biostudies-literatureXiao HTianchi Innovation Leading Talent Project276https://www.ebi.ac.uk/biostudies/studies/S-EPMC12844355biostudies-literatureUnknown31(2)The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct <i>ortho</i>-C-H cyanation of a broad range of heterocyclic <i>N</i>-oxides, including pyridine, quinoline, isoquinoline, and pyrimidine derivatives. This transformation proceeds under mild conditions without the need for external activating agents or catalysts, and has been successfully applied to structurally complex, biologically relevant molecules. Compared to existing methodologies, our approach offers several distinct advantages: the use of non-prefunctionalized heteroarene substrates, environmentally benign reaction solvMolecules (Basel, Switzerland)Formal Synthesis of <i>Ortho</i>-Cyanated <i>N</i>-Heterocycles via Direct, Metal-Free Cyanation of <i>N</i>-Oxides Under Benign Conditions.PMC1284435551052300410Wufuer RWang DXiao HfalseFormal Synthesis of <i>Ortho</i>-Cyanated <i>N</i>-Heterocycles via Direct, Metal-Free Cyanation of <i>N</i>-Oxides Under Benign Conditions.The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct <i>ortho</i>-C-H cyanation of a broad range of heterocyclic <i>N</i>-oxides, including pyridine, quinoline, isoquinoline, and pyrimidine derivatives. This transformation proceeds under mild conditions without the need for external activating agents or catalysts, and has been successfully applied to structurally complex, biologically relevant molecules. Compared to existing methodologies, our approach offers several distinct advantages: the use of non-prefunctionalized heteroarene substrates, environmentally benign reaction solv2026-01-01T00:00:00Z2026 Jan2026-06-14T03:15:08.79Z2026-06-14T03:08:56.114ZS-EPMC128443554159932510.3390/molecules31020276