Photobiocatalytic Linear Deracemization of β‐Hydroxynitriles

A photobiocatalytic strategy for the linear deracemization of β‐hydroxynitriles is presented. This method consists of a two‐step process, beginning with the oxidation of the corresponding alcohol racemate (250 mM) using tetrabutylammonium decatungstate (TBADT, 2.5–5.0 mol%) under 390 nm light irradiation in acetonitrile. The second step involves an asymmetric biocatalytic reduction, carried out sequentially by addition of the required reagents with or without solvent evaporation depending on the selected alcohol dehydrogenase (ADH) enzyme and its tolerance to the organic solvent. Under the resulting aqueous conditions (25–75 mM ketone intermediate), the enzymes exhibited high selectivity, enabling access to a series of optically active β‐hydroxynitriles, predominantly with excellent optical purities, leading to nine pairs of enantiomers in 88 to >99% ee . The integration of two sustainable technologies, photo‐ and biocatalysis, provides a straightforward route to chiral β‐hydroxynitriles. In addition, sunlight‐driven applicability and scalability are demonstrated.