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suspension was filtrated through a Celite pad, and the filtrate was
concentrated under reduced pressure. The residue was purified by
flash column chromatography (silica gel, hexane/EtOAc, 2:1) to give 5
(1.63 g, 53%) as a white solid: FT IR (neat) 3280, 2995, 2949, 2866,
2843 cm−1; 1H NMR (400 MHz in CDCl3) δ 0.79 (6H, s), 0.88 (3H,
s), 0.95 (2H, dd, J = 12.0, 2.0 Hz), 1.16 (1H, dd, J = 13.2, 4.4 Hz),
1.20 (3H, s), 1.28 (2H, m), 1.35−1.60 (3H, m), 1.61−1.65 (5H, m),
1.90 (1H, dt, J = 12.4, 3.2 Hz), 3.46 (1H, m), 3.78 (1H, dt, J = 10.4,
4.0 Hz); 13C NMR (100 MHz in CDCl3) δ 15.3, 18.4, 20.5, 21.5, 24.7,
27.9, 33.3, 33.4, 39.0, 39.3, 41.9, 44.3, 56.0, 59.1, 64.2, 73.1; MS (Cl)
m/z 254 (M+); HRMS (CI+) m/z calcd for C16H30O2 (M+) 254.2246,
found 254.2267.
2.42 (1H, dd, J = 16.8, 5.6 Hz), 2.65 (1H, dd, J = 16.8, 4.4 Hz), 3.48
(1H, d, J = 15.2 Hz), 3.52 (1H, d, J = 15.2 Hz), 3.72 (3H, s); 13C
NMR (100 MHz in CDCl3) δ 6.8, 7.2, 15.6, 18.3, 20.5, 21.4, 24.9, 33.2,
33.3, 38.3, 39.5, 39.8, 41.7, 43.8, 48.7, 52.2, 55.7, 56.5, 76.3, 168.1,
202.7; MS (Cl) m/z 438 (M+); HRMS (CI+) m/z calcd for
C25H46O4Si (M+) 438.3166, found 438.3158.
Methyl 2-Diazo-4-[(2S*,4aR*,8aR*)-2-hydroxy-2,5,5,8a-tet-
ramethyldecahydronaphthalen-1-yl]-3-oxobutanoate (12). A
1.0 M THF solution of TBAF (7.0 mL, 7.0 mmol) was added to a
solution of 11 (1.44 g, 3.28 mmol) in THF (33 mL) at room
temperature. The mixture was stirred for 30 min at the same
temperature and then quenched with distilled water. The organic layer
was partitioned with Et2O (30 mL), and the aqueous layer was
extracted with Et2O (2 × 15 mL). The combined organic layer was
dried over anhydrous MgSO4 and concentrated under reduced
pressure. The residue was successively dissolved in CH2Cl2 (33
mL), and then Et3N (1.32 g, 13.1 mmol) and TsN3 (1.29 g, 6.56
mmol) were added to the mixture at room temperature. The reaction
mixture was stirred for 4 h at the same temperature and quenched with
saturated NH4Cl. The organic layer was dried over anhydrous MgSO4
and concentrated under reduced pressure. The residue was purified by
flash column chromatography (silica gel, hexane/EtOAc, 3:1) to give
12 (1.05 g, 91%) as a white solid: FT IR (neat) 3500, 2990, 2925,
Triethylsilane Derivative of (2S*,4aR*,8aR*)-1-(2-Hydrox-
yethyl)-2,5,5,8a-tetramethyldecahydronaphthalen-2-ol (9).
Et3N (3.93 g, 38.5 mmol) and then TESOTf (6.00 g, 19.2 mmol)
were added to a solution of 5 (826 mg, 1.49 mmol) in CH2Cl2 (13
mL) at 0 °C. The mixture was stirred for 20 min at 0 °C and quenched
with distilled water (10 mL) at room temperature. The organic layer
was dried over anhydrous MgSO4 and concentrated under reduced
pressure. The residue was purified by flash column chromatography
(silica gel, hexane/EtOAc, 5:1) to give 9 (3.08 g, quant) as a colorless
1
syrup: FT IR (neat) 2954, 2911, 2876 cm−1; H NMR (500 MHz in
CDCl3) δ 0.49−0.62 (12H, m), 0.77 (3H, s), 0.78 (3H, s), 0.85 (3H,
s), 0.88 (2H, br d, J = 13.5 Hz), 0.93 (9H, t, J = 8.0 Hz), 0.96 (9H, t, J
= 8.0 Hz), 1.10−1.26 (2H, m), 1.17 (3H, s), 1.33−1.50 (4H, m),
1.52−1.77 (5H, m), 1.88 (1H, br d, J = 12.0 Hz), 3.45 (1H, dt, J =
10.0, 5.5 Hz), 3.67 (1H, dt, J = 10.0, 6.0 Hz); 13C NMR (125 MHz in
CDCl3) δ 4.4, 6.4, 6.8, 6.8, 7.1, 7.3, 15.6, 18.5, 20.6, 21.5, 24.8, 29.5,
33.2, 33.4, 39.7, 42.0, 44.4, 56.1, 58.5, 65.5; MS (Cl) m/z 483 (M+ +
H); HRMS (CI+) m/z calcd for C28H59O2Si2 (M+ + H) 483.4054,
found 483.4043.
1
2853, 2132, 1726, 1658 cm−1; H NMR (400 MHz in CDCl3) δ 0.79
(3H, s), 0.84 (3H, s), 0.88 (3H, s), 0.94 (1H, dd, 13.2, 4.0 Hz), 1.02
(1H, dd, J = 12.0, 2.4 Hz), 1.14 (1H, m), 1.15 (3H, s), 1.23−1.47 (5H,
m), 1.52−1.63 (2H, m), 1.69 (1H, ddd, J = 13.2, 6.0, 3.6 Hz), 1.94
(1H, dt, J = 12.4, 3.2 Hz), 2.09 (1H, dd, J = 6.0, 4.0 Hz), 2.94 (1H, dd,
J = 18.0, 6.0 Hz), 3.04 (1H, dd, J = 18.0, 4.0 Hz), 3.85 (3H, s); 13C
NMR (100 MHz in CDCl3) δ 15.8, 18.4, 20.6, 21.4, 23.2, 33.3, 33.4,
35.4, 38.6, 39.3, 41.8, 44.7, 52.2, 55.9, 56.2, 73.3, 162.0, 194.3; MS (Cl)
m/z 351 (M+ + H); HRMS (CI+) m/z calcd for C19H31O4N2 (M+ +
H) 351.2284, found 351.2260.
2-[(2S*,4aR*,8aR*)-2,5,5,8a-Tetramethyl-2-[(triethylsilyl)-
oxy]decahydronaphthalen-1-yl]acetaldehyde (10). (COCl)2
(3.88 g, 30.5 mmol) was added to a solution of DMSO (4.46 g,
57.1 mmol) in CH2Cl2 (50 mL) at −78 °C. After 15 min, a solution of
9 (3.08 g, 6.38 mmol) in CH2Cl2 (50 mL) was dropwise added to the
mixture at the same temperature (−78 °C). The reaction mixture was
allowed to warm to −40 °C and stirred for 1 h. The reaction was
quenched with Et3N (10 mL) at −78 °C, and the resulting mixture
was allowed to room temperature. The organic layer was washed with
distilled water, and the aqueous layer was extracted with CH2Cl2 (2 ×
50 mL). The combined organic layer was dried over anhydrous
MgSO4 and concentrated under reduced pressure. The residue was
purified by flash column chromatography (silica gel, hexane/EtOAc,
8:1) to give 10 (1.93 g, 82%) as a white solid: FT IR (neat) 2951,
Methyl (4aS*,6aR*,10aR*)-4a,7,7,10a-Tetramethyl-2-
[[(trifluoromethyl)sulfonyl]oxy]-4a,5,6,6a,7,8,9,10,10a,10b-
decahydro-1H-benzo[f ]chromene-3-carboxylate (14).
Rh2(OAc)4 (37.8 mg, 8.55 μmol) was added to a solution of 12
(1.00 g, 2.85 mmol) in benzene (14 mL) at room temperature. The
mixture was stirred for 5 min under reflux and cooled to room
temperature. The resulting mixture was filtrated through a silica gel
pad, and the filtrate was concentrated under reduced pressure. The
residue (keto−enol mixture of 13a and 13b) was successively
dissolved in THF (14 mL), and NaH (60% in oil, 171 mg, 4.28
mmol) was added to the solution at 0 °C. After 10 min, Comins
reagent (2-[N,N-bis(trifluoromethanesulfonyl)amino-5-chloropyri-
dine) (1.34 g, 3.42 mmol) was added to the mixture at the same
temperature (0 °C). The mixture was stirred for 30 min at 0 °C and
quenched with saturated NH4Cl. The organic layer was dried over
anhydrous MgSO4 and concentrated under reduced pressure. The
residue was purified by flash column chromatography (silica gel,
hexane/EtOAc, 10:1) to give 14 (1.20 g, 93%) as a white solid: FT IR
(neat) 3000, 2981, 2950, 2872, 2847, 1747, 1660 cm−1; 1H NMR (400
MHz in CDCl3) δ 0.82 (3H, s), 0.84 (3H, s), 0.90 (3H, s), 0.96 (2H,
dd, J = 12.0, 2.4 Hz), 1.16 (1H, dt, J = 13.2, 3.6 Hz), 1.24 (3H, s), 1.32
(1H, ddt, J = 13.6, 12.4, 3.6 Hz), 1.40−1.51 (2H, m), 1.55−1.69 (4H,
m), 1.77 (1H, m), 2.12 (1H, dt, J = 12.8, 3.2 Hz), 2.31 (1H, d, J = 10.4
Hz), 2.31 (1H, d, J = 8.0 Hz), 3.84 (3H, s); 13C NMR (100 MHz in
CDCl3) δ 14.8, 18.3, 19.6, 21.5, 23.5, 33.1, 33.3, 36.9, 39.1, 39.8, 41.6,
51.6, 52.5, 55.6, 79.4, 136.5, 137.9, 161.3; MS (Cl) m/z 455 (M++H);
HRMS (CI+) m/z calcd for C20H30O6F3 S (M+ + H) 455.1715, found
455.1713.
1
2935, 2874, 2711, 1726 cm−1; H NMR (400 MHz in CDCl3) δ 0.56
(6H, q, J = 8.0 Hz), 0.79 (3H, s), 0.80 (3H, s), 0.89 (3H, s), 0.92 (9H,
t, J = 8.0 Hz), 1.00 (1H, dd, J = 12.0, 2.4 Hz), 1.09−1.30 (3H, m), 1.17
(3H, s), 1.35−1.63 (5H, m), 1.68 (1H, m), 1.92 (1H, dd, J = 7.6, 4.8
Hz), 1.96 (1H, dt, J = 12.4, 3.2 Hz), 2.25 (1H, ddd, J = 16.0, 4.8, 2.0
Hz), 2.47 (1H, ddd, J = 16.0, 7.6, 3.2 Hz), 9.60 (1H, dd, J = 3.2, 2.0
Hz) 13C NMR (75 MHz in CDCl3) δ 6.8, 7.2, 15.5, 18.5, 20.4, 21.4,
24.8, 33.2, 33.6, 38.1, 40.1, 40.2, 41.7, 44.0, 56.0, 57.3, 76.4, 203.4; MS
(Cl+) m/z 366 (M+); HRMS (CI+) m/z calcd for C22H42O2 Si (M+)
366.2954, found 366.2931.
Methyl 3-Oxo-4-[(2S*,4aR*,8aR*)-2,5,5,8a-tetramethyl-2-
[(triethylsilyl)oxy]-decahydronaphthalen-1-yl]butanoate (11).
Methyl diazoacetate (920 mg, 9.19 mmol) and then SnCl2 (70.2
mg, 0.37 mmol) were added to a solution of 10 (1.35 g, 3.68 mmol) in
CH2Cl2 (37 mL) at room temperature. The mixture was stirred for 1.5
h under reflux and quenched with saturated NaHCO3 at room
temperature. The organic layer was dried over anhydrous MgSO4 and
concentrated under reduced pressure. The residue was purified by
flash column chromatography (silica gel, hexane/EtOAc, 30:1) to give
11 (1.44 g, 89%) as a white solid: FT IR (neat) 2952, 2874, 1752,
1722 cm−1; 1H NMR (400 MHz in CDCl3) δ 0.55 (6H, q, J = 8.0 Hz),
0.77 (6H, s), 0.87 (3H, s), 0.91 (9H, t, J = 8.0 Hz), 1.01 (1H, dd, J =
12.0, 2.0 Hz), 1.14 (3H, s), 1.17 (1H, m), 1.22 (1H, dd, J = 12.4, 3.2
Hz), 1.26−1.43 (3H, m), 1.51 (1H, dt, J = 13.6, 4.0 Hz), 1.55−1.69
(3H, m), 1.92 (1H, dt, J = 12.0, 3.2 Hz), 2.02 (1H, br t, J = 5.6 Hz),
Methyl (4aS*,6aR*,10aR*)-2-(2,6-Dichloropyridin-3-yl)-
4a,7,7,10a-tetramethyl-4a,5,6,6a,7,8,9,10,10a,10b-decahydro-
1H-benzo[f ]chromene-3-carboxylate (16). Pd(PPh3)4 (381 mg,
330 μmol) was added to a suspension of K2CO3 (1.09 g, 7.92 mmol),
14 (600 mg, 1.32 mmol), and (2,6-dichloropyridin-3-yl)boronic acid
(15) (1.27 g, 6.60 mmol) in 10% aqueous dioxane solution (11 mL) at
room temperature. The mixture was stirred for 15 min under reflux
and cooled at room temperature. The reaction was quenched with
saturated NH4Cl at room temperature. The organic layer was dried
8853
dx.doi.org/10.1021/jo501720b | J. Org. Chem. 2014, 79, 8850−8855