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

Fabrice Cottet; Marc Marull; Florence Mongin; David Espinosa; Manfred Schlosser

doi:10.1055/s-2004-829111

PAPER

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

Fabrice Cottet^a, Marc Marull^a, Florence Mongin^b,c, David Espinosa^b, 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

Abstract

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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.

Key words

halogen/metal permutation (‘exchange’) - halogen migration - metalations - lithium diisopropylamide - pyridines - site selectivity

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References

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