Johns, A. M.; Ahmed, T.S.; Jackson, B.W.; Grubbs, R. H.; Pederson, R.L. “High Trans Kinetic Selectivity in Ruthenium-Based Olefin Cross-Metathesis through Stereoretention” Org. Lett. 2016 18 772-775 [DOI: 10.1021/acs.orglett.6b00031]
In recent years, effective Z-selective olefin metathesis has been achieved with Ru-, W-, and Mo based organometallic complexes. Kinetic E-selective metathesis, however, has remained challenging and alternative functional group tolerant methods for the synthesis of pure trans-olefins have been developed. In a recent joint publication with the Grubbs’ group, we detail our discovery of homogenous Ruthenium metathesis catalysts that preserve olefin stereochemistry.
Poor results in an internal screen of Z-selective catalysts prompted a more detailed investigation of dithiolate-ligated ruthenium complexes.[i] Surprisingly, exposure of asymmetric internal olefins with high stereopurity (Z or E) to catalyst 1 afforded an equilibrium mixture of symmetric and asymmetric olefins while retaining the stereochemistry of the starting material in good fidelity.
This transformation was successfully extended to the cross-metathesis of two internal olefins with the same stereochemistry and the cross-metathesis of a-olefins with internal olefins of defined stereochemistry. While all catalysts explored reacted more quickly with cis-olefins, a hypothesis explaining the origin of stereoretention led to structural refinements and improved catalysts.
Thanks to the Grubbs group for collaborating on this publication and we look forward to future advances in stereoretentive and E-selective olefin metathesis.
[i] (a) Khan, R. K. M.; Torker, S.; Hoveyda, A. H. J. Am. Chem. Soc. 2013, 135, 10258. (b) Koh, M. J.; Khan, R. K. M.; Torker, S.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2014, 53, 1968. (c) Koh, M. J.; Khan, R. K. M.; Torker, S.; Yu, M.; Mikus, M. S.; Hoveyda, A. H. Nature 2015, 517, 181.