Ghosh et al.
(d, 1H, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3) δ 27.1, 29.8,
38.7, 37.7, 65.3, 65.4, 65.6, 77.4, 103.3, 175.5, 178.0.
(2S,3S)-3-(1,3-dioxolan-2-yl)pentane-1,2,5-triol which was im-
mediately used in the next reaction.
(4S,5S)-5-(Benzoyloxymethyl)-4-(1,3-dioxolan-2-yl)dihy-
drofuran-2-one (13e). A solution of (5S)-5-(benzoyloxy-
methyl)-5H-furan-2-one (9e) (180 mg, 0.825 mmol) and ben-
zophenone (22.5 mg, 0.123 mmol) in 1,3-dioxolane (110 mL)
was irradiated at 20 °C for 3 h. The title compound (193 mg,
80%) was obtained as an oil after silica gel chromatography
The above triol was dissolved in a mixture (5:1) of THF/
H2O (8 mL). The resulting solution was acidified at 23 °C to
pH 2-3 with 1 N hydrochloric acid, and the solution was
stirred for 40 h. After this period, benzene was added, and
the solvents were removed under reduced pressure. The
residure was purified by column chromatography over silica
gel (5% MeOH in CHCl3 as the eluent) to furnish 15 (145 mg,
(40% ethyl acetate in hexanes): Rf ) 0.29; [R]23 35.2 (c 1.2,
D
CHCl3); IR (neat) 2360, 2342, 1779, 1721, 1272, 1118 cm-1
;
77%): Rf ) 0.40 (15% MeOH in CHCl3); [R]23 -25.1 (c 1.05,
D
1H NMR (400 MHz, CDCl3) δ 2.53 (d, 1H J ) 11.6 Hz), 2.62-
2.73 (m, 2H), 3.83 (mc, 2H), 3.94 (mc, 2H), 4.37 (dd, 1H, J )
5.1, 12.3 Hz), 4.53 (dd, 1H, J ) 2.9, 12.3 Hz), 4.74 (ddd, 1H, J
) 2.9, 5.1, 6.9 Hz), 4.88 (d, 1H, J ) 3.4 Hz), 7.37 (dd, 2H, J )
7.7, 7.9 Hz), 7.49 (dd, 1H, J ) 1.0, 7.7 Hz), 7.92 (dd, 2H, J )
1.0, 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ 29.8, 40.1, 65.4,
65.5, 66.0, 77.6, 103.1, 128.5, 129.3, 129.6, 133.3, 166.0, 175.6.
CHCl3); H NMR (500 MHz, CDCl3) δ 1.67 (m, 1H), 2.13 (m,
1
1H), 2.31 (bs, 1H), 2.79 (m, 1H), 3.80-3.88 (m, 3H), 3.95 (dd,
1H, J ) 3.2, 10.3 Hz), 4.20 (d, 1H, J ) 3.1 Hz), 5.86 (d, 1H, J
) 4.9 Hz); 13C NMR (125 MHz, CDCl3) δ 29.2, 52.4, 68.3, 75.6,
78.2, 109.2; HRMS-ESI (m/z) [M + H]+ calcd for C6H10O3
131.0708, found 131.0709.
(3R,3aS,6aR)-3-Hydroxyhexahydrofuro[2,3-b]furan (3).
To a mixture of (3S,3aS,6aR)-3-hydroxyhexahydrofuro[2,3-b]-
furan 15 (440 mg, 3.38 mmol), 4-methylmorpholino-N-oxide
(599 mg, 5.11 mmol), and 4 Å molecular sieves (2 g) in CH2Cl2
(30 mL) was stirred for 20 min at 23 °C. Tetrapropylammo-
nium perruthenate (36 mg, 0.10 mmol) was added at 23 °C,
and the resulting mixture was stirred for 10 min. The reaction
mixture was filtered through a short silica gel column and was
eluted with CH2Cl2. Evaporation of the solvent gave a residue
which was chromatorgraphed over silica gel (40% ethyl acetate
in hexanes as the eluent) to provide the corresponding ketone
(409 mg, 94%) as an amorphous solid: Rf ) 0.3; [R]23D -126.6
(c 0.8, CHCl3); IR (neat) 1758, 1658, 1023 cm-1; 1H NMR (400
MHz, CDCl3) δ 2.23 (mc, 1H), 2.96 (dd, 1H, J ) 6.8 Hz, J )
6.8 Hz), 3.79 (mc, 1H), 3.99 (m, 1H), 4.11 (s, 2H), 6.02 (d, 1H,
J ) 5.0 Hz); 13C NMR (100 MHz, CDCl3) δ 30.4, 49.6, 67.7,
71.7, 107.9, 215.5.
(4S,5S)-4-(1,3-Dioxolan-2-yl)-5-(tetrahydropyran-2-
yloxymethyl)dihydrofuran-2-one (13f). A solution of (5S)-
5-(tetrahydropyran-2-yloxymethyl)-5H-furan-2-one (9f) (136
mg, 0.67 mmol) and benzophenone (19 mg, 0.1 mmol) in 1,3-
dioxolane (100 mL) was irradiated at 20 °C for 6 h. The title
compound (170 mg, 91%) was obtained as an oil after silica
gel chromatography (60% ethyl acetate in hexanes): Rf ) 0.25;
[R]23D 47 (c 1.0, CHCl3); IR (neat) 2960, 2877, 1780, 1131, 851
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.38-1.82 (m, 6H), 2.40-
2.46 (m, 1H), 2.60-2.75 (m, 2H), 3.39-3.48 (m, 1H), 3.61-
3.70 (m, 1H), 3.75-3.81 (m, 2H), 3.84-3.87 (m, 2H), 3.93-
3.98 (m, 2H), 4.53-4.63 (m, 2H), 4.86-4.89 (m, 1H). 13C NMR
(75 MHz, CDCl3) δ major diastereomer 18.7, 25.2, 29.9, 30.0,
40.1, 61.5, 64.7, 65.3, 68.3, 79.0, 98.2, 103.6, 176.5, minor
diastereomer 19.2, 25.2, 30.2, 30.2, 40.1, 62.2, 65.1, 65.5, 68.8,
79.1, 99.1, 103.7, 176.7.
(4S,5S)-4-(1,3-Dioxolan-2-yl)-5-hydroxymethyldihydro-
furan-2-one (13g). A solution of (5S)-5-(hydroxymethyl)-5H-
furan-2-one (154 mg, 1.35 mmol) and benzophenone (25 mg,
0.135 mmol) in 1,3-dioxolane (100 mL) was irradiated at 0 °C
for 4 h. Upon completion of the reaction, solvent was removed
under reduced pressure, followed by column chromatography
on silica gel (5% MeOH in CHCl3 as the eluent), yielding the
title compound 13g (205 mg, 80%): Rf ) 0.28 (5% MeOH in
CHCl3); [R]25D 21.8 (c 1.02, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 2.50 (dd, 1H, J ) 6.0, 17.5 Hz), 2.69 (dd, 1H, J ) 9.5, 17.5
Hz), 2.73-2.78 (m, 1H), 3.00 (bs. 1H), 3.64 (dd, 1H, J ) 4.0,
12.5 Hz), 3.86-3.91 (m, 3H), 3.96-3.99 (m, 2H), 4.50-4.52 (m,
1H), 4.84 (d, 1H, J ) 4 Hz); 13C NMR (125 MHz, CDCl3) δ
30.2, 39.8, 63.8, 65.4, 65.5, 80.9, 103.6, 176.8.
To a solution of the above ketone (250 mg, 1.95 mmol) in
ethanol (25 mL) was added sodium borohydride (89 mg, 2.35
mmol) at -18 °C. The reaction mixture was stirred at -18 °C
for 2.5 h. The reaction was quenched with saturated am-
monium chloride solution, and the mixture was warmed to
room temperature. The mixture was concentrated under
reduced pressure, and the residue was diluted with water and
ethyl acetate. The layers were separated, and the aqueous
layer was extracted with ethyl acetate (3×) and a solution of
70% CHCl3/20% MeOH/10% H2O (3×). The combined organic
extracts were dried over sodium sulfate. Evaporation of the
solvent gave a residue which was chromatographed over silica
gel (7% methanol in chloroform as the eluent) to furnish
compound 3 (178 mg, 70%) as an oil: Rf ) 0.3; [R]23D -12.4 (c
1
1.3, MeOH); IR (neat) 2951, 1641, 1347, 1211 cm-1; H NMR
(4S,5S)-4-(1,3-Dioxolan-2-yl)-5-hydroxymethyldihydro-
furan-2-one (14). To a solution of dihydrofuranone 13a (0.5
g, 1.79 mmol) in MeOH (30 mL) was added Pd/C (25 mg). The
mixture was stirred at 23 °C under an H2 balloon for 24 h.
The reaction mixture was filtered through a pad of Celite.
Removal of solvent under reduced pressure, followed by column
chromatography over silica gel (35% EtOAc in hexanes as the
eluent), yielded compound 14 (301 mg, 89%) as an oil: Rf )
(400 MHz, CDCl3) δ 1.85 (mc, 1H), 1.94 (bs, 1H), 2.27 (mc, 1H),
2.84 (mc, 1H), 3.63 (dd, 1H, J ) 7.1, 9.2 Hz), 3.89 (mc, 1H),
3.97 (mc, 1H), 4.43 (dd, 1H, J ) 6.8, 14.5 Hz), 5.68 (d, 1H,
J ) 5.2 Hz); 13C NMR (125 MHz, CDCl3) δ 25.3, 47.0, 70.3,
71.3, 73.5, 109.9;. HRMS-ESI (m/z) [M - H]+ calcd for
C6H9O3129.0552, found 129.0543.
(3R,3aS,6aR)-3-Hydroxyhexahydrofuro[2,3-b]furan (3)
(by Mitsunobu Inversion). To a stirred solution of the
alcohol 15 (400 mg, 3.07 mmol), triphenylphosphine (1.6 g, 61.4
mmol), and p-nitrobenzoic acid (770 mg, 4.61 mmol) in dry
benzene (30 mL) at 23 °C was added diisoproylazodicarboxy-
late (DIAD, 1.2 mL, 6.14 mmol). The resulting mixture was
stirred at that temperature for 1.5 h. After this period, the
mixture was concentrated under reduced pressure, and the
residue was dissolved in a mixture (4:3:1) of MeOH/Et3N/H2O
(24 mL) and treated with LiOH (450 mg, 10.7 mmol). The
reaction mixture was stirred at 23 °C for 2 h. The mixture
was concentrated under reduced pressure and the residue was
chromatographed over silica gel to provide the title compound
0.28 (50% EtOAc in hexanes); [R]23 22 (c 1.32, CHCl3); 1H
D
NMR (500 MHz, CDCl3) δ 2.54 (dd, 1H, J ) 6.0, 17.4 Hz),
2.68-2.81 (m, 2H), 3.66 (dd, 1H, J ) 3.9, 12.4 Hz), 3.88-3.95
(m, 3H), 3.97-4.02 (m, 2H), 4.53 (m, 1H), 4.91 (d, 1H, J ) 3.9
Hz); 13C NMR (125 MHz, CDCl3) δ 30.7, 40.1, 64.4, 65.8, 81.1,
103.9, 176.8; HRMS-ESI (m/z) [M + Na]+ calcd for C8H12O5
211.0582, found 211.0584.
(3S,3aS,6aR)-3-Hydroxyhexahydrofuro[2,3-b]furan (15).
To a solution of lithium aluminum hydride (76 mg, 1.98 mmols)
in THF (10 mL) at 0 °C was added lactone 14 (275 mg, 1.46
mmol) in THF (30 mL) in a dropwise manner over a period of
3 min. The resulting mixture was stirred for 4 h at 0 °C. The
reaction was quenched with a saturated aqueous sodium
sulfate solution at 0 °C. The solvent was then decanted, and
the remaining residue was washed successively with THF
(3×), EtOAc (3×), and CHCl3 (3×). The combined organic
extracts was concentrated under reduced pressure to provide
3 (326 mg, 82%) as an oil: [R]23 -12.4 (c 1.16, MeOH).
D
(3R,3aS,6aR)-3-Hydroxyhexahydrofuro[2,3-b]furanyl
Succinimidyl Carbonate (16). A solution of (3R,3aS,6aR)-
3-Hydroxyhexahydrofuro[2,3-b]furan 3 (100 mg, 0.77 mmol),
N,N′-disuccinimidyl carbonate (295 mg, 1.15 mmol), and
7828 J. Org. Chem., Vol. 69, No. 23, 2004