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dried over anhydrous sodium sulfate and concentrated, then it was
purified by column chromatography over silica gel (hexane/EtOAc,
4:1) to give the alcohol compound (346 mg, 0.83 mmol): yield 87%;
IR (KBr) 3447, 2931, 2824, 1472, 1462, 1389, 1374, 1253, 1192, 1151,
1099, 1039, 934, 919, 876, 777, cm−1; 1H NMR (400 MHz, CDCl3) δ
5.42−5.39 (t, J = 7.0 Hz, 1H), 4.68−4.66 (d, J = 6.9 Hz, 1H), 4.62−
4.60 (d, J = 6.9 Hz, 1H), 4.01 (s, 2H), 3.85−3.79 (m, 1H), 3.74−3.73
(t, J = 3.4 Hz, 1H), 3.70 (s, 1H), 3.46 (s, 3H), 3.42 (s, 3H), 3.41 (s,
3H), 3.24−3.21 (dd, J1 = 9.2 Hz, J2 = 2.9 Hz, 1H), 2.16−2.08 (m, 1H),
2.04−1.97 (m, 1H), 1.86−1.82 (m, 1H), 1.66 (s, 3H), 1.64−1.35 (m,
3H), 0.88 (s, 9H), 0.08 (s, 3H), 0.06 (s,3H); 13C NMR (100.6 MHz,
CDCl3) δ 136.0, 124.4, 97.7, 83.83, 78.7, 77.2, 70.3, 69.0, 58.8, 58.8,
55.9, 35.2, 34.6, 39.4, 25.9, 18.1, 13.9, −4.5, −4.7; HRMS-EI (m/z)
calcd for C21H42O6Si [M]+ 418.2751, found 418.2759.
To the solution of above alcohol (346 mg, 0.83 mmol) in CH2Cl2
(8 mL) were added PPh3 (0.24 g, 0.90 mmol) and CBr4 (0.30 g, 0.90
mmol) successively at 0 °C, and stirring was continued for 10 min. It
was quenched with saturated aqueous NaHCO3 solution, and the
organic layer was separated. The solvent was concentrated under
reduced pressure and then purified by column chromatography over
silica gel (hexane/EtOAc, 9:1) to give bromo compound 27 (381 mg,
0.80 mmol): yield 96%; IR (KBr) 2931, 2823, 1700, 1650, 1541, 1521,
1393, 1253, 1208, 1152, 1129, 1100, 1039, 1007, 919, 879, 777 cm−1;
1H NMR (400 MHz, CDCl3) δ 5.62−5.58 (t, J = 6.8 Hz, 1H), 4.69−
4.67 (d, J = 6.9 Hz, 1H), 4.63−4.61 (d, J = 7.0 Hz, 1H), 3.97 (s, 2H),
3.85−3.79 (m, 1H), 3.75 (s, 1H), 3.67 (s, 1H), 3.46 (s, 3H), 3.42, (s,
3H), 3.41 (s, 3H), 3.23−3.20 (dd, J1 = 9.1 Hz, J2 = 2.7 Hz, 1H), 2.12−
1.97 (m, 2H), 1.87−1.85 (m, 1H), 1.76 (s, 3H), 1.62−1.56 (m, 1H),
1.43−1.34 (m, 1H), 0.88 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H); 13C NMR
(100.6 MHz, CDCl3) δ 133.4, 129.8, 97.8, 83.9, 78.8, 77.2, 70.4, 59.0,
58.9, 56.0, 41.6, 35.2, 34.6, 30.2, 26.0, 18.3, 15.0, −4.4, −4.6.
tert-Butyl(2,3-dimethoxy-4-(methoxymethoxy)-5-((2E,6E)-
3,7,11-trimethyldodeca-2,6,10-trienyl)cyclohexyloxy)-
dimethylsilane (29). To a stirred solution of sulfide 28 (28.0 mg,
0.12 mmol) in THF (5.00 mL) at −78 °C was added n-BuLi (0.06 mL,
0.13 mmol), and the mixture was stirred for 1 h at the same
temperature. Then the solution of allyl bromide 27 (41.8 mg, 0.09
mmol) in THF (1 mL) was added, and stirring was continued for 1 h.
It was quenched with a saturated aqueous NH4Cl solution and allowed
to reach room temperature. It was extracted with ether (2 × 10 mL),
the organic phase was dried over anhydrous magnesium sulfate,
filtered and concentrated, and the residue obtained was used as is for
the next step.
Li (0.7 mg, 1 mmol) was added to the liq NH3 at −78 °C, which
gave dark blue color to the solution. Then the above coupled product
in ether (2 mL) was added and the mixture stirred for 30 min at −60
°C. It was quenched with MeOH and slowly warmed to room
temperature during which time ammonia evaporated. It was diluted
with a saturated NH4Cl solution and extracted with ether (2 × 10
mL), the organic phase was dried over anhydrous magnesium sulfate,
filtered and concentrated, and then the obtained residue was purified
by chromatography over silica gel (hexane/EtOAc, 15:1) to give the
product 29 (41.2 mg, 0.08 mmol): yield 84%; IR (KBr) 2930, 1650,
1540, 1524, 1390, 1254, 1140, 1103, 1008 cm−1; 1H NMR (400 MHz,
CDCl3) δ 5.29−5.28 (d, J = 3.3 Hz, 1H), 5.11−5.09 (d, J = 6.5 Hz,
3H), 4.67−4.60 (dd, J1 = 21.8 Hz, J2 = 6.8 Hz, 2H), 3.83−3.79 (m,
1H), 3.73−3.71 (d, J = 9.7 Hz, 2H), 3.47 (s, 3H), 3.41 (s, 3H), 3.40 (s,
3H), 3.24−3.22 (d, J = 7.4 Hz, 1H), 2.06−1.97 (m, 12H), 1.68 (s,
6H), 1.43−1.36 (m, 4H), 1.25 (s, 9H), 0.88 (s, 9H), 0.08 (s, 3H), 0.06
(s, 3H); 13C NMR (100.6 MHz, CDCl3) δ 136.4, 135.1, 131.3, 124.4,
124.2, 122.7, 97.7, 83.9, 78.9, 70.45, 58.8, 58.6, 55.8, 40.0, 39.9, 39.7,
35.2, 34.8, 29.7, 26.9, 26.8, 25.9, 25.7, 18.1, 17.7, 16.2, 16.0, −4.5,
−4.7; HRMS-EI (m/z) calcd for C31H58O5Si [M]+ 538.4054, found
538.4058.
column chromatography over silica gel (hexane/EtOAc, 3:2) to give
the alcohol compound. To a solution of this alcohol in CH2Cl2 (5 mL)
was added Dess−Martin periodinane (0.045 g, 0.10 mmol), and
stirring was continued at rt for 2 h. The reaction mixture was then
diluted with CH2Cl2, quenched with a saturated aqueous solution of
sodium bicarbonate, and washed with brine. Usual workup and flash
column chromatography (hexane/EtOAc, 9:1) afforded keto com-
pound 30 (28 mg, 0.066 mmol) in 87% over two steps: IR (KBr)
2924, 2854, 1716, 1456, 1383, 1254, 1145, 1008 cm−1; 1H NMR (400
MHz, CDCl3) δ 5.11−5.07 (m, 3H), 4.79−4.77 (d, J = 6.8 Hz, 1H),
4.73−4.71 (d, J = 6.8 Hz, 1H), 4.22−4.21 (d, J = 3.0 Hz, 1H), 4.06−
4.05 (d, J = 3.6 Hz, 1H), 3.88 (m, 1H), 3.49 (s, 3H), 3.45 (s, 3H), 3.44
(s, 3H), 2.64 (m, 1H), 2.33−1.95 (m, 12H), 1.67 (s, 3H), 1.59 (s,
3H), 1.58 (s, 3H), 1.57 (s, 3H); 13C NMR (100.6 MHz, CDCl3) δ
206.8, 137.3, 135.2, 131.2, 124.3, 124.0, 121.5, 97.9, 84.0, 82.9, 76.8,
59.2, 58.6, 56.1, 41.9, 39.7, 39.7, 38.3, 26.7, 26.6, 25.9, 25.7, 22.7, 17.6,
16.0; HRMS-EI (m/z) calcd for C25H42O5 [M]+ 422.3032, found
422.3034.
2-Methoxy-4-(methoxymethoxy)-5-((2E,6E)-3,7,11-trime-
thyldodeca-2,6,10-trienyl)cyclohex-2-enone (31). To a solution
of cyclohexanone 30 (30 mg, 0.071 mmol) in THF (1 mL) at −78 °C
was added LiHMDS (1 M solution in THF) (75 μL, 0.075 mmol) and
the stirred for 30 min at −78 °C. Methyl iodide (11 μL, 0.075 mmol)
was added, the mixture was stirred for 1 h at the same temperature,
and then the temperature was increased to 0 °C. The reaction was
quenched with NH4Cl solution and extracted with ether (2 × 5 mL),
the organic phase was dried over anhydrous magnesium sulfate,
filtered, and concentrated, and then the crude product was purified by
column chromatography over silica gel (hexane/EtOAc, 9:1) to give
the product 31 (22 mg, 0.057 mmol): yield 82%; Rf (hexane/EtOAc,
4:1) 0.53; IR (film) 2927, 1680, 1460, 1360, 1245, 1148, 981 cm−1; 1H
NMR (400 MHz, CDCl3) δ 5.92 (d, J = 5.7 Hz, 1H), 5.10 (m, 3H),
4.74 (d, J = 6.8 Hz, 1H), 4.68 (d, J = 6.8 Hz, 1H), 4.28 (m, 1H), 3.63
(s, 3H), 3.37 (s, 3H), 2.69 (m, 2H), 2.30−1.92 (m, 9H), 1.65 (s, 3H),
1.56 (s, 9H); 13C NMR (100.6 MHz, CDCl3) δ 196.3, 151.5, 137.3,
135.3, 131.2, 124.3, 124.0, 121.5, 113.3, 96.5, 70.5, 55.5, 54.8, 44.6,
41.1, 39.7, 39.7, 27.0, 26.7, 26.5, 25.7, 17.7, 16.9, 16.8; HRMS-EI (m/
z) calcd for C24H38O4 [M]+ 390.2770, found 390.2764.
2-Methoxy-4-(methoxymethoxy)-6-methyl-5-((2E,6E)-
3,7,11-trimethyldodeca-2,6,10-trienyl)cyclohex-2-enone (32).
To a solution of cyclohexanone 30 (25 mg, 0.059 mmol) in THF
(1 mL) at −40 °C was added LiHMDS (1 M solution in THF) (0.148
mL, 0.15 mmol) and the mixture stirred for 30 min at −40 °C. The
reaction mixture was cooled to −78 °C, methyl iodide (9 μL, 0.065
mmol) was added, and then the temperature was increased to 0 °C
and the mixture stirred for 1 h. The reaction was quenched with
NH4Cl solution and extracted with ether (2 × 5 mL), the organic
phase was dried over anhydrous magnesium sulfate, filtered and
concentrated, and then the crude product was purified by column
chromatography over silica gel (hexane/EtOAc, 9:1) to give the
product 32 (18.4 mg, 0.045 mmol): yield 77%; Rf (hexane/EtOAc,
4:1) 0.53; IR (film) 2921, 2851, 1682, 1640, 1456, 1365, 1148, 976
1
cm−1; H NMR (400 MHz, CDCl3) δ 5.87 (d, J = 5.5 Hz, 1H), 5.10
(m, 3H), 4.72 (d, J = 6.8 Hz, 1H), 4.66 (d, J = 6.8 Hz, 1H), 4.33 (m,
1H), 3.62 (s, 3H), 3.36 (s, 3H), 2.75 (m, 1H), 2.30−1.92 (m, 9H),
1.67 (s, 3H), 1.56 (s, 6H), 1.52 (s, 3H), 1.16 (d, J = 7.2 Hz, 3H); 13C
NMR (100.6 MHz, CDCl3) δ 196.5, 151.4, 137.4, 135.2, 131.3, 124.3,
124.0, 121.7, 113.4, 96.4, 71.0, 55.5, 54.9, 45.7, 42.8, 39.8, 39.7, 27.1,
26.8, 26.5, 25.7, 17.7, 16.2, 16.0, 12.9; HRMS-EI (m/z) calcd for
C25H40O4 [M]+ 404.2927, found 404.2924.
4-Hydroxy-2-methoxy-6-methyl-5-((2E,6E)-3,7,11-trimethyl-
dodeca-2,6,10-trienyl)cyclohex-2-enone (4). To MOM com-
pound 32 (10 mg, 0.024 mmol) was added 40% trifluoroacetic acid
in CH2Cl2 (1 mL) at 0 °C. After being stirred at room temperature for
2 h, the reaction mixture was concentrated and the residue obtained
was purified by column chromatography over silica gel (hexane/
EtOAc, 4:1) to give the product 4 (5.7 mg, 0.016 mmol): yield 64%; Rf
(hexane/EtOAc, 7:3) 0.4; IR (film) 2920, 2851, 1685, 1637, 1442,
2,3-Dimethoxy-4-(methoxymethoxy)-5-((2E,6E)-3,7,11-tri-
methyldodeca-2,6,10-trienyl)cyclohexanone (30). TBAF (0.15
mL, 0.15 mmol) was added to the solution of 21 (41.2 mg, 0.077
mmol) in THF (3 mL), and the mixture was stirred for 24 h at reflux.
After the reaction mixture was cooled to room temperature, the
solvent was concentrated under reduced pressure and then purified by
1
1376, 1247, 1148, 1080 cm−1; H NMR (400 MHz, CD3OD) δ 5.92
(d, J = 5.6 Hz, 1H), 5.22 (t, J = 7.3 Hz, 1H), 5.10 (m, 2H), 4.49 (dd, J1
H
dx.doi.org/10.1021/jo501735z | J. Org. Chem. XXXX, XXX, XXX−XXX