Regioselective approach to the synthesis of trifluoromethyl functionalized pyrroles

Pyrroles are an important class of heterocyclic compounds that are found in many bioactive molecules, such as pharmaceuticals, agrochemicals and natural products.1 Novel synthetic methodologies are constantly being developed for preparing this targeted heterocycle, since it is an important intermediate for the synthesis of other functionalized compounds.2,3 In addition, the introduction of a trifluoromethyl group into these organic compounds can greatly improve its biological activity.3 In this study, we report a new, simple and regioselective one-pot synthetic approach towards N-substituted trifluoromethyl pyrroles functionalized with a β-aminovinyl trifluoromethyl ketone. The general synthetic method involves the solvent-free reaction (in a sealed tube) of 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one (enone) with primary amines in a ratio of 1:1.5 (enone : amine). Several variables were evaluated, such as solvent effect, reaction time, temperature and amount of nucleophile. Products were purified by recrystallization from hexane and were obtained in 30 – 80% overall yield.