Cardillo et al.
(3R ,4′S )-3-Be n zyloxya m in o-3-(2′,2′-d im e t h yl[1′,3′]-
d ioxola n -4′-yl)p r op ion ic Acid Meth yl Ester (12). A stirred
mixture of 7 (100 mg, 0.27 mmol) and MgBr2‚Et2O complex
(14 mg, 0.054 mmol) in toluene (2.5 mL) and methanol (0.5
mL) was heated at 80 °C for 2 h. After evaporation of solvents
at reduced pressure, water (5 mL) was added, and the mixture
was extracted three times with EtOAc. The organic layers were
collected and dried over Na2SO4. The solvent was evaporated
at reduced pressure, and the residue was purified by flash
chromatography over silica gel (eluant EtOAc:cyclohexan 1:5)
giving 12 (76 mg, 97%) as an oil. Oxazolidin-2-one 1 remained
in the water layers, but no recovery was attempted. IR (Nujol)
ν 2995, 1745, 1681, 1048 cm-1; 1H NMR (CDCl3) δ 1.35 (s, 3H),
1.42 (s, 3H), 2.41 (dd, J ) 4.8, 15.8 Hz, 1H), 2.63 (dd, J ) 8.4,
15.8 Hz, 1H), 3.39-3.47 (m, 1H), 3.68 (s, 3H), 3.80 (dd, J )
6.6, 8.2 Hz, 1H), 4.00 (dd, J ) 6.4, 8.2 Hz, 1H), 4.24 (q, J )
6.5 Hz, 1H), 4.69 (s, 2H), 6.02-6.20 (br s, 1H), 7.26-7.42 (m,
5H); 13C NMR (CDCl3) δ 172.2, 131.0, 128.6, 128.4, 127.9,
109.4, 76.8, 75.4, 66.4, 59.7, 51.9, 38.9, 26.7, 25.4; GC-MS m/z
(%) 309 (M+, 0.5), 294 (2), 251 (1), 220 (2), 208 (31) 186 (2),
perature from 50 °C, 2 min, to 250 °C, slope 10 °C/min. IR
1
(Nujol) ν 3250, 1720, 1655, 1160, 1110, 1089 cm-1; H NMR
(CDCl3) δ 1.35 (s, 3 H), 1.46 (s, 3 H), 1.80-2.00 (br s, 1 H),
2.36 (dd, J ) 2.9, 7.0 Hz, 1 H), 3.62 (d, J ) 2.9 Hz, 1 H), 3.82
(dd, J ) 4.7, 7.0 Hz, 1 H), 4.00-4.22 (m, 3 H), 4.41-4.57 (m,
3 H); 13C NMR (CDCl3) δ 172.0, 154.0, 109.6, 81.6, 65.8, 64.5,
56.1, 44.6, 42.0, 26.7, 25.4; GC-MS m/z (%) 241 (25), 181 (15),
155 (18), 113 (20), 84 (100).
(6R, 4′S)-1-Ben zyloxy-6-(2′,2′-d im eth yl[1′,3′]d ioxola n -
4′-yl)-5,6-d ih yd r op yr im id in e-2,4-d ion e (16). To a stirred
solution of 7 (60 mg, 0.16 mmol) in CH2Cl2 (5 mL) was added
AlMe2Cl (1 M in hexane, 0.33 mL, 0.33 mmol) at 0 °C under
inert atmosphere. After 5 min the mixture was transferred
via cannula to a solution of DIPEA (0.11 mL, 0.65 mmol) in
CH2Cl2, (5 mL) and the resulting pale yellow mixture was
quenched after 10 min. The solution was washed with satu-
rated NaHCO3, and the aqueous layer was extracted twice
with CH2Cl2. The organic layers were collected and dried over
Na2SO4. The solvent was evaporated at reduced pressure, and
the residue was purified by flash chromatography over silica
gel (eluant EtOAc:cyclohexane 1:3) giving 16 (51 mg, 85%) as
an oil. IR (Nujol) ν 3436 (br), 3063, 3025, 2980, 2926, 1719,
20
160 (3), 148 (4), 101 (5), 91 (100); [R]D +16.5 (c 0.5, MeOH).
Anal. Calcd for C16H23NO5: C, 62.12; H, 7.49; N, 4.53. Found:
C, 62.09; H, 7.50; N, 4.54.
1
1680, 1434, 1381, 1156, 1070 cm-1; H NMR (CDCl3) δ 1.34
(3R,4′S)-3-Am in o-3-(2′,2′-d im eth yl[1′,3′]d ioxola n -4′-yl)-
p r op ion ic Acid Meth yl Ester (13). A mixture of 12 (80 mg,
0.26 mmol) and 10% Pd/C (50 mg) in MeOH (8 mL) was shaken
at rt under nitrogen (4 kg/cm2). After 36 h the suspension was
filtered, the solid was washed with MeOH, and the filtrate
was concentrated at reduced pressure. The residue was
purified by flash chromatography over silica gel (eluant EtOAc:
MeOH 95:5) giving oily 13 (34 mg, 65%). Spectroscopic
characterization was identical with the literature.15a IR (neat)
ν 3290, 1727, 1441 cm-1; 1H NMR (CDCl3) δ 1.32 (s, 3H), 1.40
(s, 3H), 2.41-2.55 (m, 2H), 2.82-3.18 (m, 3H), 3.70 (s, 3H),
(s, 3H), 1.40 (s, 3H), 2.55 (br t, J ) 5.0 Hz, 1H), 2.66 (dd, J )
2.7, 16.8 Hz, 1H), 2.82 (dd, J ) 7.2, 16.8 Hz, 1H), 3.48 (ddd, J
) 2.1, 2.7, 7.2 Hz, 1H), 3.81 (br q, J ) 5.0 Hz, 2H), 3.99 (dd,
J ) 5.1, 7.2 Hz, 1H), 4.05 (t, J ) 5.1 Hz, 2H), 4.10 (ddd, J )
2.1, 5.1, 7.2 Hz, 1H), 4.15 (t, J ) 5.1 Hz, 1H), 4.96 (d, J ) 11.0
Hz, 1H), 5.04 (d, J ) 11.0 Hz, 1H), 7.38-7.46 (m, 5H); 13C
NMR (CDCl3) δ 182.7, 168.4, 135.2, 130.0, 129.4, 129.0, 110.5,
77.7, 77.6, 66.2, 61.6, 55.7, 43.6, 35.6, 26.1, 25.7; GC-MS m/z
(%) 364 (M+, 0.4), 359 (0.8), 306 (1), 264 (1), 241 (1), 200 (7),
20
157 (6), 129 (3), 101 (8), 91 (100); [R]D -84.7 (c 0.3, CHCl3).
Anal. Calcd for C18H24N2O6: C, 59.33; H, 6.64; N, 7.69.
Found: C, 59.29; H, 6.64; N, 7.70.
20
3.63-4.20 (m, 3H); [R]D +11.2 (c 0.4, CHCl3).
(3R,4′S)-3-Am in o-3-(2′,2′-d im eth yl[1′,3′]d ioxola n -4′-yl)-
p r op ion ic Acid (14). To a stirred suspension of LiOH (10 mg,
0.41 mmol) in THF (6 mL) and water (1.5 mL) was added a
solution of H2O2 (30 wt %, 0.093 mL, 0.82 mmol) at 0 °C. After
15 min, the suspended solid was completely dissolved, and a
solution of 7 (50 mg, 0.14 mmol) in THF (2 mL) was added at
0 °C with stirring. After 2 h, THF was evaporated at reduced
pressure, pH was adjusted at 3 with 1 N HCl, and the mixture
was extracted three times with EtOAc. The collected organic
layers were dried over Na2SO4. The evaporation of solvent at
reduced pressure gave 14 (37 mg, 90%) as a waxy solid.
Oxazolidin-2-one 1 remained in the water layers, and recovery
was not attempted. IR (Nujol) ν 3400-2950 (br), 1740, 1689,
(4R,5S)-4-Ben zyloxya m in o-5-h yd r oxym et h ylt et r a h y-
d r ofu r a n -2-on e (18). To a solution of 7 (50 mg, 0.14 mmol)
in dry CH2Cl2 (6 mL) was added dimethylaluminum chloride
(1 M in hexane, 0.14 mL, 0.14 mmol) at rt. After 10 h, the
reaction was quenched with water (5 mL), and the mixture
was extracted three times with CH2Cl2. The collected organic
layers were dried over Na2SO4. The solvent was evaporated
at reduced pressure, and the residue was analyzed by 1H NMR,
revealing an ca. 8/2 mixture of 17 and 18. The mixture was
purified by flash chromatography over silica gel (eluant EtOAc:
cyclohexane 1:4), affording oily 18 (29 mg, 90%) as the only
product.
17: 1H NMR (CDCl3) δ 2.08 (br t, J ) 6.8 Hz, 1H), 2.46 (dd,
J ) 4.9, 17.8 Hz, 1H), 2.69 (br d, J ) 5.3 Hz, 1H), 2.80 (dd, J
) 8.1, 17.8 Hz, 1H), 3.64 (t, J ) 7.8 Hz, 3H), 3.78-3.86 (m,
3H), 4.06-4.18 (m, 1H), 4.47 (t, J ) 7.8 Hz, 3H), 4.72 (s, 2H),
5.53 (d, J ) 5.2 Hz, 1H), 7.30-7.41 (m, 5H); GC-MS m/z (%)
324 (M+, 0.6), 308 (4), 279 (1), 265 (2), 222 (64), 174 (3) 148
(7), 91 (100).
1
1046 cm-1; H NMR (CDCl3) δ 1.35 (s, 3H), 1.40 (s, 3H), 2.47
(dd, J ) 4.4, 16.3 Hz, 1H), 2.63 (dd, J ) 8.0, 16.3 Hz, 1H),
3.36 (dt, J ) 4.8, 7.0 Hz, 1H), 3.80 (dd, J ) 6.2, 8.5 Hz, 1H),
4.02 (dd, J ) 6.6, 8.5 Hz, 1H), 4.15-4.27 (m, 1H), 4.73 (s, 2H),
6.10-6.26 (br s, 1H), 7.23-7.40 (m, 5H); 13C NMR (CDCl3) δ
171.1, 136.8, 130.8, 128.7, 128.4, 128.0, 109.5, 76.6, 74.7, 66.3,
20
60.4, 38.7, 26.6, 25.2; [R]D +4.0 (c 0.7, MeOH). Anal. Calcd
18: IR (Nujol) ν 3420 (br), 3264, 3058, 3026, 2954, 2919,
for C15H21NO5: C, 61.00; H, 7.17; N, 4.74. Found: C, 59.98;
H, 7.15; N, 4.74.
1
2851, 1782, 1451, 1364, 1265, 1166 cm-1; H NMR (CDCl3) δ
1.60 (br s, 1H), 2.48 (dd, J ) 8.1, 17.4 Hz, 1H), 2.63 (dd, J )
8.7, 17.4 Hz, 1H), 3.69 (dd, J ) 4.2, 10.5 Hz, 1H), 3.78 (dd, J
) 3.0, 10.5 Hz, 1H), 4.00-4.19 (m, 1H), 4.58-4.63 (m, 1H),
4.71 (s, 2H), 6.18 (br d, J ) 8.5 Hz, 1H), 7.23-7.42 (m, 5H);
13C NMR (CDCl3) δ 179.3, 137.4, 128.5, 128.4, 128.1, 128.0,
79.7, 74.0, 60.6, 57.8, 33.8; GC-MS m/z (%) 237 (M+, 6), 219
(2), 206 (2), 130 (2), 112 (2), 105 (5), 91 (100); [R]D +8.0 (c
0.4, CHCl3). Anal. Calcd for C12H15NO4: C, 60.75; H, 6.37; N,
5.90. Found: C, 60.79; H, 6.36; N, 5.88.
(2′R,3′R,4′′S)-3-{[3′-(2′′,2′′-Dim et h yl[1′′,3′′]d ioxola n -4′′-
yl)-2′-azir idin yl]car bon yl}oxazolidin -2-on e (15). To a stirred
solution of 7 (90 mg, 0.25 mmol) in CH2Cl2 (12 mL) was added
TiCl4 (27 µL, 0.25 mmol) under inert atmosphere at 0 °C, and
after 5 min this brown mixture was transferred at room
temperature via cannula within 5 min to a solution of TEA
(0.070 mL, 0.50 mmol) in CH2Cl2 (8 mL). After 10 min the
reaction was quenched with a saturated solution of Na2CO3
(5 mL), and the mixture was extracted three times with CH2-
Cl2. The collected organic layers were dried over Na2SO4, and
the solvent was evaporated at reduced pressure. The purifica-
tion of the residue by flash chromatography over silica gel
(eluant EtOAc:cyclohexan 1:2) gave 15 (35 mg, 55%) as a waxy
solid, accompanied by an unseparable mixture of byproducts.
The purity was measured at 94% by GC-MS analysis, tem-
20
Ack n ow led gm en t. We thank Dr. T. Scoccitti for
technical support. This work was supported by MURST
(60% and Cofin 2000) and CNR.
J O0259055
5962 J . Org. Chem., Vol. 67, No. 17, 2002