of
the two-component polycondensation are summarized in
Table 1.
We found that the choice of solvent had a dramatic effect
on both the catalytic activity and enantioselectivity of the
desymmetrization of
7. In hexane, the reaction occurred
smoothly to give 8 in an almost quantitative yield. However,
Enantioselective desymmetrization reaction with chiral polymer
catalysts derived from cinchona alkaloid sulfonamide
the ee was only 10% (entry 1). Dichloromethane and ethyl
acetate gave higher enantioselectivities under the same
reaction conditions (entries 2, 3), whereas ethers led to
relatively lower enantioselectivity (entries 4-6). However,
interestingly, cyclic ethers such as dioxane and THF showed
both high reactivity and increased enantioselectivity (entries
7, 8). In the reaction conducted in THF, the polymeric catalyst
P1C showed a slightly higher ee of 94% (entry 8) when
compared to the corresponding low-molecular-weight model
catalyst 3CH (entry 12). The structurally similar polymer P1Q
also showed excellent activity under the same reaction
conditions, with an ee of 95% observed in THF (entry 11). The
effect of temperature on the reaction with polymeric catalyst
P1C was also surveyed (entries 9, 10). Although no significant
effect on the enantioselectivity was observed, the reaction
rate decreased considerably at lower reaction temperatures.
Cinchona alkaloid sulfonamides are efficient catalysts in
15-25
various asymmetric reactions.
These asymmetric
transformations have been applied to the synthesis of
biologically active compounds and chiral building blocks for
2
6,27
pharmaceutical targets.
In order to confirm the catalytic
activity of the newly explored chiral polymers P1 and P2, we
chose to investigate the enantioselective desymmetrization
of a cyclic anhydride. In the presence of the polymeric
catalyst, which is insoluble in the organic solvent used,
methanol reacted with cyclic anhydride
hemiester (Scheme 5). To identify the optimum reaction
conditions, the influence of solvent upon the P1C-catalyzed
enantioselective desymmetrization of was studied (Table 2).
7 to give the
8
7
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We then used another chiral polymeric catalysts P2,
prepared as previously by two component MH
polymerization from and aromatic diiodides. With THF
a
5
identified as the best solvent for the asymmetric reaction
with the polymeric catalyst P1, the same solvent was used in
the asymmetric reaction with P2. As shown in Table 3, the
reaction with P2 in THF occurred smoothly at room
temperature. We also found that the polymer structure of P2
considerably affected both the catalytic activity and
enantioselectivity of the reaction. A disulfonamide linker with
a biphenyl structure gave a relatively higher yield and
enantioselectivity for
8 (entries 2–4) when compared to
naphthalene-based disulfonamides (entries 5, 6). Since the
polymeric catalyst forms an insoluble suspension in THF, the
catalyst could be easily separated from the reaction mixture
by simple filtration. The recovered polymer powder could
then be reused in subsequent reactions, without any loss of
catalytic activity or enantioselectivity. The polymeric catalyst
P2Cba can be reused at least 4 times (entries 2-5).
Table 3 Enantioselective desymmetrization of cyclic anhydride 7 with polymeric
a
catalyst in THF
o
b
c
Entry
Catalyst
P2Caa
P2Cba
P2Cba
P2Cba
P2Cba
P2Cbb
P2Cbb
P2Cca
P2Cda
P2Qba
5Ca
Temperature C
Yield %
ee %
1
2
25
25
25
25
25
25
25
25
25
25
25
25
93
98
99
99
99
99
99
42
32
99
99
99
90
91
92
93
95
93
93
84
65
88
96
93
d
3
e
Scheme
6
polymeric catalyst PQ1
Enantioselective desymmetrization of cyclic anhydrides with
.
4
f
5
6
g
7
8
9
1
1
1
0
1
2
5Cb
a
Unless otherwise indicated, reactions were carried out with 7 (0.1 mmol),
b
methanol (10 equiv, 1.0 mmol), and the polymeric catalyst (10 mol%). Isolated
c
yield. Determined by chiral HPLC (Chiralcel AD-H) after derivatization to 4-
d
Figure 1 Quinine derived sulfonamide 3QF
bromophenyl ester of 8. The recovered polymer catalyst P2Cba used in entry 2
e
was used. The recovered polymer catalyst P2Cba used in entry 3 was used.
f
g
The recovered polymer catalyst P2Cba used in entry 4 was used. The
recovered polymer catalyst P2Cbb used in entry 6 was used
Table 4 Enantioselective desymmetrization of cyclic anhydride with polymeric catalyst
a
P1Q in THF
Cyclic
Cata
lyst
b
c
Entr
y
Produ
ct
Yield
ee
In order to further demonstrate the usefulness of chiral
anhydrid
Alcohol
%
%
polymeric organocatalysts, P1Q was used in the
e
7
enantioselective desymmetrization of cyclic anhydrides
(Scheme 6). The reaction occurred smoothly to give the
corresponding hemiesters 10 and 12, as summarized in Table
. In addition to methanol, benzyl alcohol and allyl alcohol
were also examined in the desymmetrization reaction of
cyclic anhydride , and gave rise to the corresponding chiral
9 and
1
P1Q
3QF
P1Q
P1Q
P1Q
3QF
P1Q
3QF
CH
3
OH
8
97
92
99
80
88
90
41
95
95
95
71
95
73
94
78
91
d
1
1
2
7
3
CH OH
8
3
4
5
7
PhCH
2
OH
OH
13
14
10
10
12
12
4
7
2
CH =CHCH
2
9
CH
CH
CH
CH
3
OH
OH
OH
OH
d
6
9
3
7
7
11
11
3
hemiesters 13 and 14 (entries 4, 5). The results obtained
3
from one of the most efficient catalyst 3QF in the same
d
8
3
asymmetric reaction were shown in Table 4. In case of the
reactions of
7, the catalytic activity of the polymer catalyst
was equivalent to that of 3QF
.
4
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a
Unless otherwise indicated, reactions were carried out with cyclic anhydride
for peak detection. Size-exclusion chromatography (SEC) was
performed using a Tosoh instrument with HLC 8020 UV (254
nm) or refractive index detection. DMF was used as the
(
0.1 mmol), alcohol (10 equiv, 1.0 mmol), and the polymeric catalyst (10 mol%).
b
c
Isolated yield. Determined by chiral HPLC (Chiralcel AD-H) after derivatization
d
to 4-bromophenyl ester of hemiester. See Ref. 3.
-1
carrier solvent at a flow rate of 1.0 mL min at 40 °C. Two
polystyrene gel columns of bead size 10 μm were used. A
calibration curve was obtained to determine the number-
n
average molecular weight (M ) and molecular weight
distribution (M /M ) values with polystyrene standards.
w
n
Conclusions
Optical rotation was recorded using a JASCO DIP-149 digital
polarimeter, using a 10-cm thermostated microcell.
In conclusion, chiral polymers containing a cinchona-
based sulfonamide structure in their main chain were
successfully synthesized by Mizoroki-Heck polymerization.
This is the first synthesis of a chiral, polymeric catalyst
containing both acidic and basic functionality by means of a
repeated MH reaction. The chiral polymers showed catalytic
activity in the enantioselective desymmetrization reactions of
cyclic anhydrides, with high levels of enantioselectivity
observed. The polymeric catalysts were easily separated from
the reaction mixture and reused several times without loss of
either catalytic activity or enantioselectivity. Since the
cinchona-based sulfonamides are known to be excellent
catalysts in various asymmetric reactions, the polymers
developed in this study will find further application as
catalysts in alternative asymmetric transformations. For
instance, the use of the chiral polymers in asymmetric
Michael-type reactions is now under investigation.
Synthesis of sulfonamide 3CH. To a stirred mixture of 1C
(0.90 g, 3.1 mmol) in CH
mmol), a solution of benzenesulfonyl chloride (0.53 g, 3.0
mmol) in CH Cl (5 mL) was slowly added under a nitrogen
2 2 3
Cl (5 mL) and NEt (0.31 g, 3.1
2
2
atmosphere, and the reaction mixture was stirred at room
temperature for 24 h. After the addition of water (5 mL), the
mixture was extracted with CH
organic extracts were dried over anhydrous Na
filtration, the solvent was removed by evaporation and the
residue was purified by column chromatography (SiO
2
Cl
2
(10 mL × 3) and the
2
SO . After
4
2
,
1
CH
2
Cl
2
/MeOH = 9/1, v/v) to afford 3CH (1.04 g, 80% yield). H
H 8.74 (d, 0.25H, J = 3.97 Hz), 8.64 (d,
NMR (400 MHz, CDCl ) δ
3
0.75H, J = 4.58 Hz), 8.36 (d, 0.25H, J = 8.85 Hz), 8.14 (d, 0.75H,
J = 8.24 Hz), 8.08 (d, 0.75H, J = 8.24 Hz), 7.95 (d, 0.25H, J =
8.24 Hz), 7.74 (t, 0.75H, J = 7.93 Hz), 7.65-7.56 (m, 1H), 7.48-
7
.30 (m, 4H), 7.22 (d, 0.25H, J = 3.97 Hz), 7.11 (t, 1.5H, J =
.63 Hz), 6.95 (t, 0.5H, J = 7.93 Hz), 5.69-5.54 (m, 1H), 5.10 (d,
7
Experimental
0.75H, J = 10.4 Hz), 5.00-4.84 (m, 2H), 4.33 (d, 0.25H, J = 10.7
Hz), 3.37-3.22 (m, 1.25H), 3.05-2.94 (m, 1.5H), 2.85-2.63 (m,
General methods
2
0
1
1
.25H), 2.33 (br s, 1H), 1.68-1.56 (m, 3H), 1.31-1.27 (m, 1H),
All solvents and reagents were purchased from Sigma-
Aldrich, Wako Pure Chemical Industries, Ltd., or Tokyo
Chemical Industry (TCI) Co., Ltd. at the highest available
purity and were used as received, unless otherwise
mentioned. Reactions were monitored by thin-layer
chromatography using pre-coated silica gel plates (Merck
.93-0.86 (m, 1H). IR (KBr) νmax 3446, 3197, 3064, 2943, 2866,
636, 1591, 1568, 1509, 1447, 1324, 1239, 1159, 1092, 1059,
-1
033, 988, 955, 922, 878, 817, 754 cm . HRMS (ESI): m/z
28 3 2
calc’d for [C25H N O S]+: 434.1897, found: 434.1898.
Synthesis of sulfonamide dimers 5Ca. A typical procedure for the
synthesis of 5 is described. To a stirred mixture of 1C (0.90 g, 3.1
5554, 60F254). Column chromatography was performed
mmol) in CH
2 2 3
Cl (5.0 mL) and NEt (0.31 g, 3.1 mmol), a solution of
using a silica gel column (Wakogel C-200, 100-200 mesh).
Melting points were recorded using a Yanaco micro melting
apparatus and the values were not corrected. NMR spectra
m-benzenedisulfonyl dichloride (0.42 g, 1.5 mmol) in CH Cl (5 mL)
2
2
was slowly added under a nitrogen atmosphere, and the reaction
mixture was stirred at room temperature for 24 h. After the
were recorded on JEOL JNM-ECS400 spectrometers in CDCl
1
3
2 2
addition of water (5 mL), the mixture was extracted with CH Cl
or DMSO-d
6
at room temperature operating at 400 MHz ( H)
1
and 100 MHz ( C{ H}). Tetramethylsilane (TMS) was used as
3
1
(10 mL × 3) and the organic extracts were dried over anhydrous
Na SO . After filtration, the solvent was removed by evaporation
1
13
2
4
3
an internal standard for H NMR, and CDCl for C NMR.
and the residue was purified by column chromatography (SiO
CH Cl /MeOH = 9/1, v/v) to afford 5Ca (727 mg, 60% yield) as a
white solid. H NMR (400 MHz, CDCl
2
,
Chemical shifts are reported in ppm using TMS as a
reference, and the J values were recorded in Hertz. The IR
spectra, recorded on a JEOL JIR-7000 FTIR spectrometer, are
2
2
1
3
H
) δ 8.73 (d, J = 4.27 Hz), 8.70
-1
reported in cm . Elemental analyses (carbon, hydrogen,
nitrogen) were performed on a Yanaco-CHN coder MT-6
analyzer. HRMS (ESI) spectra were recorded on a microTOF-Q
II HRMS/MS instrument (Bruker). High-performance liquid
chromatography (HPLC) was performed with a Jasco HPLC
system composed of a DG-980-50 three-line degasser, a PU
(d, J = 4.27 Hz), 8.64 (d, J = 4.58 Hz), 8.12-8.04 (m), 7.97 (s), 7.89-
7.83 (m), 7.75-7.49 (m), 7.30 (d, 1.3H, J = 4.58 Hz), 7.21-7.19 (m),
7.09 (d, J = 7.93 Hz), 6.94 (d, J = 7.93 Hz), 6.79 (q, J = 16.17, 8.24
Hz), 6.54 (t, J = 7.93 Hz), 6.31 (t, J = 7.63 Hz), 5.67-5.51 (m), 5.03-
4.82 (m), 4.32 (d, J = 10.7 Hz), 4.19 (d, J = 10.99 Hz), 3.35-3.07 (m),
2
.96-2.45 (m), 2.28 (br s), 1.67-1.39 (m), 1.27-1.17 (m), 0.89-0.74
13
980 HPLC pump, and a CO-965 column oven equipped with a
(
m). C NMR (100 MHz, CDCl
3 C
) δ 150.0, 149.3, 148.7, 148.1,
chiral column (Chiralpak AD-H, Daicel) with hexane/2-
propanol as an eluent. A Jasco UV-975 UV detector was used
1
44.0, 143.7, 141.0, 140.6, 140.3, 139.7, 139.1, 130.4, 130.2,
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1
1
1
5
2
2
1
8
30.1, 130.0, 129.6, 129.5, 129.4, 129.2, 128.7, 127.6, 127.5,
27.3, 126.8, 126.7, 126.3, 126.2, 125.4, 124.1, 123.9, 123.8,
22.1, 120.2, 120.1, 115.2, 115.1, 114.9, 62.7, 61.1, 61.0, 56.6,
5.6, 55.3, 52.5, 52.4, 45.8, 40.3, 39.9, 39.6, 39.1, 27.6, 27.3, 27.2,
6.1, 24.8, 8.7. IR (KBr) νmax 3609, 3421, 3209, 3073, 2942, 2866,
604, 2495, 1922, 1716, 1636, 1591, 1569, 1510, 1457, 1413,
326, 1240, 1175, 1154, 1082, 1059, 1032, 988, 956, 912, 879,
Representative procedure for asymmetric desymmetrization of
prochiral cyclic anhydride with methanol
Methanol (40.5 ꢀL, 1.00 mmol) was added dropwise to a
solution of (15.4 mg, 0.10 mmol) and P1C (4.3 mg, 0.01
7
mmol) in THF (2 mL) at room temperature with stirring, and
the mixture was stirred at room temperature for 24 h. The
reaction mixture was directly subjected to column
-1
14, 795, 759, 684, 580, 517, 418 cm . HRMS (ESI): m/z calc’d for
2 2
chromatography (SiO , Et O) to give the hemiester product 8
-
1
(16 mg, 86%) as a white solid. H NMR (400 MHz, CDCl
C
44
H
47
N
6
O
4
S
2
([M-H] ) 787.3106, found 787.3106.
3
)
δ
.68 (s, 3H), 2.85 (br s, 2H), 2.10–1.94 (m, 2H), 1.82–1.73 (m,
H
3
Synthesis of cinchona alkaloid polymers by self polycondensation
2
H), 1.61–1.38 (m, 4H).
Synthesis of P1C. A mixture of sulfonamide 3CI (0.21 g, 0.38
To determine the enantiomeric excess (ee),
8 was
mmol) in the presence of 3 mol% Pd (OAc)
2
(2.5 mg, 11.3
converted to the corresponding 4-bromophenyl ester
ꢀ
mol) and Et N (38 mg, 0.38 mmol) was stirred in 3 mL
3
28
according to a literature procedure. To a solution of
mg, 0.10 mmol) and 4-bromophenol (34.6 mg, 0.200 mmol)
in CH Cl (2 mL) at 0 °C, N,N’-dicyclohexylcarbodiimide (41.3
8 (18.6
anhydrous DMF at 100 °C for 24 h. After completion of the
reaction, the reaction mixture was cooled to room
temperature. The reaction mixture was then added dropwise
into ether (40 mL) with stirring. The solid precipitate was
filtered, then sequentially washed with diethyl ether, ethyl
2
2
mg, 0.20 mmol) and 4-dimethylaminopyridine (DMAP, 6.10
mg, 0.05 mmol) were added. The mixture was allowed to
warm to room temperature and stirred overnight. The white
solid was filtered off and the solvent was removed in vacuo.
The residue was then purified via column chromatography
acetate, CH
3
OH, and hexane to afford 176 mg (99% yield) of
max 3435, 3061, 2931, 2866, 1656,
592, 1568, 1510, 1466, 1386, 1327, 1243, 1160, 1089, 1055,
the product P1C. IR (KBr)
ν
1
1
-1
25
(SiO
2
, EtOAc/n-hexane=1/5, v/v) to afford the 4-bromophenyl
) as a colourless oil. The ee of
003, 928, 876, 815, 763, 729, 698 cm . [α]
D
= -134.7 (c 1.0,
3
ester (28.8 mg, 98% based on
8
DMSO). M
Synthesis of P1Q. A mixture of sulfonamide 3QI (224 mg,
.38 mmol) in the presence of 3 mol% Pd(OAc) (2.5 mg, 11.3
mol) and NEt (38 mg, 0.38 mmol) was stirred in 3 mL
n w n
(SEC) = 8.5 x 10 ; M /M = 1.4.
the 4-bromophenyl ester was determined to be 94% by chiral
HPLC analysis (Chiralpak AD-H column, 2-propanol/n-
0
2
hexane=1/9 v/v, 1.0 mL/min). t(1S,2R)=7.8 min, t(1R,2S)=8.3 min.
ꢀ
3
1
3 H
H NMR (400 MHz, CDCl ) δ 7.47 (d, J=8.9 Hz, 2H), 6.97 (d,
anhydrous DMF at 100 °C for 24 h. After completion of the
reaction, the reaction mixture was cooled to room
temperature. The reaction mixture was then added dropwise
into diethyl ether (40 mL) with stirring. The solid precipitate
was filtered, then sequentially washed with ether, ethyl
J=8.9 Hz, 2H), 3.70 (s, 3H), 3.06–2.98 (m, 2H), 2.16–2.03 (m,
2H), 1.96–1.89 (m, 2H), 1.82–1.61 (m, 2H), 1.58–1.41 (m, 2H).
In the same way, other polymers and monomers were
also employed as catalysts for the enantioselective
desymmetrization reaction. These results are summarized in
Table 2.
acetate, CH
3
OH, and hexane to afford 174 mg (99% yield) of
max 3435, 3061, 2931, 2866, 1656,
592, 1568, 1510, 1466, 1386, 1327, 1243, 1160, 1089, 1055,
the product P1Q. IR (KBr)
ν
1
1
-1
25
003, 928, 876, 815, 763, 729, 698 cm . [α]
3
D
= -154.7 (c 1.0,
Acknowledgements
n w n
DMSO). M (SEC) = 5.8 x 10 ; M /M = 1.6.
The authors would like to thank Dr. Naoki Haraguchi at
Toyohashi University of Technology for fruitful discussions.
This work was supported by Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology (Japan).
Representative procedure for the Synthesis of P2C by two
component polycondensation.
A typical procedure for the synthesis of P2Caa is described. A
mixture of sulfonamide dimer 5Ca (0.30 g, 0.38 mmol) and
4,4’-diiodobenzene (0.13 mg, 0.38 mmol) in the presence of 3
mol% Pd (OAc) (2.6 mg, 0.011 mmol) and NEt (77 mg, 0.76
2
3
mmol) was stirred in 3 mL anhydrous DMF at 100 °C for 24 h.
After completion of the reaction, the reaction mixture was
cooled to room temperature. The reaction mixture was then
added dropwise into ether (40 mL) with stirring. The solid
precipitate was filtered, then sequentially washed with ether,
Notes and references
1
2
3
4
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| J. Name., 2012, 00, 1-3
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Table of contents:
Synthesis of Cinchona Alkaloid Sulfonamide Polymers as Sustainable Catalysts for the
Enantioselective Desymmetrization of Cyclic Anhydrides
S. Takata, Y. Endo, S. Ullah and S. Itsuno*
Department of Environmental & Life Sciences, Toyohashi University of Technology, Toyohashi
441-8580, Japan
Mizoroki-Heck polymerization of cinchona sulfonamide gave the chiral polymers, which are active
catalysts for enantioselective desymmetrization of cyclic anhydrides to give chiral hemiesters in high
yield with high enantioselectivities.