A novel photochemical Wittig reaction for the synthesis of 2-aryl/alkylbenzofurans

Article abstract of DOI:10.1016/j.tetlet.2010.12.104

The synthesis of 2-aryl/alkylbenzofurans has been achieved in high yields under photochemical conditions from readily accessible and suitably substituted phosphonium bromides by an intramolecular photochemical Wittig reaction onto aryloxycarbonyl groups.

Full text of DOI:10.1016/j.tetlet.2010.12.104

Tetrahedron Letters 52 (2011) 1112–1116
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel photochemical Wittig reaction for the synthesis
of 2-aryl/alkylbenzofurans
⇑
Somnath Ghosh , Jhantu Das
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of 2-aryl/alkylbenzofurans has been achieved in high yields under photochemical condi-
tions from readily accessible and suitably substituted phosphonium bromides by an intramolecular pho-
tochemical Wittig reaction onto aryloxycarbonyl groups.
Received 13 November 2010
Revised 18 December 2010
Accepted 26 December 2010
Available online 7 January 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Intramolecular photochemical Wittig
reaction
Phosphoranyl radical
Betaine
Benzofurans
2-Arylbenzofurans constitute an important class of naturally
occurring oxygen heterocycles known for their various biological
activities1 and several of them have been recognized as antifungal
phytoalexins.
the literature;27 for example, 2-substituted benzofurans have been
synthesized by SRN1 reaction under photochemical conditions.28,29
Intermolecular photochemical Wittig olefination reaction was
first demonstrated by Tomioka et al.30 in 1992 using unreactive
2-Phenylbenzofuran was first prepared by Dilthey and Quint2 in
1931 and later on by Yates.3 Afterwards, a host of syntheses for the
title compounds have been reported in the literature from time to
time; and in recent times, some interesting methods for the syn-
theses of benzofurans have been described.4–11 While the synthesis
of heterocyclic compounds is commonly achieved by thermal reac-
tions, metal ion mediated synthesis of benzofuran derivatives is
also of recent importance.12–14
a-(methoxycarbonyl) benzylidene quasi-phosphonium ylides onto
acyclic carbonyl compounds in the presence of UV light, and other
works related to photo-Wittig have been reported.31–33
In connection with our interest in the synthesis of oxygen het-
erocycles,25,26 we wish to report herein, for the first time, a novel
and expeditious synthesis of 2-aryl/alkylbenzofurans by a hitherto
unknown intramolecular photochemical Wittig reaction (Scheme 1)
and also by microwave irradiation.
It is a well-known phenomenon that the use of light accelerates
certain reactions in organic synthesis and such photochemical acti-
vation of substrate without additional reagents very often mini-
mizes the formation of byproducts; and for this reason,
photochemical reactions occupy an interesting position in the
realm of green chemistry. These concepts have successfully been
employed in many organic syntheses employing visible light or
sunlight or UV light, for example, Suzuki–Miyaura and Stille-type
coupling reactions,15 Nazarov cyclisation,16 etc. and excellent re-
views on photochemical reactions have been published.17,18
While the synthesis of heterocyclic compounds is commonly
achieved by thermal reactions, photochemical syntheses of nitro-
gen and oxygen heterocycles have been previously reported19–26
by us and elegant reviews on these areas are well documented in
The present procedure for the synthesis of the title compounds
(5) consists of photo-irradiation of suitably substituted phospho-
nium salts (4) in carbon tetrachloride in the presence of triethyl-
amine and after removal of the solvent, the products are
obtained in high yields (46–87%) and in a highly pure state by a
simple column filtration over silica gel.
While a thermal version34,35 of such reactions with esters de-
rived from aromatic acids requires prolonged heating and yields
are low (ca. 21–60%), the present one is extremely efficient and
has been achieved in a very short time (30 min). We have also ob-
served that the present procedure works smoothly both for aro-
matic or aliphatic esters, thereby showing the efficacy of the same.
In order to test the generality and wider applicability of this
novel protocol, we have performed a light induced reaction on
2’-(3,5-diacetoxy-benzoyloxy)-benzyl triphenyl phosphonium bro-
mide (4i). We isolated 2-(3,5-diacetoxy)-phenylbenzofuran (5i),
the diacetate of naturally occurring benzofuran, Stemofuran A36
⇑
Corresponding author. Tel./fax: +91 033 2414 6223.
E-mail address: ghoshsn@yahoo.com (S. Ghosh).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.104

S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116
ArCOCl or
1113
CH3
OH
CH3
CH2Br
NBS / CCl4 / hν
RCOCl
°C
Py / 0
O
C
O
C
O
Ar / R
Ar / R
2
O
3
1
PPh3 /Δ
CH2PPh3Br
CCl4 / Et3N / hν
O
Ar / R
Ar / R
O
C
O
MW / Et3N / neutral Al2O3
4
5
a:
,
d:
,
,
Ar =
,
b:
c:
H3CO
H3CO
OCH3
CH3
OCH3
O
O
,
,
,
e:
g:
i:
,
f:
O
H3C
O2N
O
Cl
CH3
h:
R =
Scheme 1. Photochemical synthesis of 2-aryl/alkylbenzofurans.
in 64% yield (Scheme 2). However, the microwave irradiation of 4i
in the presence of triethylamine over neutral alumina for 6 min at
175 °C afforded 5i only in 51% yield.
alumina support to obtain the benzofurans (5a–h). The compara-
tive results of photochemical and microwave assisted experiments
are presented in Table 1.
We have also performed a microwave irradiation of all the sub-
strates (4a–h) in the presence of triethylamine over neutral
We observed that refluxing 4a in carbon tetrachloride in the
presence of triethylamine for 6 h furnished an insignificant amount
COOH
CH3
OH
CH3
1: (COCl)2, C6H6
°C
O
O
O
CH3
2: Py / 0
H3C
O
O
CH3
O
C
O
2i
O
1
O
O
CH3
NBS / CCl4 / hν
CH2PPh3Br
CH2Br
PPh3 /Δ
O
CH3
O
CH3
O
C
O
O
C
O
3i
4i
O
O
O
O
O
O
CCl4 / Et3N / hν
CH3
CH3
MW / Et3N / Neutral Al2O3
O
CH3
O
O
5i
O
O
CH3
Scheme 2. Photochemical synthesis of 2-(3,5-diacetoxy)-phenylbenzofuran.

1114
S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116
Table 1
Results of photochemical irradiation of 4
Entry
Substrate
Producta
Yieldb (%)
CH2PPh3Br
O
O
A (h
B (MW): 59
m): 52
1
O
5a
4a
CH2PPh3Br
O
O
A (h
B (MW): 68
m): 72
2
O
5b
OCH3
OCH3
OCH3
4b
CH2PPh3Br
O
O
A (hm): 87
3
4
OCH3
B (MW): 35
O
5c
4c
CH2PPh3Br
O
OCH3
OCH3
O
A (h
B (MW): 59
m): 83
OCH3
O
5d
OCH3
4d
CH2PPh3Br
O
O
A (h
B (MW): 52
m): 61
5
6
O
5e
Cl
4e
Cl
CH2PPh3Br
O
O
A (hm): 81
O
B (MW): 72
5f
NO2
4f
NO2
CH2PPh3Br
O
O
CH3
A (h
B (MW): 50
m): 65
7
8
O
5g
CH3
4g
CH2PPh3Br
O
O
A (hm): 46
B (MW): 53
O
5h
4h
CH2PPh3Br
O
CH3
O
O
CH3
O C
O
O
A (h
B (MW): 51
m): 64
5i
9
O
O
O
4i
O
O
CH3
CH3
a
All products were characterized by their satisfactory spectral data and also by comparison with literature data.
Yield refers to combined amounts of first and second crops of crystallized products obtained after chromatography.
b
of benzofuran (5a). Moreover, when the bromoester (3a) was sub-
jected to a photochemical reaction, it failed to afford 5a and only
the starting material was recovered. These experimental observa-
tions indicated that the reaction is probably governed by a radical
pathway involving a benzylic radical (II) or it may form a very
unstable P–NÈ bond (III) by an electron transfer reaction from tri-
ethylamine onto the phosphonium salt (4) under photochemical
condition to generate a phosphoranyl radical,30,37 (I) that further
combines with triethylammonium radical-cation (Scheme 3). This,
with the expulsion of benzylic hydrogen, produces a betaine (IV)
and products (5) in high purity. We also isolated triphenylphos-
phine oxide as a byproduct, which supports the mechanistic path-
way involving a betaine intermediate.
In conclusion, an operationally simple, clean and useful meth-
odology38 for the synthesis of 2-aryl/alkyl-benzofurans has been
developed by intramolecular photochemical Wittig reaction.

S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116
1115
CH2-PPh3-NEt3
CH2-PPh3
Et3N
CH2PPh3Br
,
Et3N hν
Ar / R
O
C
O
Ar / R
Ar / R
O
C
O
O
C
O
Et3N
(III)
4
(I)
Et3NHBr
- H
CH PPh3
CH-PPh3
Ar / R
O
C
O
Ar / R
O
C
O
(IV)
(II)
PPh3
O
O
O
Ar / R
Ar / R
5
Ph3PO
Scheme 3. Plausible mechanism for the synthesis of 2-aryl/alkylbenzofurans.
28. Christiaens, L.; Renson, M. Bull. Soc. Chim. Belg. 1970, 79, 235.
29. Beugelmans, R.; Ginsberg, H. Chem. Commun. 1980, 508–509.
30. Tomioka, H.; Ichikawa, N.; Murata, H. Chem. Commun. 1992, 193–195.
31. Hase, T. Synlett 1994, 817–818.
32. Shah, S.; Simpson, M. C.; Smith, R. C.; Protasiewicz, J. D. J. Am. Chem. Soc. 2001,
123, 6925–6926.
Acknowledgements
The authors wish to thank Professor D. W. Knight, Cardiff
University, UK for constructive suggestions. Financial support to
one of the authors (J.D.) from UGC, Govt. of India and CAS,
Department of Chemistry, Jadavpur University is acknowledged.
33. Du, S.; Shen, W.; Jin, H. Huaxue Tongbao 2004, 67, 75–77 (Chemistry 2004, 75–
77).
34. Hercouet, A.; Le Corre, M. Tetrahedron 1981, 37, 2867–2874.
35. McKittrick, B. A.; Scanell, R. T.; Stevenson, R. J. Chem. Soc., Perkin Trans. 1 1982,
3017–3020.
References and notes
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3635.
38. Method A: A solution of phosphonium salts (4a–i) (2 mmol) in dry carbon
tetrachloride (20 mL) and triethyl amine (5 mmol) was irradiated with a 150 W
tungsten lamp (Philips India Ltd.) for 0.5 h. The reaction was monitored by TLC
(in 10 min interval), and the products (5a–i) were isolated, after removal of the
solvent in vacuo, by a column filtration over silica gel (60–120 mesh, Merck)
(petroleum ether, 60–80 °C and ethyl acetate, 0–15% v/v mixture) and
crystallized from appropriate solvents.
1. Hou, X.-L.; Yang, Z.; Wong, H. N. C. Furans and Benzofurans. In Progress in
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England, 2002; Vol. 14, pp 139–179.
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1525–1528.
Method B: Phosphonium salts (4a–i) (1 mmol) were dissolved in dry
dichloromethane (5 mL) and triethylamine (1.5 mmol) was added to it
followed by neutral alumina (2 g). The whole slurry was mixed thoroughly
and the solvent was removed in vacuo. The solid residue was then subjected to
microwave irradiation (2450 MHz) at temperatures 145 °C (for 4 min, entry 7)
and 175 °C (for 6 min, entries 1–6 and 8) and benzofurans (5a–i) were isolated
by a column filtration over silica gel (petroleum ether, 60–80 °C and ethyl
acetate, 0–15% v/v mixture) in pure form.
8. Eidamshaus, C.; Burch, J. D. Org. Lett. 2008, 10, 4211–4214.
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W.; Zeni, G. J. Org. Chem. 2009, 74, 2153–2162.
12. Ledoussal, B.; Gorgues, A.; Le Coq, A. J. Chem. Soc., Chem. Commun. 1986, 171–
172.
2-(4-Methoxy)-phenylbenzofuran (5b): Colourless shining flakes, mp 151–52 °C
(diethyl ether–petroleum ether, 60–80 °C) (lit.35 mp 153–55 °C); 1H NMR
(300 MHz, CDCl3, 22 °C) d 7.81 (d, J = 8.7 Hz, 2H), 7.56 (dd, J = 7.4 Hz, 1.5 Hz,
1H), 7.51 (d, J = 7.8 Hz, 1H), 7.25 (m, 2H), 6.99 (d, J = 8.7 Hz, 2H), 6.90 (s, 1H),
3.88 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3, 22 °C) d 160.0, 156.1, 154.7, 129.5,
126.4, 123.7, 123.4, 122.8, 120.6, 114.2, 111.0, 99.7, 55.4 ppm.
2-(3-Methoxy)-phenylbenzofuran (5c): Colourless shining flakes, mp 66–67 °C
(diethyl ether–petroleum ether, 60–80 °C); 1H NMR (300 MHz, CDCl3, 22 °C) d
7.55 (d, J = 2.1 Hz, 1H), 7.40 (m, 5H), 7.24 (m, 1H), 6.94 (m, 2H), 3.90 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3, 22 °C) d 160.0, 157.3, 153.3, 131.3, 130.6, 130.0,
128.5, 124.5, 120.5, 117.7, 114.9, 112.1, 110.4, 101.1, 55.4 ppm; Anal. Calcd for
13. Ledoussal, B.; Gorgues, A.; Le coq, A. Tetrahedron 1987, 43, 5841–5852.
14. Gay, R. M.; Manarin, F.; Schneider, C. C.; Barancelli, D. A.; Costa, M. D.; Zeni, G. J.
Org. Chem. 2010, 75, 5701–5706.
15. Imperato, G.; Kçnig, B. Chem Sus Chem 2008, 1, 993–996.
16. Gao, S.; Wang, Q.; Chen, C. J. Am. Chem. Soc. 2009, 131, 1410–1412.
17. Hoffmann, N. Chem. Rev. 2008, 108, 1052–1103.
18. Fagnoni, M.; Dondi, D.; Ravelli, D.; Albini, A. Chem. Rev. 2007, 107, 2725–2756.
19. Ghosh, S. N.; Das, T. K.; Datta, D. B.; Mehta, S. Tetrahedron Lett. 1987, 28, 4611–
4614.
20. Ghosh, S. N.; Datta, D. B.; Datta, I.; Das, T. K. Tetrahedron 1989, 45, 3775–3786.
21. Datta, I.; Das, T. K.; Ghosh, S. N. Tetrahedron Lett. 1989, 30, 4009–4012.
22. Datta, I.; Das, T. K.; Ghosh, S. N. Tetrahedron 1990, 46, 6821–6830.
23. Ghosh, S. N.; Nandi, B.; Saima, Y. Tetrahedron Lett. 1996, 37, 3169–3170.
24. Ghosh, S. N.; Baul, S. Arkivoc 2003, 58–68.
25. Ghosh, S. N.; Datta, I.; Chakraborty, R.; Das, T. K.; Sengupta, J.; Sarkar, D. C.
Tetrahedron 1989, 45, 1441–1447.
26. Ghosh, S. N.; Banerjee, I.; Baul, S. Tetrahedron 1999, 55, 11537–11546.
27. Reviews: (a) Sharma, R. K.; Kharasch, N. Angew. Chem., Int. Ed. Engl. 1968, 7, 36–
44; (b) Lenz, G. R. Synthesis 1978, 489–518; (c) Mallory, F. B.; Mallory, C. W.
Org. React. 1984, 30, 1–456.
C15H12O2: C, 80.34; H, 5.39. Found: C, 80.39; H, 5.29.
2-(3,4-Dimethoxy)-phenylbenzofuran (5d): Colourless shining flakes, mp 123–
24 °C (diethyl ether–petroleum ether, 60–80 °C); 1H NMR (300 MHz, CDCl3,
22 °C) d 7.53 (m, 1H), 7.44 (dd, J = 8.4 Hz, 2.1 Hz, 1H), 7.39 (d, J = 1.8 Hz, 1H),
7.25 (m, 2H), 6.95 (s, 1H), 6.91 (d, J = 3.3 Hz, 1H), 4.00 (s, 3H), 3.93 (s, 3H) ppm;
13C NMR (75 MHz, CDCl3, 22 °C) d 155.9, 154.6, 149.5, 149.2, 129.4, 123.8,
123.5, 122.8, 120.5, 117.9, 111.3, 110.9, 108.0, 100.0, 55.94, 55.92 ppm; Mass
(EI) m/z (%):255.0526 (MÅ++H); Anal. Calcd for C16H14O3: C, 75.57; H, 5.55.
Found: C, 75.62; H, 5.51.

1116
S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116
2-(4-Chloro)-phenylbenzofuran (5e): Colourless shining flakes, mp 148–49 °C
137.3, 129.0, 128.9, 128.7, 126.8, 123.5, 122.6, 120.5, 111.0, 103.4, 35.1 ppm;
Anal. Calcd for C15H12O: C, 86.51; H, 5.81. Found: C, 86.47; H, 5.77.
2-(3,5-Diacetoxy)-phenylbenzofuran (5i): Colourless crystalline solid, mp 87–
88 °C (ether–petroleum ether, 60–80 °C); 1H NMR (300 MHz, CDCl3, 22 °C) d
7.59 (d, J = 7.4 Hz, 1H), 7.50 (d, J = 7.4 Hz, 3H), 7.32 (d, J = 7.0 Hz, 1H), 7.25 (m,
1H), 7.04 (s, 1H), 6.92 (s, 1H), 2.34 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3, 22 °C)
d 168.8, 155.0, 154.0, 151.5, 132.5, 128.8, 124.9, 123.1, 121.2, 115.5, 115.4,
111.3, 102.8, 21.1 ppm; Anal. Calcd for C18H14O5: C, 69.67; H, 4.55. Found: C,
69.62; H, 4.59.
(diethyl ether–petroleum ether, 60–80 °C); 1H NMR (300 MHz, CDCl3, 22 °C):
d7.79 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 7.2 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.42 (d,
J = 8.7 Hz, 2H), 7.28 (m, 2H), 7.01 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3, 22 °C)
d
154.9, 154.8, 134.3, 129.0, 128.98, 126.1, 124.6, 123.1, 121.0, 111.2,
101.7 ppm; Anal. Calcd for C14H9ClO: C, 73.53; H, 3.97. Found: C, 73.49; H, 3.92.
2-Benzylbenzofuran (5h): Colourless liquid; 1H NMR (300 MHz, CDCl3, 22 °C) d
7.55 (m, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.41 (dd, J = 5.4 Hz, 3 Hz, 5H), 7.29 (m, 2H),
6.45 (s, 1H), 4.18 (s, 2H) ppm; 13C NMR (75 MHz, CDCl3, 22 °C) d 157.9, 155.1,