Decarbonative routes to generate N-acyliminium ion intermediates for the synthesis of 3-substituted isoindolinones via an intermolecular amidoalkylation reaction

Published in: Org. Biomol. Chem., 2025,23, 7448-7455

DOI: 10.1039/D5OB00687B

Authors: Nazir Uddin,  Sudipta Roy [TCGLS Member], Santanab Giri, ^c   Gitish K. Dutta  *^a  and  Paresh Nath Chatterjee  *^d  

Abstract: An alternative and unique approach for synthesizing 3-substituted isoindolinones via Lewis acid-catalyzed C–C bond-breaking reactions has been reported. For this purpose, we successfully generated N-acyliminium ion intermediates from two different substrates [through (a) an FeCl₃ catalyzed C_sp3–C_sp2 bond-breaking reaction in isoindolinones bearing electron-rich and sterically bulky aryl substituents at the 3-position and (b) a ZnCl₂ catalyzed C_sp3–C_sp3 bond-breaking reaction in isoindolinones bearing 1,3-diketo substituents at the 3-position of the isoindolinone starting precursors], which were trapped by appropriate nucleophiles to produce more stable γ-substituted isoindolinones in good to excellent yields. The leaving ability of 1,3-diketones is higher than that of electron-rich and sterically bulky arenes in our developed method, which results in higher yields of γ-substituted isoindolinones from the starting precursor bearing the 1,3-diketo substituents at its 3-position. Theoretical investigations were also carried out to gain insight into the two different C–C bond-cleaving reactions.