Loss and Reformation of Ruthenium Alkylidene: Connecting Olefin Metathesis, Catalyst Deactivation, Regeneration, and Isomerization

Abstract

Ruthenium-based olefin metathesis catalysts are used in laboratory-scale organic synthesis across chemistry, largely thanks to their ease of handling and functional group tolerance. In spite of this robustness, these catalysts readily decompose, via little-understood pathways, to species that promote double-bond migration (isomerization) in both the 1-alkene reagents and the internal-alkene products. We have studied, using density functional theory (DFT), the reactivity of the Hoveyda-Grubbs second-generation catalyst 2 with allylbenzene, and discovered a facile new decomposition pathway. In this pathway, the alkylidene ligand is lost, via ring expansion of the metallacyclobutane intermediate, leading to the spin-triplet 12-electron complex (SIMes)RuCl (R21, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). DFT calculations predict R21 to be a very active alkene isomerization initiator, either operating as a catalyst itself, via a η-allyl mechanism, or, after spin inversion to give R21 and formation of a cyclometalated Ru-hydride complex, via a hydride mechanism. The calculations also suggest that the alkylidene-free ruthenium complexes may regenerate alkylidene via dinuclear ruthenium activation of alkene. The predicted capacity to initiate isomerization is confirmed in catalytic tests using p-cymene-stabilized R21 (5), which promotes isomerization in particular under conditions favoring dissociation of p-cymene and disfavoring formation of aggregates of 5. The same qualitative trends in the relative metathesis and isomerization selectivities are observed in identical tests of 2, indicating that 5 and 2 share the same catalytic cycles for both metathesis and isomerization, consistent with the calculated reaction network covering metathesis, alkylidene loss, isomerization, and alkylidene regeneration.

Bimolecular Cross‐Metathesis of a Tetrasubstituted Alkene with Allylic Sulfones

“…[3,4] Within the interplay of steric and electronic factors, substituted alkenes remain reluctant partners for cross-metathesis and impeded turnover kinetics can result in catalyst degradation and competing secondary processes. [5] Modification of aryl ligand substituents in ruthenium and molybdenum catalysts opens the coordination environment to accommodate sterically hindered alkene substrates, while substitution of the Nheterocyclic carbene backbone provides catalysts with improved efficiency for ring-closing metathesis to yield tetrasubstituted cycloalkenes. [6,7] Problems associated with this approach include reduced catalyst stability and limited scope of effective substrates, highlighting the need for alternative strategies.…”

Formation of active species from ruthenium alkylidene catalysts—an insight from computational perspective

“…It is well-established that the ground state for 16electron and 14-electron ruthenium alkylidene complexes, studied in this work, is singlet [18,42]. According to the PBE0/def2-SVP calculations, the triplet and quintet states of the 16-electron complex 1 are less stable than the singlet state, by 93 and 191 kJ mol −1 , respectively.…”

Ruthenium‐Alkylidene Complexes with Sterically Rigid Fluorinated NHC Ligands

“…The observed selectivity could be addressed to the rigid structure of NHCs, which forces the more bulky aromatic fragment of the unsymmetrical ligand to locate in close proximity to ruthenium center. This in turn hampers the catalyst decomposition via ruthenium‐hydride pathways and blocks any isomerization processes . For proposed mechanism of preventing the isomerization process see Supporting Information.…”