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Stereoselective Reduction of α‐Fluoro‐β‐keto Esters by NADH and NADPH‐Dependent Ketoreductases
Author(s) -
Green Thomas K.,
Damarancha Anil,
Vanagel Matthew,
Showalter Brandon,
Kolberg Sandra,
Thompson Alexander
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900644
Subject(s) - chemistry , diastereomer , stereoselectivity , kinetic resolution , enantiomer , enantiomeric excess , enzyme , biocatalysis , alkyl , nad+ kinase , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry , enantioselective synthesis , reaction mechanism , catalysis
Racemic α‐fluoro‐β‐keto esters were stereoselectively transformed to α‐fluoro‐β‐hydroxy esters through dynamic reductive kinetic resolution (DYRKR) using commercially available NAD(P)H‐dependent ketoreductases. Aromatic, alkenyl, and alkyl substrates were all reduced in high optical purities and yields. For most substrates, either anti or syn diastereomers could be produced with high enantiomeric excess, depending on the enzyme employed. The enzyme reactions with ethyl α‐fluoroacetoacetate were conveniently monitored in real time by in situ 19 F NMR spectroscopy. These commercially available enzymes provide convenient access to stereoisomers of α‐fluoro‐β‐hydroxy esters from easily accessible racemic substrates.