Toggle

Pharmaceuticals



Alkene metathesis: Efficiently synthesizing carbon–carbon bonds

By Christophe Le Ret, Global Marketing Director at Umicore - 02/05/2018

Alkene metathesis is a widely used chemical reaction that has permeated a variety of chemical sectors from pharmaceutical to agricultural chemicals. We sat down with Christophe Le Ret, Global Marketing Director at Umicore, to talk about Umicore’s metathesis offering following the acquisition of Materia’s Catalyst intellectual property and business portfolio.
 
What is metathesis and why is it so important?
Metathesis, which is also known as olefin or alkene metathesis, is a chemical reaction that can join together two components to build more complex chemicals. It is mediated through the use of catalysts, which aid in the formation of new carbon-carbon bonds through the reaction of two alkenes. Although its activity was first established during the late 20th century, it really achieved widespread recognition in 2005 when the researchers Richard Schrock, Yves Chauvin and Robert Grubbs were jointly awarded the Nobel Prize in Chemistry.
 
It is not surprising that alkene metathesis has received such recognition. For any chemical reaction, an organic chemist would be able to provide several plausible alternatives that could lead to the same products. But what sets metathesis reactions apart is the threefold advantages: they are more selective, more efficient and more versatile. Selective, since only carbon-carbon double bonds are affected, other functional groups remain unmodified. Efficient, because metathesis provides the possibility of circumventing lengthy or condition-intense synthesis routes. Versatile, due to the impressive variety of substrates that these catalysts support.
 
Which industries benefit from adopting metathesis and where has it been done so most successfully?
The creation of carbon-carbon bonds is a fundamental chemical reaction underpinning many chemistry-enabled industries. The advantages metathesis brings to chemical reactions means it can and has been applied to such a wide variety of applications. Combining the catalyst’s high efficiency and selectivity, means metathesis could potentially revolutionize its applied chemical sector. There have already been a series of applications that have benefited from metathesis catalysts. These include developing complex pharmaceutical molecules, which demand precise control over stereochemistry and functional groups. Or transforming non-edible seed oils into valuable oleochemicals. Or even in developing selective agrochemicals such as pheromones.
 
The possibilities are endless! Specifically looking at the chemical industry, metathesis has been used successfully in many manufacturing industries. These include, but are by no means limited to, the manufacture of active molecules for Hepatitis C virus treatment1 or the creation of functional polymers with temperature, corrosion or abrasion resistance properties.
 
What is Umicore doing in metathesis sector?
Umicore has been active in providing metathesis catalysts for more than a decade. We have identified and built upon an independent portfolio of intellectual property and metathesis catalysts that can be applied to the industrial scales that our customers want. We have a great deal of expertise in the field and are continuing to grow our extensive academic and industrial collaborations.
 
Before his Nobel Prize award, Robert Grubbs founded Materia – the company which commercialized what is now widely known as the ‘Grubbs metathesis catalyst range’. These catalysts are considered to be world leading in terms of providing high reaction activity and selectivity to various applications. In 2017, Umicore acquired the Materia metathesis IP and business and we have begun integrating both these catalyst ranges into one broad industrial offering. We are now able to offer the best of two companies: the most secure access to metathesis technology, an extensive portfolio of catalysts provided at the industrial scale, together with the long-term commitment of Umicore, a global company.
 
How do you see the sector evolving?
While metathesis has already been readily applied to a vast majority of sectors, I feel its true value remains to be unleashed.  Metathesis has the potential to provide a sustainable and green approach to reaction synthesis. Being able to shorten complex reaction steps can improve productivity, reduce waste and energy consumption, use less solvent, or even reduce a reaction’s CO2 emission footprint. Related to the sustainability component, metathesis reactions are increasingly being sought as alternatives to previously difficult reactions or processes. One example, that has just been published by researchers in Polymer Chemistry, used Umicore metathesis catalysts to facilitate the previously difficult process of recycling natural rubber.2
 
How is Umicore strategically positioning itself to advance this sector?
We feel that Umicore brings the collective offerings of metathesis catalysts with advanced homogeneous catalysts. Now we are working to ensure that we have the necessary manufacturing capability to offer our metathesis catalysts to our customers worldwide at the scales they need. By further advancing our academic and industrial partner collaborations, reaction bottlenecks can be overcome and the next-generation of materials created. We are eager to co-create future ground-breaking chemistry.


References
1. European Patent WO 2007/014918.
2. Slugovc C et al. Polym Chem 2018;9:1763-6.