Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Nature Communications

DOI: 10.1038/s41467-025-65313-x

Authors: Shu-Min Guo, Pengwei Xu, Constantin G. Daniliuc, Armido Studer

Institution: University of Münster

Language: English

Topic: Chemical Reactions and Mechanisms

Subfield: Physical and Theoretical Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: Alexander von Humboldt-Stiftung, Deutsche Forschungsgemeinschaft, Westfälische Wilhelms-Universität Münster