The first approach to highly substituted dihydroimidazotriazolones and their controlled post-transformations
Year: 2026
Type: preprint
Abstract: A novel class of azido-modified α , β -unsaturated Ugi adducts (enamides) has been explored as a versatile platform for post -Ugi transformations. While intramolecular azide-alkyne cycloadditions of Ugi-derived peptidomimetics have been extensively studied, the corresponding azide-alkene cycloadditions on similar scaffolds have remained unexplored. In this work, we report a systematic investigation of intramolecular azide-alkene cycloaddition involving activated enamide moieties derived from Ugi adducts. Enamides readily undergo catalyst-free intramolecular [3+2] cycloaddition under mild conditions to afford the previously unknown 3,3a,4-trisubstituted-3a,4-dihydro-3 H -imidazo[1,2-c][1,2,3]triazol-5(6 H )-one scaffold in high yields. This novel fused heterocyclic system was fully characterised and proved to be a highly versatile intermediate for divergent post -Ugi transformations. Fused dihydrotriazoles transformed into 3,5-dihydroimidazol-4-ones via an elimination of N 2 supplemented by acylamide migration. Additionally, base- or acid-mediated cascades enabled efficient one-pot access to aromatised 1,2,3-triazoles and open-chain triamides, respectively. In total, 4 generations of structural isomers and 2 other classes of compounds were involved in the work. The methodologies developed highlight the synthetic value of azido-modified enamides as divergent intermediates, providing rapid and controlled entry to structurally diverse nitrogen-rich heterocycles and peptidomimetics from simple Ugi adducts derived from α , β- unsaturated aldehydes.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7213907437