Examined herein is the basis for the outstanding metathesis productivity of leading cyclic alkyl amino carbene (CAAC) catalysts relative to their important N-heterocyclic carbene (NHC) predecessors, as recently demonstrated in the topical contexts of metathesis macrocyclization and the ethenolysis of renewable oils. The difference is traced to the stability to decomposition of the metallacyclobutane (MCB) intermediate. The CAAC catalysts are shown to undergo little to no β-H elimination of the MCB ring, a pathway to which the H2IMes catalysts are highly susceptible. Unexpectedly, however, the CAAC catalysts are found to be more susceptible to bimolecular coupling of the key intermediate RuCl2(CAAC)­(CH2), a reaction that culminates in elimination of the methylidene ligand as ethylene. Thus, an NMR study of transiently stabilized RuCl2(L)­(py)­(CH2) complexes (L = CAAC or H2IMes) revealed bimolecular decomposition of the CAAC derivative within 5 min at RT, as compared to a time scale of hours for the H2IMes analogue. The remarkable productivity of the CAAC catalysts is thus due to their resistance to β-elimination, which enables their use at part per million loadings, and to the retarding effect of these low catalyst concentrations on bimolecular decomposition.

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, RuCl 2 (L)(py)(=CH 2 ) 1 (in which L is the N-heterocyclic carbene (NHC) H 2 IMes, or a CAAC ligand: the latter vary in the NAr group (NMes, N-2,6-Et 2 C 6 H 3 , or N-2-Me,6- i PrC 6 H 3 ) and the substituents on the quaternary site flanking the carbene carbon (i.e., CMe 2 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 H 2 IMes 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, RuCl 2 (L)(=CH 2 ) 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.

Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles, with applications ranging from perfumery to production of antiviral drugs. Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be converted into the cyclic targets by catalysts that are sufficiently reactive to promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but catalyst decomposition limits yields and selectivity. Incorporation of a hemilabile o-dianiline (ODA) chelate into new catalysts of the form RuCl(NHC)(ODA)(=CHPh) accelerates macrocyclization, particularly for dienes bearing polar sites capable of H-bonding: it may also inhibit catalyst decomposition during metathesis. Significant improvements relative to prior Ru-NHC catalysts result, with fast macrocyclization of conformationally flexible dienes at room temperature.

Access to leading olefin metathesis catalysts, including the Grubbs, Hoveyda, and Grela catalysts, ultimately rests on the nonscaleable transfer of a benzylidene ligand from an unstable, impure aryldiazomethane. The indenylidene ligand can be reliably installed, but to date yields much less reactive catalysts. A fast-initiating, dimeric indenylidene complex (Ru-1) is reported, which reconciles high activity with scaleable synthesis. Each Ru center in Ru-1 is stabilized by a state-of-the-art cyclic alkyl amino carbene (CAAC, C1) and a bridging chloride donor: the lability of the latter elevates the reactivity of Ru-1 to a level previously attainable only with benzylidene derivatives. Evaluation of initiation rate constants reveals that Ru-1 initiates >250× faster than indenylidene catalyst M2 (RuCl2(H2IMes)­(PCy3)­(Ind)), and 65× faster than UC (RuCl2(C1)2(Ind)). The slow initiation previously regarded as characteristic of indenylidene catalysts is hence due to low ligand lability, not inherently slow cycloaddition at the Ru=CRR′ site. In macrocyclization and “ethenolysis” of methyl oleate (i.e., transformation into α-olefins via cross-metathesis with C2H4), Ru-1 is comparable or superior to the corresponding, breakthrough CAAC-benzylidene catalyst. In ethenolysis, Ru-1 is 5× more robust to standard-grade (99.9%) C2H4 than the top-performing catalyst, probably reflecting steric protection at the quaternary CAAC carbon.

Ruthenium catalysts for olefin metathesis are widely viewed as water-tolerant. Evidence is presented, however, that even low concentrations of water cause catalyst decomposition, severely degrading yields. Of 11 catalysts studied, fast-initiating examples (e.g., the Grela catalyst RuCl 2 (H 2 IMes)(=CHC 6 H 4 -2-O i Pr-5-NO 2 ) were most affected. Maximum water tolerance was exhibited by slowly initiating iodide and cyclic (alkyl)(amino)carbene (CAAC) derivatives. Computational investigations indicated that hydrogen bonding of water to substrate can also play a role, by retarding cyclization relative to decomposition. These results have important implications for olefin metathesis in organic media, where water is a ubiquitous contaminant, and for aqueous metathesis, which currently requires superstoichiometric “catalyst” for demanding reactions.