Aza-heterocyclic frameworks through intramolecular π-system trapping of spiro-N-acyliminiums generated from isoindolinone

Sarra Chortani (1, 2, 3) , Mohamed Othman (1, 2) , Ata Martin Lawson (1, 2) , Anis Romdhane (3) , Hichem Ben Jannet (3) , Michael Knorr (4) , Lukas Brieger (5) , Carsten Strohman (5) , Adam Daïch (1, 2)

1 URCOM - Unité de Recherche en Chimie Organique et Macromoléculaire
2 INC3M - Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire
3 CHPNR - Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité [Monastir]
4 UTINAM - Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213)
5 TU - Technische Universität Dortmund [Dortmund]

Spiro-acetoxylactams as key substrates were obtained straightforwardly by the tandem regioselective reduction/O-acylation of spiro-isoindolinone-imides. The latter were produced in large scale in three steps from homophthalic acid. These imides were useful to provide in one step isoindolinones bearing hydroxymethyl-amide functions, tethered at quaternary carbon centre with promising biological issues. Submitted to Brönsted (TFA neat) and Lewis acid (trimethylsilyltrifluoro-methanesulfonic (TMSOTf) 10 mol%), the spiro-acetoxylactams undergo π-cyclization of spiro-N-acyliminiums to provide diastereoselectively with π-aromatic original pyrrolopyrido- and pyrroloazepino-isoindoles fused or not to aromatic systems. With π-olefins, pyrrolopyridines and pyrrolo-azepines fused to isoindoline or containing amino-acids were isolated. A reaction mechanism producing all these systems is also discussed.

Domaines: Chimie

Sarra Chortani, Mohamed Othman, Ata Martin Lawson, Anis Romdhane, Hichem Ben Jannet, et al.. Aza-heterocyclic frameworks through intramolecular π-system trapping of spiro-N-acyliminiums generated from isoindolinone. New Journal of Chemistry, 2021, 45 (5), pp.2393-2403. ⟨10.1039/D0NJ04052E⟩. ⟨hal-03079155⟩