The ring closing metathesis of diethyl diallylmalonate using available Ru catalysts has become a prosaic standard for classifying catalyst activity. However, the substitution of hydrogen for larger functional groups (e.g. methyl) at the allylic 2-position can have a dramatic effect on the efficiency of the reaction. The efficiency of ring closing metathesis (RCM) of substituted malonates, for example, follows this general rule-of-thumb:
In 2007, the Grubbs group introduced a simple idea to solve this problem: less bulky ligands may accommodate more bulky substrates.1 Particularly interesting is the strong influence of ortho-substitution (or lack thereof) of the N-heterocyclic carbene (NHC) aryl rings. The substitution of the methyl groups in the mesityl NHC catalysts (such as the Hoveyda-Grubbs version 1) for hydrogen (2 and 3), or fluorine (4) provides a new class of catalysts. These new catalysts give higher RCM yields with a number of tetrasubstituted olefin substrates (>95% in some examples) over traditional known catalysts.
Employing a similar strategy, a collaborative effort between the Grubbs group and Materia has resulted in a different NHC-bearing Grubbs catalyst for these difficult RCM transformations (catalysts shown below).2 The advantage to the ortho-tolyl flanked NHC is not in reactivity but in ease of synthesis and isolation both of the ligand and the final catalyst. Interestingly, the crystal structure of the Hoveyda-Grubbs variant (6) adopted a cis-orientation of the N-tolyl groups—counter-intuitive to natural symmetry.
One has to be eager to see on what other difficult metathesis reactions these catalysts may be effective: time will tell.
1 Berlin, J. M.; Campbell, K.; Ritter, T.; Funk, T. W.; Chlenov, A.; Grubbs, R. H. Organic Letters, 2007, 9, 1339.
2 Stewart, I. C.; Ung, T.; Pletnev, A. A.; Berlin, J. M.; Grubbs, R. H.; Schrodi, Y. Highly Efficient Catalysts for the Formation of Tetrasubstituted Olefins via Ring-Closing Metathesis Organic Letters, 2007, 9, 1589.