Reactivity of Substituted Benzenes toward Oxidative Addition Relates to NMR Chemical Shift of the Ipso-Carbon.

The oxidative addition of benzene derivatives to Pd0 catalysts is a key step in cross-coupling reactions. In this work, we show that the ipso-carbon chemical shift of substituted benzenes, and in particular the δ22 component of the chemical shift tensor, correlates with the free energy barrier for oxidative addition. This correlation is traced back to the electron density in the pz orbital of the ipso-carbon (perpendicular of the ring-plane), with high electron densities favoring oxidative addition. The correlation between chemical shift and free energy barrier holds true for a variety of substituted benzenes, making chemical shift a useful descriptor for predicting the reactivity of aromatic substrates in oxidative addition.