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 19F NMR spectroscopy. These commercially available enzymes provide convenient access to stereoisomers of α‐fluoro‐β‐hydroxy esters from easily accessible racemic substrates.
Stereoselective reduction of ketones
to alcohols using baker’s
yeast is a classic experiment in the undergraduate laboratory. Here
we illustrate the reduction of racemic ethyl 2-fluoro-3-oxobutanoate
to the corresponding alcohol using a set of four commercially available
ketoreductases (KREDs). The reaction sets two stereocenters with four
stereoisomers possible, with different KREDs selecting for different
stereoisomers. Products are characterized by 1H and 19F NMR spectroscopy to establish diastereomeric and enantiomeric
excess. Students learn about dynamic reductive kinetic resolution
(DYRKR) and perform NMR Mosher ester analysis for stereochemical assignments.
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