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Synthesis 2008(17): 2764-2770  
DOI: 10.1055/s-2008-1067208
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Buchwald-Hartwig Mono-N-arylation with 2,6-Dihaloisonicotinic Acid Derivatives: A Convenient Desymmetrization Method

Anna V. Lorimer, Patrick D. O’Connor, Margaret A. Brimble*
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland 1142, New Zealand
Fax: +64(9)3737422; e-Mail: m.brimble@auckland.ac.nz;
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Publication History

Received 24 March 2008
Publication Date:
06 August 2008 (online)

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Abstract

A method for the Buchwald-Hartwig mono-N-arylation of aniline with methyl 2,6-dichloroisonicotinate using Pd(OAc)2, XPhos, and t-BuONa is reported. Use of m-anisidine under the same conditions resulted in the amidation of the methyl ester. Mono-N-arylation of m-anisidine with 2,6-dichloro-N,N-diisopropylisonicotinamide and 2,6-dibromo-N,N-diisopropylisonicotinamide, however, was successfully achieved using Pd(OAc)2/XPhos/t-BuONa or Pd(OAc)2/(±)-BINAP/K2CO3, respectively. The present study demonstrates the sensitivity of this cross-coupling method to both the steric and electronic nature of the coupling partners.

Key words

Buchwald-Hartwig N-arylation - Pd(0) cross-coupling - 2,6-dihaloisonicotinates