Mechanism of the palladium-catalyzed amination of aryl halides: Kinetic studies of the oxidative addition of aryl halides and sulfonates to phosphine complexes of Pd(0) and of the catalytic reaction of amines with aryl halides and base

Mechanistic studies on the cross-coupling reaction of aryl halides and amines catalyzed by palladium complexes were undertaken. In order to shed light onto the kinetic behavior of this catalytic reactions, extensive detailed studies on one of the fundamental steps of the catalytic cycle of a cross-coupling reaction, oxidative addition were undertaken. Mechanistic studies on the oxidative addition of aryl bromides to Pd(BINAP)₂ revealed that at conditions normally encountered during a catalytic amination of aryl bromide catalyzed by Pd(BINAP)₂, the rate of oxidative addition is controlled solely by the rate of ligand dissociation from Pd(BINAP)₂. A comparison was made to the oxidative addition mechanism for aryl iodides and triflates to Pd(BINAP)₂. A rare, stable amine-ligated arylpalladium triflate complex ligated by BINAP was isolated and structurally characterized. Oxidative addition was shown to be the turnover-limiting step for reactions of primary amines with aryl bromides catalyzed by Pd(BINAP)₂. This led to the unusual discovery of a catalytic reaction that is overall zero order in all reagents. For reaction of aniline with aryl bromides catalyzed by Pd(DPPF) ₂, oxidative addition and is turnover limiting. A rare case of product inhibition was observed for this catalyst system. P–C bond cleavage of the backbone of P–C bond of the chelating arylphosphine ligand was identified as the major pathway for catalyst decomposition. A parallel system of two catalytic cycles was found to operate for the amination of aryl chlorides catalyzed by palladium complexes of bulky alkyl phosphines. One of these dual pathways involved a base or bromide promoted oxidative addition step. An unusual acceleration of the oxidative addition step by alkoxide and aryloxide bases was observed for this anionic path. Addition of a soluble bromide reproduced the acceleration afforded by the bases, confirming the formation of an anionic zerovalent palladium species that effected the oxidative addition of aryl chloride.