Molecules in Confined Spaces: Reactivities and Possibilities in Cavitands

Template effects are at the origin of supramolecular chemistry, but the behavior of folded molecules is a relatively new undertaking. Water-soluble cavitand hosts bind hydrocarbons through hydrophobic effects and force long-chain guests into folded conformations. This brings their ends closer together, and sites that were remote in solution become neighbors in the confined space and affect each other's reactivity. Amphiphilic guests fold in the cavitand to bury hydrophobic surfaces and expose the hydrophilic surfaces to the bulk solution, This arrangement leads to product distributions in monofunctionalization reactions that are significantly altered from the statistically determined outcomes in solution. The cavitand also acts as a template for macrocyclic processes involving direct reaction of the guests' ends. We propose applying the effects of folding in cavitands to truly remote functionalization reactions and provide access to molecules that cannot be made by conventional means.