Synthesis of Chiral Trifluoromethyl Benzylamines by Heterogeneous Catalytic Reductive Amination

The synthesis of several chiral α,α,α-trifluoromethylbenzylamines by an environmentally benign exclusively heterogeneous catalytic method is described. The procedure is based on trifluoromethyl acetophenones as starting materials. The commercially available inexpensive K-10 montmorillonite was applied for the synthesis of imines from the α,α,α-trifluoromethyl ketones and chiral α-methylbenzylamines. The diastereoselective hydrogenations of the imines were carried out in the presence of 5 % Pd/BaCO₃ catalyst followed by the hydrogenolysis of the benzylic group under acidic conditions to give the respective chiral amines in good yields. The diastereomeric excess achieved in the hydrogenation was further enhanced by a secondary kinetic resolution during the hydrogenolysis step ensuring good to excellent enantioselectivities. The simplicity of this method makes it an alternative synthetic procedure for the preparation of both enantiomers of substituted chiral α,α,α-trifluoromethylbenzylamines.