Straightforward Synthesis of Octahydrobenzo[e]azulenes
J = 3.8, 1.3 Hz, 1 H), 7.24–7.15 (m, 3 H), 7.07 (dt, J = 7.1, 1.6 Hz,
temperature overnight. THF was removed under reduced pressure
and the crude mixture was taken up in a minimal amount of di-
1 H), 2.97–2.90 (m, 3 H), 2.82–2.74 (m, 2 H) ppm. 13C NMR
(101 MHz): δ = 200.8, 142.3, 134.3, 129.8, 128.4, 126.5, 126.5, 44.9, chloromethane and subjected to column chromatography on silica
27.6 ppm.
gel using heptane/ethyl acetate (1:0–2:1) as eluent. This yielded 8c
(3.59 g, 79%) as a pale yellow oil, Rf [heptane/ethyl acetate (1:1)]
3-(3-Methylphenyl)propanal (6d): Stabilized 2-iodobenzoic acid
(3.4 g, 6.2 mmol, 45% w/w) was added in one portion to 5d (0.78 g,
5.2 mmol) in THF (33 mL). The resulting suspension was heated
to reflux for 5 h. Reaction mixture was cooled, filtered through a
pad of Celite, and washed with diethyl ether (100 mL). Solution
was then washed with satd. NaHCO3 (3ϫ 50 mL) and water
(50 mL), dried with MgSO4, filtered, and concentrated under re-
duced pressure. This yielded 6d (0.68 g, 89%) as a colourless oil,
= 0.24. IR (film): ν = 3412, 2918, 2859, 1683, 1629, 1607, 1440,
˜
1343, 1251, 1077, 999, 922, 785, 699 cm–1. C15H18O2 (230.31):
calcd. C 78.23, H 7.88; found C 77.98, H 8.00. 1H NMR
(400 MHz): δ = 7.43 (t, J = 2.7 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H),
7.04–6.96 (m, 3 H), 4.52–4.42 (m, 1 H), 2.82–2.61 (m, 2 H), 2.61–
2.57 (m, 2 H), 2.44–2.41 (m, 2 H), 2.32 (s, 3 H), 2.03–1.96 (m, 2
H) ppm. 13C NMR (101 MHz): δ = 210, 157.9, 147.5, 141.5, 137.9,
129.2, 128.2, 126.6, 125.4, 67.2, 37.2, 35.2, 31. 5, 26.6, 21.3 ppm.
R [heptane/ethyl acetate (1:1)] = 0.72. IR (film): ν = 3021, 2920,
f
˜
2722, 1721, 1608, 1589, 1488, 1447, 1407, 1387, 1171, 1094, 1055,
2-[1-Hydroxy-3-(3-chlorophenyl)propyl]cyclopent-2-en-1-one (8d): 2-
Cyclopenten-1-one (7, 0.39 g, 4.7 mmol), tri-n-butylphosphane
(0.19 g, 0.95 mmol), and 2-naphthol (0.14 g, 0.95 mmol) in THF
(10 mL) were each added sequentially to a solution of 6d (1.0 g,
5.9 mmol) in THF (10 mL) under nitrogen. The solution was
stirred at room temperature for 1.5 h. THF was removed under
reduced pressure and the crude mixture was taken up in a minimal
amount of dichloromethane and subjected to column chromatog-
raphy on silica gel using heptane/ethyl acetate (1:0–2:1) as eluent.
This yielded 8d (0.86 g, 72%) as a pale yellow oil, Rf [heptane/ethyl
1
906, 883, 781, 697, 572, 534 cm–1. H NMR (400 MHz): δ = 9.81
(t, J = 1.5 Hz, 1 H), 7.18 (dd, J = 11.4, 4.1 Hz, 1 H), 7.05–6.96 (m,
3 H), 2.92 (dd, J = 9.8, 5.3 Hz, 2 H), 2.79–2.73 (m, 2 H), 2.32 (s,
3 H) ppm. 13C NMR (101 MHz): δ = 201.5, 201.6, 140.2, 138.2,
129.0, 128.5, 127.0, 125.2, 45.2, 28.0, 21.3 ppm.
2-(1-Hydroxy-3-phenylpropyl)cyclopent-2-en-1-one (8a): 2-Cyclo-
penten-1-one (7, 1.0 mL, 11.9 mmol), tributylphosphane (0.59 mL,
2.4 mmol), and 2-naphthol (0.34 g, 2.4 mmol) in THF (10 mL)
were each added sequentially to a solution of 6a (2.0 g, 15.2 mmol)
in THF (30 mL) under nitrogen. The solution was stirred at room
temperature overnight. THF was removed under reduced pressure
and the crude mixture was subjected to column chromatography
on silica gel using heptane/ethyl acetate (1:0–2:1) as eluent. This
yielded 8a (2.2 g, 84%) as a pale yellow oil, Rf [heptane/ethyl acet-
acetate (1:1)] = 0.31. IR (film): ν = 3409, 3059, 2920, 2860, 1681,
˜
1629, 1596, 1572, 1476, 1433, 1341, 1253, 1197, 1076, 998, 919,
878, 783, 696, 682 cm–1. C14H15dlO2: calcd. C 67.07, H 6.03, Cl
1
14.14; found C 66.74, H 6.05; Cl, 13.74. H NMR (400 MHz): δ =
7.44 (t, J = 2.7 Hz, 1 H), 7.24–7.13 (m, 3 H), 7.11–7.06 (m, 1 H),
4.48–4.43 (m, 1 H), 2.85–2.64 (m, 3 H), 2.64–2.57 (m, 2 H), 2.43
(ddd, J = 4.2, 2.7, 1.1 Hz, 2 H), 2.05–1.93 (m, 2 H) ppm. 13C NMR
(101 MHz): δ = 210.0, 157.9, 147.3, 143.7, 134.1, 129.6, 128.6,
126.7, 126.1, 67.0, 36.8, 35.2, 31.3, 26.6 ppm.
ate (1:1)] = 0.31. IR (film): ν = 3408, 2920, 2858, 1682, 1629, 1495,
˜
1452, 1438, 1339, 1252, 1070, 999, 919, 788, 747, 698 cm–1.
C15H18O3 (246.31): calcd. C 77.75, H 7.46; found C 78.58, H 7.88.
1H NMR (400 MHz): δ = 7.44 (td, J = 2.7 Hz, 1 H), 7.31–7.24 (m,
2 H), 7.19 (ddt, J = 8.5, 6.5, 1.5 Hz, 3 H), 4.47 (ddd, J = 6.9,
2.7 Hz, 1.3 1 H), 2.88–2.78 (m, 1 H), 2.70 (dt, J = 13.9, 8.0 Hz, 1
H), 2.62–2.56 (m, 2 H), 2.45–2.39 (m, 2 H), 2.06–1.95 (m, 2 H)
ppm. 13C NMR (101 MHz): δ = 210.1, 158.0, 147.4, 141.6, 128.4,
128.3, 125.8, 67.1, 37.1, 35.2, 31.6, 26.6 ppm.
syn-2,3-Oxirano-2-(1-hydroxy-3-phenylpropyl)cyclopentan-1-one
(9a): To a stirred solution of 2-(1-Hydroxy-3-phenylpropyl)-
cyclopent-2-en-1-one (8a, 1.23 g, 5.7 mmol) and vanadyl acetyl-
acetonate (0.021 g, 0.8 mmol) in refluxing benzene (90 mL) in a
Dean–Stark apparatus was added tert-butyl hydroperoxide
(0.81 mL, 6.3 mmol, 70 % in water) dropwise. The solution was
heated at reflux for 5 h and then cooled. The solution was washed
with saturated sodium bisulfate solution (2ϫ 40 mL) and brine
(45 mL), dried with MgSO4, filtered, and concentrated under re-
duced pressure to afford a residue that was subjected to column
chromatography on silica gel using dichloromethane as eluent. This
yielded 9a (0.98 g, 76%) as a colourless oil, Rf [dichloromethane]
2-[1-Hydroxy-3-(3-methoxyphenyl)propyl]cyclopent-2-en-1-one (8b):
2-Cyclopenten-1-one (7, 1.32 mL, 15.7 mmol), tri-n-butylphos-
phane (0.64 g, 3.1 mmol), and 2-naphthol (0.45 g, 3.1 mmol) in
THF (10 mL) were each added sequentially to a solution of 6b
(3.2 g, 19.6 mmol) in THF (50 mL) under nitrogen. The solution
was stirred at room temperature overnight. THF was removed un-
der reduced pressure and the crude mixture was taken up in a mini-
mal amount of dichloromethane and subjected to column
chromatography on silica gel using heptane/ethyl acetate (1:0_1:1)
as eluent. This yielded 8b (2.2 g, 57%) as a pale yellow oil, Rf [hept-
= 0.24. IR (film): ν = 3459, 3026, 2932, 2864, 1735, 1602, 1495,
˜
1452, 1421, 1305, 1274, 1239, 1212, 1073, 1033, 988, 921, 867, 837,
747, 699, 570 cm–1. C15H18O4 (262.30): calcd. C 72.39, H 6.94;
found C 72.66, H 7.03. C14H14O2 (M+ – 18): calcd. 214.0994, found
214.0995. 1H NMR (400 MHz, CDCl3): δ = 7.32–7.24 (m, 2 H),
7.23–7.15 (m, 3 H), 4.26–4.16 (m, 1 H), 3.94–3.83 (m, 1 H), 2.92–
2.83 (m, 1 H), 2.73 (dt, J = 13.9, 8.1 Hz, 1 H), 2.44–2.34 (m, 1 H),
2.31–2.23 (m, 1 H), 2.17–2.08 (m, 1 H), 1.94–1.83 (m, 3 H) ppm.
13C NMR (101 MHz): δ = 210.5, 141.5, 128.5, 128.4, 125.9, 64.6,
62.0, 33.8, 32.3, 31.3, 22.1 ppm.
ane/ethyl acetate (1:1)] = 0.21. IR (film): ν = 3424, 2919, 2835,
˜
1685, 1629, 1599, 1488, 1453, 1436, 1401, 1256, 1193, 1151, 1041,
998, 992, 975, 785, 695, 555 cm–1. C15H18O3 (246.31): calcd. C
73.15, H 7.37; found C 72.88, H 7.48. 1H NMR (400 MHz): δ =
7.43 (t, J = 2.7 Hz, 1 H), 7.19 (t, J = 7.8 Hz, 1 H), 6.83–6.69 (m,
3 H), 4.48 (td, J = 6.7 Hz, 1.3 1 H), 3.79 (s, 3 H), 2.85–2.64 (m, 2
H), 2.60 (ddd, J = 4.4, 3.6, 2.1 Hz, 2 H), 2.45–2.41 (m, 2 H), 2.00
(ddd, J = 8.7, 7.2, 3.5 Hz, 2 H) ppm. 13C NMR (101 MHz): δ =
210.0, 159.6, 157.9, 147.4, 143.2, 129.3, 120.8, 114.1, 111.2, 67.2,
55.1, 37.0, 35.2, 31.7, 26.6 ppm.
syn-2,3-Oxirano-2-[1-hydroxy-3-(3-methoxyphenyl)propyl]cyclo-
pentan-1-one (9b): tert-Butyl hydroperoxide (1.2 mL, 8.8 mmol,
70 % in water) was added to a refluxing solution of 8b (1.96 g,
8.0 mmol) and vanadyl acetylacetonate (0.04 g, 0.16 mmol) in
benzene (200 mL) in a Dean–Stark apparatus. The solution was
heated at reflux for 5 h. The solution was cooled, then washed with
saturated sodium bisulfate solution (2ϫ 50 mL), water (50 mL),
and brine (50 mL), dried with MgSO4, filtered, and concentrated
2-[1-Hydroxy-3-(3-methylphenyl)propyl]cyclopent-2-en-1-one (8c): 2-
Cyclopenten-1-one (7, 1.66 mL, 19.8 mmol), tri-n-butylphosphane
(0.98 mL, 4.0 mmol) and 2-naphthol (0.45 mL, 4.0 mmol) were
each added sequentially to a solution of 6c (3.67 g, 24.8 mmol) in
THF (80 mL) under nitrogen. The solution was stirred at room
Eur. J. Org. Chem. 2015, 5453–5463
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