Macromolecular helicity inversion of an optically active helical poly(phenylacetylene) by chemical modification of the side groups

Article abstract of DOI:10.1039/b701281k

An optically active helical poly(phenylacetylene) was synthesized by the copolymerization of phenylacetylenes bearing optically active hydroxy or ester groups obtained by the kinetic resolution of a racemic phenylacetylene with lipase; the helix-sense was

Full text of DOI:10.1039/b701281k

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Macromolecular helicity inversion of an optically active helical
poly(phenylacetylene) by chemical modification of the side groups{{
Shinzo Kobayashi, Kazuhide Morino and Eiji Yashima*
Received (in Cambridge, UK) 26th January 2007, Accepted 13th February 2007
First published as an Advance Article on the web 8th March 2007
DOI: 10.1039/b701281k
optically active helical polyacetylenes.6 We now report a unique
An optically active helical poly(phenylacetylene) was synthe-
and versatile method to synthesize an optically active, helical
poly(phenylacetylene) starting from an optically inactive, racemic
phenylacetylene bearing a secondary alcohol pendant (rac-1)
assisted by the kinetic resolution of the monomer with lipase in
the presence of isopropenyl acetate as an acetylating agent,
followed by the copolymerization of the resulting optically active
monomers bearing an alcohol ((S)-1) and ester group ((R)-2) as the
pendants (Scheme 1). In addition, the preferred helical sense of the
copolymer can be further inverted by the reaction of the pendant
hydroxy groups with bulky achiral isocyanates and an acid
chloride.
sized by the copolymerization of phenylacetylenes bearing
optically active hydroxy or ester groups obtained by the kinetic
resolution of a racemic phenylacetylene with lipase; the helix-
sense was inverted from one helix to another by the further
chemical modification of the hydroxy groups with achiral bulky
isocyanates or an acid chloride.
The enzyme-catalyzed reaction is one of the most useful and
powerful methods for obtaining optically active compounds
because enzymes possess a high catalytic activity and excellent
stereoselectivity for specific substrates, thus producing enantio-
merically pure compounds.1 For examples, lipases, one of the
esterases, can be used as biocatalysts in organic media and
kinetically resolve racemic alcohols, especially secondary alcohols,
into optically active alcohols and esters by enantioselective
transesterification with acetylating agents such as isopropenyl
acetate.2 To date, the kinetic resolution of racemic alcohols with
lipases has been extensively studied and has become one of the
standard techniques to obtain optically pure alcohols and esters.
Recently, the chemoenzymatic kinetic resolution with lipase was
also applied to the polymerization of racemic lactones to yield
optically active polyesters.3
The kinetic resolution of rac-1 with lipase was performed in
tetrahydrofuran (THF) in the presence of isopropenyl acetate and
7
˚
molecular sieves (4 A) (MS 4A) at 40 uC (Scheme 1). Novozyme
435 (Novozymes Corp.), a commercially available, macroporous
acrylic resin on which lipase B from Candida antarctica was
immobilized, was used as the enzymatic catalyst. The conversion
of rac-1 to (R)-2, thus producing (S)-1 as the unreacted 1, was
monitored by measuring the 1H NMR spectra of the mixture of 1
and (R)-2. After 5 h, approximately half of the rac-1 had been
converted to (R)-2 (Fig. S1), and the reaction was terminated by
filtration of Novozyme 435 from the reaction mixtures. The
obtained enantiomeric excess (ee) values of (S)-1 and (R)-2 were
determined by HPLC using chiral columns and were greater than
99% (Fig. S2).8 These results indicate that the kinetic resolution of
rac-1 proceeded ideally.
On the other hand, significant attention has recently been paid
to developing synthetic helical polymers with a controlled helix-
sense not only to mimic biological helices, such as DNA and
proteins, but also for their potential applications in functional
chiral materials, such as enantioselective catalysts, chirality sensors,
and liquid crystals.4 Polyacetylenes are some of the typical
dynamic helical polymers composed of interconvertible right-
and left-handed helical conformations separated by the rarely
occurring helical reversals. Therefore, the introduction of optically
active substituents into the pendant groups forces the main chain
to form a predominantly one-handed helical conformation,
resulting in a characteristic induced circular dichroism (ICD) in
the polyene backbone regions.5 Accordingly, the synthesis of
optically active monomers and subsequent polymerization with
transition metal catalysts are essential for the preparation of
Department of Molecular Design and Engineering, Graduate School of
Engineering, Nagoya University, Chikusa-ku, Nagoya, 464-8603, Japan.
E-mail: yashima@apchem.nagoya-u.ac.jp; Fax: +81-52-789-3185;
Tel: +81-52-789-4495
{ Electronic supplementary information (ESI) available: Synthetic details,
1H NMR and chiral HPLC measurement results of kinetically resolved
monomers, 1H NMR spectrum of poly((S)-1-co-(R)-2), and CD spectra of
homopolymers of (S)-1, (R)-2, and (S)-3. See DOI: 10.1039/b701281k
{ The HTML version of this article has been enhanced with colour
images.
Scheme 1
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formation of an excess of the preferred helical sense. The CD
intensity of the second Cotton effect (De2nd) monotonically
increased with the decrease in temperature (Fig. 1, inset).
Poly((S)-1-co-(R)-2) possesses reactive hydroxy groups at the
pendants. We anticipated that the conversion of the hydroxy
groups to more bulky carbamoyl or ester groups than the acetyl
groups through the reaction with isocyanates or acid chlorides
might enhance the helical sense excess and further invert the helical
sense of the poly((S)-1-co-(R)-2). The polymer reactions of the
hydroxy groups of poly((S)-1-co-(R)-2) with naphthyl and phenyl
isocyanates and benzoyl chloride produced the copolymers,
poly((S)-3-co-(R)-2), poly((S)-4-co-(R)-2), and poly((S)-5-co-(R)-
2), respectively (Scheme 1).7 The 1H NMR spectra of the modified
copolymers showed that the hydroxy groups were completely
converted into the corresponding carbamoyl and ester groups.
Fig. 2A shows the CD spectra of those modified copolymers
together with that of poly((S)-1-co-(R)-2) for comparison in THF
at 280 uC. As expected, the ICD pattern of the copolymers after
modification was completely inverted, thus showing mirror image
ICDs to that of poly((S)-1-co-(R)-2), indicating that the helix-sense
of poly((S)-1-co-(R)-2) was opposite to those of poly((S)-3-co-(R)-
2)–poly((S)-5-co-(R)-2).10 Poly((S)-3-co-(R)-2) bearing the most
bulky naphthylcarbamoyl groups exhibited the most intense ICD.
Although the inversion of helicity has been reported for several
helical polymers in response to various external achiral and chiral
stimuli, such as temperature, solvent, and chiral additives,11 to the
best of our knowledge, this is the first example of helicity inversion
by chemical modification using achiral compounds.12 The ICD
intensities of poly((S)-3-co-(R)-2)–poly((S)-5-co-(R)-2) also
increased when temperature was lowered (Fig. 2B), due to the
reduction of the population of the helical reversals between the
right- and left-handed helical segments of the copolymer
chains.4,5b,13 All the copolymers prepared in this study, however,
showed a rather weak ICD when compared to those of the
previously prepared helical poly(phenylacetylene)s.4e,5a,b This
means that the helical sense excesses of the copolymers may be
imperfect even at low temperature. The introduction of more
bulky pendant groups may further amplify the helical sense excess.
In conclusion, we succeeded in the synthesis of an optically
active, helical poly(phenylacetylene) (poly((S)-1-co-(R)-2)) by the
enzymatic enantioselective transesterification of a racemic pheny-
lacetylene bearing a secondary alcohol moiety (rac-1) followed by
Fig. 1 CD spectra of poly((S)-1-co-(R)-2) in THF at various tempera-
tures. Absorption spectrum of poly((S)-1-co-(R)-2) at ca. 25 uC is also
shown. Inset shows the temperature-dependent CD intensity (2nd Cotton
effect) changes of poly((S)-1-co-(R)-2) in THF.
Next we copolymerized (S)-1 and (R)-2 obtained by the kinetic
resolution of rac-1 without further purification and isolation with
Rh(cod)2BF4 (cod: cyclooctadiene) as a catalyst in water–methanol
(95 : 5, v/v) in the presence of diethylamine at 30 uC.7 The
copolymerization rapidly proceeded, and the polymer (poly((S)-1-
co-(R)-2)) precipitated within a few minutes. After 26 h, poly((S)-1-
co-(R)-2), soluble in DMSO, DMF, pyridine, CHCl3, and THF,
was obtained in an 85% yield. The molecular weight (Mn) and its
distribution (Mw/Mn) estimated by size exclusion chromatography
(SEC) were 8.9 6 104 and 2.0 (PEO-PEG standards), respectively.
The stereoregularity of poly((S)-1-co-(R)-2) was investigated using
1H NMR spectroscopy. The 1H NMR spectrum of poly((S)-1-co-
(R)-2) in DMSO-d6 showed a rather sharp singlet centered at
5.72 ppm due to the main chain’s protons, indicating that poly((S)-
1-co-(R)-2) possesses a highly cis-transoidal stereoregular structure
(Fig. S3). The composition of the (S)-1 and (R)-2 units in the
1
copolymer was determined to be 53 : 47 based on its H NMR
spectrum and elemental analysis.9
Fig. 1 shows the CD and absorption spectra of poly((S)-1-co-
(R)-2) in THF at various temperatures. The copolymer exhibited a
split-type ICD in the long absorption region of the conjugated
polymer backbone; the ICD was similar in pattern to those of the
previously reported optically active poly(phenylacetylene)s,5a,b
indicating that poly((S)-1-co-(R)-2) has a predominantly one-
handed helical conformation, even though the starting monomer
was racemic. A small chiral bias in the pendants generated by the
enzyme-assisted resolution was transformed into a main chain
conformational change with a large amplification, resulting in the
Fig. 2 (A) CD spectra of poly((S)-1-co-(R)-2), poly((S)-3-co-(R)-2), poly((S)-4-co-(R)-2), and poly((S)-5-co-(R)-2) in THF at 280 uC. (B) Temperature-
dependent CD intensity (2nd Cotton effect) changes of poly((S)-1-co-(R)-2), poly((S)-3-co-(R)-2), poly((S)-4-co-(R)-2), and poly((S)-5-co-(R)-2) in THF.
2352 | Chem. Commun., 2007, 2351–2353
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6 Helical poly(phenylacetylene)s with a controlled helicity can also be
prepared by the helix-sense-selective polymerization of an achiral
phenylacetylene or based on the noncovalent helicity induction and
chiral memory concept. (a) T. Aoki, T. Kaneko, N. Maruyama,
A. Sumi, M. Takahashi, T. Sato and M. Teraguchi, J. Am. Chem. Soc.,
2003, 125, 6346; (b) E. Yashima, K. Maeda and Y. Okamoto, Nature,
1999, 399, 449; (c) K. Maeda, K. Morino, Y. Okamoto, T. Sato and
E. Yashima, J. Am. Chem. Soc., 2004, 126, 4329; (d) H. Onouchi,
T. Miyagawa, A. Furuko, K. Maeda and E. Yashima, J. Am. Chem.
Soc., 2005, 127, 2960; (e) T. Miyagawa, A. Furuko, K. Maeda,
H. Katagiri, Y. Furusho and E. Yashima, J. Am. Chem. Soc., 2005, 127,
5018; (f) T. Hasegawa, K. Maeda, H. Ishiguro and E. Yashima, Polym.
J., 2006, 38, 912.
7 For more details, see electronic supplementary information (ESI){.
8 According to Kazlauskas’ rule, the R-secondary alcohols are preferen-
tially esterified during the lipase-catalyzed kinetic resolution of racemic
secondary alcohols. Therefore, the absolute configurations of the
optically active 1 and 2 obtained by the kinetic resolution of rac-1
with lipase were tentatively assigned as S and R, respectively. For
Kazlauskas’ rule, see: M. Cygler, P. Grochulski, R. J. Kazlauskas,
J. D. Schrag, F. Bouthillier, B. Rubin, A. N. Serreqi and A. K. Gupta,
J. Am. Chem. Soc., 1994, 116, 3180.
9 Copolymerization results of (S)-1 and (R)-2 at varying monomer feed
ratios ([(S)-1] : [(R)-2] = 1 : 9, 3 : 7, 5 : 5, 7 : 3, and 9 : 1) showed that the
polymerizability of (S)-1 is almost identical to that of (R)-2 and that the
monomer distributions in the copolymer, poly((S)-1-co-(R)-2), are
mostly random, independent of the level of monomer conversions.
10 The CD and absorption spectra of all the copolymers in THF did not
change after the samples had been allowed to stand at room temperature
for 1 day.
11 For recent reviews, see ref 4 and (a) M. M. Green, K.-S. Cheon,
S.-Y. Yang, J.-W. Park, S. Swansburg and W. Liu, Acc. Chem. Res.,
2001, 34, 672; (b) J. W. Y. Lam and B. Z. Tang, Acc. Chem. Res., 2005,
38, 745. For recent examples, see: (c) K. Tang, M. M. Green,
K. S. Cheon, J. V. Selinger and B. A. Garetz, J. Am. Chem. Soc., 2003,
125, 7313; (d) K. Morino, K. Maeda and E. Yashima, Macromolecules,
2003, 36, 1480; (e) K. K. L. Cheuk, J. W. Y. Lam, L. M. Lai, Y. Dong
and B. Z. Tang, Macromolecules, 2003, 36, 9752; (f) H. Ohira,
M. Kunitake, M. Fujiki, M. Naito and A. Saxena, Chem. Mater., 2004,
16, 3919; (g) H. Zhao, F. Sanda and T. Masuda, Macromol. Chem.
Phys., 2005, 206, 1653; (h) S. Sakurai, K. Okoshi, J. Kumaki and
E. Yashima, J. Am. Chem. Soc., 2006, 128, 5650; (i) K. Maeda,
H. Mochizuki, M. Watanabe and E. Yashima, J. Am. Chem. Soc., 2006,
128, 7639.
12 The significant difference between the CD spectrum of the sum of the
homopolymers of poly((S)-1) and poly((R)-2) (1 : 2 = 53 : 47, mol/mol)
and the CD spectrum of the copolymer (poly((S)-1-co-(R)-2)) (1 : 2 =
53 : 47, mol/mol) (Fig. S4A) indicates that the poly((S)-1-co-(R)-2)) is
not composed of the blocks of poly((S)-1) and poly((R)-2). A similar
great difference between the CD spectrum of poly((S)-3-co-(R)-2) and
the sum of the CD spectra of the corresponding homopolymers,
poly((S)-3) and poly((R)-2) (Fig. S4B), also supports the random
monomer distributions in the poly((S)-3-co-(R)-2). These results clearly
revealed the inversion of the helix-sense of the poly((S)-1-co-(R)-2) main-
chain that takes place after the chemical modification of the hydroxy
groups with bulky substituents.
13 The different temperature-dependent ICD intensity changes observed
for the copolymers (Fig. 2B) may be determined by cooperative
interactions with neighboring monomer units;5b the absolute De2nd
values tended to increase more steeply with increasing the bulkiness of
the substituents introduced when temperature was lowered.
14 For DKR of secondary alcohols, see: (a) N. Kim, S.-B. Ko, M. S. Kwon,
M.-J. Kim and J. Park, Org. Lett., 2005, 7, 4523; (b) B. Martin-Matute,
M. Edin, K. Boga´r, F. B. Kaynak and J.-E. Ba¨ckvall, J. Am. Chem.
Soc., 2005, 127, 8817. For optically pure oligo- and polyester synthesis
using DKR, see: (c) B. A. C. van As, J. van Buijtenen, A. Heise,
Q. B. Broxterman, G. K. M. Verzijl, A. R. A. Palmans and E. W. Meijer,
J. Am. Chem. Soc., 2005, 127, 9964; (d) J. van Buijtenen, B. A. C. van
As, J. Meuldijk, A. R. A. Palmans, J. A. J. M. Vekemans, L. A. Hulshof
and E. W. Meijer, Chem. Commun., 2006, 3169.
the subsequent copolymerization of the obtained optically active
phenylacetylenes in one-pot without further isolation and
purification using a rhodium catalyst. The helix-sense of the
resulting copolymer was inverted from one helix to another by
further modification of the pendant hydroxy groups with achiral
bulky isocyanates and an acid chloride. We believe that this
concept will become a novel methodology for the construction of
helical polymers with a controlled helix-sense based on racemic
monomers. In addition, the dynamic kinetic resolution (DKR) of
secondary alcohols by the enzyme-catalyzed enantioselective
transesterification coupled with the racemization of secondary
alcohols using various transition metal catalysts has been reported.
Based on this process, enantiomerically pure esters can be
quantitatively synthesized by the DKR of racemic secondary
alcohols.14 Therefore, the combination of our concept developed in
this study and DKR may lead to producing optically active, helical
homopolymers with a perfect helical sense excess. This work is
now in progress.
This work was partially supported by a Grant-in-Aid for
Scientific Research from Japan Society for the Promotion of
Science and the Ministry of Education, Culture, Sports, Science,
and Technology, Japan and the 21st Century COE Program
‘‘Nature-Guided Materials Processing’’ of the Ministry of
Education, Culture, Sports, Science, and Technology.
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Chem. Commun., 2007, 2351–2353 | 2353