Formal Total Synthesis of (+)-Occidol
3093
electrothermal melting-point apparatus. The solution is diluted with water,
extracted with ether, washed with brine, dried (MgSO ), and evaporated
4
under reduced pressure. Column chromatography was performed on silica
gel (Merck grade 60, 70–230 mesh). The spectral and analytical data of all
new compounds have been reported in the Experimental section. Micro-
analyses were carried out at the Chemistry Department, IVIC, Caracas.
5
,8-Dimethyl-1,2,3,4-tetrahydro-2-naphthol 2
Sodium borohydride (980 mg, 26 mmol) in ethanol (70 mL) was added to a
solution of 1 (2.26 g, 13 mmol) in ethanol (70 mL). The mixture was stirred
for 2 h at room temperature, decomposed with acetic acid, diluted with
water, and extracted with diethyl ether. The organic layer was washed,
dried, and purified on silica gel (hexane–diethyl ether 4:6) to obtain 2
þ
þ
21
(
2.17 g, 95%); m/z 176 (M ) and 158 (M -H O); n
2
3375 cm (OH);
max
1
H: d 1.85–1.78 (m, 2H, CH ), 2.21 (s, 3H, C5-Me), 2.26 (s, 3H, C8-Me),
2
3
C-6) and 6.84 (bs, 1H, C-7); C: d 136.7 (C-10), 135 (C-9), 130.5 (C-8),
.1–2.5 (m, 4H, C1-2H, C4-2H), 4.13–4.10 (m, 1H, CHOH), 6.79 (bs, 1H,
1
3
1
2
29.6 (C-5), 128.3 (C-6), 126.8 (C-7), 67.8 (C-2), 35.6 (C-1), 31.4 (C-3),
7.5 (C-4), 19.4 (C-12) and 19.2 (C-11). (Found: C, 82.15; H, 9.37.
C H O requires C, 81.77%; H, 9.15%.)
12 16
5
,8-Dimethyl-1,2,3,4-tetrahydro-2-cyanonaphthalene 4
Mesylchloride (1.2 mL, 14.5 mmol) was added to a solution of 2 (2.17 g,
2.3 mmol) in pyridine (12 mL). The resulting brown solution was stirred at
1
room temperature for 24 h, diluted with water, and extracted with ether.
The organic extract was washed with a 5% solution of copper sulfate,
washed with brine, dried, and evaporated to give 3 (2.41 gr, 77%); m/z 254
þ þ þ
M ), 175 (M -MeSO ) and 158 (M -MeSO OH); H: d 2.15–2.22
2 2
1
(
(
(
(
m, 2H, CH ), 2.26 (s, 3H), 2.33 (s, 3H) (C-5, C-8), 2.81–3.03 (m, 4H)
2
C-1 and C-4), 3.09 (s, 3H, MeSO ), 5.16–5.28 (m, 1H, CHOSO Me), 6.86
3
2
1
bs, 1H), and 6.92 (bs, 1H) (C-6 and C-7); C: d 136.5 (C-10), 135.5 (C-9),
3
1
3
30.2 (C-8), 129.7 (C-5), 128.7 (C-6), 126.9 (C-7), 78.5 (C-2), 38.7 (C-13),
3.5 (C-3), 28.9 (C-1), 26.4 (C-4), 19.4 (C-12) and 19.3 (C-11).
The mesylate 3 (2.0 g, 7.9 mmol), powdered sodium cyanide (1.16 g,
3.7 mmol), and hexamethylphosphoramide (28 mL) was heated at 1208C
2
for 72 h under argon. The reaction mixture was diluted with water,
extracted with ether, dried and evaporated. The resulting material was
purified on silica gel by eluting with hexane to afford a mixture of 5 and 6
þ
þ
(
641 mg, 38%); m/z 158 (M ) and 156 (M ).
Further elution (hexane–diethyl ether 8:2) yielded 4 (521 mg, 36%),
þ
þ
þ
mp 107–1108C; m/z 185 (M ), 170 (M -Me), 158 (M -HCN) and 143