Catalytic enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid mediated by a non-sensitizing chiral metallosupramolecular host.
Catalytic Enantiodifferentiating Photocyclodimerization of 2-
Anthracenecarboxylic Acid Mediated by a Non-Sensitizing Chiral
Chenfeng Ke, Cheng Yang, Tadashi Mori, Takehiko Wada, Yu Liu,* and Yoshihisa Inoue*
In remarkable contrast to the recent progress in asymmetric
syntheses in the ground state, its counterpart in photochem-
istry, or “photochirogenesis”, is still a challenge for chemists,
mostly because of the short-lived weak interactions available
in the excited state.The success in conventional asymmetric
synthesis owes largely to the use of chiral transition metal
catalysts.A similar approach seems to be applicable to the
photochemical asymmetric synthesis, but chiral metal com-
plexes have rarely been employed in chiral photochemistry,
with the exception of a few attempts.The lack of success is
probably due to the photoinduced electron transfer occurring
between metal and ligand or substrate in the complex,
resulting in the quenching of excited substrate or dissociation
of chiral ligand. The only method to achieve catalytic
photochirogenesisis the use
system.[4,5]Therefore, the development of a novel non-
sensitizing, yet catalytic, photochemical route to chiral
compounds should greatly expand the range of photochiro-
genesis. Herein, we report the first catalytic enantiodifferen-
tiating photoreaction mediated by a metallosupramolecular
host. This system enables us not only to critically control the
orientation and enantioface selectivity of substrate accom-
modated in a chiral host, but also to accelerate the photo-
reaction with a catalytic amount of host, thus providing a
convenient strategy to achieve the catalytic photochirogenesis
without using the conventional chiral photosensitization.
Enantiodifferentiating supramolecular [4+ +4] photocyclo-
dimerization of 2-anthracenecarboxylic acid (AC) (Scheme 1)
mediated by g-cyclodextrin (CD) derivatives is known to give
chiral syn-head-to-tail (syn-HT) dimer 2 and anti-head-to-
head (anti-HH) dimer 3 in good enantiomeric excess (ee).
Thus, the photocyclodimerization mediated by native g-CD
gives 2 in 51% ee, whereas the same reaction mediated by
dimethylaminoethylamino-g-CD affords 3 in 41% ee. In spite
of the good ee values obtained in these supramolecular
photochirogenic reactions, an excessamountof chiralhost has
to be used to attain the highest ee values by minimizing the
population and photoreaction of free AC in the bulk solution.
In the present study, we synthesized a series of g-CD
derivatives 5–8 as chiral hosts by the reactions of 6-O-
tosylated g-CD with the corresponding amines.The free and
metal-coordinated diamino side chains introduced onto g-CD
are expected to enhance the complexation of AC and control
its orientation and enantioface selectivity in the CD cavity
through electrostatic interaction or ligation to a divalent
metal cation. Therefore, this complexation should accelerate
the subsequent photocyclodimerization of ACs accommo-
dated in the cavity, eventually achieving the catalytic photo-
chirogenesis with enhanced chemical and optical yields.
AC (0.2 mm) is soluble in a 1:1 mixture of methanol and
an aqueous buffer solution (pH 5) at 208 8C, but forms
aggregates at lower temperatures in the absence of host,
which was revealed by a bathochromic shift of the AC
absorption (0-0 band) from 386 nm to 429 nm (Supporting
Information, Figure S1). However, in the presence of g-CD
hosts, no AC aggregate was formed even at ?508 8C. The
Scheme 1. Metallosupramolecular photocyclodimerization of 2-anthra-
cene carboxylate (AC) mediated by g-cyclodextrin derivatives possess-
ing a diamino side chain (5–8) in the presence and absence of
Cu(ClO4)2in aqueous methanol. *=chiral product; HH=head-to-
[*] Dr. C. F. Ke,[+]Prof. Y. Liu
Department of Chemistry and State Key Laboratory of
Elemento-Organic Chemistry, Nankai University
Tianjin, 300071 (China)
Dr. C. Yang,[+]Dr. T. Mori, Prof. Y. Inoue
Department of Applied Chemistry, Osaka University
2-1 Yamada-oka, Suita, 565-0871 (Japan)
Prof. T. Wada
Institute of Multidisciplinary Research for Advanced Materials
(IMRAM) Tohoku University, Miyagi (Japan)
[+] These authors contributed equally to this work.
[**] This work was supported by JST (C.Y. and Y.I.), JSPS (T.W., T.M., and
Y.I.), and the 973 Program of China (2006CB932900, C.K. and Y.L.).
C.K. thanks the National Studying Abroad Fund of China for the
support of his stay in Japan. We thank Dr. Meng Cao of Xi’an
Jiaotong University for helpful discussions.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2009, 48, 6675–6677? 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
stepwise 1:1 and 1:2 association constants were determined
for g-CD derivatives 6 and 7 by UV/Vis spectroscopic
titration in aqueous methanol solution at ?508 8C (Table 1).
The K1values for 6 and 7 are much larger than that obtained
in water at 08 8C (275 Lmol?1), for which the reduced temper-
ature, stronger electrostatic interactions in the less polar
solvent and the co-inclusion of methanol in 1:1 complex
would be jointly responsible. The last factor may also
rationalize the smaller K2values that are observed. Coordi-
nation of copper(II) to 6 appreciably reduces the K1value to
569 Lmol?1, but raises the K2value to 3200 Lmol?1, thus
enhancing the contribution of 1:2 complex (K2/K1) without
lowering the overall affinity (K1K2).
Photoirradiation of AC with and without native or
modified g-CDs 5–8 was carried out at wavelengths longer
than 320 nm in a 1:1 methanol/aqueous buffer mixture at
?508 8C to give the results shown in Table 2 (see also the
Supporting Information, Table S2). In the absence of host, the
photocyclodimerization was extremely slow because of the
bimolecular nature of photodimerization and the AC aggre-
gation mentioned above. However, the addition of the CD
host led to a substantial acceleration of photocyclodimeriza-
tion, and the irradiation of AC with 5 and 6 gave the sterically
and electrostatically less-favored HH dimers as major prod-
ucts in 51–59% combined relative yields, which are signifi-
cantly higher than those (33–37%) obtained with native g-CD
and the other modified CDs 7 and 8 as a result of the effective
interaction of AC with the diamino side chain. The ee value
with 3 also improved from ?7% with native g-CD to ?15%
with 2-aminoethylamino-g-CD 5, and up to ?48% with N,N-
diethylaminoethylamino-g-CD 6 by using a fivefold excess of
CD relative to AC. Elongation of the inter-amino distance in
7 led to a decrease in HH yield but a comparable ?47% ee for
3. In contrast, piperazine-modified g-CD 8 gave the lowest
HH yield and ee for 3, which is probably due to the chair
conformation of piperazine, in which the terminal amino
group is oriented outward and thus cannot control the
orientation of AC accommodated in the cavity.
Copper(II) perchlorate, stoichiometric to the CD host
(that is, [AC]/[CD]/[Cu]=1:5:5), was then added to the
system to examine the effects of chelation of the diamino side
chain in 5–8 to copper(II) on the photo- and stereochemical
outcomes. As shown in Table 2, the addition of copper(II)
moderately decelerated the photocyclodimerization, but sig-
nificantly shifted the product distribution to the HH dimers in
all examined cases. The enhanced HH preference may be
attributed to the coordination of two ACs to copper(II)
chelated by the side chain, and also to the reduced electro-
static repulsion in the CD cavity.
Intriguingly, the ee value of 3 was significantly enhanced
from ?48% to ?60% upon addition of copper(II) to 6,
whereas the effect of copper(II) was almost negligible for 7
and 8. This contrasting behavior is probably due to the less-
efficient chelation of the diamino side chain of the latter two
hosts. To achieve catalytic photoreaction, we reduced the
amount of 6 down to a 0.1 equiv of AC to obtain the major
product 3 in ?45% ee, which is comparable to that (?48%)
obtained with a fivefold excess of AC. The acceleration of
photocyclodimerization in the cavity and possibly the sup-
pression in the bulk solution owing to the aggregation of free
AC would be jointly responsible for this efficient catalysis
(Table 2 and the Supporting Information).
Upon addition of copper(II) (0.1 to 0.5 equiv of AC), the
conversion was reduced from 51% to 12% owing to the
decelerated photocyclodimerization both inside and outside
the cavity. Meanwhile, both the relative yield and ee of 3
increased in the presence of 0.1 equiv of 6 upon addition of
copper(II) (0.1 equiv to 0.5 equiv). Under the optimized
conditions ([AC]/[CD]/[Cu]=1:0.1:0.5), the relative yield and
ee of 3 simultaneously reached the maxima (52% and ?70%
Table 1: Association constants for the stepwise 1:1 and 1:2 complexation
of AC with native and modified g-CDs.
T [8 8C]K1[Lmol?1]K2[Lmol?1]K1K2
[a] Solvent B: aqueous phosphate buffer at pH 5; solvent BM: a 1:1
(w/w) mixture of phosphate buffer and methanol.
Table 2: Photocyclodimerization of AC in the presence of native and
modified g-CDs with and without added Cu(ClO4)2.[a]
Relative yield [%][c]
38 22 27 13 60
37 18 33 12 55
41 26 26
37 24 31
27 14 21 38 41
25 15 23 37 40
32 17 21 30 49
19 12 30 39 31
21 15 34 25 41
22 15 32 31 37
13 7 52 28 20
138 53 26 21
139 51 27 22
21 12 34 23 33
24 12 43 21 36
45 18 20 17 63
28 16 31 25 44
40 24 23 12 64
31 19 33 17 50
g-CD 5 7 67
[a] Irradiation of AC (0.2 mm) performed at l>320 nm in a 1:1 mixture
(w/w) of phosphate buffer (pH 5) and methanol at ?508 8C. [b] Conversion
after 1 h irradiation, unless noted otherwise. [c] Relative yield and ee (error
in ee<3%) determined by chiral HPLC (ODS+Daicel OJ-RH); see Ref. ;
the positive/negative ee value indicates the dominant formation of first/
second-eluting enantiomer. [d] Not determined. [e] Conversion after 12 h
irradiation. [f] Conversion after 40 h irradiation. [g] Conversion after 30 min
? 2009 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimAngew. Chem. Int. Ed. 2009, 48, 6675–6677
ee at 12% conversion and 51% and ?64% ee even at 83%
chemical and optical yields higher than those (30% and
?60% ee) obtained with a fivefold excess of 6. However, the
photoreaction of AC in the presence of 0.1 equiv each of 6
and copper(II) ([AC]/[CD]/[Cu]=1:0.1:0.1) afforded 3 in
?49% ee, which is only slightly higher than that (?45% ee)
obtained in the absence of copper(II), and is much smaller
than that (?70% ee) obtained in the presence of 0.5 equiv of
copper(II). This result clearly indicates that the coordination
of the sidearm of 6 to copper(II) is not very strong, and a
fivefold excess is needed for sufficient complexation of 6 with
copper(II). Reducing of the amount of 6 down to 1% of AC
led to a lower ee of ?24%, which however recovered to
?43% by adding a 0.5 equiv of copper(II) ([AC]/[CD]/[Cu]=
1:0.01:0.5). These observations unambiguously reveal the
catalytic role played by the chiral metallosupramolecular
host. Furthermore, the fact that only a slight reduction in ee
wasobserved even at higherconversions may indicate thatthe
product inhibition of AC binding is minimal under the
conditions employed, probably because of the less efficient
inclusion of butterfly-shaped photodimers and the acceler-
ation of AC photodimerization in the CD cavity.
In this newly developed metallosupramolecular photo-
chirogenesis system, copper(II) incorporated in diamino-CD
plays dual crucial roles in achieving the concurrent enhance-
ment of chemical and optical yields of HH dimer 3 by
facilitating the formation of HH-oriented 1:2 complexes and
simultaneously discouraging the formation and photocyclo-
dimerization of the less-favored diastereomeric syn-HH
complex (Figure 1).
In this study, we have developed a new strategy for
realizing the catalytic photochirogenesis mediated by non-
sensitizing metallosupramolecular host, which enabled us to
achieve a 64–70% (or 43%) ee and a 51–52% (or 43%) yield
for anti-HH dimer 3 by using a 0.1 (or even a 0.01) equiv of
catalyst 6·CuIIin aqueous methanol at ?508 8C. Further studies
to elucidate the detailed mechanisms and to expand the scope
of metal-assisted catalytic supramolecular photochirogenesis
are in progress.
General procedure for the preparation of 6–8: 6-TsO-g-CD (300 mg)
was dissolved in alkanediamine or piperazine (5 mL), and the mixture
was stirred at 808 8C under argon for 12 h. The resulting solution was
added dropwise to 100 mL of acetone with stirring to give a
precipitate. The white precipitate was collected by centrifugation,
washed with acetone, dissolved in water, and freeze-dried to yield the
pure product as a white powder. 6:
4.88(m,8H),3.63–3.32(m, 46H),3.16(t, 1H,J=9.2 Hz),2.74(d, 1H,
J=12 Hz), 2.49–2.42 (m, 8H), 0.82 ppm (t, 6H, J=7.2 Hz). HR-ESI-
MS: m/z 1395.5515 [M+H], calcd 1395.5507. 7:1H NMR (400 MHz,
D2O): d=4.91 (m, 8H), 3.72–3.45 (m, 45H), 3,22 (t, 1H, J=9.2 Hz),
3.08 (q, 1H, J=12 Hz), 2.85 (d, 1H, J=12 Hz), 2.60–2.41 (m, 8H),
1.36 (m, 4H), 0.94 ppm (t, 6H, J=7.2 Hz). HR-ESI-MS: m/z
1423.5799 [M+H], calcd 1423.5819. 8:
d=4.90 (m, 8H), 3.89 (m, 1H), 3.72–3.30 (m, 46H), 3.21 (t, 1H, J=
9.2 Hz), 2.91–2.67 (m, 4H), 2.42 ppm (m, 4H); HR-ESI-MS: m/z
1387.4855 [M+Na], calcd 1387.4856.
1H NMR (400 MHz, D2O): d=
1H NMR (400 MHz, D2O):
Received: May 31, 2009
Published online: July 31, 2009
enantioselectivity · supramolecular chemistry
Keywords: anthracenecarboxylic acid · copper · cyclodextrins ·
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 For details, see the Supporting Information.
Figure 1. Photocyclodimerization of AC in the presence of 6·CuII.
Cu orange, O red, N blue.
Angew. Chem. Int. Ed. 2009, 48, 6675–6677? 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim