Synthesis of Diverse Nitrogen Heterocycles via Palladium‐Catalyzed Tandem Azide–Isocyanide Cross‐Coupling/Cyclization: Mechanistic Insight using Experimental and Theoretical Studies

Abstract A rapid and elegant tandem azide–isocyanide cross‐coupling/cyclization protocol has been developed based on a nitrene transfer reaction. The palladium‐catalyzed ligand‐free methodology led to the synthesis of three different heterocyclic scaffolds with excellent atom/step/redox economy. Studies based on first‐principles‐based quantum calculations and control experiments unraveled a concerted process of nitrene transfer reaction on isocyanides, ruling out the metallaaziridine intermediate reported earlier. This finding could pave the way for novel applications of nitrene transfer reactions to generate bioactive heterocycles. magnified image