3-(1-Methyl-2,6-dithiane)-2-cyclohexenone[1]

Butyllithium (6.14 ml, 1.63 M, 10 mmol) was added to a solution of 2-methyl-1,3-dithiane (1.34 g, 10 mmoles) and tetramethylethylenediamine (1.16 g, 10 mmol) in THF (20 ml) at -78degC over 2-3 mins. The solution was allowed to warm to -15degC over 1 h and maintained between -15degC and 0degC for a further 1.75 h before being cooled to -78degC. To this was added 3-ethoxy-2-cyclohexene-1-one (1.40 g, 10 mmol), allowed to warm to 20-25degC and stirred for 16 h. Hydrochloric acid (20 ml, 1.0 N, 20 mmol) was added and the mixture was stirred for 24 h. The reaction mixture was extracted with ethyl acetate (3 x 20 ml). The combined organic extracts were washed with saturated brine (60 ml), dried (MgSO4) and concentrated in vacuo. Chromatography (1:3 ethyl acetate, petrol) yielded the dithiane (1.99 g, 87%) as white crystals which could be used without further purification. Alternatively recrystallisation from ether yielded two crops (1.01 g, 44% and 0.43 g, 19%), with identical melting points (corrected), 68-9degC (lit.,[2] m.p. 68.1-69.0degC, 1:1 ether-pentane).

delta(H) 1.59 (3H, s, CH3); 1.76-2.06 (4H, m, 5CH2 and 4'CH2); 2.40 (2H, t, J = 6.4 Hz) and 2.53 (2H, t, 5.8 Hz) (4CH2 and 6CH2); 2.60-2.80 (4H, m, 3'CH2 and 5'CH2); 6.59 (1H, s, 2CH).

m/z (C.I., NH3); 246 (M + NH4⁺).

C11H16OS2 requires C, 57.85%; H, 7.06%; N, 0.00%

found C, 57.94%; H, 6.95%; N < 0.03%

T.L.C.; Rf ~ 0.15 (1:3 ethyl acetate/petrol)

G.C. (50degC to 240degC at 10degC min(-1)); RT = 18.6 mins.

3-Acetyl-2-cyclohexene-1-one 11[3]

Mercuric oxide (27.9 g, 0.129 mol) was added to a solution of the dithiane (14.7 g, 0.064 mol) in THF/H2O (4:1, 500 ml) and cooled to 0degC. To this was added boron trifluoride etherate (54.9 g, 0.386 mol). The resulting suspension was stirred at 0degC for 1.75 h to give a solution. Water (400 ml) was added, the THF removed in vacuo, and the residue extracted with ether (6 x 500 ml). The combined organic extracts were washed with saturated sodium bicarbonate solution (1 x 500 ml) and brine (1 x 500 ml), dried (Na2SO4) and concentrated in vacuo to yield the ene-dione 11 (7.59 g, 85%), as a yellow crystalline solid, m.p. (uncorrected) 52-5degC, that could be used without further purification.

delta(H) 1.92-2.06 (2H, m, 5CH2); 2.35 (3H, s, CH3); 2.38-2.51 (4H, m, 4CH2 and 6CH2 ); 6.52 (1H, s, 2CH).

delta(C) 21.8, 23.2, 26.0, 37.7 (CH3 , 4CH2, 5CH2 and 6CH2); 132.3 (2CH); 154.4 (3C); 199.2, 201.2 (both C=O).

vmax (thin film); 2952; 1679, (alpha,beta-unsaturated ketone, lit.[4] 1709-1681); 1217 cm(-1).

m/z (C.I., NH3); 156 (M + NH4⁺), 139 (MH⁺).

T.L.C.; Rf ~ 0.15 (1:3 ethyl acetate/petrol).

Recrystallisation (petrol/ethyl acetate) yielded a yellow crystalline solid, m.p. (corrected) 50.5-51.5degC, (lit.[5] m.p. 49.8-50.3).

G.C. (50degC to 240degC at 10degC min(-1)); RT = 8.6 mins.

(+/-)-3-(1-Hydroxyethyl)-2-cyclohexene-1-one 12[6]

A solution of sodium borohydride (0.41 g, 0.0109 mol) in methanol/water (1:1, 100 ml) was added to a solution of the ene-dione 11 (5.0 g, 0.036 mol) in methanol/water (1:1, 500 ml) at 0degC. After precisely 5 mins saturated ammonium chloride solution (100 ml) was added. The methanol was removed in vacuo and the aqueous residue was extracted with ethyl acetate (8 x 400 ml) and chloroform (4 x 400 ml). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Chromatography (1:1 ethyl acetate, petrol) yielded the alcohol 12 (3.05 g, 60%) as a colourless oil.

delta(H) 1.34 (3H, d, J = 6.6 Hz, CH3); 1.92-2.08 (2H, m, 5CH2); 2.18-2.44 (4H, m, 4CH2 and 6CH2); 4.36 (1H, q, J = 6.6 Hz, 1'CH); 6.06 (1H, d, J = 1.2 Hz, 2CH).

vmax (liquid film); 3413, (br, OH); 1661 cm(-1) (alpha,beta-unsaturated ketone).

m/z (C.I., NH3); 158 (M + NH4⁺); 141 (MH⁺); high resolution measured at 158.1184; C8H12O2 + NH4 requires 158.1181 (~ 2 ppm error).

T.L.C.; Rf ~ 0.09 (1:1 ethyl acetate, petrol)

G.C. (50degC to 240degC at 10degC min(-1)); RT = 10.4 mins.

(+/-)-3-(1-Methoxyethyl)-2-cyclohexene-1-one 9

A suspension of silver(I) oxide (200 mg) and the alcohol 12 (200 mg) in iodomethane (5 ml) was heated at reflux for 2.75 h. A further portion of silver(I) oxide (100 mg) was added and heating continued for 1 h. The mixture was filtered and concentrated in vacuo to yield the ether 9 (190 mg, 86%) as a colourless oil that could be used without further purification.

delta(H) 1.27 (3H, d, J = 6.6 Hz, 2'CH3); 1.88-2.10 (2H, m, 5CH2); 2.17-2.48 (4H, m, 4CH2 and 6CH2); 3.23 (3H, s, OCH3); 3.80 (1H, q, J = 6.6 Hz, 1'CH); 5.98 (1H, s, 2CH).

vmax (liquid film); 2963; 1669 (alpha,beta-unsaturated ketone); 1109 cm(-1).

m/z (C.I., NH3); 172 (M + NH4⁺); 155 (MH⁺); high resolution measured at 155.1071; C9H14O2 + H requires 155.1072 (< 1 ppm error).

T.L.C.; Rf ~ 0.31 (1:1 ethyl acetate, petrol).

(+/-)-3-(1-tert-Butyldimethylsilyloxyethyl)-2-cyclohexene-1-one 10[7]

To a solution of the alcohol 12 (0.7 g, 5 mmol) in dichloromethane (20 ml) at 0degC was added 2,6-lutidine (1.1 g, 10 mmol) and tert-butyldimethylsilyl trifluoromethane-sulphonate (2.0 g, 7.5 mmol). The solution was allowed to warm to 20-25degC and stirred for 16 h. This was washed with saturated ammonium chloride solution (2 x 20 ml), saturated sodium bicarbonate solution (2 x 20 ml), brine (1 x 20 ml), dried (MgSO4) and concentrated in vacuo to yield the crude product. Chromatography (gradient elution 0-20% ethyl acetate, petrol) yielded the silyl ether 10 (0.9 g, ~ 70%) as a colourless oil.

delta(H) 0.05 (6H, d, J = 7.1 Hz, Si(CH3)2 ); 0.90 (9H, s, C(CH3)3); 1.28 (3H, d, J = 6.4 Hz, 2'CH3); 1.94-2.06 (2H, m, 5CH2); 2.16-2.46 (4H, m, 4CH2 and 6CH2); 4.32 (1H, q, J = 6.4 Hz, 1'CH); 6.04 (1H, d, J = 1.3 Hz, 2CH).

vmax (liquid film); 2954; 2930; 2856; 1673 (alpha,beta-unsaturated ketone); 1631; 1097; 835; 777 cm(-1).

m/z (C.I., NH3); 272 (M + NH4⁺); 255 (MH⁺); high resolution measured at 272.2043; C14H26O2Si + NH4 requires 272.2046 (~ 1 ppm error).

T.L.C.; Rf ~ 0.21 (10% ethyl acetate, petrol).