Synthesis of Highly Functionalized 4-Amino-2-(trifluoromethyl)-1H-pyrroles

Abstract

In this work, the reactivity of 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one toward primary aliphatic amines was studied. The reaction was found to be extremely selective to synthesize a series of 1-alkyl-4-aminoalkyl-2-trifluoromethyl-1H-pyrroles (13 examples, at yields up to 90%) and a series of highly functionalized β-enaminones (6 examples, at yields up to 78%), with only the amount of amine and the reaction condition needing to be controlled. The structure of the products was unambiguously determined by single crystal X-ray diffraction and 2D NMR experiments.

Regioselective synthesis of (Z)‐5‐methylene‐containing morpholin‐2‐ones

“…Despite the fact that primary amino groups tend to form the ( Z )‐regiosiomer due to the stabler hydrogen bond with the oxygen of the carbonyl group, these are easily isomerized into variable amounts of ( E )‐/( Z )‐regioisomers [48], which are particularly dependent on the solvent and temperature, but was not observed in this present work. The ( Z )‐regioisomer is easily assigned in the liquid state using the chemical shift of the NH ‐hydrogen, which is observed at approximately 12.0 ppm because of the NH···O interaction and was the strategy used in this present work [49, 50].…”

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks

“…In 2021, Zanatta's group 43 reported a method to synthesize a series of highly functionalized 1-alkyl-4-(aminoalkyl)-2-(trifluoromethyl)-1H-pyrroles and β-enaminones from 5-bromo-1,1,1-trifluoro-4methoxypent-3-en-2-one and primary aliphatic amines with high yields (Scheme 26). The structures of the products were controlled using only the dosage of the primary aliphatic amines.…”