Stereoselective Reduction of α-Fluoro-β-ketoesters: Ketoreductases and Dynamic Reductive Kinetic Resolution

Abstract

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.