Stereodivergent Approaches
J . Org. Chem., Vol. 65, No. 18, 2000 5587
1H), 3.92 (dd, 1H, J ) 6.1, 9.9 Hz), 4.01-4.23 (m, 4H), 5.64
(d, 1H, J ) 7.8 Hz), 6.07 (dd, 1H, J ) 3.4, 7.1 Hz), 7.25-7.40
(m, 6H), 8.31 (bs, 1H); 13C NMR δ 23.7, 26.8, 28.4, 37.1, 56.4,
60.6, 63.7, 65.2, 80.8, 83.4, 94.2, 102.4, 127.7, 128.4, 128.7,
136.2, 139.6, 149.9, 156.0, 162.5. Anal. Calcd for C24H32N4O6:
C, 61.00; H, 6.83; N, 11.86. Found: C, 60.92; H, 6.96; N, 11.76.
1-{(3R,5R)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-(ter t-bu tyld ip h en ylsiloxy)eth yl]isoxa zolid in -5-yl}-
u r a cil (37). The starting materials, an anomeric mixture of
18a and 18b (0.124 g, 0.2 mmol) and bis(trimethylsilyl)-
thymine (0.203 g, 0.75 mmol), gave after chromatographic
purification (toluene/ethyl acetate, 70:30) 37 (0.105 g, 77%) as
an oil: [R]D +16.6 (c 0.32, CHCl3); 1H NMR δ 1.07 (s, 9H), 1.46
(s, 9H), 1.80 (bs, 3H), 2.40 (ddd, 1H, J ) 5.4, 7.3, 13.8 Hz),
2.80 (ddd, 1H, J ) 7.0, 8.0, 13.8 Hz), 3.50 (q, 1H, J ) 6.4 Hz),
3.72 (dd, 1H, J ) 4.5, 9.8 Hz), 3.89-3.99 (m, 2H), 4.02 (d, 1H,
J ) 14.1 Hz), 4.18 (d, 1H, J ) 14.1 Hz), 4.79 (d, 1H, J ) 8.5
Hz), 5.95 (dd, 1H, J ) 5.4, 7.0 Hz), 7.04 (bs, 1H), 7.25-7.45
(m, 11H), 7.57-7.66 (m, 4H), 8.15 (bs, 1H); 13C NMR δ 12.3,
19.3, 27.0, 28.4, 37.1, 51.8, 60.5, 64.1, 64.6, 80.0, 85.5, 110.3,
127.7 (2C), 127.9, 128.4, 129.1, 130.0 (2C), 133.0, 134.8, 135.6
(2C), 135.8, 136.4, 150.0, 155.6, 163.3. Anal. Calcd for
C38H48N4O6Si: C, 66.64; H, 7.06; N, 8.18. Found: C, 66.38; H,
7.19; N, 8.34.
4.07 (d, 1H, J ) 13.3 Hz), 4.13 (d, 1H, J ) 13.3 Hz), 5.59 (d,
1H, J ) 8.1 Hz), 6.03 (t, 1H, J ) 6.4 Hz), 7.26-7.36 (m, 5H),
7.38 (d, 1H, J ) 8.1 Hz), 8.07 (bs, 1H); 13C NMR δ 23.9, 27.5,
28.4, 37.6, 57.7, 62.3, 65.9, 66.4, 81.1, 87.6, 94.5, 101.8, 128.0,
128.6, 128.9, 136.2, 139.9, 149.8, 156.6, 162.5. Anal. Calcd for
C
24H32N4O6: C, 61.00; H, 6.83; N, 11.86. Found: C, 61.28; H,
6.96; N, 12.13.
1-{(3S,5R)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-h yd r oxyeth yl]isoxa zolid in -5-yl}th ym in e (33a ). The
method described above to convert 9 to 10 was applied to 31a
(88 mg, 0.18 mmol) to give, after column chromatography
(ethyl acetate), 33a (72 mg, 90%) as a white solid: mp 157-
159 °C; [R]D -11.7 (c 0.89, CHCl3); 1H NMR δ 1.41 (s, 9H),
1.78 (d, 3H, J ) 1.1 Hz), 2.35 (ddd, 1H, J ) 4.2, 7.4, 13.9 Hz),
2.57 (bs, 1H), 2.99 (ddd, 1H, J ) 7.1, 9.0, 13.9 Hz), 3.43 (ddd,
1H, J ) 4.5, 7.4, 9.0 Hz), 3.60 (dd, 1H, J ) 5.9, 11.0 Hz), 3.68
(dd, 1H, J ) 4.8, 11.0 Hz), 3.75-3.86 (m, 1H), 3.93 (d, 1H,
J ) 13.7 Hz), 4.23 (d, 1H, J ) 13.7 Hz), 5.12 (d, 1H, J ) 9.0
Hz), 6.00 (dd, 1H, J ) 4.2, 7.1 Hz), 7.26 (q, 1H, J ) 1.1 Hz),
7.27-7.39 (m, 5H), 8.89 (bs, 1H); 13C NMR δ 12.3, 28.4, 40.4,
53.3, 62.5, 63.1, 64.9, 80.3, 83.6, 110.2, 127.9, 128.6, 129.2,
135.6, 136.7, 150.6, 156.0, 163.8. Anal. Calcd for C22H30N4O6:
C, 59.18; H, 6.77; N, 12.55. Found: C, 59.37; H, 6.90; N, 12.73.
1-{(3S,5S)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-h yd r oxyeth yl]isoxa zolid in -5-yl}th ym in e (33b). The
method described above to convert 9 to 10 was applied to 31b
(73 mg, 0.15 mmol) to give, after column chromatography
(ethyl acetate), 33b (55 mg, 82%) as an oil: [R]D -45.0 (c 1.26,
CHCl3); 1H NMR δ 1.44 (s, 9H), 1.82 (d, 3H, J ) 1.1 Hz), 2.61
(ddd, 1H, J ) 5.8, 8.2, 13.9 Hz), 2.63 (bs, 1H), 2.86 (ddd, 1H,
J ) 4.4, 7.2, 13.9 Hz), 3.54-3.83 (m, 4H), 4.10 (d, 1H, J )
13.6 Hz), 4.16 (d, 1H, J ) 13.6 Hz), 5.15 (d, 1H, J ) 8.7 Hz),
5.97 (dd, 1H, J ) 5.8, 7.0 Hz), 7.10 (q, 1H, J ) 1.1 Hz), 7.25-
7.38 (m, 5H), 8.66 (bs, 1H); 13C NMR δ 12.2, 28.3, 38.0, 53.5,
62.3, 63.1, 64.5, 80.2, 86.5, 110.6, 128.0, 128.5, 129.0, 135.4,
135.9, 150.1, 156.0, 163.4. Anal. Calcd for C22H30N4O6: C,
59.18; H, 6.77; N, 12.55. Found: C, 59.02; H, 6.91; N, 12.66.
1-{(3S,5R)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-h yd r oxyeth yl]isoxa zolid in -5-yl}u r a cil (34a ). The
method described above to convert 9 to 10 was applied to 32a
(85 mg, 0.18 mmol) to give, after column chromatography
(ethyl acetate), 34a (69 mg, 88%) as an oil: [R]D -16.2 (c 0.65,
1-{(3R,5S)-2-Ben zyl-3-[(4R)-3-(ter t-bu toxyca r bon yla m i-
n o)-2,2-d im et h yl-1,3-oxa zolid in -4-yl]isoxa zolid in -5-yl}-
t h ym in e (41a ) a n d 1-{(3R,5R)-2-Ben zyl-3-[(4R)-2,2-d i-
m et h yl-3-(ter t-b u t oxyca r b on yla m in o)-1,3-oxa zolid in -4-
yl]isoxa zolid in -5-yl}th ym in e (41b). The starting materials,
an anomeric mixture of 22a and 22b (0.210 g, 0.5 mmol) and
bis(trimethylsilyl)thymine (0.540 g, 2 mmol), gave, after
chromatographic purification (cyclohexane/ethyl acetate, 50:
50), pure 41a and 41b. For 41a : 0.109 g, 45%; sticky foam;
[R]D -18.8 (c 0.85, CHCl3); 1H NMR δ 1.47 (s, 9H), 1.50 (s,
3H), 1.55 (s, 3H), 1.80 (s, 3H), 2.19-2.39 (m, 1H), 2.94 (td,
1H, J ) 7.7, 13.4 Hz), 3.36 (dt, 1H, J ) 4.3, 7.8 Hz), 3.80 (d,
1H, J ) 13.5 Hz), 3.84-3.93 (m, 1H), 3.97 (dd, 1H, J ) 6.5,
9.0 Hz), 4.16-4.24 (m, 1H), 4.37 (d, 1H, J ) 13.5 Hz), 6.02
(bs, 1H), 7.16-7.54 (m, 6H), 8.52 (bs, 1H); 13C NMR δ 12.3,
23.9, 27.04, 28.3, 39.1, 57.2, 61.7, 65.0, 66.9, 80.9, 83.1, 94.8,
109.8, 127.7, 128.4, 129.08, 136.51, 137.0, 150.5, 153.7, 164.1.
Anal. Calcd for C25H34N4O6: C, 61.71; H, 7.04; N, 11.51.
Found: C, 61.79; H, 6.87; N, 11.42. For 41b: 90 mg, 37%; oil;
1
CHCl3); H NMR δ 1.40 (s, 9H), 2.37 (ddd, 1H, J ) 4.0, 7.3,
1
[R]D -10.5 (c 0.60, CHCl3); H NMR δ 1.50 (bs, 12H), 1.52 (s,
14.0 Hz), 2.96 (bs, 1H, ex. D2O), 3.01 (ddd, 1H, J ) 7.2, 9.0,
14.0 Hz), 3.41 (dt, 1H, J ) 4.3, 8.2 Hz), 3.59 (dd, 1H, J ) 5.9,
10.7 Hz), 3.68 (dd, 1H, J ) 4.3, 10.7 Hz), 3.74-3.85 (m, 1H),
3.92 (d, 1H, J ) 13.8 Hz), 4.22 (d, 1H, J ) 13.8 Hz), 5.25 (bs,
1H), 5.56 (d, 1H, J ) 8.2 Hz), 6.01 (dd, 1H, J ) 4.0, 7.2 Hz),
3H), 1.78 (s, 3H), 2.54 (td, 1H, J ) 7.0, 13.6 Hz), 2.79-3.08
(m, 1H), 3.52 (dt, 1H, J ) 3.2, 7.5 Hz), 3.86-3.93 (m, 2H), 4.09
(dd, 1H, J ) 7.1, 14.2 Hz), 4.10 (s, 2H), 6.00 (t, 1H, J ) 6.5
Hz), 7.13 (d, 1H, J ) 1.2 Hz), 7.26-7.40 (m, 5H), 8.77 (bs, 1H);
13C NMR δ 12.3, 23.8, 27.5, 28.4, 37.5, 57.8, 62.1, 66.0, 66.4,
81.0, 87.3, 94.5, 110.2, 127.9, 128.6, 128.9, 135.9, 136.4, 150.1,
154.2, 163.7. Anal. Calcd for C25H34N4O6: C, 61.71; H, 7.04;
N, 11.51. Found: C, 61.52; H, 6.79; N, 11.36.
7.25-7.38 (m, 5H), 7.47 (d, 1H, J ) 8.2 Hz), 9.53 (bs, 1H); 13
C
NMR δ 28.3, 40.3, 53.0, 62.5, 62.7, 65.0, 80.2, 83.7, 101.7, 127.8,
128.5, 129.1, 136.4, 139.8, 150.5, 155.9, 163.6. Anal. Calcd for
C
21H28N4O6: C, 58.32; H, 6.53; N, 12.96. Found: C, 58.49; H,
1-{(3R,5S)-2-Ben zyl-3-[(4R)-3-(ter t-bu toxyca r bon yla m i-
n o)-2,2-d im et h yl-1,3-oxa zolid in -4-yl]isoxa zolid in -5-yl}-
u r a cil (42a ) a n d 1-{(3R,5R)-2-Ben zyl-3-[(4R)-2,2-dim eth yl-
3-(ter t-b u t oxyca r b on yla m in o)-1,3-oxa zolid in -4-yl]isox-
a zolid in -5-yl}u r a cil (42b). The starting materials, an ano-
meric mixture of 22a and 22b (0.210 g, 0.5 mmol) and bis-
(trimethylsilyl)uracil (0.513 g, 2 mmol), gave, after chromato-
graphic purification (cyclohexane/ethyl acetate, 50:50), pure
42a and 42b. For 42a : 89 mg, 38%; oil; [R]D -35.9 (c 1.40,
6.22; N, 13.15.
1-{(3S,5S)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-h yd r oxyeth yl]isoxa zolid in -5-yl}u r a cil (34b). The
method described above to convert 9 to 10 was applied to 32b
(66 mg, 0.14 mmol) to give, after column chromatography
(ethyl acetate), 34b (50 mg, 83%) as an oil: [R]D -40.8 (c 0.42,
1
CHCl3); H NMR δ 1.41 (s, 9H), 2.58 (ddd, 1H, J ) 5.4, 8.1,
13.7 Hz), 2.86 (ddd, 1H, J ) 5.0, 7.0, 13.7 Hz), 3.19 (bs, 1H,
ex. D2O), 3.52-3.70 (m, 3H), 3.77 (dt, 1H, J ) 4.3, 9.2 Hz),
4.07 (d, 1H, J ) 13.5 Hz), 4.13 (d, 1H, J ) 13.5 Hz), 5.32 (d,
1H, J ) 8.6 Hz), 5.62 (d, 1H, J ) 8.1 Hz), 5.96 (dd, 1H, J )
5.4, 7.0 Hz), 7.24-7.33 (m, 5H), 7.35 (d, 1H, J ) 8.1 Hz), 9.71
(bs, 1H); 13C NMR δ 28.3, 38.1, 53.4, 62.2, 62.9, 64.3, 80.1,
86.4, 102.1, 127.9, 128.6, 129.0, 136.1, 139.8, 150.3, 156.1,
163.5. Anal. Calcd for C21H28N4O6: C, 58.32; H, 6.53; N, 12.96.
Found: C, 58.44; H, 6.49; N, 12.88.
1
CHCl3); H NMR δ 1.46 (s, 3H), 1.47 (s, 12H), 2.28-2.44 (m,
1H), 2.94 (td, 1H, J ) 8.5, 13.8 Hz), 3.27-3.40 (m, 1H), 3.33
(dt, 1H, J ) 4.6, 7.8 Hz), 3.82 (d, 1H, J ) 13.5 Hz), 3.97 (dd,
1H, J ) 6.5, 9.2 Hz), 4.13-4.21 (m, 1H), 4.37 (d, 1H, J ) 13.5
Hz), 5.55 (d, 1H, J ) 8.2 Hz), 5.99-6.09 (m, 1H), 7.26-7.47
(m, 5H), 7.63 (d, 1H, J ) 8.2 Hz), 8.29 (bs, 1H); 13C NMR δ
23.8, 27.0, 28.3, 39.1, 57.2, 62.1, 64.9, 67.0, 80.9, 83.6, 94.8,
101.4, 127.7, 128.3, 129.1, 136.7, 140.3, 150.3, 156.4, 162.9.
Anal. Calcd for C24H32N4O6: C, 61.00; H, 6.83; N, 11.86.
Found: C, 60.88; H, 7.00; N, 11.74. Fpr 42b: 0.100 g, 42%;
1-{(3R,5R)-2-Ben zyl-3-[(1R)-1-(ter t-bu toxyca r bon yla m i-
n o)-2-h yd r oxyeth yl]isoxa zolid in -5-yl}th ym in e (38). F r om
37. The method described above to convert 13a to 12a was
applied to 31a (88 mg, 0.18 mmol) to give, after column
chromatography (chloroform/methanol, 95:5), 38 (74 mg, 92%)
as a white solid: mp 100-102 °C; [R]D +23.0 (c 0.36, MeOH);
1H NMR δ 1.46 (s, 9H), 1.84 (s, 3H), 2.53 (ddd, 1H, J ) 5.7,
1
oil; [R]D -4.8 (c 0.60, CHCl3); H NMR δ 1.48 (s, 3H), 1.50 (s,
9H), 1.51 (s, 3H), 2.52 (ddd, 1H, J ) 6.3, 7.0, 13.8 Hz), 2.87-
3.02 (m, 1H), 3.49 (dt, 1H, J ) 3.3, 7.6 Hz), 3.83 (dd, 1H, J )
1.4, 9.0 Hz), 3.90 (dd, 1H, J ) 5.3, 9.0 Hz), 4.06-4.14 (m, 1H),