Synthesis 2008(2): 225-228  
DOI: 10.1055/s-2007-1000855
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Convenient Synthesis of 1-(4-Fluorophenyl)-2-(4-pyridyl)cyclopentene from Cyclopentanone

Bassam Abu Thahera, Pierre Kochb, Vicente Del Amoc, Paul Knochelc, Stefan Laufer*b
a Faculty of Science, Chemistry Department, Islamic University of Gaza, Gaza Strip, Palestine
b Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Fax: +49(7071)295037; e-Mail: stefan.laufer@uni-tuebingen.de;
c Institute of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany
Further Information

Publication History

Received 31 July 2007
Publication Date:
18 December 2007 (eFirst)

Abstract

In the framework of investigating the role of pyridyl-substituted five-membered heterocycles as potential p38 mitogen-activated protein kinase inhibitors, we synthesized the disubstituted carbocyclic analogue, 1-(4-fluorophenyl)-2-(4-pyridyl)cyclopentene. A multistep synthesis of this compound starting from cyclopentanone is reported. Cyclopentanone was converted into 1-cy-­clo­pentenyl-4-fluorobenzene using a Grignard reaction. The oxidation of this product with hydrogen peroxide and formic acid gave 2-(4-fluorophenyl)cyclopentanone. This ketone was activated using a neodymium salt (NdCl3·2LiCl) and subsequently reacted with a complexed Grignard reagent (pyMgCl·LiCl) to give the corresponding cyclopentanol derivative. Finally, dehydration of the latter alcohol led to the title compound.

    References

  • 1 Wagner G. Laufer S. Med. Res. Rev.  2006,  26: 
  • 2 Laufer SA. Margutti S. Fritz MD. ChemMedChem  2006,  1:  197 
  • 3 Wang Z. Canagarajah BJ. Boehm JC. Kassisa S. Cobb MH. Young PR. Abdel-Meguid S. Adams JL. Goldsmith EJ. Structure  1998,  6:  1117 
  • 4 Tong L. Pav S. White DM. Rogers S. Crane KM. Cywin CL. Brown ML. Pargellis CA. Nat. Struct. Biol.  1997,  4:  311 
  • 5 Fitzgerald CE. Patel SB. Becker JW. Cameron PM. Zaller D. Pikounis VB. O’Keefe SJ. Scapin G. Nat. Struct. Biol.  2003,  10:  764 
  • 6 Young PR. McLaughlin MM. Kumar S. Kassis S. Doyle ML. McNulty D. Gallagher TF. Fisher S. McDonnell PC. Carr SA. Huddleston MJ. Seibel G. Porter TG. Porter TC. Livi GP. Adams JL. Lee JC. J. Biol. Chem.  1997,  272:  12116 
  • 7 Baumstark AL. McCloskey CJ. Witt KE. J. Org. Chem.  1978,  43:  3609 ; and references cited therein
  • 8 McMurry JE. Kees KL. J. Org. Chem.  1977,  42:  2655 ; and references cited therein
  • 9a Criegee R. Kerckow A. Zinke H. Chem. Ber.  1955,  8:  1878 
  • 9b Wood CS. Mallory FB. J. Org. Chem.  1964,  29:  3373 
  • 10 Hupe E. Denisenko D. Knochel P. Tetrahedron  2003,  59:  9187 
  • 11 Gerson F. Martin WB. Wydler C. Helv. Chim. Acta  1979,  62:  2517 
  • 12 Krasovskiy A. Knochel P. Angew. Chem. Int. Ed.  2004,  43:  3333 
  • 13 Krasovskiy A. Koop F. Knochel P. Angew. Chem. Int. Ed.  2006,  45:  497 
  • 14 Culkin DA. Hartwig JF. Acc. Chem. Res.  2003,  36:  234 
  • 15 Rieke RD. Acc. Chem. Res.  1977,  10:  301 
  • 16 Itami K. Kamei T. Yoshida J. J. Am. Chem. Soc.  2003,  125:  14670 
  • 17 Furukawa N. Shibutani T. Fujihara H. Tetrahedron Lett.  1987,  28:  5845 
  • 18 Wibaut JP. Heeringa LG. Recl. Trav. Chim. Pays-Bas  1955,  74:  1003 
  • 19 Abu Thaher B. Schollmeyer D. Laufer S. Acta Crystallogr., Sect. E: Struct. Rep. Online  2007,  63:  3531 
  • 20 Panson PL. J. Am. Chem. Soc.  1954,  76:  2187 
  • 21 Utermoehlen CM. Singh M. Lehr RE. J. Org. Chem.  1987,  52:  5572 
  • 22 Alvarez-Manzaneda EJ. Chahboun R. Cabrera Torres E. Alvarez E. Alvarez-Manzaneda R. Haidour A. Ramos J. Tetrahedron Lett.  2004,  45:  4453 
  • 23 Ketley AD. McClanahan JL. J. Org. Chem.  1965,  30:  942