Synthesis of 4-(trifluoromethyl)isoquinolines. Influence of trifluoromethyl group on the Pictet–Gams ring closure reaction

Treatment of N-acyl-2-methoxy-2-(trifluoromethyl)arylethylamines under Pictet–Gams conditions afforded 4-methoxy-4-trifluoromethyl-3,4-dihydroisoquinolines which were aromatised by base catalysed methanol elimination. Earlier we described the synthesis of 2-oxazolines by conducting the Pictet–Gams sequence with N-acyl-2-hydroxy-2-(trifluoromethyl)arylethylamines. The operation of these two pathways is explained by the influence of the trifluoromethyl group.