Synthesis 2004(10): 1619-1624  
DOI: 10.1055/s-2004-829111
PAPER
© Georg Thieme Verlag Stuttgart · New York

Further Metalations and Functionalizations of Chloro-, Bromo- and Iodo(trifluoromethyl)pyridines

Fabrice Cotteta, Marc Marulla, Florence Monginb,c, David Espinosab, Manfred Schlosser*a,b
a Institut de Chimie moléculaire et biologique, Ecole Polytechnique Fédérale, BCh, 1015 Lausanne, Switzerland
Fax: +41(21)6939365; e-Mail: manfred.schlosser@epfl.ch;
b Faculté des Sciences, Université, BCh, 1015 Lausanne, Switzerland
c Present address: Lab. de Chimie org. fine et hétérocyclique, UPRESA 6014, IRCOF, BP 08, 76131 Mont Saint-Aignan, France
Further Information

Publication History

Received 10 February 2004
Publication Date:
23 June 2004 (online)

Abstract

In accordance with the concept of regioexhaustive functionalization, both 3-chloro-2-(trifluoromethyl)pyridine and 2-bromo-6-(trifluoromethyl)pyridine were converted each time into the three possible carboxylic acids (1, 4 and 5 and 6, 9 and 12, respectively). 2-Bromo-4-(trifluoromethyl)pyridine, 2-bromo-5-(trifluoromethyl)pyridine, 2-iodo-4-(trifluoromethyl)pyridine and 4-iodo-2-(trifluoromethyl)pyridine were selectively deprotonated and subsequently carboxylated at the respective 3-positions thus affording the acids 13-16. Finally, the N-pivaloyl-protected 2-amino-3-chloro-5-(trifluoromethyl)pyridine was deprotonated at the 4-position and the intermediate trapped with iodine and benzaldehyde to provide, after amide cleavage, the aminopyridines 17 and 18.

    References

  • 1 Schlosser M. Angew. Chem.  2004,  review article in press 
  • 2 Cottet F. Schlosser M. Eur. J. Org. Chem.  2004,  in press 
  • 3 Schlosser M. Cottet F. Eur. J. Org. Chem.  2002,  4181 
  • 4 Cottet F. Schlosser M. Eur. J. Org. Chem.  2002,  327 
  • 5 Gros P. Fort Y. Quéguiner G. Caubère P. Tetrahedron Lett.  1995,  36:  4791 
  • 6 Gros P. Fort Y. Caubère P. J. Chem. Soc., Perkin Trans. 1  1998,  1685 
  • 7 Cottet F. Marull M. Lefebvre O. Schlosser M. Eur. J. Org. Chem.  2003,  1559 
  • 8 Marull M. Schlosser M. Eur. J. Org. Chem.  2003,  1569 
  • 9 Haga T. Fujikawa K.-i. Koyanagi T. Nakajima T. Hayashi K. Heterocycles  1984,  22:  117 
  • 10 Wang Q. Wei H.-x. Schlosser M. Eur. J. Org. Chem.  1999,  3263 
  • 11 Bobbio C. Schlosser M. Eur. J. Org. Chem.  2001,  4533 
  • 12 Heiss C. Schlosser M. Eur. J. Org. Chem.  2003,  447