[2+2] Photodimerization of bispyridylethylenes by a controlled shift of the protonation equilibrium

Article abstract of DOI:10.1016/j.tetlet.2013.05.075

Irradiation of trans-4,4′-bispyridylethylene in the presence of 1 equiv of concd HCl produced a syn dimer with high selectivity, whereas irradiation in the presence of more than 2 equiv of concd HCl or in the absence of HCl gave a mixture of dimers and by-products with much lower selectivity. This indicated that a suitable amount of acid served as a catalyst for the [2+2] photodimerization of BPEs through cation-π interactions between the pyridinium and pyridine rings.

Full text of DOI:10.1016/j.tetlet.2013.05.075

Tetrahedron Letters 54 (2013) 3997–4000
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Tetrahedron Letters
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[2+2] Photodimerization of bispyridylethylenes by a controlled shift
of the protonation equilibrium
⇑
Shinji Yamada , Momoko Kusafuka, Mai Sugawara
Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, 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
Irradiation of trans-4,40-bispyridylethylene in the presence of 1 equiv of concd HCl produced a syn dimer
with high selectivity, whereas irradiation in the presence of more than 2 equiv of concd HCl or in the
absence of HCl gave a mixture of dimers and by-products with much lower selectivity. This indicated that
Article history:
Received 15 April 2013
Revised 13 May 2013
Accepted 17 May 2013
Available online 23 May 2013
a suitable amount of acid served as a catalyst for the [2+2] photodimerization of BPEs through cation–
interactions between the pyridinium and pyridine rings.
p
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cation–p interaction
Bispyridylethylene
[2+2] Photodimerization
Catalysis
Stereoselective reaction
Introduction
In this communication, we report that the acid amount is criti-
cal to the stereoselectivity in the [2+2] photodimerization of BPEs
in solution. In addition, the relationship between the crystal struc-
tures and photoreactivities of the BPEs (1a and 1b) and corre-
sponding N-methyl (2a and 2b) and N,N0-dimethyl salts (3a and
3b) were investigated (Fig. 1) to clarify the importance of monocat-
ionic species.
The preorientation of alkenes prior to irradiation is a powerful
strategy to achieve high stereoselectivity in solid-state [2+2] pho-
todimerization reactions.1 As a substrate, trans-4,40-bispyridyleth-
ylene (BPE) has often been employed, as the two pyridyl moieties
are effective in making complexes with templates,2 hosts,3 metal
ions,4 and imprinted polymers,5 and in the formation of coordina-
tion polymers.6 Irradiation of such systems affords syn dimers in
high yields. However, except for reports using an inclusion com-
plex with CA[8]3a and CB[8],3b there have been only a few exam-
ples of the photodimerization in solution phase due to the
difficulties associated with controlling the orientation of molecules
in solution. From a synthetic point of view, photochemical reac-
tions in solution phase remain of great importance.
Results and discussion
Irradiation of 0.5 M of 1a in a 1:1 mixture of methanol/water
solution with a 450 W high-pressure mercury lamp for 2 h through
a Pyrex filter afforded dimers 4a and 5a, as well as dipyridylethane
6a9 and hydroxymethylated compound 7a9 with lower selectivities
as shown in Table 1 (entry 1). This lower selectivity is in agreement
with that previously reported.9 On the other hand, in the presence
of 0.05 equiv of concd hydrochloric acid, the photochemical reac-
tion resulted in remarkable changes in product distribution (entry
2); the yield of the syn dimer 4a significantly increased, becoming a
major product, while that of the anti dimer 5a decreased. Increas-
ing the HCl loading to 0.8 equiv led the highest yield of 2a, with a
syn/anti ratio of 16.6 (entries 5 and 6). Further addition of HCl from
0.8 to 3.0 equiv caused a gradual decrease in 4a and increases in 5a,
6a, and 7a (entries 7–9). The addition of 3 equiv of HCl, in particu-
lar, resulted in a dramatic decrease in 4a and increase in 6a.
Figure 2 shows the plots of product distribution versus HCl
loading. This clearly shows that the formation of a syn dimer is
extremely dependent on HCl concentration, with HCl in the range
from 0.1 to 1.5 equiv being particularly effective. This means that a
We have reported that cation–p-controlled preorientation is
extremely effective in the stereoselective photodimerization of
styrylpyridines7 and azaanthracenes8 in solution phase. In these
reactions, cation–p interactions between pyridinium and aromatic
rings lead the molecules to arrange themselves in a head-to-tail
fashion, the subsequent irradiation of which affords synHT dimers.
These observations prompted us to investigate the photodimeriza-
tion of BPEs according to the strategy shown in Scheme 1: the pro-
tonation equilibrium among A–C can be shifted toward B by
adjusting the concentration of an acid, irradiation of which would
stereoselectively produce a syn dimer.
⇑
Corresponding author. Tel./fax: +81 3 5978 5349.
E-mail address: yamada.shinji@ocha.ac.jp (S. Yamada).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.075

3998
S. Yamada et al. / Tetrahedron Letters 54 (2013) 3997–4000
Scheme 1. Photodimerization of BPE through cation–p interactions under a controlled shift of the protonation equilibrium toward B.
Figure 1. Substrates for photodimerization.
Table 1
Product distribution for photodimerization reaction of 1a in the presence of HCla
Figure 3. Differences in the orientation behavior between mono- and dications in
solution.
Table 2
Product distribution for photodimerization reaction of 1b in the presence of HCl
Entry
HCL (equiv)
Conv (%)
Productsb (%)
Ratio (4a/5a)
4a
5a
6a
7a
1
2
3
4
5
6
7
8
9
0
90
37
68
74
80
83
80
78
68
19
11
5
5
5
5
6
7
7
8
14
14
10
6
4
4
4
8
49
38
13
11
9
3.4
14.0
14.8
16.0
16.6
13.3
11.1
9.7
0.05
0.1
0.5
0.8
1.0
1.5
2.0
3.0
>99
>99
>99
>99
>99
>99
>99
>99
8
10
12
18
24
2.4
Entry
Solva
HCL (equiv)
Conv (%)
Productsb (%)
a
A 0.5 M solution was used.
4b
5b
6b
7b
8b
b
Determined by 1H NMR spectra.
1
2
3
4
5
MeOH
MeOH
i-PrOH
H2O
0
67
94
83
92
95
52
32
56
71
26
13
1
1
1
2
7
3
11
0
28c
61c
22d
0e
0
3
10
28
59
1.0
1.0
1.0
2.5
H2O
5
9e
a
b
c
A 0.5 M solution was used.
Determined by 1H NMR spectra.
R2 = CH2OH.9
d
e
R2 = C(CH3)2OH.10
R2 = OH.11
controlled shift of the protonation equilibrium toward monocation
species enables cation– interactions between the pyridinium and
p
the pyridine rings, as shown in Figure 3. This working model also
explains the observed increase in the ratio of 4a to 5a with in-
creases in HCl loading. On the other hand, for fully protonated
pyridinium dications, the attractive force is no longer reduced
and a repulsive force arises, leading to the increase in 6a and 7a
as a result of lowered dimerization rates, as shown in Figure 3.
Figure 2. The product distribution for the photodimerization of 1a versus HCl
loading.

S. Yamada et al. / Tetrahedron Letters 54 (2013) 3997–4000
3999
Figure 4. The crystal structures for (a) 2a and (b) 2b.
Table 3
Solid-state photodimerization reactions of 1a, 1b, 2a, 2b, 3a, and 3b
The contribution of the cation–p interaction between the
monocations was determined by studying the concentration
dependence of the 1H NMR chemical shifts. As the concentration
of 1aꢀHCl was increased from 1.0 to 30 mM in CDCl3, the
of the pyridinium ring of 1aꢀHCl was shifted from d 8.70 to d 8.78,
whereas no shift was observed for the corresponding -proton of
1a, suggesting the contribution of the cation– interaction in the
a-proton
a
R1
R2
Producta (%)
p
Compd
HCl salt at higher concentrations (see, Supplementary data).
To show the generality of the importance of the monocation in
syn selectivity, [2+2] photodimerization of 2,20-bispyridylethylene
(1b) was carried out (Table 2). Irradiation of a 0.5 M MeOH solution
of 1b for 24 h produced a mixture of syn and anti dimers with low
selectivity (entry 1). On the other hand, the addition of 1.0 equiv of
HCl, significantly improved the syn selectivity, similar to that ob-
served for 1a, although 7b was obtained as a major product (entry
2). To reduce the yield of byproduct 7b, a change in solvent from
MeOH to i-PrOH was effective to yield 4b as a major product.12
The use of H2O as a solvent significantly improved the yield of
4b (entry 4). In the presence of 2.5 equiv of HCl, the yield of 4b
was significantly decreased with increase of 8b (entry 5).
1a
syn (1.6%) + anti (0.4%)
syn (1.6%) + anti (9%)
1b
2a
syn (>99%)
syn (>99%)
No reaction
No reaction
2b
3a
3b
Product distribution was monitored by 1H NMR spectra to
clarify its irradiation time dependence (see, Supplementary data).
As irradiation time was increased, the yield of 1b rapidly decreased
and that of the syn dimer 4b increased, whereas that of 5b was
almost unchanged. After irradiation for 11 h, 1b was almost com-
pletely consumed. These observations indicate that 4b was directly
produced through the dimerization of 1b without any isomeriza-
tion of the other products, similar to process observed for 1a
(Fig. 3). Irradiation of the isolated 4b was unchanged under the
same reaction conditions, showing that this dimerization process
is irreversible. It has been known that the quantum efficiency of
E/Z isomerization of bispyridylethylene is much lower than that
of stilbene.13 In addition, the efficiency in 4,4-BPE is much lower
than that in 2,2-BPE.13 Therefore, the E/Z isomerization would
not be observed for the photochemical reaction of 4,4-BPE. On
the other hand, it has also been reported that a polar solvent en-
hances the E/Z isomerization of BPE,10 suggesting that the dimer
8b would be produced from the [2+2] photocyclization reaction
between (E)-1b and (Z)-1b formed by photoisomerization, which
is similar to the mechanism for the photodimerization of (Z)-sty-
rylpyridines.14 Although it was reported that isomerization of 4b
to 8b proceeds in the presence of HCl,4i the isolated 4b did not un-
dergo isomerization under the present reaction conditions.
To investigate the role of the cationic charge of the molecules on
their orientation, a comparison among X-ray crystal structures of
bispyridylethylenes (1a15 and 1b15), N-methyl salts (2a16 and
2b15) and N,N0-dimethyl salts (3a15 and 3b15) was carried out
(see, Supplementary data). As the preparation of single crystals of
mono-hydrochloride is difficult due to it having two pyridyl moie-
ties, N-methyl salts were employed for comparison instead of
hydrochloride salts. The pyridine rings between neighboring
molecules for 1a and 1b, and the pyridinium rings between neigh-
boring molecules for 3a and 3b were located apart from each other
(1a: 5.772 Å; 1b: 5.654 Å; 3a: 6.281 Å; 3b: 7.023 Å). On the other
a
Determined by 1H NMR spectra.
hand, the molecules of 2a and 2b were arranged head-to-tail and
face-to-face (Fig. 4). The distances between the neighboring double
bonds were 3.885 Å and 3.701 Å, respectively. As expected from
the crystal structures of 2a and 2b, they were photoreactive and
gave the corresponding syn dimers15,17 in quantitative yields. On
the other hand, the compounds 1a, 1b, 3a, and 3b were all basically
photostable (Table 3).18 The fact that head-to-tail column struc-
tures were observed only in the mono-methyl salts 2a and 2b sup-
ports the existence of an attractive interaction between the
pyridinium and pyridine rings.
Conclusion
In summary, we clarified that the HCl loading is critical to the
product distribution in the [2+2] photodimerization of trans-BPEs.
Irradiation in the presence of 1 equiv of concd HCl produced the
syn dimer with high selectivity, whereas in the absence or in the
presence of more than 2 equiv of concd HCl a mixture of dimers
was obtained with much lower selectivity, strongly suggesting
the contribution of the cation–p interaction between the pyridini-
um and pyridine rings. This indicated that a suitable amount of
acid served as a catalyst for the [2+2] photodimerization of BPEs
through cation–p interactions.
Acknowledgments
This work was partially supported by a Grant-in-Aid for Scien-
tific Research on Innovative Areas ‘Advanced Molecular Transfor-
mations by Organocatalysts’ from MEXT.

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in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.075.
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