Substituent dependent photochemical rearrangements of halostyrylheterocycles in acid media

Article abstract of DOI:10.1016/S0040-4039(03)01056-6

New photorearrangement product 2 and hydrolysis product 3 are obtained by irradiating acidic halostyrylheterocycles 1a-f. The competing formal [1,3]hydrogen shift and ring opening of dihydrophenanthrene intermediate is responsible for the product formatio

Full text of DOI:10.1016/S0040-4039(03)01056-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4669–4672
Substituent dependent photochemical rearrangements of
halostyrylheterocycles in acid mediaꢀ
Jinn-Hsuan Ho and Tong-Ing Ho*
Department of Chemistry, National Taiwan University, Taipei, Taiwan, ROC
Received 20 March 2003; revised 23 April 2003; accepted 25 April 2003
Dedicated to Professor F. D. Lewis on his 60th birthday
Abstract—New photorearrangement product 2 and hydrolysis product 3 are obtained by irradiating acidic halostyrylheterocycles
1a–f. The competing formal [1,3]hydrogen shift and ring opening of dihydrophenanthrene intermediate is responsible for the
product formation. The halogen substituent effect on the product distribution has been studied. Photolysis of 5 can reversibly be
converted to 2. Similar photoreactivity for the styrylfuran and styrylthiophene systems is observed. © 2003 Elsevier Science Ltd.
All rights reserved.
Stilbenes are unique in terms of their diverse photoreac-
tivity.1–7 Their reactions include cis–trans photoisomer-
ization,8,9 oxidative10–12 and eliminative13,14 photo-
cyclization, photocycloaddition with various alkenes,15
photoaddition with amines16–18 and photorearrange-
ment using primary amines.8,19,20 Styrylheterocycles are
also reactive21–23 photochemically and a photorear-
rangement has been reported (Eq. (1)).24,25 It is known
that photochemical reactivity is greatly influenced by
environment.26–33 The photorearrangement of stilbenes
can be changed completely by acid-catalyzed hydrolysis
of the reactive intermediates.34,35 The competition
between the two reaction pathways can be controlled
by adjusting the concentration of hydrochloric acid. In
this work, we report the substituent dependent photo-
chemical reaction of 4%-halostyrylfurans 1a–c and 4%-
halostyrylthiophenes 1d–f.
ric acid was irradiated with a Rayonet apparatus at 350
nm for 3.5 h. After the acid was neutralized and the
solvent was evaporated, two products, 8-fluoro-6,9-
dihydronaphtho[2,1-b]furan 2a (17% yield) and (E)-4-
(oxainden-5-yl)but-3-en-2-one
isolated. The new compound 2a36 shows H NMR at
l 3.64–3.57 (m; Ar-CH2-CHꢀCF), 3.73–3.68 (m; Ar-CH2
CF) and 5.48 (dm, JHꢁF=16.9 Hz; Ar-CH2-CHꢀCF),
and shows 13C NMR at l 156.4 (d, JC1 ꢁF=248.9 Hz,
3
(83% yield) were
1
6
6 -
6
6
(1)
An N2-deoxygenated acetonitrile solution containing
5×10−3 M 4%-fluorostyrylfuran 1a and 0.5 M hydrochlo-
ꢀ Supplementary data associated with this article can be found at
doi:10.1016/S0040-4039(03)01056-6
* Corresponding author. Tel.: +886-2-2369-1801; fax: +886-2-2363-
6359; e-mail: hall@ccms.ntu.edu.tw
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01056-6

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J.-H. Ho, T.-I. Ho / Tetrahedron Letters 44 (2003) 4669–4672
gen shift from carbon 9b to 9 of intermediate 6 pro-
duces intermediate 7. In accord with this proposal,
PM3 calculations indicate that carbon 9 of 6 possess a
partial negative charge. For the intermediate 7, there
are two competing reaction pathways. One is the acid-
catalyzed formal [1,3] hydrogen shift that can occur to
give compound 2. The other is the ring-opening reac-
tion to produce 5. After hydrolysis of haloalkenyl
group of 5, the reaction leads to the formation of
product 3. The acid-catalyzed [1,9] hydrogen shift is a
10 electrons process it is probably a thermal process.
The [1,3] hydrogen shift is four electron process and
could be a photochemical allowed. Detailed experimen-
tal supported is further needed.
in addition to products of type 2 and 3. The conver-
sions and yields of the photoreactions are listed in
Table 1.
When the irradiation time is shortened, the intermedi-
ates 5a–c could be isolated and were stable in neutral
solution (Scheme 2). Some intermediates (cis-5a and
trans-5b) have been reported24 as stable products in
neutral conditions (Eq. (1)). The product distribution
and yields for shorter irradiation time are listed in
Table 2. The product distribution for the photoreaction
of 1a is similar to that in Table 1. For the photolysis of
1b at short times (Table 2), the yields of 4b and 5b are
0 and 30%, respectively. Product 5b can be converted
into 3a and 4b if the irradiation time is increased. For
the photoreaction of 1c, prolonged photolysis converts
5c exclusively to 2c and 3a. Thus, the reaction pathway
is dependent upon the halogen substituent. Based on
these results, the mechanism shown in Scheme 3 is
proposed to explain the formation of products.
Even with the presence of a heavy bromine element in
compound 1b, the reaction is still a singlet state reac-
tion. It is not sensitized by triplet sensitizer and the
reaction is not quenched by suitable triplet quencher
(e.g. piperylene). The dihydrophenanthrene intermedi-
ate 6 of p-bromostilbene is reported to come directly
from the singlet cis-stilbene by Saltiel.37 This is incon-
sistent with our system that the reaction is in the singlet
manifold.
The mechanism involves the irradiation of the trans-4%-
halostyrylheterocycles to produce cis-1, then the dihy-
drophenanthrene intermediate
photocyclization. An acid-catalyzed formal [1,9] hydro-
6
is formed via
Irradiation of 8-chloro-6,9-dihydronaphtho[2,1-b]furan
2b in 0.5 M hydrochloric acid/acetonitrile solution
shows no photoreaction. Thus, the formation of oxida-
tive photocyclization products 4 may come directly
from the redox reaction of the intermediate 6 and
hydrochloric acid. This result is similar to the photo-
reaction of the stilbene and hydrochloride in
dichloromethane.38 Because the formation of cyclized
products will compete with the acid-catalyzed formal
[1,9] hydrogen shift, the yields of photocyclization
products increased as the rate of hydrogen shift
decreased. For the fluoro substituent, the carbon 9 of
intermediate 6 bears higher partial negative charge
(−0.30) than chloro (−0.16) and bromo (0.04) sub-
stituents. The reaction rate of [1,9] hydrogen shift for
Table 1. Conversions and yields for photoreactions of 1a–f
in the presence of 0.5 M hydrochloric acid
Reactants
hw time (h)
Conversion
Yields (%)
2
3
4
1a
1b
1c
1d
1e
1f
3.5
18
24
21
48
92
100
100
78
87
90
17
55
49
12
56
36
83
0
25 19
11 40
75 13
14 24
11 54
48
Scheme 2.
Table 2. Conversions and yields for photoreactions of 1a–c
in the presence of 0.5 M hydrochloric acid during shorter
irradiation time
Reactants
hv time (h)
Conv.
Yields (%)
2
3
4
5
1a
1b
1c
1
3.5
3.5
77
61
92
14
53
34
79
14
7
0
0
42
<5
30a
17
a The product is cis/trans (4/1) mixture.
Scheme 3.

J.-H. Ho, T.-I. Ho / Tetrahedron Letters 44 (2003) 4669–4672
4671
1a might be faster that the oxidative photocyclization
reaction can not compete with it, so there is no cyclized
product 4 in this case.
2. Hammond, G. S.; Saltiel, J. J. Am. Chem. Soc. 1963, 84,
4983.
3. Hammond, G. S.; Turro, N. J. Science 1962, 142, 1541.
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Int. Ed. Engl. 1980, 19, 243.
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New York, 1983; Vol. 30, p. 1.
7. Hugelshofer, P.; Kalvoda, J.; Schaffner, K. Helv. Chim.
Acta 1960, 165, 1322.
8. Zimmerman, H. E. In Rearrangement in Ground and
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9. Hammond, G. S.; Saltiel, J.; Lamola, A. A.; Turro, N. J.;
Bradshaw, J. S.; Cowan, D. O.; Counsell, R. C.; Vogt,
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The product distributions between products 2 and 3 are
also dependent on the substituents. Because the ring-
opening step is photoreversible,39 the formation rate of
(E)-4-arylbut-3-en-2-one 3 will be effected by the acid-
catalyzed hydrolysis of haloalkenyl group of 5. For
further illustration, intermediate cis-5b was isolated and
irradiated in different acid concentrations. Photolysis of
cis-5b with 0.5 M hydrochloric acid give both products
2b and 3, but it only gives product 2b in 0.005 M
hydrochloric acid with the same irradiation period.
Compared to the reported case of 2-halopropenes,40 the
hydrolysis rate for 2-fluoropropene is 860 times greater
than that of 2-bromopropene. Since the hydrolysis rate
is accelerated by the fluorine atom, intermediate 5a
must be hydrated rapidly to product 3a. Thus the yield
of product 3a from irradiation of 1a is higher than that
of the other cases (1b and 1c). The conversion of 5 to 3
can either be photochemical or thermal depending on
the halogen substituents.
In summary, we have demonstrated that new rearrange-
ment is possible for the halogen substituted styrylhete-
rocycles when photolysis is carried out in the presence
of a protic acid. Due to the competing formal [1,3]
hydrogen shift and ring opening of dihydrophenan-
threne intermediate 7, a new product 2 and a new
hydrolysis product 3 are observed. The product ratio is
dependent on the halogen substituents. It is also shown
that photolysis of 5 can reversibly be transferred back
to 2. Halogen substituent effects indicate that yields of
products 4 increase while products 3 decrease from
fluorine to bromine. The bromine derivative 1c gives
highest yield for product 4. Finally, it is interesting to
note that similar behavior between the styrylthiophenes
and styryfurans is observed in terms of their photore-
sponse both to the acids and to the halogen substituent
effects.
24. Ho, T.-I.; Wu, J.-Y.; Wang, S.-L. Angew. Chem., Int. Ed.
1999, 38, 2558.
Supplementary material
25. Wu, J.-Y.; Ho, J.-H.; Shih, S.-M.; Hsieh, T.-L.; Ho, T.-I.
Org. Lett. 1999, 1, 1039.
26. Huyser, E. S.; Neckers, D. C. J. Org. Chem. 1964, 29,
276.
The following supplementary material is available on-
1
line: H and 13C NMR spectral data of products 2a–f,
3a–b and 5a–c.
27. Hoffmann, N.; Pete, J.-P. J. Org. Chem. 1997, 62, 6952.
28. Bryce-Smith, D.; Gilbert, A. J. Chem. Soc., Chem. Com-
mun. 1968, 19.
Acknowledgements
29. Umbricht, G.; Hellman, M. D.; Hegedus, L. S. J. Org.
Chem. 1998, 63, 5173.
30. Schulta, A. G.; Anotlinakis, E. G. J. Org. Chem. 1996,
61, 4555.
31. Mori, T.; Wada, T.; Inoue, Y. Org. Lett. 2000, 2, 3401.
32. Hayamizu, T.; Ikeda, M.; Maeda, H.; Mizuno, K. Org.
Lett. 2001, 3, 1277.
The financial supports from National Science Council
of Republic of China (Taiwan) is gracefully acknowl-
edged. The authors thank Professor F. D. Lewis for
valuable comments.
33. Ohkura, K.; Sugaoi, T.; Nishijima, K.; Kuge, Y.; Seki, K.
Tetrahedron Lett. 2002, 43, 3113.
34. Ho, T.-I.; Ho, J.-H.; Wu, J.-Y. J. Am. Chem. Soc. 2000,
122, 8575.
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J.-H. Ho, T.-I. Ho / Tetrahedron Letters 44 (2003) 4669–4672
1
36. The spectral data for compound 2a: H NMR (300 MHz,
CDCl3): l 7.64 (d, J=2.2 Hz, 1H), 7.36 (d, J=8.6 Hz,
1H), 7.09 (d, J=8.6 Hz, 1H), 6.73 (d, J=2.2 Hz, 1H),
5.52–5.44 (dm, J=16.9 Hz, 1H), 3.73–3.68 (m, 2H),
3.64–3.57 (m, 2H). 13C NMR (75 MHz, CDCl3): l 156.4
(35). HRMS (C12H9FO): calcd 188.0637, found 188.0633.
37. Saltiel, J.; Chang, D. W.-L.; Megarity, E. D. J. Am.
Chem. Soc. 1974, 96, 6521.
38. Kaupp, G.; Ringer, E. Chem. Ber. 1986, 199, 1525.
39. In thermal reaction of intermediate cis-5b in 0.5 M
hydrochloric acid/acetonitrile solution at ca. 60°C for 3 h,
only hydrolysis reaction occurs to give the product 3a.
40. Allen, A. D.; Tidwell, T. T. J. Am. Chem. Soc. 1982, 104,
3145.
(d, J1CꢁF=248.9 Hz), 153.1, 145.0, 126.5, 126.2 (d, J3CꢁF
=
3.2 Hz), 124.8, 124.7, 109.8, 104.6, 100.1 (d, J2CꢁF=16.3 Hz),
28.8 (d, J3CꢁF= 8.0 Hz), 27.8 (d, JC2 ꢁF=27.9 Hz). MS (70
eV, EI): 188 (M+, 100), 186 (55), 168 (16), 159 (88), 157