Radical 6‐Endo Addition Enables Pyridine Synthesis under Metal‐Free Conditions

Abstract Metal‐free synthesis of heterocycles is highly sought after in the pharmaceutical industry and has garnered widespread attention due to eliminating the need to remove trace metal catalysts from the reaction. We report a radical 6‐ endo addition method for pyridine synthesis from cyclopropylamides and alkynes under metal‐free conditions. Various terminal and substituted alkynes are inserted as C2 units into cyclopropylamides to synthesize versatile pyridines with 57 examples. Mechanistic investigations and computational studies indicate the unprecedented 6‐ endo ‐ trig addition of vinyl radicals to the imine nitrogen atom rather than the conventional 5‐ exo ‐ trig addition to the imine carbon atom, in which the hypervalent iodine(III) plays a critical role. This reaction easily scales up with excellent functional group compatibility and suits the late‐stage pyridine installation on complex molecules.