Transition Metal‐Controlled Direct Regioselective Intermolecular Amidation of C−H Bonds with Azodicarboxylates: Scope, Mechanistic Studies, and Applications

A simple and efficient transition metal‐catalyzed C−H amidation with azodicarboxylates has been developed. Under silver catalysis, the amide substrates undergo regioselective C−H amidation at C5‐position of the quinoline. Conversely, with palladium as the catalyst, the reaction gave β‐C( sp 3 )−H amidation products via the activation of methylene C( sp 3 )−H bonds. Mechanistic studies suggested that the single‐electron‐transfer and organometallic mechanism pathways gave rise to these surprising and distinct outcomes. Based on the mechanistic analysis, we designed a palladium‐catalyzed/silver‐promoted direct intermolecular β‐C( sp 3 )−H amidation to activate the methylene C( sp 3 )−H bonds of 5‐chloro‐8‐aminoquinoline (CQ)‐protected aliphatic amides with azodicarboxylates. Both catalytic protocols provide alternative, convenient, and simple strategies for efficiently accessing structurally unique C−N bond‐containing compounds in a regioselective manner.