(+/-)-(S*,S*)-3-(1-tert-Butyldimethylsilyloxyethyl)-3-methyl-1-rimethyl-silyloxycyclohexene

To a suspension of copper(I) iodide (1.20 g, 6.32 mmol) in ether (15 ml) at -20degC was added methyllithium (7.5 ml, 1.4 M, 10.5 mmol) to give a colourless solution. This was cooled to -78degC and to it was added a solution of the enone 10 (0.89 g, 3.51 mmol) in ether (6 ml). The mixture was allowed to warm slowly to -10degC whereupon it was cooled to -40degC. Chlorotrimethylsilane (1.14 g, 10.5 mmol) and THF (75 ml) were added and the mixture was allowed to warm slowly to 0degC and maintained at 0degC for 90 mins. Saturated sodium bicarbonate solution (100 ml) was added and the mixture was extracted with ethyl acetate (4 x 100 ml). The combined organic extracts were washed with brine (1 x 400 ml), dried (MgSO4) and concentrated in vacuo to yield the silyl enol ether (1.08 g, 90%) as a colourless oil.

delta(H) (7:1 mixture of diastereoisomers, major isomer quoted) 0.04 (6H, d, J = 4.1 Hz, Si(CH3)2); 0.19 (9H, s, Si(CH3)3); 0.90 (9H, s, C(CH3)3); 0.93 (3H, s, 3C(CH3)); 1.05 (3H, d, J = 6.3 Hz, 2'CH3); 1.10-1.70 (4H, m, 4CH2 and 5CH2); 1.94 (2H, br t, J = 5.4 Hz, 6CH2); 3.55 (1H, q, J = 6.3 Hz, 1'CH); 4.69 (1H, s, 2CH).

vmax (liquid film); 2957; 2930; 2857; 1661; 1252; 1098; 865; 839 cm(-1) .

m/z (C.I., NH3); 343 (MH⁺); high resolution measured at 343.2480; C18H38O2Si2 + H requires 343.2489 (~ 2 ppm error).

T.L.C.; Rf ~ 0.65 (1:3 ethyl acetate, petrol).

(+/-)-(S*,S*)-3-(1-tert-Butyldimethylsilyloxyethyl)-3-methylcycohexanone 15

The above silyl enol ether (180 mg, 1.06 mmol) was dissolved in chloroform ( ~2 ml) and treated with 1.0N hydrochloric acid ( ~2 ml) at 20-25degC until T.L.C. analysis showed complete reaction. The mixture was separated and the organic layer dried (MgSO4) and concentrated in vacuo to yield the ketone 15 (135 mg, 96%) as an oil.

delta(H) (7:1 mixture of diastereoisomers, major isomer quoted) 0.02 (6H, d, J = 8.8 Hz, Si(CH3)2); 0.80 (3H, s, 3C(CH3)); 0.86 (9H, s, C(CH3)3); 1.05 (3H, d, J = 6.1 Hz, 2'CH3); 1.44-2.05 (5H, m) and 2.06-2.36 (2H, m) (one of 2CH2 and 4CH2, 5CH2, 6CH2); 2.42 (1H, d, J = 13.5 Hz, one of 2CH2); 3.43 (1H, q, J = 6.1 Hz, 1'CH).

delta(C) (both isomers) ~ 0.0; 17.8; 18.0; 18.2; 19.2; 20.7; 22.1; 26.1; 29.9; 30.1; 32.2; 41.4; 44.1; 49.1; 51.0; 75.1 (1'CH); 213.4 (1C).

vmax (liquid film) 2955; 2857; 1716 (ketone); 1251; 1107; 837; 775 cm(-1)

m/z (C.I., NH3); 288 (M + NH4⁺); 271 (MH⁺); high resolution measured at 288.2340; C15H30O2Si + NH4 requires 288.2359 (~ 6 ppm error).

T.L.C.; Rf ~ 0.38 (1:3 ethyl acetate, petrol).

(+/-)-(S*,S*)-3-(1-Hydroxyethyl)-3-methylcyclohexanone 16

A solution of the silyl ether from the preceding reaction (135 mg, 0.50 mmol) in acetonitrile (0.5 ml) was treated with aqueous hydrogen fluoride (50%, 1 drop) and stirred for 16 h at 20-25degC. Saturated sodium bicarbonate solution (1 ml) was added and the acetonitrile was removed in vacuo. The aqueous residue was extracted with ethyl acetate (4 x 1 ml). The combined organic extracts were washed with brine (1 x 4 ml), dried (MgSO4) and concentrated in vacuo to yield the alcohol 16 (62 mg, 80%) as a colourless oil.

delta(H) (~7:1 ratio of diastereoisomers, major isomer quoted, D2O shake) 0.85 (3H, s, 3C(CH3)); 1.14 (3H, d, J = 6.4 Hz, 2'CH3); 1.34-2.10 (4H, m, 4CH2 and 5CH2); 2.00 (1H, d, J = 13.1 Hz, one of 2CH2); 2.19-2.37 (2H, m, 6CH2); 2.41 (1H, d, J = 13.1 Hz, one of 2CH2); 3.51 (1H, q, J = 6.4 Hz, 1'CH).

delta(C) (major isomer quoted, resonance for quaternary 3C not distinguished from minor isomer resonances); 17.5; 20.4; 21.8; 30.8; 41.0; 50.7; 74.2 (1'CH); 212.6 (1C).

vmax (liquid film) 3445 (br, OH); 2961; 2875; 1704 (ketone); 1097 cm(-1).

m/z (C.I., NH3); 174 (M + NH4⁺); 157 (MH⁺).

T.L.C.; Rf ~ 0.23 (1:1 ethyl acetate, petrol).

(+/-)-(1S*,5R*,7S*)-5-Methoxy-1,7-dimethyl-6-oxabicyclo[3.2.1]octane 17

A suspension of the alcohol 16 (62 mg, 0.40 mmol) and silver(I) oxide (62 mg) in iodomethane (4 ml) was heated at reflux for 2.5 h. The mixture was filtered and concentrated in vacuo. Chromatography (1:3 ethyl acetate, petrol) yielded the acetal 17 (28 mg, 41%) as a colourless oil. Care must be taken in isolating the product because of its volatility, some loss is difficult to avoid.

delta(H) (~ 6:1 mixture of diastereoisomers, major isomer quoted) 0.89 (3H, s, 1C(CH3)); 1.15 (3H, d, J = 6.5 Hz, 7CH(CH3)); 1.20-1.37 (1H, m, 2CH2alpha); 1.31 (1H, d, J = 10.9 Hz, 8CH2alpha); 1.40-1.70 (3H, m) and 1.70-1.83 (2H, m) (2CH2beta, 3CH2, 4CH2); 2.06 (1H, dt, J = 10.9 Hz, 2.5 Hz, 8CH2beta); 3.32 (3H, s, OCH3); 3.87 (1H, dq, J = 1.2 Hz, 6.5 Hz, 7CH).

delta(C) (major isomer quoted, resonance for quaternary 1C not distinguished from minor isomer resonances); 12.9; 19.9; 22.2; 32.3; 34.6; 45.7; 49.0; 83.3 (7CH); 107.8 (5C).

vmax (liquid film) 2956; 2870; 2854; 1461; 1081 cm(-1).

m/z (C.I., NH3); 171 (MH⁺).

T.L.C.; Rf ~ 0.38 (1:3 ethyl acetate, petrol).