Mechanochemical Regulation of Unstable Acyl Azide: Ir(III)-Catalyzed Nitrene Transfer C-H Amidation under Solvent-Free Ball Milling Conditions

In this study, we investigate the mechanochemical activation of acyl azide for direct C-H amidation with excellent C-N bond selectivity, fast rate, enhanced reactivity, solvent-free condition, and broad scope. Thermally unstable acyl azide, prone to Curtius rearrangement, was found to be controllable under mechanochemical ball milling conditions. Investigation of the mechanochemical process window of acyl azide led us to define highly selective Cp*Ir(III)-catalyzed acyl azide activation to acyl nitrene species and direct C-H amidation protocol. In addition to the expected merits of mechanochemistry, the newly developed high-speed ball milling method allows for carbamoyl azide utilization, which showed a limited scope under thermal solution conditions, registering to a list of mechanochemically preferred reactions.