3546 J . Org. Chem., Vol. 67, No. 11, 2002
Kumamoto and Tanaka
°C for 90 min with stirring. The resulting oily substance (12)
was kept under reduced pressure for 30 min. NMR data of 12
are as follows: 119Sn NMR (benzene-d6) δ 58.3, 86.3, 107.5;
partial 1H NMR data (benzene-d6) δ 2.01 (3H, m), 3.68 (1H,
ddd, J ) 4.4, 11.2, 28.0 Hz), 3.93 (1H, ddd, J ) 3.6, 11.2, 28.0
Hz), 4.63-4.64 (1H, m), 5.20-5.22 (1H, m), 5.77-5.80 (1H,
m), 7.34-7.37 (1H, m), 7.56-7.57 (1H, m).
The above prepared 12 was dissolved in benzene (3 mL),
and reacted with benzoyl chloride (137 µL, 1.18 mmol) for 1 h
at room temperature. The reaction mixture was partitioned
between CHCl3 and saturated aqueous NaHCO3. Silica gel
column chromatography (CHCl3/MeOH ) 20:1) of the organic
layer gave 13 (176 mg, 91%) as a solid. For physical data of
13, see ref 21.
LTMP Lith ia tion of 12: F or m a tion of 2′,3′-Did eh yd r o-
3′-d eoxy-3′-C-(tr ibu tylsta n n yl)th ym id in e (14) a n d Its 2′-
C-Sta n n yla ted isom er (15). Compound 12 used in this
reaction was prepared from 1.0 g (4.46 mmol) of 1. To a THF
(20 mL) solution of 2,2,6,6-tetramethylpiperidine (3.76 mL,
22.3 mmol) and HMPA (11.6 mL, 66.9 mmol) was added BuLi
(1.5 M in hexane, 15 mL, 22.3 mmol) below -70 °C under
positive pressure of dry Ar. After the mixture was stirred for
5 min, TMEDA (3.37 mL, 22.3 mmol) was added to the LTMP
solution and the whole was stirred for a further 5 min. To this
was added dropwise a solution of the above prepared 12 in
THF (20 mL) while the temperature was kept below -70 °C.
The reaction mixture was stirred for 15 min and then
partitioned between EtOAc and saturated aqueous NH4Cl. The
aqueous layer was evaporated, dried, and treated with Ac2O
(4.2 mL, 44.6 mmol) in pyridine (40 mL) at room temperature
for 3 h. Silica gel column chromatography (hexane/EtOAc )
1:2) of the reaction mixture gave the 5′-O-acetate25 (95 mg,
8%) of 1. The EtOAc layer was subjected to silica gel column
chromatography (hexane/EtOAc ) 5:2) to give 14 (1.38 g, 60%)
as an oil. Elution with hexane/EtOAc ) 1:1 gave 15 (206 mg,
9%) as an oil. Physical data of 14: UV (MeOH) λmax 267 nm (ꢀ
7600), λmin 238 nm (ꢀ 1900); 1H NMR (CDCl3) δ 0.85-0.99 (9H,
m), 1.03-1.14, 1.27-1.51, and 1.52-1.62 (18H, each as m),
1.85 (3H, d, J ) 1.1 Hz), 2.17-2.20 (1H, m), 3.72 (1H, ddd, J
) 4.0, 5.1, 12.2 Hz), 3.94 (1H, ddd, J ) 2.9, 6.1, 12.2 Hz), 4.97-
5.00 (1H, m), 5.74-5.81 (1H, m), 6.95-6.98 (1H, m), 7.37 (1H,
q, J ) 1.1 Hz), 8.19 (1H, br); FAB-MS m/z 513 (M+ + H). Anal.
Calcd for C22H38N2O4Sn: C, 51.48; H, 7.46; N, 5.46. Found:
C, 51.60; H, 7.66; N, 5.34. Physical data of 15: UV (MeOH)
(1H, dd, J ) 1.3, 11.9 Hz), 4.17 (1H, dd, J ) 2.6, 11.9 Hz),
4.77-4.80 (1H, m), 6.28 (1H, t, J ) 1.5 Hz), 6.95 (1H, dd, J )
1.5, 4.2 Hz), 7.24 (1H, q, J ) 1.3 Hz), 7.33-7.44 (6H, m), 7.63-
7.70 (4H, m), 8.13 (1H, br); FAB-MS m/z 589 (M+ + H). Anal.
Calcd for C26H29IN2O4Si: C, 53.06; H, 4.97; N, 4.76. Found:
C, 53.05; H, 4.90; N, 4.56.
3′-Br om o-2′,3′-dideh ydr o-3′-deoxyth ym idin e (17). A mix-
ture of 14 (185 mg, 0.36 mmol) and NBS (95 mg, 0.54 mmol)
in THF (5 mL) was stirred for 4 h at room temperature. The
reaction mixture was partitioned between CHCl3 and satu-
rated aqueous NaHCO3. Silica gel column chromatography
(CHCl3/MeOH ) 20:1) of the organic layer gave 17 (108 mg,
100%) as a foam: UV (MeOH) λmax 264 nm (ꢀ 9700), λmin 236
nm (ꢀ 2800); 1H NMR (CDCl3) δ 1.88 (3H, d, J ) 1.3 Hz), 2.35-
2.38 (1H, m), 3.96 (1H, ddd, J ) 2.2, 5.0, 12.8 Hz), 4.04 (1H,
ddd, J ) 2.0, 5.7, 12.8 Hz), 4.78-4.80 (1H, m), 6.02 (1H, t, J
) 1.7 Hz), 6.98 (1H, dd, J ) 1.7, 3.7 Hz), 7.62 (1H, q, J ) 1.3
Hz), 8.64 (1H, br). Anal. Calcd for C10H11BrN2O4: C, 39.62;
H, 3.66; N, 9.24. Found: C, 39.67; H, 3.49; N, 9.01. This
compound gave no assignable ion peak in FAB-MS and thus
was converted to its 5′-O-acetate [FAB-MS m/z 345 and 347
(M+ + H)] by a conventional procedure.
2′,3′-Did eh yd r o-3′-d eoxy-3′-C-p h en ylth ym id in e (18). A
mixture of 14 (167 mg, 0.33 mmol), PhI (110 µL, 0.99 mmol),
Pd(PPh3)4 (38 mg, 0.033 mmol), and CuI (12 mg, 0.066 mmol)
in DMF (1.85 mL) was stirred at room temperature for 12 h
under positive pressure of dry Ar. The reaction mixture was
partitioned between EtOAc and saturated aqueous NaHCO3.
Silica gel column chromatography (hexane/EtOAc ) 1:6) of the
organic layer gave 18 (95 mg, 97%) as a foam: UV (MeOH)
λ
max 254 nm (ꢀ 17 800), λmin 224 nm (ꢀ 6800); 1H NMR (CDCl3)
δ 1.84 (3H, d, J ) 1.3 Hz), 3.25 (1H, br), 3.90-3.94 (1H, m),
4.01-4.10 (1H, m), 5.35-5.36 (1H, m), 5.98 (1H, t, J ) 1.6
Hz), 7.15 (1H, dd, J ) 1.6, 3.1 Hz), 7.36-7.45 (5H, m), 7.68
(1H, q, J ) 1.3 Hz), 9.22 (1H, br); FAB-MS m/z 301 (M+ + H).
Anal. Calcd for C16H16N2O4: C, 63.99; H, 5.37; N, 9.33.
Found: C, 63.73; H, 5.17; N, 9.41.
3′-C-Ben zyl-2′,3′-dideh ydr o-3′-deoxyth ym idin e (19). This
compound was prepared from 14 (355 mg, 0.65 mmol) by the
procedure described for the preparation of 18. The following
amounts of reagents were used: benzyl bromide (195 µL, 1.63
mmol), Pd(PPh3)4 (75 mg, 0.065 mmol), and CuI (25 mg, 0.13
mmol) in DMF (2.0 mL). Compound 19 (160 mg, 78%) was
obtained as a foam after silica gel column chromatography
(hexane/EtOAc ) 1:6): UV (MeOH) λmax 265 nm (ꢀ 9900), λmin
234 nm (ꢀ 2500); 1H NMR (CDCl3) δ 1.82 (3H, d, J ) 1.2 Hz),
3.27 (1H, m), 3.43 (1H, d, J ) 16.6 Hz), 3.68 (1H, d, J ) 16.6
Hz), 3.84 (1H, ddd, J ) 2.4, 6.3, 12.8 Hz), 3.95 (1H, ddd, J )
2.4, 5.5, 12.8 Hz), 4.67-4.70 (1H, m), 5.31-5.32 (1H, m), 6.97-
6.98 (1H, m), 7.22-7.27 (3H, m), 7.31-7.35 (2H, m), 7.52 (1H,
q, J ) 1.2 Hz), 8.81 (1H, br); FAB-MS m/z 315 (M+ + H). Anal.
Calcd for C17H18N2O4‚1/5H2O: C, 64.21; H, 5.83; N, 8.81.
Found: C, 63.95; H, 5.62; N, 8.53.
λ
max 267 nm (ꢀ 9100), λmin 238 nm (ꢀ 2600); 1H NMR (CDCl3) δ
0.80-1.03 and 1.20-1.68 (27H, each as m), 1.83 (3H, d, J )
1.1 Hz), 2.92-2.95 (1H, m), 3.77 (1H, ddd, J ) 3.5, 6.1, 12.5
Hz), 3.96 (1H, ddd, J ) 2.8, 6.1, 12.5 Hz), 4.86-4.89 (1H, m),
6.26-6.32 (1H, m), 7.13-7.15 (1H, m), 7.36 (1H, q, J ) 1.1
Hz), 8.48 (1H, br); FAB-MS m/z 513 (M+ + H). Anal. Calcd for
C
22H38N2O4Sn: C, 51.48; H, 7.46; N, 5.46. Found: C, 51.34;
H, 7.65; N, 5.34.
2′,3′-Did eh yd r o-3′-d eoxy-3′-iod oth ym id in e (16). A mix-
ture of 14 (100 mg, 0.19 mmol) and iodine (73 mg, 0.29 mmol
as I2) in THF (4 mL) was stirred for 1 h at room temperature.
The reaction mixture was partitioned between CHCl3 and
saturated aqueous Na2S2O3. Silica gel column chromatography
(CHCl3/MeOH ) 30:1) of the organic layer gave 16 (62 mg,
93%) as a solid: mp 104-108 °C; UV (MeOH) λmax 264 nm (ꢀ
10 900), λmin 238 nm (ꢀ 4000); 1H NMR (CDCl3) δ 1.87 (3H, d,
J ) 1.3 Hz), 2.25 (1H, br), 3.95 (1H, ddd, J ) 2.0, 5.3, 12.8
Hz), 4.08 (1H, ddd, J ) 2.3, 5.7, 12.8 Hz), 4.75-4.78 (1H, m),
6.21 (1H, t, J ) 1.6 Hz), 6.97 (1H, dd, J ) 1.6, 3.7 Hz), 7.58
(1H, q, J ) 1.3 Hz), 8.25 (1H, br); FAB-MS m/z 351 (M+ + H).
Anal. Calcd for C10H11IN2O4: C, 34.31; H, 3.17; N, 8.00.
Found: C, 34.39; H, 3.03; N, 7.92.
5′-O-(ter t-Bu tyld ip h en ylsilyl)-3′-iod o-d 4T (8). A mixture
of 16 (84 mg, 0.24 mmol), tert-butyldiphenylsilyl chloride (125
µL, 0.48 mmol), and imidazole (49 mg, 0.72 mmol) in DMF
(3.0 mL) was stirred for 1 h at room temperature. The reaction
mixture was partitioned between EtOAc and saturated aque-
ous NaHCO3. Silica gel column chromatography (hexane/
EtOAc ) 2:1) of the organic layer gave 8 (102 mg, 72%) as a
foam: UV (MeOH) λmax 265 nm (ꢀ 6800), λmin 239 nm (ꢀ 2500);
1H NMR (CDCl3) δ 1.11 (3H, d, J ) 1.3 Hz), 1.12 (9H, s), 4.11
3′-C-Allyl-2′,3′-d id eh yd r o-3′-d eoxyth ym id in e (20). This
compound was prepared from 14 (307 mg, 0.60 mmol) by the
procedure described for the preparation of 18. The following
amounts of reagents were used: allyl bromide (155 µL, 1.8
mmol), Pd(PPh3)4 (70 mg, 0.06 mmol), and CuI (22 mg, 0.12
mmol) in DMF (2.0 mL). Compound 20 (110 mg, 73%) was
obtained as a foam after silica gel column chromatography
(hexane/EtOAc ) 1:4): UV (MeOH) λmax 269 nm (ꢀ 15 100),
λmin 239 nm (ꢀ 12 600); 1H NMR (CDCl3) δ 1.87 (3H, d, J ) 1.1
Hz), 2.17-2.21 (1H, m), 2.88-2.94 (1H, m), 3.04-3.10 (1H,
m), 3.81-3.86 (1H, m), 3.93-3.98 (1H, m), 4.73-4.74 (1H, m),
5.18-5.21 (1H, m), 5.21-5.24 (1H, m), 5.46-5.50 (1H, m),
5.83-5.93 (1H, m), 6.95-6.96 (1H, m), 7.51 (1H, q, J ) 1.1
Hz), 8.10 (1H, br); FAB-MS m/z 265 (M+ + H). Anal. Calcd for
C
13H16N2O4‚1/4H2O: C, 58.09; H, 6.19; N, 10.42. Found: C,
57.82; H, 6.19; N, 10.11.
2′,3′-Did eh yd r o-3′-d eoxy-3′-C-(â-styr yl)th ym id in e (21).
This compound was prepared from 14 (314 mg, 0.61 mmol) by
the procedure described for the preparation of 18. The follow-
ing amounts of reagents were used: â-bromostyrene (195 µL,
1.53 mmol, E/Z ) 7:1), Pd(PPh3)4 (70 mg, 0.06 mmol), and CuI
(23 mg, 0.12 mmol) in DMF (2.5 mL). Compound 21 (161 mg,