Synlett 2006(15): 2427-2430  
DOI: 10.1055/s-2006-950424
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Concise and Efficient Stereoselective Synthesis of the C1-C11 Fragment of Macrolactin A

Carlo Bonini*a, Lucia Chiummientoa, Valeria Videttaa, Françoise Colobertb, Guy Solladiéb
a Dipartimento di Chimica, Università degli Studi della Basilicata, via N. Sauro 85, 85100 Potenza, Italy
Fax: +39(971)202223; e-Mail: bonini@unibas.it;
b Laboratoire de Stéréochemie associé au CNRS, Université Louis Pasteur (ECPM), rue Bacquerel, 67087 Strasbourg, France
Further Information

Publication History

Received 4 July 2006
Publication Date:
08 September 2006 (online)

Abstract

A stereoselective synthesis of the C1-C11 fragment of macrolactin A, using original approaches for the introduction of the Z,E-diene stereochemistry and the C-7 stereogenic center, is reported. The adopted strategy has allowed us to build up the fragment by the assembly of three key intermediates via cross-metathesis, Still-Gennari, and Wittig olefinations. Opening of the commercially available chiral benzyl glycidol epoxide to the corresponding ­homoallylic alcohol introduced the C-7 chiral center. A cross-meta­thesis reaction was used to create the C5-C4 E double bond. The Still-Gennari reaction introduced the 2Z,4E-diene moiety and ­finally the Wittig reaction with a propargylic triphenylphosphorane introduced directly the 1,3-enyne unit in a highly efficient stereo­selective fashion.

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The stereochemical outcome of the one-pot Julia olefination is generally substrate (sulfone and aldehyde) controlled. Moreover, there are some examples where β,γ-unsaturated BT-sulfones give high levels of E stereoselectivity (see ref. 7a).

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Attempts were made to prepare the tributyl propargylic phosphorane but we had some problems obtaining it pure.

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Compound 3 : R f 0.26 (PE-Et2O-CH2Cl2, 99:2:1). 1H NMR (500 MHz, CDCl3): δ = 7.40 (dd, J 4,5 = 14.4 Hz, J 4,3 = 11.9 Hz, 1 H), 6.55 (t, J 3,2 = J 3,4 = 11.0 Hz, 1 H), 6.18 (dd, J 8,9 = 16.0 Hz, J 8,7 = 5.0 Hz, 1 H), 6.03 (dt, J 5,4 = 15.5 Hz, J 5,6 = 8.0 Hz, 1 H), 5.72 (d, J 9,8 = 16.0 Hz, 1 H), 5.61 (d, J 2,3 = 11.5 Hz, 1 H), 4.26 (m, 1 H), 3.73 (s, 3 H), 2.41 (m, 2 H), 0.89 (s, 9 H), 0.19 (s, 9 H), 0.03 (s, 6 H). 13C NMR (125 MHz, CDCl3): δ = 166.9, 146.4, 145.0, 140.4, 129.2, 115.8, 109.2, 103.3, 95.0, 71.8, 51.1, 41.3, 25.8, 18.1, -0.1, -4.6, -4.9. EI-MS: m/z (%) = 392 (100), 267 (100), 73 (50), 75 (20), 45. Anal. Calcd for C21H36O3Si2: C, 64.23; H, 9.24. Found: C, 64.32; H, 9.18.