Stereoselective Palladium-Catalyzed Functionalization of Homoallylic Alcohols: A Convenient Synthesis of Di- and Trisubstituted Isoxazolidines and β-Amino-δ-Hydroxy Esters

Authors

  • Prof. Dr. Andrei V. Malkov,

    Corresponding author
    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
    2. Present address: Department of Chemistry, Loughborough University, Loughborough, Leics LE11 3TU (UK), Fax: (+44) 1509-22-3925
    • Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
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  • Dr. Maciej Barłóg,

    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
    2. Present address: College of Science, Texas A&M University at Qatar, P.O.Box 23874, Doha 23874 (Qatar)
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  • Dr. Lucie Miller-Potucká,

    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
    2. Present address: AstraZeneca, Silk Road Business Park, Charter Way, Macclesfield, Cheshire, SK10 2NA (UK)
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  • Dr. Mikhail A. Kabeshov,

    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
    2. Present address: Department of Chemistry, Loughborough University, Loughborough, Leics LE11 3TU (UK), Fax: (+44) 1509-22-3925
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  • Dr. Louis J. Farrugia,

    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
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  • Prof. Dr. Pavel Kočovský

    Corresponding author
    1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
    • Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44) 141-330-4888
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Abstract

Enantiopure, Boc-protected alkoxyamines 12 and 13, derived from the readily available homoallylic alcohols 4 via a reaction that involves either inversion or retention of configuration, undergo a diastereoselective Pd-catalyzed ring-closing carbonylative amidation to produce isoxazolidines 16/17 (≤50:1 diastereoisomer ratio (d.r.)) that can be readily converted into the N-Boc-protected esters of β-amino-δ-hydroxy acids and their γ-substituted homologues 37. The key carbonylative cyclization proceeds through an unusual syn addition of the palladium and the nitrogen nucleophile across the C[DOUBLE BOND]C bond (1921), as revealed by the reaction of 15, which afforded isoxazolidine 18 with high diastereoselectivity.

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