Novel intramolecular photocyclization of α-arylthiophene derivatives

Article abstract of DOI:10.1021/ol3002305

Photoirradiation of α-arylthiophene derivatives linked with an alkene moiety through a three-atom spacer gave unprecedented cyclobutene-fused perhydrothiapentalene-type compounds in high yields, but neither [2 + 2] nor [4 + 2] cycloaddition products. The

Full text of DOI:10.1021/ol3002305

ORGANIC
LETTERS
2012
Vol. 14, No. 6
1488–1491
Novel Intramolecular Photocyclization of
r-Arylthiophene Derivatives
Noriyoshi Arai,* Koichiro Tanaka, and Takeshi Ohkuma*
Division of Chemical Process Engineering, Faculty of Engineering, Hokkaido
University, Sapporo, Hokkaido 060-8628, Japan
n-arai@eng.hokudai.ac.jp; ohkuma@eng.hokudai.ac.jp
Received January 28, 2012
ABSTRACT
Photoirradiation of R-arylthiophene derivatives linked with an alkene moiety through a three-atom spacer gave unprecedented cyclobutene-fused
perhydrothiapentalene-type compounds in high yields, but neither [2 þ 2] nor [4 þ 2] cycloaddition products. The reaction afforded a single
diastereomer in many cases. The chemical structure and relative configuration of a typical product were unambiguously determined by X-ray
crystallographic analysis.
Considerable attention has been paid to the photochem-
ical behavior of thiophene derivatives in a wide range of
scientific fields, for example, light emitting materials,1
photochromic compounds,2 organic photovoltaic
devices,3 and physical organic chemistry.4 However,
synthetic use of the photoreaction of thiophenes is quite
limited, and has mostly consisted of the simple rear-
rangement between regioisomers, electrocyclization,
and [2 þ 2] addition.5ꢀ10 In addition, a few examples
of [4 þ 2] addition have also been reported.11 In the
course of our study on the photoreaction of 5-mem-
bered heteroaromatic compounds,12 we found that R-
arylthiophenes linked with an alkene moiety through a
three-atom spacer cyclized to give cyclobutene-fused
perhydrothiapentalene-type compounds under UV
(>300 nm) irradiation. We report here the preliminary
results of an unprecedented type of photoreaction of
thiophene derivatives.
(1) (a) McCullough, R. D. Adv. Mater. 1998, 10, 93–116. (b) Mazzeo,
M.; Vitale, V.; Della Sala, F.; Anni, M.; Barbarella, G.; Favaretto, L.;
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(c) Masui, K.; Mori, A.; Okano, K.; Takamura, K.; Kinoshita, M.;
Ikeda, T. Org. Lett. 2004, 6, 2011–2014.
When a solution of thiophene derivative 1a in degassed
benzene was irradiated by a high-pressure mercury lamp13
through a Pyrex glass vessel for 2 h at ambient temperature
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Chem. Soc. Rev. 2004, 33, 85–97. (c) Krayushkin, M. M.; Barachevsky,
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Chem. Res. 2010, 43, 1246–1256. (c) Chen, J.; Cao, Y. Acc. Chem. Res.
2009, 42, 1709–1718. (d) Gevorgyan, S. A.; Krebs, F. C. In Handbook of
Thiophene-Based Materials; Perepichka, I. F.; Perepichka, D. F., Eds.; John
Wiley & Sons: Chichester, 2009; Vol. 2, pp 673ꢀ693.
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(13) Riko UVL-100HA photoreactor.
r
10.1021/ol3002305
Published on Web 02/24/2012
2012 American Chemical Society

(around 25 °C), an unexpected compound 2a was obtained
in high yield (Scheme 1). The product 2a was obtained
as a single diastereomer. The structure of 2a was
determined by careful NMR experiments (1H, 13C,
DEPT, HꢀH COSY, HMQC, HMBC, and DPFGSE-
NOE). The product 2a was a stable colorless crystalline
compound. We succeeded in obtaining a single crystal
suitable for X-ray crystallographic analysis to confirm
its structure unambiguously as shown in Figure 1 (CIF
in the Supporting Information).
(entries 1ꢀ6). These results show the polarity of the
solvents haslittle effect on this reaction. Methanol, a protic
solvent, was also suitable for this reaction (entry 7). On the
other hand, the reaction in benzotrifluoride gave a some-
what inferior result with recovery of only a small amount
of 1a (entry 8). The reaction rate in acetone was relatively
slow, resulting in the product in 62% yield with the
recovery of 1a in 28% yield (entry 9). Taking the results
shown in Table 2 into account, this retardation seemed to
be caused mainly by absorption by acetone rather than
quenching of the excited species with acetone, though the
detailed reaction mechanism is not clear at this stage.
Scheme 1. Photocyclization of 1a
Table 1. Solvent Screeninga
The novel cyclization forming a perhydro-oxathiapentalene
framework fused with a cyclobutene ring is significantly
different from the well-known [2 þ 2] photocyclization of
thiophenes affording cyclobutane-fused thiacycle com-
pounds.10,14ꢀ16 We were interested in this extraordinary
photoreaction of thiophene derivatives, and decided to
investigate the reaction in detail.
entry
solvent
yield of 2a (%)b
recovery of 1a (%)b
1
2
3
4
5
6
7c
8
9
benzene
hexane
1,4-dioxane
THF
92
89
90
91
85
84
84
76
62
0
0
0
0
AcOEt
1
CH3CN
CH3OH
C6H5CF3
acetone
0
0
4
28
a All reactions were carried out in a Pyrex test tube by external
1
irradiation at a concentration of 5ꢀ6 mM. b Determined by H NMR
integral ratio using 1,1,2,2-tetrachloroethane as an internal standard.
c Small amount of unidentified compound was detected.
When the irradiation was stopped in 20 min, a small
amount of anothercompoundwasdetected. Careful NMR
study revealed that this compound was the [2 þ 2] addition
product 3a (Scheme 2). This result shows the possibility
that 2a is produced through 3a as an intermediate.17 To
check this possibility, we irradiated isolated 3a under the
same reaction conditions leading to the formation of 1a as
a major product with the concomitant formation of 2a in
low yield (Scheme 3). In contrast, irradiation of 2a under
the identical conditions resulted in quantitative recovery of
2a. These results suggest that the [2 þ 2] cycloaddtion of 1a
forming 3a is reversible and the adduct 3a is not an
intermediate of the transformation to 2a.
To obtain additional information about this reaction,
we carried out several reactions that were stopped at low
conversion as above. The results are summarized in Ta-
ble 2. The [2 þ 2] adducts 3aꢀc were the only detectable
byproducts in all cases. The reaction rate was little influ-
enced by solvent polarity and the protic characteristics,
though slightly lower conversion was observed in dioxane
(entries 1ꢀ5). These data suggest that polar intermediates
are less productive in this reaction. However, the electronic
Figure 1. ORTEP drawing of compound 2a.
Our investigation beganwith carrying out the reaction in
a series of solvents using 1a as a standard substrate. The
results are summarized in Table 1. The reaction proceeded
in hexane, dioxane, THF, ethyl acetate, and acetonitrile, as
well as in benzene to give the product 2a in high yields
ꢀ
(14) Rivas, C.; Velez, M.; Crescente, O. J. Chem. Soc. D 1970, 1474.
(15) Rivas, C.; Bolivar, R. A. J. Heterocycl. Chem. 1973, 10, 967–971.
(16) Wamhoff, H.; Hupe, H. J. Tetrahedron Lett. 1978, 125–128.
(17) Another type of rearrangement of related compounds in the
ground state: Limanto, J.; Khuong, K. S.; Houk, K. N.; Snapper, M. L.
J. Am. Chem. Soc. 2003, 125, 16310–16321.
Org. Lett., Vol. 14, No. 6, 2012
1489

Table 2. Product Distribution at an Early Stage of the Reactiona
Scheme 2. Products at an Early Stage of the Reaction
properties of the substrates turned out to show some effect
on the reaction. In fact, replacement of the phenyl group on
the thiophene 2-position with the 4-methoxyphenyl group
notably retarded the reaction (entry 6), while the intro-
duction of a 4-chlorophenyl ring showed little influence
(entry 7). The yield of 2a was somewhat decreased in the
presence of triplet quenchers,18 but the reaction was not com-
pletely inhibited (entries 8 and 9). 9,10-Dicyanoanthracene
(DCA), a singlet sensitizer that is known to promote the
photoinduced pericyclic reactions,12,19 did not affect the
reaction features (entry 10).
entry
R
solvent
additive
1 (%)b 2 (%)b 3 (%)b
1
2
H
benzene none
hexane none
52
46
76
57
49
81
57
63
54
64
36
42
18
31
40
16
43
34
22
27
5
H
H
H
H
4
3
dioxane none
CH3OH none
6
4
6
5
CH3CN
none
8
6
MeO benzene none
3
7
Cl
H
H
H
benzene none
benzene p-terphenylc
<1
3
8
d
9
benzene O2
benzene DCAe
0
10
9
a All reactions were carried out in a Pyrex test tube by external
irradiation at a concentration of 5ꢀ6 mM. b Determined by H NMR
1
Scheme 3. Irradiation of 3a
integral ratio using 1,1,2,2-tetrachloroethane as an internal standard.
c An amount of p-terphenyl equimolar to 1a was added. d Benzene
saturated by O2 bubbling was used. e An amount of DCA equivalent
to half a mole of 1a was added.
thiophene to 3-substituted thiophene.5,6,20ꢀ25 Some of these
intermediates were trapped and characterized.26ꢀ28 The
thiirane ring-opening and successive cyclization are known
under thermal conditions.29 The details of the mechanism
should be disclosed in a further investigation.
Considering these experimental results and previous
reports in the literature,5,6,20 the reaction seems to proceed
mainly via the singlet excited state of 1a followed by the
formation of noncharge-separated reactive species. A
plausible reaction pathway is proposed in Scheme 4.
Photoexcitation of 1a could cause a 4π electrocyclic reac-
tion to give a “Dewar thiophene” (5-thiabicyclo[2.1.0]pent-
2-ene) type intermediate A. Then the thiirane moiety in A
reacts with the pendant alkene to afford the product 2a. A
part of 1a undergoes reversible formation of 3a. The
formation of the Dewar thiophene type intermediate is
postulated in the photoisomerization of 2-substituted
Scheme 4. Plausible Reaction Pathway
(18) Turro, N. J.; Modern Molecular Photochemistry; University
Science Books: Sausalito, CA, 1991; Chap. 9.
(19) (a) Akbulut, N.; Hartsaugh, D.; Kim, J.-I.; Schuster, G. B. J.
Org. Chem. 1989, 54, 2549–2556. (b) Calhoun, G. C.; Schuster, G. B. J.
Am. Chem. Soc. 1984, 106, 6870–6871.
(20) Kellog, R. M.; Wynberg, H. Tetrahedron Lett. 1968, 5895–5898.
(21) Wynberg, H.; Kellog, R. M.; van Driel, H.; Beekhuis, G. E. J.
Am. Chem. Soc. 1967, 89, 3501–3505.
(22) van Tamelen, E. E.; Whitesides, T. H. J. Am. Chem. Soc. 1971,
93, 6129–6140.
(26) Barltrop, J. A.; Day, A. C.; Irving, E. J. Chem. Soc., Chem.
Commun. 1979, 966–968.
(23) Barltrop, J. A.; Day, A. C.; Irving, E. J. Chem. Soc., Chem.
Commun. 1979, 881–883.
(24) Jug, K.; Schluff, H.-P. J. Org. Chem. 1991, 56, 129–134.
(25) Matsushita, T.; Tanaka, H.; Nishimoto, K. Theor. Chim. Acta
1983, 63, 55–68.
(27) (a) Rendall, W. A.; Torres, M.; Strausz, O. P. J. Am. Chem. Soc.
1985, 107, 723–724. (b) Rendall, W. A.; Clement, A.; Torres, M.;
Strausz, O. P. J. Am. Chem. Soc. 1986, 108, 1691–1692.
(28) D’Auria, M.; Racioppi, R. Heterocycles 2009, 78, 737–748.
(29) Furuhata, T.; Ando, W. Tetrahedron 1986, 42, 5301–5308.
1490
Org. Lett., Vol. 14, No. 6, 2012

We confirmed that this reaction could be conducted
under the preparative conditions to give the product 2a
in high isolated yield by using the typical substrate 1a
(entry 2), though the following examples were carried
out on a small scale for convenience. Replacement of
the phenyl group with a 4-methoxyphenyl group af-
forded 2b in 63% yield accompanied by the formation
of unidentified byproduct (entry 3). A substrate with a
4-chlorophenyl group 1c gave the product in quite good
yield (entry 4). The reaction with a methyl-substituted
compound 4 resulted in the recovery of most of 4 (entry
5). No cyclized product was observed. These results
indicate that the aromatic ring at the R position plau-
sibly plays an important role in the stabilization of
intermediates that leads to the formation of the tricyclic
compound.
Table 3. Substrate Screeninga
The substituents at the alkene moiety showed notable
effects on the reaction. The reaction of 1d with a tetra-
substituted alkenyl group revealed that the bulkiness of
the alkene did not strongly inhibit the reaction, though
the yield of the product decreased (entry 6). Both
compound 1e (the regioisomer of 1a) and the terminal
alkene 1f gave the cyclized compounds in moderate
yields, while the reaction with the simple allylic com-
pound 1g resulted in a low yield of the product (entries
7ꢀ9). Linker moieties other than ether bonds were also
usable. Thus, compounds linked with NBoc or sp3-
carbon (5 and 7) gave the corresponding products in
high yields (entries 10 and 11).
All the tricyclic products except 2e were obtained as
almost pure single diastereomers. This notably high stereo-
selectivity plausibly arises from the fact that the formation
of other possible stereoisomers can hardly cyclize due to
their severe steric strains.
In conclusion, we have developed a new photochem-
ical transformation of thiophene derivatives with an
alkene moiety that provides a variety of unique tricyclic
frameworks. With appropriate substrates, the reaction
proceeds cleanly in a short time to afford the products
in high yields.
Acknowledgment. This work was supported by a
Grant-in-Aid from the Japan Society for the Promo-
tion of Science (JSPS) (No. 21350048). We appreciate
the reviewer for thoughtful suggestions on the reaction
mechanism.
a All reactions were carried out by internal irradiation through a Pyrex
glass jacket at a concentration of 5ꢀ6 mM, until the starting material
(0.2 mmol) was completely consumed (typically 2ꢀ5 h) (for details, see the
Supporting Information). b Isolated yield. c The reaction was carried out in
a Pyrex test tube by external irradiation at a concentration of 5ꢀ6 mM.
d Determined by 1H NMR integral ratio using 1,1,2,2-tetrachloroethane as
an internal standard. e The reaction was carried out using 2 mmol of 1a at a
concentration of 0.1 M. f No cyclized product was obtained, and unreacted
4 was recovered (91%). g Obtained as a diastereomeric mixture (7:3). h The
sample contained small amounts of inseparable impurities.
Supporting Information Available. Experimental pro-
cedures, characterization data for all new compounds,
X-ray crystal information file (CIF) for 2a. This materi-
al is available free of charge via the Internet at http://
pubs.acs.org.
Next, we performed the reaction using a variety of
substrates with the different alkenyl groups and linker
moieties. The results are listed in Table 3.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 6, 2012
1491