S. Acherar et al. / Tetrahedron: Asymmetry 14 (2003) 2413–2418
2417
The reaction was stopped by filtration. Removal of the
solvent followed by column chromatography yielded
792 mg of alcohol (−)-5 (44% overall yield from ( )-5).
was stirred for 30 min at 0°C, carbon disulfide (231 mg,
184 mL, 3.04 mmol) and iodomethane (864 mg, 379 mL,
6.08 mmol) was added. The resulting mixture was
stirred for another 1 h, carefully poured into ice, and
extracted with ether. The organic layer was separated,
dried (MgSO4), filtered, and concentrated under
reduced pressure to an oily residue, which was column
chromatographed to provide 262 mg (98%) of xanthate
1
Ee >98%, [h]2D5=− 93.3 (c 1.0, CHCl3). The H and 13C
NMR data were identical with those reported for ( )-5.
4.5. (1S,4R,1%S,3%R,4%R)-4,7,7-Trimethyl-3-oxo-2-oxa-
bicyclo[2.2.1]heptane-1-carboxylic acid 4%-ethoxy-car-
bonyl-3%-methyl-3%-p-tolyl-1%-cyclopentyl ester, (−)-7
1
(–)-8. [h]2D5=−37.7 (c 1.0, CHCl3). H NMR (CDCl3,
300 MHz): l=7.31 and 7.14 (AB, 4H, J=8.1 Hz), 5.88
(tt, 1H, J=7.8, 5.3 Hz), 4.12 (m, 2H), 3.18 (t, 1H,
J=8.7 Hz), 2.66 (dd, 1H, J=14.3, 7.5 Hz), 2.57 (s, 3H),
2.53–2.44 (m, 2H), 2.33 (s, 3H), 2.19 (dd, 1H, J=14.3,
4.3 Hz), 1.43 (s, 3H), 1.19 (t, 3H, J=7.2 Hz). 13C NMR
(CDCl3, 75 MHz): l=215.1, 173.2, 144.5, 135.8, 129.0×
2, 125.6×2, 83.2, 60.4, 53.1, 48.5, 46.7, 34.6, 24.6, 20.8,
18.9, 14.2. Anal. calcd for C18H24O3S2: C, 61.33; H,
6.86; S, 18.19. Found: C, 61.49; H, 6.84; S, 18.09.
To a solution of (−)-5 (100 mg, 0.382 mmol) and
DMAP (10 mg) in pyridine (4 mL) at 0°C under argon
atmosphere was added (−)-(1S,4R)-camphanic acid
chloride (Fluka, 116 mg, 0.535 mmol). The cooling
bath was removed, and the solution was stirred at rt.
The reaction was monitored by TLC and was com-
pleted within 4 h. The mixture was diluted with CH2Cl2
and was sequentially washed with water, 1N HCl (until
pH 2), saturated NaHCO3 solution and brine. The
organic layer was dried over MgSO4, filtered, and con-
centrated in vacuo. The crude mixture was subjected to
column chromatography and afforded the camphanate
derivative (−)-7 (153 mg, 91%). Crystallization of (−)-7
from petroleum ether/ether afforded white crystals. Mp:
73°C. [h]2D5=−27.5 (c 1.0, CHCl3). IR (neat): 3084,
1785, 1741, 1174. 1H NMR (CDCl3, 300 MHz): l=7.28
and 7.13 (AB, 4H, J=8.1 Hz), 4.10 (m, 2H), 5.33 (tt,
1H, J=7.8, 5.5 Hz), 3.16 (t, 1H, J=8.5 Hz), 2.59 (dd,
1H, J=14.1, 7.5 Hz), 2.54–2.37 (m, 2H), 2.35–2.22 (m,
1H), 2.32 (s, 3H), 2.13–1.83 (m, 3H), 1.68 (ddd, 1H,
J=13.2, 9.2, 4.1 Hz), 1.41 (s, 3H), 1.18 (t, 3H, J=7.1
Hz), 1.11 (s, 3H), 1.07 (s, 3H), 0.99 (s, 3H). Anal. calcd
for C26H34O6: C, 70.56; H, 7.74. Found: C, 70.49; H,
7.71.
4.7. (1R,2R)-2-Methyl-2-p-tolyl-cyclopentanecarboxylic
acid ethyl ester, (−)-3
To a solution of xanthate (120 mg, 0.341 mmol) and
AIBN (10 mg) in toluene (3 mL) was added tri-n-
butyltin hydride (172 mg, 157 mL, 0.591 mmol), and the
reaction mixture heated under reflux for 40 min,
cooled, and concentrated in vacuo. The resulting oily
residue was chromatographed on column to provide 80
mg (96%) of (−)-3. [h]2D5=−98.0 (c 1.0, CHCl3). IR
1
(film): 3091, 3043, 1742, 1163. H NMR (CDCl3, 300
MHz): l=7.31 and 7.12 (AB, 4H, J=8.1 Hz), 4.11 (m,
2H), 3.07 (t, 1H, J=7.9 Hz), 2.32 (s, 3H), 2.26–2.05 (m,
2H), 2.00–1.71 (m, 4H), 1.30 (s, 3H), 1.19 (t, 3H, J=7.2
Hz). 13C NMR (CDCl3, 75 MHz): l=174.8, 146.1,
135.2, 128.8×2, 125.8×2, 59.9, 54.5, 49.6, 41.5, 28.1,
24.3, 22.9, 20.8, 14.2. Anal. calcd for C16H22O2: C,
78.01; H, 9.00. Found: C, 77.87; H, 8.98.
Diffraction analysis of (−)-7 (C26H34O6, M=442.53):
The colorless single crystals were analyzed at 293 K
with a Brucker Nonius Kappa-CCD automated four
circle diffractometer using graphite-monochromated
,
Mo-Ka radiation (u=0.71073 A). Crystal data: mono-
Acknowledgements
,
,
clinic, space group P21, a=13.303(1) A, b=6.311(3) A,
3
,
,
c=15.918 (1) A, i=111.141(4)°, V=1246.4(1) A , Z=
2, Dx=1.179 g/cm3, F(000)=476, and v(Mo-Ka)=0.83
cm−1. 289 parameters were refined on F2 using 2667
reflections (Shelxl: Sheldrick, G. M. SHELXL-97, Pro-
gram for Crystal Structure Refinement; University of
Go¨ttingen, Go¨ttingen, Germany, 1997) to final indices
The authors acknowledge Dr. M. Giorgi for performing
X-ray diffraction experiments and Dr. R. Faure for
running NOESY experiments. We are thankful to Prof.
C. Roussel (ENSSPICAM) for chiral HPLC analyses
performed in his laboratory.
R [F2>4|(F2)]=0.0663, wR [w=1/[|2(Fo )+(0.101P)2+
2
2
2
0.294P where P=(Fo +2Fc )/3]=0.192. CCDC 209352
contains the supplementary crystallographic data for
References
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4.6. (1R,2R,4S)-2-Methyl-4-methylsulfanylthiocarboxy-
oxy-2-p-tolyl-cyclopentanecarboxylic acid ethyl ester,
(−)-8
To a suspension of sodium hydride (73 mg, 1.52 mmol,
50% dispersion) in 10 mL of THF at 0°C was added
alcohol (−)-5 (200 mg, 0.76 mmol). After the mixture