Iron-Catalyzed Cyanoalkylation of Glycine Derivatives Promoted by Pyridine-Oxazoline Ligands

An iron-catalyzed C(sp(3))-H cyanoalkylation of glycine derivatives with cyclobutanone oxime esters was established for the incorporation of a cyano group into amino acids and peptides. In this reaction, Fe(NTf2)(2) and pyridine-oxazoline ligands form highly active catalysts that could simultaneously and selectively activate both substrates. Preliminary mechanistic studies revealed the excellent chemo-selectivity may stem from an in situ formed imine intermediate and a consecutive radical addition. The evidence suggested the interaction between glycinate substrate and the Fe-catalyst has a prominent impact on the catalytic activity, and the catalyst may also activate the imine intermediate as a Lewis acid.

Automated summary

An iron-catalyzed C(sp(3))-H cyanoalkylation reaction has been established for the incorporation of a cyano group into amino acids and peptides. The highly active catalysts formed by Fe(NTf2)(2) and pyridine-oxazoline ligands can selectively activate both substrates, leading to excellent chemo-selectivity through in situ formed imine intermediate and consecutive radical addition. The interaction between glycinate substrate and the Fe-catalyst plays a key role in the catalytic activity, with the catalyst potentially activating the imine intermediate as a Lewis acid.