Supramolecular photochirogenesis with novel cyclic tetrasaccharide: Enantiodifferentiating photoisomerization of (Z)-cyclooctene with cyclic nigerosylnigerose-based sensitizers

Article abstract of DOI:10.1002/chir.22014

Isophthalic and terephthalic acid monoesters of cyclic nigerosyl-(1→6) -nigerose (CNN), a cyclic tetrasaccharide composed of four d-glucopyranosyl residues connected by alternating α-1,3- and α-1,6-linkages, were synthesized as novel chiral supramolecular sensitizers for enantiodifferentiating photoisomerization of (Z)-cyclooctene () to planar chiral (E)-isomer (1E). Despite the saucer-shaped shallow cavity of CNN that does not immediately guarantee strong ground-state interactions with, the sensitizer-appended CNNs afforded optically active 1E in such enantiomeric excesses that are much improved than those obtained with an α-cyclodextrin analog and comparable with those obtained with a β-cyclodextrin analog. Interestingly, the enantiomeric excess values obtained were a critical function of temperature and solvent to show an inversion of the product chirality by changing the environmental variants. Nevertheless, all of the differential activation parameters calculated from the temperature-dependent enantiomeric excesses gave an excellent compensatory enthalpy-entropy relationship, indicating an operation of a single enantiodifferentiating mechanism in the present chiral photosensitization with modified CNNs. Chirality 24:921-927, 2012. 2012 Wiley Periodicals, Inc. Copyright

Full text of DOI:10.1002/chir.22014

CHIRALITY 00:000-000 (2012)
Supramolecular Photochirogenesis with Novel Cyclic Tetrasaccharide:
Enantiodifferentiating Photoisomerization of (Z)-Cyclooctene with
Cyclic Nigerosylnigerose-Based Sensitizers
2
3
2
2
4
CHENG YANG,1,2 WENTING LIANG, MASAKI NISHIJIMA, GAKU FUKUHARA, TADASHI MORI, HIROYUKI HIRAMATSU,
*
2**
YASUFUMI DAN-OH,4 KAZUO TSUJIMOTO,4 AND YOSHIHISA INOUE
1Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi,
Saitama 332-0012, Japan
2Department of Applied Chemistry, Osaka University, Suita 565-0871, Japan
3Office for University-Industry Collaboration, Osaka University, Suita 565-0871, Japan
4Hayashibara Co., Ltd., Okayama 700-0907, Japan
ABSTRACT
Isophthalic and terephthalic acid monoesters of cyclic nigerosyl-(1!6)-nigerose
(CNN), a cyclic tetrasaccharide composed of four D-glucopyranosyl residues connected by alternat-
ing a-1,3- and a-1,6-linkages, were synthesized as novel chiral supramolecular sensitizers for
enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to planar chiral (E)-isomer
(1E). Despite the saucer-shaped shallow cavity of CNN that does not immediately guarantee strong
ground-state interactions with 1Z, the sensitizer-appended CNNs afforded optically active 1E in
such enantiomeric excesses that are much improved than those obtained with an a-cyclodextrin
analog and comparable with those obtained with a b-cyclodextrin analog. Interestingly, the
enantiomeric excess values obtained were a critical function of temperature and solvent to show an
inversion of the product chirality by changing the environmental variants. Nevertheless, all of the dif-
ferential activation parameters calculated from the temperature-dependent enantiomeric excesses
gave an excellent compensatory enthalpy–entropy relationship, indicating an operation of a single
enantiodifferentiating mechanism in the present chiral photosensitization with modified CNNs.
Chirality 00:000–000, 2012. © 2012 Wiley Periodicals, Inc.
KEY WORDS: chiral photochemistry; enantiodifferentiating photoisomerization; planar chirality;
cyclooctene; cyclic nigerosylnigerose; supramolecular chemistry
INTRODUCTION
an exciplex intermediate with substrate, whereas a supramo-
lecular sensitizer utilizes the diastereomeric interactions
both in the ground and excited states to enhance the stereo-
chemical outcomes.
Achieving efficient chirality transfer and amplification is
one of the most intriguing topics in current chemistry. In
contrast to the significant success in thermal asymmetric
synthesis achieved in recent decades, there still remain
substantial barriers in realizing efficient chirality transfer in
the electronically excited state.1–4 Chiral photochemistry
possesses unique and attractive features, providing a direct
access to highly strained compounds and a much wider
temperature range expanded in particular to the lower side.
At the same time, weak and short-lived chiral interactions in
the excited state are difficult in general to precisely manipu-
late. Nevertheless, foregoing studies have revealed the criti-
cal roles of chiral source used as auxiliary or supramolecular
host5–10 and maneuverable environmental variants, such as
temperature, solvent, and pressure,11–16 as well as irradiation
wavelength.17 Thus, seeking chiral sources suitable for a
specific photochirogenic system is often the most crucial
and demanding task, along with the subsequent optimization
of environmental variants.
We have been employing the enantiodifferentiating photoi-
somerization of (Z)-cyclooctene (1Z) to planar chiral (E)-isomer
(1E) (Scheme 1) as a benchmark test for evaluating the perfor-
mance of a wide variety of chiral sources attached to a sensitiz-
ing chromophore.12–14,18–23 The chiral sensitizers hitherto
examined may be classified into two categories by the mode
of interaction with substrate molecule; thus, a conventional
molecular sensitizer uses the diastereomeric interactions in
© 2012 Wiley Periodicals, Inc.
In the present study, we employed a new class of cyclic
tetrasaccharide (Scheme 2), cyclo-{!6)-a-D-Glcp-(1!3)-a-D-
Glcp-(1!6)-a-D-Glcp-(1!3)-a-D-Glcp-(1!} or cyclic nigerosyl-
(1!6)-nigerose (CNN),24,25 as a chiral source. CNN was
enzymatically produced from starch relatively recently, and
so far, only the production, purification, and degradation beha-
viors have been investigated intensively.26–28 The X-ray crystal-
lographic analysis revealed that this tetrasaccharide possesses
only a shallow saucer-like shape with a small concave at the
center.29 As a supramolecular host, CNN is known to interact
with ethanol,30 whereas a dicarboxylic acid derivative of CNN
can selectively chelate some cations.31
Contract grant sponsor: Japan Science and Technology Agency (CY and YI).
Contract grant sponsor: Japan Society for the Promotion of Science (GF, TM,
and YI).
Contract grant sponsor: Sumitomo Foundation (CY and TM).
Contract grant sponsor: Iwatani Naoji Foundation (GF).
Contract grant sponsor: Mitsubishi Chemical Corporation Fund (TM).
*Correspondence to: Y. Inoue, Department of Applied Chemistry, Osaka
University, Yamada-oka, Suita 565-0871, Japan. E-mail: inoue@chem.eng.
osaka-u.ac.jp; C. Yang, Department of Applied Chemistry, Osaka University,
Yamada-oka, Suita 565-0871, Japan. E-mail: c.yang@chem.eng.osaka-u.ac.jp
Received for publication 22 October 2011; Accepted 12 January 2012
DOI: 10.1002/chir.22014
Published online in Wiley Online Library
(wileyonlinelibrary.com).

YANG ET AL.
2: 1H NMR (600 MHz, D2O), d (ppm): 8.31 (1H, dd, J1 =1.4 Hz, J2 =1.4 Hz),
8.00 (1H, dd, J1 =1.8 Hz, J2 = 1.5 Hz), 7.99 (1H, dd, J1 = 1.8Hz, J2 = 1.5 Hz), 7.44
(t, J= 10.8 Hz), 5.44 (1H, d, J= 4.0 Hz), 5.22 (1H, d, J= 4.0 Hz), 4.74 (1H, d,
J= 3.6 Hz), 4.72 (1H, d, J= 3.6 Hz), 4.14–4.01 (2H, m), 3.92–3.81 (2H,m),
3.65–3.36 (18H, m), 3.08 (2H, m). 13C NMR (151 MHz, D2O), d (ppm):
175.17, 174.15, 136.86, 133.89, 131.24, 128.78, 98.31, 97.76, 96.97, 96.46,
74.38, 73.66, 73.43, 72.58, 72.23, 71.53, 71.37, 71.28, 71.24, 70.76, 70.50,
70.03, 69.92, 69.76, 69.17, 67.34, 63.66, 59.99. High-resolution mass spectra:
m/z calculated for C32H44KO23 835.191, found: 835.192.
Scheme 1. Enantiodifferentiating photoisomerization of (Z)-cyclooctene
(1Z) to planar chiral (E)-isomer (1E).
3: 1H NMR (600 MHz, 1:1 D2O-DMSO-d6): d/ppm 8.07 (2H, d, J= 8.0 Hz),
8.02 (2H, d, J= 8.0 Hz), 5.62 (1H, d, J= 4.0 Hz), 5.34 (1H, d, J = 4.0Hz), 4.71
(1H, d, J = 3.6Hz), 4.66 (1H, d, J = 3.6Hz), 4.56 (1H, dd, J1 = 9.8Hz,
J2 = 9.0 Hz), 4.42 (1H, dd, J1 =9.8Hz, J2 = 9.0 Hz), 3.87–3.79 (2H, m), 3.62–3.30
(16H, m), 3.23 (1H, dd, J1 =9.8Hz, J2 = 3.6 Hz), 3.16 (1H, dd, J1 =9.6,
J2 = 9.0 Hz), 3.10 (1H, dd, J1 =9.8, J2 = 9.0 Hz), 2.90 (1H, dd, J1 =9.8,
J2 =9.0Hz). 13C NMR (150MHz), d (ppm): 174.6, 167.8, 141.3, 130.9, 129.5,
128.6, 98.5, 98.2, 96.6, 96.4, 75.9, 74.7,74.4,74.3, 74.2, 73.9, 72.6, 71.4, 70.8,
70.5, 70.2, 69.9, 69.8, 69.7, 68.7, 67.2, 60.0. High-resolution mass spectra:
m/z calculated for C32H44NaO23 819.217, found: 819.217.
Photoreaction
Scheme 2. Chemical structure of cyclic nigerosyl-(1!6)-nigerose (CNN)
and its hydrogen isophthalate and terephthalate (2 and 3).
An aqueous or organic solution (3 mL) of 1Z (1.5 mM) and sensitizer-
modified CNN 2 or 3 (0.5 mM) in a quartz cell was placed in a Unisoku
USP-203 cryostat (Osaka, Japan) with a quartz window for irradiation,
purged with nitrogen gas, kept at a given temperature, and irradiated at
254 nm under a nitrogen atmosphere with a 30-W low pressure mercury
lamp (Eikosha, Osaka, Japan) or a MAX-301 light source (a 300-W xenon
lamp fitted with a band-pass filter; Asahi Spectra Co., Tokyo, Japan). An ali-
quot of the irradiated organic solution was analyzed by gas chromatography
(GC) on a Shimadzu (Kyoto, Japan) CBP-20 (PEG) column for E/Z ratio. In
the case of aqueous samples, the irradiated solution was extracted with
pentane, and the pentane extract was subjected to the gas chromatography
analysis. To determine the enantiomeric excess (ee) value, a 20% aqueous
silver nitrate solution was added to the irradiated solution at 0–5 ꢀC to form
a stable Ag+ complex with 1E. The aqueous solution containing [Ag+•1E]
complex was washed with pentane and then added with stirring to a 28%
aqueous ammonia solution at 0ꢀC to liberate 1E, which was extracted with
pentane, and the pentane extract was subjected to chiral gas chromatogra-
phy analysis on a Supelco b-DEX120 column (Bellefonte, USA).
We became interested in the use of CNN as a potential
supramolecular host for the enantiodifferentiating photoisome-
rization of 1Z because of its inherent chirality and unique
chemical structure with a shallow cavity. CNN is the smallest
cyclic gluco-oligosaccharide that has some similarities with
the well-known analog, cyclodextrin (CD). Both are composed
of the same building blocks but differ in linkage connecting the
adjacent glucose units and also in shape and cavity size: shal-
low saucer versus truncated hollow corn. To assess the ability
of CNN as a chiral source for enantiodifferentiating photosensi-
tization, we introduced an isophthalate or terephthalate moiety
to one of the CNN’s 6-hydroxyl groups and investigated the
enantiodifferentiating photoisomerization of 1Z sensitized by
these CNN derivatives.
Preparation of CNN Isophthalate and Terephthalate 2 and 3
EXPERIMENTAL
Sensitizer-appended CNNs 2 and 3 (Scheme 2) were prepared by react-
ing isophthaloyl or terephthaloyl chloride with CNN in pyridine under a typ-
ical reaction condition employed for the synthesis of primary rim-modified
CDs.20,22,23 However, the target compounds 2 and 3 were obtained only
in low yields (<10%) after separation by reverse-phase liquid chromatogra-
phy, along with small amounts of side products. Thin-layer chromatography
analyses of the side products suggested formation of CNN isophthalates or
terephthalates esterified at one of the secondary hydroxyl groups (with Rf
similar to those of 2 and 3) as well as bridged CNN dimers (with Rf smaller
than that of native CNN. After full characterization (see the Supporting
Information), the isolated CNN monoesters 2 and 3 were directly used as
chiral sensitizers for photoisomerization of 1Z.
Instruments
Ultraviolet–visible (UV–vis) and circular dichroism spectra were measured
on JASCO (Tokyo, Japan) V-560 spectrophotometer and JASCO (Tokyo,
Japan) J-810 spectropolarimeter, respectively. Fast atom bombardment
mass spectra were recorded on a JEOL (Tokyo, Japan) JMS-DX303 mass
spectrometer. Hydrogen-1 (1H) and carbon-13 (13C) nuclear magnetic
resonance (NMR) spectra were recorded on a Bruker DRX-600 spec-
trometer (Germany).
Materials
Cyclic nigerosyl-(1!6)-nigerose was obtained from Hayashibara Co.,
Ltd. (Okayama, Japan). Terephthaloyl chloride, isophthaloyl chloride,
and other chemicals were purchased from Tokyo Chemical Industries
and used without further purification.
RESULTS AND DISCUSSIONS
Enantiodifferentiating Photoisomerization of 1Z
In the previous studies,12,13,18–20,32–34 we systematically
investigated the enantiodifferentiating photoisomerization of
1Z using a wide variety of chiral sensitizers to reveal a signif-
icant correlation between the sensitizer structure and the ee
of 1E produced. In general, aromatic sensitizers multiply sub-
stituted by bulky chiral auxiliaries with the stereogenic center
located closer to the chromophore are more advantageous in
inducing high enantioselectivity, presumably as a result of the
congested arrangement of chiral auxiliaries around the sensi-
tizing aromatic moiety.34 External factors, such as temperature,
solvent, and pressure, also affect the enantioselectivity.13,15,32
Synthesis and Characterization of 2 and 3
Cyclic nigerosyl-(1!6)-nigerose (648 mg, 1.0 mmol), dried in vacuo at
100 ꢀC overnight, was dissolved in dry pyridine (30 ml). To the solution
was added isophthaloyl or terephthaloyl chloride (240 mg, 1.2 mmol) at
0 ꢀC, and the resulting mixture was stirred for 2 h at 0 ꢀC and then
quenched with 5 ml of water. After removal of the solvent in vacuo, the
residue obtained was dissolved in 5 ml of DMF, and the solution was
poured into 30 ml of acetone to give white precipitates, which were
collected by filtration and dissolved in water. The aqueous solution was
subjected to reverse-phase liquid chromatography ((octadecylsily1)silica
gel, 26 ꢁ 300 mm) with a gradient of 3%–30% EtOH to give pure 2 in 8%
yield or 3 in 12% yield as white solid.
Chirality DOI 10.1002/chir

SUPRAMOLECULAR PHOTOCHIROGENESIS WITH NOVEL CYCLIC TETRASACCHARIDE
Intriguingly, the supramolecular enantiodifferentiating photoi-
To better understand the result, the structure of 2 was
optimized by the molecular mechanics. As shown in Figure 1,
the CNN moiety preserves its original saucer-like structure de-
spite the esterification of the primary hydroxyl group. The con-
cave is obviously too small to fully accommodate 1Z but
appears to form partial hydrophobic contacts with 1Z in water,
as evidenced by the appreciable up-field shifts and line broad-
somerization of 1Z included and sensitized by benzoate-
appended CDs in aqueous solution behaves very differently from
the conventional photosensitization in organic solvents.19,22,23
Thus, the CD derivatives bind 1Z in the hydrophobic cavity to
form the corresponding inclusion complexes in the ground
state, which allows efficient chirality transfer in the subsequent
photoisomerization even when the aromatic sensitizer possesses
only one CD as a chiral substituent.
1
ening of guest proton signals upon addition of host 2 in H
NMR spectrum. As shown in Figure 2, the olefinic (H-1) and al-
lylic (H-2) protons of 1Z were shifted up-field by 0.14 and
0.04ppm, respectively, upon addition of 2, indicating loose con-
finement and/or p–p interactions of 1Z with 2 in the ground
state. On the other hand, the aromatic moiety, tethered to the
six position of glucoside, is relatively flexible and not closely
located to the stereogenic centers of CNN. These two structural
features would be jointly responsible to the observed low
enantioselectivity.
Supramolecular Interactions
Direct examination of the ground-state complexation of 1Z
with CNN was not feasible due to the inherently weak Cotton
effects observed for 2 and 3 (vide infra). Indeed, the addition
of 1Z of up to 1 mM to an aqueous solution of 2 did not cause
any significant change in circular dichroism spectrum. Never-
theless, the expectation that saucer-shaped CNN may form a
weak complex with 1Z prompted us to run the photosensitiza-
tion with 2 and 3 in aqueous solutions at 0–40ꢀC to give 1E in
modest 1%–5% ee (Table 1). These ee values are comparable
with or slightly better than those (1%–3% ee) obtained upon
photosensitization with a-CD benzoate20 and therefore do not
immediately exclude the possibility of supramolecular photo-
sensitization with CNN isophthalate and terephthalate.
Experimentally, the existence of weak supramolecular
interaction of CNN derivatives with 1Z was confirmed by
the very rapid photoisomerization in aqueous solutions and
the appreciable decrease of ee in 10% methanol and also in
methanol and ethanol (Table 1). These results may be
accounted for in terms of the reduced hydrophobic interac-
tion in polar alcoholic solvents, which is compatible with the
TABLE 1. Enantiodifferentiating photoisomerization of 1Z sensitized by cyclic nigerosyl-(1!6)-nigerose isophthalate 2 and tere-
phthalate 3 in some solvents1
Sensitizer
Solvent
H2O
Temperature/ꢀC
Irradiation time/min
E/Z
% ee
2
0.5
15
30
40
0.5
15
3
3
3
3
3
3
3
10
60
10
60
10
10
10
60
3
3
3
3
3
0.03
0.03
0.05
0.06
0.03
0.04
0.06
0.06
0.03
0.13
0.002
0.002
0.005
0.006
c
0.05
0.06
0.05
0.08
0.03
0.09
0.24
0.03
0.02
0.05
0.04
c
ꢂ1.6
+0.8
+2.9
+4.6
ꢂ1.1
+0.3
+2.2
+0.3
+0.62
ꢂ1.4
+9.32
+5.5
+3.1
+2.3
+0.62
+3.3
+2.4
+1.5
+1.1
+1.3
+0.5
ꢂ0.3
+0.9
+0.92
0.02
10% MeOH
30
MeOH
EtOH
1-Butanol
Ethyl ether
ꢂ5
ꢂ40
ꢂ5
ꢂ40
ꢂ5
10
20
Pentane
H2O
ꢂ40
0.5
15
30
40
0.5
15
30
ꢂ5
ꢂ40
ꢂ5
25
ꢂ5
ꢂ30
ꢂ5
20
3
10% MeOH
3
3
MeOH
EtOH
10
60
60
60
20
30
10
30
60
ꢂ0.62
ꢂ2.9
ꢂ7.22
ꢂ3.4
+0.32
0.02
1-Butanol
Ethyl ether
0.006
0.002
0.01
c
Pentane
ꢂ40
ee, enantiomeric excess.
1[1Z] = 1.5 mM, [2] = 0.05 mM, [3] = 0.05 mM; Irradiated at 254 nm in a quartz cell placed in a USP-203 cryostat (Unisoku) with a 30-W low-pressure mercury lamp
(Eikosha), unless noted otherwise.
2Irradiated at 254 nm with a MAX-301 (Asahi Spectra, a 300-W xenon lamp fitted with a band-path filter).
3Not determined.
Chirality DOI 10.1002/chir

YANG ET AL.
0.5 ꢀC, CNN isophthalate 2 gave (ꢂ)-1E in 1.6% ee, whereas
terephthalate 3 afforded antipodal (+)-1E in 3.3% ee at
0.5 ꢀC. Also, in diethyl ether at ꢂ40 ꢀC, isophthalate 2 gave
(+)-1E in 9.3% ee, whereas terephthalate 3 afforded antipodal
(ꢂ)-1E in 7.2% ee at ꢂ40 ꢀC. It is to note that 2 and 3 share
the same chiral source, CNN, but differ in substitution pat-
tern, that is, meta versus para. Because the hydroxycarbonyl
substituent at different position is not likely to sterically influ-
ence the chirality transfer process in an exciplex, we deduce that
the opposite product chirality would be related to the difference
in electronic structure between isophthalate and terephthalate.
Solvent Effects
The product’s ee was significantly affected by the solvent
properties. As mentioned earlier, sensitizer 2 gave modest
enantiomeric excesses (ee’s) of ꢂ1.6% to +4.6% in water
but much decreased ee’s upon addition of 10% methanol
(Table 1). This solvent-induced ee change prompted us to fur-
ther explore the solvent effects on this enantiodifferentiating
photoisomerization by using organic solvents such as metha-
nol, ethanol, butanol, ethyl ether, and pentane. The photoi-
somerization in polar alcoholic and nonpolar hydrocarbon
solvents gave 1E in low ee (0%–2%), irrespective of the sensi-
tizer used (2 or 3). However, the use of diethyl ether as a
solvent led to the formation of antipodal 1E in the highest
ee’s of +9.3% and ꢂ7.2% at ꢂ40ꢀC upon sensitization with 2
and 3, respectively (Table 1).
Fig. 1. (a) Top view of 2 and (b) side view of [2•1Z] complex optimized by
the MM2 program; the aromatic part is emphasized as a space-filling model.
To elucidate the effects of solvent on the structure of CNN sen-
sitizers, UV–vis and circular dichroism spectra of 2 were mea-
sured in some of the solvents used earlier. As can be seen from
the UV–vis spectra of 2 (Fig. 3), the 1La band at 240–250 nm is
less dramatic reduction of ee in less polar butanol. Hence, we
cannot rigorously rule out the minor contribution of the hy-
drophobic interaction in the chirality transfer process, proba-
bly in the ground and/or excited state.
1
red-shifted, whereas the Lb band at 280–300 nm blue-shifted
by altering the solvent from butanol and ether to water and
ethanol. This suggests a greater contribution of the carboxylate
rather than carboxylic acid form of iso/terephthalate in more
polar solvents. In contrast, the circular dichroism spectra are
less informative (Fig. 4), displaying only very weak Cotton
Isophthalate versus Terephthalate Sensitization
Somewhat unexpectedly, the seemingly small difference in
the position of the hydroxycarbonyl substituent turned out to
have significant influences on the stereochemical outcomes
to afford antipodal 1E upon sensitization with CNN isophtha-
late 2 versus terephthalate 3. Thus, in aqueous solution at
1
effects of similar profiles with Δe < 1.0 Mꢂ1 cmꢂ1 for both La
1
and Lb bands. This result seems reasonable in view of the
Fig. 2. Hydrogen-1 nuclear magnetic resonance spectra of (a) 1Z (1.0 mM), (b) a mixture of 1Z (1.0 mM) and 2 (8.0 mM), and (c) 2 (8.0 mM) in D2O at 20 ꢀC;
the enlargements (top) show clear up-field shifts of olefinic H-1 and allylic H-2 proton signals, accompanied by the line broadening of all protons in the mixture (b).
Chirality DOI 10.1002/chir

SUPRAMOLECULAR PHOTOCHIROGENESIS WITH NOVEL CYCLIC TETRASACCHARIDE
Fig. 5. Eyring plots for the enantiodifferentiating photoisomerization of 1Z
Fig. 3. Ultraviolet–visible spectra of 2 measured in water (solid line), etha-
nol (dashed line), butanol (dotted line), and ethyl ether (dash-dotted line) at
20 ꢀC.
sensitized by 2 in H O ( ), 10% aqueous MeOH (○), and Et2O (▲).
▪
2
Fig. 6. Eyring plots for the enantiodifferentiating photoisomerization of 1Z
Fig. 4. Circular dichroism spectra of 2 measured in water (solid line),
ethanol (dashed line), butanol (dotted line), and ethyl ether (dash-dotted line)
at 20 ꢀC.
sensitized by 3 in H O ( ), 10% aqueous MeOH (○), EtOH (△), and Et2O (▼).
▪
2
relatively distant position of the nearest stereogenic center from
the aromatic chromophore in 2.
TABLE 2. Differential activation entropy (ΔΔS{) and enthalpy
(ΔΔH{) changes for the formation of enantiomeric 1E in
photoisomerization of 1Z mediated by 2 and 31
Temperature Dependence Studies
2
As was the case in the conventional enantiodifferentiating
photosensitization of 1Z reported earlier,12,13,18 the product’s
ee was a critical function of the reaction temperature, occa-
sionally leading to an inversion of the product chirality, as
shown in Table 1. To quantitatively elucidate the enantiodif-
ferentiating mechanism, we plotted the logarithm of the rela-
tive rate constant for giving (S)- and (R)-1E, that is, ln(kS/kR)
or ln[(100 + %ee)/(100 ꢂ %ee)], as a function of reciprocal
temperature to obtain excellent straight lines in all the exam-
ined cases (listed in Table 1), as illustrated in Figures 5 and 6.
The good straight line indicates that the enantiodifferentia-
tion mechanism does not change at least in the temperature
range employed.
ΔΔH{/kJ
ΔΔS{/J
TΔΔS{ /kJ
Sensitizer
Solvent
H2O
molꢂ1
molꢂ1 Kꢂ1
molꢂ1
2
2.2
1.5
ꢂ1.3
ꢂ0.8
ꢂ0.7
ꢂ0.3
1.8
7.8
5.4
ꢂ4.2
ꢂ2.4
ꢂ2.5
ꢂ1.0
6.1
2.3
1.6
ꢂ1.2
ꢂ0.7
ꢂ0.7
ꢂ0.3
1.8
10%MeOH
Et2O
H2O
10%MeOH
EtOH
Et2O
3
1Differential activation parameters derived from the Eyring plots.
2T = 298 K.
To more quantitatively and globally discuss the factors and
mechanism controlling the enantiodifferentiation process, we
calculated the differential activation enthalpy (ΔΔH{) and en-
tropy (ΔΔS{) from the slope and intercept of the regression
line by using the established procedures.12,33 The activation
parameters obtained are listed in Table 2. It is remarkable that,
although the activation parameters obtained are dynamic func-
tions of the sensitizer and solvent used, the ΔΔH{ and ΔΔS{
values consistently share the same sign, and the ΔΔH{ and
TΔΔS{ values are comparable in magnitude at T = 298 K for
all the sensitizer/solvent systems. The former fact suggests
the existence of equipodal temperature (T0) at which the
enthalpic gain/loss is canceled out by the entropic loss/gain,
whereas the latter accounts for the very low ee’s obtained at
ambient temperatures. Because ΔΔG{ = ΔΔH{ ꢂ TΔΔS{, the
product’s ee can be enhanced to the opposite direction to form
the antipodal products by performing the photosensitization at
temperatures lower or higher than T0, provided that ΔΔS{ ¼
0. Because of the relatively large activation parameters and
Chirality DOI 10.1002/chir

YANG ET AL.
present results also demonstrate the enantiodifferentiating
photoisomerization of cyclooctene functions as a sensitive
benchmark test for assessing chiral auxiliaries and hosts, even
in the borderline cases examined in this study.
LITERATURE CITED
1. Inoue Y. Asymmetric photochemical reactions in solution. Chem Rev
1992;92:741–770.
2. Griesbeck AG, Meierhenrich UJ. Asymmetric photochemistry and photo-
chirogenesis. Angew Chem Int Ed 2002;41:3147–3154.
3. Inoue Y, Ramamurthy V, editors. Chiral photochemistry. New York:
Marcel Dekker; 2004.
4. Müller C, Bach T. Chirality control in photochemical reactions: enantiose-
lective formation of complex photoproducts in solution. Aust J Chem
2008;61:557–564.
5. Sivaguru J, Natarajan A, Kaanumalle LS, Shailaja J, Uppili S, Joy A,
Ramamurthy V. Asymmetric photoreactions within zeolites: role of
confinement and alkali metal ions. Acc Chem Res 2003;36:509–521.
Fig. 7. Enthalpy–entropy compensation plot for the differential activation
parameters obtained for the enantiodifferentiating photoisomerization of
cyclooctene 1Z sensitized by 2 (square) and 3 (open circle).
6. Bauer A, Westkämper F, Grimme S, Bach T. Catalytic enantioselective
reactions driven by photoinduced electron transfer. Nature 2005;
436:1139–1140.
7. Tung CH, Wu LZ, Zhang LP, Chen B. Supramolecular systems as micro-
reactors: control of product selectivity in organic phototransformation.
Acc Chem Res 2003;36:39–47.
8. Tung CH, Guan JQ. Remarkable product selectivity in photosensitized
oxidation of alkenes within nafion membranes. J Am Chem Soc 1998;
120:11874–11879.
the wide applicable temperature range, the highest ee’s of
+9.3% and ꢂ7.2% were achieved by 2 and 3, respectively,
in ether at ꢂ40 ꢀC and ꢂ30 ꢀC.
Enthalpy–Entropy Compensation
In conventional enantiodifferentiating photosensitization, the
compensatory ΔΔH{–ΔΔS{ relationship is often observed, con-
firming the mechanistic consistency throughout the reaction
conditions employed.32,35 Hence, we plotted the ΔΔH{ values
against the ΔΔS{ values obtained in the present system to ob-
tain an excellent straight line passing through the origin:
ΔΔH{ = 0.29ΔΔS{–0.04 (correlation coefficient 0.99), as illus-
trated in Figure 7. This suggests that the same enantiodifferen-
tiation mechanism is operative despite the changes in solvent
and sensitizer. From the slope, we can determine that the equi-
podal temperature (T0) was calculated as 292 K for this enantio-
differentiating photosensitization.
9. Sivaguru J, Poon T, Franz R, Jockusch S, Adam W, Turro NJ. Stereo-
control within confined spaces: enantioselective photooxidation of
enecarbamates inside zeolite supercages.
J Am Chem Soc 2004;
126:10816–10817.
10. Yang H, Bohne C. Chiral discrimination in the fluorescence quenching of
pyrene complexed to b-cyclodextrin.
1995;86:209–217.
J Photochem Photobiol Chem
11. Fukuhara G, Mori T, Wada T, Inoue Y. Entropy-controlled supramolecular
photochirogenesis: enantiodifferentiating Z-E photoisomerization of cyclooc-
tene included and sensitized by permethylated 6-O-benzoyl-b-cyclodextrin.
Chem Commun 2005;4199–4200.
12. Inoue Y, Matsushima E, Wada T. Pressure and temperature control of
product chirality in asymmetric photochemistry. enantiodifferentiating
photoisomerization of cyclooctene sensitized by chiral benzenepolycar-
boxylates. J Am Chem Soc 1998;120:10687–10696.
13. Inoue Y, Yokoyama T, Yamasaki N, Tai A. An optical yield that increases
with temperature in a photochemically induced enantiomeric isomerization.
Nature 1989;341:225–226.
14. Yang C, Mori T, Wada T, Inoue Y. Supramolecular enantiodifferentiating
photoisomerization of (Z,Z)-1,3-cyclooctadiene included and sensitized
by naphthalene-modified cyclodextrins. New J Chem 2007;31:697–702.
15. Kaneda M, Nakamura A, Asaoka S, Ikeda H, Mori T, Wada T, Inoue Y.
Pressure control of enantiodifferentiating photoisomerization of cyclooc-
tenes sensitized by chiral benzenepolycarboxylates. The origin of discon-
tinuous pressure dependence of the optical yield. Org Biomol Chem
2003;1:4435–4440.
CONCLUSION
In the present study, two new cyclic tetrasaccharide sensiti-
zers 2 and 3 were prepared by introducing a hydrogen
isophthalate or terephthalate moiety to the six position of a
1,3-linked glucose unit of CNN. These CNN derivatives were
used as chiral supramolecular sensitizers for mediating the
enantiodifferentiating photoisomerization of 1Z to facially chi-
ral 1E. The photoisomerization of 1Z sensitized by these two
CNN derivatives was appreciably accelerated in aqueous solu-
tions to give antipodal 1E in modest optical yields (1%–5% ee),
which are comparable with those obtained upon supramolecu-
lar photosensitization with a-CD benzoate (1%–3% ee), suggest-
ing weak hydrophobic interactions to promote hydrophobic
contacts with chiral CNN moiety in the excited state. More
interestingly, the photosensitization in ether afforded antipodal
1E in the highest ee of +9.3% and ꢂ7.2%, respectively. Thus, the
ee of 1E was highly sensitive to sensitizer, solvent, and temper-
ature employed, and the product chirality was often switched
by altering solvent and temperature. The temperature-driven
switching of product chirality was attributed to the nonzero
differential activation entropy (ΔΔS{). The differential activa-
tion parameters were critical functions of solvent and sensitizer
but still obeyed the enthalpy–entropy compensation relation-
ship, suggesting the same enantiodifferentiation mechanism
operating irrespective of the sensitizer and solvent used. The
Chirality DOI 10.1002/chir
16. Inoue Y, Sugahara N, Wada T. Vital role of entropy in photochirogenesis.
Pure Appl Chem 2001;73:475–480.
17. Wang Q, Yang C, Ke C, Fukuhara G, Mori T, Liu Y, Inoue Y. Wavelength-
controlled supramolecular photocyclodimerization of anthracenecarboxy-
late mediated by g-cyclodextrins. Chem Commun 2011;6849–6851.
18. Inoue Y, Yokoyama T, Yamasaki N, Tai A. Temperature switching of product
chirality upon photosensitized enantiodifferentiating cis-trans isomerization
of cyclooctene. J Am Chem Soc 1989;111:6480–6482.
19. Inoue Y, Dong SF, Yamamoto K, Tong L-H, Tsuneishi H, Hakushi T, Tai
A. Inclusion-enhanced optical yield and E/Z ratio in enantiodifferentiating
photoisomerization of cyclooctene included and sensitized by b-cyclodextrin
monobenzoate. J Am Chem Soc 1995;117:11033–11034.
20. Inoue Y, Wada T, Sugahara N, Yamamoto K, Kimura K, Tong L-H, Gao
X-M, Hou Z-J, Liu Y. Supramolecular photochirogenesis. 2. Enantiodif-
ferentiating photoisomerization of cyclooctene included and sensitized
by 6-O-modified cyclodextrins. J Org Chem 2000;65:8041–8050.
21. Fukuhara G, Mori T, Wada T, Inoue Y. Entropy-controlled supramolecular
photochirogenesis: enantiodifferentiating Z-E photoisomerization of

SUPRAMOLECULAR PHOTOCHIROGENESIS WITH NOVEL CYCLIC TETRASACCHARIDE
cyclooctene included and sensitized by permethylated 6-O-modified a-tocopherol, cholecalciferol and EPA using CNN. J Jpn Soc Food Sci
b-cyclodextrins. J Org Chem 2006;71:8233–8243.
Technol 2007;54:326–331.
22. Lu R, Yang C, Cao Y, Tong L, Jiao W, Wada T, Wang Z, Mori T, Inoue Y.
Enantiodifferentiating photoisomerization of cyclooctene included and
sensitized by aroyl-b-cyclodextrins: a critical enantioselectivity control
by substituents. J Org Chem 2008;73:7695–7701.
29. Bradbrook GM, Gessler K, Cote GL, Momany F, Biely P, Bordet P, Perez S,
Imberty A. X-ray structure determination and modeling of the cyclic tetrasac-
charide cyclo-{!6)-a-D-Glcp-(1!3)-a-D-Glcp-{1!6)-a-D-Glcp-(1!3)-a--Glcp-
(1!}. Carbohydr Res 2000;329:655–665.
23. Lu R, Yang C, Cao Y, Wang Z, Wada T, Jiao W, Mori T, Inoue Y. Supramolec-
30. Funasaki N, Ishikawa S, Hirota S, Neya S, Nishimoto T. Structure and
ethanol complexation of cyclic tetrasaccharide in aqueous solution
studied by NMR and molecular mechanics. Chem Pharm Bull 2004;
52:708–713.
ular enantiodifferentiating photoisomerization of cyclooctene with modified
b-cyclodextrins: critical control by
2008;3:374–375.
a host structure. Chem Commun
31. Dunlap CA, Cote GL, Momany FA. Oxidation and metal-ion affinities of a
novel cyclic tetrasaccharide. Carbohydr Res 2003;338:2367–2373.
24. Biely P, Cote GL, Burgess-Cassler A. Purification and properties of alternanase,
a novel endo-a-1,3-a-1,6-D-glucanase. Eur J Biochem 1994;226:633–639.
32. Inoue Y, Ikeda H, Kaneda M, Sumimura T, Everitt SRL, Wada T. Entropy-
controlled asymmetric photochemistry: switching of product chirality by
solvent. J Am Chem Soc 2000;122:406–407.
33. Inoue Y, Yamasaki N, Yokoyama T, Tai A. Enantiodifferentiating Z-E
photoisomerization of cyclooctene sensitized by chiral polyalkyl benzene-
polycarboxylates. J Org Chem 1992;57:1332–1345.
25. Cote GL, Biely P. Enzymically produced cyclic a-1,3-linked and a-1,6-linked
oligosaccharides of D-glucose. Eur J Biochem 1994;226:641–648.
26. Aga H, Higashiyama T, Watanabe H, Sonoda T, Nishimoto T, Kubota M,
Fukuda S, Kurimoto M, Tsujisaka Y. Production of cyclic tetrasaccharide
from starch using a novel enzyme system from Bacillus globisporus C11.
J Biosci Bioeng 2002;94:336–342.
34. Inoue Y, Yamasaki N, Yokoyama T, Tai A. Highly enantiodifferentiating
photoisomerization of cyclooctene by congested and/or triplex-forming
chiral sensitizers. J Org Chem 1993;58:1011–1018.
35. Hoffmann R, Inoue Y. Trapped optically active (E)-cycloheptene generated
by enantiodifferentiating Z-E photoisomerization of cycloheptene sensitized
by chiral aromatic esters. J Am Chem Soc 1999;121:10702–10710.
27. Aga H, Nishimoto T, Kuniyoshi M, Maruta K, Yamashita H, Higashiyama
T, Nakada T, Kubota M, Fukuda S, Kurimoto M. 6-a-Glucosyltransferase
and 3-a-isomaltosyltransferase from Bacillus globisporus N75. J Biosci
Bioeng 2003;95:215–224.
28. Oku K, Kudou N, Kurose M, Shibuya T, Chaen H, Fukuda S. The crystal
properties of cyclic nigerosyl-(1!6)-nigerose (CNN) and powdering of
Chirality DOI 10.1002/chir