Bridging the pyridine-pyridazine synthesis gap by skeletal editing

• 成果类型: Article
• 署名作者: Purins, Mikus; Nakahara, Hikaru; Levin, Mark D.
• 署名单位: University of Chicago
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11547
• DOI: 10.1126/science.adx4762
• 发表日期: 2025-07-17
• 页码: 295-298
• 关键词: 2-azidopyridine 1-oxides; energy; nmr

摘要

Pairs of heterocycles differing by a single constitutive ring atom can exhibit stark differences in the retrosynthetic disconnections available for their preparation. Such a synthesis gap is exemplified by pyridine and pyridazine. Pyridine (a six-membered C5N ring) has risen to prominence in discovery chemistry, its ease of assembly spurring further synthetic development. Despite a host of favorable properties, pyridazine (an analogous C4N2 ring) has comparatively lagged behind-a discrepancy attributable to its often-challenging preparation, which arises from an electronically dissonant heteroatom arrangement. In this work, we achieve a single-atom skeletal edit that produces pyridazines from pyridines by direct carbon-to-nitrogen atom replacement: Azide introduction at the ortho position enables a photoinitiated rearrangement of N-amino-2-azidopyridinium cations. This transformation links the two heterocycles such that the richness of pyridine retrosynthesis becomes available to pyridazines.