Notes
J . Org. Chem., Vol. 64, No. 18, 1999 6877
more, the mixture was treated with water. Usual extraction,
solvent removal, and column chromatography (silica gel, 0-10%
EtOAc in petroleum ether) of the residue afforded pure monoben-
zyl ether 6 (13.5 g, 78%): bp 125-128 °C (0.6 mmHg), lit.23a bp
114-120 °C (0.4 mmHg); IR (film) 3397, 3063, 3028; 1H NMR
(CDCl3 ) δ 1.9 (bs, D2O exchangeable, 1H), 4.1-4.3 (m, 4H), 4.51
(m, 2H), 5.3-5.5 (m, 2H), 7.2-7.5 (m, 5H).
solution of 12 (2.1 g, 7 mmol) in DMF (30 mL) containing
imidazole (1.2 g, 1.5 mmol) was added dropwise a solution of
tert-butyldiphenylsilyl chloride (1.92 g, 7 mmol) in DMF (30 mL)
over a period of 8 h. The mixture was stirred for 1 h, treated
with water, and extracted with ether. The organic extract was
washed with water and then brine and dried. Solvent removal
and column chromatography of the residue (silica gel, 0-10%
4-Ben zyloxy-1-br om o-(2Z)-bu ten e (7). To a stirred suspen-
sion of PPh3 (18.9 g, 0.072 mol) in benzene (50 mL) was added
Br2 (14.2 mL of a 5 M solution in CCl4, 0.071 mol). To the
resulting suspension was added 6 (12.5 g, 0.07 mol) in benzene
(50 mL) containing pyridine (5 mL) over a period of 1 h. Stirring
was continued for 1 h. The solvent was evaporated, and the
residue was chromatographed (silica gel, 0-10% ether in hexane)
to afford 7 (14 g, 83%): bp 88-90 °C (0.3 mmHg), lit.23b bp 80
EtOAc in petroleum ether) afforded 13 (2.8 g, 75%): [R]22
D
+12.24 (c 2.1, CHCl3); IR (film) 3545, 3073, 3047, 3012, 2855,
1369, 1177, 995, 906; 1H NMR (CDCl3) δ 1.03 (d, J ) 6.6 Hz,
3H), 1.07 (s, 9H), 1.7 (bs, D2O exchangeable, 1H), 2.3-2.5 (m,
1H), 2.43 (s, 3H), 3.5-3.8 (m, 3H), 4.6-4.8 (m, 1H), 5.0-5.2 (m,
2H), 5.5-5.7 (m, 1H), 7.1-7.8 (m, 14H). Anal. Calcd for C30H38O5-
SSi: C, 66.88; H, 7.11. Found: C, 66.97; H, 6.97.
5-O-ter t-Bu tyldiph en ylsilyl-3-O-tosyl-2-C-m eth yl-2-deoxy-
D-r ibofu r a n ose (14). Through a stirred and cooled (-78 °C)
solution of 13 (1.08 g, 0.002 mol) in CH2Cl2 (100 mL) was bubbled
ozone until a blue color persisted. The excess ozone was removed
by flushing with argon. PPh3 (550 mg, 0.0021 mol) was added
to the mixture. The blue color disappeared immediately. The
solution was brought to room temperature, stirred for 5 h more,
and concentrated under reduced pressure. The residue was
chromatographed (silica gel, 0-25% EtOAc in petroleum ether)
to afford 14 (816 mg, 75%) as a colorless oil as a mixture of R
and â anomers. The tosylate gradually darkens in color on long
standing, possibly as a result of decomposition, and hence was
1
°C (0.13 mmHg); IR (film) 3063, 3030; H NMR (CDCl3) δ 3.8-
3.9 (m, 2H), 4.1-4.3 (m, 2H), 4.51 (s, 2H), 5.3-5.5 (m, 2H), 7.2-
7.5 (m, 5H).
1,2-O-Cycloh exyliden e-4-ben zyloxym eth yl-5-h exen -1,2,3-
tr iol. To a well stirred mixture of 1 (8.16 g, 0.048 mol), 7 (12 g,
0.05 mol), and Zn dust (19.5 g, 0.3 mol) in THF (100 mL) was
added saturated aqueous NH4Cl (10 mL) in portions over a
period of 40 min. The reaction mixture was stirred for 1.5 h until
the aldehyde 1 was found to disappear completely (TLC). The
mixture was filtered and thoroughly washed with EtOAc. The
combined organic layer was washed with 5% HCl to dissolve the
suspended turbid material and then with water and brine and
dried. Solvent removal and column chromatography (silica gel,
0-20% EtOAc in petroleum ether) of the residue sequentially
isolated the mixture of 8 and 9 (430 mg, 3%), pure 9 (1.8 g, 11%),
10 (4.1 g, 26%), and 11 (5.9 g, 37%). The Rf (20% EtOAc in
hexane) values of 8, 9, 10 and 11 are 0.60, 0.57, 0.51, and 0.45,
respectively.
immediately used for the next reaction. [R]22 +12.70 (c 3.18,
D
1
CHCl3); IR (film) 3518, 3071, 3050, 3014, 2858, 1369, 1177; H
NMR (CDCl3 ) δ 1.03, 1.06 (2s, 9H), 1.0-1.09 (m, 3H), 2.37 and
2.40 (2s, 3H), 2.2-2.6 (m, 1H), 2.7 (bs, D2O exchangeable, 1H),
3.5-3.8 (m, 2H), 4.0-4.3 (m, 1H), 4.9-5.2 (m, 1H), 5.4 (m, 1H),
7.1-7.8 (m, 14H). Anal. Calcd for C29H36O6SSi: C, 64.41; H, 6.71.
Found: C, 64.57; H, 6.95.
(2R,3R,4S)-isom er (9): [R]22D +5.72 (c 1.9, CHCl3); IR (film)
3400, 3063, 3030, 3005, 1650, 995, 920; 1H NMR (CDCl3) δ 1.4-
1.6 (m, 10H), 2.35 (m, 1H), 3.0 (bs, D2O exchangeable, 1H), 3.5-
3.6 (m, 1H), 3.65-3.83 (m, 3H), 3.9-4.2 (m, 2H), 4.51 (m, 2H),
5.0-5.2 (m, 2H), 5.8-6.0 (m, 1H), 7.2-7.5 (m, 5H).
5-O -t er t -B u t y ld ip h e n y lsily l-3-a zid o -2-C-m e t h yl-2,3-
d id eoxy-D-xylofu r a n ose (15). Compound 14 (540 mg, 1 mmol)
was heated in DMF (20 mL) with an excess of NaN3 (137 mg,
2.1 mmol) at 80 °C for 6 h. The solvent was removed in vacuo.
The crude product was dissolved in dry ether, and the insoluble
salt was filtered off. Solvent removal and column chromatogra-
phy of the residue (silica gel, 0-20% ether in petroleum ether)
(2R,3S,4R)-isom er (10): [R]22 +20.72 (c 0.4, CHCl3); IR
D
(film) 3400, 3065, 3025, 3005, 1650, 995, 920; 1H NMR (CDCl3)
δ 1.4-1.6 (m, 10H), 2.45 (m, 1H), 3.0 (bs, D2O exchangeable,
1H), 3.62-3.7 (m, 1H), 3.75-3.85 (m, 2H), 3.9-4.02 (m, 2H),
4.05-4.1 (m, 1H), 4.51 (m, 2H), 5.0-5.2 (m, 2H), 5.8-6.0 (m,
1H), 7.2-7.5 (m, 5H).
furnished pure 15 (254 mg, 62%) as clear oil: [R]22 -30.19 (c
D
1.4, CHCl3); IR (film) 3448, 3071, 3050, 2858, 2103, 1605; 1H
NMR (CDCl3) δ 1.03, 1.06 (2s, 9H), 1.0-1.1 (m, 3H), 1.7 (bs, D2O
exchangeable, 1H), 2.4-2.7 (m, 1H), 3.5-3.8 (m, 2H), 3.9-4.3
(m, 2H), 5.3-5.5 (m, 1H), 7.1-7.8 (m, 10H). Anal. Calcd for
C22H29O3N3Si: C, 64.20; H, 7.10; N, 10.21. Found: C, 64.45; H,
7.19; N, 10.35.
(2R,3S,4S)-isom er (11): [R]22D -4.38 (c 2.6, CHCl3); IR (film)
3400, 3065, 3025, 3005, 1650, 995, 920; 1H NMR (CDCl3) δ 1.4-
1.6 (m, 10H), 2.0 (bs, D2O exchangeable, 1H), 2.66 (m, 1H), 3.6-
3.77 (m, 2H), 3.8-4.1 (m, 4H), 4.51 (m, 2H), 5.0-5.2 (m, 2H),
5.8-6.0 (m, 1H), 7.2-7.5 (m, 5H). Anal. Calcd for C20H28O4: C,
72.26; H, 8.49. Found: C, 72.27; H, 8.57 for 9; C, 72.38; H, 8.37
for 10; C, 72.41; H, 8.33 for 11.
(2R,3R,4S)-3-Tosyloxy-4-ben zyloxym eth yl-5-h exen e-1,2-
d iol (16). Compound 9 (1.65 g, 5 mmol) was tosylated with
p-tosyl chloride (1 g, 5.1 mmol) in pyridine (20 mL). The resulting
tosylate was treated with 90% aqueous trifluoroacetic acid (15
mL) at 0 °C for 5 h to obtain the diol 16 (1.7 g, 84%): [R]23D +7.37
(c 3.8, CHCl3); IR (film) 3500, 3075, 3005, 1605, 1365, 1178, 995,
910; 1H NMR (CDCl3) δ 2.3-2.5 (m, 1H), 2.43 (s, 3H), 2.8 (bs,
D2O exchangeable, 2H), 3.5-3.8 (m, 5H), 4.50 (m, 2H), 4.6-4.8
(m, 1H), 5.0-5.2 (m, 2H), 5.5-5.7 (m, 1H), 7.3-7.5 (m, 7H), 7.77
(d, J ) 8 Hz, 2H). Anal. Calcd for C21H26O6S: C, 62.05; H, 6.45.
Found: C, 62.19; H, 6.27.
(2R,3S,4S)-3-Tosyloxy-4-m eth yl-5-h exen e-1,2-d iol (12). To
a cooled and well stirred solution of 4 (2.26 g, 0.01 mol) in
pyridine (20 mL) was added p-toluenesulfonyl chloride (2.09 g,
0.011 mol). The mixture was stirred overnight at room temper-
ature, treated with water, and extracted with ether. The organic
extract was washed with dilute HCl, water, and brine and dried.
Solvent removal under reduced pressure afforded the corre-
sponding tosylate in almost quantitative yield. This was mixed
with 90% aqueous trifluoroacetic acid (20 mL), stirred for 5 h at
0 °C, and diluted with water. The mixture was extracted with
CHCl3. The combined organic layer was washed with water to
make it acid-free and then brine and dried. Solvent removal and
chromatography of the residue (silica gel, 0-5% MeOH in CHCl3)
5-O-t er t -Bu t yld ip h e n ylsilyl-3-O-t osyl-2-C-b e n zyloxy-
m eth yl-2-d eoxy-D-xylofu r a n ose (18). Following a similar
procedure as for the preparation of 13, 16 (1.62 g, 4 mmol) was
monosilylated in DMF (30 mL) with TBDPSCl (1.1.g, 4 mmol)
in the presence of imidazole (680 mg, 0.01 mol) to obtain 17 (2.08
g, 81%) after purification by column chromatography. A part of
this (1 g) was dissolved in CH2Cl2 (50 mL) and subjected to
ozonolysis at -78 °C followed by reduction with PPh3 (410 mg)
in situ following a similar procedure as for the preparation of
14. Solvent removal under reduced pressure and column chro-
matography (silica gel, 0-30% EtOAc in petroleum ether) of the
residue afforded 18 (750 mg, 75%) as a colorless oil as a mixture
of R and â anomers. The tosylate gradually darkened in color,
afforded pure 12 (2.44 g, 81%): [R]22 +10.32 (c 2.6, CHCl3); IR
D
(film) 3500, 3075, 3005, 1365, 1178, 995, 910; 1H NMR (CDCl3)
δ 1.03 (d, J ) 6.6 Hz, 3H), 2.3-2.45 (m, 1H), 2.43 (s, 3H), 2.56
(bs, D2O exchangeable, 2H), 3.5-3.8 (m, 3H), 4.6-4.8 (m, 1H),
5.0-5.2 (m, 2H), 5.5-5.7 (m, 1H), 7.34 (d, J ) 8.0 Hz, 2H), 7.78
(d, J ) 8.0 Hz, 2H). Anal. Calcd for C14H20O5S: C, 55.98; H,
6.71. Found: C, 55.77; H, 6.87.
(2R,3S,4S)-1-[(ter t- Bu tyld ip h en ylsyl)oxy]-3-tosyloxy-4-
m eth yl-5-h exen -2-ol (13). To a stirred and cooled (10 °C)
possibly as a result of decomposition on long standing. [R]22
D
+10.47 (c 2.4, CHCl3); IR (film) 3518, 3071, 3050, 2858, 1369,
1
1177; H NMR (CDCl3) δ 1.04, 1.07 (2s, 9H), 2.36 and 2.38 (2s,
(23) (a) Takano, S.; Akiyama, M.; Sato, S. Ogasawara, K. Chem. Lett.
1983, 1593. (b) Naruta, Y.; Nagai, N.; Maruyama, K. Chem. Lett. 1983,
1383.
3H), 2.3-2.6 (m, 1H), 2.8 (bs, D2O exchangeable, 1H), 3.5-3.8
(m, 4H), 4.1-4.5 (m, 1H), 4.55 and 4.58 (2s, 2H), 5.0-5.3 (m,