Synthesis of helical poly(phenylacetylene)s bearing cinchona alkaloid pendants and their application to asymmetric organocatalysis

Article abstract of DOI:10.1002/pola.24988

Four novel dynamic helical poly(phenylacetylene)s bearing cinchona alkaloids as pendant groups were synthesized starting from the commercially available cinchona alkaloids, cinchonidine, cinchonine, quinine, and quinidine, by the polymerization of the cor

Full text of DOI:10.1002/pola.24988

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Synthesis of Helical Poly(phenylacetylene)s Bearing Cinchona Alkaloid
Pendants and Their Application to Asymmetric Organocatalysis
Garret M. Miyake,1,2 Hiroki Iida,1 Hai-Yu Hu,3 Zhenglin Tang,1
Eugene Y.-X. Chen,2 Eiji Yashima1,3
1Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University,
Nagoya 464-8603, Japan
2Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872
3Venture Business Laboratory, Nagoya University, Nagoya 464-8603, Japan
Correspondence to: E. Yashima (E-mail: yashima@apchem.nagoya-u.ac.jp)
Received 6 June 2011; accepted 1 September 2011; published online 22 September 2011
DOI: 10.1002/pola.24988
ABSTRACT: Four novel dynamic helical poly(phenylacetylene)s
bearing cinchona alkaloids as pendant groups were synthesized
starting from the commercially available cinchona alkaloids, cin-
chonidine, cinchonine, quinine, and quinidine, by the polymer-
ization of the corresponding phenylacetylene monomers with a
rhodium catalyst. These polymers exhibited an induced circular
dichroism (ICD) in the UV–visible region of the polymer back-
bones in solution, resulting from the preferred-handed helical
conformation induced by the optically active cinchona alkaloid
pendants. In response to the solvent used, their Cotton effect
patterns and intensities were significantly changed accompanied
by the changes in their absorption spectra probably due to the
changes in their helical conformations, such as the inversion of
the helical sense or helical pitch of the polymers. When these
helical polymers were used as polymeric organocatalysts for the
asymmetric conjugated addition and Henry reactions, the opti-
cally active products with a modest enantiomeric excess were
obtained whose enantioselectivities were comparable to those
obtained with the corresponding cinchona alkaloid-bound
monomers as the catalysts. However, we observed a unique
enhancement of the enantioselectivity and a reversal of the ste-
reoselectivity for some helical polymers, suggesting the impor-
tant role of the helical chirality during the asymmetric
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organocatalysis. 2011 Wiley Periodicals, Inc. J Polym Sci Part
A: Polym Chem 49: 5192–5198, 2011
KEYWORDS: catalysts; chiral; cinchona alkaloid; helical struc-
ture; polyacetylenes
INTRODUCTION Recently, optically active polymers that can
catalyze asymmetric reactions have attracted significant
attention.1 In general, they are composed of achiral polymers
and small molecular chiral ligands covalently attached to the
polymer main-chain as the pendant groups, and therefore,
the enantioselectivities are totally governed by the chiral
ligands. However, if the polymers could adopt a helical con-
formation with an excess of one-handedness, an intriguing
synergistic effect of the helical chirality on the enantioselec-
tivity would be anticipated, leading to asymmetric catalysts
more efficient than the chiral ligands themselves, but suc-
cessful examples are quite rare.2 In addition, when the heli-
cal polymers possess a dynamic feature in their helical con-
formations, one may anticipate that the catalytic activity and
enantioselectivity could be controlled by external stimuli,3
such as temperature and solvents, resulting from the confor-
mational change, such as the change in the helical pitch and
inversion of the helicity. Recently, Suginome and coworkers
achieved such a unique solvent-induced reversal of enantio-
selectivity using dynamic helical polyquinoxaline bearing
metal-binding phosphino pendant groups during the asym-
metric hydrosilylation of styrene,2(i,j) which enabled switch-
ing of the enantioselectivity induced by helix inversion of the
polymer main-chain in different solvents, thus producing chi-
ral products up to 97% ee with an opposite handedness.2(j)
However, such stimuli-responsive helical polymer-based
ligands2(a,c,e,j) and organocatalysts2(f,h) are very limited.
RESULTS AND DISCUSSION
Cinchona alkaloids, such as the pseudo-enantiomeric forms
(diastereomers) of cinchonidine (Cd)/cinchonine (Cn) and
quinine (Qn)/quinidine (Qd) (Scheme 1), are a class of ver-
satile asymmetric organocatalysts for a broad range of enan-
tioselective transformations.4 The cinchona alkaloids have a
reactive hydroxy group that can be readily modified with
various functional substituents while maintaining its catalytic
and enantioselective activities,4 which prompted us to
Additional Supporting Information may be found in the online version of this article.
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SCHEME 1 Synthetic route of helical poly(phenylacetylene)s bearing cinchona alkaloid derivatives as the pendant groups.
synthesize a series of optically active dynamic helical poly
(phenylacetylene)s bearing cinchona alkaloid residues as the
pendants through an ester linkage to investigate their
chiroptical properties along with their asymmetric organoca-
talytic activities. To the best of our knowledge, cinchona
alkaloid-bound helical polymers have not yet been pre-
pared.5 We anticipated that the introduction of optically
active cinchona alkaloid residues as the pendant groups
could induce an excess one-handed helical conformation in
the main chain of the polymers, which further results in a
helical array of the pendant cinchona alkaloid residues
with a predominant screw-sense along the polymer back-
bones,3(b,e,f,h) leading to an enhancement of the enantioselectiv-
ity and a reversal of stereoselectivity as compared to those of
the corresponding cinchona alkaloid-bound monomers.
the polymers exhibited intense Cotton effects biased by the
covalently bonded cinchona alkaloid pendants in the long
absorption regions of the polymer backbones in CHCl3 being
different from those of the corresponding monomers (Sup-
porting Information Fig. S3). As expected, poly-Cd1 (a) and
poly-Cn1 (c) [Fig. 1(A)] and also poly-Qn1 (g) and poly-Qd1
(i) [Fig. 1(B)] bearing pseudoenantiomeric cinchona alkaloid
pendant groups (Cd/Cn and Qn/Qd), respectively, showed
rather mirror-image CDs in their patterns, although the CD
intensities and absorption spectral patterns are more or less
different from each other. These results suggest that poly-
Cd1 and poly-Qn1 might take the preferred-handed helical
conformation with the same handedness; hence, the helical
sense of poly-Cn1 and poly-Qd1 appears to be opposite to
those of poly-Cd1 and poly-Qn1.
Four optically active poly(phenylacetylene)s bearing cinchona
alkaloid derivatives as the pendants were synthesized
according to Scheme 1. Commercially available cinchona
alkaloids were allowed to react with 4-ethynylbenzoyl chlo-
ride and the resulting monomers (Cd1, Cn1, Qn1, and Qd1)
were polymerized with [Rh(nbd)Cl]2 (nbd: norbornadiene)
as the catalyst in dimethylformamide (DMF) in the presence
of NEt3 in accordance with a previously reported method,6
giving high molecular weight (Mn ¼ 0.9 ꢀ 6.0 ꢁ 104) stereo-
regular (cis-transoidal) poly(phenylacetylene)s in high yield
(>81%) (poly-Cd1, poly-Cn1, poly-Qn1, and poly-Qd1).7
As previously reported for other helical poly(phenylacety-
lene)s with chiral pendant groups,6,8 the cinchona alkaloid-
bound poly(phenylacetylene)s were also sensitive to the
solvent and exhibited a drastic change in their CD spectral
patterns and intensities accompanied by a large blue-shift in
their absorption spectra and inversion of the Cotton effect
signs in tetrahydrofuran (THF) (poly-Cd1) (b) [Fig. 1(A)]
and dimethylformamide (DMF) (h and j) (poly-Qn1 and
ꢂ
poly-Qd1) [Fig. 1(B)] at 25 C. The blue-shifts in the absorp-
tion spectra can be ascribed to a change in the twist angle of
the conjugated double bonds; the polymers may have a
tightly twisted helical conformation in THF and DMF.6 The
inversion of the Cotton effect signs may originate from the
Figure 1 shows the circular dichroism (CD) and absorption
spectra of the poly(phenylacetylene)s in various solvents. All
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FIGURE 1 CD and absorption spectra of (A) poly-Cd1 in CHCl3 (a and d) and THF (b and e), and poly-Cn1 in CHCl3 (c and f), and
(B) poly-Qn1 in CHCl3 (g and k) and DMF (h and l), and poly-Qd1 in CHCl3 (i and m) and DMF (j and n) at 25 ꢂC. CD and absorption
spectra of poly-Cn1 could not be measured in THF because of poor solubility. The concentration of the polymers was 0.4 mg/mL.
inversion of the helical sense of the polymer backbones,
TABLE 1 Asymmetric Conjugate Addition of
2-Naphthalenethiol to 2-Cyclohexen-1-onea
while we could not rule out another possibility to explain
the changes in the CD spectral patterns; that is, a change in
the helical pitch of the polymers with the same-handedness
rather than the helix inversion.6(c) The induced CD inten-
sities of these polymers increased with the decreasing
temperature, which supports the dynamic conformational
characteristic of these polymers (Supporting Information
Figs. S4–S6).
Time Yield ee
The cinchona alkaloid-bound helical poly(phenylacetylene)s
were then used as an organocatalyst for the asymmetric con-
jugated addition of thiols to cyclic enones, which is known
to proceed with a high enantioselectivity catalyzed by the
cinchona alkaloid-derived organocatalysts.9 We anticipated
that the helical polymers with the cinchona alkaloid pend-
ants could show a better or reversed enantioselectivity com-
pared to those of the corresponding monomeric catalysts
because the polymers adopt a tunable helical conformation
with an excess handedness depending on the solvents, and
the pendants groups may arrange in a helical array with a
predominant screw-sense along the polymer backbones.
Entry Catalyst
Solvent (d)
(%)b
(%)c
1
Cd1
CHCl3
THF
3
3
98
90
14 (S)
2 (S)
2
Cd1
3
poly-Cd1
CHCl3
4
99
32 (S)
31 (S)
27 (S)
14 (S)
2 (S)
4
poly-Cd1 (2nd run)d CHCl3
4
99
5
6e
poly-Cd1 (3rd run)d
poly-Cd1
poly-Cd1
Cn1
CHCl3
CHCl3
THF
4
94
1.5
4
98
7
95
8
CHCl3
THF
3
86
32 (R)
20 (R)
30 (R)
10 (R)
16 (S)
16 (S)
38 (R)
28 (R)
9
Cn1
3
85
>99f
10
11
12
13
14
15
a
poly-Cn1
poly-Cn1
Qn1
CHCl3
THFg
CHCl3
CHCl3
CHCl3
CHCl3
4
Table 1 shows the results of the asymmetric conjugated
addition of 2-naphthalenethiol to 2-cyclohexenone using the
poly(phenylacetylene)s as well as the correspꢂonding mono-
mers as organocatalysts in CHCl3 or THF at 0 C. The conju-
gated addition occurred in the presence of the monomers
and polymers, yielding the corresponding Michael adducts in
good yields with different enantiomeric excess (ee) values
depending on the structures of the pendant cinchona alka-
loids, although the observed reactivity and enantioselectivity
were lower than those catalyzed by the modified cinchona
alkaloid-derived small organocatalysts.9(b)
4
68
4
98
poly-Qn1
Qd1
4
65
6
88
poly-Qd1
6
86
The reaction of 2-cyclohexen-1-one (0.2 M) with 2-naphthalenethiol (2
equiv) was carried out in the presence of a catalyst (1 mol%) in CHCl3
or THF at 0 ꢂC.
b
Isolated yield.
Determined by chiral HPLC analysis.
c
d
The polymer was recovered by precipitation in diethyl ether and
reused.
Interestingly, poly-Cd1 showed a much higher enantioselec-
tivity [32% ee (S)] than that catalyzed by the monomeric
counterpart Cd1 [14% ee (S)] (Entries 1 and 3) in CHCl3,
e
Polymer was grinded for 20 min before use.
Conversion (%) determined by 1H NMR analysis.
f
g
The polymer was almost insoluble in the solvent.
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TABLE 2 Asymmetric Henry Reaction of Ethyl Pyruvate with
most of the helical polymers produced the nonracemic nitro-
methyl adducts in good yields, but the enantioselectivities
of the polymers were comparable or slightly lower to those
catalyzed by the corresponding monomers. However, we
observed a unique solvent-dependent reversal of the enan-
tioselectivity of poly-Qn1 [26% ee (S)] in CHCl3 toward its
monomer Qn1 [14% ee (R)], resulting from the helical chir-
ality with an excess handedness induced in the poly-Qn1
main-chain (Entries 5 and 7).12 When DMF was used as the
solvent in which poly-Qn1 exhibited the opposite Cotton
effect signs to those observed in CHCl3, poly-Qn1 produced
the opposite R-rich product, although the enantioselectivity
became quite low (Entries 6 and 8). We noted that the
monomeric cinchona alkaloids, such as Qn1 and Qd1, never
showed such a solvent-dependent change in the enantiose-
lectivity, suggesting that the observed reversal of the enan-
tioselectivity is most likely governed by the helical chirality
of the polymer main-chains, thereby inducing the arrange-
ment of the cinchona alkaloid pendants with the opposite
screw-sense depending on the solvent used. However, the
diastereomeric poly-Qd1 did not show such solvent-depend-
ent reversal of the enantioselectivity (Entries 11 and 12),
suggesting that the enantioselectivity was significantly
affected by the helical structures induced by the catalytically
active cinchona alkaloid pendant groups that may arrange
in a preferred-handed helical array along the polymer
backbone.
Nitromethanea
Yield
(%)b
ee
(%)c
Entry
Catalyst
Solvent
Time (d)
1
Cd1
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
DMF
21
21
21
21
4
55
73
41
39
83
83
81
84
67
68
56
55
2 (R)
0
2
poly-Cd1
Cn1
3
10 (S)
6 (S)
14 (R)
2 (R)
26 (S)
4 (R)
24 (S)
12 (S)
24 (S)
6 (S)
4
poly-Cn1
Qn1
5
6
Qn1
14
7
7
poly-Qn1
poly-Qn1
Qd1
CHCl3
DMF
8
14
21
21
21
21
9
CHCl3
DMF
10
11
12
a
Qd1
poly-Qd1
poly-Qd1
CHCl3
DMF
The reaction of ethyl pyruvate (1 M) with nitromethane (10 equiv) was
carried out in the presence of a catalyst (1 mol%) in various solvents at
ꢀ20 ꢂC.
b
Isolated yield.
c
Determined by chiral HPLC analysis.
A possible helical structure of poly-Qn1 was calculated by
molecular mechanics calculations based on the crystal struc-
ture of Qn1 and a 23 unit/10 turn (23/10) helical structure
of a poly(phenylacetylene) derivative whose helical structure
was determined by X-ray diffraction analysis of a uniaxially
oriented polymer film (Supporting Information Figs. S8 and
S9).13 The calculated structure of poly-Qn1 revealed that the
Qn pendant units are tightly packed together with a right-
handed helical array along the left-handed helical main-chain
(Supporting Information Fig. S9).14 The organocatalytic activ-
ity and enantioselectivity of the molecular cinchona alkaloids
in asymmetric transformations are governed by cinchona
alkaloids themselves. In sharp contrast, the cinchona alka-
loid-bound helical poly(phenylacetylene)s possess multiple
catalytic sites generated by the neighboring cinchona alka-
loid pendants, so that the enantioselectivity may be
enhanced or reversed triggered by a conformational change
in the polymer backbones induced by external stimuli, such
as solvents and temperature.
indicating a kind of synergistic effect of the macromolecular
helicity that enhanced the enantioselectivity. To confirm this,
the cis-transoidal poly-Cd1 was converted to its trans-
enriched poly-Cd1 by grinding in a mortar for 20 min. The
resulting trans-enriched poly-Cd1 (Supporting Information
Fig. S2e)10 lost its helical conformation, thus showing almost
no CD in the polymer backbone regions (Supporting Infor-
mation Fig. S7) and the enantioselectivity in the asymmetric
conjugated addition significantly decreased [14% ee (S)]
(Entry 6); this value is identical to that catalyzed by the
monomeric form (Entry 1), clearly demonstrating the impor-
tant contribution of the induced helical chirality of the cis-
transoidal poly-Cd1 in the present asymmetric transforma-
tion. Poly-Cd1 maintained its activity after recovery and
reuse (Entries 4 and 5).
Poly-Cd1 exhibited a significant change in its CD spectral
pattern in THF, whereas such a synergistic effect was not
observed in THF (Entries 2 and 7). However, poly-Cn1, poly-
Qn1, and poly-Qd1 showed a similar level or slightly lower
enantioselectivities in CHCl3 and THF when compared to
those of the corresponding monomers, Cn1, Qn1, and Qd1,
respectively (Entries 8–15).
EXPERIMENTAL
Materials
All starting materials and anhydrous solvents were pur-
chased from Aldrich (Milwaukee, WI), Wako Pure Chemical
Industries (Osaka, Japan), or Tokyo Kasei (TCI, Tokyo, Japan)
and were used as received, except for triethylamine (Et3N),
which was dried over KOH pellets and distilled onto KOH
under nitrogen. 4-Ethynylbenzoyl chloride was synthesized
according to the previously reported method.6(b)
We next examined the asymmetric Henry reaction of ethyl
pyruvate with nitromethane11 in the presence of the cin-
chona alkaloid-bound helical poly(phenylacetylene)s and
ꢂ
monomers in various solvents at ꢀ20 C (Table 2). A similar
tendency was observed for the asymmetric Henry reaction;
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Instruments
d, ppm): 165.0, 150.2, 148.8, 145.2, 141.6, 132.4, 130.7,
129.72, 129.67, 129.5, 127.5, 127.2, 126.0, 123.4, 118.6,
114.9, 82.7, 80.7, 74.8, 59.9, 56.7, 42.6, 39.7, 27.9, 27.7, 24.3.
IR (KBr, thin film, cmꢀ1): 3258 (BCAH), 3074 (¼¼CAH),
2103 (CBC), 1724 (C¼¼O). HRMS (ESIþ, m/z): calcd for
The NMR spectra were measured using a Varian VXR-500S
spectrometer (Varian, Palo Alto, CA) operating at 500 MHz
1
for H and 125 MHz for 13C using tetramethylsilane or a sol-
vent residual peak as the internal standard. The IR spectra
were recorded on a JASCO FTIR-680 spectrophotometer
(JASCO, Tokyo, Japan). The absorption and CD spectra were
obtained in a 0.1 cm quartz cell using a JASCO V570 spectro-
photometer and a JASCO J-820 spectropolarimeter, respec-
tively. The temperature was controlled with a JASCO PTC-
423L apparatus. The concentrations of the polymers were
calculated based on the monomer units. The size exclusion
chromatography (SEC) measurements were performed with
a JASCO PU-980 liquid chromatograph equipped with a UV–
visible detector (JASCO UV-1570, 280 nm) and a column
oven (JASCO CO-1565). The number-average molecular
weight (Mn) and its distribution (Mw/Mn) were determined
C
28H27N2O2, 423.2073; found, 423.2062 [M þ H]þ. Anal.
calcd for C28H26N2O2: C, 79.59; H, 6.20; N, 6.63. Found: C,
79.33; H, 6.06; N, 6.78.
The monomers (Cn1, Qn1, and Qd1) were also prepared
from cinchonine, quinine, and quinidine, respectively, in the
same way for the synthesis of Cd1 (Scheme 1).
1
ꢂ
Cn1: Yield: 71%. mp: 144–146 C. H NMR (500 MHz, CDCl3,
d, ppm): d 8.88 (d, J ¼ 4.5 Hz, 1H, Ar), 8.29 (d, J ¼ 8.0 Hz,
1H, Ar), 8.13 (dd, J ¼ 8.5 Hz, 0.9Hz, 1H, Ar), 8.05–8.03 (m,
2H, Ar), 7.74–7.71 (m, 1H, Ar), 7.65–7.61 (m, 1H, Ar), 7.58–
7.56 (m, 2H, Ar), 7.45 (d, J ¼ 4.6 Hz, 1H, Ar), 6.77 (d, J ¼
7.4 Hz, 1H, AOCHA), 6.05–5.98 (m, 1H, ACHCH2), 5.14–5.07
(m, 2H, ACHCH2), 3.47–3.42 (m, 1H), 3.25 (s, 1H, ACCH),
2.99–2.90 (m, 2H), 2.83–2.69 (m, 2H), 2.31–2.26 (m, 1H),
1.97–1.92 (m, 1H), 1.86 (bs, 1H), 1.68–1.56 (m, 3H). 13C
NMR (125 MHz, CDCl3, d, ppm): 165.1, 150.1, 148.7, 145.6,
140.3, 132.4, 130.7, 129.8, 129.7, 129.4, 127.4, 127.1, 126.2,
123.4, 118.7, 115.1, 82.8, 80.6, 74.8, 60.0, 50.0, 49.3, 39.8,
27.8, 26.6, 24.2. IR (KBr, thin film, cmꢀ1): 3278 (BCAH),
3067 (¼¼CAH), 2103 (CBC), 1715 (C¼¼O). HRMS (ESIþ, m/
z): calcd for C28H27N2O2, 423.2073; found, 423.2064 [M þ
H]þ. Anal. calcd for C28H26N2O2: C, 79.59; H, 6.20; N, 6.63.
Found: C, 79.59; H, 6.22; N, 6.36.
ꢂ
at 40 C using Tosoh TSKgel a-3000 (30 cm) and a-5000 (30
cm) SEC columns (Tokyo, Japan) in series, and DMF contain-
ing 10 mM LiCl was used as the eluent at a flow rate of 0.5
mL/min. The molecular weight calibration curve was
obtained with poly(ethylene oxide) and poly (ethylene gly-
col) standards (Tosoh). The chiral HPLC analyses were per-
formed on a JASCO PU-2080 Plus liquid chromatograph
equipped with a Multi UV–visible detector (JASCO MD-2010
Plus) and an optical rotation detector (JASCO OR-2090 Plus)
using a Chiralpak AS-H column [0.46 (i.d.) ꢁ 25 cm, Daicel].
A 2-propanol/n-hexane mixture was used as the eluent at a
flow rate of 1.0 mL/min. The electron spray ionization mass
spectra (ESI-MS) were recorded using a JEOL JMS-T100CS
spectrometer (Akishima, Japan). The laser Raman spectra
were taken on a JASCO RMP-200 spectrophotometer. The
melting points were measured on a Yanako melting point
apparatus and were uncorrected.
Qn1: Yield: 91%. mp: 189–191 ꢂC. 1H NMR (500 MHz,
CDCl3, d, ppm): 8.73 (d, J ¼ 4.6 Hz, 1H, Ar), 8.05–8.02 (m,
3H, Ar), 7.59–7.57 (m, 2H, Ar), 7.51 (d, J ¼ 2.6 Hz, 1H, Ar),
7.42 (d, J ¼ 4.6 Hz, 1H, Ar), 7.40–7.37 (m, 1H, Ar), 6.75 (d, J
¼ 6.7 Hz, 1H, AOCHA), 5.88–5.81 (m, 1H, ACHCH2), 5.04–
5.00 (m, 2H, ACHCH2), 3.97 (s, 3H, AOCH3), 3.53–3.49 (m,
1H), 3.27 (s, 1H, ACCH), 3.23–3.17 (m, 1H), 3.12–3.07 (m,
1H), 2.73–2.66 (m, 2H), 2.31 (bs, 1H), 1.96–1.90 (m, 2H),
1.79–1.68 (m, 2H), 1.61–1.56 (m, 1H). 13C NMR (125 MHz,
CDCl3, d, ppm): 165.0, 158.1, 147.6, 144.9, 143.5, 141.7,
132.4, 132.0, 129.7, 129.6, 127.5, 127.0, 122.0, 118.8, 114.8,
101.4, 82.7, 80.7, 74.8, 59.4, 56.7, 55.8, 42.6, 39.7, 27.9, 27.7,
24.3. IR (KBr, thin film, cmꢀ1): 3282 (BCAH), 3063
(¼¼CAH), 2096 (CBC), 1720 (C¼¼O). HRMS (ESIþ, m/z):
calcd for C29H29N2O3, 453.2178; found, 453.2167 [M þ H]þ.
Anal. calcd for C29H28N2O3: C, 76.97; H, 6.24; N, 6.19. Found:
C, 76.94; H, 6.29; N, 6.10.
Synthesis of Monomers (Cd1, Cn1, Qn1, and Qd1)
A typical procedure for the synthesis of Cd1 is described
below (Scheme 1). A solution of 4-ethynylbenzoyl chloride
(1.80 g, 11.0 mmol) in anhydrous THF (50 mL) was added
dropwise to a solution of cinchonidine (Cd, 2.94 g, 10.0
mmol) in Et3N (2.78 mL, 20.0 mmol) and anhydrous THF
ꢂ
(100 mL) with vigorous stirring at 0 C under nitrogen. The
solution was allowed to warm to room temperature and
stirred overnight. The suspension was filtered and the vola-
tiles were removed from the filtrate, affording a pale yellow
solid. The residue was then purified by column chromatogra-
phy (SiO2, CHCl3/EtOAc ¼ 1/3, v/v), followed by recrystalli-
zation from EtOAc/n-hexane (1/4, v/v) to afford Cd1 as a
white crystalline solid (2.53 g, 60%). mp: 144–146 ꢂC. 1H
NMR (500 MHz, CDCl3, d, ppm): 8.88 (d, J ¼ 4.6 Hz, 1H, Ar),
8.31 (d, J ¼ 8.5 Hz, 1H, Ar), 8.13 (d, J ¼ 8.5 Hz, 1H, Ar), 8.04
(d, J ¼ 8.2 Hz, 2H, Ar), 7.74–7.71 (m, 1H, Ar), 7.64–7.61 (m,
1H, Ar), 7.57 (d, J ¼ 8.4 Hz, 2H, Ar), 7.45 (d, J ¼ 4.6 Hz, 1H,
Ar), 6.80 (d, J ¼ 6.8 Hz, 1H, ACHOA), 5.88–5.81 (m, 1H,
ACHCH2), 5.04–5.00 (m, 2H, CH2CHA), 3.53–3.48 (m, 1H),
3.25 (s, 1H, ACCH), 3.22–3.17 (m, 1H), 3.11–3.06 (m, 1H),
2.72–2.63 (m, 2H), 2.31 (bs, 1H), 1.98–1.90 (m, 2H), 1.80–
1.68 (m, 2H), 1.62–1.56 (m, 1H). 13C NMR (125 MHz, CDCl3,
Qd1: Yield: 95%. mp: 152–154 ꢂC. 1H NMR (500 MHz,
CDCl3, d, ppm): 8.72 (d, J ¼ 4.5 Hz, 1H, Ar), 8.05 (d, J ¼ 6.7
Hz, 2H, Ar), 8.02 (d, J ¼ 9.2 Hz, 1H, Ar), 7.58–7.57 (m, 2H,
Ar), 7.48 (d, J ¼ 2.2 Hz, 1H, Ar), 7.40 (d, J ¼ 4.6 Hz, 1H, Ar),
7.39–7.37 (m, 1H, Ar), 6.75 (bs, 1H, AOCHA), 6.05–5.98 (m,
1H, ACHCH2), 5.13–5.06 (m, 2H, ACHCH2), 3.98 (s, 3H,
AOCH3), 3.46–3.41 (m, 1H), 3.26 (s, 1H, ACCH), 2.98–2.96
(m, 2H), 2.88–2.84 (m, 1H), 2.79–2.73 (m, 1H), 2.32–2.28
(m, 1H), 2.00–1.95 (m, 1H), 1.87 (bs, 1H), 1.64–1.59 (m, 3H).
13C NMR (125 MHz, CDCl3, d, ppm): 165.0, 158.1, 147.7,
144.9, 143.8, 140.3, 132.4, 132.1, 129.8, 129.7, 127.4, 127.1,
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122.1, 118.7, 115.1, 101.5, 82.7, 80.7, 74.6, 59.5, 55.8, 50.0,
49.4, 39.7, 27.8, 26.5, 23.8. IR (KBr, thin film, cmꢀ1): 3275
(BCAH), 3072 (¼¼CAH), 2101 (CBC), 1709 (CAO). HRMS
Spectroscopic data of poly-Qd1. Yield: 81%, Mn ¼ 6.0 ꢁ 104;
Mw/Mn ¼ 4.9. 1H NMR (500 MHz, CDCl3, 50 ꢂC, d, ppm):
8.64 (s, 1H, Ar), 7.99 (s, 1H, Ar), 7.79 (s, 2H, Ar), 7.04–
7.45 (m, 4H, Ar), 6.97 (s, 1H, Ar), 6.75 (s, 1H, AOCHA), 5.75
(s, 1H), 5.39 (s, 1H), 4.81 (s, 1H, ACHCH2), 4.41 (s,
1H, ACHCH2), 3.94 (s, 3H, AOCH3), 3.06 (s, 1H), 2.59 (s,
2H), 2.39 (s, 1H), 0.87–1.73 (m, 7H). IR (KBr, thin film,
cmꢀ1): 3071 (¼¼CAH), 1721 (C¼¼O). Anal. calcd for
(C29H28N2O3ꢃ0.6H2O)n: C, 75.17; H, 6.35; N, 6.05. Found: C,
75.16; H, 6.32; N, 6.02.
(ESIþ, m/z): calcd for
C29H29N2O3, 453.2178; found,
453.2176 [M þ H]þ. Anal. calcd for C29H28N2O3: C, 76.97; H,
6.24; N, 6.19. Found: C, 76.97; H, 6.38; N, 6.09.
Polymerization
Polymerizations of Cd1, Cn1, Qn1, and Qd1 were carried
out according to Scheme 1 in a dry glass ampule under a
dry nitrogen atmosphere using [Rh(nbd)Cl]2 as a catalyst in
a similar way as reported previously.6 A typical polymeriza-
tion procedure is described below.
General Procedure for the Asymmetric Conjugate
Addition of 2-Naphthalenethiol to 2-Cyclohexen-1-one
In a glass-reactor, 2-naphthalenethiol (74.9 mg, 0.468 mmol)
and a polymer catalyst (2.34 lmol, 1 mol %) were dissolved
in 1 mL of THF or CHCl3. To this solution was added 2-cyclo-
hexen-1-one (22.7 lL, 0.234 mmol) via syringe. The resulting
mixture was kept at 0 ꢂC until the 2-cyclohexen-1-one was
completely consumed. The reaction mixture was directly
subjected to flash column chromatography (SiO2, CHCl3/n-
hexane ¼ 1/20, v/v) to isolate the product. The enantio-
meric excess of the product was determined by HPLC analy-
sis [Chiralpak AS-H column, 2-propanol/n-hexane ¼ 50/50
(v/v), 1.0 mL/min, k ¼ 254 nm];9(b) t[(S)-enantiomer] ¼ 8.92
The monomer Cd1 (295 mg, 0.699 mmol) was placed in a
dry ampule, which was then evacuated on a vacuum line and
flushed with dry nitrogen. After this evacuation-flush proce-
dure was repeated three times, a three-way stopcock was
attached to the ampule, and a mixture of Et3N (71 mg, 0.70
mmol) and anhydrous DMF (3 mL) were added with a
syringe. To this was added a solution of [Rh(nbd)Cl]2 (0.014
M) in DMF (0.5 mL) at 30 ꢂC. The concentrations of the
monomer and the rhodium catalyst were 0.2 and 0.002 M,
respectively. After 18 h, the resulting polymer (poly-Cd1)
was precipitated into a large amount of Et2O, washed with
Et2O, and collected by centrifugation. The product was puri-
fied by reprecipitation from CHCl3 to Et2O, and the precipi-
tated poly-Cd1 was washed with Et2O and dried in vacuo at
room temperature overnight (245 mg, 83% yield). The Mn
and Mw/Mn values were 9.2 ꢁ 103 and 2.4, respectively,
as determined by SEC using poly(ethylene oxide)s and poly
(ethylene glycol)s standards in DMF containing 10 mM LiCl
as the eluent.
min and t[(R)-enantiomer]
summarized in Table 1.
¼
10.80 min. The results are
General Procedure for the Asymmetric
Henry (Nitroaldol) Reaction of Ethyl Pyruvate
with Nitromethane
In a glass-reactor, a polymer catalyst (5.00 lmol, 1 mol%)
was added to a mixture of ethyl pyruvate (55.6 lL, 0.500
mmol), nitromethane (271 lL, 5.00 mmol), and an organic
solvent (0.5 mL) at ꢀ20 ꢂC. The resulting mixture was
stirred at ꢀ20 ꢂC for an appropriate time, and then
subjected to flash column chromatography (SiO2, ether) to
isolate the product. The enantiomeric excess of the product
was determined by HPLC analysis (Chiralpak AS-H column,
2-propanol/n-hexane ¼ 5/95 (v/v), 1.0 mL/min, k ¼ 215
Speꢂctroscopic data of poly-Cd1. 1H NMR (500 MHz, CDCl3,
50 C, d, ppm): 8.76 (s, 1H, Ar), 8.16 (s, 1H, Ar), 8.09 (s, 1H,
Ar), 7.76–7.55 (m, 4H, Ar), 7.31 (s, 1H, Ar), 7.04–6.73 (m,
3H, Ar, AOCHA), 5.70 (s, 1H), 5.55 (s, 1H), 4.80 (s, 2H), 3.24
(s, 1H), 2.94 (s, 1H), 2.87 (s, 1H), 2.44 (m, 2H), 1.69–1.26
(m, 6H). IR (KBr, thin film, cmꢀ1): 1720 (C¼¼O). Anal. calcd
for (C28H26N2O2ꢃ1.8H2O)n: C, 73.92; H, 6.56; N, 6.16. Found:
C, 73.71; H, 6.27; N, 6.22.
nm);11(c) t[(S)-enantiomer] ¼ 16.45 min and t[(R)-enantiomer]
¼
20.39 min. The results are summarized in Table 2.
CONCLUSIONS
Spectroscopic data of poly-Cn1. Yield: 87%, Mn ¼ 1.4 ꢁ 104;
Mw/Mn ¼ 2.7. 1H NMR (500 MHz, CDCl3, 50 ꢂC, d, ppm):
8.82 (s, 1H, Ar), 8.21 (s, 1H, Ar), 8.12 (s, 1H, Ar), 7.76–7.46
(m, 4H, Ar), 7.35 (s, 1H, Ar), 6.98–6.77 (m, 3H, Ar, AOCHA),
5.73 (s, 1H), 5.42 (s, 1H), 4.84 (s, 1H), 4.48 (s, 1H), 3.10–
2.40 (m, 3H), 1.63–0.84 (m, 8H). IR (KBr, thin film, cmꢀ1):
1719 (C¼¼O). Anal. calcd for (C28H26N2O2)n: C, 79.59; H,
6.20; N, 6.63. Found: C, 79.33; H, 6.35; N, 6.43.
We have synthesized a series of helical poly(phenylacety-
lene)s (poly-Cd1, poly-Cn1, poly-Qn1, and poly-Qd1) bearing
cinchona alkaloid derivatives as the pendants, which adopt a
preferred-handed helical conformation biased by the opti-
cally active cinchona alkaloid pendants. The Cotton effect
patterns of the polymers were significantly changed depend-
ing on the solvent used and accompanied by the changes in
their absorption spectra due to their conformational changes,
such as the inversion of the helical sense or the changes in
the helical pitch of the polymer backbones. These polymers
catalyzed the asymmetric conjugated addition and Henry
reactions; poly-Cd1 and poly-Qn1 exhibited a much higher
enantioselectivity than that catalyzed by the monomeric
counterparts, Cd1 and Qn1, respectively, demonstrating the
important role of the induced helical chirality of these poly-
meric catalysts in the present asymmetric transformation.
Spectroscopic data of poly-Qn1. Yield: 94%, Mn ¼ 1.1 ꢁ 104;
Mw/Mn ¼ 3.3. 1H NMR (500 MHz, CDCl3, 50 ꢂC, d, ppm):
8.59 (s, 1H, Ar), 7.92 (s, 1H, Ar), 7.78 (s, 1H, Ar), 7.29 (bs,
3H, Ar), 6.90–6.66 (m, 4H), 5.73 (s, 1H), 5.53 (s, 1H,
ACHCH2), 4.78 (s, 2H, ACHCH2), 3.88 (s, 3H, AOH3), 3.22–
1.26 (m, 11H). IR (KBr, thin film, cmꢀ1): 3074 (¼¼CAH),
1720 (C¼¼O). Anal. calcd for (C29H28N2O3)n: C, 76.97; H,
6.24; N, 6.19. Found: C, 76.96; H, 6.43; N, 6.10.
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5 Itsuno; et al. Recently prepared a novel optically active poly-
meric organocatalyst composed of a cinchona alkaloid as the
main-chain component that efficiently catalyzed asymmetric
benzylation of N-diphenylmethylidene glycine tert-butyl ester,
see: Itsuno, S.; Paul, D. K.; Salam, M. A.; Haraguchi, N. J Am
Chem Soc 2010, 132, 2864–2865.
Furthermore, the reversal of the enantioselectivity triggered
by the change in the solvent was observed for poly-Qn1 dur-
ing the asymmetric Henry reaction. These findings may be
useful to develop more efficient polymeric asymmetric cata-
lysts with a unique helical structure whose reactivity and
enantioselectivity can be controlled by the dynamic helical
conformational change regulated by various external stimuli.
6 (a) Yashima, E.; Maeda, K.; Sato, O. J Am Chem Soc 2001,
123, 8159–8160; (b) Maeda, K.; Kamiya, N.; Yashima, E. Chem
Eur J 2004, 10, 4000–4010; (c) Maeda, K.; Mochizuki, H.; Wata-
nabe, M.; Yashima, E. J Am Chem Soc 2006, 128, 7639–7650;
for recent examples, see: (d) Sakai, R.; Yonekawa, T.; Otsuka,
I.; Kakuchi, R.; Satoh, T.; Kakuchi, T. J Polym Sci Part A: Polym
Chem 2010, 48, 1197–1206; (e) Morimoto, M.; Tamura, K.;
Nagai, K.; Yashima, E. J Polym Sci Part A: Polym Chem 2010,
48, 1383–1390; (f) Luo, X. F.; Kang, N. W.; Li, L.; Deng, J. P.;
This work was supported in part by a Grant-in-Aid for Scientific
Research (S) from the Japan Society for the Promotion of Sci-
ence (JSPS), an Ogasawara Foundation (H. Iida), a Kurata Me-
morial Hitachi Science and Technology Foundation (H. Iida),
and the Global COE Program ‘‘Elucidation and Design of Materi-
als and Molecular Functions’’ of the Ministry of Education, Cul-
ture, Sports, Science, and Technology, Japan. G.M. Miyake
expresses his thanks for the National Science Foundation (NSF)
East Asia and Pacific Summer Institutes for U.S. Graduate Stu-
dents (EAPSI) and JSPS Summer Program 2009 for research
fellowships.
Yang, W. T.
J Polym Sci Part A: Polym Chem 2010, 48,
1661–1668; (g) Kakuchi, R.; Shimada, R.; Tago, Y.; Sakai, R.;
Satoh, T.; Kakuchi, T. J Polym Sci Part A: Polym Chem 2010,
48, 1683–1689.
7 For details of the characterization of the monomers and poly-
mers, see the Supporting Information. Stereoregularities of the
polymers were confirmed to be highly cis-transoidal based on
their characteristic 1H NMR and Raman spectra (Supporting In-
formation Figs. S1 and S2, respectively).
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