Examining the Factors That Govern the Regioselectivity in Rhodium-Catalyzed Alkyne Cyclotrimerization

The electronic and steric factors that favor the formation of 1,2,4- and 1,3,5-regioisomers in the intermolecular [2 + 2 + 2] cyclotrimerization of terminal alkynes are not well understood. In this work, this problem was analyzed from a theoretical and experimental point of view. Density functional theory (DFT) calculations of the [2 + 2 + 2] cyclotrimerization of p-X-substituted phenylacetylenes (X = H, NO2, NH2) catalyzed by [Rh(BIPHEP)](+) were carried out to determine the reaction mechanism in each case and analyze the effect that the electronic character of the substituents has on the regioselectivity. For the rate-determining step corresponding to the oxidative coupling leading to the rhodacyclopentadiene intermediate, we have taken into account two reaction pathways: the reaction pathway with the lowest energy barrier and the reaction pathway through the most stable transition state (Curtin-Hammett pathway). Our results show that the theoretical results conform to experimental outcomes for different p-X-substituted phenylacetylenes (X = NO2, F, H, Me, Bu-t, OMe, NMe2) only when the Curtin-Hammett reaction pathway is considered. A fairly good correlation has been obtained between the electronic nature of the substituents (as expressed by the Hammett sigma(para) constant values) and the regioisomeric ratios experimentally obtained and computationally predicted.