1040 J . Org. Chem., Vol. 67, No. 3, 2002
Notes
95.5% er (column AS; UV-detector: 214 nm; 20% i-PrOH in
hexane; flow rate 0.7 mL/min). Anal. Calcd for C14H20O5: C,
62.67; H, 7.51. Found: C, 62.69; H, 7.56.
(1H, br), 1.98 (1H, m), 1.66 (1H, m), 1.44 (9H, s), 1.27 (3H, s).
MS (EI, m/z): 278 (M+ + 1). IR (neat, cm-1): 3420, 2980, 1716,
25
1
1507, 1369, 1165. [R]D ) 12.7 (c 1.28, CHCl3). Data for 12.
-
(4R,5R)-5-(2-Ben zyloxy-eth yl)-2, 2-d ioxo-2λ6-[1, 3, 2]d i-
oxa th iola n e-4-ca r boxylic Acid Meth yl Ester (9). To a solu-
tion of diol 8 (15.391 g, 57.4 mmol) in CH2Cl2 (250 mL) were
added Et3N (17.6 mL, 126.3 mmol) and SOCl2 (6.3 mL, 86.4
mmol) at 0 °C. After stirring at room temperature for 1.5 h, the
mixture was diluted with CH2Cl2 (200 mL), washed with water
and brine, and dried over MgSO4. After removal of solvent, the
residue was dissolved in CCl4(100 mL), CH3CN(100 mL), and
H2O (120 mL). With vigorous stirring, NaIO4 (16.003 g, 74.8
mmol) and RuCl3‚H2O (120 mg) were added at 0 °C. The mixture
was stirred at room temperature for 1 h, and then EtOAc (200
mL) was added. The mixture was washed with aqueous NaHCO3
and brine and dried over MgSO4. After removal of solvent, the
residue was purified by flash chromatography to give the cyclic
HNMR (300 MHz, CDCl3): δ 5.86 (1H, br), 5.37 (1H, s), 4.55
(1H, dt, J ) 11.5, 2.2 Hz), 4.38 (1H, d, J ) 3.8 Hz), 4.33 (1H, dt,
J ) 11.6, 3.2 Hz), 2.21 (1H, dd, J ) 12.9, 2.2 Hz), 1.91 (1H, m),
1.46 (9H, s), 1.16 (3H, s). MS (EI, m/z): 246 (M+ + 1). IR (neat,
25
cm-1): 3391, 2934, 1742, 1682, 1520, 1401, 1168, 899. [R]D
)
126.7 (c 1.20, CHCl3). Anal. Calcd for C11H19O5N: C, 53.87; H,
7.81; N, 5.71. Found: C, 53.81; H, 7.53; N, 5.58.
(2S,3R)-3-Hyd r oxy-3-m et h yl-1,2-p yr r olid in ed ica r b oxy-
lic Acid 1-(1,1-Dim eth yleth yl) 2-Meth yl Ester (13). To a
stirred solution of diol 11 (1.159 g, 4.18 mmol) in CH2Cl2 (30
mL) was added MsCl (0.37 mL, 4.80 mmol) at -78 °C, and then
Et3N (0.67 mL, 4.80 mmol) was added slowly over 10 min. After
the mixture was stirred at -78 °C for 1 h, aqueous NH4Cl (5
mL) was added. The mixture was warmed to room temperature
and diluted with CH2Cl2 (100 mL), washed by brine, and dried
over Na2SO4. The solvent was removed, and the residue was
purified by flash chromatography to give the product 13 as a
1
sulfate 9 as a colorless liquid (17.1 g, yield 90%). H NMR (300
MHz, CDCl3): δ 7.29-7.42 (5H, m), 5.07 (1H, s), 4.52 (2H, s),
3.80 (3H, s), 3.67 (2H, m), 2.39(1H, dt, J ) 14.7, 5.7 Hz), 1.95
(1H, m), 1.86 (3H, s). MS (EI, m/z): 330 (M+). IR (neat, cm-1):
2960, 2877, 1772, 1749, 1388, 1214, 1062, 875, 834, 749, 700.
1
colorless liquid (1.04 g, yield 96%). H NMR (300 MHz, CDCl3):
δ 4.05 (1H, s), 3.78 (3H, s), 3.61 (2H, m), 2.40 (1H, br), 2.08 (1H,
m), 1.91 (1H, m), 1.50 (3H, s), 1.44 (9H, s). MS (EI, m/z): 260
(M+ + 1). IR (neat, cm-1): 3447, 2978, 1749, 1705, 1456, 1404,
25
[R]D ) 42.8 (c 1.14, CHCl3).
(2S,3R)-Meth yl 2-Azid o-5-ben zyloxy-3-h yd r oxy-3-m eth -
ylp en ta n oa te (10). A mixture of cyclic sulfate 9 (15.812 g, 47.9
mmol) and NaN3 (6.323 g, 97.3 mmol) in 300 mL of DMF was
heated to 80 °C with vigorous stirring. After 6 h, the mixture
was cooled to room temperature and the solvent removed in
vacuo. The residue was dissolved in 400 mL of THF and then
H2SO4 (concentrated 3 mL) and water (1.8 mL) were added at 0
°C. After the mixture was stirred at room temperature for 1 h,
K2CO3 (20 g) was added and the stirring was continued for 10
min. After removal of the yellow suspension by filtration, the
filtrate was dried over Na2SO4. The solvent was removed, and
the residue was purified by flash chromatography to give the
product 10 as a colorless liquid (12.0 g, yield 86%). 1H NMR (300
MHz, CDCl3): δ 7.31-7.37 (5H, m), 4.53 (2H, s), 3.92 (1H, s),
3.81 (3H, s), 3.77 (2H, m), 2.04 (1H, m), 1.91 (1H, m), 1.29 (3H,
s). MS (EI, m/z): 294 (M+ + 1). IR (neat, cm-1): 3471, 2955,
25
1368, 1164. [R]D ) -19.1 (c 0.90, CHCl3). Anal. Calcd for
C
12H21O5N: C, 55.58; H, 8.16; N, 5.40. Found: C, 55.51; H, 7.93;
N, 5.20.
(2S,3R)-3-Hyd r oxy-3-m eth ylp r olin e (3). To a stirred solu-
tion of 13 (200 mg, 0.77 mmol) in THF (6 mL), MeOH (2 mL),
and water (2 mL) was added LiOH‚H2O (100 mg, 2.31 mmol) at
room temperature. After stirring for 6 h, the mixture was
acidified by addition of aqueous NaHSO4 (10%) to pH 3 and then
extracted with EtOAc (50 mL × 3). The combined organic layer
was dried over Na2SO4. After removal of solvent, the residue
was dissolved in CH2Cl2 (4 mL) and TFA (4 mL) at 0 °C. After
the mixture was stirred at room temperature for 1.5 h, the
solvent was removed in vacuo. The residue was taken up in
water (1 mL), and the resulting aqueous solution passed though
a column (15 × 1 cm) of a strongly acidic ion-exchange resin
(Dowex 50 × 2, 100∼200 mesh), eluting first with water (100
mL) and then with aqueous ammonium hydroxide (2 M, 100
mL). The ammonia fraction was concentrated in vacuo, and the
residue solid was crystallized from EtOAc and EtOH (5:1), giving
a colorless solid 3 (108 mg, 97% yield). Mp: 196∼199 °C. 1H
NMR (300 MHz, D2O): δ 3.86 (1H, s), 3.54 (1H, m), 3.46 (1H,
m), 2.15 (2H, m), 1.60 (3H, s). 13C NMR (75 MHz, D2O): δ 171.2,
25
2872, 2114, 1743, 1455, 1205, 740, 699. [R]D ) -23.1 (c 1.12,
CHCl3). Anal. Calcd for C14H19O4N3: C, 57.33; H, 6.53; N, 14.32.
Found: C, 57.58; H, 6.63; N, 14.67.
(2S,3R)-2-ter t-Bu t oxyca r b on yla m in o-3,5-d ih yd r oxy-3-
m eth yl-p en ta n oic Acid Meth yl Ester (11) a n d (3S,4S)-3-
ter t-Bu toxyca r bon yla m in o-4-h yd r oxy-4-m eth yl-2-p yr on e
(12). A mixture of R-azido-â-hydroxy ester 10 (4.830 g, 16.5
mmol), Boc2O (4.4 g, 20.2 mmol), and Pd-C (10%, 500 mg) in
100 mL of EtOAc was hydrogenolyzed (1 atm) for 20 h. The solid
was removed by filtration, and the solution was concentrated
in vacuo. The residue was dissolved in MeOH (100 mL), and
20% Pd(OH)2 on C (300 mg) was added. The suspension was
stirred vigorously under H2 (1 atm) until the uptake of hydrogen
stopped. The mixture was filtered, and the filtrate was concen-
trated. Flash chromatography gave the diol 11 (3.26 g, 72%) and
the lactone 12 (0.96 g, yield 23%). Data for 11. 1H NMR (300
MHz, CDCl3): δ 5.47 (1H, d, J ) 7.1 Hz), 4.31(1H, d, J ) 7.4
Hz), 3.95 (1H, m), 3.84(1H, m), 3.77 (3H, s), 3.43 (1H, s), 2.71
78.8, 70.1, 43.7, 39.9, 24.3. MS (EI, m/z): 146 (M+ + 1). IR (film,
25
cm-1): 3375, 2966, 1632, 1401, 1263, 1105, 1025, 880. [R]D
-38.6 (c 0.40, H2O).
)
Ack n ow led gm en t. The Major State Basic Research
and Development Program (Grant G2000077500), NSFC
(Grant 20172061), the Chinese Academy of Sciences,
and the Shanghai Commission of Science and Technol-
ogy are appreciated for the financial support.
J O016227+