Christophe Le Ret , global marketing director at Umicore , introduces new ligand catalytic systems that improve reaction efficiency
PHARMACEUTICALS
Advances in palladium catalyst technology for cross-coupling reactions
Christophe Le Ret , global marketing director at Umicore , introduces new ligand catalytic systems that improve reaction efficiency
Few reactions are as essential to the modern chemical industry as cross-coupling . As a synthetic tool , it provides a reliable and flexible route to a plethora of organic compounds . This is especially true for the pharmaceuticals industry , where crosscoupling reactions have made an impressive impact across drug discovery , development and manufacturing , facilitating the production of both key intermediates and APIs at scale .
The prevalence of cross-coupling reactions within the pharmaceutical industry is due to the need for versatile , reliable and efficient tools for organic synthesis . However , without catalysts , their impact within industrial settings would be limited .
Palladium catalysts , such as those used in Suzuki couplings and Buchwald- Hartwig reactions , play a pivotal role in pharmaceutical manufacturing , enabling synthesis at much lower temperatures and pressures . This not only reduces energy consumption , but also removes the need for specialist equipment that can withstand harsh reaction conditions and widens the scope of cross-coupling to include less stable functional groups .
Cross-coupling catalysts can also improve the economic viability of chemical synthesis . By shortening the required synthesis pathway , less energy and solvent are required thereby reducing waste and cost . Platinum group metal catalysts also improve the
selectivity of many reactions , helping to minimise the formation of side products . This is particularly important in later steps of synthesis , where highcost waste can significantly impact process feasibility for industry .
Although palladium catalysts are well-established and effective at catalysing cross-coupling reactions , scientists still face some further challenges . With an increasing focus on greener industrial processes , they are continuing to develop new catalysts , to improve efficiency and discover the untapped potential for further synthetic opportunities .
Figure 1 – Umicore ’ s closed-loop approach
Current challenges of cross-coupling catalysis
Over the last 70 years , our understanding of cross-coupling has grown , with scientists adapting the mechanism to work for a wide range of reactions . As such , a wide variety of palladium-based catalysts are available today . However , it is not always obvious or easy to select the correct catalyst for a specific reaction .
Another important consideration to make when choosing palladium catalysts is the downstream processing required to separate the catalyst from the final product , which demands additional manufacturing steps and can result in higher costs . Under current legislation , the residual metal must be < 10 ppm . This is especially important in pharmaceutical production to ensure patient safety .
With an increasing focus on the environmental impact of crosscoupling reactions , chemists are faced with the challenge of synthesising more complex targets in fewer steps and minimising the use of scarce resources such as precious metals such as palladium , as well as reducing energy consumption and waste .
Overcoming the challenges
Pharmaceutical development is a multi-faceted process , requiring strong collaboration throughout the pipeline to co-create innovative and costeffective solutions . A good catalyst supplier will work collaboratively to advise on palladium catalyst selection , considering both activity and selectivity for maximised yield , as well as optimised loading .
Downstream processing and catalyst separation is important for ensuring the quality of the finished product . Further , this step provides processors with an opportunity to consider a circular and more sustainable closed-loop
SEP / OCT 2023 SPECCHEMONLINE . COM
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