Understanding titanium-catalysed radical–radical reactions: a DFT study unravels the complex kinetics of ketone–nitrile couplings

Abstract

The computational investigation of a titanium-catalysed reductive radical–radical coupling is reported. The results match the conclusions from an earlier experimental study and enable a further interpretation of the previously observed complex reaction kinetics. Furthermore, the interplay between neutral and cationic reaction pathways in titanium(III)-catalysed reactions is investigated for the first time. The results show that hydrochloride additives and reaction byproducts play an important role in the respective equilibria. A full reaction profile is assembled and the computed activation barrier is found to be in reasonable agreement with the experiment. The conclusions are of fundamental importance to the field of low-valent titanium catalysis and the understanding of related catalytic radical–radical coupling reactions.