beta-cyclodextrin as a scaffold for supramolecular chemistry, to reverse the regioselectivity of nitrile oxide cycloadditions

beta-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 complexe s, controls the relative orientations of the dipoles and the dipolarophiles in their cycloadditions. In this manner it has been possible to reverse th e usual regioselectivity of cycloadditions of nitrile oxides, as illustrate d by reactions with a terminal alkene, a terminal alkyne, and a 1,2-disubst ituted alkene. For example, iii aqueous solution, 4-tert-butylbenzonitrile oxide reacted with 6(A)-deoxy-6(A)-propynamido-beta-cyclodextrin to give th e 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 produc t ratio was 1:1.5. The role of complexation in these reactions is also demo nstrated by contrasting these results with that of the reaction of the nitr ile oxide with methyl propynoate, which afforded only the 5-substituted cyc loaddition product. Molecular recognition by the cyclodextrin scaffolds was demonstrated through treatment of 4-tert-butylbenzonitrile oxide with an e quimolar mixture of 6(A)-deoxy-6(A)-prapynamido-beta-cyclodextrin and methy l propynoate, in aqueous solution, which gave only the cycloadducts from re action of the cyclodextrin dipolarophile.