N-Functionalization of 4-amino-2-(trifluoromethyl)-1H-pyrroles: Synthesis of N-alkyl derivatives and 1,2,3-triazol-4-yl-pyrrole scaffolds

The N-functionalization of 4-amino-2-trifluoromethyl-1H-pyrroles using alkyl halides is reported. The selectivity of the alkylation reaction was highly dependent on the nature of the alkyl halide and the reaction conditions applied, that is, methyl iodide may furnish N-methyl or N,N-dimethyl pyrroles, while allyl bromide furnishes N-allyl or N,C-diallyl analogs and propargyl bromide furnishes exclusively N-propargyl pyrroles. The alkylated products were obtained between 65%-90% yields and were subjected to CuAAC reactions, which furnished conjugated 1,2,3-triazoles in good yields (72%-91%). The structures of the obtained compounds were unambiguously determined via 2D-NMR experiments.

Automated summary

The N-functionalization of 4-amino-2-trifluoromethyl-1H-pyrroles using alkyl halides is reported. The selectivity of the alkylation reaction was highly dependent on the nature of the alkyl halide and the reaction conditions applied. The alkylated products were subjected to CuAAC reactions, which furnished conjugated 1,2,3-triazoles in good yields.