Multicomponent synthesis of functionalized pyrrolo[3,4-e]isoindole-1,3,6,8-tetraones via [2 + 2 + 2] cycloaddition of maleimides with nitroenamines

Abstract

Herein, we developed a protocol for the synthesis of highly functionalized pyrrolo[3,4-e]isoindole-1,3,6,8-tetraones (PIITOs) from maleimide derivatives and nitroenamines. This strategy featured a [2 + 2 + 2] cycloaddition with the simple heating of a mixture of substrates 1 and 2 with DMF without any catalyst or promoter. As a result, a series of PIITOs 3 were produced by cleaving two C–N bonds and forming three C–C bonds in a single step. These strategies can be used to synthesize functionalized PIITOs for combinatorial and parallel syntheses via one-pot reactions without any catalyst or promoter. This approach effectively utilizes the strong electron-withdrawing nature of the nitro group (–NO₂) in nitroenamines to fully activate the reactivity of the CC bond and successfully achieve the three-component [2 + 2 + 2] cycloaddition synthesis of functionalized PIITOs.