Photolysis-generated sulfenylnitrenes enable site-selective nitrogen-atom insertion into N-heterocycles

This research delineates a photochemical methodology for generating sulfenylnitrenes from bench-stable precursors via blue-light irradiation without photosensitizers or additives. The resultant sulfenylnitrenes facilitate chemo- and site-selective incorporation of nitrogen atoms into N-heterocycles under mild, aqueous conditions. This approach transforms readily accessible pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, and triazines with high regioselectivity. Mechanistic investigations and density functional theory calculations provide insight into the origins of the observed regioselectivity. The reaction is compatible with a variety of oxidation-sensitive functional groups. It applies to the late-stage functionalization of bioactive molecules, including natural products, amino acids, C-glycosides, N-nucleosides, and pharmaceuticals. The operational simplicity, functional group tolerance, and extensive substrate scope emphasize the utility of this methodology and augment the repertoire of blue-light-mediated transformations, thereby contributing to the exploration of new chemical space for applications in medicinal chemistry and drug discovery.