Relevance of cis- and trans-dichloride Ru intermediates in Grubbs-II olefin metathesis catalysis (H2IMesCl2RuCHR)

Abstract

Using density functional theory with the B3LYP and M06 functionals, we show conclusively that the (H 2 IMes)(Cl) 2 Ru olefin metathesis mechanism is bottom-bound with the chlorides remaining trans throughout the reaction, thus attempts to effect diastereo-and enantioselectivity should focus on manipulations that maintain the trans-dichloro Ru geometry.Olefin metathesis 1 has become a powerful ubiquitous reaction for forming carbon-carbon double bonds. Improved ruthenium olefin metathesis catalysts exhibiting higher initiation rates, 2 differential monomer reactivity, 3 enantioselectivity, 4 and improved thermal stability 5 have been reported recently. A long-standing controversy 6 has been whether the mechanism involves an isomerization from the initial trans-dichloro Ru (Fig. 1b) to a cis-dichloro Ru geometry (Fig. 1c) leading to a side-on mechanism. This mechanism was proposed by Grubbs 7 to rationalize the observed reactivity and selectivity, but without direct experimental evidence. We report here first principles studies showing conclusively that the mechanism is bottom-bound, with the chlorides remaining trans throughout the reaction, which explains available experimental evidence. Thus attempts to effect stereo-and enantioselectivity should focus on manipulations that maintain the trans-dichloro Ru geometry.It is generally believed that the mechanism 8 of Ru catalyzed olefin metathesis involves a symmetric process in which a Ru carbene coordinated with a substrate olefin (square pyramidal) rearranges via a pseudorotation to a metallacyclobutane (trigonal bipyramidal) which then rearranges productively to form a coordinated product olefin and a new Ru carbene (square pyramidal). The structures for the various intermediates have been established from low temperature 1 H-NMR studies, 9 X-ray crystallography structural data of isolated stable intermediates, 10 and theoretical investigations. 11Based on their density functional theory (DFT) studies (BP86) on the relative energies of the bottom-and side-bound pathways, Cavallo and Correa concluded 11b that the preferred reaction pathway is a delicate balance between electronic, steric, and solvent effects.12 This has led to several reports considering the side-bound pathway as highly significant, if not the most likely operative pathway. 3,6 We consider that this lack of a clear understanding of the catalytic pathway (side vs. bottom) is hindering the development of selective metathesis catalysts. To provide a basis for assessing the side-and bottom-bound metathesis pathways, we applied DFT methods to investigate the relative energies and the expected E : Z olefin product ratio of the cis-and trans-dichloro Ru pathways for the metathesis of E-and Z-2-butene with the Grubbs-II benzylidene catalyst (Fig. 1a).Truhlar and Zhao reported 13 that medium-range noncovalent interactions (dispersion forces) can have a dramatic effect on the ruthenium tricyclohexylphosphine (PCy 3 ) bond dissociation energies for both the first and second generation Grubbs catalysts. The M...

On the Accuracy of DFT Methods in Reproducing Ligand Substitution Energies for Transition Metal Complexes in Solution: The Role of Dispersive Interactions

“…[47] Likewise, Goddard and coworkers calculated the binding energy of PCy 3 to a Ru complex with the M06 functional. [48] The value for DH 298K calculated in the gas phase, 39.0 kcal mol À1 , is in remarkable agreement with the experimentally determined gas-phase value of 36.9 kcal mol À1 reported by Chen and coworkers. [49] Differently, inclusion of a continuum solvation model resulted in the reduction of the PCy 3 binding energy to only 35.7 kcal mol À1 in toluene, a value that largely overestimates the experimental activation enthalpy of phosphane substitution in toluene, 27 kcal mol…”

Mapping the potential energy surfaces for ring-closing metathesis reactions of prototypical dienes by electronic structure calculations

“…Thus, it would appear that our estimates of the barriers for even the most demanding steps on the cyclisation profiles are relatively low compared to the phosphane binding energy and we find that most of the intermediates on the surfaces lie below the starting alkylidene derived from the pre-catalyst. 77 If each turnover required the dissociation of the phosphane from the pre-catalyst 1b, this barrier would be the ratedetermining step. However, once the active catalyst has formed, the rate of turnover is controlled by the propagation of 2 through the intervening complexes.…”

What is the initiation step of the Grubbs-Hoveyda olefinmetathesiscatalyst?

“…1 The mechanism of ruthenium-mediated olefin metathesis catalysed by first (1a) and second generation (1b) Grubbs complexes has been extensively studied both by experiment 2,3 and by computational modelling. 4,5 The rate constants for the initiation of the phosphane-containing catalysts are independent of the olefin concentration. The corresponding activation parameters for phosphane exchange have been measured and it is accepted that the initial dissociation of the phosphane ligand is the highest barrier on the potential energy surface.…”