Examining the factors that govern the regioselectivity in rhodium-catalyzed alkyne cyclotrimerization

Abstract

The electronic and steric factors that favour the formation of 1,2,4- and 1,3,5-regioisomers in the intermolecular [2+2+2] cyclotrimerisation of terminal alkynes are not well understood. In this work, this problem was analysed from a theoretical and experimental point of view. Density functional theory (DFT) calculations of the [2+2+2] cyclotrimerisation of p-X-substituted phenylacetylenes (X = H, NO2, and NH2) catalysed by [Rh(BIPHEP)]+ were carried out to determine the reaction mechanism in each case and analyse 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 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