A Mechanistic Investigation of the Nickel-Catalyzed Negishi Coupling of Styrenyl Aziridines

Abstract

The nickel-catalyzed cross coupling of styrenyl aziridines and organozinc nucleophiles constitutes a novel synthetic methodology, which enables carbon-carbon bond formation with a non-traditional electrophile and implements a unique class of ligands. In order to gain a better understanding of this reaction, a mechanistic investigation was conducted. Through reaction progress kinetic analysis, it was determined that the reaction has either a first- or a fractional-order dependence on [catalyst] and seems to be inhibited by the product. Dynamic NMR studies illustrated that the product exists in multiples forms in the reaction mixture and undergoes interchange. Given the unique reactivity imparted to nickel by the electron-deficient olefin ligand, the nature of the catalytic species was examined as well. The absence of nonlinear effects in the reaction system suggests that the active catalyst is likely mono-ligated. Interestingly, it was also discovered that the catalyst loading influences the chemoselectivity of the reaction. Initial rate studies further demonstrated that the rate dependence on [aziridine] and [nucleophile] changes over the tested concentration range. Thus, this investigation has provided a deeper understanding of the reaction system, yet has also raised new questions regarding the mechanism. We anticipate that these studies will provide direction for future mechanistic work and aid in the further development of this valuable synthetic methodology.