One‐pot tandem cyclization of β‐oxoamides, primary amines, and 3‐bromo‐1,1,1‐trifluoroacetone: Synthesis of 2/4‐trifluoromethyl‐substituted dihydropyrrol‐2/4‐ols

A facile one‐pot, three‐component cascade cyclization has been developed for synthesis of 2‐trifluoromethyl‐2‐ol dihydropyrroles and 4‐trifluoromethyl‐4‐ol dihydropyrroles from various substituted amines, 3‐bromo‐1,1,1‐trifluoropropan‐2‐one, and substituted β‐oxoamides using K₂CO₃ as an additive. This K₂CO₃‐promoted method offers a simple and efficient approach for achieving highly regioselective products through cascade bond formation and cyclization. Post functionalization of resulting products into various valuable trifluoromethylated heterocycles including triazoles, isoxazoles, Mannich bases and the products from Sonogashira coupling reactions has also been reported. Additionally, a straightforward and scalable protocol for synthesis of 4‐trifluoromethylpyrrole‐3‐carboxamide derivatives without K₂CO₃, utilizing diverse 1,3‐dicarbonyl compounds has been established. This method demonstrates broad substrate compatibility, efficient tolerance towards a wide range of functional groups, making it a versatile strategy for accessing highly substituted trifluoromethylated pyrroles.