Expanding the Scope of 1,2‐Diazepines Through Alternative Activation Strategies

The 1,2‐diazepine scaffold, a structural motif found in the core of several bioactive compounds, remains underrepresented in FDA‐approved drugs due to the laborious syntheses required for its preparation. In recent years, photochemical approaches with UV light have unlocked efficient access to this medium‐sized azaheterocycle from pyridinium ylides. Herein, we further expand the repertoire of activation strategies by introducing three unprecedented protocols that convert readily available starting materials into a range of ylides, which, upon UV irradiation, rapidly furnish novel 1,2‐diazepines. First, abundant carboxylic acids, including amino acids, are activated as acyl azides. Second, α‐diazoketones are converted into highly reactive ketenes through traceless blue‐light irradiation. Both intermediates serve as efficient reaction partners, providing direct access to acylated 1,2‐diazepines. Finally, oxidation of primary amides with hypervalent iodine reagents generates the corresponding isocyanates, which are readily intercepted by 1‐aminopyridinium iodide to afford 1,2‐diazepines bearing a carboxamide functionality. Altogether, these three mild protocols demonstrate broad functional group compatibility across more than 20 examples, furnishing the desired products in consistently good yields.