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S. Kobayashi et al.
LETTER
(1H, dd, J = 9.5, 3.5 Hz), 3.59 (1H, dd, J = 9.5, 5.4 Hz), 4.44-
4.68 (1H, m), 6.84 (1H, br). TLC: Rf = 0.40 (AcOEt).
over MgSO4 and evaporated. The residue was dissolved in 24
ml of toluene and the solution was refluxed for 2 h and then
580 mg (10 mmol) of allyl alcohol were added every 30 min
for 5 h under reflux. After evaporation the residue was
chromatographed on silica gel (eluent hexane:AcOEt (10:1))
giving 1.291 g (91%) of compound 12a. HRMS calcd for
C17H23NO5S [M+]: 353.1297, found: 353.1311. IR (CHCl3):
3450, 2955, 1726, 1649, 1610, 1585, 1512, 1465, 1439 cm-1.
1H NMR (CDCl3) d: 2.50-2.62 (2H, m), 3.09-3.16 (1H, m),
3.30-3.33 (2H, m), 3.68 (3H, s), 3.74 (2H, s), 3.79 (3H, s), 4.54
(2H, d, J = 5.4 Hz), 5.05 (1H, br), 5.22 (1H, dd, J = 11.1, 1.3
Hz), 5.30 (1H, dd, J = 17.5, 1.3 Hz), 5.91 (1H, ddt, J = 17.5,
11.1, 5.4 Hz), 6.85 (2H, d, J = 8.7 Hz), 7.24 (2H, d, J = 8.7
Hz).
(12) Dimethyl 3-methansulfonyloxyglutarate (5b): 12.03 g (0.105
mmol) of methanesulfonyl chloride was added dropwise to a
solution of commercially available 17.62 g (0.100 mmol) of
dimethyl 3-hydroxyglutarate in 176 ml of pyridine under ice-
cooling, and stirring further 2 h at room temperature. After
concentration of the solution under reduced pressure 100 ml of
water were added and the product was extracted with 150 ml
of CH2Cl2 several times. The combined CH2Cl2 layer was
dried over MgSO4. After usual work-up the residue was
chromatographed on silica gel to afford 23.54 g (93%) of the
compound 5b (eluent hexane:AcOEt (6:1)). HRMS calcd for
C14H19O5S [M++1]: 255.0538, found: 255.0522. IR (CHCl3):
2957, 1739, 1440, 1361, 1310, 1175 cm-1. 1H NMR (CDCl3)
d: 2.81-2.97 (4H, m), 3.09 (3H, s), 3.72 (6H, s), 5.27-5.34 (1H,
m). Dimethyl 3-p-methoxybenzylthioglutarate (5c): To a
suspension of 1.728 g (72 mmol) of NaH in THF was added a
solution of 10.18 g (60 mmol) of p-methoxybenzylmercaptan
in 60 ml of THF under ice-cooling. After stirring at the same
temperature for 30 min, 15.26 g (60 mmol) of dimethyl
mesylate 5b in 60 ml of THF was added. Stirring was
(15) (R)-4-p-Methoxybenzylthio-pyrrolidin-2-one (13): To a
mixture of 12a, palladium acetate (11 mg, 0.05 mmol),
triphenylphosphine (26 mg, 0.1 mmol) in 14 ml of THF was
added triethylamine (303 mg, 3.0 mmol) and formic acid (92
mg, 2.0 mmol) and the solution was refluxed for 30 min.
CH2Cl2 (140 ml) was poured and the organic layer was
washed with 100 ml of water. After drying over MgSO4 and
evaporation of the solvent the residue was chromatographed
on silica gel to give 198 mg (83%) of the compound13 (eluent
hexane:AcOEt (1:5)). HRMS calcd for C12H15NO2S [M+]:
237.0823, found: 237.0837. IR (CHCl3): 3441, 2958, 1745,
1702, 1611, 1586, 1512, 1486, 1465 cm-1. 1H NMR (CDCl3)
d: 2.27 (1H, dd, J = 17.0, 7.2 Hz), 2.59 (1H, dd, J = 17.0, 8.6
Hz), 3.22 (1H, dd, J = 10.1, 6.0 Hz), 3.35-3.42 (1H, m), 3.56
(1H, dd, J = 10.1, 7.2 Hz), 3.73 (2H, s), 3.80 (3H, s), 6.38 (1H,
br), 6.85 (2H, d, J = 8.7 Hz), 7.22 (2H, d, J = 8.7 Hz).
(16) (R)-4-Mercapto-pyrrolidin-2-one (14): To a solution of 1.187
g (5 mmol) of (R)-4-p-methoxybenzylthio-pyrrolidin-2-one
(13) in 5.5 ml (50 mmol) of anisole were added 12 ml of
trifluoroacetic acid and 1.50 g (10 mmol) of
continued for 2.5 h at room temperature and the solvent was
distilled under reduced pressure. Water (200 ml) was added
and the product was extracted with CH2Cl2 several times and
the combined CH2Cl2 solution was dried over MgSO4. After
evaporation of the solvent the residue was chromatographed
on silica gel to give 17.62 g (94%) of compound 5c (eluent
hexane:AcOEt (8:1)). HRMS calcd for C15H20O5S [M+]:
312.1031, found:312.1054. IR (CHCl3): 2955, 1736, 1611,
1586, 1512, 1438 cm-1. 1H NMR (CDCl3) d:2.59-2.70 (4H,
m), 3.36-3.43 (1H, m), 3.68 (3H, s), 3.77 (2H, s), 3.79 (3H, s),
6.84 (2H, d, J = 8.8 Hz), 7.25 (2H, d, J = 8.8 Hz).
(13) Monomethyl (S)-3-p-methoxybenzylthioglutarate (10a): To a
suspension of 3.12 g (10 mmol) of diester (5c) in 312 ml of 0.1
M phosphate buffer solution (500 v/w) was added 1.0 ml [103
u/mg protein (10 mg/ml)] of PLE solution, and the whole
solution was stirred at 25 °C for 6 hours. During the reaction
time the pH of the solution was kept at 7.0 ± 0.02 by the
addition of 1 M aqueous solution of NaOH. After 6 hr the pH
was adjusted at 10 and the unreacted diester was extracted
with diethyl ether. The aqueous layer was fixed at pH 2.0 by
1N HCl solution and the generated monoester was extracted
with diethyl ether several times. The combined organic layer
was dried over MgSO4 and evaporated to give the desired 2.6
g of monoester 10a. HRMS calcd for C14H18O5S [M+]:
298.0875, found: 298.0885. IR (CHCl3): 3513, 2955, 1736,
1713, 1611, 1586, 1512, 1439 cm-1. 1H NMR (CDCl3) d:2.60-
2.75 (4H, m), 3.34-3.41 (1H, m), 3.68 (3H, s), 3.78 (2H, s),
3.79 (3H, s), 6.84 (2H, d, J = 8.7 Hz), 7.24 (2H, d, J = 8.7 Hz).
(14) Methyl (R)-4-allyloxycarbonylamino-3-p-methoxybenzyl-
thioglutarate (12a): To a solution of 1.194 g (4 mmol) of
monomethyl (S)-3-p-methoxybenzylthioglutarate (10a) in 24
ml of acetone was added triethylamine (486 mg, 4.8 mmol)
and ethyl chlorocarbonate (651 mg, 6.0 mmol) under ice-
cooling. After stirring at the same temperature for 30 min,
aqueous sodium azide (390 mg (6.0 mmol) in 4.8 ml water)
was added. After 60 min the reaction mixture was poured into
200 ml of ice water and the product was extracted several
times with CH2Cl2. The combined organic layer was dried
trifluoromethanesulfonic acid successively at room
temperature for 2 h. The volatiles were removed in vacuo and
the residue (almost only anisole) was removed by washing
with hexane. The remaining insoluble part was
chromatographed on silica gel and 119 mg (34%) of
compound 14 was obtained (eluent hexane:AcOEt (1:5)). IR
(KBr): 3232, 2534, 1677, 1478, 1445, 1414, 1251 cm-1.
1H NMR (CDCl3) d: 1.96 (1H, d, J = 7.0 Hz), 2.26 (1H, dd,
J = 17.1, 6.6 Hz), 2.75 (1H, dd, J = 17.1, 7.1 Hz), 3.27 (1H,
dd, J = 9.9, 5.2 Hz), 3.55-3.70 (1H, m), 3.76 (1H, ddd, J = 9.9,
7.3, 0.7 Hz), 7.00 (1H, br s). [a]D+36.5° (c = 1.179, MeOH).
mp. 69.5-70 °C.
(17) Sulfoxide (16): 1H NMR (CDCl3) d: 2.30-2.90 (2H, m), 3.30
(3H, m), 3.80 (3H, s), 4.42 (2H, s), 6.90 (2H, d, J = 9.1 Hz),
7.22 (2H, d, J = 9.1 Hz). Naphtyl ester (19): 1H NMR (CDCl3)
d:1.60 (3H, d, J = 5.5 Hz), 2.62 (2H, d, J = 6.5 Hz), 2.67 (2H,
d, J = 7.5 Hz), 3.2-3.6(1H, m), 3.71 (3H, s), 6.08 (1H, q,
J = 6.0 Hz), 6.69 (2H, d, J = 9.1 Hz), 7.10 (2H, d, J = 9.1 Hz),
7.30-7.95 (7H, m), 8.20 (1H, br).
Article Identifier:
1437-2096,E;1999,0,S1,0909,0912,ftx,en;W07099ST.pdf
Synlett 1999, S1, 909–912 ISSN 0936-5214 © Thieme Stuttgart · New York