Stereoselectivity in (Z)-Vinylmetal Additions to the Dictyostatin C1–C9 β-Silyloxy Aldehyde

Authors

  • Andrea Ambrosi,

    1. Università degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, Centro Interdipartimentale C.I.S.I., Via G. Venezian 21, 20133 Milan, Italy, Fax: +39-02-50314072
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  • Luca Pignataro,

    1. Università degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, Centro Interdipartimentale C.I.S.I., Via G. Venezian 21, 20133 Milan, Italy, Fax: +39-02-50314072
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  • Chiara Zanato,

    1. Università degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, Centro Interdipartimentale C.I.S.I., Via G. Venezian 21, 20133 Milan, Italy, Fax: +39-02-50314072
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  • Cesare Gennari

    1. Università degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, Centro Interdipartimentale C.I.S.I., Via G. Venezian 21, 20133 Milan, Italy, Fax: +39-02-50314072
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Abstract

(Z)-Vinyl iodides 6ad were synthesized in high yield with good diastereo- and enantioselectivity using a Marshall–Tamaru, Pd-catalyzed allenylzinc reaction as the key step. The addition of 6ad to the dictyostatin C1–C9 β-silyloxy aldehyde 5 was carried out through the vinyllithium and lithium vinylzincate routes. The lithium vinylzincate additions always proceeded in higher yields and gave fewer side products than the corresponding vinyllithium additions. The configuration of the newly created C9 stereocenter was assigned through Rychnovsky's acetonide 13C NMR method. The diastereoselectivity in this particular type of (Z)-vinylmetal addition reaction appears to be controlled by a subtle balance between the intrinsic stereochemical preference of the β-silyloxy aldehyde (1,3-anti-selective) and that of the chiral lithium (Z)-vinylzincates. The latter becomes more influential with increasing stereochemical complexity, that is, passing from a stereodyad (6a,6b) to a stereotriad (6c,6d).

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