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M. E. Jung, B. A. Duclos / Tetrahedron 62 (2006) 9321–9334
removed in vacuo and the crude residue purified by flash
chromatography on silica gel (90% hexanes/ethyl acetate)
to yield the aldehyde 11 as a brownish yellow oil (634 mg,
45%). IR (neat) 2945, 2856, 1676, 1472, 1389, 1253,
the crude residue purified by flash chromatography on silica
gel (90% hexanes/ethyl acetate) to afford the alcohol 26 as
a colorless oil (80 mg, 70%). H NMR (400 MHz, CDCl3)
1
d 4.17 (d, J¼11.4 Hz, 1H), 4.01 (d, J¼11.4 Hz, 1H), 3.20
(dd, J¼10.9, 5.1 Hz, 1H), 2.05 (m, 2H), 1.85 (dt, J¼12.9,
3.3 Hz, 1H), 1.70 (s, 3H), 1.35–1.67 (m, 6H), 0.95 (s, 3H),
0.91 (s, 3H), 0.88 (s, 9H), 0.76 (s, 3H), 0.02 (s, 3H), 0.01
(s, 3H); 13C NMR (100 MHz, CDCl3) d 140.5, 132.5, 79.3,
58.2, 50.9, 39.3, 37.7, 34.9, 34.0, 28.5, 28.0, 25.9, 20.7,
19.2, 18.8, 18.1, 15.9, ꢁ3.8, ꢁ5.0. HRMS (EI) m/e
(M+Na) calcd for C21H42O2SiNa 375.2690, found 375.2685.
1
1105, 836, 773 cmꢁ1; H NMR (400 MHz, CDCl3) d 10.2
(s, 1H), 3.19 (dd, J¼11.4, 4.7 Hz, 1H), 2.57 (ddd, J¼13.4,
3.6, 3.6 Hz, 1H), 2.26 (m, 1H), 2.02 (s, 3H), 0.74–1.73 (m,
7H), 1.14 (s, 3H), 0.94 (s, 3H), 0.88 (s, 9H), 0.78 (s, 3H),
0.03 (s, 3H), 0.02 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 192.3, 154.2, 143.4, 79.1, 51.0, 39.5, 37.3, 36.8, 34.2,
28.6, 28.0, 25.9, 20.1, 19.0, 18.3, 18.1, 16.0, ꢁ3.7, ꢁ5.0;
HRMS (EI) m/e (MꢁH) calcd for C21H37O2Si 349.2563,
found 349.2568.
4.1.11. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-1-Bromo-
methyl-octahydro-6-[(1,1-dimethylethyl)dimethylsilyl-
oxy]-2,5,5,8a-tetramethylnaphthalene (27). To a stirring
solution of the allylic alcohol 26 (193 mg, 0.55 mmol) and
carbon tetrabromide (202 mg, 0.61 mmol) in dichloro-
methane (5.5 mL) cooled to 0 ꢂC was added triphenylphos-
phine (160 mg, 0.61 mmol). The reaction was allowed to
warm to 23 ꢂC and stirred for 2.5 h. Celite was added to
the reaction mixture and the solvent was removed in vacuo.
The solid mixture was purified by flash chromatography on
a very short column of silica gel (90% hexanes/ethyl acetate)
to afford the bromide 27 as a colorless oil (109 mg, 48%). 1H
NMR (400 MHz, CDCl3) d 4.13 (1H, d, J¼10.0 Hz), 3.97
(1H, d, J¼10.0 Hz), 3.20 (1H, m), 2.12 (2H, m), 1.39–1.90
(7H, m), 1.72 (3H, s), 1.00 (3H, s), 0.97 (3H, s), 0.90 (9H,
s), 0.78 (3H, s), 0.06 (3H, s), 0.04 (3H, s); 13C NMR
(100 MHz, CDCl3) d 136.8, 126.7, 79.3, 50.7, 48.1, 39.8,
37.5, 36.9, 35.8, 28.1, 25.9, 24.1, 21.2, 20.8, 18.1, 15.9,
ꢁ3.7, ꢁ4.9.
4.1.8. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-
[(1,1-dimethylethyl)dimethylsilyloxy]-a-(trimethylsilyl-
oxy)-2,5,5,8a-tetramethylnaphthalene-1-acetonitrile
(22). To a stirring solution of the aldehyde 11 (95.8 mg,
0.27 mmol), zinc iodide (4 mg, 0.016 mmol), and dichloro-
methane (0.5 mL) at 23 ꢂC was added trimethylsilyl cyanide
(43 mL, 0.32 mmol). The mixture was allowed to stir for
24 h. The reaction was quenched with pH 7 buffer and
extracted three times with dichloromethane. The combined
organic extracts were washed once with brine and dried
(MgSO4). The solvents were removed in vacuo to yield the
TMS cyanohydrin 22 as a light brown oil (118 mg, 96%).
IR (neat) 2956, 2857, 2231, 1641, 1472, 1362, 1254, 1106,
842, 774 cmꢁ1 1H NMR (400 MHz, CDCl3) d 5.07 (s,
;
1H), 3.21 (m, 1H), 2.10 (m, 1H), 1.85 (s, 3H), 1.49–1.80
(m, 8H), 1.01 (s, 3H), 0.92 (s, 3H), 0.89 (s, 9H), 0.76 (s,
3H), 0.26 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H).
4.1.9. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-
[(1,1-dimethylethyl)dimethylsilyloxy]-a-[(1,1-dimethyl-
ethyl)dimethylsilyloxy]-2,5,5,8a-tetramethylnaphtha-
lene-1-acetonitrile (23). To a stirring solution of the
aldehyde 11 (125 mg, 0.35 mmol), zinc iodide (4 mg,
0.016 mmol), and dichloromethane (0.6 mL) at 23 ꢂC was
added tert-butyldimethylsilyl cyanide (59 mg, 0.42 mmol).
The mixture was allowed to stir for 24 h. The reaction was
quenched with pH 7 buffer and extracted three times with
dichloromethane. The combined organic extracts were
washed once with brine and dried (MgSO4). The solvents
were removed in vacuo and the crude residue purified by
flash chromatography on silica gel (90% hexanes/ethyl ace-
tate) to yield the TBS cyanohydrin 23 as a colorless oil
(84 mg, 48%). 1H NMR (400 MHz, CDCl3) d 5.12 (s, 1H),
3.22 (m, 1H), 2.10 (m, 1H), 1.83 (s, 3H), 1.22–1.71 (m,
8H), 1.03 (s, 3H), 0.92 (s, 9H), 0.91 (s, 3H), 0.90 (s, 9H),
0.89 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H), 0.02 (s, 6H); 13C
NMR (100 MHz, CDCl3) d 136.3, 120.6, 79.0, 58.5, 50.9,
50.8, 39.4, 38.6, 34.8, 34.1, 32.4, 28.5, 27.9, 25.9, 22.5,
20.1, 19.2, 18.6, 18.1, 16.0, ꢁ2.9, ꢁ3.5, ꢁ5.0, ꢁ5.2.
4.1.12. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-
[(1,1-dimethylethyl)dimethylsilyloxy]-a,2,5,5,8a-penta-
methylnaphthalene-1-methanol (29). To a stirring solution
of the aldehyde 11 (141 mg, 0.40 mmol) in ether (1.4 mL)
cooled to 0 ꢂC was added methyllithium (0.57 mL,
0.80 mmol, 1.4 M in ether). The solution was allowed to
warm to 23 ꢂC and stirred for 1 h. The reaction was
quenched with a solution of 15% aqueous NH4Cl and
extracted three times with ether. The combined organic
extracts were washed once with brine and dried (MgSO4).
The solvent was removed in vacuo to yield a diastereomeric
mixture of the two alcohols 29 as a colorless oil (139 mg,
1
95%). H NMR (500 MHz, CDCl3) d 4.90 (q, J¼6.7 Hz,
1H), 4.60 (q, J¼6.8 Hz, 1H), 3.24 (m, 2H), 2.06 (m, 4H),
1.87 (s, 3H), 1.85 (s, 3H), 1.52–1.76 (m, 9H), 1.45 (d,
J¼6.8 Hz, 3H), 1.43 (d, J¼6.7 Hz, 3H), 1.05–1.38 (m,
5H), 0.98 (s, 3H), 0.96 (s, 3H), 0.93 (s, 9H), 0.80 (s, 3H),
0.08 (s, 3H), 0.07 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 144.5, 143.5, 130.7, 129.3, 79.1, 79.0, 66.1, 65.7, 51.5,
50.9, 39.3, 38.6, 35.4, 34.9, 28.6, 28.1, 25.8, 23.8, 20.5,
20.1, 18.7, 18.0, 16.0, ꢁ3.9, ꢁ5.1. HRMS (EI) m/e (M+Na)
calcd for C22H42O2SiNa 389.2846, found 389.2840.
4.1.10. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-
[(1,1-dimethylethyl)dimethylsilyloxy]-2,5,5,8a-tetra-
methylnaphthalene-1-methanol (26). A mixture of the
aldehyde 11 (117 mg, 0.33 mmol), sodium borohydride
(6.5 mg, 0.17 mmol), and ethanol (3.3 mL) was stirred to-
gether at 23 ꢂC overnight. The reaction mixture was poured
into water and extracted three times with ether. The com-
bined organic extracts were washed once with brine and
dried (MgSO4). The solvents were removed in vacuo and
4.1.13. ( )-(4aS,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-6-
[(1,1-dimethylethyl)dimethylsilyloxy]-2,5,5,8a-tetra-
methylnaphthalene-1-ethanone (30). To a stirring solution
of Dess–Martin periodinane (208 mg, 0.49 mmol) in di-
chloromethane (3 mL) at 23 ꢂC was added the alcohol 29
(139 mg, 0.38 mmol) in dichloromethane (1 mL). The mix-
ture was allowed to stir for 1 h, poured into a 1:1 mixture
of a saturated solution of NaHCO3 and a solution of 10%