Supramolecular enantiodifferentiating photoisomerization of cyclooctene with modified β-cyclodextrins: Critical control by a host structure

Article abstract of DOI:10.1039/b714300a

Enantiodifferentiating photoisomerization of (Z)-cyclooctene included and sensitized by m-methoxybenzoyl-β-cyclodextrin gave chiral (E)-isomers in up to 46% enantiomeric excess, which is the highest value ever reported for supramolecular photochirogenesis

Full text of DOI:10.1039/b714300a

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Supramolecular enantiodifferentiating photoisomerization of
cyclooctene with modified b-cyclodextrins: critical control by a host
structure{
Runhua Lu,ab Cheng Yang,c Yujuan Cao,d Zhizhong Wang,b Takehiko Wada,c Wei Jiao,b Tadashi Moric and
Yoshihisa Inoue*c
Received (in Cambridge, UK) 17th September 2007, Accepted 11th October 2007
First published as an Advance Article on the web 29th October 2007
DOI: 10.1039/b714300a
homogeneous solution.1c,e Despite the intriguing mechanistic
Enantiodifferentiating photoisomerization of (Z)-cyclooctene
features revealed for supramolecular photochirogenesis with CD-
based sensitizers, the enantioselectivity reported hitherto is rather
modest (,25% ee) even as asymmetric synthesis in the excited
state, which coincides with the fact that the CD’s chiral recognition
ability is low in general.
included and sensitized by m-methoxybenzoyl-b-cyclodextrin
gave chiral (E)-isomers in up to 46% enantiomeric excess, which
is the highest value ever reported for supramolecular photo-
chirogenesis with analogous hosts, thus demonstrating the
crucial role of the sensitizer-spacer moiety in supramolecular
photochirogenic systems.
Supramolecular photochirogenesis has drawn considerable atten-
tion in recent years as an intriguing extension of chiral
photochemistry.1 In conventional chiral photosensitization, the
transfer of chiral information occurs in an exciplex formed
between an excited chiral sensitizer and a substrate, utilizing the
weak excited-state interactions. In contrast, the chirality transfer in
a supramolecular photochirogenic system can utilize the chiral
host–guest interactions both in the ground and excited states.
Various chiral hosts, such as chirally modified zeolites,2 synthetic
templates,3 cyclodextrins (CDs),4 proteins5 and DNA6 have been
used as chirality sources to afford the photoproducts with good-to-
excellent stereoselectivities. Of these chiral hosts, CDs are
particularly attractive for the use in supramolecular photosensiti-
zation, possessing an inherently chiral hydrophobic cavity of
appropriate size and, specifically, primary and secondary hydroxyl
groups readily modifiable with a photosensitizer moiety.7
In the present study, we prepared a series of sensitizing b-CD
hosts (Scheme 1) in order to fine tune the bulkiness of the
sensitizer-spacer to be co-included with the substrate, and
compared their behavior in supramolecular enantiodifferentiating
photoisomerization of 1Z, and found that the enantioselectivity is
highly sensitive to the structural variation of the host as well as the
temperature in this supramolecular photochirogenic system.
Eventually, the use of m-methoxybenzoyl-b-CD as the sensitizing
host doubled the highest enantioselectivity (23% ee) ever obtained
for 1E with a variety of sensitizer-appended CDs.
Modified b-CDs 3 and 4 were synthesized in 31.5% and 32.3%
yield, respectively, by the reaction of b-CD with m- and
p-methoxybenzoyl chlorides in dry pyridine and subsequent
recrystallization.
6-O-Modified CDs with benzoyl and isomeric phthaloyl groups
have been used as chiral sensitizing hosts for the enantiodiffer-
entiating photoisomerization of (Z)-cyclooctene (1Z) to give
planar-chiral (E)-isomer (1E).4e–f,8 These studies revealed that the
enantioselectivity obtained upon supramolecular photosensitiza-
tion of 1Z with 6-O-benzoyl-b-CD is not sensitive to the
temperature variation (due to the negligible contribution of the
entropic term), but nicely correlates with the host occupan-
cy.1a,1c,4f,9 In contrast, the product’s enantiomeric excess (ee)
obtained upon sensitization with permethylated 6-O-benzoyl-
b-CD regains the critical temperature dependence which is
often reported for conventional photochirogenic reactions in
We first investigated the complexation behavior of these
modified b-CDs with 1Z by means of circular dichroism spectral
titrations. As exemplified in Fig. 1, host 3 exhibited a positive
1
Cotton effect for the La band (218 nm) but a negative effect for
the 1Lb band (234 nm) in 1 : 9 MeOH–H2O. Interestingly, both the
1
1La (219 nm) and Lb (234 nm) bands showed negative Cotton
effects in 1 : 3 MeOH–H2O. According to the sector rule proposed
1
by Kajtar et al.10 (Scheme 2), this sign inversion of the La band
indicates that the chromophoric m-methoxybenzoyl moiety
aDepartment of Applied Chemistry, College of Sciences, China
Agricultural University, Beijing 100094, China
bChengdu Institute of Biology, Chinese Academy of Sciences,
Chengdu 610041, China
cDepartment of Applied Chemistry, Osaka University, 2-1 Yamada-oka,
Suita 565-0871, Japan. E-mail: inoue@chem.eng.osaka-u.ac.jp
dDepartment of Chemistry and Environment, South China Normal
University, Guangzhou 510006, China
{ Electronic supplementary information (ESI) available: Experimental
section. See DOI: 10.1039/b714300a
Scheme 1
374 | Chem. Commun., 2008, 374–376
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sensitizer moiety in modified b-CD. As shown in Table 1, sensitizer
3 which has a methoxy group at the meta-position gives 1E in
good (40.8%) ee in 10% MeOH at 25 uC, while its parent
compound 1 and ortho- and para-isomers 2 and 4 afford only
modest (4–10%) ee under identical conditions. It is also interesting
to point out that the ee value falls drastically to 1.7% when the
meta-substituent is altered from methoxy to methoxycarbonyl
(host 5). These observations reveal a clear dependence of the
efficiency of chirality transfer on the structure of the sensitizer
moiety in the supramolecular photosensitized isomerization
system. The chromophore attached to modified b-CDs should
act not only as a sensitizer but also as a space filler for adjusting
the depth/position and orientation of guest penetration in the CD
cavity so as to substantially affect the chirality induction in the
guest substrate, and therefore the critical adjustment of the steric
bulk and position of the substituent introduced to the chromo-
phore is crucial as demonstrated in this work.
Upon prolonged irradiation, the E/Z ratio increased but the
enantioselectivity slightly decreased. Both the E/Z ratio and the ee
value increased on increasing the water content. Although the
temperature effect upon the ee was only marginal, yet the
irradiations at lower temperatures appreciably enhanced the ee
value from 240.8% at 25 uC to 245.8% at 25 uC, which is much
higher (almost doubled) than the prior highest (223% ee) reported
for the photosensitization with methyl phthaloyl-modified b-CD in
50% aqueous methanol at 240 uC.4e Such an enantioselectivity
(R/S ratio = 2.7) is rather significant considering the fact that
native b-CD and its derivatives bind various enantiomeric guests
only with low enantioselectivities; the enantiomer ratio rarely
exceeds 1.3.11 Our finding is therefore indicative that the inherently
poor chiral discrimination ability of b-CD in the ground state can
be remarkably improved by utilizing the supramolecular interac-
tions in both ground and excited states.
…
Fig. 1 Circular dichroism spectra of (a) 0.054 mM 3 in the absence (
)
and presence (—) of 0.192 mM 1Z in 10% MeOH, and (b) 0.071 mM 3 in
…
the absence ( ) and presence (—) of 0.192 mM 1Z in 25% MeOH.
In this study, we have shown that the supramolecular
photosensitized enantiodifferentiating isomerization of 1Z is
critically affected by an apparently small alteration of the host’s
substituent to give an unprecedentedly high ee of 46%, which is
likely to be achieved by optimizing the ground- and excited-state
chiral interactions within the CD cavity by fine-tuning the host
structure, as well as the solvent and temperature. This investigation
Scheme 2
penetrates more deeply into the chiral CD cavity in 10% MeOH
than in more hydrophobic 25% MeOH.
Upon addition of 1Z, the Cotton effect signals of both 1La and
1Lb bands became more negative, indicating that conformational
changes are induced by the inclusion of 1Z to make the
m-methoxybenzoyl moiety more parallel, or the 1Lb transition
more perpendicular, to the axis of the CD cavity. From the
differential circular dichroism spectral titration data obtained, the
complex stability constants (Ks) for 1Z in water–methanol
mixtures were determined by using the least-squares fit. The Ks
values for complexation of 1Z with 3 are 23 100, 8200 and
4200 M21 in 10%, 25% and 50% MeOH, respectively, and those
for 4 are 20 200, 13 800 and 2430 M21, respectively.
Table 1 Enantiodifferentiating photoisomerization of 1Z in the
presence of modified b-CDs in methanol–water mixtures at various
temperaturesa
Solvent
(% MeOH)
Temperature/
uC
Irradiation
time/min
E/Z
ratio
Host
% eeb
1c
2d
3
0
50
10
10
10
25
25
50
50
10
50
25
25
25
0
25
25
25
25
25
25
25
5
5
5
5
5
5
30
5
30
5
2
0.05
0.19
0.07
0.19
0.24
0.08
0.13
0.18
0.19
0.12
0.21
29.7
4.3
240.8
239.6
245.8
233.3
231.1
230.2
226.3
210.6
21.7
Aqueous solutions (5 mL) of different methanol content, which
contained 1Z (1.5 mM) and a modified b-CD (0.054 to 0.108 mM),
were irradiated at 254 nm in quartz tubes under an argon
atmosphere at temperatures varying from +25 to 25 uC. The E/Z
ratio and the ee of 1E were determined by chiral capillary gas
chromatography on a Shimadzu GC-2014 instrument fitted with a
CBP-20 or a Supelco b-Dex225 column, respectively.1b–c
4
5c
a
Irradiated at 254 nm under argon in methanol–water mixture;
[1Z] = 1.5 mM; [host] = 0.15–0.05 mM, varied depending on the
solubility. Sign of ee corresponds to that of the optical rotation of
b
It turned out that the enantioselectivity is highly sensitive to the
structure and position of the substituent introduced to the
c
obtained 1E. Ref. 4e. Ref. 9b.
d
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376 | Chem. Commun., 2008, 374–376
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