© 2016 American Chemical Society. The Ir-catalyzed C-H borylation of methyl benzoate has been studied with DFT methodology in order to understand the experimentally observed ligand-induced regioselectivity and activity when different [(ligand)Ir(Bpin)3] catalysts are employed. While bidentate ligands such as 4,4′-di-tBu-2,2′-bipyridine (dtbpy) completely inhibit ortho-borylation, the use of selected triphenylphosphine derivatives enables the reaction on that position, avoiding the meta- and para-regioisomers. The analysis of the catalytic cycles for the borylation reactions with dtbpy, PPh3, P(p-CF3C6H4)3, and P(m,m-(CF3)2C6H3)3 allows the interpretation of the observed ligand effects. The different reactivity observed for the different monodentate phosphine ligands can also be rationalized in terms of catalyst stability.