7258
R. J. Andrew et al. / Tetrahedron 56 (2000) 7255–7260
Micromass Platform quadrupole mass analyser for APCI
distilled 1-(4-methyl-1-cyclohexenyl)tetrahydro-1H-pyrrole
(9) (0.40 g, 2.4 mmol) in anhydrous ether (2 ml). After stir-
ring for 72 h at room temperature, water (5 ml) and diethyl
ether (5 ml) were added, the reaction mixture was worked
up as described above and the resultant red oil was purified
by flash column chromatography (silica gel, petroleum
ether/ethyl acetate 7:3) to give the title compound (10) as
a solid (0.28 g, 90%) and (E)-1,1,1-trifluoro-4-tetrahydro-
1H-1-pyrrolyl-3-buten-2-one (7) (0.02 g, 9%) as colourless
crystals. Recrystallisation of the title compound (10) from
n-pentane afforded colourless crystals, mp 66–67ЊC; Found:
C, 55.7; H. 6.6. C13H19F3O3 requires C, 55.7; H, 6.8%; dH
4.14 (1H, s, OH), 4.04 (1H, br t, J4.0 Hz, Heq-4), 3.62 (1H,
dq, J9.0, 7.0 Hz, OCH2CH3), 3.42 (1H, dq, J9.0, 7.0 Hz,
OCH2CH3), 2.78 (2H, m, Heq-1, Heq-5), 2.68 (1H, dd,
J15.4, 4.0 Hz, Heq-3), 2.25 (3H, m, Hax-3, Hax-7, Heq-6
or Heq-8), 2.08 (1H, m, Heq-6 or Heq-8), 1.72 (1H, ddd,
J14.3, 12.1, 5.5 Hz, Hax-6 or Hax-8), 1.56 (1H, m, Hax-6
or Hax-8), 1.14 (3H, t, J7.0 Hz, OCH2CH3) and 0.88 (3H, t,
J7.0 Hz, CH3); dC 213.40 (C-9), 124.67 (q, JC–F284 Hz,
CF3), 81.31 (C-4), 79.34 (q, JC–F29 Hz, C-2), 65.18
(OCH2CH3), 54.18 (C-1), 49.98 (C-5), 39.28 and 38.62
(C-6 and C-8), 33.43 (C-3), 24.75 (C-7), 22.27 (CH3) and
15.37 (OCH2CH3); dF Ϫ81.57 (CF3); nmax (cmϪ1) 3458
(OH), 2961, 2875, 1728 (CO), 1460, 1276, 1160, 1118,
1021; found Mϩ 280.1278, C13H19F3O3 requires Mϩ
280.1286 m/z 280 (Mϩ, 20%), 262 (16), 234 (15), 218
(34), 169 (100), 151 (7), 141 (74) and 112 (36).
1
and ES spectra. H and 13C NMR spectra were recorded
on a Bruker WH-300 spectrometer and chemical shifts,
expressed in ppm, are relative to the internal reference,
tetramethylsilane. Coupling constants are quoted in Hz.
19F NMR spectra were recorded using hexafluorobenzene
as an internal standard. Analytical thin layer chromato-
graphy (TLC) was performed on precoated Macherey-
Nagel ALUGRAM SIL G/UV254 aluminium backed plates
and compounds were visualised by UV light, iodine or
sulfuric acid. Flash column chromatography was performed
using silica gel 60 (Macherey-Nagel, 230–400 mesh).
Elemental analyses were undertaken at University College,
London.
4-(Ethyloxy)-2-hydroxy-2-(trifluoromethyl)bicyclo[3.3.1]-
nonan-9-one (8). To a stirred solution of 4-dimethylamino-
pyridine (1 mg, 8×10Ϫ3 mmol) and trifluoroacetic
anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl
vinyl ether (0.08 g, 1.1 mmol). After stirring for 19 h at
0ЊC the mixture was allowed to warm to room temperature
and the solvent removed in vacuo. To the stirred resulting
oil was added dropwise at room temperature a solution of
freshly distilled 1-(1-cyclohexenyl)tetrahydro-1H-pyrrole
(6) (0.36 g, 2.4 mmol) in anhydrous ether (2 ml). After stir-
ring for 77 h at room temperature, water (5 ml) and diethyl
ether (5 ml) were added. The two phases were separated and
the aqueous phase extracted with diethyl ether (5×5 ml).
The combined organic phases were dried (MgSO4) and the
solvent removed in vacuo. The resultant orange oil was
purified by flash column chromatography (silica gel,
petroleum ether/ethyl acetate 1:1) to give the title compound
(8) as a solid (0.26 g, 88%) and (E)-1,1,1-trifluoro-4-tetra-
hydro-1H-1-pyrrolyl-3-buten-2-one (7) (0.02 g, 9%) as
colourless crystals. Recrystallisation of the title compound
(8) from diethyl ether afforded colourless crystals, mp 75–
76ЊC; Found: C, 54.3; H. 6.1. C12H17F3O3 requires C, 54.1;
H, 6.4%; dH 4.21 (1H, s, OH), 4.03 (1H, br t, J4.0 Hz, Heq-
4), 3.63 (1H, dq, J9.0 Hz, 7.0, OCH2CH3), 3.42 (1H, dq,
J9.0, 7.0 Hz, OCH2CH3), 2.82 (2H, br s Heq-1, Heq-5), 2.63
(1H, dd, J15.4, 4.0 Hz, Heq-3), 2.29 (2H, m, Hax-3, Heq-6
or Heq-8), 2.00 (4H, m, Heq-7, Hax-6, Hax-8 and Heq-6 or
Heq-8), 1.58 (1H, m, Hax-7), 1.15 (3H, t, J7.0 Hz,
OCH2CH3); dC 213.09 (C-9), 124.68 (q, JC–F284 Hz,
CF3), 81.40 (C-4), 79.36 (q, JC–F29 Hz, C-2), 65.19
(OCH2CH3), 54.39 (C-1), 50.08 (C-5), 33.17 (C-3), 30.82
and 30.29 (C-6 and C-8), 18.29 (C-7) and 15.37
(OCH2CH3); dF Ϫ81.57 (CF3); nmax (cmϪ1) 3345 (OH),
2975, 2862, 1718 (CO), 1462, 1281, 1155, 1138, 1023,
972, 873; Found Mϩ 266.1115, C12H17F3O3 requires Mϩ
266.1130 m/z 266 (Mϩ,17%), 248 (27), 220 (20), 204
(45), 169 (97), 151 (17), 141 (100) and 98 (33).
9-(Ethyloxy)-7-hydroxy-7-(trifluoromethyl)bicyclo[4.3.1]-
decan-10-one (11). To a stirred solution of 4-dimethyl-
aminopyridine (1 mg, 8×10Ϫ3 mmol) and trifluoroacetic
anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl
vinyl ether (0.08 g, 1.1 mmol). After stirring for 19 h at
0ЊC the mixture was allowed to warm to room temperature
and the solvent removed in vacuo. To the stirred resulting
oil was added dropwise at room temperature a solution of
freshly distilled 1-(1-cycloheptenyl)tetrahydro-1H-pyrrole
(12) (0.40 g, 2.4 mmol) in anhydrous ether (2 ml). After
stirring for 76 h at room temperature, 5% aqueous acetic
acid (20 ml) was added and the mixture was heated under
reflux for 90 min. The mixture was cooled to room tempera-
ture, worked up as described above and the resultant brown
oil was purified by flash column chromatography (silica gel,
petroleum ether/ethyl acetate 3:2) to give the title compound
(11) as a solid (0.14 g, 44%) and (E)-1,1,1-trifluoro-4-tetra-
hydro-1H-1-pyrrolyl-3-buten-2-one (7) (0.03 g, 14%) as a
colourless solid. Recrystallisation of the title compound (11)
from n-pentane afforded colourless needles, mp 82–83ЊC;
Found: C, 55.7; H. 6.6. C13H19F3O3 requires C, 55.7; H,
6.8%; dH 3.97 (1H, dt, J10.2, 6.0 Hz, Hax-9), 3.53 (1H,
dq, J9.0, 7.0 Hz, OCH2CH3), 3.49 (1H, s, OH), 3.41 (1H,
dq, J9.0, 7.0 Hz, OCH2CH3), 3.19 (1H, dt, J9.8, 4.9 Hz,
Heq-1), 2.76 (1H, br t, J5.1 Hz, Heq-6), 2.18 (1H, d,
J5.2 Hz, Heq-8), 2.17 (1H, d, J10.7 Hz, Hax-8), 1.65
(8H, m, H-2, H-3, H-4, H-5), 1.18 (3H, t, J7.0 Hz,
OCH2CH3; dC 211.63 (C-10), 125.21 (q, JC–F286 Hz,
CF3, 75.54 (q, JC–F29 Hz, C-7), 73.16 (C-9), 64.13
(OCH2CH3), 55.99 (C-6), 51.83 (C-1), 30.12 (C-8), 25.78,
25.04 and 21.54 (C-2, C-3, C-4 and C-5), and 15.49
(OCH2CH3); dF Ϫ81.98 (CF3); nmax (cmϪ1) 3422 (OH),
2936, 2873, 1703 (CO), 1456, 1280, 1164, 1109, 1076;
4-(Ethyloxy)-2-hydroxy-7-methyl-2-(trifluoromethyl)bi-
cyclo[3.3.1]nonan-9-one (10). To a stirred solution of 4-
dimethylaminopyridine (1 mg, 8×10Ϫ3 mmol) and trifluoro-
acetic anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl vinyl
ether (0.08 g, 1.1 mmol). After stirring for 19 h at 0ЊC the
mixture was allowed to warm to room temperature and the
solvent removed in vacuo. To the stirred resulting oil was
added dropwise at room temperature a solution of freshly