Reactions that form bonds between carbon atoms are among the most important in the chemical industry’s toolkit: they are essential for transforming small, simple building block molecules into the complex structures of compounds found in nature and of pharmaceuticals. However, they often require catalysts containing costly precious metals like platinum or palladium, or transforming the starting material into a more reactive form by adding halogen atoms, that can lead to polluting byproducts.
The nickel compound (blue) with phosphorus (orange) attached by two bonds promotes the elimination of the two red carbon groups in this aromatic intermediate
Chemists at the King Abdullah University of Science and Technology (KAUST) have now developed a synthetic approach that forms a carbon-carbon bond between usually-inactive esters and boron-containing hydrocarbons, using nickel as a catalyst.
Nickel is a very common and relatively low cost catalyst used for many industrial reactions with organic molecules. The reactions the team has targeted are called cross-coupling reactions, in which two molecules with reactive groups are made to join together, eliminating the reactive groups and forming a bond between the carbon atoms to which the groups were originally attached.
Generally in industry, cross-coupling reactions are performed with aromatic compounds that contain iodine or bromine atoms, coupling with molecules containing boron. The catalyst for this contains palladium, and the elimination that accompanies the cross coupling generates boron-halogen waste that is corrosive. The KAUST team replace the halide aromatic with an ester, normally inactive in this type of reaction because palladium catalysts cannot eliminate carbon monoxide.
The team, led by Magnus Rueping and Luigi Cavallo, developed a nickel catalyst containing a phosphorus group attached the metal. If this group is attached to the nickel by a single chemical bond, it reacts and aromatic ester and an alkyl borane to produce a ketone product. If the group is attached by a two bonds, it produced an alkyl arene. “These experimental results were not easy to explain,” said Rueping. “Therefore, we used computational studies to help us understand the molecular mechanism and reaction pathway.”
In the Journal of the American Chemical Society, the team explains that in testing the technique, they generated intermediates that could be used to produce potential next-generation antidepressants and an antagonist to suppress cell adhesion proteins called integrins. “These results were exciting as most researchers would not have expected that this unusual site-selective reaction could be achieved by simply changing the ligands of the metal complex,” said Rueping.
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