Nitrene transfer (NT) reactions represent powerful and direct methods to convert C-H bonds into amine groups that are prevalent in many commodity chemicals and pharmaceuticals. The importance of the C-N bond has stimulated the development of numerous transition-metal complexes to effect chemo-, regio-, and diastereoselective NT. An ongoing challenge is to understand how subtle interactions between catalyst and substrate influence the site-selectivity of the C H amination event. In this work, we explore the underlying reasons why Ag(tpa)OTf (tpa = tris(pyridylmethyl)amine) prefers to activate a-conjugated C H bonds over 3 degrees alkyl C(sp(3))-H bonds and apply these insights to reaction optimization and catalyst design. Experimental results suggest possible roles of noncovalent interactions (NCIs) in directing the NT; computational studies support the involvement of pi-pi and Ag center dot center dot center dot pi interactions between catalyst and substrate, primarily by lowering the energy of the directed transition state and reaction conformers. A simple Hess's law relationship can be employed to predict selectivities for new substrates containing competing NCIs. The insights presented herein are poised to inspire the design of other catalyst-controlled C-H functionalization reactions.