Yu et al.
400 MHz) δ 7.36 (m, 5H), 5.88 (m, 1H), 5.66 (m, 1H), 5.24 (d,
J ) 1.2 Hz, 1H), 4.80 (d, J ) 12.0 Hz, 1H), 4.57 (d, J ) 12.0
Hz, 1H), 4.12 (m, 1H), 3.73 (m, 1H), 2.35 (m, 1H), 2.27 (m,
1H), 1.87 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 138.3, 132.7,
131.2, 128.8 (2C), 128.4 (2C), 128.0, 100.3, 69.5, 65.0, 29.5, 26.6;
IR (film) νmax 2978, 2875, 1640, 1277, 1190, 1087 cm-1; HRMS
(FAB+) m/z 205.1235 (M + H+, C13H16O2 requires 205.1229).
white solid: 1H NMR (CDCl3, 400 MHz) δ 7.35 (m, 5H), 5.32
(s, 1H), 5.24 (dd, J ) 3.6, 6.8 Hz, 1H), 5.01 (d, J ) 6.8 Hz,
1H), 4.72 (d, J ) 11.6 Hz, 1H), 4.52 (d, J ) 11.6 Hz, 1H), 4.26
(d, J ) 11.2 Hz, 1H), 4.06 (dd, J ) 3.6, 11.2 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) δ 154.3, 1376.6, 129.0 (2C), 128.7(2C), 128.6,
104.4, 83.0, 79.7, 71.0, 69.6; IR (film) νmax 2950, 2875, 1812,
1179, 1140, 1079, 1054 cm-1; HRMS (FAB+) m/z 237.0765 (M
+ H+, C12H12O5 requires 237.0763).
4-(Benzyloxy)-hexahydro-[1,3]dioxolo[4,5-c]oxepin-2-
one (35). Osmium tetroxide (0.1 mL, 4% in H2O, 0.007 mmol)
was added to a solution of 33 (820 mg, 4 mmol) and 4-meth-
ylmorpholine N-oxide (702 mg, 6.0 mmol) in acetone (4 mL)
and H2O (4 mL). The mixture was stirred at 25 °C for 12 h,
diluted with H2O (40 mL), and extracted with EtOAc (3 × 50
mL). The organic layers were combined, dried (Na2SO4),
filtered, and concentrated. The residue was dissolved in 1,2-
dichloroethane (5 mL), and 1,1-carbonyl diimidazole (486 mg,
3 mmol) was added. The resulting mixture was heated at
reflux for 14 h, diluted with EtOAc (30 mL), washed with H2O
(3 × 30 mL), dried (Na2SO4), filtered, and concentrated. The
residue was purified by chromatography (SiO2, 30% EtOAc in
hexanes) to afford 35 (720 mg, 68%) as a colorless oil: 1H NMR
(CD3CN, 400 MHz) δ 7.36 (m, 5H), 4.95 (m, 2H), 4.81 (d, J )
1.2 Hz, 1H), 4.68 (t, J ) 8.0 Hz, 1H), 4.58 (d, J ) 12.0 Hz,
1H), 4.06 (m, 1H), 3.59 (m, 1H), 2.01 (m, 1H), 1.96 (m, 1H),
1.78 (m, 1H), 1.67 (m, 1H); 13C NMR (CD3CN, 125 MHz) δ
154.5, 137.9, 128.8 (2C), 128.4 (2C), 128.2, 102.1, 79.7, 78.2,
70.4, 69.8, 29.2, 27.0; IR (film) νmax 2975, 2860, 1806, 1178,
1049 cm-1; HRMS (FAB+) m/z 265.1078 (M + H+, C14H16O5
requires 265.1076).
4-Hydroxy-hexahydro-[1,3]dioxolo[4,5-c]oxepin-2-
one (36). Palladium on charcoal (10%, 75 mg) was added to a
solution of 35 (700 mg, 2.65 mmol) in THF (5 mL). The mixture
was stirred under H2 (1 atm) for 60 h and filtered over Celite.
The eluent was concentrated, and the residue was purified by
chromatography (SiO2, 65% EtOAc in hexanes) to afford 36
(232 mg, 50%) as a mixture of anomers (3:2): 1H NMR (CDCl3,
400 MHz) δ 5.09 (d, J ) 7.6 Hz, 1H major), 5.04 (t, J ) 8.0
Hz, 1H minor), 4.99 (s, 1H minor), 4.87 (m, 1H major and 1H
minor), 4.66 (t, J ) 8.0 Hz, 1H major), 4.08 (m, 1H major and
1H minor), 3.65 (m, 1H major), 3.55 (t, J ) 10.4 Hz, 1H minor),
2.36 (m, 1H minor), 2.15 (m, 1H major), 1.96 (m, 1H major
and 2H minor), 1.81 (m, 1H major), 1.66 (m, 1H major and
1H minor); 13C NMR (CDCl3, 125 MHz) δ 154.4 (minor), 154.3
(major), 97.3 (major), 97.2 (minor), 81.0 (minor), 80.8 (major),
78.1 (major), 76.0 (minor), 70.1 (major), 69.7 (minor), 29.7
(major), 28.3 (minor), 27.1 (major), 25.1 (minor); IR (film) νmax
3400, 2973, 2868, 1806, 1179, 1082 cm-1; HRMS (FAB+) m/z
175.0610 (M + H+, C7H10O5 requires 175.0606).
2-(Benzyloxy)-tetrahydrofuran-3,4-diol (39). Osmium
tetroxide (0.2 mL, 20 mg/mL in toluene, 0.014 mmol) was
added to a solution of 38 (2.0 g, 11.3 mmol) and 4-methylmor-
pholine N-oxide (2.3 g, 20 mmol) in acetone (10 mL) and H2O
(10 mL). The mixture was stirred at 25 °C for 6 h, diluted with
H2O (200 mL), and extracted with EtOAc (3×100 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 60% EtOAc in hexanes) to afford 39 (1.78 g, 75%) as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.44-7.42 (m, 5H),
5.16 (s, 1H), 4.73 (d, J ) 11.6 Hz, 1H), 4.55 (m, 2H), 4.13 (m,
2H), 3.87 (m, 1H), 2.92 (s, 1H), 2.71 (s, 1H); 13C NMR (CDCl3,
125 MHz) δ 137.7, 128.9 (2C), 128.4(2C), 128.3, 107.4, 76.3,
72.7, 71.3, 69.8; IR (film) νmax 3350, 2955, 2923, 1448, 1380,
1254, 1136, 1067, 993 cm-1; HRMS (FAB+) m/z 211.0972
(M + H+, C11H14O4 requires 211.0970).
4-(Benzyloxy)-tetrahydrofuro[3,4-d][1,3]dioxol-2-one
(40). A solution of 39 (1.7 g, 8.0 mmol) and 1,1-carbonyl
diimidazole (1.95 g, 12 mmol) in 1,2-dichloroethane (20 mL)
was heated at reflux for 8 h. The mixture was cooled to 25 °C,
diluted with EtOAc (50 mL), washed with H2O (3 × 100 mL),
and dried (Na2SO4). The dried solution was filtered and
concentrated, and the residue was purified by chromatography
(SiO2, 30% EtOAc in hexanes) to afford 40 (1.62 g, 86%) as a
4-Hydroxy-tetrahydrofuro[3,4-d][1,3]dioxol-2-one (41).
Palladium on charcoal (10%, 150 mg) was added to a solution
of 40 (1.5 g, 6.3 mmol) in methanol (10 mL). The mixture was
stirred under H2 (1 atm) for 40 h and filtered over Celite. The
eluent was concentrated, and the residue was purified by
chromatography (SiO2, 50% EtOAc in hexanes) to afford 41
(752 mg, 82%) as a colorless oil: 1H NMR (CDCl3, 400 MHz)
δ 5.72 (s, 1H), 5.27 (dd, J ) 3.2, 6.4 Hz, 1H), 5.01 (d, J ) 6.4
Hz, 1H), 4.23 (m, 2H), 2.74 (s, 1H); 13C NMR (CD3OD, 125
MHz) δ 155.3, 100.1, 84.0, 80.0, 70.1; IR (film) νmax 3400, 2967,
2870, 1809, 1366, 1176 cm-1; HRMS (FAB+) m/z 147.0289 (M
+ H+, C5H6O5 requires 147.0293).
3-(Triisopropylsilyloxy)-dihydrofuran-2-(3H)-one (43).
Imidazole (1.02 g, 15 mmol) was added to a solution of
triisopropylsilyl chloride (2.90 g, 15 mmol) and 2-hydroxy-
butrylactone (900 mg, 10 mmol) in DMF (5 mL) at 25 °C. The
resulting mixture was stirred for 8 h, poured into H2O (30 mL),
and extracted with EtOAc (30 mL). The organic layer was
washed with H2O (30 mL), dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 20% EtOAc in hexanes) to afford 43 (2.17 g, 90%) as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 4.52 (t, J ) 8.9 Hz,
1H), 4.36 (m, 1H), 4.18 (m, 1H), 2.62 (m, 1H), 2.25 (m, 1H),
1.10 (m, 21H); 13C NMR (CDCl3, 125 MHz) δ 176.1, 68.7, 65.0,
33.2, 18.1 (6C), 12.5 (3C); IR (film) νmax 2943, 2866, 1787, 1463,
1218, 1135 cm-1; HRMS (ES+) m/z 257.1733 (M + H C13H27O3-
Si requires 283.1729).
3-(Triisopropylsilyloxy)-tetrahydrofuran-2-ol (44). Di-
isobutylaluminum hydride (1 M in hexanes, 2 mL, 2 mmol)
was added to a solution of 43 (500 mg, 2 mmol) in CH2Cl2 (10
mL) at -78 °C. The mixture was stirred at -78 °C for 15 min
and warmed to 25 °C. Saturated aqueous sodium potassium
tartrate (15 mL) was added, and the heterogeneous solution
was stirred for 1 h. The organic layer was separated, washed
with H2O (30 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 25% EtOAc
in hexanes) to afford 44 (445 mg, 89%) as a mixture of anomers
(5:4): 1H NMR (CDCl3, 400 MHz) δ 5.25 (m, 1H major and
1H minor), 4.40 (m, 1H major), 4.31 (m, 1H minor), 4.05 (m,
2H major and 2H minor), 3.79 (m, 1H major), 3.02 (br. s, 1H
minor), 2.20 (m, 1H minor), 2.10 (m, 1H major), 1.91 (m, 1H
major), 1.83 (m, 1H minor), 1.15-1.03 (m, 21H major and 21H
minor); 13C NMR (CDCl3, 125 MHz) δ 103.8 (minor), 97.3
(major), 72.8 (1C major, 1C minor), 67.7 (minor), 65.1 (major),
34.1 (major), 33.5 (minor), 18.2 (6C major and 6C minor), 12.4
(3C major and 3C minor); IR (film) νmax 3420, 2943, 2866, 1463,
1126, 1058 cm-1; HRMS (ES+) m/z 283.1699 (M + Na+
C13H28O3Si requires 283.1705).
4-(tert-Butyldimethylsilyloxy)-dihydrofuran-2(3H)-
one (47). Imidazole (1.36 g, 20 mmol) was added to a solution
of tert-butyldimethylsilyl chloride (1.57 g, 10.5 mmol) and 46
(700 mg, 7 mmol) in DMF (4 mL) at 25 °C. The resulting
mixture was stirred for 8 h, poured into H2O (20 mL), and
extracted with EtOAc (30 mL). The organic layer was washed
with H2O (30 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 20% EtOAc
in hexanes) to afford 47 (1.13 g, 74%) as a colorless oil: 1H
NMR (CDCl3, 400 MHz) δ 4.62 (m, 1H), 4.38 (dd, J ) 4.8, 10.0
Hz, 1H), 4.18 (dd, J ) 2.4, 10.0 Hz, 1H), 2.70 (dd, J ) 5.4,
17.6 Hz, 1H), 2.45 (dd, J ) 2.8, 17.6 Hz, 1H), 0.89 (s, 9H),
0.09 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 176.1, 76.5, 68.5,
38.5, 26.0, 18.3, -4.4, -4.5; IR (film) νmax 2963, 2866, 1780,
1169, 1130 cm-1; HRMS (FAB+) m/z 217.1262 (M + H+
C10H20O3Si requires 217.1260).
5604 J. Org. Chem., Vol. 70, No. 14, 2005