Synthesis of Tri(di)fluoroethylanilines via Copper-Catalyzed Coupling Reaction of Tri(di)fluoroethylamine with (Hetero)Aromatic Bromides

We have realized the first Ullmann type coupling reaction of tri(di)fluoroethylamine with (hetero)aromatic bromides, employing 5-20 mol% Cu2O and an oxalamide ligand [N-(2,4,6-trimethoxyphenyl)acetamide]. This efficient and practical method has the following features: i) avoids the use of expensive catalyst; ii) does not require anhydrous solvent and strict air extrusion; iii) uses bench stable and inexpensive (hetero)aromatic bromides; iv) is suitable for the synthesis of fluoroalkylated hetero-aromatic substrates; v) is suitable for gram-scale synthesis. This work also shows the “negative fluorine effect” for the alkylamines in the copper catalysed coupling reactions.