Silver-Catalyzed Domino Reaction of CF3-Substituted N-Allenamides with Primary Amines for the Construction of 2-Amido-5-fluoropyrroles

We report herein a domino reaction to construct 2-amido-5-fluoropyrroles from CF3-substituted N-allenamides. The in situ generated gem-difluorinated ene-ynamides derived from CF3-substituted N-allenamides, when subjected to silver catalysis with a primary amine, undergo simultaneous hydroamination of the ynamide moiety followed by a 5-endo-trig addition/beta-fluoride elimination sequence, enabling the construction of 2-amido-5-fluoropyrroles. This transformation features excellent functional group compatibility. By employing 2-aminophenols, functionalized benzo-oxazoles were produced.

Automated summary

We developed a domino reaction for the synthesis of 2-amido-5-fluoropyrroles from CF3-substituted N-allenamides. By employing silver catalysis with a primary amine, the in situ generated gem-difluorinated ene-ynamides derived from CF3-substituted N-allenamides undergo simultaneous hydroamination and 5-endo-trig addition/beta-fluoride elimination sequence, leading to the construction of 2-amido-5-fluoropyrroles. This method shows excellent functional group compatibility and can be used for the synthesis of functionalized benzo-oxazoles by using 2-aminophenols.