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, t Bu, 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.

Iron-Catalyzed Trimerization of Terminal Alkynes Enabled by Pyrimidinediimine Ligands: A Regioselective Method for the Synthesis of 1,3,5-Substituted Arenes

“…Various para-substituted arylacetylenes were tested. Nevertheless, only small differences in product distribution were observed, which could not be correlated with the electronic properties of the arenes . Introducing substituents that can coordinate to the iron center in the proximity of the reactive alkyne, such as esters ( 24 ), alkyl ketones ( 25 ), or 2-thiophenyl ( 26 ), leads to a reversal of selectivity in favor of the 1,2,4-isomer.…”

Variation on the π‐Acceptor Ligand within a RhI−N‐Heterocyclic Carbene Framework: Divergent Catalytic Outcomes for Phenylacetylene‐Methanol Transformations

“…The catalytic outcome is strongly dependent on the catalyst. In addition to the expected alkyne hydroalkoxylation to enol ethers ( 16 ), alkyne polymerization ( 13 ), [29] cyclotrimerization ( 14 ) [30] or dimerization ( 15 ) [12c] were also observed. The new dienol ethers ( 17 ) [31] resulting from formal addition of methanol to enynes 15 were also formed in some cases.…”

Mechanistic Studies of Transition-Metal-Catalyzed [2 + 2 + 2] Cycloaddition Reactions

“…In our group, 177 we performed a combined computational and experimental study of the [2 + 2 + 2] cyclotrimerization catalyzed by [Rh(BIPHEP)] + of a series of p-X-substituted phenylacetylenes (X = H, NO 2 , and NH 2 for the computational study and X = H, NO 2 , NMe 2 , F, Me, t Bu, and OMe in experiments). The aim was to analyze the effect of the electronic character of the phenyl substituents in the regioselectivity.…”