Role of Additives in Transition Metal Catalyzed C–H Bond Activation Reactions: A Computational Perspective

Over the years, transition metal catalyzed reactions, such as C–H activation reaction, have brought in a paradigm shift in the practice of organic synthesis. Many complex targets could be synthesized using C–H activation strategies. In pursuit of improving the performance of catalytic reactions, various additives have generally been used as a key strategy. Additives, such as Lewis acids, Brønsted acids and metal salts, were found to have a dramatic influence in improving the yield and/or selectivities of various catalytic transformations. Although the impact additives have been widely acknowledged, the molecular basis towards understanding the origin of how these additives impact the energetics of catalytic reactions have remained rather scattered all over literature. In this review, we compile a large number of important examples where molecular understanding of the role of additives was established by using modern computational chemistry tools. Notably different energetics, proposals on the likely involvement of newer intermediates, nature of the turn-over limiting step and access to lower energy pathway all could be identified by explicit inclusion of additives in the mechanistic models. We believe that explicit consideration of additives is important toward identifying a more reasonable reaction mechanism of catalytic reactions.