The confined space inside the hexameric pyrogallol[4]arene capsule (CP₆) can be exploited for the catalysis of the 1,3-dipolar cycloaddition (1,3-DC) between nitrone 3 and crotonaldehyde 4, in the presence of the non-competitive benzene solvent. Differently, when the capsule CP₆ is self-assembled in the commonly used chloroform solvent, its nano-cavity becomes catalytically incompetent. Diffusion NMR studies and product analysis show that in the presence of chloroform, which is stably encapsulated inside the pyrogallol[4]arene capsule, the reaction between the proline-based iminium derivative I and nitrone 3 does not occur inside the cavity but on the exterior of the CP₆ capsule. Differently, in the presence of a non-competitive solvent such as benzene, the 1,3-DC occurs inside the cavity of the pyrogallol[4]arene capsule. The confinement of iminium I and nitrone 3 inside the confined space of CP₆ leads to a strict control over the stereochemistry of the 1,3-DC. Thus, while the endo-stereoisomer of the isoxazolidine product 5 is favored inside the capsule, the exo-one is preferentially formed on the exterior of the capsule or in the bulk solvent. QM calculations have been performed to rationalize these stereochemical results.