Triethylamine‐Promoted One‐Pot Cascade Cyclization for the Synthesis of Trifluoromethyl‐Functionalized Dihydropyrrole Scaffolds

A concise and straightforward one‐pot cascade protocol has been developed for the synthesis of a fluorine‐enriched pyrrole framework. This transformation efficiently delivers 4‐hydroxy‐4‐(trifluoromethyl)−4,5‐dihydro‐1H‐pyrrole‐3‐carboxylate derivatives through the reaction of ethyl/methyl 3‐oxobutanoate, 3‐bromo‐1,1,1‐trifluoropropan‐2‐one, and substituted primary amines using triethyl amine as a promoter, in the presence of ethanol as a solvent. The reaction proceeds through a tandem condensation–cyclization sequence, affording the products with high regioselectivity in good yields under mild reaction conditions. The synthetic utility of the resulting 4‐trifluoromethyl‐4‐hydroxydihydropyrroles is further demonstrated through postfunctionalization into a 4‐trifluoromethyl substituted pyrroles, 1,2,3‐triazole derivative, and a Mannich base derivative. Moreover, a gram‐scale synthesis of 4‐(trifluoromethyl)‐substituted 4,5‐dihydro‐1H‐pyrrole‐3‐carboxylates has been established. This strategy features broad substrate scope, remarkable functional‐group tolerance, and simple operation, offering sustainable and synthetically versatile access to CF 3 ‐substituted pyrrole scaffolds of potential relevance in medicinal chemistry and the design of fluorine‐based functional materials.