(4aR*, 5S*, 8aR*) 5-(tert-Butyldimethylsilyl)oxy-8a-hydroxy-4a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalene-2-carbonitrile (12):

NaCN (0.176 g, 3.53 mmol) was added to a solution of tosylate 11b (1.460 g, 3.21 mmol) in HMPA (14 mL). The reaction mixture was stirred for 18 h at room temperature, diluted with Et2O (100 mL) and washed with H2O (2 ¥ 50 mL), brine (50 mL), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by chromatography (AcOEt/cyclohexane 10/90) to give 0.822 g (2.56 mmol, 79%) of 12 as a white solid.
M.p. 104-106 °C (pentane).

1H NMR: d = 0.03 (s, 3 H), 0.04 (s, 3 H), 0.84 (s, 3 H), 0.88 (s, 9 H), 1.30-1.90 (m, 8 H), 2.32 (m, 2 H), 3.86 (dd, 1 H, J = 10 Hz, J = 5 Hz), 6.39 (t, 1 H, J = 2 Hz).

13C NMR: d = -4.7 (q), -3.9 (q), 13.4 (q), 18.1 (s), 18.5 (t), 25.1 (t), 26.0 (q), 29.1 (t), 30.0 (t), 31.1 (t), 40.7 (s), 71.6 (s), 72.5 (d), 114.8 (s), 119.1 (s), 147.8 (d).

CI/NH3 MS m/z (%) 339 (M + NH4+) (20), 321 (M+) (100), 304 (25), 281 (25), 345 (95), 264 (10).

IR (neat, cm-1): 3479, 2951, 2928, 2894, 2855, 2222, 1471, 1255, 1091.

Anal. Calcd for C18H31O2NSi (MW 321.53): C, 67.24; H, 9.71; N, 4.35. Found: C, 66.96; H, 9.95; N, 4.13.
 

(4aR*, 5S*, 8aS*) 5-(tert-Butyldimethylsilyl)oxy-8a-hydroxy-4a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalene-2-carbonitrile (14):

Prepared from the alcohol13b by the same procedure as for 12 (70%)

M.p. 115-116 °C (pentane).

1H NMR: d = 0.09 (s, 3 H), 0.10 (s, 3 H), 0.91 (s, 9 H), 1.02 (s, 3 H), 1.25-1.95 (m, 8 H), 2.30 (m, 2 H), 3.59 (br s, 1 H), 4.30 (br s, 1 H), 6.33 (t, 1 H, J = 2 Hz).

13C NMR: d = -4.9 (q), -4.3 (q), 15.4 (br q), 17.6 (s), 18.0 (t), 24.5 (t), 25.8 (q), 28.3 (t), 35.6 (t), 39.2 (br s), 73.2 (br d), 110.0 (br s), 118.9 (s), 150.4 (d).

GC analysis (RTX5-MS, 0.32 mm id. ¥ 30 m, 180 °C- 300 °C, 10 °C/min), retention time 2.80 min.

EI MS m/z (%) 264 (M+? t-Bu) (10), 246 (15), 208 (7), 172 (60), 75 (100).

IR (neat, cm-1): 3491, 2949, 2929, 2857, 2221, 1471, 1255, 1099.

Anal. Calcd for C18H31O2NSi (MW 321.53): C, 67.24; H, 9.71; N, 4.35. Found: C, 67.23; H, 9.74; N, 4.45.
 

 (2R*, 4aR*, 5S*, 8aR*) 5-(tert-Butyldimethylsilyl)oxy-8a-hydroxy-4a-methyl-decahydro-naphtalene-2-carbaldehyde, lactol form (17)(2S*, 4aR*, 5S*, 8aR*) 5-(tert-Butyldimethylsilyl)oxy-8a-hydroxy-4a-methyl-decahydro-naphtalene-2-carbaldehyde (16):

Diisobutylaluminium hydride (4.3 mL, 6.45 mmol, 1.5 M solution in toluene) was added dropwise under argon to a -10°C solution a mixture of nitriles 15a/15b (67:33) (320 mg, 1.00 mmol) in CH2Cl2 (25 mL). The reaction mixture was warmed to 5 °C and quenched with 5% sulfuric acid (10 mL). The mixture was stirred for 15 min at room temperature, the aqueous phase was separated and extracted with Et2O (2 ¥ 35 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate (35 mL), brine (35 mL), dried (MgSO4) and concentrated under reduced pressure. The crude mixture of 16/17 (66:33) (250 mg) as a colorless oil was dissolved in Et2O (50 mL) and refluxed for 6 h with basic Al2O3 (2 g). The reaction mixture was cooled to room temperature and filtered. Aluminium oxide was washed with acetone and the combined organic layers concentrated under reduced pressure. The crude product was purified by chromatography (AcOEt/cyclohexane 5/95 to 15/85) to give 140 mg (0.42 mmol, 42%, 2 steps) of 17 as a white solid.

16:

1H NMR: d = 0.02 (s, 6 H), 0.80 (s, 9 H), 0.88 (s, 3 H), 1.20-1.90 (m, 12 H), 2.80 (m, 1 H), 3.81 (dd, J = 10 Hz, J = 6 Hz, 1 H), 9.66 (s, 1 H).

13C NMR: d = -4.6 (q), -3.9 (q), 13.7 (q), 18.0 (s), 19.3 (t), 20.9 (t), 26.0 (q), 29.8 (t), 30.4 (t), 34.1 (t), 34.7 (t), 37.0 (d), 41.0 (s), 73.6 (d), 74.1 (s), 205.1 (d).

GC analysis (HP1-MS, 0.32 mm id. ¥ 30 m, 150 °C- 300 °C, 10 °C/min), retention time 13.55 min.

 EI MS m/z (%) 269  (M+ ? t-Bu) (25), 251 (3), 207 (3), 193 (5), 175 (7), 159 (7), 75 (100).

 IR (neat, cm-1): 3476, 2928, 2855, 1718, 1471, 1250, 1088.

 17:

M.p. 125-127 °C (pentane)

1H NMR: d = 0.01 (s, 3 H), 0.02 (s, 3 H), 0.86 (s, 9 H), 0.89 (s, 3 H), 1.20-1.90 (m, 12 H), 2.20 (br s, 1 H), 2.98 (d, 1 H, J = 3 Hz), 3.62 (dd, 1 H, J = 11 Hz, J = 4 Hz), 5.21 (d, 1 H, J = 3 Hz).

13C NMR: d = -4.6 (q), -3.8 (q), 14.5 (q), 18.0 (s), 20.9 (t), 24.5 (t), 26.0 (q), 30.7 (t), 32.5 (t), 32.7 (t), 35.9 (t), 42.8 (d), 43.2 (s), 76.5 (d), 89.5 (s), 100.4 (d).

GC analysis (HP1-MS, 0.32 mm id. ¥ 30 m, 150 °C- 300 °C, 10 °C/min), retention time 12.60 min.

EI MS m/z (%) 269 (M+ ? t-Bu) (23), 251 (3), 223 (5), 149 (15), 119 (15), 105 (25), 75 (100).

IR (neat, cm-1): 3404, 2929, 2856, 1472, 1255, 1095

(1S*, 5S*, 6R*, 9S*, 12R*) 6,10,10-Trimethyl-11-oxa-tricyclo[7.2.1.01,6]dodecane-5,9,12-triol (24):

A solution of diolepoxide 23 (318 mg, 0.859 mmol) in a mixture acetone/water (9:1) (36 mL) with 74 drops of 95% sulfuric acid was stirred for 96 h at room temperature. The reaction mixture was neutralized with a saturated aqueous sodium bicarbonate, the aqueous phase was extracted with CH2Cl2 (3 ¥ 50 mL), the combined organic layers washed with brine (10 mL), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by chromatography (MeOH/ CH2Cl2 10/90) to give 86 mg (0.335 mmol, 39%) of 24 as a white solid.

M.p. 212-213 °C (AcOEt/hexane).

1H NMR: d = 0.96 (s, 3 H), 1.32 (s, 3 H), 1.42 (s, 3 H), 1.20-2.30 (m, 13 H), 3.72 (dd, 1 H, J = 11 Hz, J = 5 Hz), 3.89 (br s, 1H).

13C NMR: d =  16.5 (q), 20.3 (q), 22.9 (t), 26.4 (t), 27.2 (q), 28.9 (t), 30.4 (t), 32.9 (t), 46.8 (s), 73.2 (d), 79.1 (s), 79.4 (d), 80.9 (s), 86.4 (s).

GC analysis (RTX5-MS, 0.32 mm id. ¥ 30 m, 200 °C- 300 °C, 10 °C/min), retention time 5.98 min.

CI/NH3 MS m/z (%) 274 (M + NH4+, 30), 257 (MH+, 60), 239 (20), 221 (25), 198 (40), 180 (100).

IR (neat, cm-1): 3410, 2927, 2870, 1453, 1369, 1118, 998, 908, 732.

HRMS calcd for C14H25O4 (MH+) 257. 17529, found 257. 17913 ; calcd for C14H23O3 (MH+ ? H2O) 239. 16410, found 239. 16671 ; calcd for C14H21O2 (MH+ ? 2H2O) 221. 15360, found 221. 15825.