2666
M. L . N. Rao et al. / Tetrahedron Letters 53 (2012) 2662–2666
2. Hou, X. L.; Yang, Z.; Wong, H. N. C. In Progress in Heterocyclic Chemistry; Gribble,
G. W., Gilchrist, T. L., Eds.; Pergmon: Oxford, 2003.
3. Hwang, J. W.; Choi, D. H.; Jeon, J.-H.; Kim, J.-K.; Jun, J.-G. Bull. Korean Chem. Soc.
2010, 31, 965–970.
4. (a) Erber, S.; Ringshandl, R.; von Angerer, E. Anti-Cancer Drug Des. 1991, 6, 417–
426; (b) Galal, S. A. Abd El-Al, A. S.; Abdallah, M. M.; El-Diwani, H. I Bioorg. Med.
Chem. Lett. 2009, 19, 2420–2428.
5. Kim, S.; Salim, A. A.; Swanson, S. M.; Kinghorn, A. D. Anticancer Agents Med.
Chem. 2006, 6, 319–345.
6. Lau, C. K.; Bélanger, P. C.; Scheigetz, J.; Dufresne, C.; Williams, H. W. R.;
Maycock, A. L.; Guindon, Y.; Bach, T.; Dallob, A. L.; Denis, D.; Ford-Hutchinson,
A. W.; Gale, P. H.; Hopple, S. L.; Letts, L. G.; Luell, S.; McFarlane, C. S.; MacIntyre,
E.; Meurer, R.; Miller, D. K.; Piechuta, H.; Riendeau, D.; Rokach, J.; Rouzer, C. J.
Med. Chem. 1989, 32, 1190–1197.
7. Aslam, S. N.; Stevenson, P. C.; Phythian, S. J.; Veitch, N. C.; Hall, D. R. Tetrahedron
2006, 62, 4214–4226.
8. Rao, M. L. N.; Awasthi, D. K.; Banerjee, D. Tetrahedron Lett. 2010, 51, 1979–1981.
and reference cited therein.
Table 2, the reactivity of different triarylbismuths demonstrated
high coupling ability with overall 80–96%, cross-coupled yields.22
Both electronically rich and deficient triarylbismuth reagents
demonstrated high reactivity with three aryl transfers for cross-
coupling purpose in a short reaction time and is an important point
to note in these couplings.
Furthermore, the generality of these couplings with different
2-bromobenzofurans and triarylbismuths was established under
optimized conditions22 and the results are given in Table 3.
The coupling reactions of variously substituted 2-bromobenzofu-
rans with electronically different groups such as 5-acetyl, 5,7-di-
chloro, 5-bromo, and 7-methxoy reacted well to furnish the
corresponding functionalized 2-arylbenzofuans in combination
with different triarylbismuths in excellent yields. The coupling
reactions with 2,5-dibromobenzofuran reacted regioselectively
at 2-position. The reactivity of 2-bromo-5,7-dichlorobenzofuran
was also found to be similar and coupling underwent at 2-posi-
tion furnishing the corresponding 2-arylbenzofuran in high
yields.
The cross-coupling reactivity demonstrated in this study is
highly productive and led to the formation of 2-arylbenzofurans
in excellent yields in 1 h short reaction time. This is in sharp con-
trast to the reactivity earlier reported using aryl organometallic re-
agents. For example, the coupling reaction involving one C–C bond
formation using 2-bromobenzouran and aryltin reagents required
heating at 145 °C for 5 h.14 Similar couplings using aryl boronic
acids16b,c reacted under reflux conditions and long hours some
times. The coupling reaction of 2-bromobenzofuran was reported
with n-Bu3Bi at 110 °C which needed 18 h for one alkyl coupling
from trialkylbismuth reagent.23 The present aryl coupling method
with triarylbismuths is advantageous from various counts such as
three aryl couplings in atom-economic manner in one-pot opera-
tion, faster reactivity in shorter reaction times, high coupling
yields, and utilization of non-toxic bismuth reagents as organome-
tallic nucleophiles under palladium catalyzed conditions.
In summary, we have demonstrated atom-economic synthesis
of 2-arylbenzofurans from the cross-coupling reaction of 2-bro-
mobenzfurans with triarylbismuth reagents under palladium
catalytic protocol conditions. This methodology with several advan-
tages is expected to provide a facile platform in synthetic organic
chemistry for the synthesis of a plethora of 2-arylbenzofurans in
high yields.
9. (a) Bach, T.; Bartels, M. Tetrahedron Lett. 2002, 43, 9125–9127; (b) Bach, T.;
Bartels, M. Synthesis 2003, 925–939.
10. Kao, C.-L.; Chern, J.-W. J. Org. Chem. 2002, 67, 6772–6787.
11. (a) Bach, T.; Bartels, M. Synlett 2001, 1284–1286; (b) Zhang, H.; Ferreira, E. M.;
Stoltz, B. M. Angew. Chem., Int. Ed. 2004, 43, 6144–6148; (c) Jaseer, E. A.; Prasad,
D. J. C.; Sekar, G. Tetrahedron 2010, 66, 2077–2082; (d) Csékei, M.; Novák, Z.;
Kotschy, A. Tetrahedron 2008, 64, 8992–8996; (e) Willis, M. C.; Taylor, D.;
Gillmore, A. T. Org. Lett. 2004, 6, 4755–4757; (f) Nagamochi, M.; Fang, Y.-Q.;
Lautens, M. Org. Lett. 2007, 9, 2955–2958; (g) Liang, Y.; Tang, S.; Zhang, X.-D.;
Mao, L.-Q.; Xie, Y.-X.; Li, J.-H. Org. Lett. 2006, 8, 3017–3020; (h) Hussain, M.;
Hung, N. T.; Langer, P. Tetrahedron Lett. 2009, 50, 3929–3932; (i) Xie, X.; Chen,
B.; Lu, J.; Han, J.; She, X.; Pan, X. Tetrahedron Lett. 2004, 45, 6235–6237; (j)
DiMauro, E.; Vitullo, J. R. J. Org. Chem. 2006, 71, 3959–3962.
12. (a) Miyata, O.; Takeda, N.; Morikami, Y.; Naito, T. Org. Biomol. Chem. 2003, 1,
254–256; (b) Pan, C.; Yu, J.; Zhou, Y.; Wang, Z.; Zhou, M.-M. Synlett 2006, 1657–
1662; (c) Fuerst, D. E.; Stoltz, B. M.; Wood, J. L. Org. Lett. 2000, 2, 3521–3523;
(d) Rao, M. L. N.; Awasthi, D. K.; Banerjee, D. Tetrahedron Lett. 2007, 48, 431–
434; (e) Ota, T.; Hasegawa, S.; Inoue, S.; Sato, K. J. Chem. Soc., Perkin Trans. 1
1988, 3029–3035; (f) Watanabe, M.; Date, M.; Kawanishi, K.; Hori, T.;
Furukawa, S. Chem. Pharm. Bull. 1991, 39, 41–48.
13. Clough, J. M.; Mann, I. S.; Widdowson, D. A. Tetrahedron Lett. 1987, 28, 2645–2648.
14. Lin, S.-Y.; Chen, C.-L.; Lee, Y.-J. J. Org. Chem. 2003, 68, 2968–2971.
15. (a) Kitamura, Y.; Sako, S.; Udzu, T.; Tsutsui, A.; Maegawa, T.; Monguchi, Y.;
Sajiki, H. Chem. Commun. 2007, 5069–5071; (b) Wang, Z.; Elokdah, H.;
McFarlane, G.; Pan, S.; Antane, M. Tetrahedron Lett. 2006, 47, 3365–3369; (c)
Molander, G. A.; Canturk, B.; Kennedy, L. E. J. Org. Chem. 2009, 74, 973–980; (d)
Denmark, S. E.; Smith, R. C.; Chang, W. T.; Muhuhi, J. M. J. Am. Chem. Soc. 2009,
131, 3104–3118.
16. (a) Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.;
Blackburn, T.; Ramgren, S. D.; Houk, K. N.; Snickus, V.; Garg, N. K. J. Am. Chem.
Soc. 2011, 133, 6352–6363; (b) Gill, G. S.; Grobelny, D. W.; Chaplin, J. H.; Flynn,
B. L. J. Org. Chem. 2008, 73, 1131–1134; (c) James, C. A.; Coelho, A. L.; Gevaert,
M.; Forgione, P.; Snieckus, V. J. Org. Chem. 2009, 74, 4094–4103; (d) Alvey, L.;
Prado, S.; Saint-Joanis, B.; Michel, S.; Koch, M.; Cole, S. T.; Tillequin, F.; Janin, Y.
L. Eur. J. Med. Chem. 2009, 44, 2497–2505; (e) Thielges, S.; Meddah, E.; Bisseret,
P.; Eustache, J. Tetrahedron Lett. 2004, 45, 907–910; (f) Hung, N. T.; Hussain, M.;
Malik, I.; Villinger, A.; Langer, P. Tetrahedron Lett. 2010, 51, 2420–2422.
17. (a) Newman, S. G.; Aureggi, V.; Bryan, C. S.; Lautens, M. Chem. Commun. 2009, 5236–
5238; (b) Newman, S. G.; Lautens, M. J. Am. Chem. Soc. 2010, 132, 11416–11417.
18. Chen, W.; Zhang, Y.; Zhang, L.; Wang, M.; Wang, L. Chem. Commun. 2011, 47,
10476–10478.
Acknowledgments
19. (a) Rao, M. L. N.; Jadhav, D. N.; Dasgupta, P. Org. Lett. 2010, 12, 2048–2051; (b)
Rao, M. L. N.; Banerjee, D.; Dhanorkar, R. J. Tetrahedron 2010, 66, 3623–3632;
(c) Rao, M. L. N.; Venkatesh, V.; Jadhav, D. N. Eur. J. Org. Chem. 2010, 3945–
3955; (d) Rao, M. L. N.; Jadhav, D. N.; Venkatesh, V. Eur. J. Org. Chem. 2009,
4300–4306. and references cited therein.
We greatfully acknowledge the financial support received from
the Department of Science and Technology (DST), New Delhi for
this work through Green Chemistry program (DST No. SR/S5/GC-
11/2008). D.K.A. and J.B.T. thank the University Grants Commission
(UGC) New Delhi, respectively for research fellowships.
20. Organobismuth Chemistry; Suzuki, H., Matano, Y., Eds.; Elsevier: Amsterdam,
2001.
21. Barton, D. H. R.; Ozbalik, N.; Ramesh, M. Tetrahedron 1988, 44, 5661–5668.
22. Representative cross-coupling procedure: In a hot oven-dried Schlenk tube
under N2 atmosphere were added Ph3Bi (0.25 mmol, 110 mg, 1.0 equiv), 2-
bromobenzofuran (0.825 mmol, 163 mg, 3.3 equiv), Cs2CO3 (0.75 mmol,
244 mg, 3.0 equiv), Pd(OAc)2 (0.025 mmol, 5.6 mg, 0.1 equiv), PPh3
(0.1 mmol, 26 mg, 0.4 equiv), and NMP (3 mL) solvent. The resulting mixture
was stirred in preheated oil bath at 90 °C for 1 h. After the reaction is over, the
mixture was cooled, quenched with dil HCl and extracted with ethyl acetate.
The combined organic extract was washed with water, brine, and dried over
MgSO4 and concentrated. The crude was subjected to silica gel column
chromatography (230–400 mesh) using petroleum ether as the eluent to
obtain the pure 2-phenylbenzofuran (2.1) as a white solid (140 mg, 96%). The
product was characterized by spectroscopy and in comparison with the
literature data.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
1. Donnelly, D. M. X.; Meegan, M. J. I. Comprehensive Heterocyclic Chemistry In
Katritzky, A. R., Ed.; Pergamon: New York, NY, 1984. Vol. 4.
23. Gagnon, A.; Albert, V.; Duplessis, M. Synlett 2010, 2936–2940.