T. Osaki et al. / Tetrahedron 63 (2007) 8977–8986
8983
49%) and 14 (122 mg, 21%) as colorless oils. Compound 13:
[a]2D1 +3.1 (c 0.98, CHCl3). IR (KBr) nmax 3479, 2951, 2887,
(1H, dd, J¼2, 11 Hz), 5.50 (2H, s), 5.55 (1H, s), 6.11 (1H,
dd, J¼5, 10 Hz), 7.13 (1H, s), 7.25–7.41 (13H, m), 7.46
(2H, m). 13C NMR (CDCl3) d 13.6, 37.0, 55.8, 66.3, 68.7,
68.9, 70.5, 71.6, 72.2, 79.8, 85.3, 85.8, 96.0, 101.3, 110.3,
126.1, 127.0, 127.4, 127.5, 127.6, 128.2, 128.3, 128.3,
129.0, 133.6, 137.0, 138.3, 150.6, 163.1. MS (FAB): m/z
645 (MH+). Anal. Calcd for C36H40N2O9$1/2H2O: C,
66.14; H, 6.25; N, 4.29. Found: C, 66.15; H, 6.26; N, 4.24.
1
1707, 1664, 1460 cmꢁ1. H NMR (CDCl3) d 1.64 (3H, d,
J¼1 Hz), 2.11 (1H, dd, J¼10, 13 Hz), 2.67 (1H, dd, J¼5,
13 Hz), 2.80 (1H, dd, J¼3, 10 Hz), 3.34 (3H, s), 3.51 (1H,
t, J¼10 Hz), 3.82 (1H, d, J¼11 Hz), 3.88 (1H, d,
J¼11 Hz), 3.99–4.07 (3H, m), 4.50–4.64 (6H, m), 4.67
(2H, s), 5,46 (2H, s), 6.38 (1H, dd, J¼5, 10 Hz), 7.23–7.36
(15H, m), 7.80 (1H, d, J¼1 Hz). 13C NMR (CDCl3)
d 13.0, 37.2, 56.3, 63.5, 64.3, 65.3, 70.4, 72.1, 73.1, 73.9,
84.1, 86.0, 90.2, 96.8, 110.0, 127.0,127.5, 127.6, 127.6,
127.8, 128.1, 128.2, 128.4, 128.6, 134.7, 136.6. MS
(FAB): m/z 647 (MH+). HRMS (FAB): calcd for
C36H43N2O9 (MH+): 647.2969; found: 647.2980. Com-
pound 14: [a]D21 +23.0 (c 0.85, CHCl3). IR (KBr) nmax
4.1.9. 30-O,50-O-Dibenzyl-3-N-benzyloxymethyl-40-C-hy-
droxymethyl-30-C-(methoxymethyloxymethyl)thymidine
(13). To a solution of 12 (580 mg, 1.04 mmol) in CH2Cl2
(18 mL) were added Et3N (0.29 mL, 2.08 mmol) and 4,40-di-
methoxytrityl chloride (459 mg, 1.36 mmol) at room tem-
perature, and the mixture was stirred for 10 min. After
addition of saturated NaHCO3 solution, the reaction mixture
was extracted with AcOEt. The combined organic layers
were washed with H2O and saturated NaCl solution, dried
over Na2SO4, and concentrated under reduced pressure.
The yellow residue containing 16 was co-evaporated with
toluene. To a suspension of 60% sodium hydride (83 mg,
2.08 mmol) in DMF (3 mL) was added the residue in DMF
(7 mL) with ice-cooling. After stirring for 30 min, benzyl
bromide (0.15 mL, 1.25 mmol) and n-Bu4NI (192 mg,
0.52 mmol) were added and the mixture was stirred for 2 h
at room temperature. After addition of H2O, the mixture
was extracted with Et2O. The organic layer was washed
with H2O and saturated NaCl solution, dried over MgSO4,
and concentrated under reduced pressure. The yellow oily
residue was dissolved without further treatment in CH2Cl2/
MeOH (1:1, v/v, 14 mL), to which (+)-10-camphorsulfonic
acid (73 mg, 0.31 mmol) was added, and the mixture was
stirred for 10 min. After addition of saturated NaHCO3 solu-
tion, the mixture was extracted with AcOEt. The usual work-
up and purification by silica gel column chromatography
(AcOEt/n-hexane¼2:3) afforded 13 (559 mg, 83% over
three steps).
3453, 2935, 1706, 1660, 1461, 1095 cmꢁ1 1H NMR
.
(CDCl3) d 1.94 (3H, d, J¼1 Hz), 2.17 (1H, dd, J¼9,
14 Hz), 2.80 (1H, dd, J¼5, 14 Hz), 3.20 (1H, dd, J¼5,
7 Hz), 3.35 (3H, s), 3.81, 3.96 (2H, AB, J¼11 Hz), 3.84,
3.98 (2H, AB, J¼10 Hz), 3.87 (1H, dd, J¼7, 12 Hz), 4.04
(1H, dd, J¼5, 12 Hz), 4.48 (1H, d, J¼12 Hz), 4.59–4.63
(5H, m), 4.69 (2H, s), 5.49 (2H, s), 6.21 (1H, dd, J¼5,
9 Hz), 7.24–7.38 (15H, m), 7.82 (1H, d, J¼1 Hz). 13C
NMR (CDCl3) d 13.4, 36.9, 56.0, 64.9, 65.0, 66.1, 70.4,
72.2, 72.5, 73.8, 86.1, 86.2, 89.9, 96.8, 109.9, 126.9,
127.4, 127.5, 127.5, 127.6, 128.2, 128.3, 128.3, 135.3,
137.7, 137.8, 137.9. MS (FAB): m/z 647 (MH+). Anal. Calcd
for C36H42N2O9$3/4H2O: C, 65.46; H, 6.37; N, 4.30. Found:
C, 65.49; H, 6.64; N, 4.24.
4.1.8. 30-O-Benzyl-3-N-benzyloxymethyl-40-CH2O,50-O-
benzylidene-30-C-(methoxymethyloxymethyl)thymidine
(15). To a solution of 12 (53 mg, 0.095 mmol) in CH2Cl2
(1 mL) were added benzaldehyde dimethyl acetal (68 mL,
0.48 mmol) and (+)-10-camphorsulfonic acid (4 mg,
0.019 mmol) at room temperature, and the mixture was
stirred for 2 h at the same temperature. After addition of sat-
urated NaHCO3 solution, the mixture was extracted with
AcOEt. The usual work-up and purification by silica gel col-
umn chromatography (AcOEt/n-hexane¼2:3) afforded 15
(48 mg, 74% for R-isomer; 16 mg, 25% for S-isomer) as col-
orless solids. R-Isomer: Mp 54–56 ꢀC. [a]D21 +65.8 (c 1.13,
CHCl3). IR (KBr) nmax 1044, 1078, 1271, 1458, 1660,
4.1.10. 30-O,50-O-Dibenzyl-3-N-benzyloxymethyl-30-C,40-
C-(2,4-dioxapentamethylene)thymidine (17). To a solution
of 13 (229 mg, 0.35 mmol) in 1,2-dichloroethane (5 mL)
were added paraformaldehyde (229 mg) and p-toluenesul-
fonic acid monohydrate (7 mg, 0.037 mmol), and the mix-
ture was refluxed for 4.5 h. After addition of saturated
NaHCO3 solution, the mixture was extracted with CHCl3.
The usual work-up and purification by silica gel column
chromatography (AcOEt/n-hexane¼1:3 to 1:2) afforded 17
(103 mg, 47%) as a colorless oil. [a]2D6 +0.82 (c 0.50,
CHCl3). IR (KBr) nmax 3064, 3031, 2954, 1957, 1704,
1
1706, 2933 cmꢁ1. H NMR (CDCl3) d 1.88 (1H, dd, J¼8,
15 Hz), 1.92 (3H, s), 3.17 (1H, dd, J¼6, 15 Hz), 3.41 (3H,
s), 3.49, 3.92 (2H, AB, J¼12 Hz), 4.00 (1H, dd, J¼3,
12 Hz), 4.26 (1H, d, J¼12 Hz), 4.33 (1H, d, J¼13 Hz),
4.50 (1H, dd, J¼3, 13 Hz), 4.59 (2H, s), 4.63, 4.67 (2H,
AB, J¼7 Hz), 4.71 (2H, s), 5.49 (2H, s), 5.58 (1H, s), 6.05
(1H, br t, J¼7 Hz), 7.21–7.40 (13H, m), 7.54 (2H, dd,
J¼1, 7 Hz), 7.83 (1H, s). 13C NMR (CDCl3) d 13.5, 38.6,
56.2, 64.6, 65.4, 70.4, 70.9, 72.2, 84.1, 85.1, 86.7, 96.9,
101.2, 109.3, 125.9, 126.7, 127.0, 127.5, 127.6, 127.6,
128.2, 128.2, 128.4, 128.5, 129.0, 134.2, 137.5, 137.5,
137.9, 150.6, 163.4. MS (FAB): m/z 645 (MH+). Anal. Calcd
for C36H40N2O9$1/2H2O: C, 66.14; H, 6.25; N, 4.29. Found:
C, 65.91; H, 6.20; N, 4.25. S-Isomer: Mp 43–45 ꢀC. [a]D21
+24.5 (c 0.76, CHCl3). IR (KBr) nmax 1038, 1098, 1459,
1660 cmꢁ1
.
1H NMR (CDCl3) d 1.71 (3H, d, J¼1 Hz),
2.38 (1H, dd, J¼9, 14 Hz), 2.87 (1H, dd, J¼5, 13 Hz),
3.67 (1H, d, J¼11 Hz), 3.74 (1H, d, J¼13 Hz), 3.96 (1H,
d, J¼11 Hz), 4.26 (1H, d, J¼11 Hz), 4.33 (1H, d,
J¼11 Hz), 4.37 (1H, d, J¼13 Hz), 4.56–4.64 (4H, m), 4.67
(2H, s), 4.90, 5.33 (2H, AB, J¼8 Hz), 5.45 (2H, s), 6.29
(1H, dd, J¼5, 9 Hz), 7.23–7.40 (15H, m), 7.82 (1H, d,
J¼1 Hz). 13C NMR (CDCl3) d 13.0, 37.2, 62.9, 63.7, 66.2,
70.4, 72.1, 73.3, 74.0, 77.2, 87.2, 88.0, 90.9, 93.1, 109.6,
127.4, 127.6, 127. 7, 127.7, 128.0, 128.1, 128.2, 128.6,
128.7, 134.8, 136.7, 137.0, 137.9, 150.9, 163.5. MS
(FAB): m/z 615 (MH+). Anal. Calcd for C35H38N2O8$3/
4H2O: C, 66.92; H, 6.34; N, 4.46. Found: C, 66.99; H,
6.24; N, 4.41.
1
1664, 1706, 2881, 2948 cmꢁ1. H NMR (CDCl3) d 1.97
(3H, s), 2.28 (1H, dd, J¼10, 14 Hz), 3.04 (1H, dd, J¼5,
14 Hz), 3.34 (3H, s), 3.72, 3.91 (2H, AB, J¼12 Hz), 4.13,
4.15 (2H, AB, J¼11 Hz), 4.38 (1H, dd, J¼2, 12 Hz), 4.63
(2H, s), 4.70 (2H, s), 4.78, 4.87 (2H, AB, J¼11 Hz), 4.83