The Journal of Organic Chemistry solution of NaHCO3, dried (Na2SO4), and concetrated under reduced pressure. The residue was purified by flash column chromatography (hexanes/EtOAc, 10:1; TLC, Rf 0.31 for 7:1) to yield a seemingly homogeneous oily product [0.670 g, 47%; by 1H NMR a mixture of α- anomer (δ 5.93, J = 7.9 Hz):β-anomer (δ 6.03, J = 0 Hz):unknown compound (δ 6.09, J = 4.1 Hz) = 74:19:7], [α]2D0 35.81 (c 1.55, acetone), in which gradually crystals of the α-anomer formed. Hexanes were added, and the mixture was stored at 18 C. The colorless needles were collected and recrystallized (hexanes, 18 C). Data for α-24: mp 69 70 C (hexanes, 18 C); [α]2D0 39.75 (c 1.2, acetone); IR (Si) ν1max 2946, 2868, 1747, 1464, 1373, 1216, 1169, 1125, 1078, 1010 cm 1; H NMR (400.1 MHz, CDCl3) δ 5.93 (d, J = 7.9 Hz, 1H), 4.80 (dd, J = 7.9, 2.8 Hz, 1H), 4.57 (dd ≈ t, J = 2.8, 2.3 Hz, 1H), 4.10 (ddd, J = 9.6, 5.2, 2.3 Hz, 1H), 3.79 (AB part of ABX system, J = 11.0, 9.6, 5.2 Hz, 2H), 2.07 (s, 3H), 2.06 (s, 3H), 1.09 0.82 (m, 28H); 13C NMR (100.6 MHz, CDCl3) δ 169.9, 169.4, 90.3, 71.1, 70.5, 70.5, 64.6, 21.0, 20.9, 17.4 (2C), 17.2 (2C), 17.2 (2C), 17.14, 17.09, 14.0, 13.6, 13.0, 12.6. Anal. Calcd for C21H40O8Si2: C, 52.91; H, 8.46. Found: C, 52.64; H, 8.38. 1-β- and 1-α-[20-O-Acetyl-30,50-O,O-(1,1,3,3-tetraisoprop- yldisiloxanylidene)-D-ribofuranosyl]-2-nitroimidazole (β- and α-25). A solution of α- and β-24 (0.634 g, 1.33 mmol) in dry CH3CN (5 mL) was added to 2-nitroimidazole (0.107 g, 0.95 mmol) triethylsilylated according to general procedure A in dry CH3CN (2 mL) under argon. After the stirred mixture was cooled to 0 C, TfOTES (1.14 mL, 1 M solution in dry 1,2-C2H4Cl2) was added dropwise, and stirring was continued for 45 min at that temperature. Then a saturated aq solution of NaHCO3 (10 mL) was added, and the mixture was extracted with EtOAc (3 15 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was flash chromatographed (hexanes/EtOAc, 5:1; β-25, Rf 0.36; α-25, Rf 0.21) to yield nucleosides β-25 (0.152 g, 30%) and α-25 (0.158 g, 32%), both colorless needles. When the reaction mixture was allowed to warm from 10 C to rt, the β- and α-anomers were formed in yields of 16% and 32%, respectively. Data for β-25: mp 143 144 C (i-Pr2O/ hexanes); [α]2D0 +4.06 (c 0.91, acetone); IR (Si) νmax 2946, 2868, 1764, 1543, 1474, 1370, 1231, 1116, 1073, 1040 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ 7.77 (d, J = 1.0 Hz, 1H), 7.14 (d, J = 1.0 Hz, 1H), 6.34 (s, 1H), 5.46 (d, J = 4.8 Hz, 1H), 4.43 (dd, J = 9.4, 4.8 Hz, 1H), 4.28 (d, J = 13.6 Hz, 1H), 4.10 (dd, J = 9.4, 2.5 Hz, 1H), 4.00 (dd, J = 13.6, 2.5 Hz, 1H), 2.17 (s, 3H), 1.11 0.83 (m, 28H); 13C NMR (100.6 MHz, CDCl3) δ 168.5, 143.7, 128.5, 122.3, 91.0, 82.6, 72.3, 66.8, 59.3, 20.5, 17.4, 17.3, 17.2, 17.2, 16.9, 16.8, 16.70, 16.66, 13.4, 12.9, 12.8, 12.6. Anal. Calcd for C22H39N3O8Si2: C, 49.88; H, 7.42; N, 7.93. Found: C, 49.48; H, 7.61; N, 7.83. Data for α-25: mp 106 107 C (i-Pr2O/hexanes); [α]2D0 +43.78 (c 0.95, acetone); IR (Si) νmax 2946, 2868, 1748, 1545, 1484, 1374, 1225, 1169, 1117, 1053, 1033, 1009 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ 7.26 (d, J = 1.3 Hz, 1H), 7.11 (d, J = 1.3 Hz, 1H), 6.70 (d, J = 9.1 Hz, 1H), 4.86 (dd, J = 9.1, 2.3 Hz, 1H), 4.65 (t, J = 2.3 Hz, 1H), 4.22 (td, J = 8.3, 2.3 Hz, 1H), 3.92 (d, J = 8.3 Hz, 2H), 1.88 (s, 3H), 1.15 0.82 (m, 28H); 13C NMR (100.6 MHz, CDCl3) δ 169.5, 144.9, 128.7, 121.3, 80.7, 72.4, 71.2, 70.6, 66.5, 20.4, 17.41, 17.37, 17.22, 17.16, 17.1 (2C), 17.06, 17.02, 14.1, 13.7, 12.9, 12.8. Anal. Calcd for C22H39N3O8Si2: C, 49.88; H, 7.42; N, 7.93. Found: C, 49.74; H, 7.40; N, 7.88. 1-β-[20,30-Di-O-acetyl-D-ribofuranosyl]-2-nitroimidazole (β-26). Nucleoside β-18 (0.381 g, 0.67 mmol) was desilylated by general procedure B. The crude product was purified by flash chroma- tography (starting with hexanes/EtOAc, 1:1, Rf 0.18, and then hexanes/ EtOAc, 1:5) to give alcohol β-2618 (0.158 g, 71%) as yellow crystals: mp 125 126 C (1,2-C2H4Cl2/i-Pr2O) (lit.18 mp 122 123 C); [α]2D0 +29.82 (c 1.1, acetone); IR (Si) νmax 3374, 3121, 2937, 1750, 1541, 1483, 1430, 1367, 1243, 1161, 1101, 1079, 1013 cm 1; the 1H and 13C NMR data are identical to those of the literature.18 Anal. Calcd for C12H15N3O8: C, 43.77; H, 4.59; N, 12.76. Found: C, 43.86; H, 4.42; N, 12.73. ARTICLE 1-β-[20,30-Di-O-acetyl-50-O-(4-toluenesulfonyl)-D-ribofu- ranosyl]-2-nitroimidazole (β-27). A solution of 4-toluenesulfonyl chloride (0.173 g, 0.91 mmol, 3 equiv) and alcohol β-26 (0.100 g, 0.304 mmol) in dry pyridine (2 mL) was kept for 18 h at 4 C. When the starting alcohol was consumed (TLC, hexanes/EtOAc, 1:1), water (10 mL) and 2 M HCl (10 mL) were added. The mixture was extracted with EtOAc (3 10 mL). The combined organic layers were washed with saturated aq NaHCO3 (10 mL) and water (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc, 1:1, Rf = 0.41) to give tosylate β-27 (0.102 g, 69%) as a yellow foam: [α]2D0 +44.2 (c 1.0, acetone); IR (Si) νmax 1755, 1542, 1478, 1368, 1239, 1191, 1178, 1096 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ 7.79 (m, 2H), 7.49 (d, J = 1.1 Hz, 1H), 7.36 (m, 2H), 7.12 (d, J = 1.1 Hz, 1H), 6.59 (d, J = 3.8 Hz, 1H), 5.38 (dd, J = 5.6, 3.8 Hz, 1H), 5.23 (dd ≈ t, J = 6.1, 5.6 Hz, 1H), 4.44 (dd, J = 11.4, 2.4 Hz, 1H), 4.38 (dt, J = 6.1, 2.3 Hz, 1H), 4.22 (dd, J = 11.4, 2.3 Hz, 1H), 2.44 (s, 3H), 2.10 (s, 3H), 2.03 (s, 3H); 13C NMR (100.6 MHz, CDCl3) δ 169.2, 168.9, 145.7, 144.2, 132.0, 130.2 (2C), 129.1, 128.0 (2C), 121.7, 89.4, 79.6, 74.8, 68.7, 66.5, 21.7, 20.3, 20.2. Anal. Calcd for C19H21N3O10S: C, 47.20; H, 4.38; N, 8.69. Found: C, 47.48; H, 4.48; N, 8.48. 1-α-[50-O-(tert-Butyldiphenylsilyl)-D-ribofuranosyl]-2-ni- troimidazole (α-30). A mixture of tribenzoate α-20 (0.398 g, 0.714 mmol) and MeONa/MeOH (3.0 mL, 0.05 M) was stirred at 0 C. When the transesterification (TLC, hexanes/EtOAc, 1:2) was finished (2 h), AcOH (3 drops) was added immediately, and the solvent was removed under reduced pressure. The residue was purified by flash chromatog- raphy (CHCl3/MeOH, 4:1, Rf 0.39) to yield an inseparable mixture of α-28 and a side product (10 20%) with the tentatively assigned structure 29 (0.132 g): 1H NMR (400.1 MHz, CD3OD) δ (α-28) 7.62 (s, 1H), 7.13 (s, 1H), 6.71 (d, J = 4.8 Hz, 1H), 4.61 (dd ≈ t, J = 5.3, 4.8 Hz, 1H), 4.31 (m, 1H), 3.84 (dd, J = 12.2, 2.8 Hz, 1H), 3.67 (dd, J = 12.2, 4.2 Hz, 1H); (29) 6.83 (s, 1H), 6.62 (s, 1H), 6.25 (d, J = 5.3 Hz, 1H), 5.56 (t, J = 5.3 Hz, 1H). TBDPSCl (0.412 g, 0.39 mL, 1.50 mmol) was added to a solution of the mixture of α-28 and 29 (0.132 g) in dry pyridine (2.5 mL), and the mixture was stirred at rt until the starting material was consumed (2 h; TLC, CHCl3/MeOH, 4:1, for starting material, hexanes/EtOAc, 1:1, for product α-30). The reaction was quenched with water (10 mL) and 2 M HCl (10 mL), and the mixture was extracted with EtOAc (3 10 mL). The combined organic layers were washed with saturated aq NaHCO3 (10 mL) and water (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude product was purified by flash chromatography (hexanes/EtOAc, 1:1, Rf 0.38) to give α-30 (0.179 g, 52%, starting from tribenzoate α-20): mp 150 151 C (EtOAc); [α]2D0 33.6 (c 1.22, EtOH); IR (ATR) νmax 3413, 3200, 2927, 1537, 1354, 1487, 1354, 1111, 1090, 1048, 1036 cm 1 1 ; H NMR (400.1 MHz, DMSO-d6) δ 7.68 7.62 (m, 4H), 7.59 (s, 1H), 7.51 7.40 (m, 6H), 7.17 (s, 1H), 6.62 (d, J = 4.8 Hz, 1H), 5.49 (d, J = 5.8 Hz, 1H), 5.03 (d, J = 5.1 Hz, 1H), 4.55 4.49 (m, 1H), 4.34 (br s, 1H), 4.20 4.15 (m, 1H), 3.82 (AB system, J = 11.5, 3.7, 1.7 Hz, 2H), 1.03 (s, 9H); 13C NMR (100.61, DMSO-d6) δ 144.5, 135.1 (4C), 132.8, 132.7, 129.9 (2C), 128.0 (2C), 127.9 (2C), 127.1, 124.3, 89.9, 84.9, 71.0, 70.6, 63.8, 26.6 (3C), 18.8. Anal. Calcd for C24H29N3O6Si: C, 59.61; H, 6.04; N, 8.69. Found: C, 59.62; H, 5.98; N, 8.68. 1-α-[20,30-Di-O-acetyl-50-O-(tert-butyldiphenylsilyl)-D- ribofuranosyl]-2-nitroimidazole (α-18). Ac2O (0.3 mL) was added to a solution of diol α-30 (0.070 g, 0.145 mmol) in dry pyridine (0.3 mL) and dry CHCl3 (2 mL). The mixture was heated and stirred for 30 min at 50 C (TLC, hexanes/EtOAc, 1:1). After cooling, water (5 mL) and 2 M HCl (5 mL) were added. The resulting mixture was extracted with EtOAc (3 10 mL). The combined organic layers were washed with saturated aq NaHCO3 (10 mL) and water (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude 8165 dx.doi.org/10.1021/jo200727k |J. Org. Chem. 2011, 76, 8159–8167