9218 J . Org. Chem., Vol. 65, No. 26, 2000
Notes
26.77, 26.54. Anal. Calcd for C22H23ClO6: C, 63.08; H, 5.53.
Found: C, 62.89; H, 5.37.
4:1 v/v) followed by recrystallization from hexanes-ether gave
10b (0.81 g, 71%) as pale yellow needles: mp 137-138 °C; IR
1
1,4-An h yd r o-3,5-d i-O-b en zyl-2-d eoxy-L-er yth r o-p en t -1-
en itol (8a ). A solution of 7a (4.63 g, 12.5 mmol) in 80% aqueous
AcOH (80 mL) was stirred at 100 °C for 5 h. Removal of the
solvent in vacuo gave a residue that was coevaporated with
toluene once. The residue was dissolved in EtOAc (100 mL) and
treated with solid NaHCO3. Filtration and removal of the solvent
in vacuo afforded the diol as a colorless syrup, which was used
directly in the subsequent reaction.
(NaCl) 3479, 3365, 1721, 1666, 1643 cm-1; H NMR (CDCl3) δ
7.88 (d, J ) 8.5 Hz, 2H), 7.36 (d, J ) 8.5 Hz, 2H), 7.33 (br s,
5H), 7.02 (dd, J ) 11.3, 6.4 Hz, 1H), 6.43 (dd, J ) 10.7, 7.2 Hz,
1H), 6.03 (m, 1H), 5.03 (m, 1H), 4.93 (d, J ) 5.5 Hz, 2H), 4.89
(m, 1H), 4.63 (dd, J ) 11.9, 2.7 Hz, 1H), 4.55 (dd, J ) 11.9, 4.0
Hz, 1H), 3.75 (br s, 2H, D2O exchangeable); 13C NMR (CDCl3) δ
165.43, 156.25 (d, J ) 240.6 Hz), 154.24, 147.2 (d, J ) 235.3
Hz), 139.21, 135.72, 135.21 (dd, J ) 15.4, 11.0 Hz), 131.00,
128.50, 128.41, 128.19, 127.41, 118.61 (dd, J ) 16.0, 5.5 Hz),
113.96 (dd, J ) 21.9, 6.0 Hz), 103.10 (dd, J ) 27.5, 3.3 Hz), 96.29,
Triphenylphosphine (7.22 g, 27.5 mmol) and imidazole (7.52
g, 110.6 mmol) were added in aliquots to a well-stirred solution
of iodine (7.0 g, 27.5 mmol) in dry CH2Cl2 (100 mL) at 25 °C,
during which time the reaction mixture turned to a pale yellow.
The above diol in dry CH2Cl2 (20 mL) was added to the reaction
mixture, which immediately changed color to brown. After it was
stirred at 25 °C for 10 min, Et3N (5 mL) was added to the
mixture, and the reaction mixture was concentrated to half-
volume before dilution with hexane (100 mL). The mixture was
passed through a silica gel pad that was washed with a large
volume of hexanes-ether (1:1 v/v) and then ether. The solvents
from the combined organic eluants were removed, and the
residue obtained was purified via flash chromatography (hex-
anes-ether, 6:1 v/v, the silica gel was treated with 1% Et3N in
hexane before packing the column to avoid on-column decom-
position of the glycal 8a ) to afford the glycal 8a (1.65 g, 45%) as
a colorless syrup: 1H NMR (CDCl3) δ 7.4-7.2 (m, 10H), 6.62 (d,
J ) 2.7 Hz, 1 H), 5.20 (dd, J ) 2.7, 2.1 Hz, 1H), 4.75-4.60 (m,
2H), 4.61 (d, J ) 4.0 Hz, 2H), 4.56 (s, 2H), 3.59 (dd, J ) 9.9, 6.1
Hz, 1H), 3.46 (d, J ) 9.9, 5.3 Hz, 1H); 13C NMR (CDCl3) δ 150.20,
138.26, 137.83, 128.30, 128.27, 127.72, 127.61, 127.57, 127.48,
100.53, 84.81, 82.68, 73.38, 69.89, 69.55.
1,4-An h yd r o-5-O-(p-ch lor oben zoyl)-3-O-ben zyl-2-d eoxy-
L-er yth r o-p en t-1-en itol (8b). A solution of 7b (5.25 g, 12.5
mmol) in 80% aqueous AcOH (80 mL) was stirred at 100 °C for
4 h. Removal of the solvent in vacuo gave a residue that was
coevaporated with toluene once; the residue was dissolved in
EtOAc (100 mL) and treated with solid NaHCO3. Filtration, and
removal of the solvent, afforded the diol as a colorless syrup,
which was used directly in the subsequent reaction.
Triphenylphosphine (7.22 g, 27.5 mmol) and imidazole (7.52
g, 110.6 mmol) were added in aliquots to a well-stirred solution
of iodine (7.0 g, 27.5 mmol) in dry CH2Cl2 (100 mL) at 25 °C;
the reaction was completed and the product purified as described
for the preparation of 8a above to afford the glycal 8b (2.55 g,
62%) as a colorless syrup: 1H NMR (CDCl3) δ 7.97 (d, J ) 8.8
Hz, 2H), 7.43 (d, J ) 8.8 Hz, 2H), 7.4-7.25 (m, 5H), 6.63 (dd, J
) 2.7, 0.8 Hz, 1H), 5.27 (dd, J ) 2.7, 2.4 Hz, 1H), 4.79 (td, J )
5.5, 3.0 Hz, 1H), 4.72 (ddd, J ) 3.0, 2.4, 0.8 Hz, 1H), 4.56 (s,
2H), 4.35 (d, J ) 5.5 Hz, 2H); 13C NMR (CDCl3) δ 165.32, 150.45,
139.68, 137.95, 131.09, 128.77, 128.45, 128.16, 127.74, 100.70,
83.57, 82.52, 69.79, 64.70. Anal. Calcd for C19H17ClO4: C, 66.19;
H, 4.97. Found: C, 66.24; H, 4.91.
79.97, 78.31 (d, J ) 2.2 Hz), 72.60, 65.06. Anal. Calcd for C25H20
-
ClF2NO4: C, 63.63; H, 4.27; N, 2.97. Found: C, 63.41; H, 4.00;
N, 2.86.
3-F lu or o-4-(â-L-glycer op en t ofu r a n -3-u los-1-yl)a n ilin e
(12a ). Pd on C (10% w/w, 0.1 g) was added to a solution of 10a
(0.38 g, 0.936 mmol) in dry EtOH (6 mL) and Et3N (0.05 mL),
and the resulting mixture was stirred at 60 °C under 1 atm of
H2 gas for 8 h. After filtration, and removal of the solvent in
vacuo, the residue was purified via flash chromatography
(hexanes-EtOAc, 1:1 v/v) to give the hydroxy ketone 12a (0.13
g, 61%) as pale yellow crystals: mp 132-133 °C; IR (NaCl) 3446,
1
3364, 3220, 1752, 1635 cm-1; H NMR (CDCl3) δ 7.20 (dd, J )
8.5, 8.2 Hz, 1H), 6.39 (dd, J ) 8.5, 2.1 Hz, 1H), 6.30 (dd, J )
12.5, 2.1 Hz, 1H), 5.22 (dd, J ) 11.0, 6.0 Hz, 1H), 3.90 (t, J )
3.0 Hz, 1H), 3.78 (d, J ) 3.0 Hz, 2H), 3.62 (br s, 3H, D2O
exchangeable), 2.70 (dd, J ) 18.1, 6.0 Hz, 1H), 2.48 (dd, J )
18.1, 11.0 Hz, 1H); 13C NMR (CDCl3) δ 214.2, 161.26 (d, J )
243.9 Hz), 148.61 (d, J ) 9.9 Hz), 128.39 (d, J ) 6.6 Hz), 115.4
(d, J ) 14.5 Hz), 110.74 (d, J ) 2.2 Hz), 101.68 (d, J ) 25.3 Hz),
82.32, 72.1, 61.05, 43.87. Anal. Calcd for C11H12FNO3: C, 58.66;
H, 5.37; N, 6.22. Found: C, 58.29; H, 5.30; N, 6.15.
4-(5-(H yd r oxym e t h yl)-4-(b e n zyloxy)-2,5-d ih yd r o-â-L-
fu r a n -2-yl)-2,5-d iflu or oa n ilin e (11). NaOMe (0.16 g, 3 mmol)
was added to a suspension of 10b (0.8 g, 1.75 mmol) in dry
MeOH (30 mL) with stirring, and the reaction mixture was
stirred at 25 °C for 1.5 h, during which time the reaction mixture
changed to a clear solution. The reaction was quenched with
solid NH4Cl, and then ether (100 mL) was added. After filtration,
and removal of the solvent in vacuo, the residue obtained was
purified via flash chromatography (hexanes-EtOAc, 2:1 v/v) to
give 11 (0.465 g, 90%) as a yellow syrup: IR (NaCl) 3465, 3362,
1
3224, 1663, 1645, 1518 cm-1; H NMR (CDCl3) δ 7.45-7.3 (m,
5H), 7.05 (dd, J ) 11.3, 6.4 Hz, 1H), 6.45 (dd, J ) 11.0, 7.3 Hz,
1H), 6.03 (m, 1H), 4.95 (d, J ) 3.1 Hz, 2H), 4.79 (m, 1H), 4.76
(m, 1H), 3.80 (d, J ) 3.4, 2H); 13C NMR (CDCl3) δ 156.25 (d, J
) 240.6 Hz), 155.39, 147.6 (d, J ) 235.1 Hz), 135.85, 135.57 (dd,
J ) 15.4, 11.0 Hz), 128.53, 128.19, 127.42, 118.41 (dd, J ) 16.0,
5.5 Hz), 114.22 (dd, J ) 22.0, 5.5 Hz), 103.20 (dd, J ) 28.6, 3.3
Hz), 95.53, 82.33, 77.88 (d, J ) 3.3 Hz), 72.53, 62.95. Anal. Calcd
for C18H17F2NO3: C, 64.85; H, 5.14; N, 4.20. Found: C, 64.55;
H, 5.21; N, 3.98.
4-(5-((Ben zyloxy)m eth yl)-4-(ben zyloxy)-2,5-d ih yd r o-â-L-
fu r a n -2-yl)-3-flu or oa n ilin e (10a ). A freshly dried 100 mL
round-bottom flask was charged with palladium acetate (0.1 g,
0.364 mmol) and triphenylarsine (0.4 g, 1.33 mmol) under argon.
Dry MeCN (15 mL) was added, and the yellow suspension was
stirred at 25 °C for 30 min. A solution of the glycal 8a (0.592 g,
2 mmol), 9a (0.592 g, 2.5 mmol), and Et3N (0.6 mL) in MeCN
(10 mL) was added with stirring, and the resulting solution was
stirred at 70 °C for 24 h. The solvents were removed in vacuo,
and the residue was purified via flash chromatography (hex-
anes-EtOAc, 3:1 v/v) to give 10a (0.46 g, 57%) as a yellow
2,5-D iflu o r o -4-(â-L -g ly c e r o p e n t o fu r a n -3-u lo s -1-y l)-
a n ilin e (12b). Et3N (3 drops) and 10% Pd on C (0.1 g) were
added to a solution of 11 (0.42 g, 1.42 mmol) in dry EtOH (10
mL) with stirring, and the resulting mixture was stirred at 60
°C under 1 atm of H2 gas for 2 h. After filtration, and removal
of the solvent in vacuo, the residue was purified via flash
chromatography (hexanes-EtOAc, 1.5:1 to 1:1 v/v) to give the
hydroxy ketone 12b (0.33 g, 96%) as a colorless syrup: IR (NaCl)
3465, 3368, 3231, 1758, 1649, 1522 cm-1 1H NMR (CDCl3) δ
;
7.14 (dd, J ) 11.3, 6.4 Hz, 1H), 6.48 (dd, J ) 11.3, 7.3 Hz, 1H),
5.29 (dd, J ) 11.0, 5.8 Hz, 1H), 4.0 (t, J ) 3.3 Hz, 1H), 3.95 (d,
J ) 3.3 Hz, 2H), 3.92 (br s, 2H, D2O exchangeable), 2.84 (dd, J
) 18.0, 5.8 Hz, 1H), 2.49 (dd, J ) 18.0, 11.0 Hz, 1H), 2.47 (br s,
1H, D2O exchangeable); 13C NMR (CDCl3) δ 213.41, 156.45 (dd,
J ) 240.6, 2.2 Hz), 147.47 (dd, J ) 235.1, 2.2 Hz), 135.83 (dd, J
) 15.4, 12.1 Hz), 115.41 (dd, J ) 16.9, 5.5 Hz), 113.5 (dd, J )
22.0, 5.5 Hz), 103.3 (dd, J ) 27.5, 4.4 Hz), 82.0, 71.76, 61.40,
44.10. Anal. Calcd for C11H11F2NO3: C, 54.32; H, 4.56; N, 5.76.
Found: C, 54.61; H, 5.05; N, 5.51.
3-F lu or o-4-[1-(2-d eoxy-â-L-r ibofu r a n osyl)]a n ilin e (13a ).
NaB(OAc)3H (0.26 g, 1.2 mmol) was added in one aliquot to an
ice-cold solution of 12a (0.09 g, 0.3 mmol) in dry MeCN (5 mL)
with stirring under argon. After the mixture was stirred at 0
°C for 1.5 h, the reaction was quenched with MeOH (2 mL), and
1
syrup: IR (NaCl) 3471, 3368, 3229, 1664, 1630 cm-1; H NMR
(CDCl3) δ 7.45-7.2 (m, 11H), 6.35-6.3 (m, 2H), 6.10 (dd, J )
3.3, 1.2 Hz), 4.93 (br s, 3H), 4.83 (br s, 1H), 4.63 (d, J ) 3.7 Hz,
2H), 3.85 (dd, J ) 10.7, 2.4 Hz), 3.74 (dd, J ) 10.7, 4.9 Hz, 1H),
3.7 (br s, 2H, D2O exchangeable); 13C NMR (CDCl3) δ 160.95 (d,
J ) 243.9 Hz), 154.81, 147.67 (d, J ) 11.0 Hz), 138.43, 136.15,
129.63 (d, J ) 5.5 Hz), 128.41, 128.12, 127.98, 127.56, 127.34,
127.25, 119.16 (d, J ) 13.2 Hz), 110.72, 101.30 (d, J ) 25.3 Hz),
96.40, 81.49, 73.25, 72.27, 71.46.
4-[5-(((p-Ch lor oben zoyl)oxy)m eth yl)-4-(ben zyloxy)-2,5-
d ih yd r o-â-L-fu r a n -2-yl]-2,5-d iflu or oa n ilin e (10b). Reaction
of 8b with 9b, using the method described for the preparation
of 10a above, and purification of the product (hexanes-EtOAc,