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, tBu, 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 σpara constant values) and the regioisomeric ratios experimentally obtained and computationally predicted.