Palladium-Mediated C(sp 3 )-H Bond Activation of N -Methyl- N -(pyridin-2-yl)benzamide: Direct Arylation/Alkylation and Mechanistic Investigation.

Herein, we present a facile synthetic methodology to produce a range of N -(CH 2 -aryl/alkyl)-substituted N -(pyridin-2-yl)benzamides via palladium-mediated C(sp 3 )-H bond activation. The N -methyl- N -(pyridin-2-yl)benzamide precursor was first reacted with palladium(II) acetate in a stoichiometric manner to obtain the key dinuclear palladacycle intermediates, whose structures were elucidated by mass spectrometric, NMR spectroscopic, and X-ray crystallographic studies in detail. The subsequent C(sp 3 )-H bond functionalizations on the N -methyl group of the starting substrate show facile productions of the corresponding N -(CH 2 -aryl/alkyl)-substituted N -(pyridin-2-yl)benzamides with good functional group tolerance. A plausible mechanism was proposed based on density functional theory calculations in conjunction with kinetic isotope effect experiments. Finally, the synthetic transformation from the prepared N -(CH 2 -aryl)- N -(pyridin-2-yl)benzamides through debenzoylation to N -(CH 2 -aryl)-2-aminopyridine was successfully demonstrated.