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

• Published in: ACS catalysis Vol. 6; no. 2; pp. 696 - 708
• Main Authors: Anand, Megha, Sunoj, Raghavan B, Schaefer, Henry F
• Format: Journal Article
• Language: English
• Published: American Chemical Society 05.02.2016
• Subjects: reaction mechanisms; transition-metal catalysis; C−H activation; additives; transition states
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.5b02639

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.