Chemoenzymatic Oxosulfonylation-Bioreduction Sequence for the Stereoselective Synthesis of β-Hydroxy Sulfones.

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  ⋅ 6H2 O) 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). © 2021 The Authors. ChemSusChem published by Wiley-VCH GmbH.

Citation

Marina López-Agudo, Nicolás Ríos-Lombardía, Javier González-Sabín, Iván Lavandera, Vicente Gotor-Fernández. Chemoenzymatic Oxosulfonylation-Bioreduction Sequence for the Stereoselective Synthesis of β-Hydroxy Sulfones. ChemSusChem. 2022 May 06;15(9):e202101313

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PMID: 34409744

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