N-Hydroxyphthalimides as Nitrogen Radical Precursors in the Copper-Catalyzed Radical Cross-Coupling Amination of Arylboronic Acids: Synthesis of Arylamines

J Org Chem. 2024 Dec 20;89(24):17960-17965. doi: 10.1021/acs.joc.4c01366. Epub 2024 Nov 27.

Abstract

A new and practical approach for the synthesis of arylamines via copper-catalyzed radical cross-coupling amination of arylboronic acids has been developed. The key enabling advance in this protocol is the design of N-hydroxyphthalimides as precursors to generate nitrogen-based radical intermediates for cross-coupling with arylboronic acids, providing the corresponding arylamines of a high yield of up to 98%. In addition, the procedure successfully demonstrated remarkable efficiency across a wide range of functional group tolerances. Mechanistic investigations suggested that a nitrogen radical cross-coupling pathway is possible via phosphite-mediated N-O bond scission.