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

Abstract

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 states and intermediates, as compared to those devoid of such an interaction. The second additive, CsF, helps in the deprotonation of the amidic nitrogen as well as offers electrostatic stabilization to intermediates and transition states, thereby influencing the energetics of the reaction. Our findings clearly suggest that refined transition-state models inclusive of additives are highly desirable toward identifying the most preferred mechanistic pathways.

Computational exploration of Pd‐catalyzed C–H bond activation reactions

“…In these two CMD models, the nitrile directing group of the template binds to one Pd or Ag, while the arene C–H bond is brought close to another Pd to undergo the acetate‐assisted C–H bond activation. The Pd–Ag heterodimeric model has also been applied to other systems …”

A Theoretical Study on Pd-catalyzed, Friedel-Crafts Intermolecular Acylation: Does Generated In Situ Aroyl Triflate Act as A Reactive Electrophile to Functionalize C–H Bond of Arenes?

“…The solvent effect from dichloroethane was considered based on single-point calculations of the gas phase stationary points using a SMD [23] continuum solvation model and by the M06 functional [24][25][26] with SDD basis set for Pd, Ag and I and 6-311++G(d,p) [27] basis set for the rest of the atoms. This computational method (B3LYP for optimization)//(M06 for single point energy in solution) has proved more reliable in energy for metal-catalyzed reactions [28][29][30][31][32], especially for systems containing transition metal elements and weak intermolecular interactions [24][25][26]. Unless otherwise stated, all discussed energies in what follows refer to solvation free energy (∆G sol , kcal mol −1 ) values, which were estimated as ∆G sol = ∆E sol(SMD) + ∆G (gas)correction , where ∆E sol(SMD) refers to the calculated solvation single point energy and ∆G (gas)correction refers to the calculated thermal correction in the gas phase for Gibbs free energies.…”

Directing‐Group‐Assisted Transition‐Metal‐Catalyzed Direct Intermolecular C−H Amidation and Amination of Arenes

“…The directing group can be readily removed by hydrolysis under acidic conditions to provide the corresponding carboxylic acid. Anand, Schaefer, and Sunoj, further investigated the role of additives (silver acetate and cesium fluoride) in the above Pd‐catalyzed amination. A new hetero‐bimetallic Pd‐(μ‐OAc) 3 ‐Ag species was as identified as the most likely active catalyst by using M06 density functional theory calculations.…”