Developments on Metathesis for Site-selective Protein Modification

Lin, Y. A.; Chalker, J. M.; Davis, B. A. Olefin Metathesis for Site-Selective Protein Modification ChemBioChem, 2009, 10, 959-969. Site-selective protein modification poses a Catch-22. If the chemistry you want to use can modify natural amino acids, you have to worry about the selectivity of your desired site of modification vs. other sites. If the […]

Choosing the Best Metathesis Catalyst for a Reaction

I decide to run an organometallic coupling reaction. I go to the literature to see what conditions people have used for similar transformations, and I’m overwhelmed. Every paper I see uses a different combination of precatalyst, ligand, additive(s), and solvent.  Which is best? Are they different for a reason, or is it a matter of […]

Solvent-Free Homogeneous Metathesis

One of the misconceptions in the academic literature is that the well-defined (Schrock and Grubbs) olefin metathesis catalysts need to be used in dilute solutions. This isn’t surprising given the way in which these catalysts were developed, but it’s a misconception that has taken a while to debunk. There have been examples in the literature […]

Ligand Electronics in Metathesis Catalysts

Getty, K.; Delgado-Jaime, M. U.; Kennepohl, P. An electronic rationale for observed initiation rates in ruthenium-mediated olefin metathesis: charge donation in phosphine and N-heterocyclic carbene ligands. J. Am. Chem. Soc. 2007, 129, 15774-15776. The simple substitution of N-heterocyclic carbene (NHC) ligands for phosphines in ruthenium olefin metathesis catalysts resulted in a significant increase in catalyst […]

Unhindered Hoveyda-Grubbs Catalyst

ortho-Tolyl Hoveyda-Grubbs Catalyst1 –  CAS#: [927429-61-6] –  FW: 570.62 –  Color: Green –  Initiation temperature: >20 °C          Process Strengths Weaknesses CM -CM of hindered terminal olefins2 -slower than Hoveyda-Grubbs 2nd gen catalyst in some instances -unfavorable for synthesis of trisubstituted olefins RCM -Tetra-substituted olefins -Hindered substrates     ­This Hoveyda-Grubbs analog has ortho-tolyl substituents on the N-heterocyclic carbene […]

Novel Ligands for Challenging RCM Reactions

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 […]

Notable Advancement Towards Efficient Ethenolysis Reactions

Anderson, D. R.; Ung, T.; Mkrtumyan, G.; Bertrand, G.; Grubbs, R. H.; Schrodi, Y. A Kinetic Selectivity of Olefin Metathesis Catalysts Bearing Cyclic (Alkyl)(Amino)Carbenes Organometallics, 2008, 27, 563-566. Ethenolysis, the efficient cross metathesis of an internal olefin with ethylene while avoiding non-productive self-metathesis—the cross metathesis of the internal olefin with itself—remains a significant challenge for […]

Solvent Considerations in Ruthenium Catalyzed Metathesis Reactions

I dare you to find an issue of Organic Letters in the past five years that doesn’t have an example of ruthenium-catalyzed olefin ring closing metathesis. Chances are that most of the examples are run in CH2Cl2 at a concentration of <0.1 M. And they probably work pretty well. If you ask any of the […]

Macrocycles in Medicine: Total Synthesis of the Ipomoeassins

It’s not surprising that a natural product with promising therapeutic activities will quickly become a target for total synthesis by academics and medicinal chemists alike. Furthermore, it’s no longer surprising that if the natural product in question contains a macrocycle, it will be made by ring closing olefin metathesis (RCM). I recently came across the […]