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

Abstract

We report herein a domino reaction to construct 2-amido-5-fluoropyrroles from CF 3 -substituted N-allenamides. The in situ generated gem-difluorinated ene-ynamides derived from CF 3 -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/β-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.

Silver-catalyzed synthesis of nitrogen heterocycles: recent advancements

“…2-Amido-5-fluoropyrroles were fabricated by reacting CF 3 -substituted N -allenamides 88 and primary amines 89 in the presence of a silver catalyst by Miesch and co-workers in 2023. 76 This one-pot domino reaction was carried out by reacting primary amines 89 with N -allenamides 88 in the presence of 20 mol% AgNO 3 63 and 2 equiv. t BuOK in DCM at 0 °C to room temperature for 2–16 h, producing the desired 2-amido-5-fluoropyrroles 92 in moderate to good yields (Scheme 29).…”

Mechanosynthesis of Pyrrole-2-carboxylic Acids via Copper-Catalyzed Spiroannulation/Ring-Opening Aromatization of 4-Arylidene Isoxazol-5-ones with Enamino Esters

“…Meanwhile, the Yang group reported a CuBr-catalyzed selective synthesis of cyclohexanone-fused pyrroles through the substituent-controlled cyclization of O -acyl oximes with cyclic 1,3-diones . Besides, other transition metal catalysts including Au, Pd, Ag, Rh, and Ru have also been employed in pyrrole synthesis. Although these advances are useful, large amounts of solvents, external heating, long reaction time, and/or highly functionalized starting materials are often required, which will limit the practicability of these methods.…”