Now, a research group from the Toyohashi University of Technology has described a new catalytic reaction to produce such molecules in isomerically pure form. As described in Nature Communications, they did this by using a catalyst which itself was chiral.
Lead author Kazutaka Shibatomi said: “We screened a diverse array of chiral catalysts, such as Lewis acid, Brønsted acid, and Lewis base catalysts. Finally, we found an amine that gave us organohalides with up to 98% enantiomeric purity – even though our starting material was a 50/50 mixture.”
The researchers were able to demonstrate the chiral production of a range of chlorinated products, called chloroketones. These compounds can be applied as building blocks for pharmaceuticals, as the chlorine can be easily substituted by another atom to make a new molecule. Using one of their reaction products, the research team demonstrated the synthesis of Cathinone, a central nervous system stimulant.
Shibatomi said: “The substitution proceeds in a simple, classic way. While chlorine leaves the molecule on one side, the incoming group approaches from the opposite side. The product's chirality just depends on the arrangement of these atoms – so if you begin with a pure enantiomer, you retain that purity.
“This could open up a whole class of compounds that were previously a major challenge to produce as pure enantiomers."
In their paper, the authors state that studies are ongoing into applying the method to enantioselective fluorination reactions, and to reactions with other types of aliphatic carboxylic acids bearing electron-withdrawing substituents.
Nature communications: http://doi.org/b9xz