N2 - The mechanism of the transition metal catalyzed olefin metathesis reaction with the Schrock catalyst is investigated with pure (BP86) and hybrid (B3LYP) density functional theory. On the free-energy surface there is no adduct between ethylene and model catalyst (MeO)
When selecting a catalyst for RCM, it is important to consider both the reactivity of the catalyst itself and the structures of the substrate and product. The rate of olefin metathesis is strongly affected by the substitution pattern of the alkene(s), with more substituted alkenes reacting more slowly. Steric hindrance near the reacting alkenes may have an effect similar to alkene substitution.
Cross metathesis reaction between two different olefins with similar reactivities can yield an equilibrium distribution of metathesis products. In the example below where equivalent ratios of olefin-R1 and olefin-R2 are metathesized to yield an equilibrium distribution of 6 metathesis products, 25% each of the homodimers R1-R1 and R2-R2 and 50% of the crossed product R1-R2, and each having cis and trans isomers.
Secondary metathesis reactions (controlled by catalyst choice and reaction conditions) also affect the product distribution. Recoordination of an alkene on the growing polymer chain with the catalyst can lead to cyclic oligomers through a ring-closing metathesis reaction (“backbiting”). Chain transfer (cross metathesis) between a growing polymer unit and an adjacent polymer alkene also leads to broadened molecular weights. Chain transfer can also be used to improve processability of the resulting polymer – addition of an acyclic olefin (chain-transfer agent) can limit chain molecular weights and introduce terminal functional groups.
Careful balance of catalyst, monomer, and other factors can offer excellent control of the polymer structure. In terms of homogeneous catalysts, most tungsten and molybdenum catalysts (Schrock catalysts) have rapid initiation rates and can produce “living” polymerizations with excellent control of polydispersity and chain tacticity, but the low functional group tolerance limits the monomers available. Ruthenium metathesis catalysts (Grubbs catalysts) tend to have slower initiation rates, often leading to higher polydispersities, but their air stability and greater tolerance for functional groups makes them “user friendly” and enables use of a wide range of functional monomers and additives.
Cross metathesis (CM) is an attractive alternative to other olefination methods due to the large variety of commercially available olefin starting materials and to the high functional group tolerance of the ruthenium metathesis catalysts. Depending on the types of olefins involved in the metathesis reaction, cross metathesis reactions generally fall into one of three types:
Ring-opening metathesis polymerization (ROMP) uses metathesis catalysts to generate polymers from cyclic olefins. ROMP is most effective on strained cyclic olefins, because the relief of ring strain is a major driving force for the reaction – cyclooctene and norbornenes are excellent monomers for ROMP, but cyclohexene is very reluctant to form any significant amount of polymer. Norbornenes are favorite monomers for ROMP, as a wide range of monomer functionalities are easily available through Diels-Alder reactions.
Most ring-closing metathesis reactions are carried out at fairly high dilution of the substrate (10 - 50 mM) with catalyst loadings of 5 - 10 mol % and at slightly elevated temperatures (25 - 110 ºC). Molybdenum catalyst 1 exhibits extreme sensitivity to air and water such that use of a glovebox is ideal. On the other hand, ruthenium catalysts are more stable in air and Schlenck tubes are typically used. Standard workup involves concentration of the reaction mixture, aqueous extraction, and purification via silica gel chromatography, recrystallization, or distillation. Because the standard procedure can leave behind traces of ruthenium, more rigorous workup procedures have been developed that use additional ligands, supercritical fluids, and mesoporous silicates to decrease ruthenium concentrations to extremely low levels.
Because of the synthetic importance of the alkene functional group, a variety of olefination methods were developed prior to the advent of olefin metathesis. While some of these have intramolecular, ring-closing variants, others have not been applied generally for the synthesis of cyclic alkenes. Cross-coupling reactions of alkenyl halides or alkenyl nucleophiles, which establish carbon-carbon single bonds adjacent to C-C double bonds, have also emerged as complimentary alternatives to olefination reactions.
Unsubstituted α,β-unsaturated esters can likewise coordinate to the metal center and prevent reaction. Including a Lewis acid such as titanium(IV) isopropoxide in the reaction mixture does not interfere with metathesis and prevents coordination to the catalytic metal, enabling reactions of acrylates (Eq. 17).
Unsaturated lactams are a biochemically important class of heterocycles that can be prepared via ring-closing metathesis. Catalyst 1 is effective in the preparation of five- or six-membered lactams, but crotonamides must be used as unsubstituted α,β-unsaturated amides coordinate to molybdenum, preventing reaction (Eq. 16).
Cyclic boronates are formed in cross-metathesis reactions of allylic alcohols and allylboron reagents. Treatment with hydrogen peroxide and sodium hydroxide yields stereodefined allylic diols (Eq. 15).