Synthesis of the Natural Product Building Block 5-(3-Bromophenyl)-4-hydroxy-5-methylhexan-2-one and its Chiral Characterization by Using Chiroptical Spectroscopy

Authors

  • Ewoud De Gussem,

    1. Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281-S3, 9000 Gent (Belgium)
    2. The European Centre for Chirality (EC2), Groenenborgerlaan 171, 2020 Antwerp (Belgium)
    3. Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)
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  • Jelle Cornelus,

    1. Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium)
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  • Sam Pieters,

    1. Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium)
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  • Dries Van den Bossche,

    1. Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium)
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  • Prof. Dr. Johan Van der Eycken,

    1. Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium)
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  • Prof. Dr. Wouter Herrebout,

    Corresponding author
    1. The European Centre for Chirality (EC2), Groenenborgerlaan 171, 2020 Antwerp (Belgium)
    2. Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)
    • The European Centre for Chirality (EC2), Groenenborgerlaan 171, 2020 Antwerp (Belgium)
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  • Prof. Dr. Patrick Bultinck

    Corresponding author
    1. Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281-S3, 9000 Gent (Belgium)
    2. The European Centre for Chirality (EC2), Groenenborgerlaan 171, 2020 Antwerp (Belgium)
    • Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281-S3, 9000 Gent (Belgium)
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Abstract

The absolute configuration of 5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, an intermediate in the synthesis of various natural products, is assigned by using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD). Experimental spectra were compared to density functional theory (DFT) calculations of the molecule with known configuration. These three techniques independently confirm that the absolute configuration is (S)-5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, thus enabling us to assign the absolute configuration with high reliability. The reliability of the VCD analysis was assessed quantitatively by using the CompareVOA program. We found that, in cases in which the agreement between theory and experiment was very good, a value of 10 cm−1 for the triangular weighting function gave a more-realistic discriminative power between enantiomers than the default value of 20 cm−1.

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