The Journal of Organic Chemistry ’ EXPERIMENTAL SECTION 1H and 13C (J-modulated; additionally, non-J-modulated spectra were recorded of compounds containing 2-nitroimidazole) NMR spectra were measured at 300 K at 400.13 and 100.61 MHz, respectively. All chemical shifts (δ) are given in parts per million. They were referenced either to residual CHCl3 (δH 7.24)/toluene-d8 (CHD2, δH 2.09)/ CD3OD (CHD2, δH 3.31)/DMSO-d6 (CHD2, δH 2.50) or CDCl3 (δC 77.00)/toluene-d8 (CD3, δC 21.04)/CD3OD (CD3, δC 49.00)/DMSO- d6 (CD3, δC 39.50). IR spectra of ﬁlms on a silicon disk were recorded on an FT-IR spectrometer.29 Optical rotations were measured at 20 C on a polarimeter in a 1 dm cell. Melting points are uncorrected. Flash (column) chromatography was performed with silica gel 60 (230 400 mesh) and monitored by TLC, carried out on 0.25 mm thick plates, silica gel 60 F254. Spots were visualized by UV and/or by dipping the plate into a solution of (NH4)6Mo7O24 3 4H2O (23.0 g) and Ce(SO4)2 3 4H2O (1.0 g) in 10% aqueous H2SO4 (500 mL), followed by heating with a heat gun. General Procedure A: Triethylsilylation of 2-Nitroimida- zole. A mixture of 2-nitroimidazole (0.113 g, 1 mmol), hexaethyldisi- lazane (0.491 g, 2 mmol, 2 equiv), and dry pyridine (2 mL) was refluxed for 30 min. The solution was cooled (silylated compound crystallized), and volatile components were removed by bulb to bulb distillation (70 75 C, 0.4 mbar) to leave brown crystalline 1-(triethylsilyl)- 2-nitroimidazole, which was used immediately without further purification. General Procedure B: Desilylation of 2-Nitroimidazole Nucleosides with a TBDPSO Group at C-50. A mixture of the nucleoside (0.50 mmol), KF (0.407 g, 3.50 mmol, 7 equiv), and benzoic acid (0.427 g, 3.50 mmol, 7 equiv) in dry CH3CN (11.5 mL) was heated at 75 C for 7 h (monitored by TLC).27 The mixture was then cooled, filtered, and concentrated under reduced pressure. General Procedure C: Tosylation of 2-Nitroimidazole Nu- cleosides Derived from D-Pentoses with a Free 50-OH Group. A solution of p-toluenesulfonyl chloride (0.521 g, 2.73 mmol, 3 equiv) and nucleoside with a free 50-OH in dry pyridine (5 mL) was kept for 18 h at 4 C (TLC, hexanes/EtOAc, 1:2). Then water (10 mL) and 2 M HCl (10 mL) were added, 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. Hexaethyldisilazane (10). Triethylsilyl triflate (0.2 mL) was added to a stirred solution of (triethylsilyl)amine (8)24 [9.66 g, 73.6 mmol, 3.2 equiv; 70 80 C, 80 mmHg; 75% yield; n2D0 1.4250 (lit.24 bp 134 C, n2D0 1.4267)] and chlorotriethylsilane (3.47 g, 3.86 mL, 23 mmol) in dry toluene (40 mL) at 0 C. Precipitation of NH4Cl started immediately. After being stirred for 2 h at rt, the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure, and the residue was bulb to bulb distilled (70 75 C, 0.5 mbar; lit.23b bp 100 C, 1 mmHg) to give 10 (8.92 g, 79%) as a colorless liquid: n2D7 1.4502; 1H NMR (400.1 MHz, toluene-d8) δ 0.98 (t, J = 8.0 Hz, 18H), 0.53 (q, J = 8.0 Hz, 12H), 0.29 (br s, 1H, NH); 13C NMR (100.6 MHz, toluene-d8) δ 8.4, 8.0. 1,2,3-Tri-O-acetyl-5-O-(tert-butyldiphenylsilyl)-α- and 1,2, 3-Tri-O-acetyl-5-O-(tert-butyldiphenylsilyl)-β-D-arabinofur- anose (α- and β-14). A mixture of D-arabinose (0.751 g, 5 mmol) in dry pyridine (10 mL) was cooled to 20 C under argon, and TBDPSCl (t-BuPhe2SiCl) (1.374 g, 1.30 mL, 5 mmol) was added. The reaction mixture was allowed to slowly warm to rt in the cooling bath overnight (TLC, hexanes/EtOAc, 2:1). After addition of Ac2O (4 mL) the solution was stirred at rt for 6 h. Volatile components were removed under reduced pressure and the residue taken up with water (10 mL) and 2 M HCl (10 mL). The mixture was extracted with CH2Cl2 (3 10 mL). The combined organic layers were washed with saturated aq NaHCO3 (10 mL) and water (10 mL), dried (Na2SO4), and concentrated under ARTICLE reduced pressure. The crude product was purified by flash chromatog- raphy (hexanes/EtOAc, 2:1, Rf 0.63) to give the mixture of anomeric acetates (1.83 g, 71%) as an oil,25 α:β = 60:40 (by 1H NMR), [α]2D0 +19.3 (c 3.0, acetone). After a few months crystals of the α-anomer formed in the oil. They were collected after the oil was dissolved in i-Pr2O/hexanes and recrystallized (i-Pr2O/hexanes) to give the homo- geneous α-anomer: mp 92 93 C; [α]2D0 +52.1 (c 1.1, acetone). Data for α- and β-14: IR (Si) νmax 3072, 2933, 2859, 1750, 1428, 1371, 1221, 1113, 1065, 1008 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ (α-14) 7.67 (m, 6H), 7.38 (m, 9H), 6.19 (s, 1H), 5.37 (dd, J = 4.8, 1.0 Hz, 1H), 5.20 (d, J = 1.0 Hz, 1H), 4.24 (td, J = 4.8, 4.0 Hz, 1H), 3.84 (AB system, JAB = 11.1 Hz, JAX = JBX = 4.0 Hz, 2H), 2.10 (s, 3H), 2.09 (s, 3H), 2.03 (s, 3H), 1.06 (s, 9H); (β-14) 7.67 (m, 6H), 7.38 (m, 9H), 6.36 (d, J = 4.8 Hz, 1H), 5.62 (dd, J = 7.1, 6.0 Hz, 1H), 5.34 (dd, J = 7.1, 4.8 Hz, 1H), 4.12 (td, J = 6.0, 5.3 Hz, 1H), 3.81 (AB system, JAB = 11.0 Hz, JAX = JBX = 5.3 Hz, 2H), 2.06 (s, 3H), 2.05 (s, 3H), 1.88 (s, 3H), 1.06 (s, 9H); 13C NMR (100.6 MHz, CDCl3) δ (α-14) 169.8, 169.6, 169.3, 135.61 (2C), 135.59 (2C), 133.1, 133.0, 129.7 (2C), 127.7 (4C), 99.6, 84.8, 81.4, 76.7, 62.7, 26.7 (3C), 21.0, 20.7, 20.6, 19.3; (β-14) 169.9, 169.8, 169.4, 135.6 (2C), 135.5 (2C), 133.2, 132.9, 129.8 (2C), 127.7 (4C), 93.6, 81.6, 75.6, 74.1, 64.3, 26.7 (3C), 20.9, 20.8, 20.4, 19.2. Anal. Calcd for C27H34O8Si: C, 63.01; H, 6.66. Found for crystalline α-14: C, 62.36; H, 6.84. 1-α-[20,30-Di-O-acetyl-50-O-(tert-butyldiphenylsilyl)-D-ara- binofuranosyl]-2-nitroimidazole (α-15). A solution of α- and β- 14 (0.548 g, 1.06 mmol) in dry CH3CN (3 mL) was added to 2-nitroimidazole (0.113 g, 1 mmol) triethylsilylated according to general procedure A under argon in dry CH3CN (5 mL). After the stirred mixture was cooled to 20 C, TfOTES (1 mL, 1 M in dry 1,2- C2H4Cl2) was added, and stirring was continued for 3 h at 8 C (TLC, hexanes/EtOAc, 2:1). A saturated aq solution of NaHCO3 (10 mL) was added, and the mixture was extracted with EtOAc (3 10 mL). The combined organic layers were washed with water (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc, 2:1, Rf 0.21) to give protected nucleoside α-15 (0.435 g, 72%) as a yellow oil (lit.25 mp 53 C): [α]D20 +21.3 (c 1.1, acetone); the 1H NMR data agree with those of the literature;25 IR (Si) νmax 2932, 2859, 1755, 1540, 1475, 1428, 1369, 1230, 1106 cm 1; 13C NMR (100.6 MHz, CDCl3) δ 169.2, 168.9, 144.2, 135.64 (2C), 135.56 (2C), 132.8, 132.7, 130.0 (2C), 128.5, 127.8 (2C), 127.5 (2C), 121.9, 92.6, 87.4, 81.8, 76.8, 63.6, 26.7 (3C), 20.6, 20.4, 19.2. Preparation of α- and β-15 in 1,2-C2H4Cl2. A solution α- and β-14 (0.680 g, 1.32 mmol) in dry 1,2-C2H4Cl2 (4 mL) was added under argon at rt to 2-nitroimidazole (0.150 g, 1.32 mmol) trimethylsilylated according to general procedure A, followed by TfOTMS (1.32 mL, 0.5 M in dry 1,2-C2H4Cl2). After the mixture was stirred for 4 h at rt, CH2Cl2 (20 mL) and a saturated aq solution of NaHCO3 (20 mL) were added. The organic phase was separated, and the aqueous one was extracted with CH2Cl2 (3 10 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc, 3:1 and then 1:2; TLC, 2:1, Rf 0.21 for α-15 and 0.43 for β-15) to give recovered starting material (0.306 g, 45%), β-15 (0.098 g, 13%), and α-15 (0.122 g, 16%). 1,2,3-Tri-O-acetyl-5-O-(tert-butyldiphenylsilyl)-α- and Tri- O-acetyl-5-O-(tert-butyldiphenylsilyl)-β-D-ribofuranose (α- and β-17). D-Ribose (0.751 g, 5 mmol) was silylated, acetylated, and worked up in the same way as D-arabinose, except that the acetylation was performed for 6 h at 60 C. The crude product (α:β = 1:0.9) was purified by flash chromatography (hexanes/EtOAc, 3:1, Rf 0.73 for β- anomer and 0.58 for α-anomer, hexanes/EtOAc, 2:1) to give β- triacetate β-17 (0.720 g, 28%; 10 15% of it was unknown compounds) and α-triacetate α-17 (0.849 g, 33%; 6% of it was an impurity) as colorless, very viscous oils. Data for β-17: [α]2D0 +2.17 (c 1.15, acetone); 8163 dx.doi.org/10.1021/jo200727k |J. Org. Chem. 2011, 76, 8159–8167