Keitz, B. K.; Grubbs, R. H. “Probing the Origin of Degenerate Metathesis Selectivity via Characterization and Dynamics of Ruthenacyclobutanes Containing Variable NHCs.” J. Am. Chem. Soc., 2011, 133 (40), 16277-16284.
Back in September of 2010, ATM’s very own Andy Nickel wrote a post on a publication from the Grubbs group describing non-productive events during ring-closing metathesis reactions with Grubbs-type catalysts. The results showed that catalysts containing unsymmetrical alkyl-aryl NHCs lead to more non-productive or degenerate metathesis events. Perhaps in a challenge to the olefin-metathesis community, Andy stated:
“Nailing down why this is the case may not only help in the next round of catalyst design, but could also provide insight into the mechanism of catalyst-olefin coordination.”
It appears that B. K. Keitz and Prof. Grubbs accepted Andy’s challenge and commenced studies to elucidate the reason for this phenomenon employing new Piers-type phosphonium alkylidenes (Figure 1) as precursors to study ruthenacyclobutanes via low-temperature NMR spectroscopy.
Figure 1. New Piers-type phosphonium alkylidenes employed to probe the origin of degenerate events during RCM reactions.
In a procedure adopted from the Piers’ laboratory2, Ru-complex 1 was reacted with cyclopentene 4 and 1 equivalent of ethylene at -78 °C, which resulted in the formation of ruthenacyclobutane 5 in 29% yield. This was also accompanied by 21% of the unsubstituted ethylene-only ruthenacycle 6. (Scheme 1) Disappointingly, under the same conditions, when complexes 2 and 3 were employed, the ethylene-only ruthenacyclobutanes were the only ruthenacyles observed.
Low temperature NMR experiments were performed to study chemical exchange within ruthenacycle 5; however, under the conditions tested there was no evidence of exchange processes occurring. This is in stark contrast to the parent H2IMes derived rutheacyclobutane which undergoes both intra- and intermolecular exchange processes.
Studies were then undertaken to determine the kinetics for the transformation of 5 to 6 via loss of cyclopentene 4 under an ethylene atmosphere (Scheme 2). These experiments were complicated by the fact that under all reaction conditions, an unknown ruthenacycle was generated that made the kinetic analysis rather difficult. However, through a clever design of experiments and some computer modeling, kinetic parameters were determined, and it was found that rate constant (k1) for the conversion of 5 to 6 was 2 orders of magnitude smaller than observed with the parent H2IMes ruthenacycle. From subsequent Eyring plot analysis, this corresponded to an approximate 2 kcal/mol higher energy barrier for this transformation compared again to the H2IMes system. The authors caution of drawing too many conclusions from the data due to the specialized conditions employed for these studies; however, this increased energy barrier can help explain why catalysts comprising unsymmetrical alkyl-aryl NHC’s are generally less effective catalysts and why more degenerate events occur versus productive ring-closing when these mixed alkyl-aryl type catalysts are utilized.
Finally, in a personal discussion with B. K. Keitz concerning this research project, I asked him what his motivation was for performing this work:
“Our initial goal was to elucidate the entire productive RCM potential energy surface in a manner similar to Piers’ work, but using different catalysts. That was a little overambitious, but we did learn that the structure of the NHC has a profound effect on very fundamental metathesis reactions.”
Indeed, this is an important discovery and shows how what I would deem a very minor change in catalyst structure can have a large impact on the outcome of a metathesis reaction. With the ever-expanding use of olefin metathesis on an industrial scale, it’s clear that fundamental studies such as this will continue to be instrumental for the further development of the technology.
1 Stewart, I. C.; Keitz, B. K.; Kuhn, K. M.; Thomas, R. M.; Grubbs, R. H. “Nonproductive Events in Ring-Closing Metathesis Using Ruthenium Catalysts.” J. Am. Chem. Soc., 2010, 8534-8535.
2 (a) van der Eide, E. F.; Romero, P. E.; Piers, W. E. “Generation and Spectroscopic Characterization of Ruthenacyclobutane and Ruthenium Olefin Carbene Intermediates Relevant to Ring Closing Metathesis Catalysis.” J. Am. Chem. Soc., 2008, 130, 4485-4491. (b) van der Eide, E. F.; Piers, W. E. “Mechanistic insights into the ruthenium-catalysed diene ring-closing metathesis reaction.” Nat. Chem., 2010, 2, 571-576.