A series of optically active β‐hydroxy sulfones has been obtained through an oxosulfonylation‐stereoselective reduction sequence in aqueous medium. Firstly, β‐keto sulfones were synthesized from arylacetylenes and sodium sulfinates to subsequently develop the carbonyl reduction in a highly selective fashion using alcohol dehydrogenases as biocatalysts. Optimization of the chemical oxosulfonylation reaction was investigated, finding inexpensive iron(III) chloride hexahydrate (FeCl3 ⋅ 6H2O) as the catalyst of choice. The selection of isopropanol in the alcohol‐water media resulted in high compatibility with the enzymatic process for enzyme cofactor recycling purposes, providing a straightforward access to both (R)‐ and (S)‐β‐hydroxy sulfones. The practical usefulness of this transformation was illustrated by describing the synthesis of a chiral intermediate of Apremilast. Interestingly, the development of a chemoenzymatic cascade approach avoided the isolation of β‐keto sulfone intermediates, which allowed the preparation of chiral β‐hydroxy sulfones in high conversion values (83–94 %) and excellent optical purities (94 to >99 % ee).

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