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

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.