Transition-State Metal Aryl Bond Stability Determines Regioselectivity in Palladium Acetate Mediated C-H Bond Activation of Heteroarenes

Density functional calculations reveal that the stability of developing metal aryl bonds in Pd(II)-acetate C-H activation transition states determines regioselectivity in arene and heteroarene compounds. This kinetic-thermodynamic connection explains the general preference for activation of the strongest C-H bond and provides the possibility for regioselectivity prediction.