Why Can Normal Palladium Catalysts Efficiently Mediate Aerobic C-H Hydroxylation of Arylpyridines by Intercepting Aldehyde Autoxidation? A Nascent Palladium(III)-Peracid Intermediate Makes a Difference

The direct C(sp2)-H hydroxylation of 2-arylpyridines catalyzed by normal palladium catalysts via interception of aldehyde autoxidation possesses a number of advantages, including convenient operating conditions, nontoxic and inexpensive aldehydes, and being economical in terms of steps and atoms. In this paper, we report a computational study of the mechanism of this catalytic process using density functional theory, revealing a novel catalytic cycle. We find that the rate-limiting step is C-H bond activation that occurs via a concerted metalation deprotonation mechanism, which is consistent with Guin's experimental kinetic isotope effect observations. The byproduct of the C-H bond activation, Brønsted acid HCl, promotes formation of a hexacoordinated Pd(III)-peracid intermediate. It provides a reservoir for the robust high-valent Pd(IV)-OH species via an easy O-O homolysis. The pathway that does not involve HCl is also energetically feasible but albeit less probable. Furthermore, the involvement of another radical OOH ^• , besides the acylperoxo radical nPrOO ^• , is needed to recover the tetracoordinated Pd(II) catalyst during the catalytic cycle. Our computational work sheds lights on the elusive oxygenation involving a radical that is mediated by palladium catalysts and will play a positive role in the further design of a rational reaction strategy and new catalysts.