Abstract
The first synthesis of benzofuran 2 was achieved in 17% overall yield in seven steps. The key step was a halogen-metal exchange/cyclization reaction. Several examples of this reaction were reported.
Key words
benzofuran - halogen-metal exchange/cyclization reaction - arylbenzofuran
References
1a McCallion GD.
Curr. Org. Chem.
1999,
3:
67
1b Comprehensive Heterocyclic Chemistry
Vol. 4:
Katritzky AR.
Rees CW.
Pergamon Press;
Oxford:
1984.
p.531
2a Babu VH.
Kumar PS.
Srinivasan KK.
Bhat GV.
Indian J. Pharm. Sci.
2004,
66:
647
2b Hayakawa I.
Shioya R.
Agatsuma T.
Furukawa H.
Sugano Y.
Bioorg. Med. Chem. Lett.
2004,
14:
3411
3 Abdel-Kader MS.
Planta Med.
2001,
67:
388
4 Rahim RT.
Meissler JJ.
Cowan A.
Rogers TJ.
Geller EB.
Gaughan J.
Adler MW.
Eisenstein TK.
Internat. Immunopharmacol.
2001,
1:
2001
5a Frahm AW.
Muangnoicharoen N.
Phytochem.
1981,
20:
291
5b Mukherjee SK.
Walia S.
Kulshrestha SK.
Tetrahedron
1986,
42:
4817
6 Shirota O.
Pathak V.
Sekita S.
Satake M.
Nagashima Y.
Hirayama Y.
Hakamata Y.
Hayashi T.
J. Nat. Prod.
2003,
66:
1128
7a Mustafa A. In Chemistry of Heterocyclic Compounds
Vol. 29:
Weissberger A.
Taylor EC.
Wiley;
New York:
1974.
p.1-514
7b Comprehensive Heterocyclic Chemistry II
Vol. 2:
Katritzky AR.
Rees CW.
Scriven EFV.
Pergamon Press;
Oxford:
1996.
p.259
7c Hou H.-L.
Yang Z.
Wong HNC.
Furans and Benzofurans , In Progress in Heterocyclic Chemistry
Vol. 14:
Gribble GW.
Gilchrist TL.
Pergamon;
Oxford:
2002.
p.139-179
8a Nicolaou KC.
Snyder SA.
Bigot A.
Pfefferkorn J.
Angew. Chem. Int. Ed.
2000,
39:
1093
8b Habermann J.
Ley SV.
Smits R.
J. Chem. Soc., Perkin Trans. 1
1999,
2421
9 Larock RC.
Stinn DE.
Tetrahedron Lett.
1988,
29:
4687
10 Tae J.
Kim K.-O.
Synthesis
2005,
387
11a Twyman LJ.
Allsop D.
Tetrahedron Lett.
1999,
40:
9383
11b Fürstner A.
Jumbam DN.
Tetrahedron
1992,
48:
5991
12 Kraus GA.
Kim I.
Org. Lett.
2003,
5:
1191
13 Kihara M.
Yasumasa I.
Yoshimitsu N.
Heterocycles
1995,
41:
2279
14
Typical Procedure.
2 O) were added via syringe to 4 mL of THF at -78 °C. To this solution was added 1 equiv of the iodoketone (in 4 mL of THF) dropwise via syringe. After addition, the reaction was allowed to stir at -78 °C for 15 min. The reaction was allowed to slowly warm to r.t., and was quenched by the addition of 4 mL of aq NH4 Cl solution. After 5 min, the reaction was extracted into EtOAc, washed with brine (2 × 10 mL), dried over MgSO4 , filtered, and concentrated. The crude product was then dissolved in 10 mL of acetone, and 5 mL of a 10% aq PTSA solution was added with continued stirring for 4 h. Removal of acetone, followed by aqueous work up and extraction into EtOAc, afforded the crude benzofuran, which was purified via chromatography.3-(2,4,5-Trimethoxyphenyl)benzofuran (8d).
1 H NMR (CDCl3 ): δ = 7.89 (s, 1 H), 7.74 (d, J = 7.2 Hz, 1 H), 7.55 (d, J = 7.4 Hz, 1 H), 7.31 (t, J = 8.8 Hz, 2 H), 7.17 (s, 1 H), 6.68 (s, 1 H), 3.96 (s, 3 H), 3.91 (s, 3 H), 3.83 (s, 3 H). 13 C NMR (CDCl3 ): δ = 155.4, 151.6, 149.2, 143.5, 127.5, 124.4, 122.9, 122.8, 121.1, 117.6, 114.1, 112.6, 111.8, 98.5, 57.0, 56.7, 56.4. HRMS: m/z calcd for C17 H16 O4 : 284.1048; found: 284.1053.
15 Barrero A.
Alvarez-Manzaneda EJ.
Chahboun R.
Tetrahedron
1998,
54:
5635
16 Colobert F.
Broutin P.-E.
Castanet A.-S.
Tetrahedron Lett.
2002,
43:
5047
17 Jackson AH.
Martin JA.
J. Chem. Soc. C
1966,
23:
2222
18a Rigo B.
Waterlot C.
Couturier D.
De Backer M.
Can. J. Chem.
2000,
78:
1242
18b Bringmann G.
Pabst T.
Henschel P.
Michel M.
Tetrahedron
2001,
57:
1269
18c Gevorgyan V.
Yamamoto Y.
Rubin M.
Benson S.
Liu J.-X.
J. Org. Chem.
2000,
65:
6179
