Iridium-Catalyzed Enantioselective Hydrogenation of Simple Ketones Using 1,2-Diphenylethylenediamine-Derived P,N,N-Ligands with a Tertiary Amine Terminus

The employment of a facile ligand to achieve the efficient enantioselective hydrogenation of ketones is of great interest and importance. Herein, we disclose Ir-catalyzed asymmetric hydrogenation of simple ketones using readily available P,N,N-ligands derived from 1,2-diphenylethylenediamine with a tertiary amine terminus, giving rise to the corresponding alcohols with high reactivity (up to 9800 TON) and enantioselectivity (up to >99% ee). The utility of this protocol has been demonstrated by the gram-scale synthesis of (S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol using (R,R)-L4, which is the key intermediate for the synthesis of (S)-duloxetine.