A solution of (S)-citronellal (10g, 64.9mmol) in dry diethyl ether (100ml) was cooled to 0degC under argon, then treated with a solution of methylmagnesium bromide (31.5ml of a 3M solution in diethyl ether, 94.4mmol). The resulting mixture was stirred at 0degC for 15min., then saturated aqueous ammonium chloride (100ml) added. The aqueous layer was extracted with diethyl ether (2x100ml), and the combined etheral solutions dried and concentrated under reduced pressure. The crude residue was dissolved in dry N,N-dimethylformamide (50ml) and treated with imidazole (8.8g, 129.8mmol), followed by t-butyldimethylsilyl chloride (14.7g, 97.4mmol). The resulting mixture was stirred at room temperature under argon for 12h, then added to a mixture of 2M hydrochloric acid (100ml) and diethyl ether (300ml). The ether layer was washed with brine (5x100ml), dried, and concentrated under reduced pressure. Chromatography on silica gel (petroleum ether) gave (6S, 8R/S)-8-^tbutyldimethylsilyloxy-6-methyl non-2-ene (4) as a colourless oil (15.3g, 82%).

Proton nmr (300 MHz, CDCl3) delta 5.10-5.05(1H, m, CH=C), 3.88-3.80(1H, m, CHOTBS), 1.96-0.75(10H, m), 1.66(3H, s, C=CCH3), 1.58(3H, s, C=CCH3), 1.09(1.5H, d, J=6.0Hz, OCCH3, one diastereiosomer), 1.08(1.5H, d, J=6.0Hz, OCCH3, one diastereiosomer), 0.87(4.5H, SiC(CH3)3, one diastereiosomer), 0.86(4.5H, Si(CH3)3, one diastereiosomer), 0.03-0.00(6H, m, 2xSiCH3); Vmax (neat) 1611 cm^-1; m/z (CI, NH3) 302 (M+NH4)⁺, 285 (M+H)⁺, 269, 151, 132, 109, 91. Found (M+H)⁺ 285.2607. C17H37OSi requires 285.2614.

Preparation of (2E, 6S, 8R/S)-Ethyl 8-^tbutyldimethylsilyloxy-2,6-dimethyl non-2-enoate (5)

(6S, 8R/S)-8-^tbutyldimethylsilyloxy-6-methyl non-2-ene (4) (14.5g, 51mmol) was dissolved in dry dichloromethane (200ml), cooled to 0degC, and ozone bubbled through the solution for 3h. Nitrogen was then passed through the solution for 15min to remove any remaining ozone, and then triphenylphosphine (13.4g, 51mmol) added in portions. The mixture was stirred at room temperature for 30min., then carboethoxyethylenetriphenylphosphorane (18.5g, 51mmol) added. The mixture was stirred at room temperature for 15min., then concentrated under reduced pressure. The residue was extracted with hot diethyl ether / petroleum ether (2x100ml of a 1:1 mixture), and the extracts concentrated under reduced pressure. The residue was purified by chromatography on silica gel (3% diethyl ether - 97% petroleum ether) to give ethyl (2E, 6S, 8R/S)-8-^tbutyldimethylsilyloxy-2,6-dimethyl non-2-enoate (5) as a colourless oil (13.26g, 76%).

Proton nmr (300 MHz, CDCl3) delta 6.75-6.69(1H, m, CH=C), 4.19-4.12(2H, m, CO2CH2CH3), 3.87-3.81(1H, m, CHOTBS), 2.20-0.81(13H, m), 1.80(3H, s, C=CCH3), 1.56(3H, s, C=CCH3), 1.09(1.5H, d, J=6.0Hz, OCCH3, one diastereiosomer), 1.08(1.5H, d, J=6.0Hz, OCCH3, one diastereiosomer), 0.86(4.5H, SiC(CH3)3, one diastereiosomer), 0.85(4.5H, Si(CH3)3, one diastereiosomer), 0.03-0.01(6H, m, 2xSiCH3); Vmax (neat) 1710, 1603 cm^-1; m/z (CI, NH3) 343 (M+H)⁺. Found (M+H)⁺ 343.2660. C19H39O3Si requires 343.2668.

Preparation of (2R/S, 6S, 8R/S)-Ethyl 8-^tButyldimethylsilyloxy-2,6-dimethyl nonanoate

10% Palladium-on-carbon (0.5g) was added to a stirred solution of (2E, 6S, 8R/S)-ethyl 8-^tbutyldimethylsilyloxy-2,6-dimethyl non-2-enoate (5) (7.5g, 21.9mmol) in ethanol (200ml), and the mixture placed under an atmosphere of hydrogen. After stirring at room temperature for 12h, the catalyst was removed by filtration, and the solvent evaporated under reduced pressure. The crude product was purified by chromatography on silica gel (5% diethyl ether - 95% petroleum ether) to give (2R/S, 6S, 8R/S)-ethyl 8-^tbutyldimethylsilyloxy-2,6-dimethyl nonanoate as a colourless oil (4.0g, 53%)

Proton nmr (300 MHz, CDCl3) delta 4.10(2H, q, J=7.0Hz, CO2CH2CH3), 3.86-3.80(1H, m, CHOTBS), 2.42-2.35(1H, m, CHCO2Et), 1.69-0.77(30H, m), 0.03-0.00(6H, m, 2xSiCH3); Vmax (neat) 1737 cm-1; m/z (CI, NH3) 363 (M+NH4)⁺, 345 (M+H)⁺, 271, 232, 213. Found (M+H)⁺ 345.2820. C19H44O3Si requires 345.2825.

Preparation of (2R/S, 6S, 8R/S)-8-^tButyldimethylsilyloxy-2,6-dimethyl nonanoic acid (6)

To a stirred solution of ethyl (2R/S, 6S, 8R/S)-8-^tbutyldimethylsilyloxy-2,6-dimethyl nonate (1.0g, 2.9mmol) in ethanol (7ml) was added an aqueous solution of 10M potassium hydroxide (0.58ml). When the reaction had gone to completion by tlc, the ethanol was removed under reduced pressure. The residue was cooled to -10degC, then acidified with 1 M hydrochloric acid to pH 1 and extracted with ethyl acetate (5x20ml). After washing with brine the organics were dried and concentrated to yield the corresponding acid (6) as a clear liquid (0.98g, 91%).

Proton nmr (300 MHz, CDCl3) delta 3.87-3.81 (1H, m, CHOSi), 2.44 (1H, m, CHCO2H), 1.66-1.55 (1H, m, -CH-), 1.48-1.24 (8H, m, 4xCH2), 1.15 (3H, m, CH3CHO), 1.08 (3H, m, CH3CHCO2H), 0.85 (12H, m, CH3CH, C(CH3)3), 0.02 (6H, s, Si(CH3)2); Vmax (neat) 3249 br, 2957, 2928, 1738, 1709, 1567, 1531, 1514, 1463, 1415 cm^-1; m/z (CI, NH3) 334 (M+NH4)⁺, 317 (M+H)⁺, 279, 275, 225, 185, 94, 72. Found (M+H)⁺ 317.2506. C17H37O3Si requires 317.2512.