Synthesis of 2,6-disubstituted pyridin-3-yl C-2′-deoxyribonucleosides through chemoselective transformations of bromo-chloropyridine C-nucleosides

Abstract

2-Bromo-6-chloro- and 6-bromo-2-chloropyridin-3-yl deoxyribonucleosides were prepared by the Heck coupling of bromo-chloro-iodopyridines with TBS-protected deoxyribose glycal. Some of their Pd-catalyzed cross-coupling reactions proceeded chemoselectively at the position of the bromine, whereas nucleophilic substitutions were unselective and gave mixtures of products. The mono-substituted intermediates were used for another coupling or nucleophilic substitution giving rise to a small library of title 2,6-disubstituted pyridine C-deoxyribonucleosides. The title nucleosides did not exert antiviral or cytostatic effects.

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Introduction

C-Nucleosides are important analogues of natural nucleosides useful for many applications in medicinal chemistry and chemical biology.¹ Diverse aryl and hetaryl-C-2′-deoxyribonucleosides were extensively studied as candidates for novel base-pairs in the quest for extension of the genetic alphabet and some of their artificial base-pairs were efficiently replicated by DNA polymerases with high fidelity.² Moreover, some pyridine C-nucleosides have been used as probes for studying the mechanism of polymerases.³ Most of the current approaches to the synthesis of C-nucleosides suffer from moderate efficiency and/or stereoselectivity.¹ Our group has developed a modular approach⁴ based on the synthesis of halogenated (het)aryl C-nucleoside intermediates and their functionalization by Pd-catalyzed cross-couplings, aminations, carbonylations or hydroxylations. Very recently, the same approach was used even for the functionalization of C-nucleoside triphosphate derivatives.⁵ Apart from the variation of one substituent, the synthesis of a 2D library of 2,4-disubstituted pyrimidin-5-yl C-2′-deoxyribonucleosides has been developed⁶ through two consecutive regioselective cross-coupling reactions of the corresponding 2,4-dichloropyrimidine C-nucleoside intermediate. Here we report on the synthesis of a series of 2,6-disubstituted pyridine C-nucleosides.

Results and discussion

In our previous synthesis of 2,4-disubstituted pyrimidine C-nucleosides,⁶ we have advantageously used the different reactivities of the two chlorines in 2,4-dichloropyrimidine for regioselective reactions. However, in the analogous 2,6-dichloropyridine C-nucleosides, the reactivity of the chlorines is comparable and thus no selectivity would be expected. Therefore our strategy for the target 2,6-disubstituted pyridin-3-yl C-2′-deoxyribonucleosides was based on chemoselective transformations^7,8 of either 2-bromo-6-chloro- or 6-bromo-2-chloropyridin-3-yl C-deoxyribonucleoside intermediates.

The synthesis of both bromo-chloropyridine C-nucleoside intermediates started from 3′-O-TBS-protected glycal 1 which can be easily prepared in three steps from thymidine.⁹ The Heck coupling of 6-bromo-2-chloro-3-iodopyridine with glycal 1 in the presence of Pd(OAc)₂, tris(pentafluorophenyl)phosphine and silver carbonate was performed in freshly distilled chloroform at 70 °C (Scheme 1). After 10 hours all starting material was consumed and, because partial desilylation was observed by TLC, the crude reaction mixture was directly treated with Et₃N·3HF in THF to give fully deprotected ketone 2 in 52% yield (for two steps) as a pure β-anomer. The subsequent stereoselective reduction of 2 by NaBH(OAc)₃ proceeded smoothly giving rise to the desired C-2′-deoxyribonucleoside intermediate 3 in very good 85% yield. The crystal structure of 6-bromo-2-chloropyridine C-nucleoside 3 was determined by X-ray diffraction, which independently confirmed its β-configuration (Fig. 1). Re-protection of 3 by treatment with TBSCl gave the silylated C-nucleoside 4 in 78% yield. An analogous Heck coupling of 1 with 2-bromo-6-chloro-3-iodopyridine under the same conditions as above gave regioisomeric ketone 5 in 59% yield (for two steps) (Scheme 1). Subsequent reduction by NaBH(OAc)₃ afforded C-2′-deoxyribonucleoside 6 in 87% yield, which was again silylated to give the desired protected nucleoside intermediate 7 in excellent 92% yield.

Scheme 1 Reagents and conditions: (i) 1. Pd(OAc)₂, (PhF₅)₃P, Ag₂CO₃, CHCl₃, 70 °C, 10 h; 2. Et₃N·3HF, THF, rt, 15 min; (ii) NaBH(OAc)₃, AcOH, CH₃CN, 0 °C, 5 min; (iii) TBSCl, imidazole, DMF, rt, 14 h.

Fig. 1 Crystal structures of compounds (a) 3 (CCDC 927315) and (b) 8b (CCDC 927314).

Having the free (3 and 6) as well as the protected (4 and 7) key bromo-chloropyridine C-nucleoside intermediates, we investigated the chemoselectivity of cross-coupling reactions and nucleophilic substitutions. The bromine atom should be more reactive than chlorine but, on the other hand, steric and other factors can also play a role.

The cross-coupling of protected 6-bromo-2-chloropyridine C-nucleoside 4 with 1.1 equiv. of Me₃Al in the presence of Pd(PPh₃)₄ proceeded chemoselectively to give 2-chloro-6-methylpyridine 8a as the only product in excellent 87% yield (Scheme 2). When the same reaction was performed with 4 equiv. of Me₃Al and prolonged reaction time, the product of disubstitution 9a was isolated in 80% yield. Deprotection of 8a and 9a with Et₃N·3HF afforded free C-nucleosides 8b (89%) and 9b (88%). The structure of free 2-chloro-6-methylpyridine C-nucleoside 8b was also confirmed by X-ray analysis (Fig. 1). In contrast, cross-coupling of the isomeric 2-bromo-6-chloropyridine intermediate 7 with 1.1 equivalents of Me₃Al was completely nonselective and only an unseparable mixture of the starting compound and both products of mono-substitution was obtained.

Scheme 2 Reagents and conditions: (i) 1.1 equiv. Me₃Al, Pd(PPh₃)₄, heptane, 70 °C, 3 h; (ii) 4 equiv. Me₃Al, Pd(PPh₃)₄, heptane, 70 °C, 12 h; (iii) Et₃N·3HF, THF, rt, 14 h; (iv) 1. TMSA, Pd(PPh₃)₂Cl₂, CuI, Et₃N, DMF, 90 °C; 2. NH₃, MeOH, rt, 30 min; (v) LiN(SiMe₃)₂, Ph₃SiNH₂, CyJohnPhos, Pd₂(dba)₃, THF, 50 °C, 3 h; (vi) MeONa, MeOH, 120 °C, 10 d; (vii) KOH, t-butyl-XPhos, Pd₂dba₃, 100 °C.

Mono-methylated 2-chloropyridine nucleoside 8a was used for a series of follow-up transformations (Scheme 2). The Sonogashira cross-coupling with trimethylsilylacetylene catalyzed by Pd(PPh₃)₂Cl₂ followed by ammonolysis afforded 2-ethynyl-6-methylpyridine C-nucleoside 10a (56%). Pd-catalyzed Hartwig–Buchwald amination¹⁰ with a mixture of LiN(SiMe₃)₂ and Ph₃SiNH₂ gave 2-amino-6-methylpyridine C-nucleoside 11a in 68% yield. Deprotection of silylated intermediates 10a and 11a furnished free C-nucleosides 10b (65%) and 11b (82%). The reaction of unprotected 2-chloro-6-methylpyridine C-nucleoside 8b with sodium methoxide in MeOH was very sluggish (full conversion was accomplished only after 10 days of heating at 120 °C) but finally gave 2-methoxy-6-methylpyridine C-nucleoside 12 in good 77% yield. Attempted Pd-catalyzed hydroxylation¹¹ using KOH and t-butyl-XPhos did not proceed and only the starting compound and some degradation products were observed (probably due to instability of the pyridone product^4f).

The Suzuki–Miyaura cross-coupling of 2-bromo-6-chloropyridine C-nucleoside 7 with 0.9 equivalent of phenylboronic acid in the presence of Ph(PPh₃)₄ at 60 °C proceeded chemoselectively at position 2 by displacement of the bromine to afford 6-chloro-2-phenylpyridine C-nucleoside 13a in 63% yield (Scheme 3). When we used 3 equiv. of phenylboronic acid and increased the temperature to 100 °C, 2,6-diphenylpyridine C-nucleoside 14a was obtained as a product of double substitution in excellent 95% yield. An analogous reaction of regioisomeric 6-bromo-2-chloropyridine C-nucleoside 4 with 1 equiv. of phenyl boronic acid afforded an unseparable mixture of the starting compound with the product of substitution of the bromine atom at position 6. Silylated nucleosides 13a and 14a were deprotected using Et₃N·3HF to obtain free C-nucleosides 13b (91%) and 14b (81%).

Scheme 3 Reagents and conditions: (i) 0.9 equiv. PhB(OH)₂, Pd(PPh₃)₄, K₂CO₃, PhMe, 60 °C, 12 h; (ii) 3 equiv. PhB(OH)₂, Pd(PPh₃)₄, K₂CO₃, PhMe, 100 °C, 12 h; (iii) Et₃N·3HF, THF, rt, 14 h; (iv) LiN(SiMe₃)₂, CyJohnPhos, Pd₂(dba)₃, THF, 60 °C, 12 h; (v) Pd(PPh₃)₄, Me₃Al, THF, 70 °C, 12 h.

Mono-substituted 6-chloro-2-phenylpyridine C-nucleoside 13a was then used for subsequent cross-coupling reactions. Hartwig–Buchwald amination with LiN(SiMe₃)₂ gave 6-amino-2-phenylpyridine C-nucleoside 15a in excellent 91% yield. Cross-coupling with trimethylaluminum afforded 6-methyl-2-phenylpyridine C-nucleoside 16a in excellent 91% yield. Deprotection of silylated intermediates gave free C-nucleosides 15b (67%) and 16b (85%).

In order to introduce amino or methoxy groups, we have studied the reactivity of intermediates 3 and 6 in nucleophilic substitutions. Our previous studies⁶ showed good regioselectivity of nucleophilic aminations of 2,4-dichloropyrimidine C-nucleoside. Therefore, we tested reactions of 3 or 6 with methanolic ammonia or copper(I)-catalyzed reaction with liquid ammonia¹² in an autoclave using temperatures up to 120 °C but in all cases only the starting material was recovered and we did not observe any reaction. Surprisingly, attempted Buchwald–Hartwig aminations of protected intermediates 4 or 7 did not work either. Nucleophilic substitution of 6 with NaOMe proceeded only at elevated temperature (80 °C) to give an unseparable mixture of the starting compound and both mono-substituted derivatives. The same reaction at higher temperature (120 °C) led to complex mixtures. It seems that the mono-substituted intermediates (containing an electron-donating substituent) are deactivated for another nucleophilic substitution.

Next we studied nucleophilic substitutions with sodium methanethiolate (Scheme 4). The reaction of silylated intermediate 4 with 10 equivalents of NaSMe in DMF at 80 °C led to double substitution with simultaneous deprotection (due to basic conditions) affording 2,6-bis(methylsulfanyl)pyridine C-nucleoside 17 in good 79% yield. The reaction of 4 with 1.2 equivalents of sodium methanethiolate at rt in DMF gave a mixture of both mono-substituted derivatives 18a and 19a in the ratio ca. 1 : 1. Luckily, we were able to separate them using the flash purification system with a very slow gradient of hexanes to 1% EtOAc in hexanes to obtain 2-chloro-6-(methylsulfanyl)pyridine C-nucleoside 18a (48%) and 6-bromo-2-(methylsulfanyl)pyridine C-nucleoside 19a (43%). Pd-catalyzed methylation of compounds 18a or 19a with trimethylaluminum gave two regioisomeric methyl-(methylsulfanyl)pyridine C-nucleosides 20a (49%) and 21a (58%). All silylated compounds were deprotected to afford free C-nucleosides 18b–21b.

Scheme 4 Reagents and conditions: (i) MeSNa 10 equiv., DMF, 80 °C, 12 h; (ii) MeSNa 1.2 equiv., DMF, rt, 12 h; (iii) Et₃N·3HF, THF, rt, 14 h; (iv) Me₃Al, Pd(PPh₃)₄, 90 °C, 12 h.

Attempted Sonogashira chemoselective cross-couplings of 4 with (trimethylsilyl)acetylene (TMSA) (Scheme 5) were very difficult to perform since the desired 2-chloro-6-(TMS-ethynyl)pyridine C-nucleoside was unseparable from starting intermediate 4. Finally, we found out that Sonogashira cross coupling with 1 equiv. of trimethylsilylacetylene catalyzed by Pd(PPh₃)₂Cl₂ followed by direct amonolysis gave us a separable mixture of starting compound 4 (37%) and desired product 22a in acceptable 53% yield. When we performed the same reaction with the excess of trimethylsilylacetylene (10 equiv.) and increased the temperature to 90 °C, the product of disubstitution, protected 2,6-bis(ethynyl)pyridine C-nucleoside 23a, was isolated in excellent 95% yield. In order to convert the ethynyl groups to acetyl, we have prepared partially and fully deprotected bis(ethynyl)pyridine C-nucleosides 23b and 23c and attempted a gold catalyzed hydration of the triple bond.¹³ Unfortunately, only deprotection was observed despite having tried many different conditions.

Scheme 5 Reagents and conditions: (i) 1. 1 equiv. TMSA, Pd(PPh₃)₂Cl₂, CuI, Et₃N, DMF, 60 °C; 2. NH₃, MeOH, rt, 30 min; (ii) 10 equiv. TMSA, Pd(PPh₃)₂Cl₂, CuI, Et₃N, DMF, 90 °C; (iii) Et₃N·3HF, THF, rt, 14 h; (iv) NH₃, MeOH, rt, 30 min; (v) NaAuCl₄, MeOH, H₂O, 80 °C, 6–72 h; (vi) TBAF, THF, rt, 12 h.

The Stille cross-coupling reaction was used for the synthesis of bipyridine and terpyridine C-nucleosides (Scheme 6). The reaction of 4 with tributyl(2-pyridyl)stannane catalyzed by PdCl₂(PPh₃)₂ gave only compound 24a, as a product of chemoselective replacement of the bromine atom, in very good 82% yield even when we used 2 equiv. of stannane. The palladium catalyst is probably strongly coordinated to the bipyridine scaffold and any second reaction is prevented. In contrast, the Stille cross-coupling catalyzed by Pd(PPh₃)₄ cleanly afforded terpyridine C-nucleoside 25a, as a product of double substitution, in excellent 92% yield. Deprotection gave bi- and terpyridine C-nucleosides 24b and 25b which could be used in metalla-base pairs.¹⁴

Scheme 6 Reagents and conditions: (i) 2 equiv. 2-pyridylSnBu₃, PdCl₂(PPh₃)₂, DMF, 100 °C, 12 h; (ii) 2 equiv. 2-pyridylSnBu₃, Pd(PPh₃)₄, toluene, 110 °C, 12 h; (iii) Et₃N·3HF, THF, rt, 14 h.

Finally, we attempted to introduce a vinyl group by Fürstner's Fe-catalyzed cross-coupling reaction¹⁵ with vinylmagnesium bromide (Scheme 7). Unfortunately the cross-coupling did not proceed and, instead, the magnesiation of the bromopyridine occurred which, after hydrolytic work-up, gave chloropyridine 26a, as a product of debromination, in moderate 47% yield. Also this compound was deprotected to free nucleoside 26b.

Scheme 7 Reagents and conditions: (i) vinylMgBr, Fe(acac)₃, rt, 12 h; (ii) Et₃N·3HF, THF, rt, 14 h.

All the title free nucleosides were subjected to biological activity screening. The cytotoxic activity in vitro was studied on the following cell cultures: (i) human promyelocytic leukemia HL60 cells (ATCC CCL 240); (ii) human cervix carcinoma HeLa S3 cells (ATCC CCL 2.2); (iii) human T lymphoblastoid CCRF-CEM cell line (ATCC CCL 119), and (iv) hepatocellular carcinoma cells HepG2 (ATCC HB 8065). Cell viability was determined following a 3-day incubation using a metabolic 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) based method.¹⁶ The antiviral activity was tested against HCV genotype 1A, 1B and 2A replicons.¹⁷ None of the nucleosides showed any significant cytotoxicity or antiviral activity in these assays at concentrations up to 10 μM.

Conclusions

Systematic study of the chemoselectivity of cross-coupling reactions and nucleophilic substitutions of regioisomeric 2-bromo-6-chloro- and 6-bromo-2-chloropyridin-3-yl deoxyribo-nucleosides 7 and 4 was performed. The cross-couplings generally proceeded with good chemoselectivity at the position of the bromine but the choice of the starting compound depended on the separability of the mono-substituted products from the starting compound. On the other hand, nucleophilic substitution with NaSMe was unselective giving a separable mixture of both mono-substituted products, whereas the reactions with ammonia or NaOMe did not proceed or led to complex mixtures (at elevated temperature). The mono-substituted halopyridine C-nucleoside intermediates were used for another coupling or S_N to give a small library of 2,6-disubstituted pyridin-3-yl C-deoxyribonucleosides. None of the title nucleosides exerted any antiviral or cytostatic activity in concentrations up to 10 μM. Some of the disubstituted pyridine nucleosides will be converted to triphosphates and further tested for polymerase incorporation in the quest for the extension of the genetic alphabet.²

Experimental

All cross-coupling reactions were carried out in evacuated flame-dried glassware with magnetic stirring under an argon atmosphere. THF, toluene, and hexanes were dried and distilled from sodium–benzophenone. Other reagents were purchased from commercial suppliers and used as received. NMR spectra were recorded on a 400 MHz spectrometer (¹H at 400 MHz, ¹³C at 100.6 MHz), a 500 MHz spectrometer (¹H at 500 and ¹³C MHz at 125.8), and/or a 600 MHz spectrometer (¹H at 600 MHz, ¹³C at 151 MHz). The samples were measured in CDCl₃ using TMS as an internal standard or in DMSO-d₆ referenced to the residual solvent signal (¹H NMR δ 2.50 ppm, ¹³C NMR 39.7 ppm). Chemical shifts are given in ppm (δ scale) and coupling constants (J) in hertz. Complete assignment of all NMR signals was performed using a combination of 2D-NMR (H,H-COSY, H,C-HSQC, and H,C-HMBC) experiments and configurations were established by two-dimensional ROESY spectra. High performance flash chromatography (HPFC) purifications were performed with Biotage SP1 apparatus on KP-Sil and KP-C18-HS columns. Cytostatic¹⁶ and anti-HCV¹⁷ activity screening was performed according to literature procedures.

General procedure for the deprotection of the TBDMS group

Et₃N·3HF (320 μL, 1.95 mmol) was added to a solution of silylated C-nucleoside (0.4 mmol) in THF (2 mL), and the mixture was stirred at room temperature for 14 h. After the reaction was completed (TLC in hexanes–EtOAc 10 : 1), solvents were removed under reduced pressure, and the crude product was chromatographed on silica gel (20 g) eluted with a gradient of chloroform to 15% MeOH in chloroform to give free C-nucleosides.

1β-(6-Bromo-2-chloropyridin-3-yl)-1,2,3-trideoxy-3-oxo-D-ribofuranose (2). Freshly distilled CHCl₃ (20 mL) was added to an argon-purged, flame-dried flask containing Pd(OAc)₂ (390 mg, 1.74 mmol) and P(PhF₅)₃ (1.85 g, 3.47 mmol), and the mixture was stirred at room temperature for 30 min. This solution was then added via a syringe to a mixture of 6-bromo-2-chloro-3-iodopyridine (3.32 g, 10.42 mmol), glycal 1 (2.00 g, 8.68 mmol) and Ag₂CO₃ (3.58 g, 13.02 mmol) in CHCl₃ (20 mL), and the reaction mixture was stirred at 70 °C for 10 h. The reaction mixture was then cooled and filtered on a pad of Celite and eluted with CHCl₃. Solvents were removed under vacuum, the crude product was dissolved in THF (100 mL), Et₃N·3HF (2 mL; 12.3 mmol) was added and the solution was stirred at rt for 15 min. The solvents were removed under vacuum, and the crude product was chromatographed on silica gel eluting with a gradient of chloroform to 1% MeOH in chloroform to give 2 (1.38 g, 52% for two steps) as a yellow oil. HRMS (ESI) for C₁₀H₉BrClNO₃: [M − H] calculated, 303.9382; found, 303.9382. ¹H NMR (500 MHz, CDCl₃) 2.26 (dd, 1H, J_gem = 18.2 Hz, J_2′a,1′ = 10.6 Hz, H-2′a); 3.18 (dd, 1H, J_gem = 18.2 Hz, J_2′b,1′ = 6.2 Hz, H-2′b); 3.99–4.05 (m, 2H, H-5′); 4.11 (t, 1H, J_4′,5′a = J_4′,5′b = 3.4 Hz, H-4′); 5.43 (ddt, 1H, J_1′,2′a = 10.6 Hz, J_1′,2′b = 6.2 Hz, J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.52 (bd, 1H, J_5,4 = 8.1 Hz, H-5); 7.97 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): 43.70 (CH₂-2′); 61.51 (CH₂-5′); 73.30 (CH-1′); 82.08 (CH-4′); 127.52 (CH-5); 134.64 (C-3); 137.72 (CH-4); 139.64 (C-6); 147.73 (C-2); 212.08 (C-3′). IR spectrum (KBr): 3436, 3095, 3068, 1760, 1574, 1546, 1426, 1221, 1033, 829, 736.

1β-(6-Bromo-2-chloropyridin-3-yl)-1,2-dideoxy-D-ribofuranose (3). NaBH(OAc)₃ (1.53 g, 7.25 mmol) was added to a flame-dried flask containing a solution of the nucleoside 2 (1.48 g, 4.83 mmol) in a mixture of AcOH–CH₃CN 1/10 (50 mL) at 0 °C under argon. After 5 min, all of the starting material was consumed and a solution of EtOH–H₂O 1/1 (10 mL) was added to neutralize the solution. Then the solvents were evaporated in vacuum, and the crude product was chromatographed on silica gel in a gradient of chloroform to 5% MeOH in chloroform. Nucleoside 3 (1.27 g, 85%) was isolated as a white foam. HRMS (ESI) for C₁₀H₁₁BrClNO₃: [M + H] calculated, 307.9684; found, 307.9684. ¹H NMR (500 MHz, CD₃OD) 1.78 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.47 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.68 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.71 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.5 Hz, H-5′b); 3.97 (td, 1H, J_4′,5′a = J_4′,5′b = 4.7 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.32 (bdtd, 1H, J_3′,2′a = 5.9 Hz, J_3′,4′ = J_3′,2′b = 2.4 Hz, J_3′,1′ = 0.5 Hz, H-3′); 5.32 (ddq, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.7 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.57 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 8.02 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 42.98 (CH₂-2′); 63.66 (CH₂-5′); 74.10 (CH-3′); 77.18 (CH-1′); 89.27 (CH-4′); 128.66 (CH-5); 138.16 (C-3); 139.46 (C-6); 139.96 (CH-4); 148.45 (C-2). IR spectrum (KBr): 3349, 3297, 3061, 1573, 1542, 1485, 1419, 1220, 1097, 1062, 1047, 823, 735.

1β-(6-Bromo-2-chloropyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (4). Imidazole (1.27 g, 18.6 mmol) and then TBDMSCl (4.49 mg, 29.8 mmol) were added to a flame-dried flask containing a solution of the nucleoside 3 (2.3 g, 7.45 mmol) in dry DMF (50 mL) at 0 °C under argon and the solution was allowed to warm to room temperature and was stirred for 14 h. The reaction mixture was then poured into a saturated solution of NaCl (100 mL) and extracted with EtOAc (3 × 30 mL). Collected organic fractions were washed with a saturated NaCl solution, dried over MgSO₄, and the solvents were evaporated under vacuum. The crude product was chromatographed on silica gel in a gradient of hexanes to 5% EtOAc in hexanes to give the desired nucleoside 4 (3.1 g, 78%) as a colorless oil. HRMS (ESI) for C₂₂H₃₉BrClNO₃Si₂: [M + H] calculated, 536.1413; found, 536.1413. ¹H NMR (500 MHz, CDCl₃) 0.084, 0.086 and 0.094 (4 × s, 4 × 3H, CH₃Si); 0.89 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.70 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.4 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.41 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.5 Hz, H-2′b); 3.71 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.6 Hz, H-5′a); 3.76 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.3 Hz, H-5′b); 3.97 (ddd, 1H, J_4′,5′a = 4.6 Hz, J_4′,5′b = 3.3 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.38 (dtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.6 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.33 (bddq, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 5.9 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.39 (dd, 1H, J_5,4 = 8.0 Hz, J_5,1′ = 0.6 Hz, H-5); 7.90 (dd, 1H, J_4,5 = 8.0 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.49, −5.41, −4.76 and −4.62 (CH₃Si); 17.98 and 18.29 ((CH₃)₃C); 25.75 and 25.87 ((CH₃)₃C); 42.30 (CH₂-2′); 63.22 (CH₂-5′); 73.65 (CH-3′); 75.84 (CH-1′); 87.95 (CH-4′); 127.01 (CH-5); 137.08 (C-3); 138.08 (CH-4), 138.38 (C-6); 147.48 (C-2). IR spectrum (CCl₄): 3093, 3060, 2956, 2897, 1575, 1545, 1472, 1463, 1424, 1407, 1390, 1362, 1257, 1223, 1098, 1030, 1006, 939, 838, 671.

1β-(2-Bromo-6-chloropyridin-3-yl)-1,2,3-trideoxy-3-oxo-D-ribofuranose (5). Freshly distilled CHCl₃ (18 mL) was added to an argon-purged, flame-dried flask containing Pd(OAc)₂ (562 mg, 2.34 mmol) and P(PhF₅)₃ (2.49 g, 4.69 mmol), and the mixture was stirred at room temperature for 30 min. This solution was then added via a syringe to a mixture of 2-bromo-6-chloro-3-iodopyridine (4.48 g, 14.06 mmol), glycal 1 (2.70 g, 11.72 mmol) and Ag₂CO₃ (4.83 g, 17.58 mmol) in CHCl₃ (18 mL), and the reaction mixture was stirred at 70 °C for 10 h. The reaction mixture was then cooled and filtered on a pad of Celite and eluted with CHCl₃. Solvents were then removed in vacuum, the crude product was dissolved in THF (100 mL), Et₃N·3HF (3 mL; 18.5 mmol) was added and the solution was stirred at rt for 15 min. The solvents were removed under vacuum, and the crude product was chromatographed on silica gel eluting with a gradient of chloroform to 1% MeOH in chloroform to give 5 (2.12 g, 59% for two steps) as a yellow foam. HRMS (ESI) for C₁₀H₉BrClNO₃: [M − H] calculated, 303.9382; found, 303.9384. ¹H NMR (500 MHz, CDCl₃) 2.23 (dd, 1H, J_gem = 18.2 Hz, J_2′a,1′ = 10.6 Hz, H-2′a); 3.21 (dd, 1H, J_gem = 18.2 Hz, J_2′b,1′ = 6.2 Hz, H-2′b); 3.98–4.04 (m, 2H, H-5′); 4.11 (t, 1H, J_4′,5′a = J_4′,5′b = 3.3 Hz, H-4′); 5.41 (ddt, 1H, J_1′,2′a = 10.6 Hz, J_1′,2′b = 6.2 Hz, J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.37 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 8.03 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): 43.85 (CH₂-2′); 61.44 (CH₂-5′); 74.87 (CH-1′); 82.19 (CH-4′); 123.91 (CH-5); 136.72 (C-3); 137.85 (CH-4); 139.30 (C-2); 149.75 (C-6); 212.23 (C-3′). IR spectrum (KBr): 3428, 3095, 3071, 2924, 2854, 1760, 1630, 1575, 1546, 1460, 1429, 1224, 1057, 1032, 831, 735.

1β-(2-Bromo-6-chloropyridin-3-yl)-1,2-dideoxy-D-ribofuranose (6). NaBH(OAc)₃ (2.9 g, 13.7 mmol) was added to a flame-dried flask containing a solution of the nucleoside 5 (2.8 g, 9.13 mmol) in a mixture of AcOH–CH₃CN 1/10 (80 mL) at 0 °C under argon. After 5 min, all of the starting material was consumed and a solution of EtOH–H₂O 1/1 (20 mL) was added to neutralize the solution. Then the solvents were evaporated in vacuum, and the crude product was chromatographed on silica gel in a gradient of chloroform to 5% MeOH in chloroform. Nucleoside 6 (2.45 g, 87%) was isolated as a white foam. HRMS (ESI) for C₁₀H₁₁BrClNO₃: [M + H] calculated, 307.9684; found, 307.9683. ¹H NMR (500 MHz, CD₃OD) 1.76 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.51 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.1 Hz, H-2′b); 3.69 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.72 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.4 Hz, H-5′b); 3.97 (btd, 1H, J_4′,5′a = J_4′,5′b = 4.7 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.32 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 2.1 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.31 (ddq, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.8 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.44 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 8.07 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 43.18 (CH₂-2′); 66.65 (CH₂-5′); 74.09 (CH-3′); 78.88 (CH-1′); 89.32 (CH-4′); 124.95 (CH-5); 139.94 (C-2); 139.99 (CH-4); 140.20 (C-3); 149.82 (C-6). IR spectrum (KBr): 3376, 3267, 3098, 3059, 1574, 1548, 1486, 1470, 1267, 1070, 1044, 1017, 949, 932, 898.

1β-(2-Bromo-6-chloropyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (7). Imidazole (0.69 g, 10.18 mmol) and then TBDMSCl (2.45 mg, 16.3 mmol) were added to a flame-dried flask containing a solution of the nucleoside 6 (1.26 g, 4.07 mmol) in dry DMF (25 mL) at 0 °C under argon and the solution was allowed to warm to room temperature and was stirred for 14 h. The reaction mixture was then poured into a saturated solution of NaCl (100 mL) and extracted with EtOAc (3 × 50 mL). Collected organic fractions were washed with a saturated NaCl solution, dried over MgSO₄, and the solvents were evaporated under vacuum. The crude product was chromatographed on silica gel in a gradient of hexanes to 3% EtOAc in hexanes to give the desired nucleoside 7 (2.01 g, 92%) as a colorless oil. HRMS (ESI) for C₂₂H₃₉BrClNO₃Si₂: [M + H] calculated, 536.1413; found, 536.1412. ¹H NMR (500 MHz, CDCl₃) 0.085, 0.089 and 0.10 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.68 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.4 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.45 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.6 Hz, H-2′b); 3.72 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.5 Hz, H-5′a); 3.77 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.3 Hz, H-5′b); 3.97 (ddd, 1H, J_4′,5′a = 4.5 Hz, J_4′,5′b = 3.3 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.38 (bdtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.7 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.31 (ddq, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 5.9 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.26 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 7.95 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.50, −5.42, −4.76 and −4.62 (CH₃Si); 17.98 and 18.28 ((CH₃)₃C); 25.74 and 25.87 ((CH₃)₃C); 42.47 (CH₂-2′); 63.21 (CH₂-5′); 73.65 (CH-3′); 77.50 (CH-1′); 88.00 (CH-4′); 123.41 (CH-5); 138.08 (CH-4); 139.00 and 139.07 (C-2,3); 148.66 (C-6). IR spectrum (CCl₄): 3093, 3059, 2956, 2897, 1577, 1545, 1472, 1463, 1406, 1390, 1362, 1278, 1258, 1097, 939, 891, 838.

1β-(2-Chloro-6-methylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (8a). Me₃Al (1.5 mL, 1.5 mmol, 1.1 equiv., 1 M in heptane) was added to a flame-dried flask containing 4 (729 mg, 1.36 mmol) and Pd(PPh₃)₄ (161 mg, 0.14 mmol, 10 mol%) under argon. The mixture was stirred at 70 °C for 3 h, quenched by pouring into saturated NaH₂PO₄ (50 mL), and extracted with EtOAc (3 × 50 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 5% EtOAc in hexanes to give 8a (555 mg, 87%) as a colorless oil. HRMS (ESI) for C₂₃H₄₂ClNO₃Si₂: [M + H] calculated, 472.2465; found, 472.2465. ¹H NMR (500 MHz, CDCl₃) 0.083, 0.085, 0.087 and 0.093 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.70 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 9.5 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.40 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.5 Hz, H-2′b); 2.51 (s, 3H, CH₃); 3.69 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 4.9 Hz, H-5′a); 3.77 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.96 (ddd, 1H, J_4′,5′a = 4.9 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.38 (dtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.6 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.37 (bdd, 1H, J_1′,2′a = 9.5 Hz, J_1′,2′b = 5.8 Hz, H-1′); 7.06 (dm, 1H, J_5,4 = 7.8 Hz, H-5); 7.88 (dd, 1H, J_4,5 = 7.8 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.48, −5.42, −4.76 and −4.62 (CH₃Si); 17.98 and 18.29 ((CH₃)₃C); 23.71 (CH₃); 25.76 and 25.88 ((CH₃)₃C); 42.42 (CH₂-2′); 63.33 (CH₂-5′); 73.73 (CH-3′); 76.14 (CH-1′); 87.74 (CH-4′); 122.18 (CH-5); 134.16 (C-3); 136.10 (CH-4); 147.50 (C-2); 157.50 (C-6). IR spectrum (CCl₄): 3068, 2956, 2898, 1597, 1569, 1555, 1471, 1462, 1435, 1407, 1389, 1376, 1362, 1257, 1220, 1097, 1031, 1006, 939, 838.

1β-(2-Chloro-6-methylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (8b). Compound 8b was prepared from 8a (225 mg, 0.93 mmol) by the general procedure to yield 8b (103 mg, 89%) as a yellow solid. HRMS (ESI) for C₁₁H₁₄ClNO₃: [M + H] calculated, 244.0735; found, 244.0737. ¹H NMR (500 MHz, CD₃OD): 1.77 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.45 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.48 (s, 3H, CH₃); 3.68 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.71 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.7 Hz, H-5′b); 3.97 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.32 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.36 (bdd, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.7 Hz, H-1′); 7.25 (dm, 1H, J_5,4 = 7.8 Hz, H-5); 8.02 (dd, 1H, J_4,5 = 7.8 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 23.24 (CH₃); 43.20 (CH₂-2′); 63.77 (CH₂-5′); 74.16 (CH-3′); 77.44 (CH-1′); 89.12 (CH-4′); 123.97 (CH-5); 135.38 (C-3); 138.20 (CH-4); 148.33 (C-2); 159.17 (C-6). IR spectrum (KBr): 3356, 3230, 3066, 2986, 2919, 1599, 1554, 1463, 1439, 1379, 1171, 1061, 1040, 938.

1β-(2,6-Dimethylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (9a). Me₃Al (1.4 mL, 1.4 mmol, 4.0 equiv., 1 M in heptane) was added to a flame-dried flask containing 4 (193 mg, 0.36 mmol) and Pd(PPh₃)₄ (42 mg, 0.036 mmol, 10 mol%) under argon. The mixture was stirred at 70 °C for 12 h, quenched by pouring into saturated NaH₂PO₄ (50 mL), and extracted with EtOAc (3 × 50 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 9% EtOAc in hexanes to give 9a (130 mg, 80%) as a colorless oil. HRMS (ESI) for C₂₄H₄₅NO₃Si₂: [M + H] calculated, 452.3011; found, 452.3010. ¹H NMR (500 MHz, CDCl₃): 0.08 and 0.09 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.73 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 5.5 Hz, H-2′a); 2.17 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.5 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.52 (s, 3H, CH₃-2); 2.53 (s, 3H, CH₃-6); 3.67 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 5.2 Hz, H-5′a); 3.78 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.6 Hz, H-5′b); 3.95 (ddd, 1H, J_4′,5′a = 5.2 Hz, J_4′,5′b = 3.6 Hz, J_4′,3′ = 2.3 Hz, H-4′); 4.41 (bdtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.2 Hz, J_3′,1′ = 0.5 Hz, H-3′); 5.28 (dd, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.4 Hz, H-1′); 6.99 (d, 1H, J_5,4 = 8.0 Hz, H-5); 7.79 (d, 1H, J_4,5 = 7.9 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.48, −5.40, −4.70 and −4.64 (CH₃Si); 17.99 and 18.31 ((CH₃)₃C); 21.52 (CH₃-2); 23.72 (CH₃-6); 25.78 and 25.89 ((CH₃)₃C); 42.84 (CH₂-2′); 63.49 (CH₂-5′); 74.05 (CH-3′); 76.07 (CH-1′); 87.70 (CH-4′); 121.11 (CH-5); 133.37 (C-3); 134.11 (CH-4); 153.59 (C-2); 155.70 (C-6). IR spectrum (CCl₄): 3068, 2956, 2930, 2897, 2858, 1596, 1578, 1471, 1463, 1450, 1406, 1390, 1372, 1362, 1290, 1257, 1090, 940, 838.

1β-(2,6-Dimethylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (9b). Compound 9b was prepared from 9a (152 mg, 0.34 mmol) by the general procedure to yield 9b (66 mg, 88%) as a yellow solid. HRMS (ESI) for C₁₂H₁₇NO₃: [M + H] calculated, 224.1281; found, 224.1281. ¹H NMR (500 MHz, CD₃OD): 1.81 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.4 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.28 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.4 Hz, J_2′b,3′ = 1.8 Hz, H-2′b); 2.47 (s, 3H, CH₃-6); 2.49 (s, 3H, CH₃-2); 3.67–3.71 (m, 2H, H-5′); 3.95 (td, 1H, J_4′,5′a = J_4′,5′b = 4.9 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.33 (bdt, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = J_3′,2′b = 2.2 Hz, H-3′); 5.30 (dd, 1H, J_1′,2′a = 10.4 Hz, J_1′,2′b = 5.4 Hz, H-1′); 7.11 (bd, 1H, J_5,4 = 8.0 Hz, H-5); 7.88 (d, 1H, J_4,5 = 8.0 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 21.20 (CH₃-2); 23.30 (CH₃-6); 43.24 (CH₂-2′); 63.84 (CH₂-5′); 74.32 (CH-3′); 77.38 (CH-1′); 89.01 (CH-4′); 122.59 (CH-5); 134.68 (C-3); 135.88 (CH-4); 155.09 (C-2); 157.15 (C-6). IR spectrum (KBr): 3307, 1598, 1583, 1476, 1455, 1381, 1282, 1142, 1058, 1031, 976, 961.

1β-(2-Ethynyl-6-methylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (10a). DMF (3 mL) and TMSA (415 μL, 2.96 mmol) were added through a septum to an argon-purged vial containing 8a (280 mg, 0.59 mmol), Pd(PPh₃)₂Cl₂ (42 mg, 0.06 mmol), CuI (1 mg, 0.005 mmol) and Et₃N (827 μL, 5.93 mmol). The resulting mixture was stirred at 90 °C for 8 h. The reaction mixture was then cooled and filtered on a pad of Celite and eluted with CHCl₃. Solvents were then removed in vacuum, the crude product was dissolved in methanolic ammonia (26%, 10 mL) and the solution was stirred at rt for 30 min. The solvents were removed under vacuum, and the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 8% EtOAc in hexanes to give 10a (153 mg, 56% for two steps) as a colorless oil. HRMS (ESI) for C₂₅H₄₃NO₃Si₂: [M + H] calculated, 462.2854; found, 462.2853. ¹H NMR (500 MHz, DMSO-d₆): 0.07, 0.08 and 0.09 (4 × s, 4 × 3H, CH₃Si); 0.87 and 0.89 (2 × s, 2 × 9H, (CH₃)₃C)); 1.73 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.2 Hz, H-2′a); 2.22 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.5 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 2.43 (s, 3H, CH₃-6); 3.61 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 5.9 Hz, H-5′a); 3.72 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 4.0 Hz, H-5′b); 3.85 (ddd, 1H, J_4′,5′a = 5.9 Hz, J_4′,5′b = 4.0 Hz, J_4′,3′ = 1.9 Hz, H-4′); 4.37 (bdt, 1H, J_3′,2′a = 5.2 Hz, J_3′,4′ = J_3′,2′b = 1.9 Hz, H-3′); 4.50 (s, 1H, CH≡C-2); 5.37 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.5 Hz, H-1′); 7.28 (d, 1H, J_5,4 = 8.1 Hz, H-5); 7.79 (bd, 1H, J_4,5 = 8.1 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): −5.34, −5.26, −4.64 and −4.53 (CH₃Si); 17.89 and 18.10 ((CH₃)₃C); 23.72 (CH₃-6); 25.86 and 25.92 ((CH₃)₃C); 42.44 (CH₂-2′); 63.38 (CH₂-5′); 74.28 (CH-3′); 76.11 (CH-1′); 80.86 (CH≡C-2); 84.26 (CH≡C-2); 87.55 (CH-4′); 123.66 (CH-5); 133.72 (CH-4); 137.87 (C-3); 138.36 (C-2); 157.47 (C-6). IR spectrum (CCl₄): 3310, 3062, 2956, 2929, 2897, 2858, 2523, 2803, 2113, 1585, 1566, 1472, 1463, 1445, 1406, 1389, 1361, 1370, 1275, 1258, 1177, 1098, 1087, 1006, 939, 838, 652, 632.

1β-(2-Ethynyl-6-methylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (10b). Compound 10b was prepared from 10a (97 mg, 0.11 mmol) by the general procedure to yield 10b (32 mg, 65%) as a yellow foam. HRMS (ESI) for C₁₃H₁₅NO₃: [M + Na] calculated, 256.0944; found, 256.0944. ¹H NMR (500 MHz, DMSO-d₆): 1.66 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.20 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.6 Hz, J_2′b,3′ = 1.7 Hz, H-2′b); 2.43 (s, 3H, CH₃-6); 3.46 (dm, 1H, J_gem = 11.5 Hz, H-5′a); 3.51 (ddd, 1H, J_gem = 11.5 Hz, J_5′b,OH = 5.6 Hz, J_5′b,4′ = 4.8 Hz, H-5′b); 3.80 (btd, 1H, J_4′,5′a = J_4′,5′b = 5.0 Hz, J_4′,3′ = 2.2 Hz, H-4′); 4.37 (m, 1H, H-3′); 4.50 (s, 1H, CH≡C-2); 4.79 (t, 1H, J_OH,5′a = J_OH,5′b = 5.7 Hz, OH-5′); 5.12 (d, 1H, J_OH,3′ = 3.8 Hz, OH-3′); 5.34 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.6 Hz, H-1′); 7.28 (d, 1H, J_5,4 = 8.1 Hz, H-5); 7.86 (bd, 1H, J_4,5 = 8.1 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): 23.72 (CH₃-6); 42.77 (CH₂-2′); 62.41 (CH₂-5′); 72.58 (CH-3′); 76.05 (CH-1′); 81.10 (CH≡C-2); 84.10 (CH≡C-2); 88.00 (CH-4′); 123.75 (CH-5); 134.14 (CH-4); 138.33 and 138.44 (C-2,3); 157.27 (C-6). IR spectrum (KBr): 3366, 3064, 2980, 2929, 2106, 2095, 1590, 1567, 1449, 1378, 1346, 1332, 1288, 1179, 1161, 1118, 1083, 1062, 1050, 969, 938, 655, 639.

1β-(2-Amino-6-methylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (11a). LiN(SiMe₃)₂ (1.6 mL, 1.6 mmol, 3 equiv. 1.0 M solution in THF) was added to a flame-dried and argon-purged flask containing 8a (255 mg, 0.54 mmol), Ph₃SiNH₂ (297 mg, 1.1 mmol), Pd₂(dba)₃ (28 mg, 0.027 mmol, 5 mol%), and (biphenyl-2-yl)dicyclohexylphosphane (38 mg, 0.11 mmol, 20 mol%), and the mixture was stirred at 50 °C for 3 h. After cooling to room temperature, the reaction mixture was diluted with Et₂O (30 mL), and washed with 2 M HCl (10 mL) and 1 M NaOH (15 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 17% EtOAc in hexanes to give 11a (167 mg, 68%) as a colorless oil. HRMS (ESI) for C₂₃H₄₄N₂O₃Si₂: [M + H] calculated, 453.2963; found, 453.2963. ¹H NMR (500 MHz, CDCl₃) 0.07, 0.079, 0.081 and 0.09 (4 × s, 4 × 3H, CH₃Si); 0.90 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.86 (ddd, 1H, J_gem = 12.8 Hz, J_2′a,1′ = 5.6 Hz, J_2′a,3′ = 1.6 Hz, H-2′a); 2.35 (s, 3H, CH₃); 2.38 (ddd, 1H, J_gem = 12.8 Hz, J_2′b,1′ = 10.8 Hz, J_2′b,3′ = 6.5 Hz, H-2′b); 3.77 (dd, 1H, J_gem = 11.1 Hz, J_5′a,4′ = 2.4 Hz, H-5′a); 3.83 (dd, 1H, J_gem = 11.1 Hz, J_5′b,4′ = 3.0 Hz, H-5′b); 3.90 (bq, 1H, J_4′,5′a = J_4′,5′b = J_4′,3′ = 2.7 Hz, H-4′); 4.45 (bddd, 1H, J_3′,2′b = 6.5 Hz, J_3′,4′ = 2.9 Hz, J_3′,2′a = 1.6 Hz, H-3′); 5.01 (dd, 1H, J_1′,2′b = 10.8 Hz, J_1′,2′a = 5.6 Hz, H-1′); 5.31 (bs, 2H, NH₂); 6.42 (bd, 1H, J_5,4 = 7.4 Hz, H-5); 7.19 (d, 1H, J_4,5 = 7.4 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.57, −5.51, −4.72 and −4.58 (CH₃Si); 18.02 and 18.43 ((CH₃)₃C); 23.73 (CH₃); 25.80 and 25.88 ((CH₃)₃C); 39.94 (CH₂-2′); 62.93 (CH₂-5′); 73.55 (CH-3′); 80.27 (CH-1′); 88.23 (CH-4′); 112.11 (CH-5); 114.81 (C-3); 137.04 (CH-4); 155.94 (C-6); 156.38 (C-2). IR spectrum (CCl₄): 3488, 3372, 3062, 2956, 2930, 2896, 2585, 1609, 1595, 1582, 1472, 1463, 1445, 1408, 1390, 1374, 1362, 1258, 1097, 1006, 938, 837.

1β-(2-Amino-6-methylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (11b). Compound 11b was prepared from 11a (97 mg, 0.11 mmol) by the general procedure to yield 11b (85 mg, 82%) as a yellow solid. HRMS (ESI) for C₁₁H₁₆N₂O₃: [M + H] calculated, 225.1234; found, 225.1234. ¹H NMR (500 MHz, DMSO-d₆): 1.88 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 5.6 Hz, J_2′a,3′ = 1.8 Hz, H-2′a); 2.03 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 10.5 Hz, J_2′b,3′ = 6.3 Hz, H-2′b); 2.21 (s, 3H, CH₃); 3.50 (ddd, 1H, J_gem = 11.5 Hz, J_5′a,OH = 5.4 Hz, J_5′a,4′ = 3.9 Hz, H-5′a); 3.54 (ddd, 1H, J_gem = 11.5 Hz, J_5′b,OH = 4.9 Hz, J_5′b,4′ = 3.6 Hz, H-5′b); 3.73 (td, 1H, J_4′,5′a = J_4′,5′b = 3.8 Hz, J_4′,3′ = 2.8 Hz, H-4′); 4.20 (m, 1H, H-3′); 4.91 (dd, 1H, J_1′,2′b = 10.5 Hz, J_1′,2′a = 5.6 Hz, H-1′); 4.93 (t, 1H, J_OH,5′a = J_OH,5′b = 5.2 Hz, OH-5′); 5.02 (d, 1H, J_OH,3′ = 4.1 Hz, OH-3′); 5.76 (bs, 2H, NH₂); 6.34 (bdd, 1H, J_5,4 = 7.4 Hz, J_5,LR = 0.6 Hz, H-5); 7.26 (bd, 1H, J_4,5 = 7.4 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): 23.68 (CH₃); 39.76 (CH₂-2′); 61.72 (CH₂-5′); 72.13 (CH-3′); 78.13 (CH-1′); 87.82 (CH-4′); 111.08 (CH-5); 115.60 (C-3); 135.83 (CH-4); 155.00 (C-6); 156.60 (C-2). IR spectrum (KBr): 3393, 3317, 3200, 3149, 3086, 2951, 2919, 2773, 1626, 1595, 1587, 1444, 1379, 1347, 1328, 1281, 1185, 1100, 1081, 1042, 977, 938, 831.

1β-(2-Methoxy-6-methylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (12). MeONa (605 mg, 11 mmol) was added to a solution of the nucleoside 8b (53 mg, 0.22 mmol) in methanol (10 mL) and the mixture was stirred for 10 days at 120 °C. Then the solvents were evaporated under vacuum. The crude product was chromatographed on silica gel in a gradient of chloroform to 6% MeOH in chloroform to give 12 (40 mg, 77%) as a white solid. HRMS (ESI) for C₁₂H₁₇NO₄: [M + Na] calculated, 262.1050; found, 262.1050. ¹H NMR (500 MHz, CD₃OD): 1.77 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.31 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.6 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 2.40 (s, 3H, CH₃-6); 3.64 (dd, 1H, J_gem = 11.6 Hz, J_5′a,4′ = 5.1 Hz, H-5′a); 3.66 (dd, 1H, J_gem = 11.6 Hz, J_5′b,4′ = 5.2 Hz, H-5′b); 3.91 (s, 3H, CH₃O); 3.92 (td, 1H, J_4′,5′a = J_4′,5′b = 5.2 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.27 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 1.9 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.26 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.6 Hz, H-1′); 6.77 (dm, 1H, J_5,4 = 7.4 Hz, H-5); 7.71 (dd, 1H, J_4,5 = 7.4 Hz, J_4,1′ = 0.9 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 23.69 (CH₃-6); 42.93 (CH₂-2′); 53.54 (CH₃O-2); 64.01 (CH₂-5′); 74.32 (CH-3′); 76.08 (CH-1′); 88.69 (CH-4′); 116.83 (CH-5); 122.92 (C-3); 136.38 (CH-4); 155.78 (C-6); 161.26 (C-2). IR spectrum (KBr): 3386, 3079, 2988, 2951, 2923, 2853, 1603, 1588, 1461, 1444, 1383, 1327, 1246, 1192, 1116, 1089, 1082, 1049, 1031, 966, 942, 821.

1β-(6-Chloro-2-phenylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (13a). K₂CO₃ (86 mg, 0.62 mmol), Pd(PPh₃)₄ (24 mg, 0.02 mmol, 5 mol%), PhB(OH)₂ (45 mg, 0.37 mmol, 0.9 equiv.) and starting nucleoside 7 (222 mg, 0.41 mmol) were dissolved in toluene (2 mL) under argon, and the mixture was stirred at 60 °C for 12 h. The reaction mixture was concentrated under reduced pressure, and the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 1% EtOAc in hexanes to give 13a (140 mg, 63%) as a colorless oil. HRMS (ESI) for C₂₈H₄₄ClNO₃Si₂: [M + H] calculated, 534.2621; found, 534.2621. ¹H NMR (500 MHz, CDCl₃): −0.01, 0.02, 0.09 and 0.10 (4 × s, 4 × 3H, CH₃Si); 0.82 and 0.92 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.81 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.4 Hz, H-2′a); 1.96 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.3 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 3.67 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.8 Hz, H-5′a); 3.74 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.3 Hz, H-5′b); 3.85 (ddd, 1H, J_4′,5′a = 4.8 Hz, J_4′,5′b = 3.3 Hz, J_4′,3′ = 2.1 Hz, H-4′); 4.36 (dtd, 1H, J_3′,2′a = 5.5 Hz, J_3′,4′ = J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.22 (bddq, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.3 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.30 (dd, 1H, J_5,4 = 8.3 Hz, J_5,1′ = 0.7 Hz, H-5); 7.38–7.46 (m, 5H, H-o,m,p-Ph); 8.05 (dd, 1H, J_4,5 = 8.3 Hz, J_4,1′ = 0.6 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.51, −5.39, −4.80 and −4.76 (CH₃Si); 17.86 and 18.31 ((CH₃)₃C); 25.67 and 25.89 ((CH₃)₃C); 44.62 (CH₂-2′); 63.53 (CH₂-5′); 74.20 (CH-3′); 75.74 (CH-1′); 87.91 (CH-4′); 123.01 (CH-5); 128.23 and 128.95 (CH-o,m-Ph); 128.58 (CH-p-Ph); 134.90 (C-3); 137.99 (CH-4); 138.33 (C-i-Ph); 149.33 (C-6); 157.84 (C-2). IR spectrum (CCl₄): 3087, 3063, 3034, 2956, 2989, 1575, 1558, 1496, 1471, 1463, 1408, 1388, 1361, 1257, 1088, 1027, 1006, 939, 838.

1β-(6-Chloro-2-phenylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (13b). Compound 13b was prepared from 13a (160 mg, 0.30 mmol) by the general procedure to yield 13b (84 mg, 91%) as a white solid. HRMS (ESI) for C₂₂H₂₁NO₃: [M + H] calculated, 348.1594; found, 348.1593. ¹H NMR (500 MHz, CD₃OD): 2.01 (ddd, 1H, J_gem = 13.2 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 5.9 Hz, H-2′a); 2.06 (ddd, 1H, J_gem = 13.2 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.70 (m, 1H, H-5′a); 3.72 (m, 1H, H-5′b); 3.85 (btd, 1H, J_4′,5′a = J_4′,5′b = 4.7 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.31 (bdddd, 1H, J_3′,2′a = 5.9 Hz, J_3′,4′ = 2.8 Hz, J_3′,2′b = 1.9 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.24 (bddq, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.8 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.41 (m, 1H, H-p-Ph-6); 7.44–7.49 (m, 3H, H-m-Ph-6, H-p-Ph-2); 7.50 (m, 2H, H-m-Ph-2); 7.55 (m, 2H, H-o-Ph-2); 7.85 (dd, 1H, J_5,4 = 8.3 Hz, J_5,1′ = 0.6 Hz, H-5); 8.01 (m, 2H, H-o-Ph-6); 8.22 (dd, 1H, J_4,5 = 8.3 Hz, J_4,1′ = 0.5 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 44.89 (CH₂-2′); 63.86 (CH₂-5′); 74.42 (CH-3′); 77.59 (CH-1′); 89.06 (CH-4′); 121.00 (CH-5); 128.22 (CH-o-Ph-6); 129.33 (CH-m-Ph-2); 129.43 (CH-p-Ph-2); 129.72 (CH-m-Ph-6); 130.10 (CH-p-Ph-6); 130.32 (CH-o-Ph-2); 135.29 (C-3); 137.71 (CH-4); 140.31 (C-i-Ph-6); 141.23 (C-i-Ph-2); 157.47 (C-6); 159.02 (C-2). IR spectrum (KBr): 3412, 3084, 3061, 3031, 1574, 1559, 1495, 1449, 1277, 1146, 1083, 1075, 1024, 1000, 940, 831.

1β-(2,6-Diphenylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (14a). K₂CO₃ (129 mg, 0.93 mmol), Pd(PPh₃)₄ (21 mg, 0.0185 mmol, 5 mol%), PhB(OH)₂ (135 mg, 1.11 mmol, 3 equiv.) and starting nucleoside 7 (200 mg, 0.37 mmol) were dissolved in toluene (2 mL) under argon, and the mixture was stirred at 100 °C for 12 h. The reaction mixture was concentrated under reduced pressure, and the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 1% EtOAc in hexanes to give 14a (205 mg, 95%) as a colorless oil. HRMS (ESI) for C₃₄H₄₉NO₃Si₂: [M + H] calculated, 576.3324; found, 576.3323. ¹H NMR (500 MHz, CDCl₃): 0.04, 0.06, 0.12 and 0.14 (4 × s, 4 × 3H, CH₃Si); 0.86 and 0.96 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.91 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.4 Hz, H-2′a); 2.03 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.3 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 3.71 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 5.1 Hz, H-5′a); 3.80 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.90 (ddd, 1H, J_4′,5′a = 5.1 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.2 Hz, H-4′); 4.42 (bdt, 1H, J_3′,2′a = 5.4 Hz, J_3′,4′ = J_3′,2′b = 2.1 Hz, H-3′); 5.33 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.3 Hz, H-1′); 7.38–7.45 (m, 2H, H-p-Ph-2,6); 7.44–7.49 (m, 4H, H-m-Ph-2,6); 7.57 (m, 2H, H-o-Ph-2); 7.74 (dd, 1H, J_5,4 = 8.2 Hz, J_5,1′ = 0.6 Hz, H-5); 8.08 (m, 2H, H-o-Ph-6); 8.14 (bd, 1H, J_4,5 = 8.2 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.47, −5.36, −4.78 and −4.74 (CH₃Si); 17.88 and 18.33 ((CH₃)₃C); 25.70 and 25.92 ((CH₃)₃C); 44.53 (CH₂-2′); 63.61 (CH₂-5′); 74.28 (CH-3′); 76.16 (CH-1′); 87.78 (CH-4′); 119.21 (CH-5); 127.07 (CH-o-Ph-6); 128.06 (CH-m-Ph-2); 128.11 (CH-p-Ph-2); 128.59 (CH-m-Ph-6); 128.80 (CH-p-Ph-6); 129.22 (CH-o-Ph-2); 134.17 (C-3); 135.75 (CH-4); 139.16 (C-i-Ph-6); 139.94 (C-i-Ph-2); 155.58 (C-6); 157.17 (C-2). IR spectrum (CCl₄): 3110, 3086, 3064, 3034, 2956, 2897, 1602, 1588, 1576, 1563, 1495, 1472, 1463, 1442, 1406, 1389, 1361, 1280, 1258, 1096, 1030, 939, 838.

1β-(2,6-Diphenylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (14b). Compound 14b was prepared from 14a (205 mg, 0.36 mmol) by the general procedure to yield 14b (100 mg, 81%) as a white solid. HRMS (ESI) for C₂₂H₂₁NO₃: [M + H] calculated, 348.1594; found, 348.1593. ¹H NMR (500 MHz, CD₃OD): 2.01 (ddd, 1H, J_gem = 13.2 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 5.9 Hz, H-2′a); 2.06 (ddd, 1H, J_gem = 13.2 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.70 (m, 1H, H-5′a); 3.72 (m, 1H, H-5′b); 3.85 (btd, 1H, J_4′,5′a = J_4′,5′b = 4.7 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.31 (bdddd, 1H, J_3′,2′a = 5.9 Hz, J_3′,4′ = 2.8 Hz, J_3′,2′b = 1.9 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.24 (bddq, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.8 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.41 (m, 1H, H-p-Ph-6); 7.44–7.49 (m, 3H, H-m-Ph-6, H-p-Ph-2); 7.50 (m, 2H, H-m-Ph-2); 7.55 (m, 2H, H-o-Ph-2); 7.85 (dd, 1H, J_5,4 = 8.3 Hz, J_5,1′ = 0.6 Hz, H-5); 8.01 (m, 2H, H-o-Ph-6); 8.22 (dd, 1H, J_4,5 = 8.3 Hz, J_4,1′ = 0.5 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 44.89 (CH₂-2′); 63.86 (CH₂-5′); 74.42 (CH-3′); 77.59 (CH-1′); 89.06 (CH-4′); 121.00 (CH-5); 128.22 (CH-o-Ph-6); 129.33 (CH-m-Ph-2); 129.43 (CH-p-Ph-2); 129.72 (CH-m-Ph-6); 130.10 (CH-p-Ph-6); 130.32 (CH-o-Ph-2); 135.29 (C-3); 137.71 (CH-4); 140.31 (C-i-Ph-6); 141.23 (C-i-Ph-2); 157.47 (C-6); 159.02 (C-2). IR spectrum (KBr): 3412, 3110, 3083, 3059, 3031, 1602, 1587, 1574, 1562, 1493, 1282, 1075, 1046, 1028, 941.

1β-(6-Amino-2-phenylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (15a). LiN(SiMe₃)₂ (1.5 mL, 1.5 mmol, 3 equiv. 1.0 M solution in THF) was added to a flame-dried and argon-purged flask containing 14a (262 mg, 0.49 mmol), Pd₂(dba)₃ (45 mg, 0.049 mmol, 10 mol%), and (biphenyl-2-yl)dicyclohexylphosphane (35 mg, 0.098 mmol, 20 mol%), and the mixture was stirred at 60 °C for 12 h. After cooling to room temperature, the reaction mixture was diluted with Et₂O (30 mL), washed with 2 M HCl (10 mL) and 1 M NaOH (15 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 20% EtOAc in hexanes to give 15a (230 mg, 91%) as a colorless oil. HRMS (ESI) for C₂₈H₄₆N₂O₃Si₂: [M + H] calculated, 515.3120; found, 515.3118. ¹H NMR (500 MHz, CDCl₃): 0.01, 0.02, 0.085 and 0.093 (4 × s, 4 × 3H, CH₃Si); 0.82 and 0.93 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.86 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.4 Hz, H-2′a); 1.93 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.4 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 3.64 (dd, 1H, J_gem = 10.7 Hz, J_5′a,4′ = 5.2 Hz, H-5′a); 3.74 (dd, 1H, J_gem = 10.7 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.79 (ddd, 1H, J_4′,5′a = 5.2 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.1 Hz, H-4′); 4.36 (dt, 1H, J_3′,2′a = 5.4 Hz, J_3′,4′ = J_3′,2′b = 2.0 Hz, H-3′); 5.10 (dd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.3 Hz, H-1′); 6.51 (bd, 1H, J_5,4 = 8.5 Hz, H-5); 7.36 (m, 1H, H-p-Ph); 7.39 (m, 2H, H-m-Ph); 7.41 (m, 2H, H-o-Ph); 7.77 (d, 1H, J_4,5 = 8.5 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.50, −5.39, −4.78 and −4.75 (CH₃Si); 17.86 and 18.31 ((CH₃)₃C); 25.68 and 25.91 ((CH₃)₃C); 44.29 (CH₂-2′); 63.68 (CH₂-5′); 74.29 (CH-3′); 76.02 (CH-1′); 87.45 (CH-4′); 108.00 (CH-5); 124.93 (C-3); 127.90 (CH-p-Ph); 128.03 (CH-m-Ph); 128.84 (CH-o-Ph); 137.26 (CH-4); 139.65 (C-i-Ph); 155.80 (C-2); 156.81 (C-6). IR spectrum (CCl₄): 2506, 3407, 3301, 3169, 3084, 3063, 3030, 2956, 2897, 1631, 1610, 1572, 1496, 1473, 1464, 1444, 1410, 1389, 1361, 1290, 1256, 1097, 1029, 939, 838.

1β-(6-Amino-2-phenylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (15b). Compound 15b was prepared from 15a (200 mg, 0.39 mmol) by the general procedure to yield 15b (70 mg, 67%) as a yellow solid. HRMS (ESI) for C₁₆H₁₈N₂O₃: [M + H] calculated, 287.1390; found, 287.1390. ¹H NMR (500 MHz, DMSO-d₆): 1.84 (ddd, 1H, J_gem = 12.8 Hz, J_2′a,1′ = 5.9 Hz, J_2′a,3′ = 2.1 Hz, H-2′a); 1.88 (ddd, 1H, J_gem = 12.8 Hz, J_2′b,1′ = 10.1 Hz, J_2′b,3′ = 5.4 Hz, H-2′b); 3.40–3.49 (m, 2H, H-5′); 3.60 (bddd, 1H, J_4′,5′a = 5.3 Hz, J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.2 Hz, H-4′); 4.15 (m, 1H, H-3′); 4.71 (bt, 1H, J_OH,5′a = J_OH,5′b = 5.6 Hz, OH-5′); 4.85 (dd, 1H, J_1′,2′b = 10.1 Hz, J_1′,2′a = 5.8 Hz, H-1′); 4.85 (d, 1H, J_OH,3′ = 3.8 Hz, OH-3′); 6.13 (bs, 2H, NH₂); 6.54 (bd, 1H, J_5,4 = 8.6 Hz, H-5); 7.38–7.46 (m, 5H, H-o,m,p-Ph); 7.67 (bd, 1H, J_4,5 = 8.6 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): 43.08 (CH₂-2′); 62.61 (CH₂-5′); 72.71 (CH-3′); 75.47 (CH-1′); 87.54 (CH-4′); 108.25 (CH-5); 122.25 (C-3); 128.02 (CH-m,p-Ph); 129.13 (CH-o-Ph); 137.98 (CH-4); 139.50 (C-i-Ph); 154.35 (C-2); 157.89 (C-6). IR spectrum (KBr): 3358, 3217, 3059, 1621, 1600, 1571, 1496, 1444, 1217, 1181, 1158, 1074, 1047, 830.

1β-(6-Methyl-2-phenylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (16a). Me₃Al (0.92 mL, 0.92 mmol, 3.0 equiv., 1 M in heptane) was added to a flame-dried flask containing a solution of 14a (164 mg, 0.31 mmol) and Pd(PPh₃)₄ (36 mg, 0.031 mmol, 10 mol%) in THF (5 mL). The mixture was stirred at 70 °C for 12 h, quenched by pouring into saturated NaH₂PO₄ (50 mL), and extracted with EtOAc (3 × 50 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 6% EtOAc in hexanes to give 16a (144 mg, 91%) as a colorless oil. HRMS (ESI) for C₂₉H₄₇NO₃Si₂: [M + H] calculated, 514.3167; found, 514.3166. ¹H NMR (500 MHz, CDCl₃): −0.01, 0.02, 0.08 and 0.10 (4 × s, 4 × 3H, CH₃Si); 0.82 and 0.92 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.81 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.4 Hz, H-2′a); 1.93 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.3 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 2.62 (s, 3H, CH₃-6); 3.66 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 5.1 Hz, H-5′a); 3.75 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.83 (ddd, 1H, J_4′,5′a = 5.1 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.2 Hz, H-4′); 4.36 (dtd, 1H, J_3′,2′a = 5.4 Hz, J_3′,4′ = J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.5 Hz, H-3′); 5.18 (dd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.3 Hz, H-1′); 7.16 (d, 1H, J_5,4 = 8.1 Hz, H-5); 7.38 (m, 1H, H-p-Ph); 7.40–7.44 (m, 4H, H-o,m-Ph); 7.97 (d, 1H, J_4,5 = 8.1 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.49, −5.39, −4.81 and −4.76 (CH₃Si); 17.85 and 18.31 ((CH₃)₃C); 24.06 (CH₃-6); 25.68 and 25.90 ((CH₃)₃C); 44.49 (CH₂-2′); 63.59 (CH₂-5′); 74.23 (CH-3′); 76.06 (CH-1′); 87.72 (CH-4′); 122.38 (CH-5); 128.14 (CH-p-Ph); 128.18 (CH-m-Ph); 128.97 (CH-o-Ph); 132.93 (C-3); 135.53 (CH-4); 139.32 (C-i-Ph); 156.52 (C-2,6). IR spectrum (CCl₄): 3110, 3083, 3061, 3029, 2956, 2930, 2897, 2858, 1593, 1569, 1495, 1471, 1463, 1406, 1389, 1371, 1361, 1289, 1257, 1095, 1030, 1006, 939, 838.

1β-(6-Methyl-2-phenylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (16b). Compound 16b was prepared from 16a (144 mg, 0.28 mmol) by the general procedure to yield 16b (68 mg, 85%) as a white solid. HRMS (ESI) for C₁₇H₁₉NO₃: [M + H] calculated, 286.1438; found, 286.1438. ¹H NMR (500 MHz, CD₃OD): 1.93 (ddd, 1H, J_gem = 13.2 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.9 Hz, H-2′a); 1.99 (ddd, 1H, J_gem = 13.2 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 2.54 (s, 3H, CH₃-6); 3.64–3.71 (m, 2H, H-5′); 3.80 (bddd, 1H, J_4′,5′a = 5.0 Hz, J_4′,5′b = 4.5 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.27 (bdddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 1.9 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.10 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.8 Hz, H-1′); 7.32 (bd, 1H, J_5,4 = 8.1 Hz, H-5); 7.42 (m, 2H, H-o-Ph); 7.43–7.51 (m, 3H, H-m,p-Ph); 8.09 (d, 1H, J_4,5 = 8.1 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 23.38 (CH₃-6); 44.85 (CH₂-2′); 63.82 (CH₂-5′); 74.36 (CH-3′); 77.47 (CH-1′); 89.02 (CH-4′); 124.14 (CH-5); 129.40 (CH-m-Ph); 129.52 (CH-p-Ph); 130.11 (CH-o-Ph); 134.25 (C-3); 137.65 (CH-4); 140.70 (C-i-Ph); 158.02 (C-6); 158.29 (C-2). IR spectrum (KBr): 1595, 1573, 1496, 1476, 1447, 1380, 1281, 1146, 1086, 1040, 961.

1β-[2,6-Bis(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (17). MeSNa (59 mg, 0.84 mmol) was added to a solution of the nucleoside 4 (45 mg, 0.084 mmol) in DMF (2 mL) and the mixture was stirred for 12 h at 80 °C. Then the solvents were evaporated under vacuum. The crude product was chromatographed on silica gel in a gradient of chloroform to 7% MeOH in chloroform to give 17 (19 mg, 79%) as a pale yellow solid. HRMS (ESI) for C₁₂H₁₇NO₃S₂: [M + Na] calculated, 310.0542; found, 310.0542. ¹H NMR (500 MHz, CD₃OD): 1.75 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.36 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.6 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.57 (s, 3H, CH₃S-6); 2.59 (s, 3H, CH₃S-2); 3.67–3.70 (m, 2H, H-5′); 3.92 (td, 1H, J_4′,5′a = J_4′,5′b = 4.9 Hz, J_4′,3′ = 2.8 Hz, H-4′); 4.30 (dddd, 1H, J_3′,2′a = 6.1 Hz, J_3′,4′ = 2.8 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.27 (ddq, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.6 Hz, J_1′,4 = J_1′,5 = J_1′,3′ = 0.7 Hz, H-1′); 6.93 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 7.65 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 11.46 and 11.56 (CH₃S-2,6); 41.24 (CH₂-2′); 62.13 (CH₂-5′); 72.62 (CH-3′); 75.06 (CH-1′); 87.16 (CH-4′); 115.88 (CH-5); 130.16 (C-3); 132.32 (CH-4); 155.15 (C-2); 157.48 (C-6). IR spectrum (KBr): 3411, 2989, 2924, 1565, 1543, 1430, 1418, 1335, 1308, 1217, 1049, 962, 840, 778.

1β-[2-Chloro-6-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (18a). MeSNa (48 mg, 0.69 mmol, 1.2 equiv.) was added to a solution of the nucleoside 4 (310 mg, 0.58 mmol) in DMF (5 mL) and the mixture was stirred for 12 h at rt. Then the solvents were evaporated under vacuum. The crude product was purified using high performance flash chromatography with a gradient of hexanes to 1% EtOAc in hexanes to give products 18a (141 mg, 48%) as a white solid and 19a (136 mg, 43%) as a white solid. Compound 18a: HRMS (ESI) for C₂₃H₄₂ClNO₃SSi₂: [M + H] calculated, 504.2185; found, 504.2183. ¹H NMR (500 MHz, CDCl₃) 0.082, 0.084 and 0.09 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.70 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 9.5 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.37 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.5 Hz, H-2′b); 2.56 (s, 3H, CH₃S-6); 3.69 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 4.8 Hz, H-5′a); 3.76 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.95 (ddd, 1H, J_4′,5′a = 5.7 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.38 (dtd, 1H, J_3′,2′a = 5.7 Hz, J_3′,4′ = J_3′,2′b = 2.5 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.35 (ddq, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 5.8 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz,H-1′); 7.08 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.6 Hz, H-5); 7.80 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.48, −5.40, −4.75 and −4.62 (CH₃Si); 13.51 (CH₃S-6); 17.99 and 18.30 ((CH₃)₃C); 25.77 and 25.88 ((CH₃)₃C); 42.47 (CH₂-2′); 63.32 (CH₂-5′); 73.72 (CH-3′); 76.01 (CH-1′); 87.76 (CH-4′); 120.24 (CH-5); 132.38 (C-3); 135.72 (CH-4); 147.97 (C-2); 158.71 (C-6). IR spectrum (CCl₄): 3078, 3058, 2956, 2897, 1587, 1537, 1472, 1439, 1408, 1390, 1373, 1361, 1318, 1258, 1096, 939, 838.

1β-[6-Bromo-2-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (19a). HRMS (ESI) for C₂₃H₄₂BrNO₃SSi₂: [M + H] calculated, 548.1680; found, 548.1675. ¹H NMR (500 MHz, CDCl₃) 0.09, 0.098, 0.100 and 0.11 (4 × s, 4 × 3H, CH₃Si); 0.91 and 0.93 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.68 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.4 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.38 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.6 Hz, H-2′b); 2.59 (s, 3H, CH₃S-2); 3.70 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.9 Hz, H-5′a); 3.78 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.95 (ddd, 1H, J_4′,5′a = 4.9 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.39 (dtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.7 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.27 (ddq, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 5.9 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.15 (dd, 1H, J_5,4 = 8.0 Hz, J_5,1′ = 0.6 Hz, H-5); 7.67 (dd, 1H, J_4,5 = 8.0 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.48, −5.41, −4.76 and −4.61 (CH₃Si); 13.35 (CH₃S-2); 17.99 and 18.30 ((CH₃)₃C); 25.78 and 25.89 ((CH₃)₃C); 41.82 (CH₂-2′); 63.24 (CH₂-5′); 73.73 (CH-3′); 75.03 (CH-1′); 87.57 (CH-4′); 122.85 (CH-5); 134.71 (CH-4); 135.45 (C-3); 139.46 (C-6); 157.09 (C-2). IR spectrum (CCl₄): 3057, 2956, 2897, 1571, 1543, 1472, 1463, 1414, 1390, 1374, 1310, 1288, 1216, 1097, 1030, 961, 939, 838.

1β-[2-Chloro-6-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (18b). Compound 18b was prepared from 18a (141 mg, 0.28 mmol) by the general procedure to yield 18b (66 mg, 86%) as a white solid. HRMS (ESI) for C₁₁H₁₄ClNO₃S: [M + Na] calculated, 298.0275; found, 298.0277. ¹H NMR (500 MHz, CD₃OD): 1.77 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.42 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.6 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 2.53 (s, 3H, CH₃S-6); 3.68 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.70 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.6 Hz, H-5′b); 3.95 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.31 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 1.9 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.34 (ddq, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.6 Hz, J_1′,4 = J_1′,5 = J_1′,3′ = 0.7 Hz, H-1′); 7.21 (dd, 1H, J_5,4 = 8.2 Hz, J_5,1′ = 0.6 Hz, H-5); 7.90 (dd, 1H, J_4,5 = 8.2 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 13.48 (CH₃S-6); 43.23 (CH₂-2′); 63.77 (CH₂-5′); 74.19 (CH-3′); 77.38 (CH-1′); 89.11 (CH-4′); 121.34 (CH-5); 133.08 (C-3); 137.46 (CH-4); 149.04 (C-2); 160.92 (C-6). IR spectrum (KBr): 3333, 3284, 1048, 1585, 1576, 1543, 1425, 1317, 1219, 957, 832.

1β-[6-Bromo-2-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (19b). Compound 19b was prepared from 19a (136 mg, 0.25 mmol) by the general procedure to yield 19b (62 mg, 78%) as a white solid. HRMS (ESI) for C₁₁H₁₄BrNO₃S: [M + Na] calculated, 341.9770; found, 341.9771. ¹H NMR (500 MHz, CD₃OD): 1.73 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.42 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.55 (s, 3H, CH₃S-2); 3.67 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.70 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.6 Hz, H-5′b); 3.93 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.8 Hz, H-4′); 4.31 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.8 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.24 (ddq, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.7 Hz, J_1′,4 = J_1′,5 = J_1′,3′ = 0.7 Hz, H-1′); 7.24 (dd, 1H, J_5,4 = 8.0 Hz, J_5,1′ = 0.6 Hz, H-5); 7.74 (dd, 1H, J_4,5 = 8.0 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 13.38 (CH₃S-2); 42.71 (CH₂-2′); 63.72 (CH₂-5′); 74.22 (CH-3′); 76.47 (CH-1′); 88.96 (CH-4′); 124.18 (CH-5); 136.32 (C-3); 136.36 (CH-4); 140.71 (C-6); 158.53 (C-2). IR spectrum (KBr): 3380, 3324, 3066, 1569, 1540, 1409, 1307, 1209, 1045, 948.

1β-[2-Methyl-6-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (20a). Me₃Al (0.48 mL, 0.48 mmol, 2.0 equiv., 1 M in heptane) was added to a flame-dried flask containing a solution of 18a (130 mg, 0.24 mmol) and Pd(PPh₃)₄ (28 mg, 0.024 mmol, 10 mol%) in THF (3 mL). The mixture was stirred at 90 °C for 12 h, quenched by pouring into saturated NaH₂PO₄ (50 mL), and extracted with EtOAc (3 × 50 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 6% EtOAc in hexanes to give 20a (61 mg, 49%) as a colorless oil. HRMS (ESI) for C₂₄H₄₅NO₃SSi₂: [M + H] calculated, 484.2731; found, 484.2731. ¹H NMR (500 MHz, CDCl₃) 0.08 and 0.09 (2 × s, 2 × 6H, CH₃Si); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.72 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.15 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.5 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.48 (s, 3H, CH₃-2); 2.54 (s, 3H, CH₃S-6); 3.67 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 5.2 Hz, H-5′a); 3.77 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.6 Hz, H-5′b); 3.94 (ddd, 1H, J_4′,5′a = 5.2 Hz, J_4′,5′b = 3.6 Hz, J_4′,3′ = 2.3 Hz, H-4′); 4.41 (bdt, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.2 Hz, H-3′); 5.26 (bdd, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.5 Hz, H-1′); 6.99 (bd, 1H, J_5,4 = 8.2 Hz, H-5); 7.68 (d, 1H, J_4,5 = 8.2 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.48, −5.39, −4.69 and −4.64 (CH₃Si); 13.52 (CH₃S-6); 17.99 and 18.31 ((CH₃)₃C); 21.92 (CH₃-2); 25.78 and 25.90 ((CH₃)₃C); 42.86 (CH₂-2′); 63.50 (CH₂-5′); 74.06 (CH-3′); 76.03 (CH-1′); 87.67 (CH-4′); 118.61 (CH-5); 131.61 (C-3); 133.44 (CH-4); 154.56 (C-2); 157.15 (C-6). IR spectrum (CCl₄): 3062, 2956, 2897, 1583, 1560, 1472, 1450, 1408, 1389, 1373, 1361, 1315, 1258, 1098, 1088, 939, 838.

1β-[2-Methyl-6-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (20b). Compound 20b was prepared from 20a (54 mg, 0.11 mmol) by the general procedure to yield 20b (20 mg, 69%) as a white solid. HRMS (ESI) for C₁₂H₁₇NO₃S: [M + H] calculated, 256.1002; found, 256.1002. ¹H NMR (500 MHz, CD₃OD): 1.84 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.4 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.28 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.5 Hz, J_2′b,3′ = 1.8 Hz, H-2′b); 2.52 (s, 3H, CH₃-2); 2.58 (s, 3H, CH₃S-6); 3.66–3.72 (m, 2H, H-5′); 3.95 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.34 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 1.8 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.29 (bddq, 1H, J_1′,2′a = 10.4 Hz, J_1′,2′b = 5.5 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.6 Hz, H-1′); 7.22 (dt, 1H, J_5,4 = 8.4 Hz, J_5,LR = 0.6 Hz, H-5); 7.96 (bd, 1H, J_4,5 = 8.4 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 13.92 (CH₃S-6); 20.73 (CH₃-2); 43.21 (CH₂-2′); 63.78 (CH₂-5′); 74.30 (CH-3′); 77.06 (CH-1′); 89.13 (CH-4′); 120.06 (CH-5); 133.70 (C-3); 137.11 (CH-4); 155.32 (C-2); 159.20 (C-6). IR spectrum (KBr): 3301, 2989, 2929, 2857, 1580, 1560, 1448, 1435, 1386, 1270, 1088, 1050, 1026.

1β-[6-Methyl-2-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (21a). Me₃Al (0.40 mL, 0.40 mmol, 2.0 equiv., 1 M in heptane) was added to a flame-dried flask containing solution of 19a (103 mg, 0.20 mmol) and Pd(PPh₃)₄ (23 mg, 0.020 mmol, 10 mol%) in THF (2 mL). The mixture was stirred at 90 °C for 12 h, quenched by pouring into saturated NaH₂PO₄ (50 mL), and extracted with EtOAc (3 × 50 mL). The crude product was chromatographed on silica gel eluting with a gradient of hexanes to 5% EtOAc in hexanes to give 21a (53 mg, 58%) as a colorless oil. HRMS (ESI) for C₂₄H₄₅NO₃SSi₂: [M + H] calculated, 484.2731; found, 484.2732. ¹H NMR (500 MHz, CDCl₃) 0.08, 0.09 and 0.10 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.92 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.69 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.4 Hz, J_2′a,3′ = 5.7 Hz, H-2′a); 2.35 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.5 Hz, H-2′b); 2.48 (s, 3H, CH₃-6); 2.58 (s, 3H, CH₃S-2); 3.67 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 5.2 Hz, H-5′a); 3.78 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.7 Hz, H-5′b); 3.93 (ddd, 1H, J_4′,5′a = 5.2 Hz, J_4′,5′b = 3.7 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.38 (dtd, 1H, J_3′,2′a = 5.7 Hz, J_3′,4′ = J_3′,2′b = 2.6 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.33 (bdd, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 5.8 Hz, H-1′); 6.82 (bd, 1H, J_5,4 = 7.7 Hz, H-5); 7.66 (dd, 1H, J_4,5 = 7.7 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.46, −5.39, −4.75 and −4.59 (CH₃Si); 12.94 (CH₃S-2); 18.01 and 18.32 ((CH₃)₃C); 24.09 (CH₃-6); 25.80 and 25.91 ((CH₃)₃C); 42.06 (CH₂-2′); 63.39 (CH₂-5′); 73.86 (CH-3′); 75.41 (CH-1′); 87.41 (CH-4′); 118.46 (CH-5); 132.52 (CH-4); 132.99 (C-3); 154.61 (C-2); 156.42 (C-6). IR spectrum (CCl₄): 3060, 2956, 2897, 1585, 1573, 1472, 1463, 1407, 1390, 1374, 1361, 1311, 1258, 1210, 1097, 1077, 1031, 971, 963, 939, 838.

1β-[6-Methyl-2-(methylsulfanyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (21b). Compound 21b was prepared from 21a (108 mg, 0.22 mmol) by the general procedure to yield 21b (46 mg, 81%) as a white solid. HRMS (ESI) for C₁₂H₁₇NO₃S: [M + Na] calculated, 278.0821; found, 278.0822. ¹H NMR (500 MHz, CD₃OD): 1.73 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.1 Hz, H-2′a); 2.39 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 2.47 (s, 3H, CH₃-6); 2.55 (s, 3H, CH₃S-2); 3.66–3.72 (m, 2H, H-5′); 3.93 (td, 1H, J_4′,5′a = J_4′,5′b = 5.0 Hz, J_4′,3′ = 2.8 Hz, H-4′); 4.30 (dddd, 1H, J_3′,2′a = 6.1 Hz, J_3′,4′ = 2.8 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.31 (bdd, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.7 Hz, H-1′); 6.94 (dt, 1H, J_5,4 = 7.8 Hz, J_5,LR = 0.6 Hz, H-5); 7.73 (dd, 1H, J_4,5 = 7.8 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 13.15 (CH₃S-2); 23.99 (CH₃-6); 43.01 (CH₂-2′); 63.84 (CH₂-5′); 74.31 (CH-3′); 76.92 (CH-1′); 88.80 (CH-4′); 119.77 (CH-5); 133.88 (C-3); 134.17 (CH-4); 156.15 (C-2); 158.08 (C-6). IR spectrum (KBr): 3395, 3060, 2926, 1584, 1471, 1432, 1374, 1172, 1069, 1049, 963, 946, 911, 827, 722.

1β-(2-Chloro-6-ethynylpyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (22a). DMF (2 mL) and TMSA (35 μL, 0.25 mmol, 0.8 equiv.) were added through a septum to an argon-purged vial containing 4 (170 mg, 0.32 mmol), Pd(PPh₃)₂Cl₂ (22 mg, 0.032 mmol), CuI (1 mg, 0.005 mmol) and Et₃N (89 μL, 0.64 mmol). The resulting mixture was stirred at 60 °C for 12 h. The reaction mixture was then cooled and filtered on a pad of Celite and eluted with CHCl₃. Solvents were then removed under vacuum, the crude product was dissolved in methanolic ammonia (28%, 10 mL) and the solution was stirred at rt for 1 h. The solvents were removed under vacuum, and the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 3% EtOAc in hexanes to give 22a (81 mg, 53% for two steps) as a colorless oil. A portion of starting material 4 (65 mg, 37%) was also isolated during chromatography. HRMS (ESI) for C₂₄H₄₀ClNO₃Si₂: [M + H] calculated, 482.2308; found, 482.2307. ¹H NMR (500 MHz, CDCl₃): 0.08, 0.086 and 0.093 (4 × s, 4 × 3H, CH₃Si); 0.89 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.71 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.4 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.44 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 6.0 Hz, J_2′b,3′ = 2.6 Hz, H-2′b); 3.16 (s, 1H, C≡CH); 3.71 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.7 Hz, H-5′a); 3.77 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.4 Hz, H-5′b); 3.98 (ddd, 1H, J_4′,5′a = 4.7 Hz, J_4′,5′b = 3.4 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.38 (dtd, 1H, J_3′,2′a = 5.6 Hz, J_3′,4′ = J_3′,2′b = 2.6 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.38 (bddq, 1H, J_1′,2′a = 9.4 Hz, J_1′,2′b = 6.0 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.39 (dd, 1H, J_5,4 = 7.9 Hz, J_5,1′ = 0.6 Hz, H-5); 8.01 (dd, 1H, J_4,5 = 7.9 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.50, −5.42, −4.77 and −4.63 (CH₃Si); 17.98 and 18.28 ((CH₃)₃C); 25.74 and 25.86 ((CH₃)₃C); 42.31 (CH₂-2′); 63.20 (CH₂-5′); 73.63 (CH-3′); 76.12 (CH-1′); 78.03 (C≡CH); 81.51 (C≡CH); 87.89 (CH-4′); 129.39 (CH-5); 135.96 (CH-4); 138.26 (C-3); 140.34 (C-6); 148.22 (C-2). IR spectrum (CCl₄): 3309, 2956, 2898, 2123, 1582, 1546, 1472, 1463, 1441, 1390, 1361, 1336, 1258, 1174, 1097, 1060, 939, 838.

1β-(2-Chloro-6-ethynylpyridin-3-yl)-1,2-dideoxy-D-ribofuranose (22b). Compound 22b was prepared from 22a (91 mg, 0.19 mmol) by the general procedure to yield 22b (41 mg, 85%) as a yellow solid. HRMS (ESI) for C₁₂H₁₂ClNO₃: [M − H] calculated, 252.0433; found, 252.0433. ¹H NMR (500 MHz, CD₃OD): 1.78 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 5.9 Hz, H-2′a); 2.50 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.8 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.69 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.72 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.5 Hz, H-5′b); 3.80 (s, 1H, CH≡C); 3.99 (td, 1H, J_4′,5′a = J_4′,5′b = 4.7 Hz, J_4′,3′ = 2.9 Hz, H-4′); 4.33 (bdt, 1H, J_3′,2′a = 5.9 Hz, J_3′,4′ = J_3′,2′b = 2.4 Hz, H-3′); 5.37 (bddq, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.8 Hz, J_1′,4 = J_1′,5 = J_1′,3′ = 0.5 Hz, H-1′); 7.53 (bd, 1H, J_5,4 = 7.9 Hz, H-5); 8.14 (dd, 1H, J_4,5 = 7.9 Hz, J_4,1′ = 0.9 Hz, H-4). ¹³C NMR (125.7 MHz, CD₃OD): 43.05 (CH₂-2′); 63.67 (CH₂-5′); 74.11 (CH-3′); 77.44 (CH-1′); 80.40 (CH≡C); 82.12 (CH≡C); 89.23 (CH-4′); 128.05 (CH-5); 138.01 (CH-4); 139.22 (C-3); 141.99 (C-6); 149.13 (C-2). IR spectrum (KBr): 3302, 3275, 2121, 1630, 1581, 1545, 1363, 1332, 1208, 1130, 1072, 1064, 1045, 995, 846.

1β-[2,6-Bis(trimethylsilylethynyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (23a). DMF (4 mL) and TMSA (360 μL, 2.6 mmol) were added through a septum to an argon-purged vial containing 4 (138 mg, 0.26 mmol), Pd(PPh₃)₂Cl₂ (18 mg, 0.026 mmol), CuI (1 mg, 0.005 mmol) and Et₃N (725 μL, 5.2 mmol). The resulting mixture was stirred at 90 °C for 12 h. The reaction mixture was then cooled and filtered on a pad of Celite and eluted with CHCl₃. The solvents were removed under vacuum, and the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 1% EtOAc in hexanes to give 23a (150 mg, 95%) as a colorless oil. HRMS (ESI) for C₃₂H₅₇NO₃Si₄: [M + H] calculated, 616.3488; found, 616.3490. ¹H NMR (500 MHz, CDCl₃): 0.083, 0.085 and 0.089 (3 × s, 4 × 3H, CH₃Si); 0.24 and 0.26 (2 × s, 2 × 9H, (CH₃)₃Si)); 0.90 and 0.91 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.74 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 9.6 Hz, J_2′a,3′ = 5.7 Hz, H-2′a); 2.41 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 6.0 Hz, J_2′b,3′ = 2.3 Hz, H-2′b); 3.72 (dd, 1H, J_gem = 10.8 Hz, J_5′a,4′ = 4.6 Hz, H-5′a); 3.77 (dd, 1H, J_gem = 10.8 Hz, J_5′b,4′ = 3.4 Hz, H-5′b); 3.98 (ddd, 1H, J_4′,5′a = 4.6 Hz, J_4′,5′b = 3.4 Hz, J_4′,3′ = 2.5 Hz, H-4′); 4.39 (dtd, 1H, J_3′,2′a = 5.7 Hz, J_3′,4′ = J_3′,2′b = 2.4 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.54 (ddq, 1H, J_1′,2′a = 9.6 Hz, J_1′,2′b = 6.0 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.36 (dd, 1H, J_5,4 = 8.1 Hz, J_5,1′ = 0.7 Hz, H-5); 7.92 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.8 Hz, H-4). ¹³C NMR (125.7 MHz, CDCl₃): −5.51, −5.41, −4.74 and −4.56 (CH₃Si); −0.32 and −0.30 ((CH₃)₃Si); 18.37 and 18.32 ((CH₃)₃C); 25.88 and 25.90 ((CH₃)₃C); 43.17 (CH₂-2′); 63.49 (CH₂-5′); 74.07 (CH-3′); 76.82 (CH-1′); 88.06 (CH-4′); 94.68 and 100.17 (2 × C≡CSi); 100.91 (C≡CSi-2); 103.29 (C≡CSi-6); 126.94 (CH-5); 133.37 (CH-4); 140.32 (C-2); 141.47 (C-3); 141.73 (C-6). IR spectrum (CCl₄): 3067, 2958, 2899, 2161, 1576, 1553, 1472, 1463, 1444, 1408, 1390, 1362, 1258, 1252, 1232, 1097, 1031, 939, 846.

1β-(2,6-Bis(ethynyl)pyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (23b). Methanolic ammonia (25%, 10 mL) was added to a flask containing nucleoside 23a (287 mg, 0.47 mmol) and the mixture was stirred for 30 min at room temperature. Then the solvents were evaporated under vacuum and the crude product was chromatographed on silica gel in a gradient of hexanes to 6% EtOAc in hexanes to give 23b (167 mg, 76%) as a colorless oil. HRMS (ESI) for C₂₆H₄₁NO₃Si₂: [M + Na] calculated, 494.2517; found, 494.2516. ¹H NMR (500 MHz, DMSO-d₆): 0.07, 0.08 and 0.09 (4 × s, 4 × 3H, CH₃Si); 0.86 and 0.89 (2 × s, 2 × 9H, (CH₃)₃C)); 1.76 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.2 Hz, H-2′a); 2.28 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.5 Hz, J_2′b,3′ = 1.9 Hz, H-2′b); 3.61 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 6.1 Hz, H-5′a); 3.72 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 4.0 Hz, H-5′b); 3.88 (ddd, 1H, J_4′,5′a = 6.1 Hz, J_4′,5′b = 4.0 Hz, J_4′,3′ = 1.9 Hz, H-4′); 4.37 (bdt, 1H, J_3′,2′a = 5.2 Hz, J_3′,4′ = J_3′,2′b = 1.9 Hz, H-3′); 4.38 (s, 1H, CH≡C-6); 4.67 (s, 1H, CH≡C-2); 5.37 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.5 Hz, H-1′); 7.59 (bd, 1H, J_5,4 = 8.1 Hz, H-5); 7.92 (dd, 1H, J_4,5 = 8.1 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): −5.35, −5.27, −4.66 and −4.55 (CH₃Si); 17.88 and 18.09 ((CH₃)₃C); 25.85 and 25.91 ((CH₃)₃C); 42.14 (CH₂-2′); 63.32 (CH₂-5′); 74.29 (CH-3′); 76.11 (CH-1′); 79.93 (CH≡C-2); 80.78 (CH≡C-2); 82.39 (CH≡C-6); 85.52 (CH≡C-6); 87.72 (CH-4′); 127.56 (CH-5); 134.11 (CH-4); 139.54 (C-2); 140.93 (C-6); 141.11 (C-3). IR spectrum (CCl₄): 3309, 3066, 2956, 2897, 2115, 1579, 1554, 1472, 1463, 1445, 1406, 1390, 1361, 1275, 1258, 1180, 1098, 1083, 1006, 939, 838.

1β-[2,6-Bis(ethynyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (23c). Compound 23c was prepared from 23a (192 mg, 0.31 mmol) by the general procedure to yield 23c (51 mg, 67%) as an orange solid. HRMS (ESI) for C₁₄H₁₃NO₃: [M + Na] calculated, 266.0788; found, 266.0786. ¹H NMR (500 MHz, DMSO-d₆): 1.68 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 10.2 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.26 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 1.8 Hz, H-2′b); 3.59 (m, 2H, H-5′); 3.84 (td, 1H, J_4′,5′a = J_4′,5′b = 4.9 Hz, J_4′,3′ = 2.2 Hz, H-4′); 4.21 (m, 1H, H-3′); 4.36 (s, 1H, CH≡C-6); 4.65 (s, 1H, CH≡C-2); 4.83 (bt, 1H, J_OH,5′a = J_OH,5′b = 5.6 Hz, OH-5′); 5.17 (d, 1H, J_OH,3′ = 3.8 Hz, OH-3′); 5.36 (bdd, 1H, J_1′,2′a = 10.2 Hz, J_1′,2′b = 5.7 Hz, H-1′); 7.59 (bd, 1H, J_5,4 = 8.1 Hz, H-5); 8.01 (dd, 1H, J_4,5 = 8.2 Hz, J_4,1′ = 0.7 Hz, H-4). ¹³C NMR (125.7 MHz, DMSO-d₆): 42.60 (CH₂-2′); 62.31 (CH₂-5′); 72.54 (CH-3′); 76.04 (CH-1′); 80.14 (CH≡C-2); 80.63 (CH≡C-6); 82.48 (CH≡C-6); 85.35 (CH≡C-2); 88.16 (CH-4′); 127.67 (CH-5); 134.56 (CH-4); 139.50 (C-2); 140.82 (C-6); 141.78 (C-3). IR spectrum (KBr): 3428, 3299, 3070, 2107, 1579, 1558, 1447, 1235, 1078, 1050, 1026, 846.

1β-[2-Chloro-6-(2-pyridyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (24a). DMF (2.5 mL) was added to a flame-dried and argon-purged flask, containing 4 (100 mg, 0.19 mmol), and PdCl₂(PPh₃)₂ (7 mg, 0.0095 mmol, 5 mol%). After 5 min of stirring at room temperature, tributyl(2-pyridyl)stannane (0.25 mL, 0.76 mmol, 4.0 equiv.) was added, and mixture was heated to 100 °C for 12 h. The crude reaction mixture was diluted with Et₂O (300 mL), washed with 2 M HCl (80 mL) and saturated NaHCO₃ (100 mL). After evaporation of the solvents under reduced pressure, the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 3% EtOAc in hexanes to obtain 24a (82 mg, 82%) as a colorless oil. HRMS (ESI) for C₂₇H₄₃ClN₂O₃Si₂: [M + H] calculated, 535.2574; found, 535.2574. ¹H NMR (500 MHz, CDCl₃): 0.098, 0.100, 0.107 and 0.109 (4 × s, 4 × 3H, CH₃Si); 0.91 and 0.92 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.77 (ddd, 1H, J_gem = 12.7 Hz, J_2′a,1′ = 9.6 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.46 (ddd, 1H, J_gem = 12.7 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.4 Hz, H-2′b); 3.74 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.8 Hz, H-5′a); 3.81 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 4.00 (ddd, 1H, J_4′,5′a = 4.8 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.42 (dtd, 1H, J_3′,2′a = 5.7 Hz, J_3′,4′ = J_3′,2′b = 2.5 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.45 (ddq, 1H, J_1′,2′a = 9.6 Hz, J_1′,2′b = 5.9 Hz, J_1′,3′ = J_1′,4 = J_1′,5 = 0.7 Hz, H-1′); 7.33 (dd, 1H, J_5,4 = 7.5 Hz, J_5,6 = 4.8 Hz, J_5,3 = 1.2 Hz, H-5-py); 7.82 (td, 1H, J_4,5 = J_4,3 = 7.8 Hz, J_4,6 = 1.8 Hz, H-4-py); 8.14 (dd, 1H, J_4,5 = 8.0 Hz, J_4,1′ = 0.8 Hz, H-4); 8.35 (bd, 1H, J_5,4 = 8.0 Hz, H-5); 8.40 (dt, 1H, J_3,4 = 8.0 Hz, J_3,5 = J_3,6 = 1.0 Hz, H-3-py); 8.67 (ddd, 1H, J_6,5 = 4.8 Hz, J_6,4 = 1.8 Hz, J_6,3 = 0.9 Hz, H-6-py). ¹³C NMR (125.7 MHz, CDCl₃): −5.47, −5.37, −4.75 and −4.62 (CH₃Si); 18.00 and 18.31 ((CH₃)₃C); 25.77 and 25.90 ((CH₃)₃C); 42.47 (CH₂-2′); 63.30 (CH₂-5′); 73.76 (CH-3′); 76.30 (CH-1′); 87.89 (CH-4′); 119.89 (CH-5); 121.43 (CH-3-py); 124.06 (CH-5-py); 136.73 (CH-4); 137.21 (CH-4-py); 137.65 (C-3); 147.92 (C-2); 148.96 (CH-6-py); 154.50 (C-2-py); 154.79 (C-6). IR spectrum (CCl₄): 2956, 2897, 1588, 1568, 1472, 1463, 1445, 1390, 1361, 1340, 1258, 1218, 1174, 1071, 1054, 939, 838.

1β-[2-Chloro-6-(2-pyridyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (24b). Compound 24b was prepared from 24a (207 mg, 0.39 mmol) by the general procedure to yield 24b (102 mg, 86%) as a white solid. HRMS (ESI) for C₁₅H₁₅ClN₂O₃: [M + H] calculated, 307.0844; found, 307.0844. ¹H NMR (500 MHz, CD₃OD): 1.84 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.54 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.72 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.75 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.5 Hz, H-5′b); 4.01 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.36 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.44 (ddq, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.7 Hz, J_1′,4 = J_1′,5 = = J_1′,3′ = 0.7 Hz, H-1′); 7.46 (ddd, 1H, J_5,4 = 7.6 Hz, J_5,6 = 4.9 Hz, J_5,3 = 1.2 Hz, H-5-py); 7.96 (ddd, 1H, J_4,3 = 8.0 Hz, J_4,5 = 7.6 Hz, J_4,6 = 1.8 Hz, H-4-py); 8.25 (dd, 1H, J_4,5 = 8.0 Hz, J_4,1′ = 0.8 Hz, H-4); 8.30 (bd, 1H, J_5,4 = 8.0 Hz, H-5); 8.35 (dt, 1H, J_3,4 = 8.0 Hz, J_3,5 = J_3,6 = 1.1 Hz, H-3-py); 8.65 (ddd, 1H, J_6,5 = 4.9 Hz, J_6,4 = 1.8 Hz, J_6,3 = 0.9 Hz, H-6-py). ¹³C NMR (125.7 MHz, CD₃OD): 43.20 (CH₂-2′); 63.76 (CH₂-5′); 74.19 (CH-3′); 77.64 (CH-1′); 89.22 (CH-4′); 121.14 (CH-5); 122.68 (CH-3-py); 125.72 (CH-5-py); 138.33 (CH-4); 138.80 (C-3); 139.05 (CH-4-py); 149.22 (C-2); 150.14 (CH-6-py); 155.57 (C-2-py); 156.02 (C-6). IR spectrum (KBr): 3420, 3336, 3096, 3066, 1587, 1573, 1547, 1478, 1434, 1256, 1173, 1149, 993, 1063, 1047, 993.

1β-[2,6-Bis(2-pyridyl)pyridin-3-yl]-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (25a). Toluene (3.0 mL) was added to a flame-dried and argon-purged flask, containing 4 (159 mg, 0.29 mmol), and Pd(PPh₃)₄ (65 mg, 0.058 mmol, 20 mol%). After 5 min of stirring at room temperature, tributyl(2-pyridinyl)stannane (0.38 mL, 1.16 mmol, 4.0 equiv.) was added, and the mixture was heated to 110 °C for 12 h. The crude reaction mixture was diluted with Et₂O (300 mL), and washed with 2 M HCl (80 mL) and saturated NaHCO₃ (100 mL). After evaporation of the solvents under reduced pressure, the crude product was chromatographed on silica gel eluting with a gradient of hexanes to 12% EtOAc in hexanes to obtain 25a (197 mg, 92%) as a colorless oil. HRMS (ESI) for C₃₂H₄₇N₃O₃Si₂: [M + H] calculated, 578.3229; found, 578.3229. ¹H NMR (500 MHz, CDCl₃): 0.08, 0.09, 0.11 and 0.13 (4 × s, 4 × 3H, CH₃Si); 0.90 and 0.93 (2 × s, 2 × 9H, ((CH₃)₃C)); 1.91 (ddd, 1H, J_gem = 12.8 Hz, J_2′a,1′ = 10.0 Hz, J_2′a,3′ = 5.6 Hz, H-2′a); 2.50 (ddd, 1H, J_gem = 12.8 Hz, J_2′b,1′ = 5.4 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.73 (dd, 1H, J_gem = 10.7 Hz, J_5′a,4′ = 5.2 Hz, H-5′a); 3.81 (dd, 1H, J_gem = 10.7 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.93 (ddd, 1H, J_4′,5′a = 5.2 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.3 Hz, H-4′); 4.42 (bdt, 1H, J_3′,2′a = 5.5 Hz, J_3′,4′ = J_3′,2′b = 2.2 Hz, H-3′); 5.74 (bdd, 1H, J_1′,2′a = 10.0 Hz, J_1′,2′b = 5.4 Hz, H-1′); 7.33 (dd, 1H, J_5,4 = 7.6 Hz, J_5,6 = 4.9 Hz, J_5,3 = 1.2 Hz, H-5-py-2); 7.39 (m, 1H, H-5-py-6); 7.87 (td, 1H, J_4,5 = J_4,3 = 7.7 Hz, J_4,6 = 1.2 Hz, H-4-py-2); 7.91 (H-4-py-6); 8.11 (dt, 1H, J_3,4 = 7.9 Hz, J_3,5 = J_3,6 = 1.1 Hz, H-3-py-2); 8.36 (bd, 1H, J_4,5 = 8.3 Hz, H-4); 8.53 (bd, 1H, J_5,4 = 8.3 Hz, H-5); 8.58 (bd, 1H, J_3,4 = 8.0 Hz, H-3-py-6); 8.67 (ddd, 1H, J_6,5 = 4.9 Hz, J_6,4 = 1.9 Hz, J_6,3 = 1.0 Hz, H-6-py-2); 8.75 (ddd, 1H, J_6,5 = 5.0 Hz, J_6,4 = 1.7 Hz, J_6,3 = 0.8 Hz, H-6-py-6). ¹³C NMR (125.7 MHz, CDCl₃): −5.46, −5.33, −4.77 and −4.65 (CH₃Si); 17.98 and 18.34 ((CH₃)₃C); 25.76 and 25.93 ((CH₃)₃C); 44.75 (CH₂-2′); 63.65 (CH₂-5′); 74.42 (CH-3′); 76.58 (CH-1′); 87.92 (CH-4′); 121.11 (CH-5); 121.95 (CH-3-py-6); 122.89 (CH-5-py-2); 123.89 (CH-5-py-6); 124.54 (CH-3-py-2); 136.57 (CH-4); 136.74 (CH-4-py-2); 138.4 (CH-4-py-6); 138.77 (C-3); 147.89 (CH-6-py-2,6); 152.35 (C-6); 153.65 (C-2); 155.12 (C-2-py-6); 157.91 (C-2-py-2). IR spectrum (CCl₄): 3088, 3065, 2956, 2929, 2897, 285, 7, 1590, 1586, 1577, 1566, 1556, 1472, 1462, 1456, 1434, 1425, 1389, 1361, 1257, 1173, 1147, 1095, 1040, 1031, 1006, 939, 838.

1β-[2,6-Bis(2-pyridyl)pyridin-3-yl]-1,2-dideoxy-D-ribofuranose (25b). Compound 25b was prepared from 25a (209 mg, 0.36 mmol) by the general procedure to yield 25b (110 mg, 87%) as a white solid. HRMS (ESI) for C₂₀H₁₉N₃O₃: [M + H] calculated, 350.1499; found, 350.1498. ¹H NMR (500 MHz, CD₃OD): 1.94 (ddd, 1H, J_gem = 13.3 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.2 Hz, H-2′a); 2.35 (ddd, 1H, J_gem = 13.3 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.72 (dd, 1H, J_gem = 11.7 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.74 (dd, 1H, J_gem = 11.7 Hz, J_5′b,4′ = 4.5 Hz, H-5′b); 3.89 (btd, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.9 Hz, H-4′); 4.30 (dddd, 1H, J_3′,2′a = 6.2 Hz, J_3′,4′ = 2.9 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.6 Hz, H-3′); 5.62 (dd, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.7 Hz, H-1′); 7.44 (ddd, 1H, J_5,4 = 7.5 Hz, J_5,6 = 4.9 Hz, J_5,3 = 1.2 Hz, H-5-py-6); 7.48 (m, 1H, H-5-py-2); 7.93 (ddd, 1H, J_4,3 = 8.0 Hz, J_4,5 = 7.5 Hz, J_4,6 = 1.8 Hz, H-4-py-6); 7.98–8.01 (m, 2H, H-3,4-py-2); 8.38 (bd, 1H, J_5,4 = 8.3 Hz, H-5); 8.40 (bd, 1H, J_4,5 = 8.3 Hz, H-4); 8.46 (dt, 1H, J_3,4 = 8.0 Hz, J_3,5 = J_3,6 = 1.1 Hz, H-3-py-6); 8.65 (ddd, 1H, J_6,5 = 4.9 Hz, J_6,4 = 1.8 Hz, J_6,3 = 0.9 Hz, H-6-py-6); 8.68 (dt, 1H, J_6,5 = 4.9 Hz, J_6,4 = J_6,3 = 1.4 Hz, H-6-py-2). ¹³C NMR (125.7 MHz, CD₃OD): 45.16 (CH₂-2′); 63.87 (CH₂-5′); 74.36 (CH-3′); 77.73 (CH-1′); 89.01 (CH-4′); 121.89 (CH-5); 122.68 (CH-3-py-6); 124.62 (CH-5-py-2); 125.31 (CH-5-py-6); 125.85 (CH-3-py-2); 137.62 (CH-4); 138.47 (CH-4-py-2); 138.73 (CH-4-py-6); 138.91 (C-3); 149.38 (CH-6-py-2); 150.11 (CH-6-py-6); 155.26 (C-6); 155.51 (C-2); 157.08 (C-2-py-6); 159.27 (C-2-py-2). IR spectrum (KBr): 3415, 3088, 3062, 2929, 1590, 1575, 1565, 1557, 1473, 1455, 1434, 1425, 1353, 1254, 1201, 1174, 1150, 1095, 1071, 1050, 1021, 942, 855.

1β-(2-Chloropyridin-3-yl)-1,2-dideoxy-3,5-di-O-(t-butyldimethylsilyl)-D-ribofuranose (26a). Vinylmagnesium chloride (1 M solution in THF, 1 mL, 1.0 mmol) was added dropwise to a flame-dried flask containing a solution of the nucleoside 4 (100 mg, 0.19 mmol) and Fe(acac)₃ (13 mg, 0.038 mmol) in dry THF (3.0 mL) under Ar. The reaction mixture was then stirred at rt for 12 h. Then the mixture was poured onto a mixture of ice (100 mL) and NH₄Cl (1 g), and extracted with chloroform (3 × 100 mL). Evaporation of the organic phase followed by column chromatography on silica gel eluting with a gradient of hexanes to 4% EtOAc in hexanes afforded the nucleoside 26a (40 mg, 47%) as a colorless oil. HRMS (ESI) for C₂₂H₄₀ClNO₃Si₂: [M + Na] calculated, 480.2128; found, 480.2126. ¹H NMR (500 MHz, CDCl₃): 0.086, 0.088, 0.090 and 0.10 (4 × s, 4 × 3H, CH₃Si); 0.89 and 0.92 (2 × s, 2 × 9H, ((CH₃)₃C); 1.73 (ddd, 1H, J_gem = 12.6 Hz, J_2′a,1′ = 9.5 Hz, J_2′a,3′ = 5.5 Hz, H-2′a); 2.44 (ddd, 1H, J_gem = 12.6 Hz, J_2′b,1′ = 5.9 Hz, J_2′b,3′ = 2.5 Hz, H-2′b); 3.71 (dd, 1H, J_gem = 10.9 Hz, J_5′a,4′ = 4.8 Hz, H-5′a); 3.78 (dd, 1H, J_gem = 10.9 Hz, J_5′b,4′ = 3.5 Hz, H-5′b); 3.99 (ddd, 1H, J_4′,5′a = 4.8 Hz, J_4′,5′b = 3.5 Hz, J_4′,3′ = 2.6 Hz, H-4′); 4.39 (dt, 1H, J_3′,2′a = 5.5 Hz, J_3′,4′ = J_3′,2′b = 2.6 Hz, H-3′); 5.40 (dd, 1H, J_1′,2′a = 9.5 Hz, J_1′,2′b = 5.9 Hz, H-1′); 7.23 (dd, 1H, J_5,4 = 7.7 Hz, J_5,6 = 4.6 Hz, H-5); 8.03 (dd, 1H, J_4,5 = 7.6 Hz, J_4,6 = 1.3 Hz, H-4); 8.28 (bd, 1H, J_6,5 = 4.6 Hz, H-6). ¹³C NMR (125.7 MHz, CDCl₃): −5.49, −5.42, −4.76 and −4.62 (CH₃Si); 17.99 and 18.28 ((CH₃)₃C); 25.75 and 25.86 ((CH₃)₃C); 42.32 (CH₂-2′); 63.28 (CH₂-5′); 73.71 (CH-3′); 76.14 (CH-1′); 87.82 (CH-4′); 122.68 (CH-5); 135.86 (CH-4); 137.67 (C-3); 147.93 (CH-6); 148.50 (C-2). IR spectrum (CCl₄): 2956, 2899, 1582, 1566, 1472, 1463, 1449, 1390, 1362, 1336, 1258, 1209, 1172, 1057, 1031, 1006, 968, 838.

1β-(2-Chloropyridin-3-yl)-1,2-dideoxy-D-ribofuranose (26b). Compound 26b was prepared from 26a (80 mg, 0.17 mmol) by the general procedure to yield 26b (32 mg, 82%) as a white solid. HRMS (ESI) for C₁₀H₁₂ClNO₃: [M + Na] calculated, 252.0398; found, 252.0398. ¹H NMR (500 MHz, CD₃OD): 1.78 (ddd, 1H, J_gem = 13.1 Hz, J_2′a,1′ = 10.1 Hz, J_2′a,3′ = 6.0 Hz, H-2′a); 2.50 (ddd, 1H, J_gem = 13.1 Hz, J_2′b,1′ = 5.7 Hz, J_2′b,3′ = 2.0 Hz, H-2′b); 3.70 (dd, 1H, J_gem = 11.8 Hz, J_5′a,4′ = 5.0 Hz, H-5′a); 3.72 (dd, 1H, J_gem = 11.8 Hz, J_5′b,4′ = 4.6 Hz, H-5′b); 3.99 (td, 1H, J_4′,5′a = J_4′,5′b = 4.8 Hz, J_4′,3′ = 2.7 Hz, H-4′); 4.33 (dddd, 1H, J_3′,2′a = 6.0 Hz, J_3′,4′ = 2.7 Hz, J_3′,2′b = 2.0 Hz, J_3′,1′ = 0.7 Hz, H-3′); 5.38 (ddpent, 1H, J_1′,2′a = 10.1 Hz, J_1′,2′b = 5.7 Hz, J_1′,4 = J_1′,5 = J_1′,6 = J_1′,3′ = 0.7 Hz, H-1′); 7.41 (ddd, 1H, J_5,4 = 7.7 Hz, J_5,6 = 4.8 Hz, J_5,1′ = 0.6 Hz, H-5); 8.17 (ddd, 1H, J_4,5 = 7.7 Hz, J_4,6 = 2.0 Hz, J_4,1′ = 0.8 Hz, H-4); 8.27 (ddd, 1H, J_6,5 = 4.8 Hz, J_6,4 = 2.0 Hz, J_6,1′ = 0.5 Hz, H-6). ¹³C NMR (125.7 MHz, CD₃OD): 43.11 (CH₂-2′); 63.72 (CH₂-5′); 74.13 (CH-3′); 77.46 (CH-1′); 89.17 (CH-4′); 124.54 (CH-5); 137.86 (CH-4); 138.87 (C-3); 149.10 (CH-6); 149.33 (C-2). IR spectrum (KBr): 3359, 1630, 1580, 1571, 1450, 1442, 1389, 1181, 1073, 1063, 1043, 1023, 951.

Crystallographic data for 4

M = 308.55 g mol⁻¹, monoclinic system, space group P2₁, a = 8.9755 (9) Å, b = 6.9472 (5) Å, c = 9.1777 (9) Å, β = 90.968 (9)°, Z = 2, V = 572.19 (9) ų, D_c = 1.791 g cm⁻³, μ(Cu-Kα) = 7.002 mm⁻¹, crystal dimensions of 0.58 × 0.56 × 0.21 mm. Data were collected at 170 (2) K on an Xcalbur Onyx CCD diffractometer with graphite monochromated Cu-Kα radiation. The structure was solved by charge flipping methods¹⁸ using the CRYSTALS suite of programs¹⁹ and anisotropically refined by full matrix least squares on F value to final R = 0.036 and R_w = 0.042 using 2220 independent reflections (Θ_max = 77.3°) and 147 parameters. The absolute configuration on stereogenic centers was confirmed by refinement of the Flack parameter (resulting value −0.02 (2)). The structure was deposited into the Cambridge Structural Database under number CCDC 927315.

Crystallographic data for 8b

M = 243.69 g mol⁻¹, monoclinic system, space group P2₁, a = 5.3111 (3) Å, b = 11.1077 (6) Å, c = 19.5383 (13) Å, β = 96.676 (6)°, Z = 4, V = 1144.84 (12) ų, D_c = 1.414 g cm⁻³, μ(Cu-Kα) = 2.908 mm⁻¹, crystal dimensions of 0.49 × 0.37 × 0.26 mm. Data were collected at 190 (2) K on an Xcalbur Onyx CCD diffractometer with graphite monochromated Cu-Kα radiation. The structure was solved by charge flipping methods¹ using the CRYSTALS suite of programs² and anisotropically refined by full matrix least squares on F squared value to final R = 0.038 and R_w = 0.095 using 4688 independent reflections (Θ_max = 77.4°) and 291 parameters. The absolute configuration on stereogenic centers was confirmed by refinement of the Flack parameter (resulting value −0.008 (12)). The structure was deposited into the Cambridge Structural Database under number CCDC 927314.

Acknowledgements

This work was supported by institutional support from the Academy of Sciences of the Czech Republic (RVO: 61388963) and Charles University, by a grant from the Czech Science Foundation (P207/11/0344) and by Gilead Sciences, Inc. The authors thank Mrs Eva Tloušťová (IOCB) for cytostatic and Dr Y.-J. Lee and Dr G. Bahador (Gilead Sciences, Inc.) for anti-HCV screening.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of all NMR spectra. CCDC 927314 and 927315. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ob40774h

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