A cyclodextrin molecular reactor for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles

Abstract

6A-Deoxy-6A-propynamido-β-cyclodextrin reacts with 4-tert-butylphenyl azide in aqueous solution, to form the 5-(aminocarbonyl)-substituted triazole in preference to the 4-(aminocarbonyl)- substituted analogue, in a ratio of 25:1. The cyclodextrin moiety templates the reaction through the formation of a host-guest complex of the dipole with the dipolarophile, controlling the regio-selectivity of cycloaddition. In a control reaction under similar conditions, with propiolamide instead of the cyclodextrin derivative, 5- and 4-(aminocarbonyl)-1-(4-tert-butylphenyl)-1,2,3-triazole were formed in a ratio of 1:4. As well as reversing the regioselectivity, the cyclodextrin substituent increases the rate of cycloaddition, by at least two orders of magnitude for the reaction to give the 5-substituted cycloadduct. Even the rate of formation of the 4-substituted cycloadduct is increased by a factor of two. Less marked effects are observed with phenyl azide and 4-tert-butylbenzyl azide as dipoles. © 2005 Taylor & Francis.