Unlocking the synthetic potential of aziridine and cyclopropane-fused quinolin-2-ones by regioselective fragmentation of its three-membered rings

• Published in: Arabian journal of chemistry 2020-01, Vol.13 (1), p.2702-2714
• Main Authors: Diaz, Javier, Rodenas, Daniel, Ballester, Francisco-Jose, Alajarin, Mateo, Orenes, Raul-Angel, Sanchez-Andrada, Pilar, Vidal, Angel
• Format: Article
• Language: English
• Subjects: 3-aminoquinolin-2-ones; 6π-electrocyclic ring opening; [1,5]-H shift; Aziridino[2,3-c]quinolin-2-ones; Benzazepin-2-ones; Cyclopropa[c]quinolin-2-ones
• ISSN: 1878-5352; 1878-5379
• DOI: 10.1016/j.arabjc.2018.07.002

Aziridine- and cyclopropa-fused quinolones, obtained by annulation of the quinoline core to substituted aziridines and cyclopropanes, undergo regioselective ring-fragmentation of the three membered ring to afford 3-aminoquinolin-2-ones and 1-benzazepin-2-ones. [Display omitted] The cyclization of cis-2-(2-azidophenyl)-1-benzyl-3-ethoxycarbonylaziridines and trans-2-(2-azidophenyl)-3-nitrocyclopropane-1,1-dicarboxylates yielded the respective aziridino[2,3-c]quinolin-2-ones and cyclopropa[c]quinolin-2-ones. Ring-opening of the aziridine-fused species under silica gel catalysis provided 3-aminoquinolin-2-ones whereas the ring-expansion of the cyclopropane-fused derivatives by the action of sodium hydride gave 1-benzazepin-2-ones, in both cases in a regioselective manner. A computational study using DFT methods revealed that the mechanism for the transformation of cyclopropa[c]quinolin-2-ones into 1-benzazepin-2-ones involves the initial deprotonation step of its amide function followed by two pericyclic events: a 6π-electrocyclic ring opening and a subsequent [1,5]-H shift.