Tetrahedron Letters 52 (2011) 1112–1116

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Tetrahedron Letters

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

Somnath Ghosh ⇑, Jhantu DasDepartment of Chemistry, Jadavpur University, Kolkata 700 032, India

a r t i c l e i n f o

Article history:Received 13 November 2010Revised 18 December 2010Accepted 26 December 2010Available online 7 January 2011

Keywords:Intramolecular photochemical WittigreactionPhosphoranyl radicalBetaineBenzofurans

0040-4039/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.tetlet.2010.12.104

⇑ Corresponding author. Tel./fax: +91 033 2414 622E-mail address: ghoshsn@yahoo.com (S. Ghosh).

a b s t r a c t

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.

� 2011 Elsevier Ltd. All rights reserved.

2-Arylbenzofurans constitute an important class of naturallyoccurring oxygen heterocycles known for their various biologicalactivities1 and several of them have been recognized as antifungalphytoalexins.

2-Phenylbenzofuran was first prepared by Dilthey and Quint2 in1931 and later on by Yates.3 Afterwards, a host of syntheses for thetitle compounds have been reported in the literature from time totime; and in recent times, some interesting methods for the syn-theses of benzofurans have been described.4–11 While the synthesisof heterocyclic compounds is commonly achieved by thermal reac-tions, metal ion mediated synthesis of benzofuran derivatives isalso of recent importance.12–14

It is a well-known phenomenon that the use of light acceleratescertain 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 therealm of green chemistry. These concepts have successfully beenemployed in many organic syntheses employing visible light orsunlight or UV light, for example, Suzuki–Miyaura and Stille-typecoupling 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 commonlyachieved 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

ll rights reserved.

3.

the literature;27 for example, 2-substituted benzofurans have beensynthesized by SRN1 reaction under photochemical conditions.28,29

Intermolecular photochemical Wittig olefination reaction wasfirst demonstrated by Tomioka et al.30 in 1992 using unreactivea-(methoxycarbonyl) benzylidene quasi-phosphonium ylides ontoacyclic carbonyl compounds in the presence of UV light, and otherworks 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 noveland expeditious synthesis of 2-aryl/alkylbenzofurans by a hithertounknown intramolecular photochemical Wittig reaction (Scheme 1)and also by microwave irradiation.

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 areobtained in high yields (46–87%) and in a highly pure state by asimple column filtration over silica gel.

While a thermal version34,35 of such reactions with esters de-rived from aromatic acids requires prolonged heating and yieldsare low (ca. 21–60%), the present one is extremely efficient andhas 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 thisnovel protocol, we have performed a light induced reaction on2’-(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

ArCOCl or RCOCl

O

CH2Br

CO

PPh3 /Δ

Ar = ,

Py / 0 °C

,

R = CH3 ,

,,

,

1 2 3

45

a: b: c: d:

e: f:

h:g:

i: ,,

O

CH3

CO

OH

CH3

O

CH2PPh3Br

CO

O Ar / R

Ar / R Ar / R

Ar / R

H3COOCH3 OCH3

H3CO

Cl O2N OO CH3H3C

OO

NBS / CCl4 / hν

CCl4 / Et3N / hν

MW / Et3N / neutral Al2O3

Scheme 1. Photochemical synthesis of 2-aryl/alkylbenzofurans.

S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116 1113

in 64% yield (Scheme 2). However, the microwave irradiation of 4iin the presence of triethylamine over neutral alumina for 6 min at175 �C afforded 5i only in 51% yield.

We have also performed a microwave irradiation of all the sub-strates (4a–h) in the presence of triethylamine over neutral

2: P

1

4i

5i

OH

CH3

O

CH2PPh3Br

CO

O

CCl4 / Et3N / hν

COOH

O CH3OH3C

OO 1: (COC

O

CH3

O CH3

O

O

O

CH3

O CH3

O

O

Scheme 2. Photochemical synthesis of 2

alumina support to obtain the benzofurans (5a–h). The compara-tive results of photochemical and microwave assisted experimentsare presented in Table 1.

We observed that refluxing 4a in carbon tetrachloride in thepresence of triethylamine for 6 h furnished an insignificant amount

O

CH2Br

CO

PPh3 /Δ

y / 0°C

2i

3i

O

CH3

CO

NBS / CCl4 / hν

l)2, C6H6

O

CH3

O CH3

O

O

O

CH3

O CH3

O

O

MW / Et3N / Neutral Al2O3

-(3,5-diacetoxy)-phenylbenzofuran.

Table 1Results of photochemical irradiation of 4

Entry Substrate Producta Yieldb (%)

1O

CH2PPh3BrO

4a5a

O A (hm): 52B (MW): 59

2 O

CH2PPh3BrO

4b OCH3

5b

O

OCH3

A (hm): 72B (MW): 68

3O

CH2PPh3BrO

4c

OCH3 5c

O OCH3 A (hm): 87B (MW): 35

4O

CH2PPh3BrO

4d

OCH3

OCH3

5d

O OCH3

OCH3

A (hm): 83B (MW): 59

5O

CH2PPh3BrO

4e Cl

5e

O

Cl

A (hm): 61B (MW): 52

6 O

CH2PPh3BrO

4f NO2

5f

O

NO2

A (hm): 81B (MW): 72

7O

CH2PPh3BrO

CH3

4g

5g

O CH3 A (hm): 65B (MW): 50

8

4h

O

OCH2PPh3Br

5h

O A (hm): 46B (MW): 53

9

4i

O

CH2PPh3Br

CO

O

CH3

O CH3

O

O

5i

O

O

CH3

O CH3

O

O

A (hm): 64B (MW): 51

a All products were characterized by their satisfactory spectral data and also by comparison with literature data.b Yield refers to combined amounts of first and second crops of crystallized products obtained after chromatography.

1114 S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116

of benzofuran (5a). Moreover, when the bromoester (3a) was sub-jected to a photochemical reaction, it failed to afford 5a and onlythe starting material was recovered. These experimental observa-tions indicated that the reaction is probably governed by a radicalpathway involving a benzylic radical (II) or it may form a veryunstable P–N� bond (III) by an electron transfer reaction from tri-ethylamine onto the phosphonium salt (4) under photochemicalcondition 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 beendeveloped by intramolecular photochemical Wittig reaction.

O

CH2PPh3Br

CO

Ar / R O CO

Ar / R

Ph3PO

4

(IV)

O CO

Ar / R

O

CH

CO

Ar / R

PPh3

O CO

Ar / R

OOPPh3

5

O

(II)

(III)Et3N

hν

- H Et3NHBr

Ar / RAr / R

CH2-PPh3-NEt3

(I)

CH2-PPh3

CH-PPh3

Et3NEt3N ,

Scheme 3. Plausible mechanism for the synthesis of 2-aryl/alkylbenzofurans.

S. Ghosh, J. Das / Tetrahedron Letters 52 (2011) 1112–1116 1115

Acknowledgements

The authors wish to thank Professor D. W. Knight, CardiffUniversity, UK for constructive suggestions. Financial support toone of the authors (J.D.) from UGC, Govt. of India and CAS,Department of Chemistry, Jadavpur University is acknowledged.

References and notes

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172.13. 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.

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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.

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44; (b) Lenz, G. R. Synthesis 1978, 489–518; (c) Mallory, F. B.; Mallory, C. W.Org. React. 1984, 30, 1–456.

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123, 6925–6926.33. 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,

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Prod. 2002, 63, 820–827.37. Bentrude, W. G.; Fu, Juian-Juian L.; Rogers, P. E. J. Am. Chem. Soc. 1973, 95, 3625–

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 Wtungsten 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 thesolvent 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) andcrystallized from appropriate solvents.Method B: Phosphonium salts (4a–i) (1 mmol) were dissolved in drydichloromethane (5 mL) and triethylamine (1.5 mmol) was added to itfollowed by neutral alumina (2 g). The whole slurry was mixed thoroughlyand the solvent was removed in vacuo. The solid residue was then subjected tomicrowave 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 isolatedby a column filtration over silica gel (petroleum ether, 60–80 �C and ethylacetate, 0–15% v/v mixture) in pure form.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) d7.55 (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 forC15H12O2: 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 (M�++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(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) d7.55 (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,

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) d7.59 (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.