Induction of point chirality by E/Z photoisomerization

Article abstract of DOI:10.1002/anie.201104614

Shining a light on it: E/Z photoisomerization generates an asymmetric center and the corresponding separable enantiomers in an azobenzene-based prochiral molecule. This asymmetric center is formed by light-induced changes to the substituents on the centra

Full text of DOI:10.1002/anie.201104614

DOI: 10.1002/anie.201104614
Chirality
Induction of Point Chirality by E/Z Photoisomerization**
P. K. Hashim and Nobuyuki Tamaoki*
Point chirality originates from having four different substitu-
ents bonded to a central atom to give nonplanar molecules
with nonsuperimposable mirror images.[1] The induction of
point chirality in molecular systems is of particular interest in
connection with the origin of homochirality in nature, as seen
in amino acids.[2–4] Our interest is to propose a new concept for
the introduction of point chirality and also to understand how
small differences in the substituents on the central carbon
atom can cause detectable asymmetry in the structure.
Previous work has shown that a small difference in the
substituents such as position isomerism of pyridyl groups[5] or
Scheme 1. Schematic representation showing asymmetry induction by
the presence of different isotopes[6] can cause detectable
asymmetry in a molecule. However, chemical bonds need to
be broken and made to make even such small differences in
the substituents; this observation inspired us to envisage a
molecular system in which the asymmetry can be introduced
by photoisomerization of the substituents without any bond
cleavage.
Herein, a new class of azobenzene-based prochiral
molecules and the on/off switching of point chirality is
reported. We designed a molecule consisting of a carbon
atom having two photoisomerizable azobenzene moieties and
a methyl and a benzene group (Scheme 1). The conforma-
tional difference caused by the E/Z photoisomerization of
one of the azobenzene moieties was successfully utilized for
the generation of point chirality in the molecule. To the best
of our knowledge this is the first example of the induction of
point chirality in which two of the substituents around an sp3
carbon atom are geometric isomers.
E/Z photoisomerization of an azobenzene derivative.
respectively, of the initial absorbance seen at 327 nm. The
isobestic points observed at 279 nm and 387 nm are indicative
of almost independent conversion between the three isomers,
that is, EE, EZ, and ZZ by E/Z photoisomerizations of
azobenzene moieties (see the Supporting Information for
details).
An insight into the chiral nature of molecule 1 was
obtained from HPLC studies using a chiral stationary phase.[7]
The HPLC chromatogram for compound 1 before irradiation
showed a single peak at a retention time Rt = 13.47 (Fig-
ure 1a). Irradiation of 1 at 366 nm generated three new peaks
at Rt = 23.43, 26.89, and 46.44 in addition to the initial peak
(Figure 1b). The solution that had been irradiated at the
366 nm PSS was then irradiated with light of wavelength
436 nm. This resulted in the first peak increasing in intensity,
with a diminished intensity of the fourth peak and increased
intensities of the second and third peaks (Figure 1c). The
intensities of the second and third peaks changed during
irradiation but they remained equal in intensity to each other.
Generally, in normal-phase HPLC, including HPLC using a
A solution of 1 in ethyl acetate exhibits a typical
absorption spectrum for azobenzene derivatives; this spec-
trum features an intense p–p transition band at 327 nm and a
*
weak and broad n–p* transition band at 400–500 nm.
Irradiation of the solution at 366 nm caused a gradual
decrease in the intensity of the p–p* transition band, with a
notable increase in the n–p* transition band owing to
photochemical E/Z isomerization of the azobenzene moieties.
The reverse spectral changes were observed upon irradiation
at 436 nm. The solutions at the photostationary state (PSS)
under 366 and 436 nm light showed about 15 and 80%,
[*] P. K. Hashim, Prof. N. Tamaoki
Research Institute for Electronic Science, Hokkaido University
N20, W10, Sapporo, Hokkaido 001-0020 (Japan)
E-mail: tamaoki@es.hokudai.ac.jp
Homepage: http://tamaoki.es.hokudai.ac.jp/index-e.html
[**] We thank Dr. Thomas Reji for helpful discussions and Perur Nishad
for assistance with the graphics. This work was supported by a
grant-in-aid for science research in the priority area “New Frontiers
in Photochromism (No. 471)” from the Ministry of Education,
Culture, Sports, Science, and Technology (MEXT) (Japan).
Figure 1. Chromatogram of (E,E)-1 monitored at 279 nm, the wave-
length of an isosbestic point: a) before irradiation, b) the PSS after
irradiation at 366 nm (EE/EZ/ZZ=2:14:84), c) the PSS after irradiation
at 436 nm (EE/EZ/ZZ=62:33:5), and d) (E,Z)-1A the first eluted
enantiomer obtained by HPLC using a chiral stationary phase with a
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201104614.
flow rate at 2 mLminꢀ1
.
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11729

Communications
chiral stationary phase, the polar (Z)-azobenzene derivative
tion generates equal amounts of (E,Z)-1A and (E,Z)-1B from
(E,Z)-1A or (E,Z)-1B via (E,E)-1 or (Z,Z)-1. The thermal back
isomerization from (E,Z)-1A to (E,E)-1 was found to occur
(rate constant 3.8 ꢀ 10ꢀ6 sꢀ1 at 308C), as observed by the
change in the HPLC profile (see the Supporting Information).
The intensity of the CD band of (E,Z)-1A gradually decreased
over one week in the dark with a rate constant of 4 ꢀ 10ꢀ6 sꢀ1
at 308C. The rate constants obtained from UV absorption
(3.88 ꢀ 10ꢀ6 sꢀ1 at 308C as a sum of ZZ!EZ and EZ!EE),
HPLC, and CD studies on the thermal back reaction were all
in reasonable agreement within the experimental error. These
results suggest that the Z–E isomerization directly removes
the asymmetry in the molecule.
In conclusion we have introduced a novel prochiral
molecule in which two azobenzene moieties were connected
to a common carbon atom having methyl and benzene units.
On irradiation at a suitable wavelength, E/Z photoisomeriza-
tion of one of the azobenzene moieties ocurred to generate a
change in the substituents around the central carbon atom
and thus asymmetry was induced in compound 1. Moreover,
Z/E thermal isomerization regenerated the initial achiral
molecule and this on/off switching of the induced asymmetry
was repeatedly accomplished by light and heat respectively.[8]
It is expected that this method could be used for the
asymmetric synthesis or the enrichment of one of the
enantiomers of 1 or related compounds in the presence of a
physical or chemical chiral source in addition to the action of
light.[9] Such a photoisomerization favoring one of the
enantiomers as a product at PSS is under investigation.
elutes slower than the corresponding E isomer. Since the
E isomer of the azobenzene derivative is thermodynamically
stable, the compound should exist as the E,E isomer before
irradiation. From the above information and the obtained
results the second and third HPLC peaks can be assigned as
enantiomers of the (E,Z)-1 isomer. To fully assign the HPLC
peaks we isolated the second and third fractions of the HPLC
chromatogram, preparatively (Figure 1d) and obtained their
CD and NMR spectra. The CD spectrum of the second eluted
fraction shows one positive (282 nm) and two negative bands
(at 330 nm and 430 nm), and the mirror image of this
spectrum was observed in the case of the third fraction
(Figure 2). The NMR spectra for the second and third
fractions were identical, and contained peaks corresponding
Figure 2. CD spectra of enantiomers of (E,Z)-1 in ethyl acetate: first
eluted enantiomer (E,Z)-1A (solid line) and second eluted enantiomer
(E,Z)-1B (dotted line). The concentration of the solution was
Received: July 5, 2011
Published online: November 4, 2011
3.75ꢀ10ꢀ4 molLꢀ1
.
Keywords: azo compounds · chirality · circular dichroism ·
isomerization · photochromism
to both (E)- and (Z)-azobenzene moieties at d = 7.90, 7.85
and at d = 6.85, 6.76, respectively (see the Supporting
Information). From these results, we could unambiguously
assign the first peak in the HPLC as (E,E)-1, where both the
azobenzene units are in the trans form, and the second and
third peaks as (E,Z)-1A and (E,Z)-1B, respectively. (E,Z)-1A
and (E,Z)-1B both have one azobenzene unit in the trans form
and the other in the cis form but they have opposite
stereostructures. The fourth peak in the HPLC chromatogram
can be assigned as (Z,Z)-1, in which both the azobenzene
units are in the cis form. Hence, it is clear that the geometric
difference in the substituents caused by the E/Z photo-
isomerization of one of the azobenzene moieties generated
asymmetry in the structure, and this asymmetry results in
separable enantiomers with detectable differences in the CD
spectra.
The racemization behavior of the (E,Z)-1 enantiomers
was investigated by HPLC and CD experiments. The HPLC
chromatograms obtained after irradiation with 436 nm of the
isolated second ((E,Z)-1A) or third ((E,Z)-1B) fraction were
completely the same as the chromatogram shown in Figure 1c
obtained for the 436 nm PSS from (E,E)-1 (see the Support-
ing Information). This suggests the photochemical racemiza-
.
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