Abstract
Herein, we report density functional theory calculations to investigate the reaction mechanism and the selectivity of the cycloisomerization of alkynoic acids inside a gold-functionalized resorcinarene-based cavitand. This cavitand has experimentally been shown to catalyze the cycloisomerization of a number of substituted alkynoic acids to give the corresponding γ-lactones. Three representative substrates, with different substitution patterns, are considered in the calculations, and for each of them, the geometries and energies of various binding modes are first characterized. Next, the cycloisomerization reaction mechanism is evaluated, which is shown to consist of an intramolecular addition of the carboxylic acid to the gold-activated alkyne triple bond, followed by a protodeauration step. Both 5-exo-dig and 6-endo-dig cyclizations were considered, leading to γ- or δ-lactones, respectively, and the involvement of the triflate counterion in the cyclization step is discussed. Finally, the influence of the cavitand walls on the reactivity is evaluated by using a model catalyst in which the walls were removed.