Direct Synthesis of Benzoylpyridines from Chloropyridines via a Palladium-Carbene Catalyzed Carbonylative Suzuki Cross-Coupling Reaction

Abstract

The use of N-heterocyclic carbene-type ligands with palladium catalysts allows the activation of chloropyridines and chloroquinoline towards carbonylative cross-coupling with phenylboronic acid for the synthesis of unsymmetrical biaryl ketones.

Key words

palladium - N-heterocyclic carbene ligand - pyridyl chloride

References

• For reviews, see:
• 1a Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
• 1b Suzuki A. In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol 1:  Negishi EI. John Wiley and Sons, Inc.; Hoboken: 2002.  p.249-262  
• 2 For a recent review, see: Littke AF. Fu GC. Angew. Chem. Int. Ed.  2002,  41:  4176 
• 3a Ishiyama T. Kizaki H. Miyaura N. Suzuki A. Tetrahedron Lett.  1993,  34:  7595 
• 3b Ishiyama T. Kizaki H. Hayashi T. Suzuki A. Miyaura N. J. Org. Chem.  1998,  63:  4726 
• 4a Couve-Bonnaire S. Carpentier J.-F. Mortreux A. Castanet Y. Tetrahedron Lett.  2001,  42:  3689 
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• 5a Zhang C. Huang J. Trudell MT. Nolan SP. J. Org. Chem.  1999,  64:  3804 
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• 6 As our investigations neared completion, palladium-imidazolium carbonylative coupling of more actived aryl diazonium ions with aryl boronic acids was reported: Andrus MB. Ma Y. Zang Y. Song C. Tetrahedron Lett.  2002,  43:  9137 
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9

In a number of coupling reactions of aryl chlorides, it was found that a 1:1 Pd-ligand ratio (ligand = N-heterocyclic carbene, phosphine, …) led to optimum reaction rates (see ref. 2 and ref. 5b for N-heterocyclic carbene ligands).

10

TOF: turnover frequencies defined as the number of moles of substrate transformed per mole of catalyst and per hour calculated after one hour of reaction.