High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones: Formal Syntheses of (R)-Fluoxetine and (S)-Duloxetine
2012 (English)In: ChemCatChem, ISSN 1867-3880, Vol. 4, no 12, 2082-2089 p.Article in journal (Refereed) Published
A total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru(p-cymene)Cl2]2 and [RhCp*Cl2]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 (>99?% ee) of the formed 1,3-amino alcohols.
Place, publisher, year, edition, pages
2012. Vol. 4, no 12, 2082-2089 p.
amino acids, asymmetric synthesis, enantioselectivity, hydrogenation, transition metals
IdentifiersURN: urn:nbn:se:su:diva-84808DOI: 10.1002/cctc.201200308ISI: 000311698800032OAI: oai:DiVA.org:su-84808DiVA: diva2:581481
FunderSwedish Research CouncilKnut and Alice Wallenberg Foundation