Palladium–Silver Cooperativity in an Aryl Amination Reaction through C–H Functionalization

The mechanism of palladium-acetate-catalyzed ortho-amination of N-arylbenzamides by using O-benzoyl hydroxylpiperidine [PhCOON(C5H10)] has been examined by using DFT(M06, B3LYP) computational methods. Particular emphasis is placed on the role of additives such as cesium fluoride and silver acetate. The lowest-energy pathway has been identified by carefully examining 15 or more configurationally different possibilities in each important step of the reaction. The key mechanistic events include (i) the aryl C–H activation of the substrate through a cyclometalation deprotonation; (ii) N–O activation of the reactant PhCOONR2 (where −NR2 = pypiridyl); and (iii) reductive elimination wherein the −N(C5H10) substituent gets transferred to the substrate. A heterobimetallic active species [Pd(μ-OAc)3Ag] is identified as catalytically superior over the conventionally proposed monometallic palladium acetate. A cooperative interaction between Pd(II) and Ag(I) is found to offer additional stabilization to the transition...