Chiral building blocks for the synthesis of nitrogen-containing natural products, 5. The enantioselective synthesis of optically active, benzene nucleus-substituted 1-phenylethylamines from the corresponding acetophenones

An efficient two-step procedure for the synthesis of enantiomerically pure, benzene nucleus-substituted 1-phenylethylamines 1 is described, with predictable absolute configuration at the stereogenic center: Imine formation from the substituted acetophenones 6 with (S)- or (R)-1-phenylethylamine [(S)-7 or (R)-7] and subsequent hydrogenation of the resulting Schiff bases 8 over Raney nickel leads to the secondary amines 9 and 10 in high diastereoselectivities. These dibenzylamines are cleaved regioselectively, usually next to the less substituted aromatic ring, giving the desired chiral 1-phenylethylamines 1 in high yields and enantiomeric purities. Scope and limitations of this new and facile approach to the versatile building blocks 1 are reported.