DFT Study on the Mechanism and Regioselectivity of Gold(I)-Catalyzed Synthesis of Highly Substituted Furans Based on 1-(1-Alkynyl)cyclopropyl Ketones with Nucleophiles

The mechanism and regioselectivity of gold(I)-catalyzed synthesis of highly substituted furans based on 1-(1-alkynyl)cyclopropyl ketones with nucleophiles have been investigated using density functional theory calculations done at the BH and HLYP/6-31G(d, p) (SDD for Au) level of theory. Solvent effects on these reactions have been explored by calculations that included a polarizable continuum model (PCM) for the solvent (dichloromethane). Our calculations suggest that the first step of the cycle is the cyclization of the carbonyl oxygen onto the triple bond to form a new and stable five-membered resonance structure of an oxonium ion and a carbocation intermediate. Furthermore, the seven-membered carbocation intermediate proposed by Zhang and Schmalz was found and characterized as a transition structure on the potential energy surface. The attack of the carbonyl oxygen to the gold-coordinated alkynes results in the formation of a resonance structure intermediate, which upon subsequent trapping with alcohols followed by migration of a hydrogen atom results in the formation of the final products and regeneration of the catalyst. The key reaction step is the attack of the oxygen atom of the CH3OH on the C-C sigma bond of the cyclopropane moiety to yield new organogold intermediates through formation of a C-O bond and cleavage of a C-C bond. The cleavage of the C-C bond is strongly favored kinetically in the case of the C-1-C-2 bond and required only 19.8 kcal/mol of energy, while the activation energy for cleavage of the C-1-C-3 bond was found to be 31.8 kcal/mol and indicates that the ring-opening cycloisomerization for cyclopropyl ketones has high regioselectivity. Our computational results are consistent with the experimental observations of Zhang and Schmalz for the gold(I)-catalyzed synthesis of highly substituted furans based on 1-(1-alkynyl)cyclopropyl ketones with nucleophiles.