1,3-Dipolar Cycloaddition Synthesis of 3-Trifluoroacetyl Pyrroles

Significance

Reported is the lithium bromide-promoted synthesis of 3-trifluoroacetylpyrroles 3 by the reaction of N-alkylidene 2-amino esters 2 with trifluoroacetyl vinyl ethyl ether 1. The reaction proceeds using triethylamine as base as well as inorganic bases, such as sodium or potassium ­hydroxide. Electron-donating substituents on the aryl moiety afford 3-trifluoroacetylpyrroles 3 in moderate to good yields, but the reaction proceeds much faster and in better yields for EWG-substituted aryls. Mechanistically, it was suggested that the reaction proceeds by formation of a lithium enolate under LiBr/Et₃N conditions, which undergoes 1,3-cycloaddition followed by ethanol elimination and spontaneous oxidation. The structure of one product was confirmed by X-ray crystal analysis.