Directed, metal-catalysed C–H activation reactions rely on the binding of a Lewis basic functional group to the metal centre to ensure precise control of regioselectivity. However, groups that bind the metal centre too strongly have the potential to decrease turnover frequency and inhibit productive catalysis. Herein, we have used kinetic studies of iridium-catalysed hydrogen isotope exchange reactions, with NMR spectroscopy and mass spectrometry as the analytical techniques, to investigate the binding and release behaviour of a representative series of monosubsituted aromatic systems bearing a Lewis basic directing group. It was found that pyridine and pyrimidine exhibit anomalous behaviour, with a single-binding/dual labelling process dominating, or at least being competitive with, a binding/labelling/dissociation pathway. In contrast, with other directing groups (e.g. ketone, nitro, ester) initial formation of an appreciable population of d1-isotopologue is observed, and this is subsequently converted to the corresponding d2-isotopologue, suggesting a mainly binding/labelling/dissociation pathway. These data reveal three classes of substrate with rather different behaviour and for which reaction design and optimisation needs to be approached rather differently.
