Synthesis of enantiopure 2-aryl-2-methoxypropionic acids and determination of their absolute configurations by X-ray crystallography

Satoshi Sekiguchi, Junpei Naito, Hiromi Taji, Yusuke Kasai, Akinori Sugio, Shunsuke Kuwahara, Masataka Watanabe, Nobuyuki Harada

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    5 Citations (Scopus)

    Abstract

    Racemic 2-aryl-2-methoxypropionic acids were enantioresolved by the use of (S)-(-)-phenylalaninol 4. For instance, racemic 2-methoxy-2-phenylpropionic acid (±)-7 was condensed with phenylalaninol (S)-(-)-4 yielding a diastereomeric mixture of amides, which was easily separated by HPLC on silica gel affording the first-eluted amide (-)-13a and the second-eluted amide (+)-13b: α = 3.19, Rs = 3.49. The absolute configuration of amide (-)-13a was determined to be (R;S) by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-13a was converted to oxazoline (R;S)-(-)-14a, from which enantiopure 2-methoxy-2-phenylpropionic acid (R)-(-)-7 was recovered. Other 2-aryl-2-methoxypropionic acids, (R)-(-)-8, (R)-(-)-9, (R)-(+)-10, (R)-(-)-11, and (R)-(-)-12, were similarly prepared in enantiopure forms with the use of phenylalaninol (S)-(-)-4, and their absolute configurations were clearly determined by X-ray crystallography or by chemical correlation.

    Original languageEnglish
    Pages (from-to)251-264
    Number of pages14
    JournalChirality
    Volume20
    Issue number3-4
    DOIs
    Publication statusPublished - 2008 Mar 3

    Keywords

    • 2-aryl-2-methoxypropionic acids
    • 2-methoxy-2-phenylpropionic acid
    • Absolute configurations
    • Diastereomeric amides
    • HPLC separation on silica gel
    • Oxazolines
    • Phenylalaninol
    • X-ray crystallography

    ASJC Scopus subject areas

    • Analytical Chemistry
    • Catalysis
    • Pharmacology
    • Drug Discovery
    • Spectroscopy
    • Organic Chemistry

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  • Cite this

    Sekiguchi, S., Naito, J., Taji, H., Kasai, Y., Sugio, A., Kuwahara, S., Watanabe, M., & Harada, N. (2008). Synthesis of enantiopure 2-aryl-2-methoxypropionic acids and determination of their absolute configurations by X-ray crystallography. Chirality, 20(3-4), 251-264. https://doi.org/10.1002/chir.20416