Palladium-catalyzed direct arylation of azine and azole N-oxides: reaction development, scope and applications in synthesis.
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.
Campeau
Louis-Charles
LC
Center for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Canada K1N 6N5.
Stuart
David R
DR
Leclerc
Jean-Philippe
JP
Bertrand-Laperle
Mégan
M
Villemure
Elisia
E
Sun
Ho-Yan
HY
Lasserre
Sandrine
S
Guimond
Nicolas
N
Lecavallier
Melanie
M
Fagnou
Keith
K
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
D003497:Cyclic N-Oxides; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D026941:Sodium Channel Blockers; D010165:Palladium