Ruthenium-Catalyzed Direct Asymmetric Reductive Amination for the Synthesis of a Chiral Primary Amine Intermediate En Route to a PDE2A Inhibitor, TAK-915

Here, we report a novel, efficient ruthenium-catalyzed direct asymmetric reductive amination of an α-alkoxy ketone, a structural motif for which it is more challenging to implement such a transformation than 1,3-dicarbonyl compounds. The discovery of a novel ruthenium catalyst that was highly stable to air and moisture, as well as being readily prepared from commercially available reagents, enabled rapid access to a key synthetic chiral primary amine en route to TAK-915, an active pharmaceutical ingredient for a PDE2A inhibitor.