A team of chemists at Southern University of Science and Technology, working with a colleague from Zhejiang University, both in China, has engineered a metal–ligand complex that incorporates a reactive pocket to pre-organize prochiral substrates. Their paper is published in the journal Science.
Carbon radicals are being used as an intermediate in a variety of synthetic transformations. Because they have just one electron, they tend to be highly reactive, allowing for speedy reactions with little energy release.
Unfortunately, when working with prochiral substrates, where three different groups are attached to a single radical center, the ability to control the reaction becomes untenable. Prior research has shown that the underlying cause of these difficulties lies with the differences inherent in the alkyl group, where non-stereoselective reactions tend to dominate.
To overcome such problems, the team developed a metal–ligand complex with a pocket that allows a reaction to pre-organize the substrates. As a reaction begins, the researchers note, the smaller parts of a molecule become wedged into the tighter, inner parts of the ligand, forcing the larger parts to an outer region. This allows reactions occurring in the pocket to be localized. The team added features around the edges of the pocket to direct nonbonding interactions that occurred during the main reaction.
The idea, the team notes, is to hold the prochiral radical in place so a reaction can take place by itself and then allow subsequent reactions to take place in the outer part of the ligand, but still on the same side, resulting in the production of a single enantiomer.
When designing the ligand, the researchers were focused on finding a way to conduct asymmetric amination reactions using well-known, copper-based chemistry to form α-chiral alkyl amines.
Testing of their ligand showed it could accommodate both photocatalytic and thermal radical processes and that it could be used with a host of functional groups. During testing, the team produced more than 50 amines, clearly demonstrating the utility and versatility of their approach.
More information:
Yu-Feng Zhang et al, Asymmetric amination of alkyl radicals with two minimally different alkyl substituents, Science (2025). DOI: 10.1126/science.adu3996
© 2025 Science X Network
Citation:
New catalyst allows asymmetric radical reactions using an engineered ligand (2025, May 1)
retrieved 1 May 2025
from
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
