We have demonstrated that Ox3 is able to bind the monocationic form of a family of diamines, with the ammonium group deeply inserted in the cavity of the receptor, and the second amino group protruding from the host cavity and thus accessible for a chemical transformation. These host-guest properties have been exploited in a supramolecular protection strategy for the monofunctionalization of various diamines. Selective monofunctionalization was readily obtained with different types of reagents and only one product was detected by NMR in most cases. A high host-guest affinity and a control of the host-guest stoichiometry were shown to be key parameters to achieve high iteroselectivity.