Electricity-driven nitrogen insertion enables sustainable heterocycle synthesis

Researchers from the National University of Singapore (NUS) have developed an electrochemical reaction manifold that promotes efficient nitrogen atom insertion into saturated carbocycles to access either functionalised quinolines or N-alkylated saturated N heterocycles, both of which are privileged scaffolds in synthetic chemistry and pharmaceutical science.

The research team was led by Associate Professor Koh Ming Joo and Professor Zhao Yu from the NUS Department of Chemistry. The research breakthrough was published in the scientific journal Nature Synthesis on 18 December 2025.

N heterocycles have garnered significant attention from academia and industry as building blocks for drug development. Therefore, developing practical and efficient procedures to access these motifs remains a central pursuit in synthetic chemistry. Among various N-heterocycle synthetic strategies, skeletal editing of readily available cyclic compounds through nitrogen atom insertion represents an unconventional and highly desirable approach. However, direct nitrogen atom insertion into saturated, unstrained carbocycles via C–C single-bond cleavage remains rare due to the high thermodynamic and kinetic stability of these σ bonds. Existing methods of nitrogen atom insertion into cyclic hydrocarbons rely on the stoichiometric use of strong oxidising agents and suffer from limited functional group compatibility.