Supporting Information
Highly Active Polymeric Organocatalyst: Chiral Ionic Polymers Prepared from
10,11-Didehydrogenated Cinchonidinium Salt
Md. Mehadi Hassan, Naoki Haraguchi and Shinichi Itsuno*
Department of Environmental & Life Sciences, Toyohashi University of Technology,
Toyohashi 441-8580 Japan
Materials and general considerations. 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 noted.
Reactions were monitored by thin-layer chromatography using precoated silica gel plates
(Merck 5554, 60F254). Column chromatography was performed using a silica gel column
(Wakogel C-200, 100–200 mesh). Melting points were recorded using a Yanaco micro
melting apparatus and were uncorrected. NMR spectra were recorded on JEOL JNMECS400 spectrometers in CDCl3 or DMSO-d6 at room temperature operating at 400 MHz
(1H) and 100 MHz (13C{1H}). TMS was used as an internal standard for 1H-NMR and
CDCl3 for 13C-NMR. Chemical shifts were reported in ppm using TMS as a reference,
and the J values were recorded in Hertz. IR spectra were recorded on a JEOL JIR-7000
FTIR spectrometer and are reported in cm−1. 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). HPLC analyses
were performed with a JASCO HPLC system composed of a 3-line degasser DG-980,
HPLC pump PV-980, column oven CO-965, equipped with a chiral column
(CHIRALCEL OD-H, Daicel) using hexane/2-propanol as eluent. A UV detector
(JASCO UV-975 for the JASCO HPLC system) was used 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 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 made to determine the number-average molecular
weight (Mn) and molecular weight distribution (Mw/Mn) values with polystyrene standards.
Optical rotation was recorded using a JASCO DIP-149 digital polarimeter using a 10-cm
thermostated microcell.
Synthesis of 3: To a solution of (-)-cinchonidine 1 (1.47 g, 5.0 mmol) in CHCl3 (15 mL)
was added a solution of bromine (0.78 mL, 15 mmol) at 0 oC in 15 min. The resulting
mixture was stirred and warmed to room temperature. Et3N (1.41 mL) was then added to
the mixture and stirred for 4 h. The mixture was treated with aq. NaHCO3 solution and
extracted with CHCl3. The combined extract was washed with brine and dried over
anhydrous MgSO4. The solvent was removed and the obtained solid was dried under
vacuum to give the crude product of 2 in 94% yield.
1
H NMR spectrum of 2 in CDCl3
13
C NMR spectrum of 2 in CDCl3
Dried powedered KOH (0.78 g, 13.5 mmol) was added to a solution of 2 (1.69 g, 4.5
mmol) in dry THF (30 mL). After stirring for 10 min, Aliquat 336 (0.363 g, 0.9 mmol)
was added to the mixture and stirred for 18 h at room temperature. Aqueous NaHCO3 (30
mL) solution was added to the mixture and extracted with CHCl3. The combined extract
was dried over MgSO4 and evaporated to give the brown solid, which was purified by
precipitation of the THF solution into hexane. The solid precipitate was filtered, washed
with hexane to afford 3 (0.98 g, 74% yield). Mp156-157 °C. []D25 = 153.7 (c, 1.0, CH2Cl2).
C NMR (400 MHz, CDCl3): δ 150.1, 149.5, 148.2, 130.2, 129.7, 126.7, 125.8, 123.2, 118.6,
13
87.7, 71.6, 68.8, 61.5, 59.9, 57.9, 42.7, 31. 7, 29.1, 26. 3. IR KBr ν 3648, 2102, 1591, 1236, 1120.
HRMS (ESI): m/z calcd for [C19H20N2O] +: 292.1578; found: 292.1576.
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NMR spectrum of 3
Synthesis of 4: A mixture of 3 (1.71 mmol, 0.502 g) with benzylbromide (1.75 mmol,
0.299 g) was stirred in a mixture of 15 mL (EtOH: DMF: CHCl3 = 5:6:2) at 90 oC for 8 h.
After completion of the reaction, the reaction mixture was cooled at room temperature.
After cooling, the reaction mixture was concentrated and added to ether (300 mL). The
solid precipitated was filtered, washed with ether (100 mL) and hexane to afford 4 (0.74
g, 93% yield). Mp 154 °C. [α]D 25 = -127.3 (c, 1.0, DMSO). 13C-NMR (100 MHz, DMSOd6): δ= 22.2, 23.4, 26.1, 36.3, 50.4, 60.7, 63.0, 64.6, 67.8, 73.9, 84.4, 120.7, 124.2, 124.7,
127.8, 128.2, 129.5, 130.1, 130.2, 130.7, 134.3, 145.8 148.0, 150.7, 160.3.
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NMR spectrum of 4
Synthesis of dimer 7a: A mixture of 3 (0.585 g, 2.0 mmol) with 6a (0.275 g, 1.0 mmol)
was stirred in a mixture of 15 mL (EtOH: DMF: CHCl3 = 5:6:2) at 90 oC for 8 h. after
completion of the reaction, the reaction mixture was cooled at room temperature. After
cooling, the reaction mixture was concentrated and added to MeOH-ether (300 mL). The
solid precipitated was filtered, washed with ether (100 mL) and hexane to afford 7a (0.
67 g, 78% yield).
Synthesis of dimer 7b: The same procedure was followed as described for 7a using 3
and 6b (0.25 g, 1.0 mmol). 7b was obtained in 87% yield (0.74 g).
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Synthesis of dimer 7c: The same procedure was followed as described for 7a using 3 and
6c (0.28 g, 1.0 mmol). 7c was obtained in 96% yield (0.66 g).
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Synthesis of dimer 7d: The same procedure was followed as described for 7a using 3
and 6d (0.28 g, 1.0 mmol). 7d was obtained in 96% yield (0.66 g).
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NMR spectrum of 7d
Synthesis of dimer 9a: A mixture of 7a (0.43 g, 0.5 mmol) and 50% KOH aqueous
solution (0.25 mL) in CH2Cl2 (10 mL) was stirred for 10 min at room temperature. After
the addition of allyl bromide (0.17 mL, 2 mmol), the mixture was stirred vigorously at
room temperature for 4h. The mixture was diluted with water (5 mL) and was extracted
with CH2Cl2 (3 x 15 mL). The combined organic layer was then dried over MgSO4,
filtered and concentrated in vacuo. The crude solid were reprecipated from CH2Cl2hexane to yield (0.34 g, 73%) of the desired product 9a as a brown solid.
Mp 136 °C.
Synthesis of dimer 9b: The same procedure was followed as described for 9a using 7b
and allyl bromide (0.17 mL, 2 mmol). 9b was obtained in 64% yield (0.29 g).
Mp 144-145 °C.
Synthesis of dimer 9c: The same procedure was followed as described for 9a using 7c
and allyl bromide (0.17 mL, 2 mmol). 9c was obtained in 67% yield (0.31 g).
Mp 168 °C.
Synthesis of dimer 9d: The same procedure was followed as described for 9a using 7d
and allyl bromide (0.17 mL, 2 mmol). 9d was obtained in 61% yield (0.28 g).
Mp 171 °C.
Synthesis of dimer 9dMe: The same procedure was followed as described for 9a using
7d (0.64 g, 0.75 mmol) and methallyl bromide (0.23 mL, 2.25 mmol). 9dMe was obtained
in 73% yield (0.35 g). Mp 144-145 °C.
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Synthesis of ionic polymer 14aa: A mixture of dimer 7a (0.429 g, 0.5 mmol) in CH3OH
(5 mL) and disodium naphthalene-2,6-disulfonate 13a (0.17 g, 0.5 mmol,) in water (5
mL) was stirred at room temperature for 6 h. The ionic polymer precipitated was filtered
and washed with water, ether, and hexane to yield 14aa (0.46 g, 82%). []D25 = -153.5 (c
1.0, DMSO).
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Synthesis of ionic polymer 14ba: The same procedure was followed as described for
14aa using 7b and 13a. 14ba was obtained in 83% yield (0.46 g). []D25 = -141.1 (c 1.0,
DMSO).
Synthesis of ionic polymer 14ca: The same procedure was followed as described for
14aa using 7c and 13a. 14ca was obtained in 96% yield (0.48 g). []D25 = -163.2 (c 1.0,
DMSO).
Synthesis of ionic polymer 14cb: The same procedure was followed as described for
14aa using 7c and disodium naphthalene-2,7-disulfonate 13b. 14ca was obtained in 80%
yield (0.40 g). []D25 = -135.6 (c 1.0, DMSO).
Synthesis of ionic polymer 14cc: The same procedure was followed as described for
14aa using 7c and disodium naphthalene-1,5-disulfonate 13c. 14ca was obtained in 76%
yield (0.38 g). []D25 = -141.2 (c 1.0, DMSO).
Synthesis of ionic polymer 14da: The same procedure was followed as described for
14aa using 7d and 13a. 14da was obtained in 95% yield (0.48 g). []D25 = -141.2 (c 1.0,
DMSO).
Synthesis of ionic polymer 15aa: The same procedure was followed as described for
14aa using 9a and 13a. 15aa was obtained in 76% yield (0.45 g). []D25 = -89.3 (c 1.0,
DMSO).
Synthesis of ionic polymer 15ba: The same procedure was followed as described for
14aa using 9b and 13a. 15ba was obtained in 95% yield (0.55 g). []D25 = -47.7 (c 1.0,
DMSO).
Synthesis of ionic polymer 15ca: The same procedure was followed as described for
14aa using 9c and 13a. 15ca was obtained in 80% yield (0.43 g). []D25 = -19.6 (c 1.0,
DMSO).
Synthesis of ionic polymer 15da: The same procedure was followed as described for
14aa using 9d and 13a. 15da was obtained in 87% yield (0.47 g). []D25 = -18.8 (c 1.0,
DMSO).
Synthesis of ionic polymer 15dc: The same procedure was followed as described for
14aa using 9d and 13c. 15dc was obtained in 58% yield (0.31 g). []D25 = -21.2 (c 1.0,
DMSO).
Synthesis of ionic polymer 15daMe: The same procedure was followed as described for
14aa using 9dMe and 13a. 15daMe was obtained in 94% yield (0.52 g). []D25 = -37.5
(c 1.0, DMSO).
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.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
1H
0
.
5
0
.
4
0
.
3
0
.
2
0
.
1
6
.
0
5
.
0
4
.
0
3
.
0
2
.
0
1
.
0
0
n
NMR spectrum of 14cb
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
.
0
5
.
0
4
.
0
3
.
0
n
1H
NMR spectrum of 14cc
2
.
0
1
.
0
0
0
.
5
0
.
4
0
.
3
0
.
2
0
.
1
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
1H
0
.
2
0
.
1
9
0
.
1
8
0
.
1
7
0
.
1
6
0
.
1
5
0
.
1
4
0
.
1
3
0
.
1
2
0
.
1
1
0
.
1
0
.
0
9
0
.
0
8
0
.
0
7
0
.
0
6
0
.
0
5
0
.
0
4
0
.
0
3
0
.
0
2
0
.
0
1
.
0
5
.
0
4
.
0
3
.
0
2
.
0
1
.
0
0
n
NMR spectrum of 14da
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
.
0
5
.
0
4
.
0
3
.
0
n
1H
NMR spectrum of 15aa
2
.
0
1
.
0
0
0
.
3
0
.
2
0
.
1
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
0
M
.
i
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
1H
0
.
4
0
.
3
0
.
2
0
.
1
.
0
5
.
0
4
.
0
3
.
0
2
.
0
1
.
0
0
n
NMR spectrum of 15ba
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
.
0
5
.
0
4
.
0
3
.
0
n
1H
NMR spectrum of 15ca
2
.
0
1
.
0
0
0
.
4
0
.
3
0
.
2
0
.
1
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
1H
0
.
1
9
0
.
1
8
0
.
1
7
0
.
1
6
0
.
1
5
0
.
1
4
0
.
1
3
0
.
1
2
0
.
1
1
0
.
1
0
.
0
9
0
.
0
8
0
.
0
7
0
.
0
6
0
.
0
5
0
.
0
4
0
.
0
3
0
.
0
2
0
.
0
1
.
0
6
.
0
5
.
0
4
.
0
3
.
0
2
.
0
1
.
0
0
n
NMR spectrum of 15da
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
.
0
5
.
0
4
.
0
3
.
0
n
1H
NMR spectrum of 15dc
2
.
0
1
.
0
0
0
.
1
7
0
.
1
6
0
.
1
5
0
.
1
4
0
.
1
3
0
.
1
2
0
.
1
1
0
.
1
0
.
0
9
0
.
0
8
0
.
0
7
0
.
0
6
0
.
0
5
0
.
0
4
0
.
0
3
0
.
0
2
0
.
0
1
0
a
b
u
n
d
a
n
c
e
1
X
:
p
a
r
t
s
p
e
r
M
0
i
.
l
0
l
9
i
o
n
:
P
r
o
t
o
.
0
8
.
0
7
.
0
6
.
0
5
.
0
4
.
0
3
.
0
n
1H
NMR spectrum of 15daMe
2
.
0
1
.
0
0
Plausible reaction mechanism of asymmetric benzylation with 3-ethynyl
cinchonidinium salt catalyst:
As demonstrated in Figure 1, the enolate intermediate may approach from the left hand
side of the 3-ethynyl cinchonidinium salt catalyst (A, B). Other approaches (C, D, E)
seem to be unfavorable. Since 3-ethynyl cinchona alkaloids are more polar and basic than
the parent 3-vinyl compounds, the enolate intermediate may make favorable interaction
with the catalyst in the transition state (B). Moreover, sterically less bulky alkynyl group
may provide a suitable space for the enolate intermediate (A), which can accelerate the
reaction rate.
Figure 1. Plausible reaction mechanism of asymmetric benzylation with 3-ethynyl
cinchonidinium salt catalyst.