1180 J. Am. Chem. Soc., Vol. 119, No. 6, 1997
Osborne et al.
reduced pressure and chromatographed on silica gel (eluting with 1:1
EtOAc/petroleum ether) to afford 8b (0.97 g, 92% yield) as a white
foam. TLC (1:1 EtOAc/petroleum ether) Rf ) 0.42. 1H NMR (360
MHz, CDCl3) δ 0.07, 0.08, 0.09, 0.11 (12 H, 4 s, 2 (CH3)2Si), 0.89,
0.92 (18 H, 2 s, 2 (CH3)3CSi), 1.60-1.65 (2 H, m, 8-Ha,b), 1.73-1.79
(2 H, m, 9-Ha,b), 1.99 (1 H, ddd, J ) 6.0, 8.2, 13.0 Hz, 2′-Ha), 2.25 (1
H, ddd, J ) 2.3, 5.6, 13.0 Hz, 2′-Hb), 2.34 (2 H, dd, J ) 7.8, 15.8 Hz,
7-Ha,b), 3.00 (3 H, s, CH3SO2), 3.76 (1 H, dd, J ) 2.7, 11.4 Hz, 5′-Ha),
3.85 (1 H, dd, J ) 2.8, 11.4 Hz, 5′-Hb), 3.94 (1 H, dd, J ) 2.6, 5.1 Hz,
4′-H), 4.20 (2 H, t, J ) 6.4 Hz, 10-Ha,b), 4.39 (1 H, ddd, J ) 2.3, 5.1,
6.0 Hz, 3′-H), 6.31 (1 H, dd, J ) 5.6, 8.2 Hz, 1′-H), 7.45 (1 H, s, 6-H),
8.50 (1 H, br s, NH). 13C NMR (90 MHz, CDCl3) δ -5.4, -5.4, -4.8,
-4.7 ((CH3)2Si), 17.9, 18.4 ((CH3)3CSi), 25.2 (8), 25.7, 25.9 ((CH3)3-
CSi), 26.9 (7), 28.8 (9), 37.3 (CH33SO2), 41.3 (2′), 63.1 (5′), 69.6 (10),
72.3 (3′), 84.9 (1′), 87.9 (4′), 114.3 (5), 136.0 (6), 150.0 (2), 163.1 (4).
IR (film; NaCl) ν 3230, 3195, 2936, 1699, 1684, 1472, 1347, 1173,
936 cm-1. FAB MS (3-NBA) m/z 607 (M+ + 1).
3′,5′-Bis-O-(tert-butyldimethylsilyl)-C5-(thiobenzoylethyl)-2′-de-
oxyuridine (9a). Compound 8a (2.04 g, 3.52 mmol) was dissolved in
DMF (10 mL), and Et3N (2.45 mL, 17.6 mmol, 5.0 equiv) and
thiobenzoic acid (0.62 mL, 5.26 mmol, 1.5 equiv) were added. The
reaction mixture was stirred under N2 overnight, diluted with Et2O,
and washed with saturated NaHCO3 and brine. The aqueous layer was
washed once with Et2O and the combined organic layers were dried
over Na2SO4, concentrated under reduced pressure, and chromato-
graphed on silica gel (eluting with 25% EtOAc in petroleum ether) to
afford 9a (1.87 g, 86% yield) as a slightly orange-pink glass. TLC
(3:7 EtOAc/petroleum ether) Rf ) 0.43. 1H NMR (300 MHz, CDCl3)
δ 0.05 (12 H, s, 2 (CH3)2Si), 0.88 (18 H, s, 2 (CH3)3CSi), 1.92 (1 H,
ddd, J ) 6.0, 8.0, 13.1 Hz, 2′-Ha), 2.17 (1 H, ddd, J ) 2.3, 5.8, 13.1
Hz, 2′-Hb), 2.61-2.74 (2 H, m, 7-Ha,b), 3.27-3.32 (1 H, m, 8-H), 3.68-
3.78 (2 H, m, 5′-Ha,b), 3.88-3.91 (1 H, m, 4′-H), 4.33-4.37 (1 H, m,
3′-H), 6.28 (1 H, dd, J ) 5.8, 8.0 Hz, 1′-H), 7.44 (1 H, m, 6-H), 7.43-
7.47 (2 H, m, ArH), 7.55-7.59 (1 H, m, ArH), 7.93-7.98 (2 H, m,
ArH), 8.91 (1 H, br s, NH). 13C NMR (90 MHz, CDCl3) δ -5.6, -5.4,
-4.9, -4.7 ((CH3)2Si), 17.9, 18.3 ((CH3)3CSi), 25.7, 25.8 ((CH3)3CSi),
27.7 (7), 28.0 (8), 41.0 (2′), 62.9 (5′), 72.2 (3′), 84.8 (1′), 87.7 (4′),
112.5 (5), 127.2, 128.5, 133.8, 136.7 (Ar), 136.9 (6), 150.2 (2), 163.3
(4), 191.5 (Ar). IR (film; NaCl) ν 3176, 3058, 2957, 2930, 2858, 1690,
1463, 1364, 1257, 1105, 1032, 839, 779, 673 cm-1. DCI MS (CH3)
m/z 621 (M+ + 1).
petroleum ether) to afford 10a (0.65 g, 90% yield) as a white foam.
TLC (7:1:2 CH2Cl2/MeOH/petroleum ether) Rf ) 0.44. 1H NMR (360
MHz, CD3CN/CDCl3) δ 2.06-2.21 (2 H, m, 2′-Ha,b), 2.55-2.66 (2 H,
m, 7-Ha,b), 3.18-3.24 (2 H, m, 8-Ha,b), 3.69 (2 H, d, J ) 3.1 Hz, 5′-
H
a,b), 3.84 (1 H, dd, J ) 3.2, 6.7 Hz, 4′-H), 4.36-4.40 (1 H, m, 3′-H),
6.16 (1 H, t, J ) 6.6 Hz, 1′-H), 7.41-7.46 (2 H, m, ArH), 7.54-7.58
(1 H, m, ArH), 7.75 (1 H, s, 6-H), 7.87-7.90 (2 H, m, ArH), 9.23 (1
H, s, NH). 13C NMR (90 MHz, CD3CN/CDCl3) δ 26.4 (7), 26.9 (8),
39.4 (2′), 60.9 (5′), 69.8 (3′), 84.4 (1′), 86.6 (4′), 111.2 (5), 126.3, 128.0,
132.8, 136.2 (Ar), 137.2 (6), 149.6 (2), 162.6 (4), 190.8 (SCOPh). IR
(film; NaCl) ν 3407, 2935, 1667, 1469, 1275, 1207, 1094, 916, 690
cm-1. FAB MS (3-NBA) m/z 393 (M+ + 1).
C5-(Thiobenzoylbutyl)-2′-deoxyuridine (10b). Compound 9b (0.90
g, 1.39 mmol) and n-tetrabutylammonium fluoride monohydrate (1.27
g, 4.84 mmol, 3.5 equiv) were dissolved in THF (28 mL). The reaction
mixture was stirred under N2 for 3 h after which the solvent was
removed under reduced pressure. The residue was chromatographed
on silica gel (eluting with 5% MeOH in CH2Cl2) to afford 10b (0.60
g, 100% yield) as a white foam. TLC (10% MeOH in CH2Cl2) Rf )
0.35. 1H NMR (360 MHz, CD3OD) δ 1.71-1.75 (4 H, m, 8-Ha,b
,
9-Ha,b), 2.31-2.35 (2 H, m, 2′-Ha,b), 2.43 (2 H, t, J ) 6.2 Hz, 7-Ha,b),
3.14-3.18 (2 H, m, 10-Ha,b), 3.82 (1 H, dd, J ) 3.6, 12.0 Hz, 5′-Ha),
3.89 (1 H, dd, J ) 3.1, 12.0 Hz, 5′-Hb), 4.01 (1 H, dd, J ) 3.3, 6.5 Hz,
4′-H), 4.50 (1 H, ddd, J ) 3.8, 6.5, 8.9 Hz, 3′-H), 6.38 (1 H, t, J ) 6.7
Hz, 1′-H), 7.53-7.58 (2 H, m, ArH), 7.66-7.68 (1 H, m, ArH), 7.94
(1 H, s, 6-H), 8.00-8.03 (2 H, m, ArH). 13C NMR (90 MHz, CD3-
OD) δ 27.2 (7), 28.6 (8), 29.4 (9), 30.2 (10), 41.2 (2′), 62.8 (5′), 72.2
(3′), 86.4 (1′), 88.8 (4′), 115.3 (5), 128.0, 129.8 (Ar), 134.5 (6), 138.4
(Ar), 152.2 (2), 165.9 (4), 193.4 (SCOPh). IR (KBr) ν 2949, 2869,
1724, 1656, 1272, 1096, 916, 689 cm-1. FAB MS (3-NBA) m/z 421
(M+ + 1).
5′-O-(4,4′-Dimethoxytrityl)-C5-(thiobenzoylethyl)-2′-deoxyuri-
dine (11a). Compound 10a (0.27 g, 0.71 mmol) was dissolved in
pyridine (5 mL), the mixture was cooled to 0 °C, and 4,4′-dimeth-
oxytrityl chloride (0.29 g, 0.85 mmol, 1.2 equiv) was added. The
reaction mixture was stirred under N2 for 6 h and the excess
4,4′-dimethoxytrityl chloride was then quenched with MeOH (1 mL).
The solvent was removed under reduced pressure; the residue was
coevaporated once with CH3CN and chromatographed on silica gel
(eluting with a step gradient of 33-100% Et2O in petroleum ether) to
afford 11a (0.36 g, 75% yield) as a white foam. TLC (65:5:30 CH2-
Cl2/MeOH/petroleum ether) Rf ) 0.42. 1H NMR (360 MHz, CD3CN/
CDCl3) δ 2.37-2.55 (4 H, m, 2′-Ha,b, 7-Ha,b), 3.49-3.57 (2 H, m,
8-Ha,b), 3.99-4.02 (8 H, m, 5′-Ha,b, 2 OCH3), 4.20 (1 H, dd, J ) 3.1,
6.6 Hz, 4′-H), 4.63-4.67 (1 H, m, 3′-H), 6.46 (1 H, t, J ) 6.8 Hz,
1′-H), 7.06-7.10 (4 H, m, ArH), 7.36-8.12 (14 H, m, 6-H, ArH), 9.27
(1 H, s, NH). 13C NMR (90 MHz, CD3CN/CDCl3) δ 26.3 (7), 26.6
(8), 39.2 (2′), 54.2 (OCH3), 62.7 (5′), 70.3 (3′), 84.3 (1′), 85.0 (4′),
86.5 (OC(Ph)3), 112.0 (Ar), 112.3 (5), 125.9, 126.1, 127.2, 127.9, 128.2,
129.2, 132.7, 135.9 (Ar), 136.9 (6), 149.2 (2), 157.8 (4), 189.8 (SCOPh).
IR (film; NaCl) ν 3452, 1670, 1608, 1509, 1465, 1447, 1250, 1207,
3′,5′-Bis-O-(tert-butyldimethylsilyl)-C5-(thiobenzoylbutyl)-2′-
deoxyuridine (9b). Compound 8b (0.95 g, 1.56 mmol) was dissolved
in DMF (6.2 mL), and Et3N (1.1 mL, 7.82 mmol, 5.0 equiv) and
thiobenzoic acid (0.28 mL, 2.35 mmol, 1.5 equiv) were added. The
reaction mixture was stirred under N2 overnight. The reaction mixture
was diluted with Et2O and washed with saturated NaHCO3 and brine.
The organic layer was dried over Na2SO4 and concentrated under
reduced pressure, and chromatographed on silica gel (eluting with 3:1
petroleum ether/EtOAc) to afford 9b (0.93 g, 92% yield) as a slightly
orange-pink foam. TLC (1:1 EtOAc/petroleum ether) Rf ) 0.58. 1H
NMR (360 MHz, CDCl3) δ 0.07, 0.07, 0.08, 0.09 (12 H, 4 s, 2 (CH3)2-
1176, 1034 cm-1
.
5′-O-(4,4′-Dimethoxytrityl)-C5-(thiobenzoylbutyl)-2′-deoxyuri-
dine (11b). Compound 10b (0.45 g, 1.00 mmol) was dissolved in
pyridine (6 mL), the mixture was cooled to 0 °C, and 4,4′-dimeth-
oxytrityl chloride (0.41 g, 1.20 mmol, 1.2 equiv) was added. The
mixture was stirred under N2 for 18 h after which the excess 4,4′-
dimethoxytrityl chloride was quenched with MeOH (1 mL). The
solvent was removed under reduced pressure and the residue then
chromatographed on silica gel (eluting with a step gradient of 33-
100% Et2O in petroleum ether) to afford 11b (0.43 g, 59% yield) as a
tan foam. TLC (1:1 acetone/petroleum ether) Rf ) 0.42. 1H NMR
(360 MHz, CD3CN) δ 1.31-1.41 (4 H, m, 8-Ha,b, 9-Ha,b), 1.78-1.84
(1 H, m, 2′-Ha), 1.92-1.98 (1 H, m, 2′-Hb), 2.14-2.29 (2 H, m, 7-Ha,b),
2.84 (2 H, t, J ) 6.8 Hz, 10-Ha,b), 3.26 (2 H, d, J ) 3.4 Hz, 5′-Ha,b),
3.94 (1 H, br s, 3′-OH), 3.73 (6 H, s, 2 OCH3), 3.91 (1 H, dd, J ) 3.5,
7.0 Hz, 4′-H), 4.45-4.48 (1 H, m, 3′-H), 6.23 (1 H, t, J ) 6.8 Hz,
1′-H), 6.84-6.86 (4 H, m, ArH), 7.19-7.92 (15 H, m, 6-H, ArH), 9.12
(1 H, br s, NH). 13C NMR (90 MHz, CD3CN) δ 27.3 (7), 28.7 (8),
29.2 (9), 29.9 (10), 40.8 (2′), 55.9 (OCH3), 64.5 (5′), 72.1 (3′), 85.2
(1′), 86.8 (4′), 87.3 (OC(Ph)3), 114.1 (Ar), 115.2 (5), 127.9, 128.0,
128.9, 129.1, 129.8, 131.0 (Ar), 134.5 (6), 136.7, 139.9, 138.0, 145
Si), 0.89, 0.90 (18 H, 2 s, 2 (CH3)3CSi), 1.63-1.72 (4 H, m, 8-Ha,b
,
9-Ha,b), 2.00 (1 H, ddd, J ) 6.0, 8.1, 13.1 Hz, 2′-Ha), 2.23 (1 H, ddd,
J ) 2.3, 5.7, 13.1 Hz, 2′-Hb), 2.34 (2 H, t, J ) 7.1 Hz, 7-Ha,b), 3.05-
3.10 (2 H, m, 10-Ha,b), 3.75 (1 H, dd, J ) 2.8, 11.3 Hz, 5′-Ha), 3.84 (1
H, dd, J ) 3.0, 11.3 Hz, 5′-Hb), 3.93 (1 H, dd, J ) 2.7, 5.2 Hz, 4′-H),
4.39 (1 H, ddd, J ) 2.3, 5.2, 6.0 Hz, 3′-H), 6.32 (1 H, dd, J ) 5.7, 8.1
Hz, 1′-H), 7.43 (1 H, s, 6-H), 7.43-7.46 (2 H, m, ArH), 7.53-7.58 (1
H, m, ArH), 7.94-7.97 (2 H, m, ArH), 8.35 (1 H, br s, NH). 13C
NMR (90 MHz, CDCl3) δ -5.4, -5.4, -4.8, -4.7 ((CH3)2Si), 18.0,
18.4 ((CH3)3CSi), 25.7, 25.9 ((CH3)3CSi), 27.1 (7), 28.3 (8), 28.6 (9),
29.3 (10), 41.2 (2′), 63.1 (5′), 72.3 (3′), 84.9 (1′), 87.8 (4′), 114.7 (5),
127.2, 128.5 (Ar), 133.2 (6), 135.7, 137.1 (Ar), 150.0 (2), 163.0 (4),
191.8 (Ar). IR (film; NaCl) ν 2954, 2930, 1695, 1668, 1471, 1207,
1095, 886 cm-1. FAB MS (3-NBA) m/z 649 (M+ + 1).
C5-(Thiobenzoylethyl)-2′-deoxyuridine (10a). Compound 9a (1.17
g, 1.90 mmol) was dissolved in THF (40 mL), and n-tetrabutylammo-
nium fluoride monohydrate (1.80 g, 6.9 mmol, 3.5 equiv) was added.
The reaction mixture was stirred under N2 for 3 h after which the solvent
was removed under reduced pressure to give a pink solid. The residue
was chromatographed on silica gel (eluting with 65:5:30 CH2Cl2/MeOH/