Palladium(II)-Catalyzed Direct Ortho Arylation of 4‑Methyl‑N‑phenylpyridin-2-amines via C–H Activation/C–C Coupling and Synthetic Applications

The direct ortho arylation of 4-methyl-N-phenylpyridin-2-amines via palladium­(II)-catalyzed C–H activation is described. Treatment of 4-methyl-N-phenylpyridin-2-amine with potassium aryltrifluoroborate using 10 mol % of palladium­(II) acetate as the catalyst, 2 equiv of copper­(II) acetate as the oxidant, and 1 equiv of p-benzoquinone in tert-butyl alcohol gave ortho-arylated products in modest to excellent yields. This reaction shows good functional group compatibility. A series of 1H NMR titration experiments and controlled experiments elucidating the reaction mechanism were carried out. The key intermediate, 4-methyl-N-phenylpyridin-2-amine palladacycle, was isolated and characterized by X-ray crystallography. The advanced transformations of ortho-phenylated 4-methyl-N-phenylpyridin-2-amine to N-(4-methylpyridin-2-yl)-9H-carbazole, biphenyl-2-amine, and 3-methyl-6-phenylpyrido­[1,2-a]­benzimidazole were successfully demonstrated as potential synthetic applications.