A Convenient Two-Step Synthesis of 2-Arylbenzofurans

Abstract

A novel and convenient two-step synthesis of 2-arylbenzofurans is described which proceeds via a selective cross-pinacol-type coupling between a salicylaldehyde and an aromatic aldehyde, followed by an acid-promoted cyclization. One advantage of this method is that separation of the three possible pinacol products that can form during the cross-coupling is not necessary. This method is also applied to the synthesis of the 2-arylbenzofuran-containing natural product, homoegonol.

Key words

pinacols - pinacol-type coupling - cross-coupling - benzofurans - 2-arylbenzofurans

References

• 1a Friedrichsen W. In Comprehensive Heterocyclic Chemistry II   Vol. 2:  Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996.  p.259 
• 1b Donnelly DMX. Meegan MJ. In Comprehensive Heterocyclic Chemistry   Vol. 4:  Katritzky AR. Rees CW. Pergamon Press; London: 1984.  p.531 
• 1c Cagniant P. Cagniant D. In Advances in Heterocyclic Chemistry   Vol. 18:  Katritzky AR. Boulton AJ. Academic Press; New York: 1975.  p.337 
• 1d Hou X.-L. Yang Z. Yeung K.-S. Wong HNC. Prog. Heterocycl. Chem.  2005,  17:  142 
• 1e Hou X.-L. Yang Z. Wong HNC. Prog. Heterocycl. Chem.  2003,  15:  167 
• 1f McCallion GD. Curr. Org. Chem.  1999,  3:  67 
• For selected recent references, see:
• 2a Csekei M. Novak Z. Kotschy A. Tetrahedron  2008,  64:  8992 
• 2b Takashi O. Daisuke N. Rie T. Akimori W. Org. Lett.  2008,  10:  4967 
• 2c Grigg R. Sridharan V. Sykes DA. Tetrahedron  2008,  64:  8952 
• 2d Chen P. Wang J. Liu K. Li C. J. Org. Chem.  2008,  73:  339 
• 2e Roberta B. Sandro C. Ilse DS. Giancarlo F. Synthesis  2007,  873 
• 2f Russo O. Messaoudi S. Hamze A. Olivi N. Peyrat J.-F. Brion J.-D. Sicsic S. Isabelle B.-B. Alami M. Tetrahedron  2007,  63:  10671 
• 2g Li J.-H. Li J.-L. Wang D.-P. Pi S.-F. Xie Y.-X. Zhang M.-B. Hu X.-C. J. Org. Chem.  2007,  72:  2053 
• 3a Ackermann L. Kaspar LT. J. Org. Chem.  2007,  72:  6149 
• 3b Willis MC. Taylor D. Gillmore AT. Tetrahedron  2006,  62:  11513 
• 3c Carril M. SanMartin R. Tellitu I. Dominguez E. Org. Lett.  2006,  8:  1467 
• 3d Fang Y. Li C. J. Org. Chem.  2006,  71:  6427 
• 3e Chen C.-Y. Dormer PG. J. Org. Chem.  2005,  70:  6964 
• 3f Martinez A. Fernandez M. Estevez JC. Estevez RJ. Castedo L. Tetrahedron  2005,  61:  1353 
• 3g Willis MC. Taylor D. Gillmore AT. Org. Lett.  2004,  6:  4755 
• 4a Franck P. Hostyn S. Beata DH. Agnes PB. Monsieurs K. Matyus P. Maes BUW. Tetrahedron  2008,  64:  6030 
• 4b Ebisawa M. Ueno M. Oshima Y. Kondo Y. Tetrahedron Lett.  2007,  48:  8918 
• 4c Prado S. Toum V. Brigitte SJ. Michel S. Koch M. Cole ST. Tillequin F. Janin YL. Synthesis  2007,  1566 
• For I₂-mediated cyclizations, see:
• 5a Pan C.-F. Yu J. Zhou Y.-Q. Wang Z.-Y. Zhou M.-M. Synlett  2006,  1657 
• For the cyclization using DDQ, see:
• 5b Takeshi K. Koji I. Heterocycles  2005,  65:  1641 
• 5c Fujita M. Qi G.-Z. Verkerk UH. Dzwiniel TL. McDonald R. Stryker JM. Org. Lett.  2004,  6:  2653 
• For other reagents, see:
• 5d Aslam SN. Stevenson PC. Phythian SJ. Veitch NC. Hall DR. Tetrahedron  2006,  62:  4214 
• 5e Lattanzi A. Senatore A. Massa A. Scettri A. J. Org. Chem.  2003,  68:  3691 
• 6a Shen Q. Peng Q. Shao J.-L. Liu X.-L. Huang Z.-H. Pu X.-Z. Ma L. Li Y.-M. Chan ASC. Gu L.-Q. Eur. J. Med. Chem.  2005,  40:  1307 
• 6b Mashraqui SH. Patil MB. Sangvikar Y. Ashraf M. Mistry HD. Daub ETH. Meetsma A. J. Heterocycl. Chem.  2005,  42:  947 
• 6c Jørgensen M. Krebs FC. Bechgaard K. J. Org. Chem.  2000,  65:  8783 
• 7a Rele S. Talukdar S. Banerji A. Chattopadhyay S. J. Org. Chem.  2001,  66:  2990 
• 7b Furstner A. Hupperts A. J. Am. Chem. Soc.  1995,  117:  4468 
• 7c Furstner A. Hupperts A. Rock A. Janssen E. J. Org. Chem.  1994,  59:  5215 
• 8a Yuan Y. Men H.-B. Lee C. J. Am. Chem. Soc.  2004,  126:  14720 
• 8b Katerina C. Miloslav N. Pavel P. Jiri S. Collect. Czech. Chem. Commun.  2000,  65:  1939 
• 8c Jean G. Nicole B. Pierre D. J. Heterocycl. Chem.  1990,  27:  10 
• 9a Duan XF. Zeng J. Lü JW. Zhang ZB. J. Org. Chem.  2006,  71:  9873 
• 9b Duan XF. Zeng J. Lü JW. Zhang ZB. Synthesis  2007,  713 
• 9c Duan XF. Zeng J. Zhang ZB. Zi GF. J. Org. Chem.  2007,  72:  10283 
• 10 Duan XF. Feng JX. Zi GF. Zhang ZB. Synthesis  2009,  277 
• 11a Segal R. Ilana MG. Sokoloff S. Zaitschek DV. J. Chem. Soc. C  1967,  2402 
• 11b Schreiber FG. Stevenson R. Chem. Lett.  1975,  1257 
• 11c Schreiber FG. Stevenson R. J. Chem. Soc., Perkin Trans. 1  1976,  1514 
• 11d Teles HL. Hemerly JP. Pauletti PM. Pandolfi JRC. Araujo AR. Valentini SR. Young MCM. Bolzani VS. Silva DHS. Nat. Prod. Res.  2005,  19:  319 
• 13 Fürstner A. Davies PW. J. Am. Chem. Soc.  2005,  127:  15024 
• 14 Date M. Kawanishi K. Hori T. Watanabe M. Furukawa S. Chem. Pharm. Bull.  1989,  37:  2884 
• 15 Farago J. Kotschy A. Synthesis  2009,  85 

12

In several of the reactions, a small amount of alkenes formed as byproducts during the cross-coupling which hindered the acid-promoted cyclization of the pinacol products. Although it was not necessary to separate the three pinacols, the alkene by-product was removed by chromatography.