Metastable liquid crystal as time-responsive reaction medium: Aging-induced dual enantioselective control

Article abstract of DOI:10.1021/ja4016556

A metastable liquid crystal (LC) was found to serve as a time-responsive reaction medium, in which the enantioselectivity of a photoreaction was perfectly switched through isothermal annealing of the reaction system. When the LC salt of an enantiopure amine with a photoreactive acid was irradiated with UV/vis light, in situ photodimerization of the acid moiety proceeded smoothly to afford the (+)-isomer of the photodimer with high enantioselectivity (+86% ee). In contrast, photoirradiation of an aged sample, isothermally annealed for 20 h, gave predominantly the (-)-isomer (-94% ee). Systematic studies revealed that the reversal in selectivity originated from metastability of the LC system, which gradually transformed into a crystalline phase during annealing. This finding demonstrates the potential use of metastable aggregates as dynamic time-responsive media, reminiscent of biological systems.

Full text of DOI:10.1021/ja4016556

Communication
pubs.acs.org/JACS
Metastable Liquid Crystal as Time-Responsive Reaction Medium:
Aging-Induced Dual Enantioselective Control
Yasuhiro Ishida,*,†,‡ Yuki Matsuoka,‡ Yukiko Kai,§ Kuniyo Yamada,† Kenta Nakagawa,⊥ Toru Asahi,⊥
and Kazuhiko Saigo#
†RIKEN Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
‡PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
§Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo
113-8656, Japan
⊥Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 2-2
Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
#School of Environmental Science and Engineering, Kochi University of Technology, Miyanokuchi, Tosayamada-cho, Kami, Kochi
782-8502, Japan
S
* Supporting Information
The phenomenon reported here was unexpectedly found
ABSTRACT: A metastable liquid crystal (LC) was found
to serve as a time-responsive reaction medium, in which
the enantioselectivity of a photoreaction was perfectly
switched through isothermal annealing of the reaction
system. When the LC salt of an enantiopure amine with a
photoreactive acid was irradiated with UV/vis light, in situ
photodimerization of the acid moiety proceeded smoothly
to afford the (+)-isomer of the photodimer with high
enantioselectivity (+86% ee). In contrast, photoirradiation
of an aged sample, isothermally annealed for 20 h, gave
predominantly the (−)-isomer (−94% ee). Systematic
studies revealed that the reversal in selectivity originated
from metastability of the LC system, which gradually
transformed into a crystalline phase during annealing. This
finding demonstrates the potential use of metastable
aggregates as dynamic time-responsive media, reminiscent
of biological systems.
through our ongoing studies on liquid crystalline (LC) salts,
consisting of an enantiopure amphiphilic amine (e.g., 1, Scheme
1) and a photoreactive acid (e.g., 2), as chiral reaction media.3
Scheme 1. In Situ Photodimerization of Acid 2 in a Chiral
Liquid-Crystalline Reaction Environment Based on Amine 1
n asymmetric chemical transformations, a well-designed chiral
Isource usually gives one enantiomer as the major product.
However, there have been reported several notable exceptions,1
in which a single chiral source can provide both enantiomers
through the switching of selectivity depending on reaction
conditions, such as reaction time,2a,d temperature,2b,e solvent,2f
presence of an additive,2c or catalyst preparation method.2g
These phenomena, termed “reversal of enantioselectivity” or
“dual enantioselective control”, have attracted a considerable
degree of attention recently, owing to their scientific curiosity
and their practical utility.1 Here we report an unprecedented type
of enantioselectivity reversal. Unlike earlier examples,1,2 our
report describes a kinetically controlled system in which two
samples treated under identical conditions, except for the aging
time before the reaction, showed stereochemical outcomes that
were almost perfect opposites of one another. A thorough
investigation of this phenomenon revealed unique aspects of
nonequilibrated supramolecular aggregates as time-dependent
dynamic systems reminiscent of biological systems.
Such LC salts are expected to serve as a new type of reaction
environment that provides structural order while permitting
molecular mobility.4,5 As a model reaction to demonstrate the
utility of chiral LC reaction media, we have studied the [4+4]
photocyclodimerization of 2-anthracenecarboxylic acid (2).
Although the photodimerization of anthracene derivatives is
Received: February 14, 2013
© XXXX American Chemical Society
A
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Journal of the American Chemical Society
Communication
one of the most well-explored photoreactions,6 its stereocontrol
still remains an attractive challenge.7 Because of the dissymmetric
shape of 2, its dimerization can provide six isomers through
regioisomerism [head-to-head (HH) or head-to-tail (HT),
diastereoisomerism (syn or anti), and stereoisomerism (+ or
correction ability that is characteristic of supramolecular
aggregates. We therefore used a well-annealed sample for the
same in situ photodimerization. Salt 1·2, in its Sm2 phase, was
kept at 45 °C for 20 h before being photoirradiated for 1 h. From
the well-annealed salt, the antiHH dimer was again obtained as the
major product. To our great surprise, however, the stereo-
chemical outcome was almost the exact opposite to that of our
original experiment, and the antiHH dimer was obtained in −94%
ee (Figure 1, procedure II).
In an attempt to explain this phenomenon, we systematically
examined the effects of various reaction conditions, such as the
annealing time, the photoirradiation time, and the temperature
(Figure 2 and Table S1). When the annealing time at 45 °C was
−)]. The resulting dimers are denoted synHH, (+)-antiHH
,
(−)-antiHH, (+)-synHT, (−)-synHT, and antiHT (Scheme 1,
bottom). As a chiral source to control the stereochemistry of
this reaction, we developed an enantiopure amphiphilic amino
alcohol (1), which has a high propensity to form LC salts with
various carboxylic acids, for example, 2.3c,d In fact, the salt of 1
with 2 (1·2) exhibits two types of smectic phases with bilayer-like
structures (Sm1 and Sm2), as confirmed by differential scanning
calorimetry (DSC; Figure S8) and by X-ray diffraction analysis
(XRD; Figure S9). Considering the XRD patterns at a wide-angle
region, the Sm1 phase is considered to be smectic A phase, while
the Sm2 phase is likely to be a higher order smectic phase, such as
smectic B, smectic F, or smectic I phases.8
Owing to the benefits of LCs as reaction media, as described
above, irradiation of the LC salt 1·2 with UV/vis light gave
photodimers of acid 2 in satisfactory yields and excellent
selectivities. In a typical procedure, 1·2 was melted at 115 °C,
slowly cooled to 45 °C at 0.33 °C min−1 to form the Sm2 phase,
and then irradiated with UV/vis light (>380 nm) at 45 °C for 1 h
to afford the antiHH dimer selectively in +86% ee (Figure 1,
procedure I).3c,d To improve the selectivity further, we
hypothesized that long-time isothermal annealing before photo-
irradiation might have a favorable effect as a result of the error-
Figure 2. Effect of annealing time at 45 °C on the regio-, diastereo-, and
enantioselectivity of the photodimerization of 2. (a) Experimental
procedure. (b,c) Plots of the product ratio (synHH, filled square; antiHH
,
filled circle; synHT, open square; antiHT, open circle) (b) and the ee of the
antiHH dimer (c) versus the annealing time at 45 °C. The enantiomers
that showed positive and negative CD signals at 300 nm are denoted by
+ and −, respectively.
changed from 0 to 20 h, the system retained an excellent
regioselectivity (HH versus HT) and diastereoselectivity (syn
versus anti), giving the antiHH dimer as the main product (Figure
2a). However, the enantiomeric excess (ee) of the main product
(the antiHH dimer) changed dramatically on changing the
annealing time (Figure 2b). In the initial stage of annealing (0−1
h), the change in enantioselectivity was sluggish (+86 and +81%
ee). Annealing for 5 h caused an abrupt drop in the ee for the
antiHH dimer to +12%, and further annealing for 10 h caused an
inversion in the sense of the enantiomeric induction, giving the
antiHH dimer in −44% ee. When the annealing time was
prolonged to 20 h, an almost perfect reversal in enantioselectivity
was achieved, and the antiHH dimer was obtained in −94% ee.
Therefore, the selectivity reversal is a relatively slow event that
takes about 20 h to reach its completion.
In the above photoreaction, the irradiation was discontinued
when the conversion of 2 reached 23−34% to permit fair
comparison of the selectivities in the early stages of the process
(Table S1, entries 3−7). In general, the conversion of a starting
material can affect the enantioselectivity of a reaction, particularly
when the products can participate in reaction pathways.1b
However, even when the photoirradiation time was prolonged in
our reaction system, the yield of the main product [the (+)- or
Figure 1. (a) Reversal of enantioselectivity in the asymmetric
photodimerization of 2. Salt 1·2 was melted at 115 °C, cooled to 45
°C at a rate of 0.33 °C min−1, annealed at 45 °C for <1 min (procedure I)
or for 20 h (procedure II), irradiated with UV/vis light (λ > 380 nm),
and methylated with Me3SiCHN2. (b) Chiral HPLC (Daicel Chiralpak
IB) traces for the enantiomers of the antiHH dimer obtained by the in situ
photoreaction of salt 1·2. The enantiomers that showed positive and
negative CD signals at 300 nm are denoted by + and −, respectively.
B
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Journal of the American Chemical Society
Communication
Figure 3. Phase transition of salt 1·2. (a) Proposed phase transition diagram on cooling from an isotropic melt (i−v) and subsequent isothermal
annealing (v−vi). (b) DSC traces for the first cooling (top) and the second heating (bottom) processes (scanning rate, 5.0 °C min−1). (c) XRD patterns
during cooling from 105 to 35 °C at a rate of 1.0 °C min−1. (d−f) Time-dependent changes in the spectroscopic profiles. Salt 1·2 was melted at 115 °C,
cooled to 45 °C at a rate of 0.33 °C min−1, kept at 45 °C for the indicated period, and subjected to XRD (d), UV/vis absorption (e), or CD
measurements (f). The insets show the time-dependent changes in XRD intensity (2θ = 5.4°), UV absorption (395 nm), and the CD intensity (390 nm),
respectively.
(−)-antiHH dimer] was simply improved up to 84 and 89%
without losing selectivity to any serious extent (Table S1, entry 3
versus entries 8 and 9; entry 7 versus entries 10 and 11).
We also investigated the effects of the annealing temperature.
When salt 1·2 in its Sm2 phase was annealed at 35 °C for 20 h
before photoirradiation, the same reversal in enantioselectivity
occurred (Table S1, entries 1 and 2) as in the case of annealing at
45 °C. In sharp contrast, when the salt was annealed at 80 or 110
°C, at which temperatures the salt forms the Sm1 and isotropic
(Iso) phases, respectively, the reaction system did not show any
sign of a reversal in enantioselectivity (Table S1, entries 12−15).
From these results, we concluded that the reversal in
enantioselectivity is a phenomenon that is specific to the Sm2
phase.
On the basis of these observations, we hypothesized that the
origin of the selectivity reversal is the metastability of the Sm2
phase.9 In the hypothesized phase diagram, a phase more stable
than the Sm2 phase exists (Figure 3a, red line) which was not
detected in our DSC (Figure 3b) or variable-temperature XRD
studies (Figure 3c) for salt 1·2, probably because the Sm2 phase
has a longer lifetime than the time scale over which these
measurements were performed. During cooling from the Sm1
phase (Figure 3a; ii to v), the transition into the new phase would
be bypassed because of the high kinetic energy barrier (iii). As a
result, the Sm2 phase can exist in a supercooled state (iv).
However, because of its metastability, the Sm2 phase can
transform into a more-stable phase as time passes or by the action
of an appropriate stimulus (v and vi).
characteristic of the Sm2 phase with a lamellar structure. When
1·2 was annealed for 1 h, the XRD pattern was fairly similar to
that of the original material, but a number of small reflections
emerged in the wide-angle region, indicating partial crystal-
lization of the salt. As the annealing time was extended, the
reflections arising from the crystalline (Cry) phase increased in
intensity, whereas those attributable to the Sm2 phase weakened.
After annealing for 20 h, no change in the XRD pattern was
observed, indicating that the phase transition was complete.
Therefore, the Sm2 phase was confirmed to be a metastable state
that is capable of persisting for several hours while gradually
transforming into the Cry phase.
We also examined time-dependent changes in the UV/vis
spectra of salt 1·2 on annealing at 45 °C. We focused on
absorptions in the range 300−450 nm that were attributable to
the 1La and 1Lb bands of the anthracene moiety of 2.10 Because
these bands do not overlap with the absorption of 1, monitoring
of these bands should provide reliable information regarding the
microenvironment of the photoreactive unit 2. As shown in
Figure 3e, marked changes in the UV/vis spectra were observed
throughout the annealing process, suggesting there were
corresponding changes in the environment of the molecules of
2 during the phase transition. As additional evidence of such
structural rearrangement, the induced circular dichroism (CD)
spectra also showed marked changes in response to the progress
of the phase transition (Figure 3f).11 In its initial state, salt 1·2
displayed a weak Cotton effect with a negative sign at 300−450
nm. However, as the phase transition proceeded, the sign of the
Cotton effect became positive, and its intensity continued to
increase during 8 h.
To confirm our hypothesis, we evaluated the lifetime of the
Sm2 phase at 45 °C by means of XRD studies. Salt 1·2 was
pretreated as described above (cooled from 115 to 45 °C at a rate
of 0.33 °C min−1) to form the Sm2 phase, and then kept at 45 °C
for 15 h. Throughout the annealing process, time-dependent
changes in the nanostructure were monitored by XRD analyses
(Figure 3d). In its original state, 1·2 showed a set of reflections
It is worth noting that time-dependent changes in the
enantioselectivity toward the antiHH dimer (Figure 2a) and
those in XRD, UV/vis, and CD profiles (insets of Figures 3d−f)
showed similar trends to one another. After an induction period
of 1−2 h, the system underwent a marked change and reached its
C
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Journal of the American Chemical Society
Communication
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final static state after 8−20 h. This commonality reinforces our
hypothesis that the changes observed in these measurements
originate from a single event: the phase transition between the
Sm2 phase and the Cry phase. The Sm1 phase, however, did not
show any signs of time-dependent changes in these measure-
ments (Figures S10−S12), which is also in good agreement with
the results of the photodimerization at 80 °C (Table S1, entries
12 and 13).
In conclusion, we have identified a novel type of reversal in
enantioselectivity in an asymmetric photoreaction that is induced
by a phase transition of a metastable LC. Unlike related
phenomena previously reported,1,2 the novel reversal in
enantioselectivity can be induced by means of a simple process:
isothermal annealing. This finding raises an important note of
caution with regard to general studies on asymmetric synthesis,
in that the history of samples can have a significant effect on the
enantioselectivity of an asymmetric reaction, particularly when a
rapid equilibrium is not guaranteed. Furthermore, this
phenomenon implies unexplored functions of nonequilibrium-
state supramolecular assemblies. Although stimuli-responsive
properties of LCs that are capable of adopting multiple
equilibrated states have been well explored,12 there have been
remarkably few studies on the dynamics and kinetics of
metastable LCs,8 probably because the lability of these materials
has rendered them unsuitable for use in fundamental studies or in
practical applications. The present study is a rare successful
example of the utilization of the metastability of an LC as a
unique function. Further studies on metastable LCs and related
supramolecular aggregates could lead to the creation of
intriguing materials with dynamic and time-responsive proper-
ties.13
(8) de Vries, A. Mol. Cryst. Liq. Cryst. 1985, 131, 125.
(9) (a) Wunderlich, B. Macromol. Symp. 1997, 113, 51. (b) Keller, A.;
Cheng, S. Z. D. Polymer 1998, 39, 4461. (c) Tang, B.; Ge, J. J.; Zhang, A.;
Calhoun, B.; Chu, P.; Wang, H.; Shen, Z.; Harris, F. W.; Cheng, S. Z. D.
Chem. Mater. 2001, 13, 78. (d) Elmahdy, M. M.; Dou, X.; Mondeshki,
ASSOCIATED CONTENT
* Supporting Information
Preparation and characterization of salt 1·2 and details of the in
situ photodimerization of acid 2. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
M.; Floudas, G.; Butt, H.-J.; Spiess, H. W.; Mullen, K. J. Am. Chem. Soc.
̈
2008, 130, 5311.
(10) Olivier, J.-H.; Camerel, F.; Barber, J.; Retailleau, P.; Ziessel, R.
AUTHOR INFORMATION
Corresponding Author
y-ishida@riken.jp
Notes
Chem.Eur. J. 2009, 15, 8163.
■
(11) To ensure the accuracy of CD measurements on condensed
matter, it is necessary to evaluate the linear birefringence (LB) and the
linear dichroism (LD) that are produced by artifacts or by intrinsic
macroscopic anisotropies in the samples. Therefore, the advanced high-
accuracy universal polarimetry method was used to examine non-
annealed and annealed samples of salt 1·2, which clearly showed that LB
and LD were negligible in both samples (Figure S13). For solid-state CD
measurements, see: (a) Kobayashi, J.; Asahi, T.; Sakurai, M.; Takahashi,
M.; Okubo, K.; Enomoto, Y. Phys. Rev. B 1996, 53, 11784. (b) Kuroda,
R.; Harada, T.; Shindo, S. Rev. Sci. Instrum. 2001, 72, 3802. (c) Tanaka,
M.; Nakamura, N.; Koshima, H.; Asahi, T. J. Phys. D: Appl. Phys. 2012,
45, 175303.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank H. Minamikawa and T. Shimizu for performing the
XRD measurements.
■
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