High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones: Formal Syntheses of (<i>R</i>)‐Fluoxetine and (<i>S</i>)‐Duloxetine

Abstract

Abstract A total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru( p ‐cymene)Cl 2 ] 2 and [RhCp*Cl 2 ] 2 , and used as catalysts for the asymmetric transfer hydrogenation of four different heteroaromatic ketones in 2‐propanol. The reactions were performed on a Chemspeed automated high‐throughput screening robotic platform. Optimal catalysts were identified for the individual heterocyclic substrate classes. Based on these results, the formal syntheses of the antidepressant drugs ( R )‐fluoxetine and ( S )‐duloxetine were conducted by using the found catalysts in the key reaction step, which results in high isolated yields (94 %) and excellent product enantioselectivities (&gt;99 % ee ) of the formed 1,3‐amino alcohols.