Anionic Bisoxazoline Ligands Enable Copper-Catalyzed Asymmetric Radical Azidation of Acrylamides

Asymmetric radical azidation for the synthesis of chiral alkylazides remains a tremendous challenge in organic synthesis. We report here an unprecedented highly enantioselective radical azidation of acrylamides catalyzed by 1 mol % of a copper catalyst. The substrates were converted to the corresponding alkylazides in high yield with good-to-excellent enantioselectivity. Notably, employing an anionic cyano-bisoxazoline (CN-Box) ligand is crucial to generate a monomeric Cu-II azide species, rather than a dimeric Cu-II azide intermediate, for this highly enantioselective radical azidation.

Automated summary

An unprecedented highly enantioselective radical azidation of acrylamides catalyzed by 1 mol% of a copper catalyst is reported. The use of a specific ligand is crucial for generating a monomeric Cu-II azide species for this highly enantioselective transformation.