Cu catalysts do chiral amide synthesis

Abstract

A pair of copper catalysts can create chiral amides in a new, light-driven process, offering a useful alternative to the standard method for making these staples of medicinal chemistry ( Nature 2021, DOI: 10.1038/s41586-021-03730-w ). “Amides are ubiquitous functional groups in bioactive molecules, such as peptides,” says Gregory C. Fu , a chemist at the California Institute of Technology who co-led the work. The conventional route to chiral amides involves producing a single enantiomer of an amine and then reacting it with a carboxylic acid derivative. In contrast, the Caltech team’s method needs only a single step and controls the stereochemistry of the amide as it forms. The reaction relies on two different Cu catalysts and combines an amide with an alkyl bromide to form a chiral secondary amide—where the nitrogen atom is bonded to a hydrogen and two carbons, one of which is chiral. The first catalyst is a