Mechanistic Studies of the Palladium-Catalyzed Amination of Aryl Halides and the Oxidative Addition of Aryl Bromides to Pd(BINAP)2 and Pd(DPPF)2:  An Unusual Case of Zero-Order Kinetic Behavior and Product Inhibition

Mechanistic studies of the amination of aryl bromides catalyzed by palladium complexes containing the chelating phosphines BINAP and DPPF are reported. The coupling of primary alkyl- and arylamines, secondary cyclic alkylamines, and secondary arylalkylamines with bromoarenes in the presence of stoichiometric base and Pd(BINAP)2 (1a) as catalyst, and the reaction of aniline with 4-Br-C6H4-t-Bu in the presence of base catalyzed by Pd(DPPF)2 (2), were studied. The stoichiometric oxidative additions of PhBr to 1a and to 2 were turnover limiting, and kinetic studies were also conducted on this individual step. The stoichiometric oxidative addition of PhBr to 1a showed an inverse first-order dependence on added ligand when the PhBr concentration was low but depended solely on the rate of chelating ligand dissociation at high PhBr. There was no measurable solvent effect. In addition, the rates were indistinguishable in the presence and in the absence of amines and salts that are present in the catalytic amination reactions. Similar qualitative data for the oxidative addition of PhBr to 2 was obtained by 1H NMR spectroscopy. The observed rate constants for the overall amination reactions catalyzed by 1a were shown to be zero order in aryl halide, amine, base, and added ligand, while they were first order in catalyst. These data indicated that the kinetic behavior of the overall reaction was dictated solely by the rate of ligand dissociation from 1a, as observed for the oxidative addition. When secondary amines were used, deviation from this behavior was observed. This anomalous behavior resulted from decay of catalyst rather than a change in the turnover-limiting step. A catalyst decomposition pathway that involves backbone P−C bond cleavage of the chelating bisphosphine ligands was revealed by the stoichiometric oxidative addition studies. Quantitative rate data were also obtained for reaction of 4-Br-C6H4-t-Bu with aniline in the presence of base catalyzed by 2. The observed rate constants were zero order in amine and base, inverse first order in added ligand, and first order in aryl bromide. At low concentration of added ligand, the reaction appeared to be first order in amine. However, this deviation from the expected behavior was due to reversible reaction of the catalyst with product.