Relay C–H Functionalization Enables De Novo Synthesis of Pyridines and Pyridones

The realization of sequential and controllable C–H functionalization in one step can maximize the utilization of C–H bonds to rapidly create valuable scaffolds and dramatically increase the atom and functional group utilization. In this work, we describe an iron-catalyzed relay C–H functionalization proto col that enables de novo synthesis of a wide range of pyridines and pyridones. This transformation involves three-fold C–H functionalization (two Csp3–H and one Csp2–H) and allows the simultaneous generation of three chemical bonds and two rings in one step. The reaction features operational simplicity, broad substrate scope (>70 examples), good functional group compatibility, and the suitability to derivation of some bioactive molecules. Various control and kinetic isotope effect experiments were performed to understand the reaction mechanism. DFT investigations support an interesting imine α-carbon radical addition/1,5-hydrogen atom transfer/homolytic aromatic substitution cascade process.