Solvent effects on Grubbs’ pre-catalyst initiation rates

Abstract

Initiation rates for Grubbs and Grubbs-Hoveyda second generation pre-catalysts have been measured accurately in a range of solvents. Solvatochromic fitting reveals different dependencies on key solvent parameters for the two pre-catalysts, consistent with different mechanisms by which the Grubbs and Grubbs-Hoveyda pre-catalysts initiate.The alkene metathesis reaction is now a standard transformation in academic laboratories, and has been applied to the synthesis of a wide range of natural 1,2 and unnatural products, 3 fine chemicals, 4,5 and polymers. 6 The availability of robust and commercially available pre-catalysts such as 1 and 2 has enabled the rapid growth of alkene metathesis in the synthetic repertoire. Although transition metal catalysts have enabled many efficient large scale processes to be carried out in industry, 5,7 the application of alkene metathesis to industrial processes has been more limited. 7,8For industrial-scale syntheses, the implications of the reaction solvent must be considered carefully; these include costs of purchase, purification, drying, recycling and/or disposal, and the health and safety implications of transport, transfer, storage and use. There are also sustainability issues raised by projected uncertainty of supply and by legislative changes. 9These considerations have led major pharmaceutical companies to encourage their discovery chemists to anticipate scaleup in their laboratory practice and reaction design, 9 replacing solvents which are problematic for scale-up, wherever practicable, and at the earliest stage possible.The classical set of solvents for RCM is dichloromethane (DCM), 1,2-dichloroethane (DCE), benzene and toluene; of these, toluene raises the fewest issues while the other three are problematic. It has been reported that other solvents, including acetic acid, 10 methyl tert-butyl ether (MTBE), 11 dimethyl carbonate 12 and hexafluorobenzene (HFB) 13,14 are particularly effective for RCM, mostly on the basis of reaction yields or qualitative comparisons of kinetic profiles, so the precise locus of any solvent effect is not clear. If solvent effects on reaction chemistry could be revealed in detail, solvents could be selected for scale-up on the basis of both chemical efficacy and sustainability, and from a strong experimental starting point. We therefore sought to reveal the effects of solvent on the initiation rates of 1 and 2, which are currently the most popular metathesis pre-catalysts.Initiation rates were measured for 1 and 2 by reaction of the pre-catalyst with ethyl vinyl ether 15 in a number of solvents.Initiation rates for 1 were obtained following the method of Sanford et al.; 16 the rate-determining step in this reaction is known to be dissociation of the phosphane ligand. The integral versus time data was processed using a simple first order treatment (eqn (1)).For solvents where deuterated analogues were unavailable commercially, 10% v/v chloroform-d was added to enable a deuterium lock.Initiation rates for pre-catalyst 1 cover only a ca. fou...

Ring opening metathesis polymerization of triazole‐bearing cyclobutenes: Diblock copolymer synthesis and evaluation of the effect of side group size on polymerization kinetics

“…These data showed that toluene and THF produced polymers with lower PDI (PDI < 1.2) and resulted in higher conversions (>82% based on GPC) than chloroform. This was primarily attributed to differences in the initiation rates as has been reported previously by Ashworth et al and Sanford et al, where initiation rates of Grubbs' catalysts are higher in THF and toluene than in chloroform. The 1 H‐NMR results from these experiments were consistent with the previously published trends and indicated that G2 reached equilibrium between the inactive and active catalyst species 2–4 times faster in d 8 ‐THF than in CDCl 3 (see Supporting Information Figs.…”

“…mPEGCB exhibited the smallest k 1 value compared to the other two monomers. This was attributed to the presence of the oxygen atoms from the PEG side chains, which can affect the overall polarizability of the solvent and thus change the ligand dissociation rate constants . The mPEGCB monomer showed the largest k 2 / k −1 value (4.03) indicating that its reaction intermediate will favor coordination to the cycloolefins to open the cyclobutene ring, rather than recoordination with PCy 3 to deactivate the catalyst.…”

In a Quest for Selectivity Paired with Activity: A Ruthenium Olefin Metathesis Catalyst Bearing an Unsymmetrical Phenanthrene‐Based N‐Heterocyclic Carbene

“…In contrast, almost quantitative conversion is achieved in the first 10 minutes of the reaction (Figure ). This change of “reactivity” can be explained not only by temperature increase giving more energy to transition states, but also by an aromatic solvent effect, which probably can destabilize substrate–catalyst complex …”

Wholly biomass derivable sustainable polymers by ring-opening metathesis polymerisation of monomers obtained from furfuryl alcohol and itaconic anhydride

“…Thus, the decrease in concentration of catalyst 10 was found to be first order ( Figure 10) and allowed the rate of initiation of the polymerisation of monomer 8a (k i8a ) to be determined as 1.76 x 10 -4 s -1 at 298 K. This value compares well with the value of 1.4 x 10 -4 s -1 previously determined for initiation of other metathesis reactions in dichloromethane at 298 K using catalyst 10. 37,38 This is to be expected as the rate determining step of metathesis initiation by complex 10 is known to be dissociation of its tricyclohexylphosphine ligand, a process which is independent of the alkene to be metathesised. 39 Figure 10: First order kinetic plots for the determination of ki8a (red), kp8a (blue) and kp8b (green).…”