Blue-Light-Promoted Sulfenylnitrenes for Late-Stage Skeletal Editing of N-Heterocycles: Application to Tethered C-Glycosides and N-Nucleosides

Skeletal editing has emerged as a powerful approach for restructuring core molecular frameworks to attain structurally distinct analogues characterized by enhanced chemical diversity and therapeutic potential. This report presents a class of bench-stable sulfenylnitrene precursors that yield sulfenylnitrenes without photosensitizers or additives upon exposure to blue-light irradiation. This operationally mild and straightforward protocol facilitates late-stage, single nitrogen-atom insertion into N-heterocycles, including pyrroles, indoles, and imidazoles, culminating in the generation of valuable and synthetically challenging heterocyclic scaffolds such as pyrimidines, quinazolines, and triazines. The transformation occurs efficiently in aqueous media, accommodating a broad range of functional groups, including oxidation-sensitive motifs. Notably, this approach enables the selective modification of structurally intricate, bioactive compounds, encompassing natural products, amino acids, protecting-group-free C-glycosides, tethered N-nucleosides, and pharmaceuticals. The extensive substrate scope, high compatibility with functional groups, and scalability of this method make it a practical and versatile toolkit for late-stage functionalization and scaffold diversification. This research significantly broadens the horizons of visible-light-mediated transformations and provides a robust platform for exploring novel chemical spaces in drug discovery.