9182 J . Org. Chem., Vol. 63, No. 25, 1998
Shankar and Coates
authentic sample (99% purity by GC analysis).13b The minor
olefin was not identified. Further elution with 5-10% ether/
hexane afforded unreacted 14-OpNB (40 mg, 2%), and elution
with neat ether afforded the alcohol fraction (218 mg, 18%)
consisting of three major alcohol products (A-C, GC ratio 19:
65:15) and several minor alcohol products (15%). This mixture
was combined with the same alcohol fraction (122 mg) from
an identical 1-g scale solvolysis. The alcohol products were
separated by flash chromatography on silica gel using 10% and
15% ether/hexane as eluant. Alcohol B (164 mg, 9%) was
identical with 14-OH based on TLC, GC, and 1H NMR
comparisons, and by vt NMR spectra (1H and 13C) at +80 °C.
Minor alcohol A was isolated as a white solid (15 mg, 85%
purity by GC, 1%) and was identified as (1R,4R,5R,8R,9S)-
8.3 Hz), 2.45 (3H, s), 1.57 (3H, s), 0.87, 0.86 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 144.39, 135.06, 134.44, 129.64, 127.73,
122.88, 85.38, 45.84, 45.59, 39.41, 37.18, 32.79, 32.09, 29.70,
28.47, 22.82, 22.66, 21.61, 15.83; IR (CCl4) νmax 2953, 2926,
2858, 1371 cm-1
. Anal. Calcd for C21H30O3S: C, 69.57; H,
8.34; S, 8.85. Found: C, 69.66; H, 8.40; S, 8.80.
Solvolysis of 15-OTs. A solution of 15-OTs (750 mg, 2.07
mmol) in 60% aqueous acetone (56 mL, v/v) and pyridine (487
µL, 454 mg, 6.21 mmol) was purged with N2, sealed under
nitrogen in a 100-mL, resealable glass tube, and heated at 75
°C for 45 min. The reaction was stopped by rapid cooling to 0
°C, and 1:1 hexane/ether (75 mL) was added. The organic
layer was washed with satd CuSO4 (3 × 15 mL), water (3 ×
25 mL), and brine (25 mL); dried (Na2SO4); and concentrated
to give a yellow oil (480 mg). The product mixture was first
separated into olefin and alcohol fractions by chromatography
on silica gel. Elution with 2% EtOAc/hexane afforded the
olefin fraction (36 mg, 7%) which was a complex mixture that
was not further characterized. Elution with 5% EtOAc/hexane
gave recovered 15-OTs (61 mg, 8%), and elution with 10-50%
EtOAc/hexane gave the alcohol fraction (336 mg, 85%) which
consisted of one major alcohol 17 (74%), 15-OH (9%), and four
other minor alcohols, based on GC analysis. Further purifica-
tion by rechromatography using 10% EtOAc/hexane as eluant
afforded 15-OH (40 mg, 9%) which was identified by compari-
son with an authentic sample, and 17 (238 mg, 61%). Recrys-
tallization from pentane afforded 17 (149 mg, 40%) as colorless
crystals suitable for single-crystal X-ray analysis: mp 107-
109 °C; [R]25D -29.7° (c 0.50, EtOH); 1H NMR (C6D6, 750 MHz)
δ 1.98 (2H, m), 1.86 (1H, dt, J ) 10.9, 4.5 Hz), 1.81 (1H, ddd,
J ) 13.4, 3.8, 2.1 Hz), 1.68 (1H, dd, J ) 12.1, 7.3 Hz), 1.61
(1H, m), 1.52 (1H, m), 1.42 (2H, dt, J ) 12.3, 4.2 Hz), 1.29
(1H, qd, J ) 11.9, 4.6 Hz), 1.22 (1H, dd, J ) 12.2, 9.2 Hz),
1.21 (1H, br), 1.19 (1H, ddd, J ) 7.5, 4.9, 2.7 Hz), 1.11 (3H, s),
1.07-1.04 (2H, m), 0.98 (3H, s), 0.79 (3H, s); 1H NMR (CDCl3,
500 MHz) δ 2.11 (1H, m), 2.01 (1H, ddd, J ) 12.1, 7.5, 4.8
Hz), 1.89 (1H, m), 1.87 (1H, dt, J ) 9.0, 4.6 Hz), 1.76 (1H, m),
1.70 (1H, dd, J ) 12.4, 7.7 Hz), 1.51 (1H, app. dt, J ) 11.2, 4.6
Hz), 1.44 (1H, s, OH), 1.39 (1H, ddd, J ) 17.1, 12.2, 4.9 Hz),
1.24 (3H, s), 1.20 (2H, m), 0.98 (3H, s), 0.81 (3H, s); 13C NMR
(C6D6, 125 MHz) δ 75.4 (C), 59.8 (CH), 58.5 (CH), 56.5 (CH),
51.5 (CH2), 47.3 (C), 46.1 (CH2), 36.0 (CH), 35.6 (CH2), 32.1
(CH2), 27.2 (CH3), 27.1 (CH2,), 21.7 (CH3,), 20.4 (CH3); 13C NMR
(CDCl3, 125 MHz) δ 76.2 (C), 59.7 (CH), 58.3 (CH), 56.3 (CH),
51.2 (CH2), 47.3 (C), 45.6 (CH2), 35.7 (CH), 35.4 (CH2), 31.7
(CH2), 27.1 (CH3), 26.9 (CH2), 21.7 (CH3,), 20.3 (CH3); IR (CCl4)
1
5,8-cyclocaryophyllan-4â-ol (16) by comparison of H and 13C
NMR spectral data with the literature14 and by direct com-
parison of the 1H NMR spectrum with that of 16 in Supporting
Information.14 Particularly significant identification criteria
were the overlapping doublet of triplets at δH 2.31 and the
coincidence of 12 13C NMR resonances within (0.04 ppm. The
other minor alcohol (C) was not isolated in pure form.
(E)-15-Nor ca r yop h yll-4-en -8â-ol (15-OH). A solution of
LiAlH4 (380 mg, 10 mmol) in anhydrous Et2O (10 mL) was
vigorously stirred at room temperature under N2 as a solution
of 13 (2.06 g, 10 mmol) in Et2O (20 mL) was added via a
cannula over 30 min. The reaction was stopped after 30 min
by hydrolysis33 at 0 °C. The salts were filtered and washed
with ether; the filtrate was concentrated; and the residue was
dissolved in CH2Cl2 (ca. 20 mL). The organic layer was washed
with water (3 × 15 mL), dried (Na2SO4), and concentrated to
give 1.97 g of a colorless oil. Purification by chromatography
on silica gel with 20% EtOAc/hexane as eluant, followed by
bulb-to-bulb distillation at 125 °C and 0.2 mmHg gave 15-OH
as a colorless oil (1.83 g, 88%) containing 3% of the cis isomer,
according to GC analysis. The 1H and 13C NMR spectra at
room temperature showed line broadening attributed to the
presence of slowly interconverting conformers: [R]25 -26.7°
D
(c 1.35, EtOH); 1H NMR (CDCl3, 400 MHz) δ 5.37 (1H, br),
3.65 (1H, br), 2.27 (1H, br), 2.06 (2H, br), 1.91 (2H, br), 1.70-
1.29 (10H, br), 0.96, 0.95 (2 × 3H, 2s); 13C NMR (CDCl3, 100
MHz) δ 125.0, 122.43, 73.20, 46.88, 44.85, 39.77, 37.73, 33.46,
33.42, 29.88, 28.34, 23.08, 22.56, 16.0; IR (CCl4) νmax 3441,
2936, 2776, 1346 cm -1. Anal. Calcd for C14H24O: C, 80.71;
H, 11.61. Found: C, 80.72; H, 11.63.
(E)-15-Nor ca r yop h yll-4-en -8â-yl Tosyla te (15-OTs). Al-
cohol 15-OH (1.76 g, 8.45 mmol) was stirred as a neat liquid
and cooled at 0 °C under N2, as 1.51 M n-BuLi in hexane (11.3
mL, 11.9 mmol) was added. After 3 h at room temperature.
tosyl chloride (5.62 g, 29.6 mmol) in anhydrous THF (25 mL)
was added via cannula over 10 min. The heterogeneous
reaction mixture was stirred overnight at room temperature.
Excess tosyl chloride was allowed to react with 3-(N,N-
dimethylamino)propylamine (15 mL, 150 mmol) at room
temperature for 1 h, and satd NH4Cl (5 mL) was added. The
solution was diluted with 1:1 hexane/ether (75 mL). The
organic layer was washed with 10% HCl (2 × 20 mL), satd
NaHCO3 (2 × 25 mL), and brine (25 mL); dried (Na2SO4); and
concentrated to give a yellow solid (3.66 g). Flash column
chromatography on silica gel (500 g) using 15% EtOAc/hexane
as eluant and recrystallization from hexane afforded 1.81 g
(83%) of 15-OTs as white crystals, mp 88-89 °C. The
8â-stereochemistry was confirmed by X-ray crystallography
(see Supporting Information). TLC Rf 0.6 (5% EtOAc/hexane);
1H NMR (CDCl3, 400 MHz) δ 7.84 (2H, d, J ) 8.3 Hz), 7.37
(2H, d, J ) 8.3 Hz), 5.35 (1H, t, J ) 7.8 Hz), 4.52 (1H, d, J )
ν
max 3611, 2950, 2860 cm-1; EIMS (relative intensity) m/z 208
(M+, 26), 193 (17, M+-CH3), 175 (19) 150 (25) 175 (37), 123
(100), 109 (31), 95 (48), 81 (62), 71 (66), 55 (28), 43 (99). Anal.
Calcd for C14H24O: C, 80.71; H 11.61. Found: C, 80.67; H
11.41.
Ack n ow led gm en t. We thank Drs. Scott R. Wilson
and Teresa Prussak-Wieckowski for the X-ray crystal-
lographic analyses and the National Institutes of Health
for financial support (GM 13956).
Su p p or tin g In for m a tion Ava ila ble: Detailed procedures
for preparation 12, 13, and 14-OH; and X-ray crystallographic
data and SHELXTL figures for 15-OTs and 17; spectra for 17
(1H and 13C NMR, DEPT 90 and 135, COSY, HMQC, HMBC,
IR, and EIMS) (43 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(33) Micovic, V. M.; Mihailovic, M. L. J . Org. Chem. 1953, 18, 1190.
J O971984M