Site-selectivity is an enduring challenge in C-H activation chemistry; over-reaction results in waste of often precious substrate and complicates the isolation and purification of products. This work provides insight into substrate binding and reactivity that we anticipate will be of interest and importance to researchers applying C-H activation across the broad field of chemical synthesis. using the ARCHIE-WeSt High-Performance Computer at the University of Strathclyde, and we thank Mr Jonathan Buzzard, Dr Karina Kubiak-Ossowska, and Dr Richard Martin for their assistance with this facility. We thank Dr Andrew Dalgleish and Dr Nathan Knight for helpful discussions around the interpretation of the computational study, and Dr Susanna Wood for helpful comments on a draft of this manuscript.