584
L. Fonteneau et al. / Tetrahedron: Asymmetry 13 (2002) 579–585
(1H, s, CH=C). 13C NMR, l ppm, 21.83 (CH3), 23.07
(C4), 31.30 and 33.24 (C3 and C5), 67.16 (CH(CH3)2),
137.16 (C1), 143.00 (C2), 164.92 (COO).
5.8. (−)-(S)-Isopropyl 3-hydroxycyclohex-1-ene-1-car-
boxylate 5a
A solution of isopropyl 3-oxo-1-cyclohexene-1 carboxyl-
ate 1a (1.6 g, 8.8 mmol) in EtOH–Tween 80 (5 mL) was
added to culture of G. candidum (1 L) and the mixture
was incubated for 8 h. The suspension was filtered and
the filtrate was saturated with sodium chloride, filtered
again through Celite and extracted with AcOEt (three
times). The organic phase was concentrated to 150 mL,
washed with brine and dried over MgSO4. After evapo-
ration of the solvent, the crude residue was purified by
flash chromatography (cyclohexane/AcOEt, 8:2) to give
(−)-(S)-5a (830 mg, 52%, 90% e.e.). [h]2D0 −36 (c 1,
MeOH).
5.5. Isopropyl 3-oxocyclopent-1-ene-1-carboxylate 1b
Oxidation of 6b (8 g, 52 mmol) as described above
1
afforded 1b (2.53 g, 29%), bp 66–69°C (6 mmHg). H
NMR (CDCl3), l ppm, J Hz: 1.2 (6H, d, J=6.38,
(CH3)2CH-), 2.43–2.49 (2H, m, H2C), 2.76–2.82 (2H, m,
H2C), 5.01 (1H, sext, J=6.38, CHOR), 6.66 (1H, s,
CHꢁC). 13C NMR, l ppm, 21.67 (CH3), 27.42 (C5)
35.52 (C4) and 69.38 (CH(CH3)2), 137.78 (C2), 163.80
and 164.83 (C1) and (COO), 209.12 (C3).
5.6. ( )-Isopropyl 3-hydroxycyclohex-1-ene-1-carboxyl-
ate 5a
5.9. (1S,3S)- and (1R,3S)-Isopropyl 3-hydroxycyclo-
hexane-1-carboxylate 4a and 7a
To a solution of 1a (2 g, 11 mmol) in methanol (60 mL)
cooled at −25°C was added NaBH4 (208 mg, 0.5
equiv.). The reaction was monitored by GC analysis.
Water (10 mL) was added and the mixture was acidified
with 5N aqueous HCl solution. After removal of
methanol, the aqueous phase was saturated with NaCl
and extracted with ether (three times). The organic
phase was washed with saturated NaHCO3, brine and
dried over Na2SO4. The solvent was evaporated and the
product was purified by flash chromatography
(CH2Cl2/AcOEt, 9:1) to yield 5a (1.3 g, 60%). IR
(−)-(S)-Isopropyl 3-hydroxycyclohex-1-ene-1 carboxyl-
ate 5a (492 mg, 2.67 mmol) in ethyl acetate (20 mL)
was hydrogenated at 1 atm over Pd–C (10%, 70 mg) for
3 h. The mixture was filtered on Celite and the solvent
was evaporated. The diastereomeric products were
purified by flash chromatography (dichloromethane–
ethyl acetate, 85:15) to give (1S,3S)-4a (135 mg, 27%)
and (1R,3S)-7a (205 mg, 42%).
1
(1S,3S)-4a: H NMR (CDCl3), l ppm, J Hz: 1.2 (6H,
1
(CHCl3) 3600 cm−1, 1700 cm−1. H NMR (CDCl3), l
d, J=6.38, (CH3)2CH-), 1.5–1.6 (4H, m, CH2), 1.8–1.9
(2H, m, CH2), 2.7 (1H, m, CH(CH3)2), 4.1 (1H, m,
CHOH), 5.0 (1H, sext, J=6.38, CHOR). 13C NMR, l
ppm, 19.8 (C5), 21.8 (CH3), 28.19 (C2) 32.19 (C6), 35.5
(C1), 38.1 (C4), 66.2 (C3), 67.30 (CH(CH3)2, 175.37
(COO). [h]2D0 +9.4 (c 1, MeOH). (S)-O-Acetyllactate
derivatives13 were injected on a OV 1701 capillary
column 150°C (7 min) then 150–185°C (3°C/min),
retention times (1R,3R) 18.3 min, (1S,3S) 18.5 min
(90% e.e.).
ppm, J Hz: 1.2 (6H, d, J=6.37, (CH3)2CH-), 1.5–1.9
(4H, m, CH2), 2.2 (2H, m, CH2), 4.3 (1H, m, CHOH),
5–5.1 (1H, sext, J=6.37, CHOR), 6.8 (1H, br s,
CHꢁC). 13C NMR, l ppm, 19.08 (C5), 21.82 (CH3),
24.19 (C6) 31.19 (C4), 65.98 (CH(CH3)2, 67.90 (C3),
133.08 (C2), 139.00 (C1), 166.77 (COO). Anal. calcd for
C10H16O3: C, 65.19; H, 8.75. Found: C, 65.13; H,
8.75%.
(S)-O-acetyllactate derivatives were obtained as
described13 and injected on a OV 1701 capillary
column, 150°C (7 min) then 150–185°C (3°C/min),
retention times (S)-5a 20.7 min, (R)-5a 20.9 min.
1
(1R,3S)-7a: H NMR (CDCl3), l ppm, J Hz: 1.2 (6H,
d, J=6.37, (CH3)2CH-), 1.5–1.9 (4H, m, CH2), 2.2 (2H,
m, CH2), 4.3 (1H, m, CHOH), 5–5.1 (1H, sext, J=6.37,
CHOR), 6.8 (1H, br s, CHꢁC). 13C NMR, l ppm,
19.08 (C5), 21.82 (CH3), 24.19 (C6) 31.19 (C4), 65.98
(CH(CH3)2, 67.90 (C3), 133.08 (C2), 139.00 (C1), 166.77
(COO). [h]2D0 −4 (c 1, MeOH). (S)-O-Acetyllactate
derivatives were injected on BP 20 capillary column
130°C–185°C (3°C/min), retention times (1R,3S) 28.9
min, (1S,3R) 29.3 min (90% e.e.).
5.7. ( )-Isopropyl 3-hydroxycyclopent-1-ene-1-carboxyl-
ate 5b
To a cooled solution (−20°C) of 1b (700 mg, 4.16
mmol) and CeCl3 (1.55 g, 1 equiv.) in methanol (28
mL) was added NaBH4 (78 mg, 0.5 equiv.) and the
mixture stirred for 30 min. A few drops of a 5N
aqueous HCl solution were added followed by the
addition of H2O (20 mL). The mixture was saturated
with NaCl and extracted with AcOEt (three times). The
organic phase was washed with brine and dried over
Na2SO4. Removal of solvent and flash chromatography
(CH2Cl2/AcOEt, 7:3) yielded 5b (500 mg, 71%). IR
5.10. (+)-(R)-Isopropyl 3-hydroxycyclohex-1-ene-1-car-
boxylate 5a
A solution of ( )-isopropyl 3-hydroxy-1-cyclohexene-1
carboxylate 5a (1.2 g, 6.5 mmol) in EtOH–Tween (5
mL) solution was added to a 1 L culture of G. candidum
and the incubation was carried on for 3 days. The
suspension was filtered. The filtrate was saturated with
NaCl and filtered again with Celite then extracted with
AcOEt (three times). The organic phase was concen-
trated to 150 mL, washed with brine and dried over
MgSO4. After evaporation of the solvent, the crude
1
(CHCl3) 3600 cm−1, 1700 cm−1. H NMR (CDCl3), l
ppm, J Hz: 1.2 (6H, d, J=6.37, (CH3)2CH-), 1.65–1.8
(1H, m, CH2), 2.2–2.45 (1H, m, CH2), 2.55–2.75 (1H,
m, CH2), 4.8 (1H, br s, CHꢁC)), 4.9–5.04 (1H, sext,
J=6.37, CHOR). 13C NMR, l ppm, 21.75 (CH3), 29.84
(C5) 33.39 (C4), 67.91 (CH(CH3)2) 67.90 (C3), 139.12
(C1), 142.73 (C2), 164.87 (CꢁO).