title: Palladium-catalyzed direct arylation of azine and azole N-oxides: reaction development, scope and applications in synthesis.
abstract: Palladium-catalyzed direct arylation reactions are described with a broad range of azine and azole N-oxides. In addition to aspects of functional group compatibility, issues of regioselectivity have been explored when nonsymmetrical azine N-oxides are used. In these cases, both the choice of ligand and the nature of the azine substituents play important roles in determining the regioisomeric distribution. When azole N-oxides are employed, preferential reaction is observed for arylation at C2 which occurs under very mild conditions. Subsequent reactions are observed to occur at C5 followed by arylation at C4. The potential utility of this methodology is illustrated by its use in the synthesis of a potent sodium channel inhibitor 1 and a Tie2 Tyrosine Kinase inhibitor 2.
authors.affiliation: Center for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Canada K1N 6N5.
authors.forename: Louis-Charles
authors.initials: LC
authors.lastname: Campeau
authors.forename: David R
authors.initials: DR
authors.lastname: Stuart
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Leclerc
authors.forename: Mégan
authors.initials: M
authors.lastname: Bertrand-Laperle
authors.forename: Elisia
authors.initials: E
authors.lastname: Villemure
authors.forename: Ho-Yan
authors.initials: HY
authors.lastname: Sun
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lasserre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guimond
authors.forename: Melanie
authors.initials: M
authors.lastname: Lecavallier
authors.forename: Keith
authors.initials: K
authors.lastname: Fagnou
mesh_terms: D002384:Catalysis; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D003497:Cyclic N-Oxides; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D026941:Sodium Channel Blockers; D010165:Palladium