Alternative and Sustainable Route to Explore a New Class of Amidines by Photochemical Synergistic Effect of Copper/Nitroxyl Radical Catalysis via Halogen-Atom Transfer

Abstract

Amidines are a vital class of bioactive compounds and often necessitate multiple components for their synthesis. Therefore, exploring efficient and sustainable methodologies for their synthesis is indispensable. Herein, we disclose an alternative and greener method for synthesizing an unexplored new class of amidines through the photochemical synergistic effect of copper/nitroxyl radical catalysis. This approach facilitates site-selective radical amination of unactivated imine C(sp²)−H bond in C,N,N-cyclic imines over favored selectivity via halogen-atom transfer (XAT). This greener method ticks 11 out of 12 green chemistry metrics (GCM), effectively sidestepping the need for oxidants, bases, ligands, multistep processes, and harsh conditions, distinguishing it from conventional methods described in previous studies. Kinetic, spectroscopic, and computational tools have been employed to elucidate the synergistic effect of Cu/nitroxyl radical, the role of light, XAT, the influence of substituents, and the order of the reaction in the catalytic cycle.