1504 J . Org. Chem., Vol. 62, No. 5, 1997
Notes
79.5, 65.4, 33.7, 26.7, 26.6, 19.2. Anal. Calcd for C27H32O3-
mmol) (mixture R/â) was converted to 7 by reaction with
ethyldiisopropylamine (0.43 mL, 2.48 mmol), tert-butyl hydro-
peroxide (1.12 mL of a 3 M solution in toluene, 3.35 mmol), and
titanium tetraisopropoxide (0.43 mL, 1.45 mmol). After 40 min,
the solvent was removed and the crude purified by filtration
through a small column of neutral silica gel (hexane/ethyl
acetate 100:1) to afford 0.183 g (67%) of compound 7 which was
immediately used in the synthesis of nucleosides. 7: 1H NMR
(CDCl3) δ 7.60-7.20 (m, 5H), 6.30 (q, 1H, J ) 2.4 Hz), 4.88 (q,
1H, J ) 2.4 Hz), 4.75 (dddd, 1H, J ) 4.3, 6.8, 7.7, 10.6 Hz), 4.64
(d, 1H, J ) 12.1 Hz), 4.57 (d, 1H, J ) 12.1 Hz), 3.59 (dd, 1H, J
) 6.8, 10.3 Hz), 3.50 (dd, 1H, J ) 4.3, 10.3 Hz), 2.68 (qt, 1H, J
) 2.4, 2.4, 10.5, 15.2 Hz), 2.36 (qt, 1H, J ) 2.4, 2.4, 7.7, 15.2
Hz); 13C NMR (CDCl3) δ 145.1, 138.0, 128.4, 127.7, 127.6, 99.0,
79.8, 73.3, 72.3, 31.6.
SeSi: C, 65.43; H, 6.51. Found: C, 65.47; H, 6.53. 4â: [R]25
D
-110.8° (c ) 1.01, CHCl3); 1H NMR (CDCl3) δ 7.66-7.10 (m,
15H), 5.77 (dd, 1H, J ) 3.4, 6.5 Hz), 4.18 (dddd, 1H, J ) 5.6,
5.7, 7,3, 7.3 Hz), 3.76 (dd, 1H, J ) 5.6, 10.5 Hz), 3.62 (dd, 1H, J
) 5.7, 10.5 Hz), 2.41-2.22 (m, 1H), 2.18-2.07, 2.03-1.80
(complex multiplets, 3H), 0.99 (s, 9H); 13C NMR (CDCl3) δ 135.6,
134.0, 129.6, 128.9, 127.6, 127.2, 84.0, 82.2, 66.3, 35.0, 27.6, 26.8,
19.2. Anal. Calcd for C27H32O3SeSi: C, 65.43; H, 6.51. Found:
C, 65.26; H, 6.48.
(1S)-1-[[(ter t-Bu t yld ip h en ylsilyl)oxy]m et h yl]-2,3-d ih y-
d r ofu r a n (6). Compound 4 (0.7 g, 1.4 mmol) (mixture R/â) was
dissolved in anhydrous dichloromethane (8 mL) under argon
atmosphere. The solution was then cooled to 0 °C, and ethyl-
diisopropylamine (0.41 mL, 2.38 mmol) was added. To this
mixture was added tert-butyl hydroperoxide (1.07 mL of a 3 M
solution in toluene, 3.22 mmol) dropwise over a period of 5 min.
Subsequent addition of titanium tetraisopropoxide (0.41 mL, 1.4
mmol) gave a yellowish solution that was allowed to stir at low
temperature for 45 min and then warmed to room temperature.
The solvent was removed under low pressure, and the crude
obtained was purified through a small column of neutral silica
gel (hexane/ethyl acetate 150:1) to afford 0.25 g (52%) of glycal
6, which was immediately used in the synthesis of nucleosides:
1H NMR (CDCl3) δ 7.75-7.40 (m, 10H), 6.27 (q, 1H, J ) 2.4 Hz),
4.85 (q, 1H, J ) 2.4 Hz), 4.65 (dddd, 1H, J ) 4.9, 5.7, 7.4, 10.5
Hz), 3.75 (dd, 1H, J ) 5.7, 10.7 Hz), 3.68 (dd, 1H, J ) 4.9, 10.7
Hz), 2.64 (qt, 1H, J ) 2.4, 2.4, 10.4, 15.2 Hz), 2.46 (qt, 1H, J )
2.4, 2.4, 7.4, 15.2 Hz), 1.05 (s, 9H); 13C NMR (CDCl3) δ 145.1,
135.6, 129.6, 127.6, 99.0, 81.2, 65.8, 31.2, 26.8, 19.2.
Meth yl 5-O-Ben zyl-r,â-D-glycer o-p en tofu r a n osid e (3). A
solution of compound 2 (9 g, 24.3 mmol) in dry THF (27 mL)
under argon atmosphere was treated with tetrabutylammoniun
fluoride (7 g, 26.7 mmol) dissolved in dry THF (27 mL). The
resulting reaction mixture was allowed to stir at room temper-
ature for 1 h. The solvent was then removed under low pressure,
and the crude obtained was subjected to flash chromatography
(hexane/ethyl acetate 3:1) to afford 2.81 g (88%) of the 5-O-
deprotected derivative. The alcohol thus obtained was dissolved
in dry THF (35 mL), and the resulting solution added to a
suspension of NaH (1.26 g, 42.7 mmol) in 35 mL of dry THF.
The mixture was stirred for 50 min at room temperature, and
then benzyl bromide (2.8 mL, 23.2 mmol) was added. Stirring
was maintained overnight, and the reaction was then quenched
by the addition of methanol followed by evaporation of the
solvent at reduced pressure. The crude was chromatographed
over silica gel using hexane first and then increasing amounts
of ethyl acetate to afford 2.7 g (56%) of product 3 as an
unseparable R/â mixture. Anal. Calcd for C13H18O3: C, 70.24:
H, 8.16. Found: C, 70.45; H, 8.21.
1-[5-O-(ter t-Bu tyld ip h en ylsilyl)-3-d eoxy-2-Se-p h en yl-2-
selen o-â,r-D-er yth r o-p en tofu r a n osyl]u r a cil (86a a n d 13)
a n d 1-[5-O-(ter t-Bu tyld ip h en ylsilyl)-3-d eoxy-2-Se-p h en yl-
2-se le n o-â,r-D-er yt h r o-p e n t ofu r a n osyl]-5-(p h e n ylse le n -
en yl)u r a cil (9). Phenylselenenyl chloride (0.036 g, 0.185 mmol)
was added to a solution of glycal 6 (0.042 g, 0.125 mmol) in 1
mL of dry ether at room temperature, kept under argon, and
protected from light. After 5 min, bis(trimethylsilyl)uracil (0.064
g, 0.25 mmol) was added followed by AgOTf (0.054 g, 0.21 mmol).
The reaction was monitored by TLC in ethyl acetate/hexane )
1:10. After 1 h, workup of the reaction afforded a crude which
was chromatographed over silica gel, eluting first with hexane
and then EtOAc/hexane (up to 1:1) to give 0.023 g (25%) of
compound 9 and 0.046 g (60%) of a mixture of 8/13. Radial
chromatography using EtOAc/hexane allowed the separation of
compound 8 and 13 as hygroscopic foams: 8: UV (MeOH) λmax
264 nm; 1H NMR (CDCl3) δ 7.9 (bs, 1H), 7.73-7.22 (m, 16H),
6.16 (d, 1H, J ) 6.0 Hz), 5.28 (dd, 1H, J ) 2.2, 8.1 Hz), 4.34-
4.28 (m, 1H), 4.07 (dd, 1H, J ) 2.2, 11.7 Hz), 3.76 (td, 1H, J )
6.0, 7.6, 7.6 Hz), 3.68 (dd, 1H, J ) 2.3, 11.7 Hz), 2.54 (ddd, 1H,
J ) 5.7, 7.6, 13.2 Hz), 2.11 (dt, 1H, J )7.6, 7.6, 13.2 Hz), 1.09
(s, 9H); 13C NMR (CDCl3) δ 162.4, 149.8, 139.7, 135.7, 135.6,
135.3, 130.2, 130.1, 129.3, 128.6, 128.0, 102.5, 90.3, 79.4, 65.3,
44.1, 32.6, 26.8, 19.7. 9: 1H NMR (CDCl3) δ 8.12 (bs, 1H), 7.68-
7.22 (m, 21H), 6.10 (d, 1H, J ) 7.4 Hz), 4.24-4.16 (m, 1H), 3.83
(dd, 1H, J ) 3.1, 11.4 Hz), 3.69 (td, 1H, J ) 7.4, 8.2, 8.8 Hz),
3.60 (dd, 1H, J ) 3.0, 11.4 Hz), 2.40 (ddd, 1H, J ) 4.7, 8.2, 13.0
Hz), 2.11 (dt, 1H, J ) 8.8, 8.8, 13.0 Hz), 1.09 (s, 9H); 13C NMR
(CDCl3) δ 162.4, 149.9, 143.6, 135.7, 135.6, 135.5, 132.1, 130.1,
130.0, 129.3, 129.2, 128.7, 128.0, 127.9, 127.9, 127.5, 90.4, 78.4,
65.6, 42.6, 33.5, 27.1, 19.6. (13): 1H NMR (CDCl3) δ 7.78-7.18
(m, 17H), 6.13 (d, 1H, J ) 4.6 Hz), 5.67 (dd, 1H, J ) 2.0, 8.1
Hz), 4.55-4.45 (m, 2H), 3.84 (dd, 1H, J ) 3.4, 11.2 Hz), 3.65
(dd, 1H, J ) 3.7, 11.2 Hz), 2.64 (dt, 1H, J ) 7.7, 7.7, 14.0 Hz),
2.23 (ddd, 1H, J )3.5, 6.4, 14.0 Hz), 1.05 (s, 9H); 13C NMR
(CDCl3) δ 162.7, 149.5, 139.9, 135.5, 133.2, 129.9, 129.2, 128.0,
127.9, 127.8, 100.7, 88.0, 79.7, 65.4, 46.1, 33.7, 26.8, 19.2.
1-[5-O-(ter t-Bu tyld ip h en ylsilyl)-3-d eoxy-2-Se-p h en yl-2-
selen o-â-D-er yth r o-p en tofu r a n osyl]th ym in e (10).6a A solu-
tion of glycal 6 (0.084 g, 0.25 mmol) in 1 mL of dry ether at room
temperature, kept under argon and protected from light, was
treated with phenylselenenyl chloride (0.096 g, 0.5 mmol). After
5 min, bis(trimethylsilyl)thymine (0.168 g, 0.62 mmol) and
AgOTf (0.128 g, 0.5 mmol) were added. The reaction was
monitored by TLC using ethyl acetate/hexane ) 1:10. After 2
h, workup of the reaction afforded a crude which was chromato-
graphed over silica gel, eluting first with hexane and then
EtOAc/hexane (up to 1:2). The residue obtained (0.153 g, 95%)
was further purified by means of radial chromatography using
EtOAc/hexane ) 1:4 to give compound 10 as a foam: UV (MeOH)
λmax 266 nm; 1H NMR (CDCl3) δ 8.28 (bs, 1H), 7.65-7.06 (m,
16H), 6.10 (d, 1H, J ) 8.1 Hz), 4.17-4.10 (m, 1H), 3.94 (dd, 1H,
J ) 2.2, 11.5 Hz), 3.68 (dt, 1H, J ) 8.1, 8.1, 10.1 Hz), 3.60 (dd,
1H, J ) 2.5, 11.5 Hz), 2.48 (ddd, 1H, J ) 3.9, 8.1, 13.0 Hz), 2.09
(ddd, 1H, J ) 8.7, 10.1, 13.0 Hz), 1.37 (s, 3H), 1.04 (s, 9H); 13C
NMR (CDCl3) δ 163.2, 150.3, 135.9, 135.5, 135.2, 134.8, 133.0,
130.1, 130.0, 129.1, 128.5, 128.0, 127.8, 111.1, 89.6, 77.9, 65.9,
42.5, 32.8, 27.1, 19.5, 11.8.
P h en yl 5-O-Ben zyl-1-selen o-r,â-D-glycer o-p en tofu r a n o-
sid e (5). As described for the synthesis of compound 4,
transglycosylation was carried out starting from compound 3
(0.6 g, 2.71 mmol)) by treatment with BF3‚OEt2 (0.272 mL, 2.16
mmol) and phenylselenol (0.316 mL, 2.97 mmol) in 8 mL of
anhydrous dichloromethane. After 15 min workup provided a
reaction crude which was purified by flash chromatography in
hexane using polarity gradient with ethyl acetate to give 0.57 g
(61%) of the 1-seleno glycoside 5 as an anomeric mixture. This
R/â mixture was separated by radial chromatography using ethyl
acetate/hexane ) 1:60 to give 0.38 g of R anomer and 0.19 g of
â anomer as syrups. 5R: [R]25 +215.6° (c ) 1.0, CHCl3); 1H
D
NMR (CDCl3) δ 7.68-7.16 (m, 10H), 6.01 (dd, 1H, J ) 2.9, 6.7
Hz), 4.56 (s, 2H), 4.51-4.38 (m, 1H), 3.59 (dd, 1H, J ) 4.3, 10.4
Hz), 3.55 (dd, 1H, J ) 4.9, 10.5 Hz), 2.51-2.37 (m, 1H), 2.17-
2.01 (m, 2H), 1.83-1.70 (m, 1H); 13C NMR (CDCl3) δ 138.2,
133.9, 128.9, 128.3, 127.6, 127.2, 84.8, 78.0, 73.3, 71.5, 33.6, 27.0.
Anal. Calcd for C18H20O2Se: C, 62.25: H, 5.80. Found: C,
1
62.47; H, 5.84. 5â: [R]25 -117.6° (c ) 0.98, CHCl3); H NMR
D
(CDCl3) δ 7.72-7.16 (m, 10H), 5.86 (dd, 1H, J ) 2.9, 6.5 Hz),
4.57 (s, 2H), 4.40-4.27 (m, 1H), 3.67 (dd, 1H, J ) 6.4, 10.1 Hz),
3.56 (dd, 1H, J ) 4.9, 10.1 Hz), 2.47-2.33, 2.28-2.17, 2.13-
2.05, 1.94-1.80 (complex multiplets, 4H); 13C NMR (CDCl3) δ
134.8, 134.1, 129.6, 128.9, 128.3, 127.6, 127.5, 127.3, 84.0, 80.8,
73.4, 73.2, 28.0. Anal. Calcd for C18H20O3Se: C, 62.25: H, 5.80.
Found: C, 62.31; H, 5.83.
6-Ch lor o-9-[5-O-(ter t-b u t yld ip h en ylsilyl)-3-d eoxy-2-Se-
p h e n yl-2-se le n o-â,r-D -er yt h r o-p e n t ofu r a n osyl]-9H -p u -
r in e (116a a n d 15). A solution of glycal 6 (0.084 g, 0.25 mmol)
in 1 mL of anhydrous ether at room temperature was allowed
to react with phenylselenenyl chloride (0.072 g, 0.37 mmol)
(1S)-1-[(Ben zyloxy)m eth yl]-2,3-d ih yd r ofu r a n (7). Using
a procedure similar to that used for 6, compound 5 (0.5 g, 1.45