Synthesis of N-CD ₃ aryl amines <i>via</i> iron-catalysed site-selective aromatic C–H amination

The strategic incorporation of deuterium atoms into pharmaceutical compounds can profoundly influence their pharmacokinetic profiles and metabolic stability. This is particularly relevant for the ubiquitous N-methyl motif in bioactive molecules, where metabolic oxidation of the methyl group often represents a major pathway. Despite this potential, synthetic methods for the direct introduction of the N-CD₃ group through C-H functionalization remain elusive. We report herein an iron-catalysed protocol for the synthesis of N-CD₃ anilines through site-selective aromatic C-H amination. An iron-aminyl radical is proposed as the key intermediate that facilitates site-selective homolytic aromatic substitution (HAS) through chelating with basic functional groups, including amides, urea and carbamate. The resulting <i>ortho</i>-amino products serve as versatile synthetic intermediates for valuable heterocycles. Importantly, the Weinreb amide proves effective as a directing group, offering the advantage of transforming into diverse carbonyl molecules.