Liang et al.
SCHEME 1
Suzuki coupling reactions,9 and triple cyclic Heck reactions
affording fused bicyclic or tetracyclic compounds, respectively;
we also used a double ring-closing metathesis (RCM) reac-
tion10,11 to construct bicyclic quinolizidine alkaloids12 and
tricyclic benzodipyrans and their analogues.13 Here, we report
an efficient and versatile method of the synthesis of multisub-
stituted benzodifurans from bis(alkynyl)dihydroxybenzenes and
bis(allyloxy)bis(alkynyl)benzenes.
Similarly, compound 5 was synthesized from the Sonagashira
coupling reaction of diiodide 2 with trimethylsilyl ethyne.15
Double allylation of 5 afforded compound 6, which was
desilylated in the presence of KF in methanol to give 7. Com-
pounds 9a-c were then prepared from 7 by its reaction with
the corresponding allylic halides in the presence of K2CO3 and
a catalytic amount of CuI in DMF, respectively.4b Unsymmetric
compound 10 with different allylic groups at the terminal
positions of the carbon-carbon triple bonds was obtained from
the allylation of compound 8, which was prepared from the
monoallylic alkylation of compound 7 (Scheme 2).
Results and Discussion
Synthesis of Starting Materials. Dibromide 1 and diiodide
213 were selected as the starting materials for synthesis of the
substrates. Their Sonogashira coupling14 with terminal alkynes
followed by hydrolysis gave products 3a-e, which were treated
with allyl bromide in the presence of K2CO3 in DMF to give
4a-e in acceptable yields (Scheme 1).
Pd-Catalyzed Double Cyclization of 2,4-Bis(allyloxy)-1,5-
bis(alkynyl)benzenes. For the synthesis of 2-substituted-3-
allylbenzofurans, Balme et al. reported a Pd(PPh3)4-catalyzed
allylative heteroannulation of o-alkynyl-allyloxybenzenes in a
mixed solvent (THF/CH3CN 4:1).4c When Pd2(dba)3‚CHCl3 and
PPh3 were used as the catalyst, the reaction of 4a in CH3CN
under reflux afforded double cyclization product 11a and
monocyclization product 12a in 23 and 69% yields, respectively
(entry 1, Table 1). As shown in Table 1, the reaction of 4a at
100 °C in toluene gave 11a in 44% yield along with the
monocyclic product 12 (39%, entry 2, Table 1). However, when
the reaction was conducted in DMF at 100 °C, the desired
(3) (a) Cagniant, P.; Cagniant, D. AdV. Heterocycl. Chem. 1975, 18, 343.
(b) Donnelly, D. M. X.; Meegan, M. J. In ComprehensiVe Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford,
1984; Vol. 4, pp 657-712. (c) Sundberg, R. J.; Van Nguyen, P. In Progress
in Heterocyclic Chemistry; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon
Press: Oxford, 1993; Vol. 5, p 129. (d) Ono, M.; Kawashima, H.; Nonaka,
A.; Kawai, T.; Haratake, M.; Mori, H.; Kung, M. P.; Kung, H. F.; Saji, H.;
Nakayama, M. J. Med. Chem. 2006, 49, 2725.
(4) (a) Arcadi, A.; Cacchi, S.; Del Rosario, M.; Fabrizi, G.; Marinelli,
F. J. Org. Chem. 1996, 61, 9280 and references therein. (b) Monteiro, N.;
Balme, G. Synlett 1998, 746. (c) Monteiro, N.; Arnold, A.; Balme, G. Synlett
1998, 1111. (d) Cacchi, S.; Fabrizi, G.; Moro, L. Synlett 1998, 741. (e)
Liao, Y.; Smith, J.; Fathi, R.; Yang, Z. Org. Lett. 2005, 7, 2707. (f) Liang,
Y.; Tang, S.; Zhang, X. D.; Mao, L. Q.; Xie, Y. X.; Li, J. H. Org. Lett.
2006, 8, 3017. (g) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Org.
Lett. 2006, 8, 2803. (h) Youn, S. W.; Eom, J. I. Org. Lett. 2005, 7, 3355
and references therein. (i) Katritzky, A. R.; Ji, Y.; Fang, Y.; Prakash, I. J.
Org. Chem. 2001, 66, 5613.
(5) (a) Rene, L.; Buisson, J. P.; Royer, R.; Averbeck, D. Eur. J. Med.
Chem. Chim. Ther. 1977, 12, 31. (b) Royer, R.; Bisagni, E.; Hudry, C.;
Cheutin, A.; Desvoye, M. L. Bull. Soc. Chim. Fr. 1963, 1003. (c) Chambers,
J. J.; Kurrasch-Orbaugh, D. M.; Parker, M. A.; Nichols, D. E. J. Med. Chem.
2001, 44, 1003. (d) Chawla, H. P. S.; Grover, P. K.; Anand, N.; Kamboj,
V. P.; Kar, A. B. J. Med. Chem. 1970, 13, 54.
(6) (a) Park, K. K.; Lim, H.; Kim, S.-H.; Bae, D. H. J. Chem. Soc., Perkin
Trans. 1 2002, 310. (b) Park, K. K.; Kim, S.-H.; Park, J. W. J. Photochem.
Photobiol., A 2004, 163, 241. (c) Abdul-Azizl, M.; Auping, J. V.; Meador,
M. A. J. Org. Chem. 1995, 60, 1303. (d) Terent’ev, A. P.; Grinev, A. N.;
Bon-Khvar, P. Zh. Obshch. Khim. 1954, 24, 2050. (e) Worden, L. R.;
Burgstahler, A. W.; Kaufman, K. D.; Weis, J. A.; Schaaf, T. K. J.
Heterocycl. Chem. 1969, 6, 191.
(10) Schmidt, B.; Hermanns, J. Curr. Org. Chem. 2006, 10, 1363 and
references cited therein.
(11) (a) Grubbs, R. H. Handbook of Metathesis; Wiley-VCH: Weinheim,
Germany, 2003; Vols. 1-3. For recent reviews, see: (b) Fu¨rstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3012. (c) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18. (d) Schrock, R. R. In Carbene Chemistry; Bertrand, G.,
Ed.; Marcel Dekker: New York, 2002; pp 205-230. (e) Grubbs, R. H.;
Trnka, T. M.; Sanford, M. S. In Current Methods in Inorganic Chemistry;
Kurokawa, H., Yamamoto, A., Eds.; Elsevier: Amsterdam, 2003; Vol. 3,
pp 187-231. (f) Arjona, O.; Csa´ky¨, A. G.; Plumet, J. Eur. J. Org. Chem.
2003, 611. (g) Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003,
42, 1900. (h) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003,
42, 4592. (i) Hoveyda, A. H.; Gillingham, D. G.; Van Veldhuizen, J. J.;
Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol.
Chem. 2004, 2, 8. (j) Deiters, A.; Martin, S. F. Chem. ReV. 2004, 104,
2199. (k) McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. ReV.
2004, 104, 2239. (l) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem., Int. Ed. 2005, 44, 4490. (m) Schrock, R. R. Angew. Chem., Int. Ed.
2006, 45, 3748. (n) Chauvin, Y. Angew. Chem., Int. Ed. 2006, 45, 3741.
(o) Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 3760.
(12) (a) Ma, S.; Ni, B. Org. Lett. 2002, 4, 639. (b) Ma, S.; Ni, B. Chem.
Eur. J. 2004, 10, 3286. (c) Ma, S.; Ni, B.; Liang, Z. J. Org. Chem. 2004,
69, 6305.
(7) (a) Ma, S.; Xu, B. J. Org. Chem. 1998, 63, 9156. (b) Ma, S.; Xu, B.;
Ni, B. J. Org. Chem. 2000, 65, 8532.
(8) Ma, S.; Ni, B.; Lin, S.; Liang, Z. J. Organomet. Chem. 2005, 690,
5389.
(13) Liang, Z.; Ma, S.; Yu, J.; Xu, R. Tetrahedron 2007, 63, 977.
(14) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467.
(15) Rosillo, M.; Dom´ınguez, G.; Casarrubios, L.; Amador, U.; Pe´rez-
Castells, J. J. Org. Chem. 2004, 69, 2084.
(9) Ma, S.; Ni, B. J. Org. Chem. 2002, 67, 8280.
9220 J. Org. Chem., Vol. 72, No. 24, 2007