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.
Bibliographical noteFunding Information:
The authors acknowledge the financial support received from the National Natural Science Foundation of China (Projects 21873052, 21872075, 21503089, and 21533003) and the open fund of the State Key Laboratory of Molecular Reaction Dynamics.
© 2019 American Chemical Society.