Synthesis of α-trifluoromethyl-phenethylamines from α-trifluoromethyl β-aryl enamines and β-chloro-β-(trifluoromethyl)styrenes

A novel synthetic approach towards α-trifluoromethyl-phenethylamines was elaborated by reduction of the electron deficient β-aryl-α-trifluoromethyl enamines and imines with sodium cyanoborohydride in the presence of trifluoroacetic acid. The starting imines were prepared by the reaction of primary amines with β-aryl-α-trifluoromethyl enamines or β-chloro-β-(trifluoromethyl)styrenes.

Graphical abstractA novel synthetic approach towards α-trifluoromethyl-phenethylamines was elaborated by reduction of the electron deficient β-aryl-α-trifluoromethylenamines and imines with sodium cyanoborohydride in the presence of trifluoroacetic acid.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New synthetic pathways towards α-trifluoromethylated phenylethylamines are disclosed. ► Corresponding enamines and β-chloro-β-trifluoromethylstyrenes are used as starting materials. ► Two pharmacophores, the β-phenethylamine and the CF3-groups, are present in the products. ► Saturated trifluoromethylated alcohols are produced as side products. ► Possible mechanisms of formation of side products are discussed.