Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9049
between silica gel and crude product ranged from 100 to 50:1
(w/w). Optical rotations were measured at 21 ( 2 °C. Melting
points are uncorrected. 1H NMR spectra were recorded at 500.12
MHz, and chemical shifts are referenced to either TMS (0.0,
CDCl3) or external dioxane (3.75, D2O). 13C NMR spectra were
recorded at 125.75 MHz, and 13C chemical shifts are referenced
to CDCl3 (77.00, CDCl3) or external dioxane (68.11, D2O).
Electrospray mass spectra were recorded on samples suspended
in THF or CH3OH.
138.6, 134.5, 133.5, 130.5, 130.0, 128.9, 128.8, 128.7, 128.1, 128.0,
117.8, 82.1, 77.1, 75.1, 73.7, 73.0, 36.5, 34.3; HRMS (ESI) calcd
for (M + Na+) C22H24O4 375.1566, found 375.1583.
12: Rf 0.51 (hexanes/EtOAc, 4:1); [R]D +13.8 (c 1.3, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 8.02 (dd, 2 H, J ) 1.0, 8.1 Hz),
7.60 (dd, 1 H, J ) 7.3, 7.5 Hz), 7.47-7.31 (m, 7 H), 5.96-5.90
(m, 1 H), 5.31 (ddd, 1 H, J ) 3.1, 6.2, 6.7 Hz), 5.22 (dd, 1 H, J
) 1.5, 15.4 Hz), 5.17 (dd, 1 H, J ) 1.0, 10.3 Hz), 4.67 (d, 1 H, J
) 12.2 Hz), 4.63 (d, 1 H, J ) 12.2 Hz), 4.47-4.44 (m, 1 H), 4.33
(ddd, 1 H, J ) 2.8, 6.5, 9.3 Hz), 3.70 (dd, 1 H, J ) 6.4, 9.8 Hz),
3.58 (dd, 1 H, J ) 5.0, 9.8 Hz), 2.57 (ddd, 1 H, J ) 7.2, 7.8, 12.2
Hz), 2.45-2.42 (m, 2 H), 2.05 (dddd, 1 H, J ) 3.3, 4.9, 5.0, 14.1
Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.5, 138.6, 134.1, 133.5,
130.4, 130.0, 128.8, 128.7, 128.1, 128.0, 118.2, 83.4, 78.4, 77.2,
73.8, 72.9, 38.0, 34.6; HRMS (ESI) calcd for (M + Na+) C22H24O4
375.1566, found 375.1583.
Met h yl 5-O-Ben zyl-3-d eoxy-r-D-th r eo-p en t ofu r a n osid e
(8) a n d Meth yl 5-O-Ben zyl-2-d eoxy-r-D-th r eo-p en tofu r a -
n osid e (9). To a solution of 7 (5.0 g, 19.6 mmol) in THF (100
mL) at 0 °C was added LiAlH4 (1.87 g, 49.0 mmol). The solution
was heated at reflux for 12 h. EtOAc (10 mL) was added, and
the reaction mixture was stirred for 10 min followed by the
addition of water (5 mL). The solution was diluted with EtOAc
(200 mL), filtered through Celite, and concentrated. The com-
pound was purified by chromatography (hexanes/EtOAc, 4:1) to
yield 8 (4.15 g, 82%) and 9 (0.31 g, 6%) as a colorless oils.
8: Rf 0.34 (hexanes/EtOAc, 2:1); [R]D +15.0 (c 0.9, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 7.41-7.34 (m, 5 H), 4.87 (s, 1 H),
4.73 (d, 1 H, J ) 11.9 Hz), 4.58 (d, 1 H, J ) 11.9 Hz), 4.38 (ddd,
1 H, J ) 2.0, 4.2, 9.8 Hz), 4.07-4.00 (m, 2 H), 3.77 (dd, 1 H, J
) 1.9, 10.3 Hz), 3.48 (dd, 1 H, J ) 1.9, 10.3 Hz), 3.38 (s, 3 H),
2.45 (dddd, 1 H, J ) 4.8, 4.9, 9.8, 9.9 Hz), 1.82 (dd, 1 H, J ) 2.5,
13.7 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 137.4, 129.0, 128.5,
128.4, 110.4, 77.4, 74.5, 74.2, 71.5, 54.9, 34.2; HRMS (ESI) calcd
for (2M + Na+) C26H36O8 499.230238, found 499.23550.
9: yield 0.31 g, 6%; Rf 0.30 (hexanes/EtOAc, 5:1); [R]D +71.1
(c 1.3, CHCl3); 1H NMR (500 MHz, CDCl3, δ) 7.40-7.36 (m, 5
H), 5.20 (dd, 1 H, J ) 5.0, 5.4 Hz), 4.67-4.60 (m, 2 H), 4.57-
4.55 (m, 1 H), 4.17 (dd, 1 H, J ) 4.7, 5.9 Hz), 3.85 (d, 2 H, J )
4.8 Hz), 3.40 (s, 3 H), 2.82 (bs, 1 H), 2.23-2.14 (m, 2 H); 13C
NMR (125.7 MHz, CDCl3, δ) 137.9, 128.9, 128.3, 128.2, 104.7,
78.7, 74.2, 72.8, 69.1, 55.6, 43.1; HRMS (ESI) calcd for (2M +
Na+) C26H36O8 499.230238, found 499.23540.
Meth yl 2-O-Ben zoyl-5-O-ben zyl-3-d eoxy-r-D-th r eo-p en to-
fu r a n osid e (10). To a solution of 8 (2.60 g, 10.9 mmol) in
pyridine (10 mL) at 0 °C was added benzoyl chloride (1.7 mL,
14.1 mmol) dropwise. The reaction mixture was warmed to room
temperature and stirred for 30 min before being diluted with
CH2Cl2 (100 mL). The organic layer was washed successively
with 5% HCl, a saturated aqueous NaHCO3 solution, and water.
The organic layer was then dried, filtered, and concentrated, and
the compound was purified by chromatography (hexanes/EtOAc,
6:1) to yield 10 (3.61 g, 97%) as a colorless oil: Rf 0.41 (hexanes/
EtOAc, 5:1); [R]D +14.0 (c 2.2, CHCl3); 1H NMR (500 MHz,
CDCl3, δ) 8.02 (dd, 2 H, J ) 1.0, 8.1 Hz), 7.59 (dd, 1 H, J ) 7.3,
7.5 Hz), 7.46-7.30 (m, 7 H), 5.35 (dd, 1 H, J ) 1.5, 6.4 Hz), 5.17
(s, 1 H), 4.69 (d, 1 H, J ) 12.3 Hz), 4.63 (d, 1 H, 12.3 Hz), 4.54-
4.49 (m, 1 H), 3.71 (dd, 1 H, J ) 6.5, 10.1 Hz), 3.63 (dd, 1 H, J
) 6.5, 10.1 Hz), 3.46 (s, 3 H), 2.62 (dddd, 1 H, J ) 6.4, 6.5, 8.4,
12.3 Hz), 1.93 (dddd, 1 H, J ) 1.5, 5.0, 5.1, 14.2 Hz); 13C NMR
(125.7 MHz, CDCl3, δ) 166.1, 138.5, 133.6, 130.2, 130.0, 128.9,
129.8, 128.1, 128.0, 107.6, 78.3, 77.6, 73.8, 72.9, 55.1, 32.9;
HRMS (ESI) calcd for (M + Na+) C20H22O5 365.1359, found
365.1381.
2-Ally l-5-b e n z y lo x y m e t h y l-3-p h e n y lc a r b o n y lo x y -
(2S,3S,5S)-tetr a h yd r o-3-fu r a n ol (11) a n d 2-Allyl-5-ben zy-
loxym eth yl-3-p h en ylca r bon yloxy-(2R,3S,5S)-tetr a h yd r o-3-
fu r a n ol (12). To a solution of 10 (3.42 g, 10.0 mmol) and
allyltrimethylsilane (3.3 mL, 20.0 mmol) in acetonitrile (100 mL)
at -20 ° C was added TMSOTf (3.6 mL, 20.0 mmol). The reaction
mixture was stirred for 4 h at that temperature and then diluted
with CH2Cl2. The solution was washed with an aqueous satu-
rated NaHCO3 solution and water before it was dried and
concentrated. The compound was purified by chromatography
(hexanes/EtOAc, 8:1) to yield a 1.4:1 mixture of 11 and 12 (3.15
g, 89% combined yield) as a colorless oils.
11: Rf 0.62 (hexanes/EtOAc, 4:1); [R]D +10.0 (c 0.6, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 8.05 (dd, 2 H, J ) 1.0, 8.1 Hz),
7.61 (dd, 1 H, J ) 7.3, 7.5 Hz), 7.47-7.29 (m, 7 H), 5.89-5.87
(m, 1 H), 5.55-5.53 (m, 1 H), 5.15-5.07 (m, 2 H), 4.65 (d, 1 H,
J ) 12.2 Hz), 4.62 (d, 1 H, J ) 12.2 Hz), 4.00 (dd, 1 H, J ) 2.3,
6.8 Hz), 3.98-3.87 (m, 1 H), 3.70 (dd, 1 H, J ) 6.3, 9.9 Hz), 3.59
(dd, 1 H, J ) 4.8, 9.9 Hz), 2.62-2.55 (m, 3 H), 1.98 (dddd, 1 H,
J ) 1.7, 5.8, 5.8, 7.5 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.2,
2-Allyl-5-ben zyloxym eth yl-(2S,3S,5S)-tetr a h yd r o-3-fu r a -
n ol (13). To a solution of 11 (800 mg, 2.27 mmol) in CH3OH (10
mL) was added 1 M NaOCH3 in CH3OH (0.5 mL). After being
stirred for 1 h at room temperature, the reaction mixture was
neutralized with Amberlite IR-120 (H+) resin, filtered, and
concentrated. The compound was purified by chromatography
(hexanes/EtOAc, 6:1) to yield 13 (560 mg, 100%) as a colorless
1
oil: Rf 0.31 (hexanes/EtOAc, 3:1); [R]D +61.0 (c 1.0, CHCl3); H
NMR (500 MHz, CDCl3, δ) 7.40-7.33 (m, 5 H), 5.96-5.88 (m, 1
H), 5.22 (dd, 1 H, J ) 3.5, 17.1 Hz), 5.10 (dd, 1 H, J ) 2.0, 11.2
Hz), 4.71 (d, 1 H, J ) 12.2 Hz), 4.58 (d, 1 H, J ) 12.2 Hz), 4.27-
4.23 (m, 1 H), 4.04 (br. s, 1 H), 3.82-3.70 (m, 3 H), 3.45 (dd, 1
H, J ) 2.1, 10.3 Hz), 2.51-2.48 (m, 2 H), 2.36 (ddd, 1 H, J )
5.3, 10.2, 12.9 Hz), 1.97 (dd, 1 H, J ) 2.8, 13.8 Hz); 13C NMR
(125.7 MHz, CDCl3, δ) 137.6, 135.5, 128.9, 128.4, 128.2, 117.1,
84.3, 76.7, 74.0, 72.2, 71.9, 37.5, 34.1; HRMS (ESI) calcd for (M
+ Na+) C15H20O3 271.1304, found 271.1323.
2-Allyl-5-ben zyloxym eth yl-(2R,3S,5S)-tetr a h yd r o-3-fu r a -
n ol (14). Compound 14 was prepared from 12 (600 mg, 1.7 mmol)
as described for the synthesis of 13 from 11. Purification by
chromatography (hexanes/EtOAc, 6:1) yielded 14 (420 mg, 100%)
as a colorless oil: Rf 0.28 (hexanes/EtOAc, 3:1); [R]D +43.6 (c
1
1.1, CHCl3); H NMR (500 MHz, CDCl3, δ) 7.39-7.30 (m, 5 H),
5.89-5.81 (m, 1 H), 5.15-5.10 (m, 2 H), 4.96 (d, 1 H, J ) 12.2
Hz), 4.58 (d, 1 H, J ) 12.2 Hz), 4.33 (dd, 1 H, J ) 2.5, 12.0 Hz),
4.10-4.04 (m, 3 H), 3.71 (dd, 1 H, J ) 2.3, 10.2 Hz), 3.49 (dd, 1
H, J ) 2.7, 10.2 Hz), 2.40-2.35 (m, 1 H), 2.25-2.15 (m, 2 H),
1.88 (dd, 1 H, J ) 3.0, 13.8 Hz); 13C NMR (125.7 MHz, CDCl3,
δ) 137.6, 134.8, 128.9, 128.4, 128.3, 117.7, 87.6, 77.2, 75.1, 74.1,
73.0, 38.5, 36.4; HRMS (ESI) calcd for (M + Na+) C15H20O3
271.1304, found 271.1323.
5-Ben zyloxym et h yl-(2S,3a S,6a S)-p er h yd r ofu r o[3,2-b]-
fu r a n -2-ylm eth a n ol (15). To a solution of compound 13 (400
mg, 1.61 mmol) and N-methylmorpholine oxide (227 mg, 1.94
mmol) in acetone/water (5:1, 10 mL) at 0 °C was added OsO4 (4
mg, 0.10 mmol). The reaction mixture was stirred for 12 h at
room temperature and then concentrated. The resulting residue
was dissolved in CH2Cl2 (10 mL), and solid sodium sulfite was
added. The mixture was filtered through Celite, silica gel (100-
200 mesh, 10 g) was added to the filtrate, and the mixture was
cooled to 0 °C. Sodium metaperiodate (690 mg, 3.22 mmol) was
added in a solution of water (2 mL). The reaction mixture was
stirred at room temperature for 1 h followed by filtration through
Celite. The filtrate was dried and concentrated, and the com-
pound was purified by chromatography (hexanes/EtOAc, 2:1) to
yield 15 (371 mg, 92%, 3:2 mixture of isomers) as a colorless oil:
Rf 0.19 (hexanes/EtOAc, 4:1); 1H NMR (500 MHz, CDCl3, δ)
7.34-7.26 (m, 5 H), 5.62-5.59 (m, 0.6 H), 5.38 (dd, 0.4 H, J )
6.3 11.7 Hz), 4.79-4.76 (m, 0.6 H), 4.69-4.68 (m, 0.4 H), 4.63-
4.42 (m, 3 H), 4.19-4.11 (m, 1 H), 3.80 (d, 0.6 H, J ) 4.3 Hz),
3.67 (dd, 0.4 H, J ) 2.7, 10.3 Hz), 3.54-3.42 (m, 2 H), 2.35-
2.99 (m, 3 H), 1.79 (dddd, 1 H, J ) 2.2, 6.7, 8.4, 13.8 Hz); 13C
NMR (125.7 MHz, CDCl3, δ) 138.5, 137.8, 129.0, 128.8, 128.7,
128.3, 128.2, 128.1, 128.0, 100.6, 100.5, 85.5, 84.3, 84.2,
83.1, 80.2, 79.9, 73.7, 73.6, 73.1, 70.0, 41.7, 41.0, 37.2, 35.9;
HRMS (ESI) calcd for (M + Na+) C14H18O4 273.1097, found
273.1104.
2-[5-Ben zyloxym eth yl-3-h yd r oxy-(2R,3S,5S)-tetr a h yd r o-
2-fu r a n yl]a ceta ld eh yd e (16). Compound 16 was prepared from
14 (400 mg, 1.61 mmol) as described for the preparation of 15
from 13. The compound was purified by chromatography (hex-