Cross-Metathesis Powered by Apeiron Synthesis Catalyst
What is Cross-Metathesis Reaction
Cross metathesis is one of the types of olefin metathesis reactions in which two different alkenes react in the presence of a catalyst. Typically, it occurs between two terminal olefins, producing the desired product along with gaseous ethylene. [Cross Metathesis] The release of ethylene from the reaction mixture drives the metathesis reaction to completion. However, internal olefins can also be used in cross metathesis, for example in the so-called ethenolysis, where unsaturated fatty acid esters react with pressurized ethylene to form two new terminal olefins.
Challenges of cross-metathesis reaction
Selectivity of cross-metathesis reaction
The main obstacle in a cross-metathesis reaction is its selectivity. First, cross-metathesis competes with the self-metathesis reaction. In short, each of the starting olefins may react with itself rather than with the other olefin. As a result, instead of the desired cross-product, two other olefins known as homodimerization products can also be formed. The second problem concerns the geometry of the newly formed double bonds, which can be either E or Z (often referred to as trans or cis, respectively). This doubles the number of possible metathesis products.
Cross-Metathesis vs isomerization
Another challenge in running an efficient cross-metathesis reaction is avoiding isomerization and the formation of secondary metathesis side products. This is especially problematic when using the standard first- and second-generation ruthenium catalysts originally developed by Nobel Prize winner Prof. Grubbs and further modified by Prof. Hoveyda. The reason behind it is decomposition of these compounds with formation of ruthenium hydride species (Ru-H) that catalyzed olefin isomerization and leads to wide range of products. Of note is that the decomposition of this catalyst is even more significant when olefins containing carboxylic (–COOH) or hydroxy (–OH) groups are used as substrates.
Apeiron Synthesis solution for clean cross-metathesis
Catalyst designed for efficient metathesis
To address these issues, Aperion Synthesis developed catalysts tailored for use in cross-metathesis reactions. We balanced the steric profile of the carbene ligands and the electronic parameters of the ruthenium center to deliver the most efficient and selective metathesis outcomes possible. Among our portfolio, catalysts containing iodo anions (nitro-Grela-I₂ SIPr) and those with CAAC ligands (UltraNitroCat, UltraCat, and SlashCat) stand out. They are able to prevent side isomerization reactions and provide clean cross-metathesis products, even for challenging olefinic substrates containing carboxylic acid or hydroxy groups.
Overcoming challenging cross-metathesis with Aperion Synthesis catalysts
The Problem
You do not need to trust us alone on the promised efficiency of our catalysts. You can check this yourself in a recent JACS publication from the Renata Lab from Rice University (Texas, USA) describing a concise synthesis of fostriecin. (J. Am. Chem. Soc. 2025, 147, 29, 25454–25461) [https://pubs.acs.org/doi/10.1021/jacs.5c05269 ]. It features a challenging cross-metathesis step between two building blocks heavily decorated with functional groups, including a free alcohol moiety. To overcome this problem, researchers thoroughly investigated many reaction conditions. However, popular commercial catalysts, as well as common metathesis tricks such as running the reaction under an ethylene atmosphere, provided yields below 20%.
Catalyst Optimization
Notably, among the 16 catalysts tested, Apeiron’s Nitro-Grela-I₂ SIPr, used under constant nitrogen sparging, delivered the best results. It achieved a 48% yield on a 71 mg scale using three consecutive catalyst additions (3 × 10%) (see ESI page 33 for details). Of note is that this transformation was scaled up to gram scale while maintaining an impressive 41% isolated yield. This allowed for the preparation of sufficient substrate for further enzymatic transformation and demonstrated that even the most challenging cross-metathesis is achievable with the help of an Aperion Synthesis catalyst.
Reach out to us with your cross-metathesis problems
If you need to run a cross-metathesis reaction, contact us directly. Our catalysts deliver clean reactions and facilitate easy product separation, from challenging small-scale setups in total synthesis to demanding industrial-scale olefin metathesis processes.