Cyclic processes involving medium-sized rings show low rates because internal strains-torsions and transannular interactions-are created during the reactions. High dilution is often used to slow the competing bi- and higher-molecular processes but cannot accelerate the desired cyclization reaction. Here we apply cavitands to the formation of medium- to large-sized rings through conversion of long-chain diisocyanates to cyclic ureas. The reactions take place in aqueous (D2O) solution, where hydrophobic forces drive the starting materials into the cavitands in folded conformations. The guest assumes the shape to fill the space properly, which brings the reacting ends closer together than they are in bulk solvent. Complexation overcomes some of the internal strains involved in precyclization shapes of the guest molecules and accelerates the cyclization. The results augur well for applications of water-soluble cavitands to related processes such as remote functionalization reactions.