UNIST Develops Synthesis Method for Selectively Attaching Boron to Desired Molecular Positions [Reading Science]

Selective Hydroboration of Terminal Alkynes Achieved Using Nickel Catalyst

Direct Capture of Reaction Intermediate Raises Expectations for Pharmaceutical and Electronic Material Synthesis

A Korean research team has developed a new chemical synthesis method that allows for the selective attachment of boron (B) to specific positions within a molecule. This advancement enables greater flexibility in designing key intermediates for pharmaceuticals and functional materials, and the team has also directly identified the crucial reaction intermediates, thereby elucidating the underlying reaction mechanism.

On June 14, the Ulsan National Institute of Science and Technology (UNIST) announced that a research group led by Professor Seongyu Hong and Professor Jan-Uwe Rohde from the Department of Chemistry has developed a hydroboration reaction method using a nickel catalyst to selectively introduce boron into terminal alkynes.

Nickel Catalyst Hydrogen-Borylation Reaction Pathway. A schematic diagram of the process selectively bonding boron to an alkyne using a nickel catalyst. After nickel forms a reaction intermediate, boron replaces it, producing the target organoboron compound. The research team directly identified the nickel intermediate through electron paramagnetic resonance spectroscopy (EPR) and high-resolution mass spectrometry to elucidate the reaction pathway. Provided by the research team

An alkyne is a molecule in which two carbon atoms are connected by a triple bond. When boron is bonded to this structure, it can subsequently connect to various molecular fragments, making it an important intermediate for synthesizing pharmaceuticals and electronic materials.

The synthesis method developed by the research team involves opening the triple bond of the alkyne and attaching hydrogen and boron to each of the two carbons, respectively. While existing synthesis methods typically attach boron to the terminal carbon of the molecule, this new technique is distinctive in that it selectively bonds boron to the internal carbon of the molecule.

Nickel Intermediate Captured, Shedding Light on Reaction Mechanism

The research team applied the intermediate obtained using this method to the synthetic pathway of the anticancer drug bexarotene and also synthesized pargyline derivatives, which contain an alkyne structure, confirming the method’s potential for broader applications.

Notably, the researchers succeeded in directly capturing the nickel intermediate formed during the reaction. Their analysis showed that nickel temporarily occupies the site where boron will be introduced, and then is displaced by boron as the reaction proceeds.

The team detected this intermediate using Electron Paramagnetic Resonance Spectroscopy (EPR) and high-resolution mass spectrometry, and through computational chemical analysis, they clarified the reason why boron selectively bonds to the internal carbon of the molecule.

Research team photo. (From the left) Professor Sungyu Hong, Professor Jan-Uwe Rod, Researcher Jungwoo Lee, Researcher Geonha Kim, Researcher Seoyoung Jung. Provided by UNIST

Professor Jan-Uwe Rohde explained, "It is difficult to understand the reaction process of catalytic reactions by analyzing only the final products. The significance of this study lies in experimentally confirming the transient nickel intermediate and proving why boron attaches to a specific position."

Professor Seongyu Hong added, "We demonstrated that it is possible to introduce boron at the desired position using inexpensive nickel instead of costly precious metal catalysts. This technique could be used to expand synthetic pathways for pharmaceutical candidates and functional organic molecules."

The results of this study were published in the international journal for catalytic chemistry, 'ACS Catalysis,' on April 17.

This content was produced with the assistance of AI translation services.