Formal pyridine meta-azidation and its application for the synthesis of diazepines, ring-fused δ-carbolines and 1,2,3-triazolylpyridines.

The nitrogen atom serves as an important structural element in pharmacologic studies, highlighting the critical role of nitrogen-containing heterocycles in drug discovery. Late-stage peripheral functionalization and structural editing of nitrogen-containing heterocycles have garnered increasing attention due to their potential for the preparation of diversifying drug-like libraries. In particular, the structural diversification of pyridine cores by introducing N atoms or N-containing functionalities shows promise, but remains underexplored. Here, we report a synthetic strategy that combines the introduction of the versatile azide moiety with molecular editing. This approach comprises an initial peripheral regioselective meta-azidation of pyridines through dearomatized oxazino pyridine intermediates, and a subsequent molecular editing step via a photo-mediated singlet nitrene insertion process. We have demonstrated the utility of this strategy by the synthesis of seven-membered diazepines. Furthermore, ring-fused δ-carbolines and 1,2,3-triazolylpyridines can be also accessed through chemical manipulation of the azide functionality.