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Synlett 2003(1): 0107-0111
DOI: 10.1055/s-2003-36222
LETTER
© Georg Thieme Verlag Stuttgart · New York

The β-Lactone Route to β-Hydroxy or α,β-Unsaturated γ- and δ-Lactones. Syntheses of (±)-Massoialactone and (±)-Prelactone B

Lycia Fourniera, Anouk Gaudel-Siria, Philip J. Kocieňskib, Jean-Marc Pons*a
a Laboratoire de Réactivité en Synthèse Organique (RéSO), UMR CNRS 6516, Faculté des Sciences de St-Jérôme, boîte D12, 13397 Marseille Cedex 20, France
Fax: +33(4)91288841; e-Mail: jean-marc.pons@univ.u-3mrs.fr;
b Department of Chemistry, Leeds University, Leeds, LS29JT, UK
Further Information

Publication History

Received 18 October 2002
Publication Date:
18 December 2002 (online)

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Abstract

Aqueous HF promotes the translactonization of silyloxy β-lactones into β-hydroxy or α,β-unsaturated γ- and δ-lactones. The reaction is studied from a theoretical point of view and applied to the racemic synthesis of two natural bioactive δ-lactones.

Key words

silylketene - lactone - transition state - HF - translactonization.

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Typical Procedure: 4-Hydroxy-5-pentyl dihydrofuran-2-one 6: [23] To a solution of β-lactones 2 (4/1 mixture of diastereomers: 250 mg, 0.9 mmol) was added aq HF (1 mL). After 4 h stirring at 50 °C, the reaction was extracted with ether (4 × 4 mL). The organic phases were dried over MgSO4 and concentrated in vacuo. A purification by flash chromatography (petrol ether:ether 1:1) yielded hydroxy lactone 6 (150 mg, 0.87 mmol, 97%) as a 4/1 mixture of 2 diastereomers. Compound 6: IR(film): ν = 3400, 2900, 1760, 1590, 1150 cm-1. 1H NMR (500 MHz, CDCl3) major isomer: δ = 4.47 (1 H, broad t, J = 3.9 Hz), 4.36 (1 H, ddd, J = 9.1, 5.7, 3.6 Hz), 2.79 (1 H, ABX, J AB = 17.5, J AX = 5.2 Hz), 2.54 (1 H, ABX, J AB = 17.5, J BX = 0.9 Hz), 1.80-1.50 (2 H, m), 1.44-1.24 (6 H, m), 0.92 (3 H, t, J = 7.0 Hz).

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Geometries of reactants, intermediates and products were determined by minimization of energy with respect to all geometric parameters. Transition states were located by minimizing the gradient norm of the energy and characterized by one, and only one, negative eigenvalue of the Hessian matrix. Finally, transition states reported were shown to belong to the studied reaction by Intrinsic Reaction Coordinate (IRC) for semiempirical and ab initio calculations.

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The SMx solvatation models found in AMPAC were contributed from the University of Minesota by G. D. Hawkins, D. A. Liotard, C. J. Cameron and D. G. Truhlar.

22

The relative stereochemistry of the major diastereomer of β-lactones 11 was deduced from the one of Prelactone B. It is however consistent with the 1,3-induction generally observed in β-lactone formation. [6d]