UNIST develops nickel-catalyzed method to place boron at desired molecular sites

Organoboron compounds are widely used as key intermediates in the synthesis of new drug candidates and functional molecules because they can be readily converted into a broad range of organic compounds. A South Korean research team has now developed a new synthesis method that allows boron to be attached at a desired position within such compounds.

A team led by professors Hong Seong-yu and Rod Jannuub of the Department of Chemistry at UNIST (Ulsan National Institute of Science and Technology) announced Sunday they had developed a nickel-catalyst-based reaction method for selectively attaching boron to terminal alkynes.

Alkynes are a class of molecules in which two carbon atoms are connected by a triple bond. Attaching boron to an alkyne allows it to bond easily with other molecules, making borylated alkynes useful intermediates in the synthesis of pharmaceuticals and electronic materials.

The synthesis method works by opening one of the triple bonds in an alkyne and attaching hydrogen and boron to the two carbon atoms separately. Conventional methods tend to direct boron toward the terminal carbon at the end of the molecule, limiting the range of intermediate structures that can be produced. The new approach selectively places boron on an internal carbon instead.

The team applied intermediates obtained through this method to the synthesis pathway of the anticancer drug bexarotene. They also synthesized derivatives by modifying part of the structure of pargyline, a drug with an alkyne structure.

The nickel used in the reaction acts as a placeholder, temporarily occupying the site where boron will eventually bind. Nickel guides hydrogen to attach to one carbon of the alkyne while bonding to the opposite carbon to form an intermediate. When boron enters the reaction, nickel detaches and boron takes its place.

"These results provide an important clue to understanding how nickel-hydrogen catalytic reactions work," said Professor Rod Jannuub.

Professor Hong Seong-yu said the study "demonstrates that regioselectivity in reactions can be controlled through electronic tuning of catalyst ligands and weak non-covalent interactions, laying the groundwork for designing new nickel catalysts and developing selective organic synthesis reactions in the future." He added that the findings "could lead to the development of more economical and efficient precision chemical synthesis strategies."

The findings were published April 17 in ACS Catalysis, an international journal in the field of catalytic chemistry.