(+/-)-3-(1-Methoxyethyl)-3-methyl-1-trimethylsilyloxycyclohexene, as a mixture of diastereoisomers.

Methyllithium (0.83 ml, 1.4 M, 1.17 mmol) was added to a suspension of copper(I) iodide (111 mg, 0.58 mmol) in ether (3 ml) at -15degC to give a colourless solution. Chlorotrimethylsilane (63 mg, 0.58 mmol) and the enone 9 (90 mg, 0.58 mmol) were added at -78degC to give a yellow suspension. After 5 mins THF (4 ml) was added and after 30 mins TMEDA (68 mg, 0.58 mmol) was added. The mixture was allowed to warm to -40degC then added to a mixture of 0.1 N hydrochloric acid (10 ml) and petrol (10 ml). The phases were separated and the organic layer washed with saturated sodium bicarbonate solution (3 x 10 ml), dried (Na2SO4) and concentrated in vacuo to yield the silyl enol ether (82 mg, ~ 51%) as a colourless oil, but contaminated by unreacted enone 9 (12% by proton nmr). This was used directly in the next synthetic step.

delta(H) (5:3 mixture of diastereoisomers, * denotes minor isomer) 0.15*, 0.16 (9H, s, Si(CH3)3); 0.91*, 0.93 (3H, s, 3C(CH3)); 1.02, 1.04* (3H d, J = 6.3 Hz, 2'CH3); 1.16-1.32 and 1.54-1.72 (total 4H, each m, 4CH2 and 5CH2); 1.82-2.08 (2H, m, 6CH2); 2.91, 2.98* (1H, q, J = 6.3 Hz, 1'CH); 3.29*, 3.30 (3H, s, OCH3); 4.62*, 4.80 (1H, s, 2CH).

T.L.C.; Rf ~ 0.73 (1:1 ethyl acetate, petrol).

(+/-)-3-(1-Methoxyethyl)-3-methylcyclohexanone 13, as a mixture of diastereoisomers.

The silyl enol ether (180 mg, 0.74 mmol) was dissolved in CHCl3 and treated with excess 1.0 N hydrochloric acid until T.L.C. analysis showed complete reaction. The mixture was separated and the organic layer dried (MgSO4) and concentrated in vacuo to yield ketone 13 (90 mg, 72%) as an oil.

proton nmr analysis showed a 5:3 mixture of diastereoisomers, ( * denotes minor isomer); delta(H) 0.78 (3H, s, 3C(CH3)); 0.98, 1.01* (3H, d, J = 6.3 Hz, 2'CH3); 1.30-1.52 (1H, m, one of 4CH2 and 5CH2); 1.58-1.96 (3H, m, three of 4CH2 and 5CH2); 1.91*, 2.06 (1H, d, J = 13.9 Hz* and 13.6 Hz respectively, one of 2CH2); 2.12-2.28 (2H, m, 6CH2); 2.33, 2.39* (1H, d, J = 13.6 Hz and 13.9* Hz respectively, one of 2CH2); 2.85*, 2.90 (1H, d, J = 6.3 Hz, 1'CH); 3.21*, 3.25 (3H, s, OCH3).

delta(C) 12.4; 20.0; 21.7; 22.0; 29.6; 30.2; 30.6; 33.0; 40.7; 40.9; 43.0; 48.8; 51.1; 57.3; 83.2 and 83.9 (1'CH); 212.1 and 212.6 (1C).

vmax (liquid film); 2877; 2822; 1713, (ketone); 1464; 1375; 1231; 1191; 1107 cm(-1).

m/z (C.I., NH3); 188 (M + NH4⁺); 171 (MH⁺); high resolution measured at 188.1651;

C10H18O2 + NH4 requires 188.1651 (0 ppm error).

T.L.C.; Rf ~ 0.29 (1:3 ethyl acetate, petrol).

Methyl (+/-)-3-(6-(1-methoxyethyl)-6-methyl-2-cyclohexanone)-2-phenyl-

sulphinylpropionate as a mixture of diastereoisomers.

To a solution of the silyl enol ether (70 mg, 0.29 mmol) in THF (2 ml) was added methyllithium (0.23 ml, 1.40 M, 0.32 mmol) at 0degC. After 5 mins the solution was cooled to -78degC and a solution of the acrylate 45 (91 mg, 0.44 mmol) in THF (0.75 ml) was added to give a yellow solution. After 55 mins acetic acid (23 mg, 0.38 mmol) was added and the mixture allowed to warm to 20-25degC. This was partitioned between ethyl acetate (5 ml) and disodium hydrogen phosphate solution (20 mM, pH 8, 5 ml). After separation the aqueous layer was extracted with ethyl acetate (2 x 5 ml) and the combined organic phases were washed with brine (1 x 15 ml), dried (MgSO4) and concentrated in vacuo to yield the sulphoxide (151 mg) as a crude yellow oil that was used directly in the next synthetic step.

Methyl (+/-)-(E)-3-(6-(1-methoxyethyl)-6-methyl-2-cyclohexanone)acrylate 14 as a mixture of diastereoisomers.

A suspension of the sulphoxide (~ 0.25 mmol) and calcium carbonate (30 mg, 0.30 mmol) in tetrachloromethane (5 ml) was heated at reflux for 5 h. Concentration in vacuo and chromatography (1:3 ethyl acetate, petrol) yielded two main fractions.

Fraction A (21 mg, 33% from the silyl enol ether) as a yellow oil, mainly 2 diastereoisomers by proton nmr.

vmax (liquid film); 2950; 2823; 1724; 1264; 1166; 1108 cm(-1).

m/z (C.I., NH3); 272 (M + NH4⁺); 255 (MH⁺); high resolution measured at 272.1868; C14H22O4 + NH4 requires 272.1862 (~ 3 ppm error).

T.L.C.; Rf ~ 0.21 (1:3 ethyl acetate, petrol).

Fraction B (13 mg, 20% from the silyl enol ether) as a yellow oil, mainly 1 diastereoisomer;

delta(H) 0.91 (3H, s, 6'C(CH3)); 1.07 (3H, d, J = 6.3 Hz, 2"CH3); 1.40-2.10 (4H, m, 4'CH2, 5'CH2); 2.10-2.50 (2H, m, 3'CH2); 2.91 (1H, q, J = 6.3 Hz, 1"CH); 3.22 (1H, d, J = 10.3 Hz, 1'CH); 3.24 (3H, s, OCH3); 3.72 (3H, s, COOCH3); 5.79 (1H, d, J = 15.7 Hz, 2CH); 7.00 (1H, dd, J = 10.3, 15.7 Hz, 3CH).

delta-C 12.1; 17.8; 21.7; 30.5; 40.4; 46.6; 51.6; 57.3; 60.6; 81.5 (1"CH); 124.2 (2CH); 143.4 (3CH); 166.1 (1C); 210.0 (2'C).

vmax 2950; 2823; 1724; 1264; 1166; 1108 cm(-1).

m/z (C.I., NH3); 272 (M + NH4⁺); 255 (MH⁺); high resolution measured at 272.1877; C14H22O4 + NH4 requires 272.1862 (~ 5 ppm error).

T.L.C.; Rf ~ 0.18 (1:3 ethyl acetate, petrol).