β-Cyclodextrin has been used as a molecular scaffold, whereby tethering dipolarophiles to the cyclodextrin and then allowing preassociation of the modified cyclodextrins with aromatic nitrile oxides, as host−guest complexes, controls the relative orientations of the dipoles and the dipolarophiles in their cycloadditions. In this manner it has been possible to reverse the usual regioselectivity of cycloadditions of nitrile oxides, as illustrated by reactions with a terminal alkene, a terminal alkyne, and a 1,2-disubstituted alkene. For example, in aqueous solution, 4-tert-butylbenzonitrile oxide reacted with 6A-deoxy-6A-propynamido-β-cyclodextrin to give the corresponding 4- and 5-substituted isoxazoles, in a 15:1 ratio. With DMF as the solvent, to reduce the extent of host−guest complexation, the product ratio was 1:1.5. The role of complexation in these reactions is also demonstrated by contrasting these results with that of the reaction of the nitrile oxide with methyl propynoate, which afforded only the 5-substituted cycloaddition product. Molecular recognition by the cyclodextrin scaffolds was demonstrated through treatment of 4-tert-butylbenzonitrile oxide with an equimolar mixture of 6A-deoxy-6A-propynamido-β-cyclodextrin and methyl propynoate, in aqueous solution, which gave only the cycloadducts from reaction of the cyclodextrin dipolarophile.