Palladium-mediated C-H functionalisation reactions provide a powerful approach for selective transformation of individual C-H bonds on sp 3 -rich scaffolds. Given the increasing importance of these compounds in medicinal chemistry, the ability to selectively introduce novel functionality at particular locations in the molecular framework could provide a highly useful tool in drug development. Building upon pioneering work on the use of stoichiometric quantities of palladium(II) salts to mediate selective reactions of C-H bonds in sp 3 -rich scaffolds, catalytic reactions employing a directing group to coordinate to the palladium(II) catalyst to control the site of reaction have proved to be especially effective. In most cases, the directing group incorporates one or more heteroatoms which can act as ligands for the palladium and deliver it to an adjacent C-H bond. Nitrogen-rich scaffolds are of particular importance in a wide range of chemistry-related fields, so nitrogen-linked directing groups have been the focus of considerable attention. In 2005 Daugulis introduced the 8aminoquinoline and picolinamide directing groups, and since then a number of nitrogen-linked directing groups for C-H activation have been reported (Figure ). Typically, these directing groups deliver the palladium catalyst to a nearby C-H bond via the formation of a 5-or 6-membered palladacycle, though transannular functionalisation reactions have been observed in some cases. Figure . Amide-linked directing groups employed in Pd-catalysed C-H functionalisation reactions of sp 3 -rich scaffolds. Two major drawbacks of many of these reactions are the requirement for excess silver salt in the C-H activation reaction, as well as difficulty in removing the directing group from the product molecule to recover a free amine for use in further synthetic manipulation. In recent work we have shown that selective monoarylation of bicyclic amine scaffolds can be achieved efficiently under silver-free conditions using the 2-picolinamide directing group. The picolinamide group can readily be removed under mild reductive conditions using Zn/HCl. We envisaged (Fig. ) that by manipulating the electronic and steric properties of the picolinamide directing group, it should be possible to enhance the efficiency and selectivity of Pd-catalysed C-H functionalisation reactions, as well as potentially enabling C-H functionalisation at different reaction sites within a molecule.