Manganese is superior to silver and cerium at catalysing pharma building blocks for drug design and manufacture.
Rice chemist Julian West and graduate student Yen-Chu Lu have discovered that an Earth-abundant salt of manganese can further simplify the process of synthesising fluoroketones which are precursor molecules for drug design and manufacture. By attaching negatively charged fluorine atoms to ketones, the functional groups can be directed to undergo desired reactions when used in anti-cancer drugs and other compounds. In a previous study, West noted that replacing hydrogen atoms with fluorines “is like armour plating at that position” and helps drugs last longer in the body.
Up until recently, the complex method of forming fluoroketones involves the use of expensive silver as catalysts. Fortunately, the West lab found a way to replace silver with a recyclable cerium-based compound that can efficiently promote reactions. However, reusing the compound requires difficult reoxidation, hence the need for a better catalyst.
Now, Lu and West noticed that manganese possesses several advantages over cerium, such as low cost and easy availability. This sparked their interest in exploring manganese as a next-level catalyst and so, conducted experiments to test their hypothesis. The results revealed that the reagent used in their study, known as Selectfluor, could re-oxidise the manganese sufficiently for multiple reactions and allowed for high reaction efficiencies.
“The amount of product we got with cerium was good, but for it to work, we had to use as much cerium as starting material,” said West. “With manganese, we required less than a 10th as much catalyst – and more importantly, it just works better. We would rather use a trace amount of catalyst to save on material costs and to simplify purification.”
The only weakness found in manganese during their experiments was that manganese was much slower. As opposed to the half-hour time needed by cerium to synthesise a batch of molecules, manganese-enabled reactions required several hours to produce the same amount. However, considering the relative cut in costs, even this limitation should prove to be no obstacle.
“In our view, that’s a fair tradeoff, because you’re reducing the amount of reagents you need to add and getting more of the compound that you want,” West said.
In addition, when the researchers performed a direct comparison between the catalytic performances of silver and manganese, they found that manganese was able to deliver more product molecules with half the amount of catalyst. Given these results, the team believes that this Earth-abundant element could provide a more robust, simple, and scalable approach to catalyse the fluorination of ketones, bringing us one step closer to achieving state-of-the-art catalysis.
Source: Lu, Y.-C., & West, J. G. (2021). C–C Bond Fluorination via Manganese Catalysis. American Chemical Society Catalysis, 11, 12721-12728.