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Synlett 2009(4): 565-568  
DOI: 10.1055/s-0028-1087910
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Hydrosilylation-RCM-Protodesilylation: Application to the Synthesis of ω-Alkenyl α,β-Unsaturated Lactones

Cyril Bressy, Frédéric Bargiggia, Mathieu Guyonnet, Stellios Arseniyadis, Janine Cossy*
Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 Rue Vauquelin, 75231 Paris Cedex 05, France
Fax: +33(1)40794660; e-Mail: janine.cossy@espci.fr;
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Publication History

Received 23 October 2008
Publication Date:
16 February 2009 (online)

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Abstract

A simple and efficient one-pot procedure has been developed for the synthesis of α,β-unsaturated lactones bearing a pendant E-olefin. This new methodology, which features a hydrosilylation, a ring-closing metathesis (RCM) and a protodesilylation reaction, allows to perform RCM on substrates containing an alkyne moiety. The utility of this methodology was further demonstrated in the ­total synthesis of (+)-goniothalamin and (-)-pironetin, two natural products with interesting biological activities.

Key words

hydrosilylation - ring-closing metathesis - protodesilylation - α,β-unsaturated lactones - goniothalamin - pironetin

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The reaction was monitored by TLC.

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General Procedure for the One-Pot Hydrosilylation-RCM-Protodesilylation To a solution of alkyne (1 equiv) in CH2Cl2 (0.1 M solution) at 0 ˚C was added triethoxysilane (1.2 equiv) followed by Cp*Ru(MeCN)3PF6 (0.01 equiv). The flask was immediately allowed to warm to r.t. and stirred until complete conversion of the starting material. Grubbs’ second-generation catalyst was then added (0.05 equiv), and the reaction mixture was stirred at 40 ˚C until complete conversion. The reaction mixture was then allowed to reach r.t. before AgF (2.4 equiv) was added followed by MeOH (0.01 M), H2O (0.01 M), and THF (0.1 M). Stirring was continued in the absence of light until complete consumption of the silylated intermediate, and the reaction mixture was filtered through Celite, extracted with CH2Cl2, dried over MgSO4, and evaporated under reduced pressure. The crude residue was purified by flash column chromatography on SiO2 using a gradient of eluents to afford the desired lactone.
Representative Characterization Data for Selected Products Compound 2a: IR: 2960, 2920, 2870, 1720, 1380, 1240, 980, 820 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.81 (dt, J = 9.6, 4.3 Hz, 1 H), 6.07 (dt, J = 9.6, 1.8 Hz, 1 H), 5.82 (dtd, J = 15.4, 5.8, 1.0 Hz, 1 H), 5.58 (ddt, J = 15.4, 6.6, 1.5 Hz,
1 H), 4.87 (qapp, J = 7.3 Hz, 1 H), 2.45-2.39 (m, 2 H), 2.04 (qapp, J = 6.8 Hz, 2 H), 1.41 (happ, J = 7.3 Hz, 2 H), 0.90 (t, J = 7.3 Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 164.2 (s), 144.7 (d), 135.5 (d), 126.9 (d), 121.6 (d), 78.3 (d), 34.2 (t), 29.8 (t), 21.9 (t), 13.6 (q). ESI-HRMS: m/z calcd for C10H14NaO2 [M + Na]+: 189.0891; found: 189.0886.
Compound 2c: IR: 2920, 1720, 1640, 1390, 1250, 820 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.87 (ddd, J = 9.8, 5.0, 3.0 Hz, 1 H), 6.01 (dt, J = 9.8, 2.0 Hz, 1 H), 5.78 (ddt, J = 17.2, 10.1, 6.6 Hz, 1 H), 5.01 (dqapp, J = 17.2, 2.0 Hz, 1 H), 5.01 (dqapp, J = 10.1, 3.3 Hz, 1 H), 4.41 (m, 1 H), 2.35-2.29 (m, 2 H), 2.14-2.01 (m, 2 H), 1.86-1.71 (m, 1 H), 1.70-1.56 (m, 2 H), 1.56-1.42 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 163.5 (s), 144.0 (d), 137.0 (d), 120.4 (d), 114.0 (t), 76.8 (d), 32.3 (t), 31.2 (t), 28.4 (t), 22.9 (t). ESI-HRMS: m/z calcd for C10H14NaO2 [M + Na]+: 189.0891; found: 189.0886.