Deng et al.
added to 20 mL of EtOH in a three-neck flask (50 mL) equipped
with a reflux condenser. The resulting mixture was heated at reflux
for 24 h. After the reaction mixture had been cooled to room
temperature, it was extracted with ether (20 mL × 3). The combined
organic layer was dried over anhydrous MgSO4, filtered through
cotton, and evaporated in vacuo. The residue was purified by flash
chromatography (5% ethyl acetate in hexane) to give 192 mg (89%
yield) of 15 as a yellow oil. 1H NMR: δ 4.11 (q, 2 H, J ) 7.1 Hz),
2.43 (dd, 1 H, J ) 14.7, 5.1 Hz), 2.07 (dd, 1 H, J ) 14.7, 9.2 Hz),
1.14-2.00 (m, 8 H), 1.23 (t, 3 H, J ) 7.1 Hz), 0.95 (d, 3 H, J )
6.6 Hz). 13C NMR: δ 173.6, 60.1, 44.1, 40.5, 39.3, 34.5, 32.4,
23.2, 18.9, 14.3. IR νmax (thin film): 2954, 2870, 1737, 1459, 1375,
1330, 1251, 1190, 1135, 1033, 734 cm-1. MS (EI) m/z: 170 (M+,
26), 155(7), 142(10), 125 (17), 97 (12), 88 (100), 84 (49), 67 (18),
61 (32), 55 (51). HRMS: exact mass calcd for C10H18O2 (M+)
170.1307, found 170.1307.
3-Methyl-2-(phenylthiomethyl)cyclopentan-1-ol 39b. Two di-
astereomers were obtained in a ratio of 7:1. Major diastereomer
39b: 71% yield. Minor diastereomer 39b-minor: 11% yield.
39b. 1H NMR: δ 7.51-7.30 (m, 5 H), 4.19 (m, 1 H), 3.33 (dd,
1 H, J ) 12.8, 4.7 Hz), 3.02 (dd, J ) 12.8, 8.3 Hz), 2.92 (s, 1 H,
-OH), 2.05-1.50 (m, 6 H), 1.19 (d, 3 H, J ) 6.2 Hz). 13C NMR:
δ 136.9, 129.1 (2 C), 128.9 (2 C), 126.0, 78.7, 54.6, 38.5, 36.5,
33.3, 31.5, 20.0. MS m/z: 222 (M+, 59), 123 (19), 100 (100), 97
(53), 70 (64), 55 (18). HRMS: exact mass calcd C13H18OS (M+)
222.1078, found 222.1073.
1
39b-minor. H NMR: δ 7.39-7.17 (m, 5 H), 4.39 (m, 1 H),
3.18 (dd, 1 H, J ) 12.2, 4.4 Hz), 3.01 (dd, 1 H, J ) 12.2, 11.0
Hz), 2.02-1.10 (m, 6 H), 1.52 (s, 1 H, -OH), 1.04 (d, 3 H, J )
6.5 Hz). 13C NMR: δ 136.8, 129.05 (2 C), 128.90 (2 C), 126.0,
73.95, 51.9, 37.2, 32.29, 32.25, 31.5, 19.1. MS m/z: 222 (M+, 31),
123 (13), 100 (69), 95 (44), 84 (100), 70 (64). HRMS: exact mass
calcd C13H18OS (M+) 222.1078, found 222.1077.
3-Methyl-6-(phenylthio)hex-1-en-3-ol 23. To freshly prepared
vinyllithium (31.2 mmol) was added dropwise ketone 22 (3.10 g,
16.0 mmol) in 5 mL of Et2O via syringe. The mixture was stirred
for 2 h at -78 °C, and then the temperature was raised to -20 °C
and maintained there for 30 min before the addition of 40 mL of
satd aq NaHCO3 (40 mL). The mixture was extracted with ether
(50 mL × 3). The combined organic layer was dried over anhydrous
MgSO4, filtered through cotton, and evaporated in vacuo. The
residue was purified by flash chromatography to give 3.07 g (87%
(1R*,2R*,3S*)-1,3-Dimethyl-2-(phenylthiomethyl)cyclopentan-
1-ol 39c. Two diastereomers were obtained in a ratio of 6:1. Major
diastereomer 39c: 78% yield. Minor diastereomer 39c-minor: 14%
yield.
39c. 1H NMR: δ 7.43-7.23 (m, 5 H), 3.10 (dd, 1 H, J ) 12.6,
5.1 Hz), 2.99(dd, 1 H, J ) 12.6, 8.5 Hz), 2.74 (br, 1 H), 1.93-
1.66 (m, 5 H), 1.36 (m, 1 H), 1.33 (s, 3 H), 1.14 (d, 3 H, J ) 6.0
Hz). 13C NMR: δ 136.7, 129.1 (2 C), 129.0 (2 C), 126.1, 81.1,
55.7, 40.1, 38.6, 33.9, 30.3, 24.1, 20.9. MS m/z: 236 (M+, 26),
218 (19), 178 (8), 123 (10), 100 (100), 69 (17), 59 (23). HRMS:
exact mass calcd C14H20OS (M+) 236.1235, found 236.1236.
1
yield) of 23 as a colorless oil. H NMR: δ 7.36-7.18 (m, 5 H),
5.90 (dd, 1 H, J ) 17.3, 10.7 Hz), 5.21 (dd, 1 H, J ) 17.3, 1.2
Hz), 5.07 (dd, 1 H, J ) 10.7, 1.2 Hz), 2.98-2.93 (m, 2 H), 1.80-
1.60 (m, 4 H), 1.39 (s, 1 H, -OH), 1.30 (s, 3 H). 13C NMR: δ
144.9, 136.9, 128.9 (4 C), 125.8, 112.1, 73.1, 41.3, 34.0, 27.9, 23.8.
MS (EI) m/z: 222 (M+, 24), 204 (19), 136 (51), 123(100), 110
(41), 95 (62), 84 (43), 79 (35), 71 (40), 55 (10). HRMS: exact
mass calcd for C13H18OS (M+) 222.1078, found 222.1082.
1
39c-minor. H NMR: 7.39-7.19 (m, 5 H), 3.05-2.91 (m, 2
H), 2.42 (m, 1 H), 2.17 (m, 1 H), 1.97 (m, 1 H), 1.85-1.64 (m, 3
H), 1.30 (s, 3 H), 0.94 (d, 3 H, J ) 7.2 Hz). 13C NMR: δ 136.8,
129.05 (2 C), 128.90 (2 C), 126.0, 73.95, 51.9, 37.2, 32.3, 31.5,
19.1. MS m/z: 236 (M+, 22), 218 (25), 178 (6), 123 (14), 110
100), 69 (22), 55 (12). HRMS: exact mass calcd C14H20OS (M+)
236.1231, found 236.1235.
(1R*,2R*)-1-Methyl-2-(phenylthiomethyl)cyclopetan-1-ol58 25.
To a stirred solution of alcohol 23 (656 mg, 2.95 mmol) in 10 mL
of THF at -78 °C under argon was added n-BuLi (3.20 mmol,
2.00 mL) via syringe. Freshly prepared LDBB (7.40 mmol in 20
mL THF) at -78 °C was cannulated to the reaction flask. The
mixture was stirred at -78 °C for 12 h before the addition of phenyl
disulfide (966 mg, 4.40 mmol) in 5 mL of THF. After the mixture
had been stirred for 30 min further, satd aq NaHCO3 (20 mL) was
added, and the mixture was allowed to warm to room temperature.
The resulting mixture was extracted with ether (20 mL × 3). The
combined organic layer was dried over MgSO4, filtered through
cotton, and evaporated in vacuo. The resulting residue was purified
by flash chromatography to give 531 mg (81% yield) of 25 as a
trans-3,3-Dimethyl-2-(phenylthiomethyl)cyclopentan-1-ol 39d.
1H NMR: δ 7.40-7.20 (m, 5 H), 4.17 (m, 1 H), 3.21 (dd, 1 H, J
) 12.9, 3.93 Hz), 2.79 (dd, 1 H, J ) 12.9, 11.1 Hz), 2.11 (m, 1
H), 1.70-1.20 (m, 4 H), 1.05 (s, 3 H), 0.85 (s, 3 H). 13C NMR: δ
136.1, 129.2 (4 C), 126.4, 79.9, 56.2, 41.6, 39.3, 34.0, 31.5, 29.0,
23.1. IR νmax (neat): 3401(br), 3058, 2953, 2867, 1584, 1480, 1463,
1439, 1366, 1090, 1061, 1026, 739, 691 cm-1. MS(EI) m/z: 236
(M+, 45), 218 (7), 126 (40), 110 (100), 97 (18), 70 (99), 55 (39).
HRMS: exact mass calcd for C14H20OS (M+) 236.1235, found
236.1236.
(1R*,2S*)-1,3,3-Trimethyl-2-(phenylthiomethyl)cyclopentan-
1
1
yellow oil and 51 mg (8%) of 23. H NMR: δ 7.36-7.10 (m, 5
1-ol 39e. H NMR: δ 7.42-7.13 (m, 5 H), 3.06 (dd, 1 H, J )
H), 3.05 (dd, 1 H, J ) 12.4, 6.4 Hz), 2.79 (dd, J ) 12.4, 8.0 Hz),
2.10-1.90 (m, 2 H), 1.80-1.40 (m, 4 H), 1.39 (m, 1 H), 1.22 (s,
3 H). 13C NMR: δ 136.7, 129.16 (2 C), 129.01 (2 C), 126.1, 80.5,
48.8, 41.2, 35.0, 29.8, 22.9, 20.2. IR νmax (neat) 3387 (br), 3058,
2960, 2872, 1583, 1480, 1438, 1376, 1313, 1090, 1025, 738, 691
cm-1. MS (EI) m/z: 222 (M+, 16), 204 (8), 123(12), 110 (58), 95
(44), 84 (100), 79 (14), 71 (5), 58 (7). HRMS: exact mass calcd
for C13H18OS (M+) 222.1078, found 222.1085.
Cyclized products 39a-e were obtained by treating their THF
solution with n-BuLi and LDBB sequentially, and the reactions
were performed at the indicated temperatures and times. See the
preparation of cyclized product 25 for a representative procedure.
trans-2-(Phenylthiomethyl)cyclopentan-1-ol 39a. 1H NMR: δ
7.42-7.19 (m, 5 H), 4.02 (m, 1 H), 3.01 (m, 2 H), 2.60 (br, 1 H,
-OH), 2.12-1.85 (m, 3 H), 1.90-1.50 (m, 3 H), 1.50-1.30 (m, 1
H). 13C NMR: δ 136.8, 129.2 (4 C), 126.1, 78.7, 47.3, 37.8, 34.5,
30.2, 21.9. MS (EI) m/z: 208 (M+, 20), 190 (8), 123 (17), 110
(100), 98 (96). HRMS: exact mass calcd for C12H16OS (M+):
208.0922, found 208.0917.
12.6, 5.1 Hz), 2.91 (dd, 1 H, J ) 12.6, 10.4 Hz), 2.2 (br, 1 H,
-OH), 1.93-1.69 (m, 4 H), 1.46 (m, 1 H), 1.38 (s, 3 H), 1.11 (s,
3 H), 0.91 (s, 3 H). 13C NMR: δ 136.3, 129.1 (4 C), 126.2, 81.3,
58.3, 41.0, 39.8, 39.0, 30.92, 30.86, 25.6, 23.4. MS m/z 250 (M+,
30), 232 (16), 123 (100), 110 (67), 81 (58), 67 (29), 55 (40).
HRMS: exact mass calcd for C15H22OS (M+) 250.1391, found
250.1379.
2-(4-Phenylsulfanylbutyl)prop-2-en-1-ol 42. To a flame-dried,
three-neck round-bottom flask equipped with an argon inlet, a
magnetic stirring bar, and a rubber septum, to a solution of TMEDA
(1.66 mL, 11.0 mmol) in hexane (2 mL) was added n-BuLi (1.66
mL, 1.51 M solution in hexane, 11.0 mmol) while the mixture was
maintained below -10 °C. A vigorous reaction occurred, resulting
in a thick white slurry, which was stirred at this temperature for
30 min. After the reaction mixture had been cooled to -78 °C, a
solution of 2-methyl-2-propen-1-ol 40 (421 µL, 5.00 mmol) in 2
mL of hexane was added dropwise. The mixture was allowed to
stir overnight (∼12 h) before it was warmed to ambient temperature.
Then, the mixture was cooled to -78 °C, and phenyl 3-bromopropyl
sulfide (965 mg, 4.16 mmol) in 2 mL of THF was added. The
mixture was allowed to warm slowly to ambient temperature
overnight (∼ 12 h), and the reaction was quenched with satd aq
(58) “*” Means that the compound is racemic and thus that these are
relative configurations.
2370 J. Org. Chem., Vol. 71, No. 6, 2006