1504
Vol. 59, No. 12
A solution of 41 (455 mg) in THF (1.5 ml) was treated with a solution of temperature for 4 h. The reaction mixture was treated with triethylamine,
tetrabutylammonium fluoride (1.0 M in THF, 0.98 ml, 0.98 mmol) at room
temperature under argon atmosphere for 30 min. The reaction mixture was
diluted with Et2O, washed with H2O, brine, and dried over Na2SO4. The or-
ganic solvent was removed by evaporation, and the resulting residue was pu-
rified by column chromatography on silica gel (hexane/EtOAc, 1/1—1/2) to
and concentrated to give an alcohol as a colorless oil. To a stirred solution of
the alcohol in CH2Cl2 (2 ml), DMSO (2 ml) and triethylamine (0.98 ml,
7.0 mmol) was added SO3·Py (560 mg, 3.50 mmol) at 0 °C under argon
atmosphere. After being stirred at the same temperature for 30 min, the reac-
tion was quenched with H2O. The reaction mixture was diluted with CHCl3,
washed with brine, and dried over MgSO4. The organic solvent was removed
1
give 42 as a pale yellow oil (248 mg, 84% from 39). H-NMR (200 MHz,
CDCl3) d: 7.33 (m, 4H), 5.79 (dd, Jꢀ16, 5.2 Hz, 1H), 5.68 (dt, Jꢀ16, by evaporation to yield an aldehyde as a yellow oil.
5.6 Hz, 1H), 4.44 (s, 2H), 4.40 (m, 1H), 4.12 (q, Jꢀ7.1 Hz, 2H), 3.82 (d,
To a stirred solution of dimethyl 3-[(3-methoxymethyl)phenyl]-2-oxo-
Jꢀ5.6 Hz, 2H), 3.40 (s, 3H), 3.11 (t, Jꢀ7.6 Hz, 2H), 2.87 (dd, Jꢀ13, 5.3 Hz, propanephosphonate 31 (470 mg, 1.64 mmol) in THF (12 ml) was added
1H), 2.80 (dd, Jꢀ13, 7.4 Hz, 1H), 2.78 (s, 3H), 2.29 (t, Jꢀ7.3 Hz, 2H), sodium hydride (62.7% in mineral oil, 54.0 mg, 1.40 mmol) in several por-
1.73—1.47 (m, 4H), 1.43—1.19 (m, 4H), 1.25 (t, Jꢀ7.3 Hz, 3H).
tions at 0 °C under argon atmosphere and stirring was further continued at
7-[{(2E,4S)-4-Hydroxy-5-[3-(methoxymethyl)phenyl]pent-2-enyl}- ambient temperature for 90 min. To the stirred suspension was added a solu-
(methylsulfonyl)amino]heptanoic Acid (10) A solution of 42 (226 mg, tion of the above-described aldehyde (392 mg, 1.46 mmol) in THF (2 ml) at
0.47 mmol) in MeOH (5 ml) and 2 N NaOH (2.5 ml) was stirred at ambient
temperature for 1.5 h. After acidification with 2 N HCl (3.0 ml) under cool-
ing, the reaction mixture was extracted with EtOAc three times, washed with
brine, and dried over Na2SO4. The combined organic layers were evaporated
to give a crude mixture, which was purified by column chromatography on
silica gel (CHCl3/MeOH, 30/1—20/1) to afford 10 as a pale yellow oil
(209 mg, 99%). IR (film) cmꢂ1: 3430, 2932, 2862, 1731, 1714, 1449, 1412,
1384, 1327, 1148, 1094, 1035, 967, 785, 705, 518. 1H-NMR (300 MHz,
CDCl3) d: 7.33—7.09 (m, 4H), 5.79 (dd, Jꢀ15, 5.6 Hz, 1H), 5.69 (dt, Jꢀ15,
6.0 Hz, 1H), 4.45 (s, 2H), 4.41 (m, 1H), 3.82 (d, Jꢀ6.0 Hz, 2H), 3.41 (s,
3H), 3.12 (t, Jꢀ7.5 Hz, 2H), 2.87 (dd, Jꢀ14, 5.1 Hz, 1H), 2.79 (dd, Jꢀ14,
0 °C and stirring was continued for 1 h. The reaction was quenched with
acetic acid, diluted with EtOAc, washed with water, then brine, and dried
over MgSO4. The organic solvent was removed by evaporation and the re-
sulting residue was purified by column chromatography on silica gel
(EtOAc) to give an enone 48 as a pale yellow oil (313 mg, 66% in 4 steps).
1H-NMR (300 MHz, CDCl3) d: 7.40—7.15 (m, 4H), 6.68 (dd, Jꢀ16.0,
8.0 Hz, 1H), 6.21 (d, Jꢀ16.0 Hz, 1H), 5.55—5.45 (m, 1H), 5.30—5.23 (m,
1H), 4.43 (s, 2H), 4.25—4.11 (m, 2H), 3.84 (s, 2H), 3.68 (s, 3H), 3.45—
3.35 (m, 1H), 3.39 (s, 3H), 2.51—2.22 (m, 5H), 2.05—1.91 (m, 2H), 1.85—
1.55 (m, 3H).
(5Z)-7-((2R)-2-{(1E,3S)-3-Hydroxy-4-[3-(methoxymethyl)phenyl]but-
7.8 Hz, 1H), 2.78 (s, 3H), 2.33 (t, Jꢀ7.2 Hz, 2H), 1.70—1.49 (m, 4H), 1-enyl}-5-oxopyrrolidin-1-yl)hept-5-enoic Acid (11) Compound 11 was
1.42—1.22 (m, 4H). MS (APCI) m/z: 426 (MꢂH)ꢂ. HR-MS-FAB (m/z):
426.1937 (Calcd for C21H32NO6S, 426.1950).
prepared from 48 according to the same procedure as described for the
preparation of 6 from (R)-29 as a colorless oil (46% from 48); IR (film)
cmꢂ1: 3396, 2929, 1726, 1661, 1449, 1420, 1243, 1190, 1097, 1036, 973,
790, 756, 704. 1H-NMR (300 MHz, CDCl3) d: 7.32—7.11 (m, 4H), 5.70
(dd, Jꢀ16, 5 Hz, 1H), 5.60—5.48 (m, 2H), 5.34—5.25 (m, 1H), 4.44 (s,
2H), 4.50—4.39 (m, 1H), 4.20 (dd, Jꢀ15, 5.0 Hz, 1H), 4.03 (dt, Jꢀ8.0,
6.2 Hz, 1H), 3.49 (dd, Jꢀ15, 8.0 Hz, 1H), 3.42 (s, 3H), 2.92—2.78 (m, 2H),
2.50—2.05 (m, 7H), 1.77—1.61 (m, 3H). MS (APCI) m/z: 400 (MꢂH)ꢂ.
HR-MS-FAB (m/z): 400.2130 (Calcd for C23H30NO5: 400.2124).
{(2R)-2-[(tert-Butyldimethylsilyloxy)methyl]-5-oxo-1-pyrrolidinyl}ac-
etate (49) To a stirred solution of (R)-26 (300 mg, 1.31 mmol) in DMF
(5 ml) was added sodium hydride (60% in mineral oil, 60 mg, 1.57 mmol) at
room temperature under argon atmosphere, and then stirring was continued
Methyl 7-Hydroxy-5-heptynoate (45) To a stirred solution of 5-
hexynic acid 44 (1.12 g, 10.0 mmol) in THF (5 ml) was added a solution of
ethylmagnesium bromide (1.02 M in THF, 20 ml, 20.4 mmol) at 0 °C under
argon atmosphere. After being stirred at room temperature for 1 h, the result-
ing gray suspension was treated with paraformaldehyde (600 mg) and the re-
action mixture was refluxed for additional 4 h. After being cooled to room
temperature, the reaction mixture was poured into 1 N HCl, extracted with
EtOAc, washed with brine, and dried over Na2SO4. The organic layer was
evaporated to afford an oily product, which was dissolved in MeOH (5 ml)
and treated with a solution of trimethylsilyldiazomethane (2.0 M in hexane,
3.0 ml). The resulting mixture was evaporated and purified by column chro-
matography on silica gel (hexane/EtOAc, 4/1—1/1) to yield 45 (940 mg, at 50 °C for 30 min. To the stirred suspension was added methyl bromo-
60%). 1H-NMR (200 MHz, CDCl3) d: 4.24 (dt, Jꢀ6.2 Hz, 2H), 3.69 (s, 3H), acetate (0.19 ml, 1.96 mmol) at 0 °C and stirring was continued at 50 °C for
2.44 (t, Jꢀ7.0 Hz, 2H), 2.30 (tt, Jꢀ7.0, 2.0 Hz, 2H), 1.90—1.75 (m, 2H), additional 1 h. After being cooled to room temperature, the reaction was
1.56 (t, Jꢀ6.0 Hz, 1H).
Methyl 7-{(2R)-2-[(tert-Butyldimethylsilyloxy)methyl]-5-oxo-1-pyrro- tracted with EtOAc three times. The combined organic layers were washed
lidinyl}-5-heptynoate (47) To stirred solution of 45 (340 mg, with H2O twice, brine, and dried over MgSO4. The organic solvent was re-
quenched with saturated aqueous NH4Cl. The reaction mixture was ex-
a
2.18 mmol) and triphenylphosphine (680 mg, 2.60 mmol) in CH2Cl2 (5 ml)
was added tetrabromomethane (860 mg, 2.60 mmol) at 0 °C under argon
atmosphere. After being stirred for 30 min, the reaction was quenched with
MeOH. The resulting mixture was diluted with EtOAc, washed with water
twice, brine, and dried over Na2SO4. The organic solvent was removed by
evaporation, and the resulting residue was purified by column chromatogra-
phy on silica gel (hexane/EtOAc, 9/1) to give a bromide 46 as a colorless oil
(330 mg, 69%).
To a stirred solution of (R)-26 (330 mg, 1.50 mmol) in DMF (6 ml) was
added sodium hydride (62.7% in oil dispersion, 57.0 mg, 1.50 mmol) at
room temperature under argon atmosphere. Stirring was continued for
30 min to result in precipitates. To the resulting suspension was added a so-
lution of the bromide 46 (330 mg, 1.50 mmol) in DMF (1 ml), and stirring
was continued for additional 1 h. The resulting pale brown solution was
poured into saturated aqueous NH4Cl, extracted with EtOAc, washed with
moved by evaporation and the resulting residue was purified by column
chromatography on silica gel (hexane/EtOAc 3/2) to give an ester 49 as a
colorless oil (241 mg, 61%). 1H-NMR (200 MHz CDCl3) d: 4.47 (d,
Jꢀ17.6 Hz, 1H), 3.95 (d, Jꢀ17.6 Hz, 1H), 3.92—3.74 (m, 1H), 3.72 (s, 3H),
3,74—3.56 (m, 2H), 2.60—2.35 (m, 2H), 2.35—2.05 (m, 1H), 1.80—1.60
(m, 1H), 0.87 (s, 9H), 0.04 (s, 6H).
(5R)-5-[(tert-Butyldimethylsilyloxy)methyl]-1-(2-hydroxyethyl)-2-
pyrrolidinone (50) To a stirred solution of 49 (240 mg, 0.796 mmol) in
MeOH (5 ml) was added sodium borohydride (450 mg, 11.9 mmol) at 0 °C
under argon atmosphere. After being stirred at room temperature for 3 h, the
reaction was quenched with H2O. The reaction mixture was extracted with
EtOAc three times. The combined organic layers were washed with brine,
and dried over MgSO4. Removal of the solvent by evaporation gave an alco-
1
hol 50 as a colorless oil (225 mg, ꢃ100%). H-NMR (200 MHz CDCl3) d:
3.90—3.66 (m, 3H), 3.77 (dd, Jꢀ10.5, 3.3 Hz, 1H), 3.61 (dd, Jꢀ10.5,
H2O, brine, and dried over Na2SO4. The organic solvent was removed by 4.2 Hz, 1H), 3.58—3.40 (m, 3H), 2.49 (ddd, Jꢀ17.1, 10.2, 7.2 Hz, 1H), 2.35
evaporation, and the resulting residue was purified by column chromatogra-
phy on silica gel (hexane/EtOAc, 4/1—1/1) to give 47 as a pale yellow oil
(418 mg, 78%). 1H-NMR (300 MHz, CDCl3) d: 4.58 (dt, Jꢀ16.6, 3.0 Hz,
1H), 3.93—3.80 (m, 1H), 3.75 (dd, Jꢀ11.2, 4.0 Hz, 1H), 3.68 (s, 3H),
3.75—3.61 (m, 2H), 2.55—2.32 (m, 4H), 2.24 (tt, Jꢀ6.6, 3.0 Hz, 2H),
2.25—2.05 (m, 1H), 1.95—1.75 (m, 3H), 0.88 (s, 9H), 0.05 (s, 6H).
Methyl (5Z)-7-[(2R)-2-{(1E)-4-[3-(Methoxymethyl)phenyl]-3-oxo-1-
buten-1-yl}-5-oxo-1-pyrrolidinyl]-5-heptenoate (48) A solution of 47
(418 mg, 1.17 mmol) in benzene/cyclohexane/cyclohexene (5 ml/5 ml/1 ml)
was vigorously stirred under hydrogen atmosphere in the presence of Lindlar
catalyst (50 mg) for 1.5 h. The catalyst was removed by filtration. The filtrate
was evaporated to dryness. The resulting residue was treated with p-toluene-
sulfonic acid monohydrate (46 mg, 0.24 mmol) in MeOH (6 ml) at room
(ddd, Jꢀ17.1, 10.2, 5.1 Hz, 1H), 2.22—2.04 (m, 1H), 1.92—1.79 (m, 1H),
1.62 (br s, 1H), 0.89 (s, 9H), 0.07 (s, 6H).
S-(2-{(2R)-2-[(tert-Butyldimethylsilyloxy)methyl]-5-oxo-1-pyrro-
lidinyl}ethyl)ethanethioate (51) To a stirred solution of 50 (225 mg,
0.796 mmol) in THF (3 ml) and N,N-diisopropylethylamine (0.34 ml,
1.97 mmol) was added methanesulfonyl chloride (0.076 ml, 0.987 ml) at 0 °C
under argon atmosphere. Stirring was continued at room temperature for 2 h.
To the reaction mixture was added potassium carbonate (341 mg,
2.47 mmol) and a solution of potassium thioacetate (188 mg, 1.65 mmol) in
DMF (5 ml) and the stirring was continued at 50 °C for additional 90 min.
After being cooled to room temperature, the reaction was quenched with 1 N
HCl. The reaction mixture was extracted with EtOAc twice. The combined
organic layers were washed with H2O twice, brine, and dried over MgSO4.