Palladium-catalyzed aryl amination: Mechanism, methodology, and synthetic applications

The mechanism and synthetic scope of palladium-catalyzed aryl amination reactions were investigated. Mechanistic studies of the reactions between palladium(II) aryl halides and organostannanes were conducted to elucidate the pathway of ligand exchange in transmetallation reactions. Our mechanistic studies show that in all cases reaction of the organotin compounds with the starting aryl halide complex occurred after formation of a three-coordinate monophosphine palladium aryl halide intermediate. Using P(o-Tol) 3-ligated palladium catalysts, mechanistic studies of the palladium-catalyzed coupling between aryl bromides and tin amides were conducted as a means to evaluate the pathway of this reaction as well as the general potential of low valent amido complexes to be reactive intermediates in catalysis. A combination of kinetic studies and independent synthesis of reaction intermediates indicated that the three-coordinate platinum-group amido complex {lcub}Pd[P(o-Tol) 3](Ar)(NMe2){rcub} was an intermediate in these reactions. A similar mechanism was found for the reaction between aryl halides and amines catalyzed by an unusual cyclometallated palladium(II) metallacycle. Our mechanistic studies led to the discovery of the tin-free reaction of aryl halides with secondary amines in the presence of base and tri-o-tolyphopshine palladium complexes to form arylamine products. Similarly, a combination of DPPF (DPPF = 1,1-bis-(diphenylphosphino)ferrocene) and Pd(dba) 2 (dba = dibenzylideneacetone) catalyzed the amination of aryl triflates in the presence of stoichiometric amounts of base. A combination of BINAP and Pd(dba)2 also catalyzed the amination of aryl triflates, but P(o-Tol)3-ligated complexes were not effective catalysts. Catalytic amination of aryl halides and triflates has become a convenient method for the preparation of a wide variety of arylamines. Palladium-catalyzed amination chemistry was used to form pure discrete triarylamine macromolecules. A convergent approach and an exponential growth strategy were used to synthesize electronically interesting dendritic and linear arylamine oligomers, respectively.