Mechanistic Insight into Cu-Catalyzed C-N Coupling of Hindered Aryl Iodides and Anilines Using a Pyrrol-ol Ligand Enables Development of Mild and Homogeneous Reaction Conditions

Mechanistic studies of the Cu-catalyzed C-N coupling of sterically hindered aryl iodides with sterically hindered anilines are carried out to shed light on how a recently reported pyrrol-ol ligand affects the reaction. Kinetic, spectroscopic, and computational tools help to probe the nature of the active catalyst species and the rate-determining step in the cycle. In contrast to most known Cu systems, oxidative addition is found to precede coordination of the amine. These studies help to design an efficient process under mild conditions using a fully homogeneous system as well as protocols that enable high yields by temperature scanning and controlled addition of the base. The insights obtained for the XX-type ligand may lead to a general approach for challenging substrate classes in Cu-catalyzed coupling reactions.

Automated summary

Mechanistic studies of Cu-catalyzed C-N coupling have been conducted to investigate the effects of a recently reported pyrrol-ol ligand on the reaction of sterically hindered aryl iodides with sterically hindered anilines. Kinetic, spectroscopic, and computational techniques were used to determine the active catalyst species and the rate-determining step. It was found that oxidative addition precedes amine coordination, which is in contrast to most known Cu systems. These findings could lead to the development of a general approach for challenging substrates in Cu-catalyzed coupling reactions.