A novel photodimerization of 4-aryl-4H-pyrans for cage compounds

Article abstract of DOI:10.1016/j.tetlet.2013.04.016

Irradiation of 4-aryl-4H-pyrans in either the solid state or in solution gave rise to the formation of novel oxa-cage compounds, 3,9-dioxatetraasteranes, derived from a double [2 + 2] cycloaddition reaction. Meanwhile, an unexpected oxetane formed by the Paternò-Büchi reaction of benzophenone with the pyrans, was established by ¹H NMR data as well as by X-ray crystallographic analysis. Experimental observations and theoretical calculations confirmed that the photodimerization was effectively catalyzed by the triplet excited state of benzophenone, while the Paternò-Büchi reaction was competitive with the process.

Full text of DOI:10.1016/j.tetlet.2013.04.016

Tetrahedron Letters 54 (2013) 3325–3328
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel photodimerization of 4-aryl-4H-pyrans for cage compounds
⇑
Hongxing Xin , Xiaohe Zhu , Hong Yan , Xiuqing Song
College of Life Science and Bio-engineering, Beijing University of Technology, Beijing 100124, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Irradiation of 4-aryl-4H-pyrans in either the solid state or in solution gave rise to the formation of novel
oxa-cage compounds, 3,9-dioxatetraasteranes, derived from a double [2 + 2] cycloaddition reaction.
Meanwhile, an unexpected oxetane formed by the Paternò–Büchi reaction of benzophenone with the
pyrans, was established by 1H NMR data as well as by X-ray crystallographic analysis. Experimental
observations and theoretical calculations confirmed that the photodimerization was effectively catalyzed
by the triplet excited state of benzophenone, while the Paternò–Büchi reaction was competitive with the
process.
Received 3 February 2013
Revised 26 March 2013
Accepted 2 April 2013
Available online 11 April 2013
Keywords:
Photodimerization
Ó 2013 Elsevier Ltd. All rights reserved.
3
,9-Dioxatetraasterane
Cage compound
Laser flash photolysis
DFT calculation
Cage compounds, especially those which possess rigid and
highly symmetric structures, such as cubane, pentaprismane, and
homocubane, have attracted considerable attention of chemists.
(Table 1, entry 1). The photoreaction was effectively catalyzed by
benzophenone (BP) (entry 2).
1
When 0.1 M MeOH solutions of 1a–h contained in a ACE reactor
cooled at 3 °C were irradiated in the presence of 0.05 equiv of BP,
the cage-dimeric 3,9-dioxatetraasteranes 2a–h mainly crystallized
from the solution during the irradiation and gave final yields of
about 10% (entries 3–10). These results suggest that the formation
of cage dimers in solution proceeds more effectively than in the so-
lid state owing to the favorable energy transfer in solution. How-
ever, irradiation of 4-(3-nitrophenyl)-4H-pyran failed to give the
desired [2 + 2] product even after a prolonged reaction time. The
similar behavior is observed in the photodimerization of 2-vinylfu-
These compounds have emerged as important building blocks for
2
the synthesis of polycyclic synthetic and natural products. Fur-
thermore, the functionalization reactions such as photochemical
3
carboxylation have led to the synthesis of new derivatives with
4
interesting pharmacological properties. However, this only in-
volves derivatives and not new basic structures. Their molecular
architecture presents still a challenging subject. Recently, photodi-
merization of 1,4-dihydropyridines has been reported to yield
head-to-tail cage dimers, 3,9-diazatetraasteranes, that hold prom-
5
7
8
ise as novel HIV protease inhibitors for their C
2
symmetry. How-
ran and 4-azachalcones, which is attributed to the efficient non-
radiative deactivation from nitro groups of the molecules in the
ever, the photochemical reaction of similar heterocyclic systems,
-aryl-4H-pyrans 1, has not been investigated because of the low
9
4
excited state.
photoreactivity. In this Letter, we report a unique double [2 + 2]
photodimerization of 4-aryl-4H-pyrans, in which the centrosym-
metric 3,9-dioxatetraasteranes 2 are obtained and enrich the pool
of interesting oxa-cage compounds (Scheme 1).
Much more interestingly, an unexpected oxetane 3c and other
photoproducts (4 and 5) were isolated (Scheme 2), along with 2c.
4
-Aryl-4H-pyrans 1a–h were prepared by a cyclocondensation
reaction of an aryl aldehyde and ethyl acetoacetate, catalyzed by
6
ZnCl
lid state and solution photoreactions were performed using a
00 W high-pressure mercury lamp fitted with a quartz filter (k
290 nm). Irradiation of 1a at room temperature for 72 h afforded
the formation of a novel double [2 + 2] photoadduct 2a in 7% yield
2
under ultrasound irradiation as previously described. All so-
5
>
⇑
Corresponding author. Tel./fax: +86 10 67396642 (H.Y.).
E-mail address: hongyan@bjut.edu.cn (H. Yan).
The authors contributed equally to this work.
Scheme 1. Formation of 3,9-dioxatetraasteranes 2 from 4-aryl-4H-pyrans 1.
0
040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.016

3
326
H. Xin et al. / Tetrahedron Letters 54 (2013) 3325–3328
Table 1
of the neighboring double bonds. Additionally, the methylene pro-
a
Photodimerization of 4-aryl-4H-pyrans 1a–h in solid state and solution
tons at ester groups are nonequivalent probably due to the
asymmetric environment around the cage structure. The centro-
symmetry of the cage structure is eventually determined by X-ray
crystallography of 2g (Fig. 1).
Entry Pyran Medium Sensitizer (equiv) Time (h) Product/yieldb (%)
1
2
3
4
5
6
7
8
9
1
1a
1a
1a
1b
1c
1d
1e
1f
Solid
Solid
–
72
24
15
15
15
15
24
24
15
15
2a/7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2
2
2
2
2
2
2
2
2
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
CO (0.05)
2a/10
2a/10
2b/7
2c/8
2d/10
2e/12
2f/9
Regarding the structure of oxetane 3c, its 1H NMR spectrum
exhibits two singlets at d = 2.07 and 2.20 ppm attributed to the
methyl group of pyran ring at C-6 and C-2, respectively. The signal
appearing as a singlet at 4.50 ppm for the H-4 proton is the less af-
fected and displays a small upfield shift upon formation of the oxe-
tane ring, owing to differences in the shielding effect of
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
c
1g
1h
2g/9
2h/8
0
13
neighboring groups. In the C NMR spectra, the characteristic sig-
a
Irradiation was performed with a 500 W high-pressure mercury lamp at room
nals for the oxetane ring resonate at 83.6, 105.9, and 113.5 ppm for
the bridgehead carbon atoms. Finally, X-ray structural analysis of
temperature; initial [1] = 0.1 M in methanol.
b
Yield of purified products.
Other minor products 3c, 4, and 5 were isolated.
3
c was carried out which shows nicely the planarity of the oxetane
c
ring and the anticipated cis disposition between the four- and six-
membered rings (Fig. 1).
The formation of compound 5 is unexceptional,10 being a conse-
quence of hydrogen abstraction by photoexcited BP from the sol-
vent followed by a combination of the resultant ketyl and
hydroxymethyl radicals. The formation of benzhydrol 4 is a result
When photodimerzation of 1 underwent BP-sensitized irradia-
tion, oxetane 3c was obtained via a Paternò–Büchi reaction. The re-
sult indicated that BP plays the role of triplet sensitizer, and the
triplet excited state of 4-aryl-4H-pyrans is crucial for the photodi-
merization. In order to obtain direct mechanistic evidence based
on the detection of possible reaction intermediates, laser flash pho-
tolysis of deaerated acetonitrile solution of BP in the presence of 1c
was performed at 355 nm (Nd:YAG, 7 ns laser pulse, unfocused ca.
13 mJ/pulse). The absorption spectrum at 520 nm is made up of
two components. The fast component decays with a first-order rate
1
1
of proton transfer from polar solvent (methanol) to ketyl radical.
It is noteworthy that the oxetane 3c is formally derived from a Pa-
ternò–Büchi photocycloaddition between 4H-pyran and triplet BP.
The other oxetane products from the reaction were detected in
trace by GC–MS but were not isolated.
The structures of 3,9-dioxatetraasteranes 2a–h were unequivo-
1
13
6
ꢁ1
12
cally determined on the basis of the ESI-MS, H, and C NMR spec-
tra including DEPT and 2D COSY. First of all, compounds 2 indicate a
symmetric structure according to which the number of carbon sig-
of 1.8 ꢀ 10 s , which is assigned to the triplet state of BP (Fig. 2).
The slow component appears with small signal intensity, and then
rapidly decays, which is likely due to the presence of the biradical
1
3
13
3
nals in the C NMR spectra is halved but the molecular ion in the
MS spectrum points to the dimer structure. In the higher field of
intermediate PB- DR as shown in Scheme 3. At longer times, the
transient species at 520 nm is quenched within 1.06 s to generate
l
1
the H NMR spectrum, a characteristic singlet signal that was as-
new species with an absorption maximum (kmax) at 420 nm. The
0
signed to the H-4 and H-4 in the two pyran rings appears at d
absorption band at 420 nm is attributed to neither the triplet BP
3
4
.2 ppm, whereas the absorption in the starting materials 1 is
nor the biradical PB- DR, but the intensity of the absorption in-
shifted downfield to 4.7 ppm as a result of the anisotropic effect
creases with the same rate as that for the decay at 520 nm (insert
Scheme 2. Photochemical reaction of 1c in methanol in the presence of benzophenone.
Figure 1. Molecular structures of 2g and 3c (displacement ellipsoids at the 50% probability level).

H. Xin et al. / Tetrahedron Letters 54 (2013) 3325–3328
3327
posed for our reaction (Scheme 3). The first step in the double
2 + 2] photocycloaddition is the excitation of the 4H-pyran 1, giv-
[
3
⁄
ing the lowest triplet 1 that happens either directly through en-
ergy transfer from the triplet BP or by intersystem crossing (ISC) of
singlet excited states. After an attack of the triplet excited double
bond to the neighboring
p bond, an initially formed triplet biradi-
3
cal intermediate PD- DR can undergo ISC to the ground state birad-
ical which is close to the cycloadduct syn. Subsequently, the
formation of second cyclobutane ring takes place with a favorable
distance between the two radical centers, indicating that their
intersystem crossing will be fast. As a consequence, syn-dimeric
intermediate will be highly photoreactive to absorb another pho-
ton for intramolecular [2 + 2] cycloaddition to the final product 2
as described in the previous process.
1
5
1
6
For the Paternò–Büchi reaction, a triplet biradical is formed
during the attack of the triplet-excited benzophenone on the dou-
ble bond (Scheme 3). The biradical PB- DR is more stable than the
3
Figure 2. Transient absorption spectra recorded at 0.2
l
s (j), 0.32
s (.) upon 355 nm laser excitation of an acetonitrile solution of BP
1.0 M) in the presence of 1c (0.32 M). Inset: the temporal signal profiles at 420 and
20 nm.
ls (d), 0.47 ls
(
(
N), and 1.06
l
regioisomer derived from the attack by the oxygen at the 3-posi-
tion of the pyran, since the half-filled n orbital of the oxygen is ex-
pected to attack alkenes preferably at the site of higher frontier
5
1
7
electron density. The perpendicular orientation of the spin-bear-
of Fig. 2), suggesting the occurrence of triplet–triplet energy trans-
fer. Therefore, from the above facts, the absorption spectrum at
ing 2p orbitals at the radical sites allows fast intersystem cross-
1
8
ing, and subsequent ring closure gives the oxetane 3. On the
other hand, hydrogen abstraction occurs from methanol by the
triplet BP, and then affords compounds 4 and 5.
4
20 nm is assigned to the triplet state of the pyran 1c, which was
photosensitized by the triplet BP. The change in absorption spectra
indicates that triplet energy transfer occurs from triplet BP to 1c,
from which the cage dimer 2c is produced by photodimerization.
Based on the previous mechanistic studies on the related photo-
The processes proposed in Scheme 3 are also energetically fea-
sible, as shown in Figure 3. The photodimerization of 1 to triplet 1
ꢁ1
is exothermic by 28 kcal mol , and all subsequent steps proceed
downhill. When BP is involved, endothermic triplet energy transfer
1
4
chemical reactions, the possible reaction pathways were pro-
Scheme 3. Proposed mechanism for the photochemical reaction of 4-aryl-4H-pyrans in the presence of benzophenone.
⁄
Figure 3. Energy profile for the BP-sensitized photodimerization of 1 at the UB3LYP/6-31G level of calculation. aTET is the efficiency for the triplet energy transfer.

3
328
H. Xin et al. / Tetrahedron Letters 54 (2013) 3325–3328
from triplet BP to 1 occurs with a triplet energy gap of 5 kcal molꢁ1,
References and notes
which is irreversible due to fast deactivation of the acceptor mole-
1
9
1. (a) Zhang, M. M.; Zheng, B.; Huang, F. H. Chem. Commun. 2011, 47, 10103; (b)
Zhang, M. M.; Zhu, K. L.; Huang, F. H. Chem. Commun. 2010, 46, 8131; (c) Wang,
F.; Zhang, J. Q.; Ding, X.; Dong, S. Y.; Liu, M.; Zheng, B.; Li, S. J.; Wu, L.; Yu, Y. H.;
Gibson, H. W.; Huang, F. H. Angew. Chem. Int. Ed. 2010, 49, 1090.
cule. Additionally, the Paternò–Büchi reaction between triplet BP
and the substrate is expected to be an exothermic process and
could compete with the formation of the major product 2.
2
3
4
.
.
.
Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97, 671.
Bashir-Hashemi, A. Angew. Chem. 1993, 105, 585.
Hasegawa, T.; Nigo, T.; Kakita, T.; Toyoda, H.; Toya, H.; Ueda, I. Chem. Pharm.
Bull. 1993, 41, 1760.
2
In summary, we have successfully achieved the synthesis of C -
symmetric 3,9-dioxatetraasteranes 2 through the [2 + 2] photodi-
merization of 4-aryl-4H-pyrans for the first time. In the presence
of BP as triplet sensitizer, the Paternò–Büchi reaction of BP with
the pyrans is competitive with the process and gives the oxetene
products. Further studies are concerned with an investigation of
the structural variations and biological activity of the functional-
ized cage compounds.
5. Wollmann, J.; Baumert, C.; Erlenkamp, G.; Sippl, W.; Hilgeroth, A. ChemBioChem
008, 9, 874.
Ni, C. L.; Song, X. H.; Yan, H.; Song, X. Q.; Zhong, R. G. Ultrason. Sonochem. 2010,
7, 367.
7. D’Auria, M.; Emanuele, L.; Mauriello, G.; Racioppi, R. J. Photochem. Photobiol., A
000, 134, 147.
2
6
.
1
2
8
.
Yaylı, N.; Üçüncü, O.; Ya ßs ar, A.; Yaylı, N.; Burnaz, N. A.; Karao g˘ lu, Sß . A.; Küçük,
M. J. Photochem. Photobiol., A. 2009, 203, 85.
Acknowledgments
9. (a) Sonoda, Y.; Tsuzuki, S.; Goto, M.; Tohnai, N.; Yoshida, M. J. Phys. Chem. A
010, 114, 172; (b) Sonoda, Y. Molecules 2011, 16, 119.
2
1
1
0. Blokker, V.; De Mayo, P.; Muthuramu, K. J. Org. Chem. 1988, 53, 5567.
1. Adam, W.; Walther, B. Tetrahedron 1996, 52, 10399.
This work was financially supported by the National Natural
Sciences Foundation (No. 20872009) , Natural Sciences Foundation
of Beijing (No. 200710005002) and Doctoral Fund of Innovation of
Beijing University of Technology. We thank the Technical Institute
of Physics and Chemistry, Chinese Academy of Sciences, for the la-
ser flash photolysis experiments.
12. Yamaji, M.; Shima, K.; Nishimura, J.; Shizuka, H. J. Chem. Soc., Faraday Trans.
997, 93, 1065.
3. (a) Abe, M.; Kawakami, T.; Ohata, S.; Nozaki, K.; Nojima, M. J. Am. Chem. Soc.
004, 126, 2838; (b) Abe, M.; Terazawa, M.; Nozaki, K.; Masuyama, A.; Hayashi,
1
1
2
T. Tetrahedron Lett. 2006, 47, 2527.
1
4. (a) Zhu, X. H.; Li, W. P.; Yan, H.; Zhong, R. G. J. Photochem. Photobiol., A 2012,
2
2
41, 13; (b) Zhu, X. H.; Ni, C. L.; Yan, H.; Zhong, R. G. J. Photopolym. Sci. Technol.
009, 22, 379.
15. (a) Kelly, J. F. D.; Kelly, J. M.; McMurry, T. B. H. J. Chem. Soc., Perkin Trans. 2 1999,
993; (b) Wilsey, S. J. Org. Chem. 2000, 65, 7878.
Supplementary data
1
1
1
6. Freilich, S. C.; Peters, K. S. J. Am. Chem. Soc. 1985, 107, 3819.
7. Griesbeck, A. G.; Abe, M.; Bondock, S. Acc. Chem. Res. 2004, 37, 919.
Supplementary data (Experimental details, 1H and 13C NMR
spectra of all new compounds, and X-ray crystallographic data
for 2g and 3c) associated with this article can be found, in the on-
line version, at http://dx.doi.org/10.1016/j.tetlet.2013.04.016.
18. Salem, L.; Rowland, C. Angew. Chem. Int. Ed. Engl. 1972, 11, 92.
9. Yamaji, M.; Wakabayashi, S.; Ueda, S.; Shizuka, H.; Tobita, S. Chem. Phys. Lett.
002, 368, 41.
1
2