Finding the Right Metathesis Catalyst

White D.E.; Stewart I.C.; Seashore-Ludlow B.A.; Grubbs R.H.; Stoltz B.M. A General Enantioselective Route to the Chamigrene Natural Product Family. Tetrahedron 2010, 66, 4648-86.

Finding the right metathesis catalyst for your reaction is easy – when the Grubbs group is next door…

The Stolz group recently published the syntheses of several members of the chamigrene family of natural products using ring closing metathesis (RCM) as one of the key steps. Chamigrenes are characterized by a spiro[5.5]undecane core bearing an all-carbon quaternary stereocenter at the spirocycle junction. Enantioselective allylation¹ was used to generate the desired enantiomer of the all-carbon quaternary stereocenter. RCM was employed to provide the tri- or tetrasubstituted olefin in the B-ring and the spirocyclic core. Some of the RCM reactions were pretty challenging generating fully substituted chlorinated olefins.² Attempts to generate the desired product with second generation Grubbs and Hoveyda catalysts led to modest conversions and produced large amounts of impurities. The bis-o-tolyl-catalyst, however, afforded rapid and very clean conversion and furnished the desired spirocycle in 97% isolated yield. Interestingly, small changes in the structure of the molecule led to complete loss of the efficiency of the reaction with the bis-o-tolyl-catalyst. Efforts to understand the unique reactivity of the intermediate diene are ongoing, but the take home message is clear. Don’t give up when the most common catalysts are not working; there are a lot of choices beyond the second generation Grubbs and Hoveyda.

¹ Stolz et al, J. Am. Chem. Soc. 2004, 126, 15044; Angew. Chem.,Int. Ed. 2005, 44, 1931.
² For an example of RCM to trisubstituted chloroolefins see: Weinreb et al, Org. Lett. 2003, 5, 2505.

Be Sociable, Share!

•