Cyclometallated Iron(II) Alkoxides in Iron-Catalyzed C–H Activations by Weak O-Carbonyl Chelation

Iron catalysts represent an economically attractive tool for C–H activations because of their low costs and low toxicities. Despite an exponential increase of interest in this area, detailed mechanistic understanding remains at a nascent stage. Herein, a detailed investigation of the C–H activation mechanism with [Fe(PMe₃)₄] unraveled an unexpected iron(II) alkoxide intermediate that was fully characterized and was found to be a more active catalyst in phenone-assisted C–H activations with respect to the previously reported mer-iron hydride cyclometallated counterpart. Mechanistic studies by stoichiometric experimentation, reaction profiling through electron paramagnetic resonance (EPR) and in operando NMR spectroscopy, deuterium labeling, crystallographic analyses, and density functional theory (DFT) calculations provided strong evidence for an oxidative addition of the pivalophenone to a low-valent iron intermediate toward the formation of a transient fac-hydride complex, which very quickly rearranges to an iron alkoxide complex. According to detailed DFT studies, it is proposed that the isolated iron(II) alkoxide is a highly reactive precatalyst, which can easily access the on-cycle fac-hydride complex, thereby translating into highly efficient catalysis. These mechanistic insights form the basis for further developments in iron-catalyzed C–H activation with prospects for stereoselective transformations.