A research team at Ulsan National Institute of Science and Technology (UNIST) has developed a chemical synthesis method that, without expensive precious-metal catalysts, can selectively attach boron at desired positions within a molecule using only nickel. The result is seen as a breakthrough that can greatly increase the design freedom of drug candidates and functional organic molecules.
UNIST said on the 14th that a joint research team led by chemistry professors Hong Seong-yu and Jan-Uwe Rohde developed a nickel-catalyzed reaction that selectively attaches boron to terminal alkynes. The results were published in April in ACS Catalysis, an international journal in catalytic chemistry.
An alkyne is a molecule in which two carbons are connected by a triple bond, and attaching boron to it allows easy consolidation with other molecules, making it a key intermediate for synthesizing pharmaceuticals and electronic materials. The problem is that existing synthetic methods proceed only in the direction of placing boron on the terminal carbon of the molecule, which has severely limited the structures of intermediates that can be made.
The method developed by the team is distinguished by opening one bond of the alkyne triple bond to attach hydrogen and boron to the two carbons, respectively, while selectively positioning boron on the internal carbon of the molecule. The reaction proceeds in such a way that nickel temporarily occupies the site where boron will go and then gives way when boron is introduced.
The team demonstrated practical potential by applying the intermediate obtained by this synthetic method to the synthesis route of the anticancer drug "bexarotene" and successfully synthesizing derivatives by modifying the structure of the alkyne-class drug "pargyline."
Another achievement of this study is that the nickel intermediate formed during the synthesis was directly observed. The team captured the intermediate using electron paramagnetic resonance (EPR) spectroscopy and high-resolution mass spectrometry, which can distinguish even mass differences smaller than a single hydrogen atom, and also elucidated, through computational chemistry analysis, the principle by which boron selectively bonds to the internal carbon.
Professor Hong Seong-yu said, "This is a case showing that boron can be attached at desired positions on alkynes using inexpensive nickel without relying on precious-metal catalysts," adding, "It will help expand synthesis routes for drug candidates and functional organic molecules."
This research was conducted with support from the group research ERC project and the individual basic research program of the National Research Foundation of Korea (NRF).