Mechanistic analysis of azine N-oxide direct arylation: evidence for a critical role of acetate in the Pd(OAc)2 precatalyst.
Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C-H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metalation-deprotonation (CMD) pathway. Competition experiments were conducted with N-oxides of varying electronic characters, and results revealed an enhancement of rate when using a more electron-deficient species, which is in support of a CMD transition state. The effect of base on reaction rate was also examined and it was found that a carboxylate base was required for the reaction to proceed. This led to the conclusion that Pd(OAc)(2) plays a pivotal role in the reaction mechanism as more than merely a precatalyst, but also as a source of acetate base required for the C-H bond cleavage step.
Center for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5.
Ho-Yan
HY
Sun
Serge I
SI
Gorelsky
David R
DR
Stuart
Louis-Charles
LC
Campeau
Keith
K
Fagnou