Eco-friendly, in-water, and catalyst-free assembly of acylethenylpyrroloimidazoindoles from 3H-indoles and acylpyrrolylacetylenes

Abstract

The merging of fundamentally and biologically important heterocyclic structures, such as pyrroles, indoles, and imidazoles, in molecules of dihydropyrrolo[1′,2′:3,4]imidazo[1,2-a]indoles functionalized by E-acylethenyl groups was achieved in water on the platform of commercial 3H-indoles using readily available acylpyrrolylacetylenes as additional building blocks. The yields of the ensembles reached 88% (100 °C, 8 h), which is noticeably better than that produced using conventional solvents (MeCN, MeNO₂, DMSO, and CF₃CH₂OH), wherein the reaction proceeds at a rate of approximately 10 times longer (96 h) with lower yields of the target products (not higher than 80%). The reaction presumably proceeds in a micellar-like microreactor self-assembled in a two-phase aqueous medium that secures favorable mutual orientation of the merging molecules, providing a facile [2+3] concerted cycloaddition to finally form fused polyheterocyclic systems. The performed DFT calculations are in agreement with such mechanistic considerations, particularly those underlying the crucial role of water in the studied cascade process.