Despite its inertness toward pericyclic reactions Under common conditions, naphthalenes readily undergo Diels-Alder reactions when coencapsulated with a suitable dienophile within the cavity of a self-assembled host. Localization of the reactant pair significantly reduces the entropic cost of the reaction, and preorganization within the host cavity controls both the regio- and stereoselectivity of the reaction: electronically disfavored exo adducts were obtained. and with substituted naphthalenes, the reaction takes place on the less electron-rich, unsubstituted ring Our findings highlight the fact that judicious tuning of substrate size and shape within molecular flasks can unveil new and unusual reactivities for otherwise unreactive molecules.