N.-W. Jan, H.-J. Liu, M.-T. Hsieh, K.-S. Shia
FULL PAPER
90% yield) as a colorless oil. [α]1D9 = –255.3 (c = 2.85, CHCl3). IR
134.1 (C), 126.1 (CH), 125.9 (CH), 110.3 (CH), 55.4 (OCH3), 43.0
(CH), 36.0 (CH2), 35.0 (CH2), 32.2 (CMe2), 29.5 (CH2), 28.3
1
(CH Cl ): ν = 2958, 2869, 1715, 1644, 1604, 1495, 1463 cm–1. H
˜
2
2
NMR (400 MHz, CDCl3, 25 °C): δ = 7.20–7.14 (m, 2 H, ArH), [CH(CH3)2], 26.8 (CH), 26.7 [CH(CH3)2], 24.0 (CH2), 22.7 (CH3),
7.04 (t, J = 3.7 Hz, 1 H, ArH), 6.77 (d, J = 8.4 Hz, 1 H,
CH=CCO2Me), 6.30 (d, J = 15.8 Hz, 1 H, CH=CHAr), 5.96 (dd,
J = 15.8, 8.4 Hz, 1 H, CH=CHAr), 3.80 (s, 3 H, ArOCH3), 3.70
(s, 3 H, CO2Me), 3.29 (sept., J = 6.9 Hz, 1 H, CHMe2), 3.05 (d, J
= 8.4 Hz, 1 H, CHCH=CH), 2.34–2.15 (m, 2 H), 1.63–1.52 (m, 1
H), 1.28–1.23 (m, 1 H), 1.22 [d, J = 6.9 Hz, 6 H, CH(CH3)2], 0.98
(s, 3 H, CH3), 0.94 (s, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 167.6 (CO2Me), 156.1 (Carom.), 138.5 (CH),
136.8 (C), 131.8 (C), 131.2 (CH), 130.1 (C), 127.7 (CH), 124.2
(CH), 124.1 (CH), 110.3 (CH), 55.4 (OCH3), 51.4 (CO2CH3), 47.5
(CH), 32.4 (CMe2), 29.6 (CH2), 28.6 [CH(CH3)2], 26.7 (CH), 26.1
[CH(CH3)2], 23.8 (CH2), 22.5 (2 CH3) ppm. HRMS (EI): calcd. for
C22H30O3 342.2195; found 342.2211.
22.6 (CH3) ppm. HRMS (EI): calcd. for C21H30O3 330.2195; found
330.2191.
(11aS)-7-Methoxy-1,1-dimethyl-8-(propan-2-yl)-1,2,3,10,11,11a-
hexahydro-5H-dibenzo[a,d][7]annulen-5-one (13): To a solution of
compound (–)-12 (101 mg, 0.31 mmol) in CH2Cl2 (8 mL) was
added trifluoroacetic anhydride (TFAA, 1 mL) and trifluoroacetic
acid (TFA, 0.5 mL) sequentially at 0 °C. The resulting mixture was
allowed to stir at room temperature for 6 h, and then H2O (10 mL)
was added. The aqueous layer was separated and extracted with
CH2Cl2 (3ϫ15 mL). The combined organic extracts were washed
with brine, dried with MgSO4, filtered, and concentrated to give
the crude residue, which was purified by flash chromatography on
silica gel (EtOAc/n-hexane, 1:49) to afford compound (–)-13
(50 mg, 52% yield) as a colorless oil. Upon further elution with
EtOAc/n-hexane (1:3), starting material (–)-12 (16 mg) was reco-
Methyl (6S)-6-{2-[4-Methoxy-3-(propan-2-yl)phenyl]ethyl}-5,5-di-
methylcyclohex-1-ene-1-carboxylate (11): To a stirred solution of
compound (–)-10 (201 mg, 0.59 mmol) in EtOAc (9 mL) and vered intact. [α]1D9 = –138.8 (c = 1.12, CHCl ). IR (CH Cl ): ν =
˜
3
2
2
MeOH (1 mL) was added Pd/C (104 mg, 10 wt.-%) in one portion.
The resulting mixture was hydrogenated under an atmosphere of
H2 (1 atm) at room temperature. After the reaction was complete
(ca. 30 min), the mixture was filtered through Celite and concen-
trated to give the crude product, which was purified by flash
chromatography on silica gel (EtOAc/n-hexane, 1:9) to afford com-
pound (–)-11 (196 mg, 97% yield) as a colorless oil. [α]1D9 = –97.3
2959, 2867, 1666, 1602, 1566, 1496, 1463 cm–1 1H NMR
.
(400 MHz, CDCl3, 25 °C): δ = 7.17 (s, 1 H, ArH), 7.09 (t, J =
3.7 Hz, 1 H, CH=CCO), 6.94 (s, 1 H, ArH), 3.84 (s, 3 H, ArOCH3),
3.30 (sept., J = 6.9 Hz, 1 H, CHMe2), 2.81–2.72 (m, 1 H, CH2Ar),
2.70–2.61 (m, 1 H, CH2Ar), 2.40–2.18 (m, 2 H, CH2CH=C), 1.91–
1.82 (m, 2 H), 1.63–1.52 (m, 2 H), 1.22 [d, J = 6.9 Hz, 3 H,
CH(CH3)2], 1.18 [d, J = 6.9 Hz, 3 H, CH(CH3)2], 0.88 (s, 3 H,
(c = 0.60, CHCl ). IR (CH Cl ): ν = 2955, 2869, 1714, 1644, 1608, CH3), 0.79 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3,
˜
3
2
2
1
1498, 1463 cm–1. H NMR (400 MHz, CDCl3, 25 °C): δ = 6.96 (d, 25 °C): δ = 196.6 (C=O), 155.7 (Carom.), 141.6 (C), 139.8 (C), 137.3
J = 2.2 Hz, 1 H, ArH), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H, ArH), 6.89 (CH), 136.0 (C), 132.9 (C), 126.6 (CH), 110.3 (CH), 55.5 (Ar-
(t, J = 3.7 Hz, 1 H, CH=CCO2Me), 6.73 (d, J = 8.2 Hz, 1 H, ArH), OCH3), 42.1 (CH), 31.7 (CMe2), 30.8 (CH2), 30.6 (CH2), 29.3
3.78 (s, 3 H), 3.74 (s, 3 H), 3.26 (sept., J = 6.9 Hz, 1 H, CHMe2), (CH2), 27.7 [CH(CH3)2], 26.9 (CH), 26.4 [CH(CH3)2], 24.0 (CH2),
2.59–2.46 (m, 2 H, CH2Ar), 2.33 (t, J = 5.9 Hz, 1 H), 2.29–2.13 22.7 (CH3), 22.3 (CH3) ppm. HRMS (EI): calcd. for C21H28O2
(m, 2 H), 1.81–1.72 (m, 1 H), 1.59–1.51 (m, 1 H), 1.46–1.36 (m, 1
H), 1.18 [dd, J = 6.9, 0.9 Hz, 6 H, CH(CH3)2], 1.01 (s, 3 H, CH3),
0.85 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
168.7 (CO2Me), 154.8 (Carom.), 137.7 (CH), 136.6 (C), 135.0 (C),
134.6 (C), 126.0 (CH), 125.8 (CH), 110.2 (CH), 55.3 (ArOCH3),
51.4 (CO2CH3), 43.3 (CH), 35.9 (CH2), 34.9 (CH2), 32.1 (CMe2),
29.5 (CH2), 28.2 [CH(CH3)2], 26.7 [CH(CH3)2], 26.7 (CH), 23.7
(CH2), 22.6 (2 CH3) ppm. HRMS (FAB): calcd. for C22H32O3
344.2351; found 344.2357.
312.2089; found 312.2079.
(11aS)-7-Methoxy-1,1-dimethyl-8-(propan-2-yl)-2,10,11,11a-tetra-
hydro-1H-dibenzo[a,d][7]annulene (14) and (11aS)-7-Methoxy-1,1-
dimethyl-8-(propan-2-yl)-2,3,4,10,11,11a-hexahydro-1H-dibenzo-
[a,d][7]annulene (15): To a solution of compound (–)-13 (22 mg,
0.07 mmol) in MeOH (2 mL) was added NaBH4 (13 mg,
0.35 mmol) at 0 °C. The resulting mixture was allowed to stir at
room temperature for 30 min, and then H2O (2 mL) was added.
The aqueous layer was separated and extracted with EtOAc
(3ϫ10 mL). The combined organic extracts were washed brine,
dried with MgSO4, filtered, and concentrated to give the crude resi-
due, which was dried under vacuum and employed in the next reac-
(6S)-6-{2-[4-Methoxy-3-(propan-2-yl)phenyl]ethyl}-5,5-dimethyl-
cyclohex-1-ene-1-carboxylic Acid (12): To a solution of compound
(–)-11 (193 mg, 0.56 mmol) in methanol (5 mL) was added KOH
solution [1.0 in MeOH/H2O (1:1), 5 mL] at room temperature. tion without further purification. To a solution of the above crude
The resulting mixture was kept stirring under reflux for 6 h. After
cooling to room temperature, the solution was adjusted to pH 1
with 1 HCl. The aqueous layer was separated and extracted with
EtOAc (3ϫ15 mL). The combined organic extracts were washed
with brine, dried with MgSO4, filtered, and concentrated to give
the crude residue, which was purified by flash chromatography on
silica gel (EtOAc/n-hexane, 1:3) to afford (–)-12 (180 mg, 97 %
yield) as a colorless oil. [α]1D9 = –73.2 (c = 2.67, CHCl3). IR
product in CH2Cl2 (3 mL) was added Et3N (29 mg, 0.28 mmol) and
MsCl (16 mg, 0.14 mmol) sequentially at 0 °C. The resulting mix-
ture was allowed to stir at room temperature for 4 h, and then H2O
(4 mL) was added. The aqueous layer was separated and extracted
with EtOAc (3ϫ10 mL). The combined organic extracts were
washed with brine, dried with MgSO4, filtered, and concentrated
to give the crude residue, which was purified by flash chromatog-
raphy on silica gel (EtOAc/n-hexane, 1:19) to afford an inseparable
(CH Cl ): ν = 3372, 1681, 1638, 1498, 1463 cm–1
.
1H NMR mixture of compounds 14 and (–)-15 (19 mg) in a 4:1 ratio as deter-
˜
2
2
1
(400 MHz, CDCl3 , 25 °C): δ = 7.09 (t, J = 3.7 Hz, 1 H,
CH=CCO2H), 6.99 (d, J = 2.2 Hz, 1 H, ArH), 6.94 (dd, J = 8.3,
2.2 Hz, 1 H, ArH), 6.73 (d, J = 8.3 Hz, 1 H, ArH), 3.78 (s, 3 H,
ArOMe), 3.26 (sept., J = 6.9 Hz, 1 H, CHMe2), 2.70–2.53 (m, 2 H,
CH2Ar), 2.34 (t, J = 5.8 Hz, 1 H), 2.32–2.15 (m, 2 H), 1.84–1.74
(m, 1 H), 1.62–1.54 (m, 1 H), 1.51–1.40 (m, 1 H), 1.25–1.21 (m, 1
H), 1.19 [dd, J = 6.9, 1.3 Hz, 6 H, CH(CH3)2], 1.03 (s, 3 H, CH3),
0.87 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
173.8 (CO2H), 154.8 (Carom.), 140.7 (CH), 136.7 (C), 135.1 (C),
mined by H NMR spectroscopy. To a solution of the above mix-
ture in EtOAc (15 mL, 4ϫ10–3 ) was added Pd/C (8 mg, 10 wt.-
%) in one portion. The resulting mixture was hydrogenated under
an atmosphere of H2 (1 atm) at room temperature. After the reac-
tion was complete (ca. 2 h), the reaction solution was filtered
through Celite, and the filtrate was concentrated to give the crude
product, which was purified by flash chromatography on silica gel
(EtOAc/n-hexane, 1:19) to afford compound (–)-15 (16.5 mg, 79%
yield over three steps) as a colorless oil. [α]1D9 = –201.4 (c = 1.17,
4274
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Eur. J. Org. Chem. 2010, 4271–4275