Kinetic Analysis Uncovers Hidden Autocatalysis and Inhibition Pathways in Titanium(III)-Catalyzed Ketone-Nitrile Couplings

Abstract

Through kinetic analysis, we demonstrate that the formation of catalyst and substrate reservoirs plays a crucial role in the titanium(III)-catalyzed ketone-nitrile coupling reaction. Together with the insight from previous studies, a kinetic model is assembled that reflects the observed influence of ZnCl2 and Et3N byproducts as well as the hydrochloride additive, which is employed frequently in titanium(III) catalysis. We further propose for the Cp2TiCl2-catalyzed reaction that the acceleration phase of the reaction originates from a hidden autocatalytic cycle, which leads to a change in the rate-determining step over the course of the reaction.