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)RuCl₂ (³R21, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). DFT calculations predict ³R21 to be a very active alkene isomerization initiator, either operating as a catalyst itself, via a η³-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 catalyst decomposition is a fundamental, long-standing challenge in olefin metathesis. Emerging ruthenium–cyclic(alkyl)(amino)carbene (CAAC) catalysts, which enable breakthrough advances in productivity and general robustness, are now known to be extraordinarily susceptible to this pathway. The details of the process, however, have hitherto been obscure. The present study provides the first detailed mechanistic insights into the steric and electronic factors that govern bimolecular decomposition. Described is a combined experimental and theoretical study that probes decomposition of the key active species, RuCl₂(L)(py)(═CH₂) 1 (in which L is the N-heterocyclic carbene (NHC) H₂IMes, or a CAAC ligand: the latter vary in the NAr group (NMes, N-2,6-Et₂C₆H₃, or N-2-Me,6-ⁱPrC₆H₃) and the substituents on the quaternary site flanking the carbene carbon (i.e., CMe₂ or CMePh)). The transiently stabilized pyridine adducts 1 were isolated by cryogenic synthesis of the metallacyclobutanes, addition of pyridine, and precipitation. All are shown to decompose via second-order kinetics at −10 °C. The most vulnerable CAAC species, however, decompose more than 1000-fold faster than the H₂IMes analogue. Computational studies reveal that the key factor underlying accelerated decomposition of the CAAC derivatives is their stronger trans influence, which weakens the Ru−py bond and increases the transient concentration of the 14-electron methylidene species, RuCl₂(L)(═CH₂) 2. Fast catalyst initiation, a major design goal in olefin metathesis, thus has the negative consequence of accelerating decomposition. Inhibiting bimolecular decomposition offers major opportunities to transform catalyst productivity and utility, and to realize the outstanding promise of olefin metathesis.

Whereas a number of highly Z-selective ruthenium-based olefin metathesis catalysts bearing N-heterocyclic carbene ligands have been reported in recent years, Z-selectivity has so far been difficult to achieve for phosphine-based catalysts. Guided by predictive density functional theory (DFT) calculations, we have developed phosphine-based ruthenium olefin metathesis catalysts giving 70–95% of the Z-isomer product in homocoupling of terminal alkenes such as allylbenzene, 1-octene, allyl acetate, and 2-allyloxyethanol. Starting from a moderately selective catalyst, [P(Cy)₃](-S-2,4,6-Ph-C₆H₂)ClRu(═CH-o-OⁱPrC₆H₄) (4, Cy = cyclohexyl, ⁱPr = isopropyl), obtained by substituting a chloride of the Hoveyda–Grubbs first-generation catalyst with 2,4,6-triphenylbenzenethiolate, we moved on to replace Cl and PCy₃ by chelating, anionic phosphine ligands. Such ligands increase selectivity by limiting rotation around the P–Ru bond and by specifically directing the steric bulk of the phosphine substituents toward the selectivity-inducing thiolate ligand. In particular, DFT calculations predicted that o-(dialkylphosphino)phenolate ligands should improve selectivity and activity compared to 4. The most promising of these compounds (8b), based on the o-(di-tert-butylphosphino)phenolate ligand, directs the two P-bonded tert-butyl substituents toward the 2,4,6-triphenylbenzenethiolate and has little steric hindrance trans to the thiolate. This compound metathesizes terminal olefins such as allylbenzene and 1-octene with Z-selectivities above 80% and allylacetate above 90%. Although these phosphine-based ruthenium monothiolate catalysts in general achieve somewhat lower activities and Z-selectivities than their second-generation counterparts, they also offer examples giving less substrate and product isomerization and thus higher yields.

Pyridine as a stabilizing donor ligand drastically improves the performance of ruthenium monothiolate catalysts for olefin metathesis in comparison with previous versions based on a stabilizing benzylidene ether ligand. The new pyridine-stabilized ruthenium alkylidenes undergo fast initiation and reach appreciable yields combined with moderate to high Z selectivity in self-metathesis of terminal olefins after only a few minutes at room temperature. Moreover, they can be used with a variety of substrates, including acids, and promote self-metathesis of ω-alkenoic acids. The pyridine-stabilized ruthenium monothiolate catalysts are also efficient at the high substrate dilutions of macrocylic ring-closing metathesis and resist temperatures above 100 °C during catalysis.

In ruthenium catalysts for olefin metathesis, carbene ligands of high trans influence/effect suppress decompositionviaβ-H elimination, but increase susceptibility to bimolecular decomposition.