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.