Multicomponent synthesis of pyrrolo3,4-eiso-indole-1,3,6,8-tetraones by 2+2+2 cycloaddition of N-pyridin-2-ylenaminones with maleimides

In this paper, we developed a three-component protocol for the synthesis of diverse pyrrolo3,4-eisoindole-1,3,6,8-tetraones (PIITOs) 3 using N-pyridin-2-yl enaminones 1 and maleimide derivative 2 as substrates, catalyzed by copper(Ⅱ) acetate with pyridin-2-yl as a directing group. These strategies can be used to synthesize functionalized PIITOs for combinatorial and parallel syntheses via one-pot reactions. This approach effectively utilizes the N-pyridin-2-yl of enaminones as a traceless directing group that participates in the reaction in situ. It automatically disengages from the directing group after the reaction is completed, fully activating the reactivity of the α-C of enaminones. This method successfully achieves the three-component 2+2+2 cycloaddition synthesis of functionalized PIITOs. The synthesized products were characterized by ¹H NMR, ¹³C NMR and HRMS. Additionally, the structure of target compound 3a was confirmed by X-ray crystallography. The method has simple operation, simple route, simple substrate and wide range, so it can synthesize a variety of products, and provides a new method for screening PIITOs with potential biological activities.