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High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones: Formal Syntheses of ( R )‐Fluoxetine and ( S )‐Duloxetine
Author(s) -
Buitrago Elina,
Lundberg Helena,
Andersson Hans,
Ryberg Per,
Adolfsson Hans
Publication year - 2012
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201200308
Subject(s) - catalysis , chemistry , transfer hydrogenation , amide , chemoselectivity , reboxetine , enantioselective synthesis , taurine , combinatorial chemistry , organic chemistry , thioamide , substrate (aquarium) , medicinal chemistry , amino acid , ruthenium , biochemistry , oceanography , receptor , reuptake inhibitor , serotonin , geology
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 (>99 % ee ) of the formed 1,3‐amino alcohols.