Chemoenzymatic Asymmetric Synthesis of Pyridine‐Based α‐Fluorinated Secondary Alcohols

Fluoro‐substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma‐ and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α‐position. Starting from readily available picoline derivatives prochiral α‐halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.