Regioselective reactions with supramolecular control are of great interest. Herein, the pars-regiose-lectivity in the Mannich reaction of phenol with formaldehyde and dimethylamine was achieved with the use of beta-cyclodextrin (beta-CD), giving 4-(N,N-dimethylaminomethyl)phenol (p-AP) as major product. H-1 NMR and ITC measurements of the binding of beta-CD with the reactants and the products o- and p-AP revealed a new mechanism, in which beta-CD includes p-AP instead of phenol to control the reaction regioselectivity. This product-inclusion mechanism is remarkably different to the known react...
