Chromatographic enantioseparation by poly(biphenylylacetylene) derivatives with memory of both axial chirality and macromolecular helicity

Article abstract of DOI:10.1002/chir.22687

Novel poly(biphenylylacetylene) derivatives bearing two acetyloxy groups at the 2- and 2′-positions and an alkoxycarbonyl group at the 4′-position of the biphenyl pendants (poly-Ac's) were synthesized by the polymerization of the corresponding biphenylylacetylenes using a rhodium catalyst. The obtained stereoregular (cis-transoidal) poly-Ac's folded into a predominantly one-handed helical conformation accompanied by a preferred-handed axially twisted conformation of the biphenyl pendants through noncovalent interactions with a chiral alcohol and both the induced main-chain helicity and the pendant axial chirality were maintained, that is, memorized, after complete removal of the chiral alcohol. The stability of the helicity memory of the poly-Ac's in a solution was lower than that of the analogous poly(biphenylylacetylene)s bearing two methoxymethoxy groups at the 2- and 2′-positions of the biphenyl pendants (poly-MOM's). In the solid state, however, the helicity memory of the poly-Ac's was much more stable and showed a better chiral recognition ability toward several racemates than that of the previously reported poly-MOM when used as a chiral stationary phase for high-performance liquid chromatography. In particular, the poly-Ac-based CSP with a helicity memory efficiently separated racemic benzoin derivatives into enantiomers.

Full text of DOI:10.1002/chir.22687

Received: 15 November 2016
DOI: 10.1002/chir.22687
Revised: 22 December 2016
Accepted: 23 December 2016
S P E C I A L I S S U E A R T I C L E
Chromatographic enantioseparation by poly(biphenylylacetylene)
derivatives with memory of both axial chirality and
macromolecular helicity
1
,2
1
1
2
1
Ryoma Ishidate | Tomoyuki Ikai | Shigeyoshi Kanoh | Eiji Yashima | Katsuhiro Maeda
1
Graduate School of Natural Science and
Abstract
Technology, Kanazawa University,
Kanazawa, Japan
Novel poly(biphenylylacetylene) derivatives bearing two acetyloxy groups at the 2‐
and 2′‐positions and an alkoxycarbonyl group at the 4′‐position of the biphenyl pen-
dants (poly‐Ac’s) were synthesized by the polymerization of the corresponding
biphenylylacetylenes using a rhodium catalyst. The obtained stereoregular (cis‐
transoidal) poly‐Ac’s folded into a predominantly one‐handed helical conformation
accompanied by a preferred‐handed axially twisted conformation of the biphenyl
pendants through noncovalent interactions with a chiral alcohol and both the
induced main‐chain helicity and the pendant axial chirality were maintained, that
is, memorized, after complete removal of the chiral alcohol. The stability of the
helicity memory of the poly‐Ac’s in a solution was lower than that of the analogous
poly(biphenylylacetylene)s bearing two methoxymethoxy groups at the 2‐ and 2′‐
positions of the biphenyl pendants (poly‐MOM’s). In the solid state, however, the
helicity memory of the poly‐Ac’s was much more stable and showed a better chiral
recognition ability toward several racemates than that of the previously reported
poly‐MOM when used as a chiral stationary phase for high‐performance liquid
chromatography. In particular, the poly‐Ac‐based CSP with a helicity memory effi-
ciently separated racemic benzoin derivatives into enantiomers.
2
Department of Molecular Design and
Engineering, Graduate School of
Engineering, Nagoya University, Nagoya,
Japan
Correspondence
E. Yashima, Department of Molecular
Design and Engineering, Graduate School of
Engineering, Nagoya University, Chikusa‐
ku, Nagoya 464‐8603, Japan.
Email: yashima@apchem.nagoya‐u.ac.jp
K. Maeda, Graduate School of Natural
Science and Technology, Kanazawa
University, Kakuma‐machi, Kanazawa
9
20‐1192, Japan.
Email: maeda@se.kanazawa‐u.ac.jp
Funding information
KAKENHI from the Japan Society for the
Promotion of Science (JSPS), Grant/Award
Number: 16H04154 (K.M.) and 25220804
(E.Y.)
KEYWORDS
biphenyl, chiral stationary phase, enantioseparation, helicity induction, high‐performance liquid
chromatography, memory, polyacetylene
1
| INTRODUCTION
investigation of the biological activities of individual enantio-
mers has become requisite to avoid serious chemical antago-
Most biologically and pharmacologically active compounds
including drugs, cosmetics, agrochemicals, and food additives
are chiral, and their physiological properties, such as pharmaco-
dynamics, pharmacokinetics, and toxic and metabolic activities,
nisms. Therefore, in many fields of science and technology
related to chiral compounds, the precise analysis of the enantio-
meric compositions and the preparation of both enantiopure
isomers have become increasingly important. It is well known
that the direct resolution of enantiomers by high‐performance
liquid chromatography (HPLC) using chiral stationary phases
1
-4
are often different between enantiomers. Therefore, careful
(
CSPs) is one of the most useful methods for both analytical
[
This article is part of the Special Issue: Proceedings of 28th International
and preparative purposes, and a large number of CSPs for HPLC
have been developed so far.
of one‐handed helical poly(triphenylmethyl methacrylate)
Symposium on Molecular Chirality, Heidelberg 2016. See the first articles
for this special issue previously published in Volume 29:1. More special
articles will be found in this issue as well as in those to come.]
5-12
Particularly since the discovery
1
20
© 2017 Wiley Periodicals, Inc.
wileyonlinelibrary.com/journal/chir
Chirality. 2017;29:120–129.

ISHIDATE ET AL.
121
13-17
18-21
(PTrMA)
and polysaccharide derivatives,
showing an
excellent resolution ability as CSPs, a variety of helical poly-
12,22-24
mers have been prepared for using them as CSPs.
We recently discovered a quite unique helical polymer, a
poly(biphenylylacetylene) derivative (poly‐MOM‐a) bearing
methoxymethoxy (MOM) groups at the 2‐ and 2′‐positions
and an n‐dodecyloxy group at the 4′‐position of the biphenyl
pendant, which folds into a preferred‐handed helical
conformation through noncovalent weak interactions with
(
R)‐ or (S)‐1‐phenylethanol ((R)‐ or (S)‐1) in the solid state
as well as in solution, through which the axial chirality of
2
5
the biphenyl pendants is also biased. The induced macro-
molecular helicity and the axial chirality of the biphenyl
pendants could be memorized even after complete removal
of the optically active alcohol. This unique feature of poly‐
MOM‐a allowed us to develop an unprecedented CSP for
HPLC, whose helical chirality as well as axial chirality
was directly switched in the column by sequential treatment
with an eluent containing (R)‐ or (S)‐1, leading to the
reversible switching of the elution order of the enantiomers.
However, the chiral recognition ability of the poly‐MOM‐a‐
based CSP was rather poor due to the lack of effective
interaction sites with the enantiomers. In addition, we previ-
ously found that the introduction of the methoxy groups or
n‐propoxy groups at the 2‐ and 2′‐positions of the biphenyl
pendants instead of the MOM groups resulted in complete
disappearance of the helicity memory or no helicity
induction, respectively, indicating that the alkoxymethoxy
groups at the 2‐ and 2′‐positions play an important role in
the helicity induction and its memory.
SCHEME 1 Structures of poly(biphenylylacetylene) derivatives
bearing various substituents at the 2‐, 2′‐ and 4′‐positions of the
biphenyl pendant groups. Schematic representation of a preferred‐
handed macromolecular helicity and axial chirality induction in
poly(biphenylylacetylene)s through noncovalent interaction with a chiral
alcohol ((S)‐ or (R)‐1) and subsequent memory of the helicity and axial
chirality after complete removal of the chiral alcohol
2
2
| MATERIALS AND METHODS
.1 | Instrument
Melting point measurements were performed using a Yanako
melting point apparatus and were uncorrected. Nuclear mag-
netic resonance (NMR) spectra were measured using a JNM‐
ECA 500 (Jeol, Tokyo, Japan) spectrometer operating at
1
13
On the other hand, we recently reported that an analogous
500 MHz for H and 125 MHz for C in CDCl using
3
poly(biphenylylacetylene)
poly‐MOM‐b
bearing
a
tetramethylsilane (TMS) as the internal standard. IR spectra
were recorded with a Jasco (Hachioji, Japan) Fourier Trans-
form IR‐460 spectrophotometer. The molecular weights of
the polymers were measured by size exclusion chromatogra-
phy (SEC) on a Jasco PU‐2080 liquid chromatograph
equipped with a Shodex (Tokyo, Japan) KF‐805 L (30 cm)
column and a photodiode array detector (Jasco MD‐2018) at
40 °C using tetrahydrofuran (THF) as the eluent at a flow rate
of 1.0 mL/min. Polystyrene standards (Tosoh, Tokyo, Japan)
were used for obtaining the molecular weight calibration
curves. Absorption and circular dichroism (CD) spectra were
measured in a 1.0 mm quartz cell on a Jasco V‐570 spectro-
photometer and a Jasco J‐725 spectropolarimeter, respec-
tively. The temperature was controlled with a Jasco ETC‐
505 T (absorption spectroscopy) and a Jasco PTC‐348WI
apparatus (CD spectroscopy). The chromatographic
enantioseparation experiments were performed using a
Jasco PU‐2080 liquid chromatograph equipped with a
multi‐wavelength detector (Jasco MD‐2018) and a CD
detector (Jasco CD‐2095) at ca. 10 °C. TGA was conducted
on a SEIKO EXSTAR6000 TG/DTA 6200 (Seiko Instru-
ments, Chiba, Japan) under a heating rate of 30 °C/min.
butoxycarbonyl ester group at the 4′‐position of the biphenyl
pendant also showed a similar helicity induction and memory
effect and the macromolecular helicity memory of poly‐
MOM‐b was more stably maintained compared with that of
26
poly‐MOM‐a. Moreover, the poly‐MOM‐b‐based CSP
with a helicity memory efficiently resolved several racemic
compounds such as chiral binaphthyl compounds and metal
tris(acetylacetonato)s. These results suggest that the
introduction of a butoxycarbonyl ester group onto the biphe-
nyl pendant can contribute to both the stabilization of the
helicity memory and improvement of the chiral recognition
ability.
In this study, we synthesized two novel poly
(
biphenylylacetylene)s (poly‐Ac‐b and poly‐Ac‐c) bearing
two ester (acetyloxy) groups at the 2‐ and 2′‐positions
instead of two MOM groups in addition to an ester
(alkoxycarbonyl) group at the 4′‐position of the biphenyl
pendant and investigated the effects of the ester groups at
the 2‐ and 2′‐positions on the helicity induction and memory
effects along with their chiral recognition abilities as CSPs
for HPLC (Scheme 1).

1
22
ISHIDATE ET AL.
VCD spectra were measured in a 0.50 mm BaF cell with a
NMR (500 MHz, CDCl , rt): δ 7.76 (d, J = 1.4 Hz, 1H, Ar‐
2
3
Jasco JV‐2001YS spectrometer equipped with a temperature
controller (Eyela NCB‐1200) (Eyela, Tokyo, Japan). The
concentration was 12 mg/mL in methylcyclohexane
H), 7.74–7.71 (dd, J = 1.4, 6.4 Hz, 1H, Ar–H), 7.36 (d,
J = 7.8 Hz, 1H, Ar–H), 7.25–7.18 (m, 3H, Ar–H), 6.40–
6.05 (broad, 2H, Ar‐OH), 4.35 (t, J = 6.9 Hz, 2H, COCH2),
3.14 (s, 1H, C≡C‐H), 1.77 (quint, J = 6.4 Hz, 2H,
CH CH ), 1.49 (sex, J = 7.8 Hz, 2H, CH CH ), 0.99 (t,
(
MCH) and temperature was ca. –10 °C. All spectra were
−
1
collected for ~4 h at a resolution of 4 cm . Elemental anal-
yses were done at the Research Institute for Instrumental
Analysis of Advanced Science Research Center, Kanazawa
University, Kanazawa, Japan.
2
2
2
2
J = 7.3 Hz, 3H, CH CH ).
2
3
2.3.2 | Preparation of Ac‐b
2
.2 | Materials
To
a solution of (2,2′‐dihydroxy‐4′‐butoxycarbonyl‐4‐
biphenylyl)acetylene (168 mg, 0.541 mmol) in anhydrous
diethyl ether (5.4 mL) was added pyridine (219 μL,
Anhydrous THF, diethyl ether, and dichloromethane were
obtained from Kanto Kagaku (Tokyo, Japan). Triethylamine
2
.70 mmol) and acetic anhydride (255 μL, 2.70 mmol). After
(Et N) was dried over KOH pellets and distilled onto KOH
3
stirring at room temperature for 12 h, the mixture was diluted
with diethyl ether and the solution was washed with 1 N HCl
aqueous solution and water. The organic layer was dried over
Na SO before evaporating the solvent. The residue was then
purified by chromatography on silica gel with n‐hexane–ethyl
acetate (5/1, v/v) as the eluent to give the desired product as a
white solid (208 mg, 98% yield). Mp: 95.1–95.7 °C. IR (KBr):
under nitrogen. Acetic anhydride, hydrochloric acid and N,
N‐dimethyl‐4‐aminopyridine (DMAP) were purchased from
Wako Pure Chemical Industries (Osaka, Japan). 1‐
Dodecanol, 1‐tetradecanol, MCH, and 1‐ethyl‐3‐(3‐
dimethylaminopropyl)carbodiimide hydrochloride (EDC)
were from Tokyo Kasei (TCI, Tokyo, Japan). (R)‐ and (S)‐1
2
4
were
obtained
from
Kanto
Kagaku.
Pyridine,
−
1 1
ν = 3253 (≡CH), 2104 (C≡C), 1771, 1710 (C=O) cm . H
NMR (500 MHz, CDCl , rt): δ 7.99–7.96 (dd, J = 1.8,
[(norbornadiene)rhodium(I) chloride]2 [Rh(nbd)Cl ] and
2
3
sodium hydroxide were available from Sigma‐Aldrich (St.
Louis, MO). The porous spherical silica gel (Daiso gel SP‐
6.4 Hz, 1H, Ar–H), 7.82 (d, J = 1.4 Hz, 1H, Ar‐H), 7.45–
7.42 (dd, J = 1.7, 6.3 Hz, 1H, Ar‐H), 7.37 (d, J = 8.0 Hz,
1H, Ar‐H), 7.31 (d, J = 1.7 Hz, 1H, Ar‐H), 7.26 (d,
1000‐7) with a mean particle size of 7 μm and a mean pore
diameter of 100 nm was kindly provided by Osaka Soda
J = 8.0 Hz, 1H, Ar‐H), 4.35 (t, J = 6.4 Hz, 2H, COCH2),
(Osaka, Japan). (2,2′‐Bis(methoxymethoxy)‐4′‐dodecyloxy‐
3
.16 (s, 1H, C≡C‐H), 2.06 (d, J = 10.5 Hz, 6H, 2COCH3),
2
5
4‐biphenylyl)acetylene
(MOM‐a)
and
(2,2′‐bis
1
.77 (quint, J = 6.9 Hz, 2H, CH CH ), 1.48 (sex,
2
2
(methoxymethoxy)‐4′‐butoxycarbonyl‐4‐biphenylyl)acety-
J = 7.8 Hz, 2H, CH CH ), 0.99 (t, J = 7.3 Hz, 3H, CH CH ).
26
2
2
2
3
lene (MOM‐b) were prepared according to the previously
reported methods.
13
C NMR (125 MHz, CDCl , rt): δ 169.02, 168.86, 165.50,
3
1
1
47.92, 147.59, 134.55, 131.70, 131.12, 130.96, 130.52,
29.79, 127.11, 126.37, 123.87, 123.45, 99.89, 82.23,
2
.3 | Synthesis
78.80, 65.26, 30.71, 20.70, 19.25, 13.77. Anal. Calcd for
C H O : C, 70.04; H, 5.62. Found: C, 69.75; H, 5.40.
23 22 6
(
(
2,2′‐Diacetyloxy‐4′‐butoxycarbonyl‐4‐biphenylyl)acetylene
Ac‐b) and (2,2′‐diacetyloxy‐4′‐n‐tetradecyloxycarbonyl‐4‐
biphenylyl)acetylene (Ac‐c) were prepared according to the
route shown in Scheme S1.
2
.3.3 | Preparation of (2,2′‐
Bis(methoxymethoxy)‐4′‐carboxyl‐4‐biphenylyl)
acetylene
2
.3.1 | Preparation of (2,2′‐dihydroxy‐4′‐
To a solution of MOM‐b (2.40 g, 6.02 mmol) in THF/metha-
nol (2/1, v/v) (6.0 mL) was added sodium hydroxide (0.36 g,
9.03 mmol). After stirring at 0 °C for 2 h and then at room
temperature for 12 h, the mixture was diluted with ethyl ace-
tate and the solution was washed with 1 N HCl aqueous solu-
tion and water. After filtration, the solvent was removed by
evaporation to give the desired product as a white solid
butoxycarbonyl‐4‐biphenylyl)acetylene
To a solution of compound MOM‐b (800 mg, 2.01 mmol) in
THF/methanol (1/1, v/v) (270 mL) was slowly added conc.
HCl (2.24 mL). After stirring at room temperature for 48 h,
the solvent was removed under reduced pressure. The residue
was diluted with ethyl acetate and the solution was washed
with water and brine, then dried over Na SO . After filtra-
tion, the solvent was removed by evaporation and the crude
product was purified by silica gel chromatography using n‐
hexane—ethyl acetate (5/1, v/v) as the eluent to give the
(2.04 g, 99% yield). This was used for the next reaction with-
2
4
1
out further purification. H NMR (500 MHz, CDCl , rt): δ
3
7.92 (d, J = 1.7 Hz, 1H, Ar‐H), 7.85–7.81 (dd, J = 1.1,
6.8 Hz, 1H, Ar–H), 7.38 (s, 1H, Ar‐H), 7.34 (d, J = 8.0 Hz,
1H, Ar‐H), 7.24–7.19 (m, 2H, Ar–H), 5.12 (d, J = 29.2 Hz,
1
desired product as a white solid (616 mg, 99% yield). H

ISHIDATE ET AL.
123
4
H, 2OCH O), 3.36 (d, J = 4.0 Hz, 6H, 2OCH ), 3.11 (s, 1H,
2.3.6 | Preparation of Ac‐c
2
3
C≡C‐H).
To a solution of (2,2′‐dihydroxy‐4′‐n‐tetradecyloxycarbonyl‐
‐biphenylyl)acetylene (70.0 mg, 0.155 mmol) in anhydrous
4
diethyl ether (1.55 mL) was added pyridine (63.0 μL,
0.781 mmol) and acetic anhydride (73.3 μL, 0.775 mmol).
After stirring at room temperature for 12 h, the mixture
was diluted with diethyl ether and the solution was washed
with 1 N HCl aqueous solution and water. The organic layer
was dried over Na SO before evaporating the solvent. The
2
.3.4 | Preparation of (2,2′‐
Bis(methoxymethoxy)‐4′‐n‐
tetradecyloxycarbonyl‐4‐biphenylyl)acetylene
To a solution of (2,2′‐bis(methoxymethoxy)‐4′‐carboxyl‐4‐
biphenylyl)acetylene (100 mg, 0.292 mmol), 1‐tetradecanol
2
4
residue was then purified by chromatography on silica gel
with n‐hexane–ethyl acetate (5/1, v/v) as the eluent to give
the desired product as a white solid (78.1 mg, 94% yield).
Mp: 63.4–64.3 °C. IR (KBr): ν = 3248 (≡CH), 2104
(
81.8 mg, 0.382 mmol), DMAP (46.6 mg, 0.381 mmol) in
anhydrous dichloromethane (3.0 mL) was added EDC
89.4 mg, 0.45 mmol) at 0 °C. The mixture was stirred
(
at room temperature for 3 h. After evaporating the solvent,
the mixture was diluted with ethyl acetate and the solution
was washed with water, then dried over Na SO . The
solvent was removed under reduced pressure and the crude
product was purified by silica gel chromatography using
n‐hexane–ethyl acetate (10/1, v/v) as the eluent to give
−
1
1
(
C≡C), 1766, 1718 (C=O) cm . H NMR (500 MHz,
CDCl , rt): δ 7.98–7.96 (dd, J = 1.7, 6.3 Hz, 1H, Ar–H),
3
2
4
7
6
.82 (d, J = 1.7 Hz, 1H, Ar‐H), 7.44–7.42 (dd, J = 1.2,
.3 Hz, 1H, Ar‐H), 7.37 (d, J = 8.0 Hz, 1H, Ar‐H), 7.32
(d, J = 1.2 Hz, 1H, Ar‐H), 7.26 (d, J = 8.0 Hz, 1H, Ar‐
H), 4.33 (t, J = 6.9 Hz, 2H, COCH ), 3.16 (s, 1H, C≡C‐
2
the desired product as a white solid (152 mg, 97% yield).
1
H), 2.06 (d, 6H, J = 13.1 Hz, 2COCH
), 1.77 (quint,
3
H NMR (500 MHz, CDCl , rt): δ 7.85 (d, J = 1.2 Hz,
3
J = 7.4 Hz, 2H, CH CH ), 1.44 (quint, J = 6.3 Hz, 2H,
2
2
1H, Ar–H), 7.76–7.74 (dd, J = 1.1, 6.3 Hz, 1H, Ar–H),
7.37 (s, 1H, Ar‐H), 7.29 (d, J = 8.0 Hz, 1H, Ar‐H),
7.23–7.18 (m, 2H, Ar–H), 5.10 (d, J = 24.6 Hz, 4H,
2OCH O), 4.33 (t, J = 6.9 Hz, 2H, COCH ), 3.34 (d,
CH CH ), 1.36–1.20 (m, 23H, CH CH ), 0.88 (t,
2
2
2
2
13
J = 6.8 Hz, 3H, CH CH ). C NMR (125 MHz, CDCl3,
2
3
rt): δ 168.99, 168.84, 165.51, 147.95, 147.62, 134.55,
2
2
1
1
3
2
7
31.73, 131.12, 130.96, 130.55, 129.78, 127.11, 126.38,
23.89, 123.46, 82.24, 78.79, 77.27, 77.02, 76.76, 65.59,
1.92, 29.65, 29.60, 29.53, 29.37, 29.30, 28.68, 26.00,
2.70, 20.69, 20.67, 14.13. Anal. Calcd for C H O : C,
J = 4.6 Hz, 6H, 2OCH ), 3.11 (s, 1H, C≡C‐H), 1.77
3
(quint,
J = 6.9 Hz, 2H, CH CH ), 1.44 (quint,
2 2
J = 6.3 Hz, 2H, CH CH ), 1.36–1.22 (m, 20H, CH CH ),
2
2
2
2
33 42 6
0.88 (t, J = 6.9 Hz, 3H, CH3).
4.13; H, 7.92. Found: C, 73.98; H, 8.00.
2
.3.5 | Preparation of (2,2′‐dihydroxy‐4′‐n‐
2.3.7 | Preparation of (2,2′‐
tetradecyloxycarbonyl‐4‐biphenylyl)acetylene
Bis(methoxymethoxy)‐4′‐dodecyloxycarbonyl‐4‐
biphenylyl)acetylene (MOM‐c)
To
tetradecyloxycarbonyl‐4‐biphenylyl)acetylene (120 mg,
.22 mmol) in THF/methanol (1/1, v/v) (29.6 mL) was
a
solution of (2,2′‐bis(methoxymethoxy)‐4′‐n‐
To a solution of (2,2′‐bis(methoxymethoxy)‐4′‐carboxyl‐4‐
biphenylyl)acetylene (150 mg, 0.438 mmol), 1‐dodecanol
(108 μL, 0.580 mmol) and DMAP (70.9 mg, 0.580 mmol)
in anhydrous dichloromethane (8.0 mL) was added EDC
(128.5 mg, 0.670 mmol) at 0 °C. The mixture was stirred at
room temperature for 3 h. After evaporating the solvent, the
mixture was diluted with ethyl acetate and the solution was
washed with water, then dried over Na SO . The solvent
0
slowly added conc. HCl (246 μL). After stirring at room
temperature for 30 h, the solvent was removed under
reduced pressure. The residue was diluted with ethyl acetate
and the solution was washed with water and brine, then
dried over NaSO . After filtration, the solvent was removed
by evaporation and the crude product was purified by silica
4
2
4
gel chromatography using n‐hexane–ethyl acetate (3/1, v/v)
was removed under reduced pressure and the crude product
was purified by silica gel chromatography using n‐hexane–
ethyl acetate (8/1, v/v) as the eluent to give the desired prod-
uct as a white solid (219 mg, 98% yield). IR (KBr): ν = 3231
as the eluent to give the desired product as a white solid
1
(
84.7 mg, 84% yield). H NMR (500 MHz, CDCl , rt): δ
3
7.74–7.72 (dd, J = 1.7, 6.3 Hz, 1H, Ar‐H), 7.71 (d,
−
1
1
J = 1.7 Hz, 1H, Ar–H), 7.35 (d, J = 8.0 Hz, 1H, Ar‐H),
(≡CH), 2105 (C≡C), 1719 (C=O) cm . H NMR
7
4
1
.24–7.16 (m, 3H, Ar–H), 6.0–5.88 (broad, 2H, Ar‐OH),
(500 MHz, CDCl , rt): δ 7.85 (d, J = 1.1 Hz, 1H, Ar–H),
3
.33 (t, J = 6.9 Hz, 2H, COCH ), 3.14 (s, 1H, C≡C‐H),
7.76–7.74 (dd, J = 1.1, 6.3 Hz, 1H, Ar–H), 7.37 (d,
J = 1.2 Hz, 1H, Ar‐H), 7.30 (d, J = 8.0 Hz, 1H, Ar‐H),
7.23–7.18 (m, 2H, Ar–H), 5.10 (d, J = 24.0 Hz, 4H,
2OCH O), 4.33 (t, J = 6.9 Hz, 2H, COCH ), 3.34 (d,
2
.77 (quint, J = 6.9 Hz, 2H, CH CH ), 1.44 (quint,
2
2
J = 8.0 Hz, 2H, CH CH ), 1.38–1.20 (m, 20H, CH CH ),
0
2
2
2
2
.88 (t, J = 6.9 Hz, 3H, CH CH ).
2 3
2
2

1
24
ISHIDATE ET AL.
J = 4.6 Hz, 6H, 2OCH ), 3.10 (s, 1H, C≡C‐H), 1.77 (quint,
between the phenyl groups of the biphenyl units was set to
be Æ53.2° (right‐ and left‐handed twists (cisoid), respec-
tively) on the basis of the crystal structure of Ac‐b deter-
mined by X‐ray analysis (Figure S17) and the n‐
butoxycarbonyl group at the 4′‐position of the biphenyl pen-
dant was replaced by a methoxycarbonyl group for simplicity.
3
J = 6.9 Hz, 2H, CH CH ), 1.47–1.26 (m, 18H, CH CH ),
2
2
2
2
1
3
0
.88 (t, J = 6.9 Hz, 3H, CH3). C NMR (125 MHz, CDCl3,
rt): δ 166.43, 154.74, 154.59, 133.21, 131.33, 131.20,
1
9
2
2
29.24, 125.73, 123.05, 122.87, 118.91, 116.28, 95.22,
5.16, 83.49, 77.54, 77.37, 65.39, 56.19, 56.11, 32.01,
9.76, 29.73, 29.68, 29.66, 29.46, 29.40, 28.84, 26.13,
2.79, 14.23. Anal. Calcd for C H O : C, 72.91; H, 8.29.
3
1 42 6
2.6 | Preparation of HPLC columns
Found: C, 72.78; H, 8.37.
A solution of poly‐Ac‐b (60 mg) in (R)‐1 after standing at
5 °C for 2 h was coated on silica gel (0.39 g) according to
2
2
.4 | Polymerization
28
the literature method. The poly‐Ac‐b content on the silica
gel was estimated to be 13 wt% by thermogravimetric analy-
sis. After fractionating with sieves, the packing material was
packed into a stainless‐steel column (25 × 0.20 cm (i.d.)) by a
slurry method using an ECONO‐PACKER MODEL CPP‐
Polymerizations of Ac‐b, Ac‐c, and MOM‐c were conducted
with [Rh(nbd)Cl] as a catalyst under a dry nitrogen atmo-
sphere according to the method reported previously (Scheme
S2), and the results are summarized in Table S1.
2
2
5
29
0
85 (Chemco, St. Louis, MO). The plate number of the col-
umn was estimated for benzene with n‐hexane/2‐propanol
97/3, v/v) as the eluent at a flow rate of 0.2 mL/min at about
0 °C and was 2800. The hold‐up time (t ) was estimated
2
.4.1 | Spectroscopic data of poly‐Ac‐b
(
1
−
1 1
IR (KBr): ν = 1770, 1720 (C=O) cm . H NMR (500 MHz,
CDCl , 55 °C): δ 7.85–6.50 (br, 6H, Ar‐H), 6.20–5.83 (br,
0
3
using 1,3,5‐tri‐tert‐butylbenzene as the nonretained
1H, C=C‐H), 4.42–4.00 (br, 2H, OCH ), 2.05–1.20 (br, 6H,
30
2
compound.
2COCH ), (br, 4H, 2CH CH ), 1.05–0.75 (br, 3H, CH CH ).
3
2
2
2
3
Calcd for C H O ·0.1H O: C, 69.72; H, 5.65. Found: C,
23
22
6
2
69.49; H, 5.65.
3 | RESULTS AND DISCUSSION
Two new biphenylylacetylene monomers bearing two
acetyloxy groups at the 2‐ and 2′‐positions and an n‐
butoxycarbonyl (Ac‐b) or an n‐tetradecyloxycarbonyl group
(Ac‐c) at the 4′‐position of the biphenyl residue were pre-
pared as outlined in Scheme S1. The polymerizations of
Ac‐b and Ac‐c were performed in THF using a rhodium cat-
2
.4.2 | Spectroscopic data of poly‐Ac‐c
−
1
1
IR (KBr): ν = 1772, 1721 (C=O) cm . H NMR
500 MHz, CDCl , 55 °C): δ 7.85–6.50 (br, 6H, Ar‐H),
(
3
6
1
0
.20–5.85 (br, 1H, C=C‐H), 4.44–4.00 (br, 2H, OCH2),
.90–1.50 (br, 6H, 2COCH ), 1.40–1.15 (m, 24H, CH CH ),
.90–0.80 (br, 3H, CH CH ). Anal. Calcd for
3
2
2
alyst ([Rh(nbd)Cl] , nbd: norbornadiene) according to a pre-
2
3
2
25
C H O ·0.1H O: C, 73.88; H, 7.93. Found: C, 73.58; H,
viously reported method, affording the corresponding poly
(biphenylylacetylene)s, poly‐Ac‐b and poly‐Ac‐c, respec-
tively, in high yields (>95%) (Scheme S2 and Table S1).
3
3
42
6
2
7.97.
The number average molecular weight (M ) and its distribu-
n
2
.4.3 | Spectroscopic data of poly‐MOM‐c
5
tion (M /M ) were estimated to be 5.1 × 10 and 1.7 (poly‐
w
n
−1
1
5
IR (KBr): ν = 1719 (C=O) cm . H NMR (500 MHz,
CDCl , 55 °C): δ 7.77–6.40 (br, 6H, Ar‐H), 6.07–5.90 (br,
Ac‐b) and 6.1 × 10 and 1.9 (poly‐Ac‐c), respectively, by size
exclusion chromatography (SEC) with polystyrene standards
in THF. The main‐chain stereoregularity of poly‐Ac‐b and
poly‐Ac‐c was determined to be highly cis‐transoidal based
3
1H, C=C‐H), 4.95–4.55 (br, 4H, 2OCH O), 4.33–4.12 (br,
2
2H, OCH ), 3.15–2.88 (br, 6H, 2OCH ), 1.78–1.63 (br, 2H,
2
3
1
31,32
CH ), 1.45–1.10 (br, 18H, CH ), 0.90–0.80 (br, 3H, CH ).
Calcd for C H O ·0.1H O: C, 72.66; H, 8.30. Found: C,
on an H NMR analysis (Figures S7 and S8).
Poly‐Ac‐
2
2
3
c is soluble even in saturated hydrocarbons, such as n‐hexane
and MCH, whereas poly‐Ac‐b is insoluble in these solvents,
but soluble in THF, chloroform, and a chiral alcohol 1. As
reported in our previous article, the stability of the helicity
memory of poly‐MOM‐a in solution was largely affected
by the solvents; the helicity memory of poly‐MOM‐a was
stably maintained in n‐hexane, while it was quickly lost
31
42
6
2
72.45; H, 8.16.
2
.5 | IR and VCD calculations
The IR and VCD spectra for a pair of enantiomeric model
biphenyl compounds (M‐Ac‐c) of Ac‐c were calculated using
the Density Functional Theory (DFT) method at the B3LYP
level and the 6‐31G* basis set in the Gaussian09 program
25
within a few minutes once dissolved in THF. Therefore,
the helicity induction and memory effect were investigated
in detail for poly‐Ac‐c in MCH, whereas poly‐Ac‐b with a
2
7
(Pittsburgh, PA) (Figure S16). The initial dihedral angle

ISHIDATE ET AL.
125
helicity memory was used to prepare a coated‐type CSP for
HPLC and its chiral recognition ability was examined under
normal phase conditions toward various racemates because
poly‐Ac‐c is readily soluble in eluents under normal phase
conditions and its chiral resolving ability as a coated‐type
CSP could not be evaluated. For comparison, poly‐MOM‐c
bearing MOM groups at the 2‐ and 2′‐positions and an n‐
dodecyloxycarbonyl group at the 4′‐position of the biphenyl
residue, which was soluble in MCH, was also prepared
because the previously reported poly‐MOM‐b was insoluble
2
6
in MCH (Scheme S2 and Table S1).
Poly‐Ac‐c exhibited an intense induced circular dichro-
ism (ICD) in the absorption region of the polyacetylene back-
bone in the presence of (S)‐ or (R)‐1 in MCH at 25 °C
(Figure 1(i) and (iv)), indicating that a preferred‐handed heli-
FIGURE 2 CD and absorption spectra of poly‐MOM‐a (orange
broken lines), poly‐MOM‐c (purple broken lines) and poly‐Ac‐c (red
lines) in MCH and poly‐MOM‐b (green broken lines) in toluene in the
presence of (R)‐1 (toluene/1 (90/10, v/v)), and poly‐Ac‐b in (R)‐1 (blue
lines) at 25 °C after standing at 25 °C for 2 h. [polymer] = 1.0 mM
cal conformation was induced in poly‐Ac‐c through
noncovalent interaction with the chiral alcohol. The ICD
intensity gradually increased with time and an increase in
the concentration of 1 in MCH and reached a plateau value
after standing at 25 °C for 1 h in an MCH/(R)‐1 mixture
(90:10, v/v) (Figures S10 and S11). A slight increase in the
ICD intensity was also observed at −10 °C (Figure 1(ii)).
Although poly‐Ac‐c exhibited strong ICDs in n‐hexane and
MCH, the ICD intensity significantly decreased in toluene
and no detectable ICD signal was observed in THF and chlo-
roform (Figure S12), probably due to very weak interactions
between the poly‐Ac‐c and the chiral alcohol 1 in these sol-
vents. A similar tendency was also observed for the poly‐
of poly‐Ac‐c, indicating a preferred‐handed helix formation
of poly‐Ac‐b in (R)‐1 whose helix‐sense excess may be
slightly lower than that of poly‐Ac‐c.
It is noteworthy that the Cotton effect patterns of poly‐
Ac‐b and poly‐Ac‐c were different from those of poly‐
MOM‐a, poly‐MOM‐b, and poly‐MOM‐c (Figure 2). These
results suggest that the helical structure induced in the poly‐
Ac’s is slightly different from that of the poly‐MOM’s, prob-
ably due to the difference in the bulkiness of the substituents
at the 2‐ and 2′‐positions of the biphenyl pendants (MOM
and acetyloxy groups), while the substituents introduced at
the 4′‐position (alkoxy and ester groups) (Scheme 1) hardly
affect the main‐chain helical structures because they are
located far from the polymer backbones.
25,26
MOM’s.
Since poly‐Ac‐b is insoluble in MCH and n‐
hexane, but soluble in 1, we then measured the CD spectrum
of poly‐Ac‐b in (R)‐1, which showed intense, but slightly
weak Cotton effects (Figure 1(v)) when compared to those
25
In our previous report, we demonstrated that the
helicity induction in poly‐MOM‐a with nonracemic 1
showed an intense positive nonlinear relationship between
the enantiomeric excess (ee) of 1 and the observed ICD inten-
33
sities (“majority rule”). The changes in the ICD intensity of
poly‐Ac‐c versus the ee’s of 1 in MCH were then measured at
2
5 and −10 °C to check the effect of the substituents at the 2‐
and 2′‐positions on the chiral amplification behavior. The CD
intensities of poly‐Ac‐c, corresponding to the helical sense
excesses, were slightly out of proportion to the ee’s of 1,
showing a convex deviation from linearity (Figure S13).
However, the nonlinearities observed for poly‐Ac‐c were
25
weaker than those for poly‐MOM‐a, indicating the critical
role of the substituents at the 2‐ and 2′‐positions of the biphe-
nyl pendants in achieving a high chiral amplification,
resulting from close interactions between the neighboring
pendant biphenyl groups along the helical polymer backbone
with a high cooperativity.
FIGURE 1 CD and absorption spectra of poly‐Ac‐c with (R)‐1
measured in MCH (MCH/(R)‐1 = 90/10, v/v) at 25 (i) and −10 °C (ii)
after standing at 25 °C for 2 h, and the isolated poly‐Ac‐c in MCH at
−10 °C recovered from ii (iii) and those with (S)‐1 measured in MCH
(
(
MCH/(S)‐1 = 90/10, v/v) at 25 °C (iv) and poly‐Ac‐b in (R)‐1 at 25 °C
v). [polymer] = 1.0 mM

1
26
ISHIDATE ET AL.
As previously reported, both the macromolecular helicity
and the axial chirality can be induced in the poly‐MOM’s by
R)‐ or (S)‐1 in the solid state as well as in solution and fur-
ther memorized after complete removal of the chiral alcohol
(
2
5,26
1.
We then investigated if a similar macromolecular
helicity and axial chirality memory could be possible for
poly‐Ac‐c possessing the acetyloxy groups at the 2‐ and 2′‐
positions instead of the MOM groups.
After helicity induction in poly‐Ac‐c in a mixture of
MCH/(R)‐1 (90:10, v/v) at 25 °C for 2 h, the polymer was iso-
lated by precipitation into methanol to completely remove
1
(
R)‐1, which was confirmed by its H NMR spectrum (Figure
S14). The isolated poly‐Ac‐c dissolved in MCH at −10 °C
showed an almost identical CD spectrum to that observed
before isolation (Figure 1(ii) and (iii)). Therefore, it was
revealed that a preferred‐handed helicity induced in poly‐
Ac‐c was retained after complete removal of (R)‐1, as is the
FIGURE 4 VCD (top) and IR (bottom) spectra of the isolated poly‐
Ac‐c in MCH at −10 °C prepared by the treatment with (R)‐1 (red lines)
and (S)‐1 (blue lines)
2
5,26
case for the poly‐MOM’s.
The stability of the helicity
memory of the poly‐Ac‐c was investigated by following the
CD intensity changes in MCH at −10 and 25 °C with time;
its half‐life periods (t1/2) were estimated to be ~24 h and
twisted conformation of the biphenyl pendants is also
induced through noncovalent interactions with the chiral
alcohol 1, and the alkoxycarbonyl (ester) groups at the 4′‐
position appear to be arranged in a preferred‐handed helical
array along the helical polymer backbone, as observed for
3
4
10 min, respectively (Figure 3). By comparing the t1/2
values for poly‐MOM‐c and poly‐MOM‐a (Figure 3a), the
stability of the macromolecular helicity memory in MCH at
26,35
poly‐MOM‐b.
The calculated VCD and IR spectra for
−
10 °C decreased in the following order: poly‐MOM‐
a pair of enantiomeric model biphenyl compounds of Ac‐c
(M‐Ac‐c) with either a left‐ or right‐handed axially twisted
structure are roughly consistent with the observed ones for
the isolated poly‐Ac‐c after helicity induction by (R)‐ and
(S)‐1, respectively (Figure S16).
c > poly‐MOM‐a > poly‐Ac‐c, indicating that the acetyloxy
groups introduced at the 2‐ and 2′‐positions of the biphenyl
pendants destabilize the helicity memory compared to the
MOM groups, while the alkoxycarbonyl (ester) groups at the
4
′‐position tend to stabilize the helicity memory. In the solid
Considering the relationship between the signs of the
Cotton effects and the helical sense determined by high‐reso-
lution atomic force microscopy observations for the analo-
state, however, the poly‐Ac‐c maintained its helicity memory
for an extremely long time, at least for 1 month at 25 °C, with
no detectable decrease in the ICD intensity (Figure S15).
The poly‐Ac‐c’s after treatment with (R)‐1 and (S)‐1 and
subsequent isolation exhibited mirror image vibrational cir-
cular dichroism (VCD) signals in the C=O stretching band
region of the two acetyloxy (~1770 cm ) and n‐
tetradecyloxycarbonyl groups (~1720 cm ) (Figure 4).
These results indicated that a preferred‐handed axially
36,37
gous helical poly(phenylacetylene)s
together with the
present VCD results, the isolated poly‐Ac‐c with a helicity
memory induced by (R)‐1 showing a negative second Cotton
effect at around 370 nm seems to have a right‐handed helical
main‐chain structure with a left‐handed helical array of the
pendant biphenyl groups which axially twist into the left‐
handed direction.
−
1
−
1
FIGURE 3 Plots of the ICD intensity
t 0
(Δε2nd) changes (CD /CD ) of the isolated
poly‐Ac‐c (red circle), poly‐MOM‐a (green
circle) and poly‐MOM‐c (blue circle) at
−
10 °C (a) and those of the isolated poly‐
Ac‐c (red circle) at 25 °C (b) in MCH with
time. CD represents the initial ICD intensity
of the isolated polymers measured in MCH at
10 (a) and 25 °C (b) after helicity induction
in MCH/(R)‐1 (90:10, v/v) at 25 °C for 2 h
poly‐MOM‐a and poly‐Ac‐c) or 48 h (poly‐
MOM‐c). [polymer] = 1.0 mM
0
−
(

ISHIDATE ET AL.
127
FIGURE 5 Structures of racemates (2–13)
TABLE 1 Chromatographic resolution of racemates (2–13) on poly‐
Ac‐b‐ and poly‐MOM‐b‐based CSPs
The chiral recognition ability of poly‐Ac‐b with a macro-
molecular helicity memory was evaluated as a CSP for
HPLC, which was prepared as follows. Poly‐Ac‐b dissolved
in (R)‐1 was kept standing at 25 °C for 2 h to induce a pre-
ferred‐handed helical structure (Figure 1(v)), which was then
a
b
Poly‐Ac‐b
Poly‐MOM‐b
Racemates
k
1
α
k
1
α
28
2
3
4
5
6
7
8
9
10.3
6.50
1.24
1.07
1.51
3.17
0.32
0.62
1.67
4.95
6.63
15.8
1.17 (−)
ca.1 (+)
ca.1 (−)
ca.1 (+)
ca.1 (+)
1.0
6.80
4.50
1.21
1.01
1.41
1.95
0.18
0.27
1.09
—
1.08 (−)
1.15 (+)
1.18 (+)
1.28 (−)
1.31 (−)
1.0
coated on macroporous silica gel. After the poly‐Ac‐b‐
coated silica gel was packed into a stainless‐steel column
29
(
25 x 0.20 cm (i.d.)), a hexane/2‐propanol mixture (97/3, v/
v) was thoroughly passed through the column in order to
remove (R)‐1 completely. The results of the resolution of vari-
ous racemates 2–13 (Figure 5).are summarized in Table 1. For
comparison, the chromatographic resolution results using poly‐
MOM‐b as a coated‐type CSP composed of the biphenyl units
with the same 4′‐butoxycarbonyl substituent, but different 2‐
1.0
ca. 1 (+)
ca. 1 (−)
1.0
1.0
26
and 2′‐substituents, are also shown inTable 1. Figure 6 shows
the chromatograms for the resolution of 12 on the poly‐Ac‐b‐
based CSP. The enantiomers were eluted at the retention
times of t and t , showing complete separation. The reten-
10
11
12
13
1.18 (−)
1.25 (+)
1.35 (+)
1.22 (+)
—
—
—
1
2
—
—
tion factors, k [= (t –t )/t ] and k [= (t –t )/t ], where
1
1
0
0
2
2
0
0
the hold‐up time (t ) was 3.86 min, were 6.63 and 8.97,
a
0
Column: 25 x 0.20 (i.d.) cm; eluent: hexane—2‐propanol (97:3, v/v); Flow rate:
.2 mL/min; temperature: 10 °C. The sign of the Cotton effect at 254 nm of the
respectively, resulting in the separation factor α (= k /k )
0
2 1
first‐eluted enantiomer is shown in parentheses.
of 1.35.
b
Data cited from Ref. 26.
Poly‐Ac‐b could not separate racemates 3–6, including
the metal tris(acetylacetonato)s (4–6), which were
separated on poly‐MOM‐b, while benzoin (10) was well
resolved on poly‐Ac‐b, but not resolved on poly‐MOM‐b.
Analogous benzoin derivatives (11–13) were also effi-
ciently resolved on poly‐Ac‐b. The observed difference in
the chiral recognition abilities between the two CSPs may
be ascribed to the difference in the helical structures
between poly‐Ac‐b and poly‐MOM‐b, as already described
as a result of different substituents at the 2‐ and 2′‐posi-
tions of the biphenyl groups, which may further induce
the helical arrangement of the pendants in a different heli-
cal array. We noted that the chiral recognition ability of the
poly‐Ac‐b‐based CSP toward racemates 2 and 10 remained
unchanged even after 1 week, indicating that the helicity
and axial chirality memory of the poly‐Ac‐b was quite sta-
ble in the solid state.
FIGURE 6 HPLC chromatograms for the resolution of 12 on poly‐
Ac‐b‐based CSP prepared by treatment with (R)‐1. Eluent: hexane–2‐
propanol (97:3, v/v)

1
28
ISHIDATE ET AL.
7
8
9
. Francotte ER. Enantioselective chromatography as a powerful alter-
native for the preparation of drug enantiomers. J Chromatogr A.
4
| CONCLUSION
2
001;906(1–2):379‐397.
In conclusion, we prepared two novel poly
biphenylylacetylene) derivatives (poly‐Ac’s) bearing two
. Andersson S, Allenmark SG. Preparative chiral chromatographic
resolution of enantiomers in drug discovery. J Biochem Biophys
Methods. 2002;54(1–3):11‐23.
(
acetyloxy groups at the 2‐ and 2′‐positions and an
alkoxycarbonyl group at the 4′‐position of the biphenyl pen-
dants. Both the macromolecular helicity and axial chirality of
the biphenyl pendants were induced in the poly‐Ac’s through
noncovalent weak interactions with a chiral alcohol and were
almost entirely memorized after complete removal of the chi-
ral alcohol, although the memory of the poly‐Ac’s in solution
was less stable than those of the poly‐MOM’s composed of
the biphenyl units bearing two MOM groups at the 2‐ and
. Yamamoto C, Okamoto Y. Optically active polymers for chiral sep-
aration. Bull Chem Soc Jpn. 2004;77(2):227‐257.
1
1
1
0. Okamoto Y, Ikai T. Chiral HPLC for efficient resolution of enantio-
mers. Chem Soc Rev. 2008;37(12):2593‐2608.
1. Ward TJ, Ward KD. Chiral separations: A review of current topics
and trends. Anal Chem. 2012;84(2):626‐635.
2. Shen J, Okamoto Y. Efficient separation of enantiomers using ste-
reoregular chiral polymers. Chem Rev. 2016;116(3):1094‐1138.
2′‐positions. Poly‐Ac with a macromolecular helicity mem-
ory showed better chiral recognition ability toward several
racemates including the benzoin derivatives than the corre-
sponding poly‐MOM when used as a CSP for HPLC. The
difference in the bulkiness of the substituents introduced at
the 2‐ and 2′‐positions of the biphenyl pendants has a signif-
icant influence on the induced helical structures, resulting in
the difference in their chiral recognition abilities. We believe
that these findings will contribute to the development of more
practically useful poly(biphenylylacetylene)‐based CSPs
showing a high chiral recognition ability along with a switch-
13. Okamoto Y, Suzuki K, Ohta K, Hatada K, Yuki H. Optically active
poly(triphenylmethyl methacrylate) with one‐handed helical confor-
mation. J Am Chem Soc. 1979;101(16):4763‐4765.
1
1
1
4. Yuki H, Okamoto Y, Okamoto I. Resolution of racemic compounds
by optically active poly(triphenylmethyl methacrylate). J Am Chem
Soc. 1980;102(20):6356‐6358.
5. Okamoto Y, Honda S, Okamoto I, et al. Novel packing material for
optical resolution: (+)‐poly(triphenylmethyl methacrylate) coated on
macroporous silica gel. J Am Chem Soc. 1981;103(23):6971‐6973.
6. Okamoto Y, Mohri H, Hatada K. Chromatographic optical resolution
by optically active poly(diphenyl‐2‐pyridylmethyl methacrylate)
with a highly one‐handed helical structure. Polym J. 1989;21(5):
25
able elution order toward diverse racemates.
4
39‐445.
ACKNOWLEDGEMENT
17. Okamoto Y. Precision synthesis, structure and function of helical
polymers. Proc. Jpn. Acad., Ser. B. 2015;91(6):246‐261.
We thank Professor S. Akine (Kanazawa University) for help
in X‐ray crystallographic analysis. This work was supported
in part by JSPS KAKENHI (Grant‐in‐Aid for Scientific
Research (B), no. 16H04154 (K.M.) and Grant‐in‐Aid for
Scientific Research (S), no. 25220804 (E.Y.).
1
8. Okamoto Y, Yashima E. Polysaccharide derivatives for chromato-
graphic separation of enantiomers. Angew Chem Int Ed.
1
998;37(8):1021‐1043.
1
9. Yashima E. Polysaccharide‐based chiral stationary phases for high‐
performance liquid chromatographic enantioseparation.
J
Chromatogr A. 2001;906(1–2):105‐125.
REFERENCES
20. Ikai T, Okamoto Y. Structure control of polysaccharide derivatives
for efficient separation of enantiomers by chromatography. Chem
Rev. 2009;109(11):6077‐6101.
1
. Ariëns EJ. Stereochemistry: A source of problems in medicinal
chemistry. Med Res Rev. 1986;6(4):451‐466.
2
1. Shen J, Ikai T, Okamoto Y. Synthesis and application of
immobilized polysaccharide‐based chiral stationary phases for
enantioseparation by high‐performance liquid chromatography. J
Chromatogr A. 2014;1363:51‐61.
2
. Kasprzyk‐Hordern B. Pharmacologically active compounds in the
environment and their chirality. Chem Soc Rev. 2010;39(11):4466‐
4
503.
2
2
2. Nakano T. Optically active synthetic polymers as chiral stationary
phases in HPLC. J Chromatogr A. 2001;906(1–2):205‐225.
3
4
5
6
. Brooks WH, Guida WC, Daniel KG. The significance of chirality in
drug design and development. Curr Top Med Chem.
2
011;11(7):760‐770.
3. Yashima E, Maeda K, Iida H, Furusho Y, Nagai K. Helical polymers:
Synthesis, structures, and functions. Chem Rev. 2009;109(11):
. Zhou Q, Yu L‐S, Zeng S. Stereoselectivity of chiral drug transport:
A focus on enantiomer–transporter interaction. Drug Metab Rev.
6
102‐6211.
2
014;46(3):283‐290.
24. Yashima E, Ousaka N, Taura D, Shimomura K, Ikai T, Maeda K.
Supramolecular helical systems: Helical assemblies of small mole-
cules, foldamers, and polymers with chiral amplification and their
functions. Chem Rev. 2016;116(22):13752‐13990.
. Pirkle WH, Pochapsky TC. Considerations of chiral recognition rel-
evant to the liquid chromatography separation of enantiomers. Chem
Rev. 1989;89(2):347‐362.
2
5. Shimomura K, Ikai T, Kanoh S, Yashima E, Maeda K. Switchable
enantioseparation based on macromolecular memory of a helical
polyacetylene in the solid state. Nat Chem. 2014;6(5):429‐434.
. Taylor DR, Maher K. Chiral separations by high‐performance liquid
chromatography. J Chromatogr Sci. 1992;30(3):67‐85.

ISHIDATE ET AL.
129
2
6. Ishidate R, Shimomura K, Ikai T, Kanoh S, Maeda K. Macromolec-
ular helicity induction and memory in a poly(biphenylylacetylene)
bearing an ester group and its application to a chiral stationary phase
for high‐performance liquid chromatography. Chem. Lett.
34. The stability of the helicity memory of poly‐Ac‐c was highly depen-
dent on the solvents; once dissolved in THF at –10°C, the CD
quickly disappeared within a few minutes.
3
5. Shi ZC, Murayama Y, Kaneko T, Teraguchi M, Aoki T. Helix‐sense‐
selective polymerization of 3,5‐bis(hydroxymethyl)phenylacetylene
connected with a rigid and ‐conjugated substituent. Chem Lett.
2013;42(9):1087‐1089.
2
015;44(7):946‐948.
2
7. Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 09, Revision
E.01. Wallingford CT: Gaussian; 2009.
2
8. Okamoto Y, Aburatani R, Hatada K. Chromatographic chiral resolu-
tion : XIV. Cellulose tribenzoate derivatives as chiral stationary
phases for high‐performance liquid chromatography. J Chromatogr
A. 1987;389:95‐102.
36. Sakurai SI, Okoshi K, Kumaki J, Yashima E. Two‐dimensional hier-
archical self‐assembly of one‐handed helical polymers on graphite.
Angew Chem Int Ed. 2006;45(8):1245‐1248.
3
7. Sakurai SI, Okoshi K, Kumaki J, Yashima E. Two‐dimensional sur-
face chirality control by solvent‐induced helicity inversion of a
helical polyacetylene on graphite. J Am Chem Soc. 2006;128(17):
5650‐5651.
2
9. Okamoto Y, Kawashima M, Hatada K. Chromatographic resolution:
XI. Controlled chiral recognition of cellulose triphenylcarbamate
derivatives supported on silica gel. J Chromatogr A. 1986;363(2):
1
73‐186.
3
3
3
0. Koller H, Rimböck K‐H, Mannschreck A. High‐pressure liquid
chromatography on triacetylcellulose: Characterization of a sorbent
for the separation of enantiomers. J Chromatogr A. 1983;282:89‐94.
SUPPORTING INFORMATION
Additional Supporting Information may be found online in
the supporting information tab for this article.
1. Simionescu CI, Percec V, Dumitrescu S. Polymerization of acetyle-
nic derivatives. XXX. Isomers of polyphenylacetylene. J. Polym.
Sci. Pol. Chem Ed. 1977;15(10):2497‐2509.
How to cite this article: Ishidate R, Ikai T, Kanoh S,
Yashima E, Maeda K. Chromatographic
enantioseparation by poly(biphenylylacetylene)
derivatives with memory of both axial chirality and
macromolecular helicity. Chirality. 2017;29:120–129.
https://doi.org/10.1002/chir.22687
2. Kishimoto Y, Eckerle P, Miyatake T, Ikariya T, Noyori R. Living
polymerization of phenylacetylenes initiated by Rh(C≡CC
2,5‐norbornadiene)[P(C . J Am Chem Soc. 1994;116(26):
2131‐12132.
6 5
H )
(
6 5 3 2
H ) ]
1
3
3. Green MM, Garetz BA, Munoz B, Chang H, Hoke S, Cooks RG.
Majority rules in the copolymerization of mirror image isomers. J
Am Chem Soc. 1995;117(14):4181‐4182.