Diastereodifferentiating the [2+2] photocycloaddition of ethylene to arylmenthyl cyclohexenonecarboxylates: Stacking-driven enhancement of the product diastereoselectivity that is correlated with the reactant ellipticity

Article abstract of DOI:10.1002/chem.201000429

Upon diastereodifferentiating the [2+2] photocycloaddition of ethylene to a series of p-substituted (-)-8-phenylmenthyl cyclohexenonecarboxylates, the diastereoselectivity was critically controlled by the nature of the substituent introduced to the chiral auxiliary, and the p-nitro-substituted substrate afforded the cycloadducts in 90% diastereomeric excess (de) and with 97% isolated yield. Detailed experimental and theoretical conformation analyses revealed that the stacking interaction of the aromatic auxiliary with the cyclohexenone moiety plays the decisive role in determining the substrate conformation and is, therefore, responsible for the dramatic enhancement of the de. Of particular interest, the product de was directly related to the ellipticity of the substrate, enabling us to predict the de prior to photoirradiation.

Full text of DOI:10.1002/chem.201000429

DOI: 10.1002/chem.201000429
Diastereodifferentiating the [2+2] Photocycloaddition of Ethylene to
Arylmenthyl Cyclohexenonecarboxylates: Stacking-Driven Enhancement of
the Product Diastereoselectivity That Is Correlated with the Reactant
Ellipticity
Ken Tsutsumi,[a] Yuuki Yanagisawa,[a] Akinori Furutani,[a] Tsumoru Morimoto,[a]
Kiyomi Kakiuchi,*[a] Takehiko Wada,[b] Tadashi Mori,[c] and Yoshihisa Inoue*[c]
Abstract: Upon diastereodifferentiat-
ing the [2+2] photocycloaddition of
ethylene to a series of p-substituted
(À)-8-phenylmenthyl cyclohexenone-
carboxylates, the diastereoselectivity
was critically controlled by the nature
of the substituent introduced to the
chiral auxiliary, and the p-nitro-substi-
tuted substrate afforded the cycload-
ducts in 90% diastereomeric excess
(de) and with 97% isolated yield. De-
tailed experimental and theoretical
conformation analyses revealed that
the stacking interaction of the aromatic
auxiliary with the cyclohexenone
moiety plays the decisive role in deter-
mining the substrate conformation and
is, therefore, responsible for the dra-
matic enhancement of the de. Of par-
ticular interest, the product de was di-
rectly related to the ellipticity of the
substrate, enabling us to “predict” the
de prior to photoirradiation.
Keywords: chirality · circular di-
chroism · diastereoselectivity · eth-
ylene · photocycloaddition
Introduction
gated a range of asymmetric [2+2] photocycloadditions to
reveal that the diastereodifferentiating photoreaction using
chiral auxiliaries is one of the most promising methods for
asymmetric induction.[3,4] So far, we have examined a variety
of chiral auxiliaries in the diastereoselective [2+2] photocy-
cloaddition of cyclohexenones to the smallest olefin, ethyl-
ene, and found that menthyl derivatives are the most effec-
tive chiral auxiliaries for obtaining [2+2] photoadducts in
high diastereomeric excesses (Scheme 1).[4]
Chiral menthyl auxiliaries have been widely applied not
only to photoreactions but also to various thermal reac-
tions,[5] such as Michael additions,[6] radical reactions,[7]
Diels–Alder reactions,[8] and Friedel–Crafts reactions.[9]
However, little is known about the factors and mechanisms
operating in the asymmetric induction process, in particular
the roles of the aromatic substituent introduced to the
menthyl auxiliary. In the present study, to gain deeper in-
sights into the mechanism of chiral induction, we systemati-
cally investigated the diastereodifferentiating [2+2] photocy-
cloaddition of ethylene to cyclohexenones modified with a
series of chiral p-substituted 8-phenylmenthyl auxiliaries.
The original conformations in the ground state, which are
believed to control the subsequent photochemical asymmet-
ric induction, were elucidated through X-ray crystallograph-
ic and circular dichroism (CD) spectral analyses as well as
Photochemical [2+2] cycloaddition constitutes an important
and versatile synthetic method for the construction of com-
plex (poly)cyclic molecules.[1] Recent progress in chiral pho-
tochemistry has driven us to develop reliable synthetic
routes to asymmetric photocycloaddition, because the pho-
tocycloadducts obtained are often valuable precursors to
biologically active natural products, such as terpenoids with
polyquinane skeletons.[2] Our and other groups have investi-
[a] Dr. K. Tsutsumi, Y. Yanagisawa, Dr. A. Furutani, Dr. T. Morimoto,
Prof. K. Kakiuchi
Graduate School of Materials Science
Nara Institute of Science and Technology (NAIST)
Takayama, Ikoma, Nara 630-0101 (Japan)
Fax : (+81)743 72 6089
E-mail: kakiuchi@ms.naist.jp
[b] Prof. T. Wada
Institute of Multidisciplinary Research for
Advanced Materials, Tohoku University
2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan)
[c] Dr. T. Mori, Prof. Y. Inoue
Department of Applied Chemistry, Osaka University
2-1 Yamada-oka, Suita 565-0871 (Japan)
Fax : (+81)6 6879 7923
E-mail: inoue@chem.eng.osaka-u.ac.jp
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FULL PAPER
Table 1. Diastereoselective [2+2] photocycloaddition of ethylene to cy-
clohexenonecarboxylates 1a–d with chiral 8-arylmenthyl auxiliaries at
À78 or À408C[a]
Ar
Solvent
Yield [%][b]
de [%][c]
1[d]
2
3
CH2Cl2
toluene
MCH[e]
84
87
86
40
55
44
4
5
6
CH2Cl2
toluene
MCH[e]
96
99
86
24
41
22
Scheme 1. Diastereoselective [2+2] photocycloaddition of ethylene to cy-
clohexenones.
7[d]
8[d]
9[d]
CH2Cl2
toluene
MCH[e]
95
99
96
50
75
81
theoretical calculations. We further attempted to correlate
the magnitude of the observed Cotton effect of the starting
material with the diastereoselectivities of the photocycload-
duct obtained.
10[f]
11[f]
12[g]
13[h]
14[g]
CH2Cl2
toluene
toluene
MCH[e]
MeCN
94
92
100
86
88
81
75
82
90
97
[a] A 0.05m solution of 1 in each solvent was purged with ethylene at
258C for 5 min and then irradiated under an ethylene atmosphere at À78
or À408C in a Pyrex flask (>280 nm), by using a 500 W high-pressure
Hg lamp as the light source. [b] Isolated yield by column chromatography
Results and Discussion
Diastereodifferentiating the photocycloaddition of cyclohex-
enonecarboxylates 1 with ethylene: The diastereodifferenti-
ating [2+2] photocycloadditions of a series of (À)-8-(p-sub-
stituted-phenyl)menthyl-modified cyclohexenone carboxy-
lates (1a–d) were performed under comparable conditions
to elucidate the roles of the aryl substituent introduced to
the menthyl moiety. The preparations of substrates 1a, 1c,
and 1d have been reported,[4,10] and the new chiral cyclohex-
enone 1b with the (À)-8-(4-isopropylphenyl)menthyl auxili-
ary was prepared by using a modified version of the report-
ed procedure.[4,10] The photoreaction was carried out in a va-
riety of solvents at À78 or À408C by irradiating an ethyl-
ene-saturated solution of 1 in a Pyrex flask at wavelengths
of >280 nm with a 500 W high-pressure mercury lamp, and
the products were analyzed by NMR spectroscopy.
The results are summarized in Table 1. The photoreaction
proceeded smoothly in each solvent to give two diastereo-
meric isomers 2 and 3 in high isolated yields, whereas the
diastereoselectivity turned out to depend critically on the
substituent introduced and the solvent used. The absolute
configuration of the major photoadduct 2 was determined
unequivocally as 1S,6S by a direct comparison with the X-
ray crystallographic structure of the major photoadduct ob-
tained from a related compound.[11] The NMR spectral fea-
ture of 2 is similar to that of the compound. In addition, we
transformed 2 into the methyl ester derivative according to
the literature procedure[11] and obtained a similar optical ro-
tation to that obtained for a specimen obtained from a
menthyl ester of which the configuration had been unambig-
1
on silica gel. [c] Determined by H NMR spectroscopy. [d] Reference [4].
[e] MCH: methylcyclohexane. [f] Reference [10]. [g] At À408C.
[h] 0.005m.
uously derived from an X-ray structure determination previ-
ously.[11]
Cyclohexenone 1a bearing the phenylmenthyl auxiliary
gave the photoadducts with a moderate diastereomeric
excess (de) of 40–55% in dichloromethane, toluene, and
methylcyclohexane (MCH; see Table 1, entries 1–3). Intro-
duction of a bulky isopropyl substituent at the para-position
of the phenyl ring in 1b significantly reduced the de (to 22–
41%) in all the solvents examined (entries 4–6). In contrast,
the use of the (4-methoxyphenyl)menthyl auxiliary in 1c
(entries 7–9) considerably enhanced the diastereoselectivity
with a clear tendency for increasing diastereoselectivity with
decreasing solvent polarity, thus affording moderate (50%)
de in dichloromethane but much better (81%) de in MCH.
Interestingly, the 4-nitrophenyl derivative 1d afforded the
photoadducts in high chemical (>86%) and optical yields
(>81% de) at À788C, irrespective of the solvent used (en-
tries 10–13). In particular, the best result (97% yield and
90% de) was obtained in polar acetonitrile at À408C
(entry 14); note that the reaction temperature was higher
than that (À788C) used for the other solvents due to the
higher freezing point of acetonitrile.
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K. Kaikiuchi, Y. Inoue et al.
Theoretical calculation of the conformer distribution of 1:
The presence and population of conformers of the starting
material 1 in the ground state can affect the diastereoselec-
tivity of the photocycloaddition. Although the cyclohexane
ring of the menthol moiety is fixed in the chair form, there
are at least four major conformations for 1 associated with
fected by the relative stability of the major conformers in
the ground state. The relative energies and the Boltzmann
distributions of the most stable ST and SC conformers were
calculated by the DFT method at the B3LYP 6-31G* level
to give the results shown in Table 2.[12]
The energy differences are about 2.0–6.7 kJmolÀ1 in favor
of the ST conformer. There is a good correlation between
the Boltzmann distribution and the de values. Thus, the sub-
strate with larger energy difference provides a higher de
value, and 1d gives the largest relative energy and the best
diastereoselectivity.
À
the rotations around the mentholꢁs C2 C8 bond and the cy-
clohexenone–carbonyl bond, the former of which leads to
stacked and unstacked (axial and trans) conformers and the
latter (s)-cis and (s)-trans conformers, as illustrated in
Figure 1. Thus, the conformer distributions were calculated
X-ray crystallographic analyses
of 1a–d: To obtain the experi-
mental support for the stable
conformer, X-ray crystallo-
graphic analyses were per-
formed for single crystals of
1a–d (Figure 2). All of the X-
ray structures obtained reveal
that the ST conformer is the
most stable among others. Fur-
thermore, the C1–C3 and to a
lesser extent the C2–C4 dis-
tance (Figure 2) are appreciably
shorter for 1c and 1d than for
1a and 1b (Table 3), which is
consistent with the higher con-
formational stability of the ST
conformer (Table 2) as a conse-
quence of the better stacking in
1c and 1d. We previously indi-
cated that the electrostatic and/
or dipole–dipole interactions
between the C=O moiety of cy-
clohexanone and the OMe
group attached to the aromatic
ring could stabilize the ST con-
Figure 1. Conformer distributions of 1c and 1d based on MMFF calculations.
for 1c and 1d by the MMFF method.[12] The results of the
calculation indicate that the stacked conformers, in which
the cyclohexenone ring and the aromatic ring are located
face-to-face, are more stable than the unstacked ones. Of
the four major conformations, the stacked (s)-trans (ST) is
the most stable, which is in accord with the results obtained
in our previous studies.[4]
The ST conformer affords the (1S,6S)-isomer 2 upon pho-
tocycloaddition to ethylene since the aromatic ring shields
the re-face of cyclohexenyl ring and the photoreaction is
faster than the bond rotation. On the contrary, the SC con-
former is presumed to yield the (1R,6R)-isomer 3. In our
previous single crystal X-ray crystallographic study, we re-
vealed that the major diastereomer of a related photoadduct
possesses the 1S,6S configuration.[11] Since 2 is of 1S,6S con-
figuration, it is likely therefore that the diastereodifferentia-
tion upon photocycloaddition is directly manipulated or af-
Table 2. Boltzmann distributions of the stable ST and SC conformers cal-
culated by the DFT method at the B3LYP 6-31G* level.
Substrate
Relative energy[a] [kJmolÀ1
]
ST/SC[b]
1a
1b
1c
1d
À2.000
À2.412
À2.983
À6.673
64:34
73:27
82:18
94:6
[a] Value for the ST conformer based on the SC one as 0 kJmolÀ1
[b] Boltzmann distribution.
.
formation of 1c.[4,10] In the case of 1d, the intramolecular
donor–acceptor interaction between the cyclohexenoneꢁs
HOMO and the nitrophenylꢁs LUMO (Figure 3)[12] may fur-
ther stabilize the stacking conformation. It is reasonable
therefore that these substrates, 1c and 1d, give the larger
relative energies (Table 2) and the higher diastereoselectivi-
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ACHTUNGTRENNUNG[2+2] Photocycloaddition of Ethylene
FULL PAPER
1
spectroscopy. In the H NMR spectra measured in CDCl3,
the olefinic proton signals of 1a–d appeared at a significant-
ly higher field than that of unsubstituted menthyl cyclohexe-
nonecarboxylate 1e.[13] Thus, the olefinic peak appeared at
d=6.13 for 1a,[14] 6.34 for 1b,[15] 6.16 for 1c,[14] and
5.92 ppm for 1d,[14] which are significantly upfield-shifted
from the original chemical shift at d=6.54 ppm observed for
1e.[13] It is likely that the upfield shift of the olefinic protons
is caused by the stacking of the cyclohexenone ring with the
aromatic group in solution.
We further measured the differential NOE of 1d in
CD2Cl2 at À788C. As shown in Figure 4, irradiation of the
Figure 2. X-ray structures of 1a–d.
Table 3. Distances between cyclohexenoneꢁs C3/C4 and phenylꢁs C1/C2.
À
À
Substrate
C1 C3 [ꢂ]
C2 C4 [ꢂ]
1a
1b
1c
1d
4.24
4.08
3.71
3.56
3.72
3.70
3.68
3.54
Figure 4. 1H NMR spectrum (differential NOE) of 1d at À788C.
olefinic proton Ha led to an NOE enhancement of the
signal of aromatic protons Hb and Hc (Hb: 0.41, Hc:
0.80%). In contrast, no clear NOE was observed at RT.
These results indicate that the enone moiety and the phenyl
ring are located in close proximity or stacked to each other
at low temperatures. The X-ray crystallographic analyses re-
vealed that the Ha–Hb and Ha–Hc distances in the ST con-
former of 1d are 3.792 and 3.670 ꢂ, respectively, which are
short enough to observe the NOE. Some of the protons in
the SC conformer are susceptive to NOE in its stacked form
but not in the unstacked ones, and the fact that the NOE is
more clearly observed at À788C indicates that the stacked
conformers are stabilized at lower temperatures, although
the ST and SC conformers are difficult to unambiguously
differentiate by the NMR spectroscopic analyses.
Figure 3. Molecular orbitals of 1d calculated by the DFT method at the
B3LYP 6-31G* level.
ties (Table 1) as a consequence of the better conformational
stabilization through the donor–acceptor interactions.
NMR studies of 1a–d: The above theoretical calculations
and the X-ray crystallographic data are in good agreement
with the trend of the diastereoselectivity of the photocy-
cloaddition. To obtain further experimental evidence for the
stacking interactions in solution, we performed the confor-
mational analyses of the starting materials 1 by using NMR
CD spectral analyses of 1: To obtain further insights into the
ST and SC conformers, we measured the CD spectra of 1.
As shown in Figure 5, 8-phenylmenthyl ester 1a gave an ap-
parent exciton couplet at the major band, whereas menthyl
ester 1e and (À)-8-phenylmenthol exhibited only weak
Cotton effects in the same region. This is reasonable, since
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7451

K. Kaikiuchi, Y. Inoue et al.
Figure 6. Excitonic CD spectrum model.
1a, 1b, 1c, and 1d at varying temperatures (Figure 7). The
CD spectra of 1a showed a redshift with an appreciable in-
tensity enhancement by lowering the temperature with an
apparent isodichroic point (Figure 7a). Similarly, the CD in-
tensity of 1b was enhanced at low temperatures (Figure 7b).
In the cases of 1c and 1d, a stronger negative exciton cou-
plet was observed even at room temperature and the inten-
sity was further increased with an apparent isodichroic point
at lower temperatures (Figure 7c and d).
Figure 5. CD spectra of 1a, 1e, and (À)-8-phenylmenthol in methylcyclo-
hexane at 258C.
The UV/Vis spectra also showed similar but much smaller
augmentation in intensity (Figure 8), which is attributable to
the peak sharpening and the increased concentration due to
the shrinking of the solution at low temperatures. To cancel
the effect of the volume change, we calculated the anisotro-
py factor (g=De/e) by using the relevant CD and UV/Vis
spectra obtained at each temperature. By using the g factor,
which is free from the change in solution volume or sub-
strate concentration, we can directly evaluate the effect of
temperature on the conformation. As can be seen from
Figure 8, the g factor of 1c and 1d significantly increases at
lower temperatures, which indicates the increased popula-
tion of the ST conformer. This CD spectral behaviour nicely
only 1a has two allowed p–p* transitions in a molecule. The
electric transition moments of the enone and phenyl chro-
mophores are coupled spatially to each other to produce the
strong intramolecular exciton coupling observed.
According to the exciton chirality theory,[16] the helical
sense of the spatial arrangement of two mutually coupling
transition moments determines the sign of the observed ex-
citon couplet. In the present case, the helical sense of the
two transition moments are opposite to each other for the
ST versus SC conformer, as illustrated in Figure 6. In the ST
conformer, the two transition
moments are positioned coun-
ter-clockwise to give a nega-
tive couplet, which means a
negative–positive sequence in
the CD sign from the longer
wavelength. On the contrary,
the two moments are twisted
clockwise in the SC conformer
to give a positive couplet. The
negative exciton coupling ob-
served for 1a (Figure 5) indi-
cates that the ST conformer is
more dominant than the SC
conformer, provided that the
magnitude of the exciton cou-
pling is comparable for both of
the conformers.
Since the population of con-
formers is a critical function of
the temperature in general, we
measured the CD spectra of Figure 7. CD spectra of 1a–d at 25, 0, À40, À78, and À1008C.
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ACHTUNGTRENNUNG[2+2] Photocycloaddition of Ethylene
FULL PAPER
Conclusion
In summary, we found that the
diastereoselectivity of the [2+2]
photocycloaddition of cyclohex-
enone to ethylene can be en-
hanced by introducing a p–p
stacking arylmenthyl auxiliary
to cyclohexenone, which func-
tions as a shield blocking the
attack of ethylene from one of
the diastereofaces of the cyclo-
hexenone ring. The theoretical
and CD spectral conformation
analyses revealed that the
stacked (s)-trans (ST) confor-
mer is more stable than the
stacked (s)-cis (SC) and other
unstacked conformers, and is
more populated at lower tem-
peratures to give the photocy-
Figure 8. UV/Vis spectra (top) and g factor profiles (bottom) of 1c and 1d at 25, 0, À40, À78, and À1008C
(left) and in acetonitrile at 25, 0, and À408C (right).
coincides with the higher diastereoselectivities obtained in
the photocycloaddition at lower temperatures.
Table 4. The CD intensity De of 1c and 1d and the diastereoselectivity
of photoproducts obtained at various temperatures.
Substrate Solvent
T
lent De
Yield[a] de[b]
ln([2]/
[3])
[8C] [nm]
A
]
[%]
[%]
Correlation between CD intensity and diastereoselectivity:
In the above discussion, we have elucidated that: 1) the aryl
and cyclohexenone moieties of 8-arylmenthyl cyclohexeno-
necarboxylates 1 are stacked to each other to form the ST
or SC conformer, 2) the magnitude of the Cotton effect of 1
reflects the population of stacked ST and SC conformers,
and 3) the conformer distribution in the ground state is the
major source of the diastereoselectivity achieved in the sub-
sequent photocycloaddition to ethylene. This scenario imme-
diately prompted us to examine the correlation of the CD
intensity of the starting material with the diastereoselectivity
of the photoadduct obtained.
For this purpose, we employed 1c and 1d as representa-
tive substrates (as they gave the highest De and de values),
and their CD spectra were measured and the photoreactions
were carried out at various temperatures to give the results
summarized in Table 4. Both the De and de values increased
with decreasing temperature to reach the largest values at
the lowest temperatures employed, that is, at À788C for 1c
and at À408C for 1d. Interestingly, the plots of ln([2]/[3])
against the De value at each CD extrema gave good linear
relationships, as shown in Figure 9. This indicates that the
productꢁs de obtained under a specific condition can be pre-
dicted by just measuring the CD spectrum of the substrate
at least for 1c and 1d. Although the number of the applica-
ble cases is rather limited in the present system, these are
the first examples that reveal such a clear correlation be-
tween the substrate CD intensity and the product diastereo-
selectivity.
1
2
3
4
5
6
7
8
1c
MCH[c]
25 237
223
À8.7
59
33
0.686
1.072
1.696
2.254
2.143
11.7
0
237 À10.2
223 15.4
À40 237 À13.3
224 18.7
32
82
96
97
49
69
81
79
À78 237 À16.2
224
25 266
230
21.9
-8.0
9
1d
MeCN
10
11
12
13
14
15
16
17
14.4
À4.8
À9.4
16.6
À5.7
210
0
266
230
210
93
97
84
90
2.442
2.944
À40 267 À11.4
230
209
20.5
À7.1
[a] Isolated yield by column chromatography on silica gel. [b] Deter-
mined by H NMR spectroscopy. [c] MCH: methylcyclohexane.
1
cloadducts in higher diastereoselectivities of up to 90% de.
A good linear relationship was found between the substrate
CD intensity and the product de for a couple of strongly
stacked substrates, enabling us to predict the diastereoselec-
tivity from the CD spectral examination before performing
the photoirradiation.
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K. Kaikiuchi, Y. Inoue et al.
precipitated dicyclohexylurea was re-
moved by filtration through a glass
filter, and the filtrate was washed with
0.5n HCl and then with a saturated
aqueous solution of NaHCO3. During
this procedure, additional precipitated
dicyclohexylurea was again removed
by filtration of both layers to facilitate
their separation. The organic layer was
dried (MgSO4) and concentrated in
vacuo. The residue was purified by
flash chromatography (AcOEt/hexane
5:95) to give ester 1b (1.45 g, 86%).
Colorless solid; m.p. 89.0–90.98C;
[a]2D5 =À25.9 (c=1.0 in dichlorome-
thane); IR (KBr): n˜ =2959, 1713, 1688,
1229 cmÀ1
;
1H NMR
(500 MHz,
CDCl3, 258C, TMS): d=7.15 (d, J=
8.6 Hz, 2H), 7.08 (d, J=8.6 Hz, 2H),
6.34 (s, 1H), 4.99 (td, J=10.7, 4.3 Hz,
1H), 2.84–2.79 (m, 1H), 2.36–2.26 (m,
3H), 2.10–2.07 (m, 2H), 1.93–1.88 (m,
2H), 1.86–1.83 (m, 1H), 1.78–1,73 (m,
1H), 1.69–1.65 (m, 1H), 1.55–1.48 (m,
1H), 1,29 (s, 3H), 1.21 (d, J=6.7 Hz,
3H), 1.19 (d, J=6.7 Hz, 3H), 1.18 (s,
Figure 9. Plots of the logarithm of the diastereomeric ratio, ln([2]/[3]), for 1c and 1d versus De at varying
wavelengths.
3H), 1.11 (td, J=13.0, 3.3 Hz, 1H), 1.01–0.86 ppm (m, 5H); 13C NMR
(126 MHz, CDCl3, 258C, TMS): d=200.1 (s), 165.5 (s), 149.3 (s), 148.7
(s), 145.3 (s), 132.4 (d), 125.9 (d, 2C), 125.1 (d, 2C), 75.7 (d), 50.2 (d),
41.7 (t), 39.0 (s), 37.6 (t), 34.5 (t), 33.2 (d), 31.3 (d), 28.5 (q), 26.6 (t), 24.8
(q), 24.3 (t), 24.1 (q), 23.7 (q), 22.1 (t), 21.7 ppm (q); HRMS (EI): m/z:
calcd for C26H36O3: 396.2664; found: 396.2666.
Experimental Section
General: Mostly commercially available reagents were used without fur-
ther purification. All reactions and manipulations of air- and moisture-
sensitive compounds were carried out under an atmosphere of dry nitro-
gen by using standard vacuum line techniques. Melting points were deter-
mined on a Yanaco MP-500D micro melting point apparatus. Optical ro-
tations were determined on a JASCO DIP-1000 digital polarimeter by
using the sodium D line. Infrared spectra (IR) were obtained on a
JASCO FT/IR-420 spectrometer; absorption peaks are reported in recip-
rocal centimeters. High-resolution mass spectra (HRMS) were obtained
on a JEOL JMS-700 instrument. Flash column chromatography was per-
formed with Merck silica gel 60N. Proton nuclear magnetic resonance
spectra (1H NMR) and carbon nuclear magnetic resonance spectra
X-ray crystallographic analyses: Measurements were made on a Rigaku
RAXIS-RAPID Imaging Plate diffractometer with MoKa radiation at
296 K.
Compound 1b: C26H36O3; colorless needle (0.40ꢃ0.20ꢃ0.18 mm); mono-
clinic; space group=P21(#4); Z=2; a=6.140(4), b=19.964(12), c=
9.593(5) ꢂ; b=96.06(2)8; V=1169.4(12) ꢂ3; 1calcd =1.126 gcmÀ3
.
Of
11323 reflections, up to 2q=55.08, 5307 were independent (Rint =0.039)
and 2603 with I>3.00s(I). The structure was solved with direct methods
and refined with full matrix against all F2 data. Hydrogen atoms were cal-
culated in “riding” positions. wR=0.0740 and R=0.0580.
(13C NMR) were recorded on
a JEOL JNM-ECP500 spectrometer.
1H NMR spectra are reported as chemical shifts in parts-per-million
(ppm) relative to tetramethylsilane (TMS) as the internal standard. Data
are reported as follows: chemical shift in ppm (d), multiplicity (s = sin-
glet, d = doublet, t = triplet, q = quartet, td = triplet of doublet, brs
= broad singlet, m = multiplet), coupling constant (Hz), and integration.
13C NMR spectra are reported as chemical shifts in ppm based on the
middle peak of CDCl3 (d=77.0 ppm), and signal assignments (s, d, t, and
q) were made from DEPT experiments. High resolution mass spectra
(HRMS) were obtained on a JOEL JMS-700. UV/Vis spectra were re-
corded on a SHIMADZU UV-1600PC UV/Vis spectrophotometer. CD
specific rotations were measured in a 1 dm thermostated quartz cell on a
JASCO J-720 polarimeter with PTC-348WI as a temperature control
unit.
Compound 1d: C23H29O5N; colorless needle (0.40ꢃ0.17ꢃ0.10 mm); or-
thorhombic; space group=P212121 (#19); Z=4; a=6.5573(3), b=
15.6471(7), c=21.3024(9) ꢂ; V=2185.68(17) ꢂ3; 1calcd =1.214 gcmÀ3. Of
4804 reflections, up to 2q=54.98, 4804 were independent (Rint =0.000)
and 1815 with I>1.00s(I). The structure was solved and refined in a
manner analogous to 1b. wR2=0.0981 and R=0.0574. CCDC-766289
(1b) and -766290 (1d) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
Photoreaction of 1 with ethylene: Irradiations were carried out in a
Pyrex flask (>280 nm) installed in a water-cooled quartz immersion ap-
paratus, by using a HALOS 500 W high-pressure Hg lamp as the light
source. A 0.050m solution of 1 (0.10 mmol) was purged with ethylene for
5 min at 258C and irradiated at a given temperature under ethylene until
the enone was almost completely consumed. The reaction was monitored
by TLC on silica gel. After the solvent was evaporated, the residue was
purified chromatographically to give a photoadduct. The de value of pho-
Syntheses of 1a–d: (À)-(1R,2S,5R)-5-Methyl-2-(1-methyl-1-phenylethyl)-
cyclohexyl 3-oxo-1-cyclohexenecarboxylate (1a) was prepared according
to Langeꢁs procedure.[3a,b] (À)-(1R,2S,5R)-5-Methyl-2-[1-methyl-1-(4-me-
thoxyphenyl)ethyl]cyclohexyl 3-oxo-1-cyclohexenecarboxylate (1c) and
(À)-(1R,2S,5R)-5-methyl-2-[2-(4-nitrophenyl)propan-2-yl]cyclohexyl-3-
oxo-1-cyclohexenecarboxylate (1d) were prepared according to literature
procedures.[4,10]
1
toadduct was determined by H NMR spectroscopy.
(À)-(1R,2S,5R)-2-[2-(2-Isopropylphenyl)propan-2-yl]-5-methylcyclohexyl
3-oxo-1-cyclohexenecarboxylate
(1b):
1,3-Dicyclohexylcarbodiimide
(DCC; 2.64 g, 12.8 mmol) was added to a mixture of 3-oxo-1-cyclohexe-
necarboxylic acid (0.66 g, 4.7 mmol), (+)-(R)-8-(4-isopropylphenyl)men-
thol (1.17 g, 4.3 mmol), and dimethylaminopyridine (DMAP; 0.21 g,
1.7 mmol) in dry CH2Cl2 (21 mL) at 08C. The mixture was stirred for
5 min at that temperature and then for 2.5 h at room temperature. The
Acknowledgements
We thank Mr. S. Katao and Mr. F. Asaoma for their assistance in X-ray
crystallography and 1H NMR NOEDF spectroscopy, respectively, and
7454
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 7448 – 7455

ACHTUNGTRENNUNG[2+2] Photocycloaddition of Ethylene
FULL PAPER
Ms. Y. Nishikawa for her help in HRMS measurements. This work was
supported by a Grant-in Aid for Scientific Research on Priority Areas
(B: no. 21310081 and 417) from the Ministry of Education, Culture,
Sports, Science and Technology of the Japanese Government (MEXT)
and the Foundation for Nara Institute of Science and Technology.
[11] K. Tsutsumi, H. Nakano, A. Furutani, K. Endo, A. Merpuge, T.
Shintani, T. Morimoto, K. Kakiuchi, J. Org. Chem. 2004, 69, 785.
[12] The calculations were performed by using the Spartan’06 software
molecular modeling package for Windows available from Wavefunc-
tion, Irvine, CA.
[13] The substrate 1e was reported,
see reference [4]. Compound 1e:
1H NMR
(400 MHz,
CDCl3,
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258C, TMS): d=6.54 (s, 1H),
4.55 (m, 1H), 2.36–2.17 (m, 4H),
1.83–1.80 (m, 2H), 1.65–0.75 (m,
9H), 0.68–0.51 ppm (m, 9H).
[14] Compound
1a:
1H NMR
(500 MHz, CDCl3, 258C, TMS):
d=7.31–7.37 (m, 3H), 7.22–7.15 (m, 2H), 6.13 (s, 1H), 4.98 (td, J=
11.8, 4.4 Hz, 1H), 2.31–1.98 (m, 5H), 1.89–1.82 (m, 4H), 1.70 (m,
1H), 1.49 (m, 1H), 1.33–1.14 (m, 7H), 1.06–0.84 ppm (m, 5H); 1c:
1H NMR (500 MHz, CDCl3, 258C, TMS): d=7.12 (d, J=8.5 Hz,
2H), 6.71 (d, J=8.5 Hz, 2H), 6.16 (s, 1H), 4.95 (td, J=10.7, 4.3 Hz,
1H), 3.68 (s, 3H), 2.33–2.00 (m, 5H), 1.93–1.65 (m, 5H), 1.50–1.40
(m, 1H), 1.26 (s, 3H), 1.14 (s, 3H), 1.02–0.84 ppm (m, 6H); 1d:
1H NMR (500 MHz, CDCl3, 258C, TMS): d=8.07 (d, J=9.2 Hz,
2H), 7.41 (d, J=9.2 Hz, 2H), 5.92 (s, 1H), 4.95 (td, J=10.7, 4.3 Hz,
1H), 2.28–2.05 (m, 5H), 1.92–1.75 (m, 5H), 1.60–1.46 (m, 1H), 1.34–
1.15 (m, 7H), 1.03–0.86 ppm (m, 5H).
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Received: February 18, 2010
Published online: May 12, 2010
Chem. Eur. J. 2010, 16, 7448 – 7455
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7455