N ‐Directed Rh‐Catalyzed Regioselective Amidation of Quinoxaline‐2(1 H )‐ones Using Dioxazolones

Quinoxalin‐2(1 H )‐ones are privileged nitrogen‐containing heterocycles with broad pharmaceutical relevance, yet efficient and regioselective methods for C─N bond formation on these scaffolds remain scarce. Herein, we report a highly efficient and regioselective Rh(III)‐catalyzed ortho ‐amidation of 3‐arylquinoxalin‐2(1 H )‐ones using aryl dioxazolones as versatile amidating reagents. The developed protocol, employing [RhCp*Cl 2 ] 2 in the presence of KPF 6 and AgSbF 6 , enables the synthesis of thirty‐four novel N ‐alkyl‐3‐phenylquinoxalin‐2(1 H )‐one amide derivatives with moderate to excellent yields. Systematic exploration of substrate scope revealed that both steric and electronic factors on the quinoxalinone core and the dioxazolone partner critically influence reaction efficiency, with electron‐donating substituents enhancing yields and steric hindrance diminishing reactivity. The methodology was successfully extended to the late‐stage functionalization of pharmacologically relevant quinoxalinone derivatives and demonstrated on gram scale, featuring its scalability and synthetic utility. Mechanistic investigations, supported by control experiments, suggest a catalytic cycle involving reversible C─H activation, nitrene insertion, and proto‐demetalation, with CO 2 as the sole by‐product. The synthesized compounds were thoroughly characterized by IR, NMR, HRMS, and single‐crystal x‐ray diffraction. This work constitutes the first documented example of regioselective amidation on structurally modified quinoxaline frameworks and provides a robust platform for the synthesis of amide‐functionalized heterocycles with promising applications in pharmaceutical and agrochemical development.