Facile one-pot synthesis of 5-alkylidene-2,3,5,6,7,8-hexahydroimidazo[1,2-a]pyridines

Abstract

A straightforward and efficient one-pot protocol for the synthesis of 5-alkylidene-2,3,5,6,7,8-hexahydroimidazo[1,2-a]pyridines is reported. When subjected to reaction with ethylenediamine in refluxing dioxane, bis-α,β-alkynic ketones, i.e., 1,9-diarylnona-2,7-diyne-1,9-diones, afford 5-alkylidene-2,3,5,6,7,8-hexahydroimidazo[1,2-a]pyridines. Generation of three new C–N bonds, along with one C–C bond cleavage, during the reaction leads to the construction of unknown fused five- and six-membered heterocyclic ring systems. The reaction proceeds through an imidazoline intermediate. Similarly, the reaction of bis-α,β-alkynic ketones with 1,2-propylenediamine produces 2-methyl-substituted hexahydroimidazo[1,2-a]pyridines. The skeletal diversity of the synthesized hexahydroimidazo[1,2-a]pyridines may be of use in pharmaceutical and medicinal chemistry as novel molecular entities and structural leads.