Synthesis of Chiral Diamine Ligands Derived from Cinchona Alkaloids and Their Catalytic Performance for Asymmetric Transfer Hydrogenation

The asymmetric transfer hydrogenation using 2-propanol as the hydrogen source is a practical and versatile method for obtaining secondary alcohols because of the inexpensive reagents and operational simplicity. Six chiral diamine ligands were synthesized from two natural Cinchona alkaloids, quinine and cinchonine, under mild conditions. They were first tested by asymmetric transfer hydrogenation of acetophenone in iridium and rhodium catalytic systems using 2-propanol as the hydrogen source. Both the iridium and rhodium complexes of these ligands showed high activity for this reaction, and the enantioselectivity was influenced deeply by the structure of the chiral ligands. The complexes of 9-amino (9-deoxy) epiquinine and 9-amino (9-deoxy) epicinchonine proved to be effective catalysts, whereas their benzamides and 4-chlorobenzamides provided only moderate enantiomeric excess (ee). The Ir-complex of 9-amino (9-deoxy) epicinchonine was also applied in the hydrogenation of seven aromatic ketone substrates, resulting in a high catalytic activity (80%–90%) and high enantioselectivity (95%–97% ee, except 72% ee for 4-chloroacetophenone). This is the first case using Cinchona alkaloids skeleton in the iridium-catalyzed asymmetric reactions.