AbstractAn effective synthetic approach was proposed to partially and fully hydrogenated imidazo[1,2‐a]pyridines based on cyclizations of polyfluoroalkyl‐3‐oxo esters and ethylenediamine with aldehydes. It was found that acetic and propionic aldehydes react similar to the α,β‐unsaturated crotonic and cinnamic aldehydes. The cyclizations of trifluoroacetoacetic ester with ethylenediamine and aldehydes led to the formation of ethyl 5‐hydroxy‐5‐trifluoromethyloctahydroimidazo[1,2‐a]pyridin‐6‐carboxylates, except for the reaction with acetaldehyde, where the main product was 7‐hydroxy‐7‐trifluoromethylhexahydroimidazo[1,2‐a]pyridin‐5(1H)‐one. The cyclizations of polyfluoroalkyl‐3‐oxo esters resulted in 6‐(polyfluoroalkyl‐1‐hydroxyalkyl)‐tetrahydroimidazo[1,2‐a]pyridin‐5(3H)‐ones, except for transformations with cinnamaldehyde, from which ethyl 5‐hydroxy‐7‐phenyl‐5‐polyfluoroalkyloctahydroimidazo‐[1,2‐a]pyridin‐6‐carboxylates were isolated as by‐products. These bicycles containing long polyfluoroalkyl substituents (RF>C2F5) underwent haloform cleavage to form ethyl 7‐phenyl‐5‐oxooctahydroimidazo[1,2‐a]pyridin‐6‐carboxylate. The regio‐ and stereoisomeric structure of the synthesized bicycles was determined using 1H, 19F, 13C NMR spectroscopy and X‐ray. The domino mechanism was proposed for the formation of new tetra‐, hexa‐ and octahydroimidazo[1,2‐a]pyridines.