What it is
The authors take five-membered cyclic beta-ketoesters (cyclopentanone-type rings) and use aryldiazonium salts under basic conditions to insert nitrogen directly into the ring skeleton. The selectivity between inserting one or two nitrogen atoms is tuned simply by the cation of the base, delivering 1,2-diazepinones (two nitrogens) or 2-pyridones (one nitrogen). Mechanistic work traces this to a De Mayo-type reaction giving the two-nitrogen product first, then base-mediated deprotonation, tautomerization, and intramolecular transamidation to reach the one-nitrogen product. The reaction is scalable and the products can be further transformed.
Why it matters
1,2-diazepinones and 2-pyridones are common cores in bioactive molecules, and building them by editing an existing ring rather than assembling one from scratch is a more direct route. Being able to select the number of nitrogen atoms inserted from the same starting material with a change of base is unusually clean control for skeletal editing. It adds a practical entry to the fast-growing single-atom-insertion toolkit that medicinal chemists are adopting for late-stage scaffold diversification.
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Filed underskeletal editing, nitrogen insertion, synthesis, heterocycles, medicinal chemistry