A direct arylation of pyrazolo[1,5-a]pyridines with aryl iodides selectively occurring at the C-3 and C-7 positions via palladium-catalyzed C–H activation is described. In these reactions, (a) cesium(I) fluoride and (b) silver(I) carbonate were employed as the additive to afford 3- and 7-arylated pyrazolo[1,5-a]pyridines, respectively, in modest to good yields. These reactions showed good compatibility with functional groups, and the catalytic mechanisms of these reactions were proposed. Finally, the synthetic application on the potent p38 kinase inhibitors was demonstrated.

A direct ortho aroylation of 2-phenoxypyridines with aldehydes leading to aryl ketones by the use of palladium(II) acetate, tert-butyl hydroperoxide, and chlorobenzene as the catalyst, oxidant, and solvent, respectively, is presented. Intra- and intermolecular kinetic isotope effects, radical trapping, and controlled experiments were carried out to support the proposed catalytic mechanism for the reaction. Syntheses of (2-hydroxyphenyl)(phenyl)methanones and 1-hydroxy-9H-fluoren-9-ones directed from ortho-aroylated 2-phenoxypyridines were demonstrated.

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.

The hypervalent iodine(III) reagent-induced the direct intramolecular C–N cyclization of N-(biphenyl)pyridin-2-amines to 6-arylbenzimidazoles and N-pyridinyl-9H-carbazoles is presented. The substituent electronic effects governing the formation of benzimidazoles and carbazoles from the reaction of N-(biphenyl)pyridin-2-amines with hypervalent iodine(III) reagents is investigated. Radical trapping and UV–vis spectroscopic experiments on the detection of the cation radical are carried out. Rational mechanisms for these reactions are presented. The selective intramolecular C–N and C–O cyclization of N-(biphenyl)acetamides based on the substituent electronic effects is also presented.

A one-pot synthesis of ortho-arylated 9-(pyridin-2-yl)-9H-carbazoles via C–H bond activation is presented. Silver nitrate and tert-butyl alcohol were found to be the best oxidant and solvent for the process, respectively. The product yields are from modest to excellent, and the reaction showed sufficient functional group tolerance. p-Benzoquinone served as an important ligand for the transmetalation and reductive elimination steps in the catalytic process. The key intermediate of the reaction, a 9-(pyridin-2-yl)-9H-carbazole palladacycle, was isolated, and its structure was unequivocally confirmed by X-ray crystallography. No kinetic isotope effect (kH/kD = 1.00 ± 0.17) for the C–H bond activation step was observed. In addition, a Hammett experiment gave a negative ρ value, −2.16 ± 0.02. The directing group, pyridinyl, was demonstrated to be a removable functional group. Finally, a rational catalytic mechanism is presented on the basis of all experimental evidence.