Combining Photocatalytic Oxidation of β-Chlorohydrins with Carbonyl Bioreduction in a Deracemization Approach

Enantiopure β-chlorohydrins are valuable intermediates in organic synthesis, acting as chiral building blocks for obtaining biologically active compounds. This work presents a one-pot two-step linear sequence for the efficient deracemization of β-chlorohydrins by combining a photocatalytic alcohol oxidation with a stereoselective carbonyl bioreduction using alcohol dehydrogenases. Despite the thermodynamic challenges of the oxidation step for this family of substrates, three efficient photochemical conditions under white light irradiation are found using catalytic 2,4,6-triphenylpyrylium tetrafluoroborate or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in this case in stoichiometric or by in situ regeneration of the catalyst. In addition, its sunlight-driven applicability and its implementation in flow chemistry are demonstrated. After testing the scope of these methodologies, 2-chloro-1-arylethanols are found as suitable substrates. For those β-halohydrins oxidized with complete conversion, the deracemization strategy is successfully achieved, yielding 12 enantiopure (R)- and (S)-β-halohydrins. Furthermore, 2-chloro-1-phenylethanol enantiomers are subjected to an additional chemical cyclization under basic conditions, providing both (R)- and (S)-styrene oxide in a three-step one-pot process and without loss of the optical activity.