Synthesis of Unprotected β-Arylethylamines by Iron(II)-Catalyzed 1,2-Aminoarylation of Alkenes in Hexafluoroisopropanol

Angew Chem Int Ed Engl. 2023 Feb 20;62(9):e202215257. doi: 10.1002/anie.202215257. Epub 2023 Jan 18.

Abstract

β-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides a direct entry to unprotected β-arylethylamines with remarkable functional group tolerance, allowing key drug-oriented functional groups to be installed in a two-step process. The use of hexafluoroisopropanol as a solvent in combination with an iron(II) catalyst proved essential to reaching high-value nitrogen-containing molecules.

Keywords: Aliphatic Amine; Alkene; Aminoarylation; Hexafluoroisopropanol; Iron.