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

Abstract

Abstract 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.