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Enantioselective Rearrangement Coupled with Water Addition: Direct Synthesis of Enantiomerically Pure Saturated Carboxylic Acids from α,β-Unsaturated Aldehydes

Authors

  • Till Winkler,

    1. Institute of Molecular Enzymtechnology at the Heinrich-Heine-University Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich (Germany)
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  • Prof. Dr. Harald Gröger,

    Corresponding author
    1. Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld (Germany)
    • Harald Gröger, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld (Germany)

      Werner Hummel, Institute of Molecular Enzymtechnology at the Heinrich-Heine-University Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich (Germany)

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  • Prof. Dr. Werner Hummel

    Corresponding author
    1. Institute of Molecular Enzymtechnology at the Heinrich-Heine-University Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich (Germany)
    • Harald Gröger, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld (Germany)

      Werner Hummel, Institute of Molecular Enzymtechnology at the Heinrich-Heine-University Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich (Germany)

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Abstract

A novel type of organic synthesis enabling a direct one-pot transformation of α,β-unsaturated aldehydes into saturated carboxylic acids is described. As sole reagent water is required, which is integrated completely in the product. This tandem process proceeds under perfect atom economy, and consists of two coupled redox biotransformations without the need of external co-substrates for cofactor regeneration. The initial reduction of the C[DOUBLE BOND]C double bond of an α,β-unsaturated aldehyde is catalyzed by an NADPH-dependent ene reductase, leading to the formation of the saturated aldehyde and NADP+. The aldehyde intermediate is then oxidized to the corresponding carboxylic acid, thus regenerating NADPH for the next catalytic cycle. When using prochiral α,β-unsaturated aldehydes as substrates the corresponding carboxylic acids are formed enantioselectively with up to >99 % ee as demonstrated, e.g., for the transformation of citral to (S)-citronellic acid.

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