The long-accepted scientific community's understanding of the oxidative addition reaction on palladium complexes turned out to be incomplete. Chemists from Germany have discovered that it can proceed not only by a two-electron mechanism, but also by a radical mechanism. Moreover, this occurs when both the palladium complex and the substrate are sterically hindered. The study was published in the Journal of the American Chemical Society.
Phosphine complexes of palladium are most often used to catalyze cross-coupling reactions, such as the Suzuki reaction. In this reaction, an organic halogen derivative reacts with an organic boronic acid to form a carbon-carbon bond and link the two organic fragments. Chemists Akira Suzuki, Richard Heck, and Eiichi Negishi received the 2010 Nobel Prize in Chemistry for their discovery of cross-coupling reactions.
The catalytic cycle of almost any cross-coupling reaction begins with the oxidative addition of a halogen derivative to a phosphine complex of palladium. In this process, the carbon-halogen bond is broken, and its components - a halogen and an organic fragment - are added to the palladium atom. The mechanism of this reaction has been known since the last century. It is known that it occurs as a two-electron concerted process in which the carbon-halogen bond is broken, and bonds with palladium are formed, and all this happens simultaneously.
But recently, chemists led by Franziska Schoenebeck from the RWTH Aachen University have discovered a new mechanism for oxidative addition to phosphine palladium complexes. It turns out that it can proceed radically, so that the palladium complex rips a halogen atom from the substrate to form an aryl radical.
The chemists discovered this when they performed a cross-coupling reaction with 1-bromo-2-(tert-butyl)benzene, which has a bulky tert-butyl group next to the bromine atom. Because of this, the reaction simply didn’t work with most catalysts—the large tert-butyl group blocked the reaction center from the palladium complex. But to the scientists’ surprise, when they used a complex with a very bulky phosphine ligand, the reaction worked. This result didn’t match the classical cross-coupling mechanism, and the chemists tried to figure out what was going on.
They suggested that when the approach of the palladium complex to the substrate is greatly hampered by surrounding groups, oxidative addition can proceed via a radical mechanism. The scientists then performed quantum chemical calculations, which showed that this is indeed possible, and the radical reaction should proceed much faster than the concerted one.
To confirm this experimentally, the chemists used an even more difficult substrate, which had two tert-butyl groups next to the bromine atom. The scientists mixed it with a palladium catalyst and in just one minute they obtained a product in which the bromine atom was attached to the tert-butyl group. According to the chemists, this result confirms the hypothesis about the radical mechanism of the reaction: the aryl radical formed after the radical oxidative addition tore off the hydrogen atom from the tert-butyl group, and the new radical formed in this way attached the bromine atom.
The chemists have discovered that oxidative addition reactions can occur even when both the catalyst and substrate are so large that they would seem unable to react with each other. They believe this will expand the possibilities of cross-coupling reactions.
We recently talked about how chemists learned to carry out the Suzuki reaction with anilines.