Synthesis of Chiral Exocyclic Amines by Asymmetric Hydrogenation of Aromatic Quinolin-3-amines

Asymmetric hydrogenation of aromatic quinolin-3-amines was successfully developed with up to 94% enantiomeric excess (ee). Introduction of the phthaloyl moiety to the amino group is crucial to eliminate the inhibition effect caused by the substrate and product, to activate the aromatic ring, and to improve the diastereo-selectivity. This new methodology provides direct and facile access to chiral exocyclic amines. Notably, this report is the first on the highly enantioselective hydrogenation of aromatic amines.