Kinetico-Mechanistic Studies of Cu(II)-Mediated Cyclizationof Imines via C-H Bond Activations

Abstract

Herein, we focus on the kinetico-mechanistic studies of a carboxylate and Cu(II)-assisted synthesis of imidazo[1,5-a]pyridines encompassing C(sp3)−H amination and cyclization of imines coupled with C(sp2)−H cyanation using time-resolved UV-Vis reaction monitoring and ex-situ analyses. Thus, kinetic studies have been carried out, providing a proof of the elementary steps involved, allowing for batch analysis of the compounds present in solution via MS. The experimental data obtained are consistent with the formation of a cyclometalated complex (k1) involving a C(sp3)−H bond cleavage followed by a reductive elimination/proton abstraction event (k2), both showing high enthalpy-demanding transition states. The two processes show a well-defined Eyring behavior with values of ΔH≠ and ΔS≠ within the expected range. Further insights on the intermediate fast C(sp2)–cyanation are also presented together with control reactions.