´
A. Rodrıguez, M. Nomen, B. W. Spur, J.-J. Godfroid
FULL PAPER
the (R)-acetate 17. 17 was hydrolyzed as described above (method
BЈ). The crude product was purified by flash chromatography af-
fording 6 (1.2 g, 80%). The ee value was determined to be 92%
using the analysis described in method A.
(CH3ϪCOO), 24.3 (CH2ϪCϭ), 24.5 (CH2ϪCH2ϪCOO), 26.9
(CH2ϪCH2ϪCϭ), 28.5 and 28.7 {(CH2)2}, 33.8 (CH2ϪCOO), 41.3
(CH2ϪCO), 51.2 (CH3O), 70.3 (CHϪOAc), 149.9 (Cϭ), 151.6
(CHϭ), 170.6 (CH3ϪCOO), 174.1 (COOCH3), 204.8 (CO).
1
Method E: A crude mixture of 17 and 18 (1.7 g), obtained from the
enzymatic reaction, was converted into 17 and 18a as described in
method B. The residue was dissolved in DMF (25 mL) and CsF
(2.3 g, 15.0 mmol) was added. The solution was cooled to 0°C and
acetic acid glacial (0.86 mL, 15.0 mmol) was added. The mixture
was brought to room temperature and stirred until the mesylate
was consumed. The reaction was poured over EtOAc/ice-water
(2:1) (100 mL) and the organic phase was separated, washed with
saturated solution of NaHCO3 (25 mL), water (4 ϫ 25 mL) and
brine (25 mL), and dried over Na2SO4 affording the (R)-acetate 17.
17 was hydrolyzed as described above (method BЈ). The crude prod-
uct was purified by flash chromatography affording 6 (1.1 g, 73%).
The ee value was determined to be 91% using the analysis described
in method A.
Hydroxy derivative (6): H NMR (CDCl3, 300 MHz): δ ϭ 1.2Ϫ1.4
{m, 4 H, (CH2)2}, 1.5 (quint, J ϭ 7.6 Hz, 2 H, CH2ϪCH2ϪCϭ),
1.6 (quint, J ϭ 7.3 Hz, 2 H, CH2ϪCH2ϪCOO), 2.1 (br. t, J ϭ
7.6 Hz, 2 H, CH2ϪCϭ), 2.3 (t, J ϭ 7.3 Hz, 2 H, CH2ϪCOO), 2.3
(dd, J ϭ 18.5, 1.8 Hz, 1 H, 1H CH2CO), 2.6 (br. s, 1 H, OH), 2.8
(dd, J ϭ 18.5, 6.1 Hz, 1 H, 1 H CH2ϪCO), 3.6 (s, 3 H, CH3O), 4.9
(m, 1 H, CHϪOH), 7.2 (m, 1 H, CHϭ). Ϫ 13C NMR (CDCl3,
75.5 MHz): δ ϭ 24.2 (CH2ϪCϭ), 24.7 (CH2ϪCH2ϪCOO), 27.1
(CH2ϪCH2ϪCϭ), 28.6 and 28.7 ((CH2)2), 33.9 (CH2ϪCOO), 44.9
(CH2ϪCO), 51.3 (CH3O), 68.5 (CHϪOH), 148.0 (Cϭ), 155.9
(CHϭ), 174.4 (COO), 206.3 (CO).
Methyl-7-[5-oxo-3(R)-[(triethylsilyl)oxy]-1-cyclopenten-1-yl]-hepta-
noate (20): To a solution of 6 (45 g, 0.18 mol) and Et3N (78.2 mL,
0.56 mol) in THF (350 mL) at 0°C was added dropwise Et3SiCl
(47.1 mL, 0.28 mol). The solution was stirred at 20°C until TLC
showed completion of the reaction and then filtered through celite
and concentrated. The residue was dissolved in hexane (200 mL),
filtered again through celite and the solvent was evaporated under
reduced pressure affording crude 20 that was purified by bulb-to-
bulb distillation (150Ϫ160°C/0.1 mm). 20 was obtained as a light
yellow oil (58.4 g, 88%). Deprotection of a small sample and analy-
sis by chiral HPLC showed that no epimerization had occurred
during silylation and distillation. Ϫ 1H NMR(CDCl3, 300 MHz):
δ ϭ 0.6 (q, J ϭ 8.0 Hz, 6 H, CH2ϪSi), 0.9 (t, J ϭ 8.0 Hz, 9 H,
CH3ϪCH2ϪSi), 1.2Ϫ1.4 {m, 4 H, (CH2)2}, 1.4Ϫ1.5 (m, 2 H,
CH2ϪCH2ϪCϭ), 1.5Ϫ1.7 (m, 2 H, CH2ϪCH2ϪCOO), 2.1Ϫ2.2
(m, 2 H, CH2ϪCϭ), 2.3 (dd, J ϭ 18.3, 2.1 Hz, 1 H, 1H CH2ϪCO),
2.3 (t, J ϭ 7.5 Hz, 2 H, CH2ϪCOO), 2.7 (dd, J ϭ 18.3, 5.7 Hz, 1
H, 1H CH2ϪCO), 3.7 (s, 3 H, CH3O), 4.9 (m, 1 H, CHϪOTES),
7.0 (m, 1 H, CHϭ). Ϫ 13C NMR (CDCl3, 75.5 MHz): δ ϭ 4.7
(3 C, CH2ϪSi), 6.6 (3 C, CH3ϪCH2ϪSi), 24.3 (CH2ϪCϭ), 24.7
(CH2ϪCH2ϪCOO), 27.1 (CH2ϪCH2ϪCϭ), 28.7 and 28.9
{(CH2)2}, 33.9 (CH2ϪCOO), 45.5 (CH2ϪCO), 51.3 (CH3O), 68.6
(CHϪOTES), 147.2 (Cϭ), 156.5 (CHϭ), 174.1 (COO), 206.1 (CO).
Method F: A crude mixture of 17 and 18 (1.7 g), obtained from the
enzymatic reaction, was converted into 17 and 18a as described in
method B. The residue was dissolved in dioxane/H2O 1:1 (20 mL)
and treated with NaOAc·3H2O (2.0 g, 15 mmol) and CsF (2.3 g,
15 mmol) at room temperature for 12 hours. The dioxane was eva-
porated under vacuum and the residue extracted with EtOAc
(50 mL), washed with water (20 mL) and brine (20 mL), and dried
over Na2SO4 affording a mixture of (R)-acetate 17 and (R)-hydroxy
6. Hydrolysis as described above (method BЈ) and flash chromatog-
raphy afforded 6 (1.12 g, 75%). The ee value was determined to be
81% using the analysis described in method A.
Method G: A crude mixture of 17 and 18 (1.7 g), obtained from
the enzymatic reaction, was converted into 17 and 18a as described
in method B. The residue was dissolved in MeOH (15 mL) and
cooled to 0°C followed by the addition of a 0.2 solution of guani-
dine in MeOH (16.5 mL, 3.3 mmol). The mixture was stirred until
TLC checking showed completion and then neutralized with glacial
acetic acid (0.19 mL, 3.3 mmol). The solvent was removed under
reduced pressure and the residue was partitioned between water
(25 mL) and EtOAc (25 mL). The aqueous layer was further ex-
tracted with EtOAc (25 mL) and the combined organic layers were
washed with water (20 mL) and brine (20 mL), and dried over
Na2SO4. The crude product was purified by flash chromatography
affording 6 (1.23 g, 82%). The ee value was determined to be 80%
using the analysis described in method A.
Mesylate derivative (18a): 1H NMR (CDCl3, 300 MHz): δ ϭ 1.3
{m, 4 H, (CH2)2}, 1.5 (m, 2 H, CH2ϪCH2ϪCϭ), 1.6 (m, 2 H,
CH2ϪCH2ϪCOO), 2.2 (tt, J ϭ 7.7, 1.4 Hz, 2 H, CH2ϪCϭ), 2.3
(t, J ϭ 7.5 Hz, 2 H, CH2ϪCOO), 2.5 (dd, J ϭ 18.9, 1.8 Hz, 1 H,
1H CH2ϪCO), 2.8 (dd, J ϭ 18.9, 6.3 Hz, 1 H, 1H CH2ϪCO), 3.0
(s, 3 H, CH3ϪS), 3.6 (s, 3 H, CH3O), 5.7 (m, 1 H, CHϪOMs), 7.1
(dt, J ϭ 2.6, 1.4 Hz, 1 H, CHϭ). Ϫ 13C NMR (CDCl3, 75.5 MHz):
(S)-1-Iodo-1(E)-octen-3-ol (7): In a flame dried flask under argon
containing a solution of an n-butylboronic complex of diphenyl -
prolinol (1.6 g, 5.0 mmol) in toluene (250 mL) was added 1-iodo-
1(E)-octen-3-one (19) (25.0 g, 0.10 mol) and the solution was co-
oled to Ϫ78°C. To this mixture was added a 4 solution of cat-
echolborane in toluene (50.0 mL, 0.20 mol) over 12 hours. After 24
hours at Ϫ78°C the reaction was quenched by dropwise addition
of MeOH (10 mL) and the reaction was allowed to reach 0°C over
1 hour. The solution was extracted six times with 4 NaOH
(50 mL), extracted twice with 10% HCl (50 mL), washed once with
brine (200 mL), dried over Na2SO4 and evaporated under reduced
pressure to afford 7 (24.1 g, 95%). The ee value was determined to
be >96% by 1H NMR of the Mosher ester derivative and by chiral
HPLC analysis: Chiracel OF (250 ϫ 4.6 mm), mobile phase: hex-
ane/iPrOH 97.5:2.5, flow rate: 0.5 mL/min, λ ϭ 210 nm, RT (R-
isomer) ϭ 14.7 min, RT (S-isomer) ϭ 16.6 min. Ϫ 1H NMR
(CDCl3, 300 MHz): δ ϭ 0.9 (t, J ϭ 6.9 Hz, 3 H, CH3), 1.2Ϫ1.4
δ
ϭ
24.3 (CH2ϪCϭ), 24.5 (CH2ϪCH2ϪCOO), 26.8
(CH2ϪCH2ϪCϭ), 28.5 and 28.6 {(CH2)2Ϫ(CH2)2ϪCOO}, 33.7
(CH2ϪCOO), 38.4 (CH3ϪS), 41.3 (CH2ϪCO), 51.2 (CH3O), 75.6
(CHϪOMs), 149.9 (CHϭ), 151.4 (Cϭ), 174.1 (COOCH3), 202.9
(CO).
1
Acetate derivative (17): H NMR (CDCl3, 300 MHz): δ ϭ 1.2Ϫ1.4 {m, 6 H, (CH2)3ϪCH3}, 1.4Ϫ1.6 (m, 2 H, CH2ϪCHϪOH), 4.1
{m, 4 H, (CH2)2}, 1.4 (m, 2 H, CH2ϪCH2ϪCϭ), 1.5 (m, 2 H, (dq, J ϭ 6.3, 1.1 Hz, 1 H, CHϪOH), 6.3 (dd, J ϭ 14.4, 1.1 Hz, 1
CH2ϪCH2ϪCOO), 2.0 (s, 3 H, CH3ϪCO), 2.1 (br. t, J ϭ 7.5 Hz, H, ϭCHϪI), 6.6 (dd, J ϭ 14.4, 6.3 Hz, 1 H, ϭCHϪCHϪOH). Ϫ
2 H, CH2ϪCϭ), 2.2 (t, J ϭ 7.5 Hz, 2 H, CH2ϪCOO), 2.3 (dd, J ϭ
18.9, 2.1 Hz, 1 H, 1H CH2ϪCO), 2.8 (dd, J ϭ 18.9, 6.3 Hz, 1 H,
1H CH2ϪCO), 3.6 (s, 3 H, CH3O), 5.7 (m, 1 H, CHϪOAc), 7.1
(m, 1 H, CHϭ). Ϫ 13C NMR (CDCl3, 75.5 MHz): δ ϭ 20.7
13C NMR (CDCl3, 75.5 MHz): δ ϭ 13.9(CH3), 22.4 (CH2ϪCH3),
24.7 (CH2ϪCH2ϪCO), 31.5 (CH2ϪCH2ϪCH3), 36.5
(CH2ϪCHϪOH), 74.6 (CHϪOH), 77.0 (ϭCHϪI), 148.8 (ϭ
CHϪCHϪOH).
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Eur. J. Org. Chem. 1999, 2655Ϫ2662