When reviewing the scientific literature related to ruthenium-catalyzed olefin metathesis, it is common place to observe the use of relatively high catalyst loadings. Typically, catalyst loadings employed are in the range of 1-5 mol% or greater depending on the specific application. An immediate question arises: Are these types of catalyst loadings required…or is it a misconception that these processes require catalyst loadings at this level? The answer is not completely cut and dry, as some specific applications do require these levels of catalyst loadings, but to quote from a 2002 report by Mol and Dinger titled “High Turnover Numbers with Ruthenium-Based Metathesis Catalysts” published in Advanced Synthesis and Catalysis1:
“The results reported here strongly imply that the ruthenium-based catalysts are, in all likelihood, often being used well below their maximum capabilities in many metathesis reactions…”
Mol’s report examines maximizing the effective turnover number (TON) of three different olefin metathesis reactions: (1) the self-metathesis of an ?-olefin (1-octene), (2) the self-metathesis of internal olefins (trans-4-decene or methyl oleate), and (3) the ring-closing metathesis of diethyl diallylmalonate. This is a nice choice of reactions and substrates to study as it examines processes when ethylene will (1 & 3) and will not (2) be generated as a by-product, as ethylene is known to enhance catalyst decomposition.2
In order to push the limits of the various catalysts tested, they employed extremely low catalyst loadings. In some cases, loadings were < 1 part per million (ppm) or 0.0001 mol%. The overall conversions of the various reactions never reached 100%; however, that was not the goal of this study. Rather it showed that Ru-catalyzed olefin metathesis was operational at catalyst loadings that were orders of magnitude lower than generally reported and supplied effective TON in some cases over 600,000. It is also noteworthy that the reactions were run without the need of a solvent, highlighting the “green” capability of this technology.
The idea of examining low loading Ru-catalyzed olefin metathesis processes was also recently reported in a collaborative publication between the Grubbs group and Caltech’s Center for Catalysis and Chemical Synthesis.3 The main focus of this paper was to examine the effect of backbone substitution of the NHC ligand of various 2nd generation Grubbs-Hoveyda catalysts, and how this added steric bulk on the NHC backbone would affect catalyst efficiency.
The study made use of the Symyx™ robotic technology, and examined ring closing metathesis reactions of various substituted diethyl diallylmalonates (di-, tri-, tetra-substituted RCM reactions). Employing the 2nd generation Grubbs-Hoveyda catalyst, the ring closing of diethyl diallylmalonate was quantitative using as little as 25 ppm (0.0025 mol%). In order to observe subtle differences between the parent catalyst and the various backbone substituted species, even lower catalyst loading experiments were performed (15 ppm). These results indicate that increasing the sterics of the NHC backbone provides some added stability to the catalyst, presumably by limiting catalyst decomposition via a C-H activation pathway of the N-aryl substituent.
So the next time you go and reach for some Grubbs catalyst, rethink that 5 mol% catalyst loading. You very well may be able to get away with significantly less, which will undoubtedly bring a smile to the face of your supervisor!
1 Dinger, M. B.; Mol, J. C. “High Turnover Numbers with Ruthenium-Based Metathesis Catalysts.” Adv. Synth. Catal. 2002, 344, 671-677.
2 Ulman, M.; Grubbs, R. H. “Ruthenium Carbene-Based Olefin Metathesis Initiators: Catalyst Decomposition and Longevity.” J. Org. Chem. 1999, 64, 7202-7207.
3 Kuhn, K. M.; Bourg, J. B.; Chung, C. K.; Virgil, S. C.; Grubbs, R. H. “Effects of NHC-Backbone Substitution on Efficiency in Ruthenium-Based Olefin Metathesis.” J. Am. Chem. Soc. 2009, 131, 5313-5320.