New Insights into Xantphos/Pd-Catalyzed C−N Bond Forming Reactions: A Structural and Kinetic Study

Both (Xantphos)Pd(dba) and Pd(Xantphos) 2 were identified in mixtures of Pd 2 (dba) 3 and Xantphos by use of 31 P NMR and independent syntheses. At high ligand concentrations, Pd(Xantphos) 2 was found to be the predominant species. Reaction calorimetry was employed to determine whether the formation of Pd(Xantphos) 2 affects the rate at which the Pd-catalyzed C−N bond formation occurs between 4- tert -butylbromobenzene and morpholine. Indeed, the concentration of Xantphos dramatically influences the activity of the catalyst, with high concentrations of Xantphos inhibiting the reaction rate due to the formation of Pd(Xantphos) 2 . Two plausible hypotheses for the low activity of Pd(Xantphos) 2 as a precatalyst are (1) a slow rate of Xantphos dissociation from Pd(Xantphos) 2 inhibits the formation of an active (Xantphos)Pd 0 species and (2) the high degree of insolubility of Pd(Xantphos) 2 results in the precipitation of a significant fraction of the precatalyst from the reaction mixture. Although the equilibrium constant for ligand dissociation could not be determined by either magnetization transfer or variable-temperature experiments due to its slow rate, the more soluble Pd(4,7-di- tert -butylXantphos) 2 complex demonstrated different activity relative to Pd(Xantphos) 2 . A comprehensive study of these two complexes indicates that the lower activity of the bis-ligated Pd species is a result of a combination of aforementioned processes, i.e., the slow rate of ligand dissociation and the insolubility of Pd(Xantphos) 2, with the rate of ligand dissociation serving as the primary turnover-limiting factor.