[2+2] Photodimerization of (E)-styrylthiazoles through cation-π-controlled preorientation

Article abstract of DOI:10.1016/j.tetlet.2016.04.085

Cation-π-controlled preorientation of (E)-styrylthiazoles was performed in both solution and solid phases. Irradiation of (E)-styrylthiazoles in the presence of HCl produced synHT dimers in good selectivities, while little selectivity was observed without

Full text of DOI:10.1016/j.tetlet.2016.04.085

Tetrahedron Letters 57 (2016) 2451–2454
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Tetrahedron Letters
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[2+2] photodimerization of (E)-styrylthiazoles through
cation–
p
-controlled preorientation
⇑
Shinji Yamada , Kaoru Yamagami, Saki Oaku
Department of Chemistry, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Cation–p-controlled preorientation of (E)-styrylthiazoles was performed in both solution and solid
phases. Irradiation of (E)-styrylthiazoles in the presence of HCl produced synHT dimers in good selectiv-
ities, while little selectivity was observed without HCl. X-ray structures for the HCl salts of (E)-styrylth-
Received 19 March 2016
Revised 18 April 2016
Accepted 21 April 2016
Available online 22 April 2016
iazoles showed a head-to-tail arrangement through cation–
molecules. Irradiation of these HCl salts produced synHT dimers in excellent yields.
Ó 2016 Elsevier Ltd. All rights reserved.
p interactions between the two neighboring
Keywords:
[2+2] photodimerization
Cation–p interaction
Styrylthiazole
Cyclobutane framework
Preorientation
Introduction
cyclobutanes have various synthetic applications. There have been
several reports on [2+2] photodimerization reactions of hetero-
cyclic olefins containing thiophene,12 pyrylium salt,13 oxazole,14
or benzothiazole15 moieties. However, the effect of the acid has
not yet been investigated, although the quaternary onium salts
were used for the photodimerization reactions.16 In this Letter,
we report the applicability of this method to styrylthiazoles in both
solution and solid phases.
[2+2] photodimerization of (E)-alkenes is an effective method
for the construction of cyclobutane framework structures.1 This
method has been applied to the synthesis of naturally occurring
products possessing a cyclobutane framework such as dictazole
B,2a dipiperamide A,2b incarvillateine,2c katsumadain C,2d, and
dimeric pyrrole-imidazole alkaloids.3 In addition, several photocy-
cloadducts are used as ligands,4 and metal–organic frameworks.5
Therefore, controlling the regio- and stereoselectivities in [2+2]
photodimerization reactions of alkenes is of great synthetic
importance.
Results and discussion
We prepared 2-, 4-, and 5-strylthiazoles17–19 (1a–1c, respec-
tively) according to reported methods, which were shown in
Figure 1. Irradiation of 1a–1c in a 0.8 M MeOH solution with a
450 W high-pressure mercury lamp for 18–24 h at 23 °C in the
presence or absence of HCl afforded dimers 2–5 as well as (Z)-1a.
The results are shown in Table 1. The conversion and product ratios
were determined on the basis of 1H NMR. As anti dimers 4 and 5
existed as an inseparable mixture, their yields were listed together.
Photolysis in the presence of 1.0 equiv of concd hydrochloric acid
caused a significant increase in the yield of dimer 2a compared
to the reaction in the absence of an acid (entry 2). The ratio of
the synHT dimer 2a to synHH dimer 3a clearly shows the effective-
ness of HCl on the regio- and stereoselectivities, which is in agree-
ment with our previous results.8–10 As the 2-thiazole moiety is
deprotected to give an aldehyde,20 the thiazole dimers are thought
to have a potential synthetic utility.
The preorientation of molecules prior to irradiation is a promis-
ing technique for attaining regio- and stereoselective [2+2] photo-
cycloaddition reactions. Various organized media6 and
supramolecular entities7 are effective for preorientation of sub-
strates, the subsequent irradiation of which produced correspond-
ing dimers in high stereoselectivities. We have reported that the
preorganization of pyridine derivatives, such as styrylpyridines,8
styrylbutadienes,9 azastylbenes,10 and azachalcones11 can be
achieved both in acidic solution or in crystal as HCl salts through
a cation–p interaction, the irradiation of which produces synHT
dimers in high regio- and stereoselectivities. In order to show the
generality and utility of this approach, we focused on the
photodimerization of heterocyclic olefins as the heterocyclic
⇑
Corresponding author. Tel./fax: +81 3 5978 5349.
E-mail address: yamada.shinji@ocha.ac.jp (S. Yamada).
http://dx.doi.org/10.1016/j.tetlet.2016.04.085
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

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S. Yamada et al. / Tetrahedron Letters 57 (2016) 2451–2454
Table 1
Photodimerization of thiazoles 1a–1ca
Entry
Compd
HCl (equiv)
Time (h)
Conv (%)
Productsb (%)
4 + 5
Ratio (2/3)
2
3
(Z)-1
1
2
3
4
5
6
7
8
9
1a
1a
1b
1b
1b
1c
1c
1c
1cc
0
1.0
0
1.0
3.0
0
1.0
3.0
3.0
24
20
18
18
18
18
18
18
18
79
94
60
66
69
83
93
96
95
43
76
13
17
24
28
88
93
81
31
9
13
4
4
20
9
17
3
7
0
0
20
0
0
9
12
67
79
72
32
3
1.4
8.4
1.0
4.3
6.0
1.4
9.8
13.3
13.5
7
6
0
14
0
a
b
c
A 0.8 M solution was employed unless otherwise noted.
Determined by 1H NMR.
A 0.2 M solution was employed.
The photochemical reaction of 1b resulted in photoisomeriza-
tion to give (Z)-1b as a major product with lower yields of the
dimers (entry 3). The addition of HCl had little effect on increasing
the yields of the dimers, although the selectivity of the synHT
dimer was improved (entries 4 and 5).
On the other hand, in the case of 1c, the acid was observed to
have a significant effect. Irradiation of 1c without an acid yielded
2c–4c with no selectivity (entry 6), while in the presence of
1.0 equiv of HCl the selectivity was significantly improved to give
the synHT dimer in high yield (entry 7). In the presence of 3.0 equiv
of HCl the ratio of 2/3 was further improved (entry 8). A dilution of
the solution from 0.8 M to 0.2 M lowered the dimerization rate and
increased the yield of (Z)-1c without a change in the selectivity
(entry 9). This suggests that the dimerization and isomerization
reactions compete with each other and the higher concentration
is favorable for the formation of the dimer.
Figure 2. Plots of yields of products 1c–3c by irradiation time.
Figure 2 shows changes in the product distribution versus irra-
diation time in the presence of 3.0 equiv of HCl in CD3OD. As irra-
diation time increased, the starting material rapidly decreased and
synHT dimer and (Z)-1c increased. However, (Z)-1c decreased after
2 h, indicating that (Z)-1c is in equilibrium with (E)-1c, which is
readily consumed to give dimers under these reaction conditions.
The structure of the synHT dimer 2c was confirmed by X-ray
crystallographic analysis.21 As shown in Figure 3, the thiazole ring
and the phenyl group are displaced onto the neighboring cyclobu-
tane ring with cis configuration. The 1H NMR spectrum of 2c shows
that the peaks of the four methine protons appeared at d 4.76–4.81
and 4.31–4.35, with a ratio of 1:1. The dimer 3c with peaks at d
4.68–4.69 and 4.42–4.44, which are close to those of 2c, is assigned
as synHH. On the other hand, dimers 4c and 5c with the methine
peaks at 3.62 and 3.91 (each 2H, triplet) and 3.73–3.78 (4H, multi-
plet) are assigned as anti dimers, as the methine protons of anti
dimers for related compounds are generally observed in much
higher field than those of the syn dimers. The structures of 2a–5a
and 2b–5b were assigned through comparison with those of 2c–
5c (SI).
Figure 3. X-ray structure for 2c.
Figure 1. Styrylthiazoles 1a–1c.
Figure 4. Photodimerization of 2c through cation–p interactions.

S. Yamada et al. / Tetrahedron Letters 57 (2016) 2451–2454
2453
Table 2
Table 3
Solid-state photodimerization of 1a–1c and their HCl salts
The distances between two neighboring molecules
Compd
d1 (Å) (centroid-
d2 (Å) (two
d3 (Å) (two double
plane)
centroids)
bonds)
1b
4.258
3.389
4.336
3.601
3.654
3.801
3.840, 5.031
3.669
3.647
1aÁHCl
1bÁHClÁ2H2O 3.569
1cÁHClÁ2H2O 3.509
3.689
Entry
Compd
Conva (%)
Productsa (%)
2
3
4 + 5
(Z)-1
1
2
3
4
5
6
1a
59
99
89
94
98
88
40
>99
49
>99
37
96
35
0
29
0
29
4
18
0
22
0
34
0
7
0
0
0
0
0
tiveness of the cation–p-controlled solid-state [2+2] photodimer-
ization reaction, where the E/Z photoisomerization reaction was
prevented by the confined environment.
1aÁHCl
1b
1bÁHClÁ2H2O
To elucidate the reason for the significant differences in the pro-
duct selectivities according to the use of neutral compounds or HCl
salts, X-ray structural analyses were carried out. The crystals suit-
able for the X-ray structural analysis were obtained for 1b, 1aÁHCl,
1bÁHClÁ2H2O, and 1cÁHClÁ2H2O,22 whereas, those for 1a and 1c
were not available. Figure 5 shows two neighboring molecules
extracted from the X-ray packing diagrams. The molecules of 1b
were arranged in a non-parallel manner, the double bonds of
which were displaced in a crossed position (Fig. 3a). On the other
hand, the molecules of 1bÁHClÁ2H2O were arranged parallel to each
other in a head-to-tail fashion (Fig. 3c). The X-ray crystal structures
of 1aÁHCl and 1cÁHClÁ2H2O are shown in Figure 3b and d, respec-
tively, with the two molecules arranged head-to-tail and face-to-
face. These structural features are very similar to those of
1bÁHClÁ2H2O.
1c
1cÁHClÁ2H2O
Determined by 1H NMR.
a
The effect of HCl on the regio- and stereoselectivities is similar
to those reported in our previous results,8–11 where cation–
inter-
p
actions were shown to contribute to the preorientation of the pro-
tonated molecules in a head-to-tail arrangement as shown in
Figure 4. This proposed preorientation in solution is supported by
the X-ray structures of the HCl salts described below. The lower
yield of dimer 2b and the higher yield of (Z)-1b observed on the
irradiation of 1b is speculated to be due to significant differences
in the absorption property of UV light between (E)-1b and (Z)-1b
(Table 1, entries 4–6). The
e values of the longest absorption band
for (E)-1b and (Z)-1b are 1.36 Â 106 (kmax = 272.5 nm) and
1.21 Â 103 (kmax = 275.5 nm), respectively. This is thought to be
responsible for the photostability of (Z)-1b, leading to a high yield
of (Z)-1b and lower yields of the dimers (SI).
Table 3 shows three types of distances, d1–d3, between the two
molecules: d1 is the distance of the perpendicular from the cen-
troid of the thiazole ring to the plane involving the benzene ring;
d2 is the distance between the centroids of the thiazole and ben-
zene rings; and d3 is the distance between the double bonds. As
shown in Table 3, intermolecular distances d1 and d2 of the three
HCl salts are much shorter than those of 1b, suggesting a signifi-
Next, we examined the solid-state photodimerization reactions
of 1a–1c and their HCl salts. When the powdered crystals of 1a,
placed between two Pyrex plates, were irradiated with a 250 W
high-pressure mercury lamp for 16 h, four dimers were produced
(Table 2, entry 1). On the other hand, irradiation of 1aÁHCl pro-
duced synHT dimer 2a in quantitative yield (entry 2), which was
confirmed by 1H NMR. In the cases of 1b and 1c, similar results
were obtained. Irradiation of 1b and 1c resulted in lower selectiv-
ities (entries 3 and 5), whereas irradiation of their HCl salts gave
much higher selectivities (entries 4 and 6). One remarkable feature
was that the markedly lower yield of 2b in the solution phase reac-
tion described above (Table 1, entries 3–5) was significantly
improved in the solid phase reaction. This clearly shows the effec-
cant contribution of the cation–p interactions between the two
molecules of the HCl salts. Moreover, the d3 for the HCl salts are
shorter than the Schmidt’s requirement,22 which is responsible
for the high yields of synHT dimers 2a–2c.
It is well documented that stereoselectivity in solid-state pho-
tochemical reactions depends on the conversion of the substrate
as the crystal lattice is broken as the reaction proceeds.23 However,
in the present case, the selectivities were maintained until the end
of the reaction. This suggests that the dimer units are retained by
the cation–p interactions throughout the reaction.
Figure 5. X-ray structures for (a) 1b, (b) 1aÁHCl, (c) 1bÁHClÁ2H2O, and (d) 1cÁHClÁ2H2O. The water molecules of 1bÁHClÁ2H2O and 1cÁHClÁ2H2O were omitted for clarity.

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S. Yamada et al. / Tetrahedron Letters 57 (2016) 2451–2454
ˇ ´
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In summary, [2+2] photodimerization reactions for a series of
(E)-styrylthiazoles 1a–1c were investigated in both solution and
solid phases. Irradiation of 1a–1c in the presence of HCl produced
synHT dimers in good selectivities, while little selectivity was
observed without HCl. X-ray structures for the HCl salts of 1a–1c
showed a head-to-tail arrangement through cation–p interactions
between two neighboring molecules. Irradiation of these HCl salts
produced synHT dimers in excellent yields. These results confirmed
that a cation–p-controlled preorientation method can be applied to
heterocyclic olefins in both solution and solid phases, enabling
regio- and stereoselective [2+2] photodimerization reactions.
ˇ
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Acknowledgment
This work was financially supported by a Grant-in-Aid for Sci-
entific Research on Innovative Areas ‘Advanced Molecular Trans-
formations by Organocatalysts’ from MEXT, Japan.
Supplementary data
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Supplementary data (typical experimental procedures, full
characterization of new compounds, copies of 1H NMR spectra,
X-ray crystallographic data) associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2016.04.085. These data include MOL files and InChiKeys of the
most important compounds described in this article.
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21. Crystallographic data for the structures 1b, 1aÁHCl, 1bÁHClÁ2H2O, 1cÁHClÁ2H2O
and 2c have been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 1456667, 1456656, 1456655,
1456654 and 1456657, respectively. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
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