Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide

Article pubs.acs.org/joc

Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors Martin Kurfirť ,† Lucie Č ervenkova ́ Š t’astna,́ † Martin Drací̌ nský,‡ Monika Müllerova,́ † Vojteč h Hamala,† Petra Curí̌ nova,́ † and Jindrǐ ch Karban*,† †

Institute of Chemical Process Fundamentals of the CAS, v. v. i, Rozvojová 135, 16502 Praha, Czech Republic Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 542/2, 16610 Praha, Czech Republic

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S Supporting Information *

ABSTRACT: Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the Tf2O/Ph2SO promoter system. Lowtemperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions. This study demonstrates how the stereoselectivity depends on acceptor reactivity and glycosyl donor configuration. Reactive acceptors favor formation of 1,2-transβ-glycosides with both D-gluco and D-galacto donors, whereas poorly reactive acceptors favor formation of 1,2-cis-α-glycosides with D-galacto donors but are unselective with D-gluco donors.

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INTRODUCTION

Deoxofluorinated carbohydrates are synthetic carbohydrate analogs in which one or more hydroxyl groups have been replaced by fluorine. They play a prominent role among carbohydrate mimics because of the similarity between fluorine and oxygen in terms of the van der Waals atomic radii (1.47 vs 1.52) and electronegativity (4.0 vs 3.5).1 Thus, they were exploited to design enzyme inhibitors2 and metabolically stable fluorinated carbohydrate haptens3,4 and used as probes of noncovalent interactions within the active site of a biological target.5 19F NMR using deoxofluorinated carbohydrates recently emerged as a tool to characterize carbohydrate recognition by their cognate proteins.6,7 Realization of the full potential of deoxofluorinated oligosaccharides necessitates not only access to selectively fluorinated glycosyl donors and acceptors, but also knowledge of their anomeric diastereoselectivity in glycosylation. Replacement of a protected hydroxyl group by fluorine in a glycosyl donor can influence anomeric stereoselectivity through multiple effects like destabilization of cationic transition states by the inductive effect of fluorine,8 stabilization of transient oxocarbenium ion conformers by electrostatic interaction with the C−F bond dipole,9 or attenuation of the hydrogen-bond acceptor capacity with respect to the parent oxygen substituent.1 However, except for an in-depth study of 2-deoxy-2-fluoro-hexopyranosyl trichloroacetimidate donors by Bucher and Gilmour,10−13 there have been no systematic studies investigating anomeric diastereoselectivity of fluorinated donors. Herein, we report the preparation of C-3 and C-4 deoxofluorinated glucosazide and galactosazide thiodonors 1−4 (Figure 1) and evaluation of their glycosylation © XXXX American Chemical Society

Figure 1. Structures of deoxofluorinated glycosazide thiodonors.

stereoselectivity with common model carbohydrate acceptors. These donors are gluco- and galactosaminyl donors in which the amino functionality has been masked as an azide to permit formation of α-glycosidic linkage. D-Glucosamine and Dgalactosamine occur as both α- and β-linked glycosides but the synthesis of β-linkage is facilitated by neighboring-group participation of an acyl-protected amine. Because the presence of an azide at C-2 does not guarantee α-selectivity,14 knowledge obtained by glycosylation of model acceptors will facilitate assembly of fluorinated oligosaccharides and reduce loss of time through trial and error. As we describe here, the anomeric stereoselectivity of donors 1−4 mostly correlates with acceptor reactivity and for deoxofluorinated D-galactoconfigured donors 3 and 4 can be interpreted in terms of a shift from an associative to dissociative mechanism. Received: March 19, 2019

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DOI: 10.1021/acs.joc.9b00705 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Scheme 1. Synthesis of Glycosazide Donors 1−4

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complete activation of the glycosyl donor.28 This generates unstable covalent reactive intermediates in equilibrium with transient ion pairs. Covalent intermediates can be detected spectroscopically. Treatment of β-anomer of 1 (β-1) with Ph2SO (1.3 equiv) and Tf2O (1.3 equiv) in CD2Cl2 at −80 °C monitored by low-temperature NMR led to complete consumption of β-1 and formation of three species (Figure 2). On the basis of the data in the literature,29,30 the characteristic NMR resonances were assigned as anomeric αtriflate 20, (δH1 6.09, 3JH1,H2 3.6 Hz, δC1 104.6), and both anomers of the oxosulfonium triflate: α-21 (δH1 6.38, 3JH1,H2 3.5 Hz, δC1 104.8) and β-21 (δH1 5.65, 3JH1,H2 8.3 Hz δC1

RESULTS AND DISCUSSION We opted for thioglycoside donors because they are highly versatile and stable in protecting group manipulation. The hydroxyl groups were protected as inert and “arming” (i.e., less deactivating) benzyl ether to avoid the effects of more deactivating and potentially participating acyl protecting groups. The preactivation protocol using the Ph2SO/Tf2O promoter system was chosen because it is capable of activating strongly disarmed thiodonors.15 Moreover, using this protocol, we can compare our data with those obtained for nonfluorinated conformationally restricted glucosazide donors.16 Synthesis of Deoxofluorinated Glycosyl Donors. Introduction of fluorine at the C-3 and C-4 positions was accomplished by exploiting versatile 1,6-anhydropyranose chemistry suitable for stereoselective installation of fluorine by nucleophilic displacement (Scheme 1).17−22 The key synthetic intermediates 6, 12, and 16 were prepared from known 1,6-anhydropyranoses 5,23 11,20 and 1524,25 as we described recently.20 Oxidative debenzylation and subsequent Latrell−Dax reaction effected C-4 inversion in 6 to provide 8.20 Alcohols 8, 12, and 16 were O-benzylated to obtain 9, 13, and 17, respectively. trans-Diaxial disposition of fluorine and hydroxyl in 12 could lead to epoxide formation during conventional O-benzylation. Therefore, benzylation of 12 was conducted by adding sodium hydride to a premixed solution of 12 and BnBr in dimethylformamide (DMF) to trap the incipient alkoxide before epoxide ring closure could occur.19,26 Treatment of 6, 9, 13, and 17 with phenyl trimethylsilyl sulfide/ZnI227 effected cleavage of the internal acetal yielding phenyl 1-thioglycosides 7, 10, 14, and 19 which were Obenzylated to provide the target 3-deoxy-3-fluoro- and 4deoxy-4-fluoro thiodonors 1−4 (Scheme 1). Except for 14, the phenyl 1-thioglycosides were obtained as separable mixtures of anomers after treatment with PhSTMS/ZnI2. The individual anomers were isolated and separately benzylated. Observation of Reactive Covalent Intermediates. In the preactivation protocol, addition of the acceptor is preceded by addition of the promoter at a low temperature to achieve

Figure 2. Section of the variable-temperature 1H NMR showing H-1 resonances of species resulting from activation of β-1 by the Ph2SO/ Tf2O system. B


Article

The Journal of Organic Chemistry 102.2). A marked increase in the relative abundance of β-21 resonances when using excess Ph2SO (2.6 equiv) supports their assignment (Figure S3).31 Identical covalent intermediates were also produced when α-1 was activated (see the Supporting Information). Intermediates 20 and α-21 decompose between −40 and −30 °C, whereas β-oxosulfonium triflate β-21 seems to anomerize into α-21 between −60 and −40 °C (Figure S3 in Supporting Information).30 The principal product of decomposition is 1,6-anhydropyranose 6. Formation of 1,6-anhydrobridge by participation of O-6 in preactivation-based glycosylation was also observed by others.32 The remaining donors 2−4 furnished analogous intermediates upon Ph2SO/Tf2O treatment (see Table S1 in Supporting Information). Glycosylation of Model Acceptors. Having established that our donors can be activated by the Ph2SO/Tf2O system, we proceeded to glycosylation of model acceptors (Table 1). Recent research by Codée’s group revealed that diastereoselectivity in preactivation-based glycosylation with 2-azido-2deoxyhexopyranosyl donors is highly sensitive to acceptor nucleophilicity, β-selectivity being favored with more nucleophilic glycosyl acceptors and α-selectivity with less nucleophilic

ones.14,16,31,33 Therefore, the diastereoselectivity of glycosyl donors 1−4 in preactivation-based glycosylation was evaluated against a set of carbohydrate acceptors A−I of varying nucleophilicities, from reactive unhindered secondary (A) and primary (B) alcohols, through less reactive pyranose equatorial alcohols (C−E), to least reactive pyranose axial alcohols (G−I).29 The anomeric configuration of the glycosylation products was determined from the magnitudes of the respective 3JH1,H2 coupling. The anomeric stereoselectivity was determined by integration of characteristic signals in 1H and 19F NMR spectra after aqueous workup. To avoid anomerization, the reaction was run in the presence of a base (2,4,6-tri-tert-butylpyrimidine) and was quenched with Et3N at −40 °C.34 The results obtained in glycosylation reactions with deoxofluorinated glycosyl donors are summarized in Table 1.35 Generally, D-gluco donors 1 and 2 showed gradual loss of selectivity along the acceptor reactivity scale from good βselectivity observed for the most reactive acceptors A and B (entries 1 and 2), to modest values found for equatorial acceptors (entries 3 and 5), to poor selectivity obtained for furanoid (entry 6) and axial acceptors (entries 8 and 9). A slight exception to the trend is the acceptor G which displayed modest β-selectivity, although the axial C-4 hydroxyl is sterically highly hindered (entry 7).33,36 We did not observe a shift from β- to α-selectivity characteristic for reactions of conformationally restricted glucosazide thiodonors such as phenyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-1-thioβ-D-glucopyranoside when going to weakly reactive acceptors G and I.16 Unlike the D-gluco-donors α-1 and 2, D-galacto-donors β-3 and 4 exhibited clear reversal of stereoselectivity with decreasing acceptor reactivity. They displayed moderate βselectivity with the most reactive acceptors A and B (entries 1 and 2), but yielded predominantly α-glycoside with the axial acceptors G−I (entries 7−9). Glycosylation of the C-4 equatorial acceptors E was almost unselective (entry 5), which is in agreement with the general trend. However, glycosylation of the equatorial C-3 hydroxyl of the acceptor C contradicted the trend strikingly because it furnished αdisaccharides 3C and 4C with good α-selectivity (entry 3). As both D-gluco donors 1 and 2 displayed a moderate β-preference when reacting with acceptor C, the stereochemistry at C-4 of the donor is critical for the stereochemical outcome with acceptor C. To assess the effect of the bulky 4,6-O-benzylidene acetal in C, we prepared related acceptor D, in which the benzylidene group was replaced by methyl ether, and reacted it with D-galacto donors 3 and 4. Interestingly, glycosylation of acceptor D was almost unselective and corresponded with the trend characteristic for the other acceptors (Table 1, entry 4). This suggests that the steric bulk or conformational effects of 4,6-O-benzylidene acetal in C together with D-galacto stereochemistry of the donor could disfavor the transition state leading to β-glycoside. The moderate yields obtained in glycosylation of acceptors G and H with 4 (Table 1, entries 7 and 8) were due to difficulties in chromatographic purification. Glycosylation of H with 4 was run three times because the minor anomer 4H-β decomposed during chromatography. Considering the instability of 4H-β, the values of α/β 4:1, 3.1:1, and 3.4:1 obtained after aqueous workup attest to good reproducibility of anomeric ratios. Mechanistic Discussion. Mechanisms involved in preactivation-based glycosylation have been thoroughly studied.28

Table 1. Stereoselectivity α/β and Yielda in Glycosylation of A−I with 1−4

a

Yield after chromatography. bc = 0.033 mol/L; n.a. = not available. C


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The Journal of Organic Chemistry

Scheme 2. Suggested Mechanisms in Glycosylation with D-Galacto Donor 3 and Relative Energies of Geometry-Optimized Conformers of the Oxocarbenium Ion Derived From 3a

a

Polarizable continuum model was used for implicit dichloromethane solvation. OBn groups were replaced with OMe to simplify calculation.

occasionally determine the stereochemical outcome of glycosylation. Good β-selectivity in glycosylation of reactive acceptors A and B with gluco-donors 1 and 2 probably also results from SN2-like displacement of α-triflate. Loss of selectivity observed for unreactive acceptors is difficult to rationalize. It may indicate low facial selectivity of the presupposed lowest-energy oxocarbenium conformer (the calculated lowest-energy conformer adopts conformation close to skew-boat 2SO, see Figure 3 and Table S2 in Supporting Information). Alternatively,

In agreement with the concept recently advocated by Codée et al., the stereoselectivity reversal observed for D-galacto-donors can be interpreted as the result of the shift from an SN2-like to SN1-like mechanism.16,37 According to this concept, the most reactive acceptors furnish β-product by glycosidation of covalent α-triflate or α-oxosulfonium triflate (or the corresponding contact ion pairs) through the SN2-like mechanism with inversion of configuration (Scheme 2).38 Acceptors G−I, considered not sufficiently nucleophilic to effect displacement of the covalent α-triflate,38,39 react with a more electrophilic solvent-separated oxocarbenium ion. Computational optimization of D-galacto-configured oxocarbenium ion geometry at the density functional theory (DFT) level indicated the half-chair 4 H3 conformer as the dominant one in solution (Scheme 2, see also Table S2 in Supporting Information).40 An acceptor approaches the 4H3 conformer from the bottom face, giving rise to the α-product through an energetically favorable chairlike transition state.41 The α-anomer can also arise through SN2 substitution of βoxosulfonium triflate by reactive acceptors. To estimate the contribution of β-oxosulfonium triflate substitution to the stereochemical outcome, we performed glycosylation of acceptor B with glycosyl donor β-3 using 3.0 equiv of diphenyl sulfoxide (not shown in Table 1). Assuming that D-galacto donor β-3 behaves in a manner similar to D-gluco donor 1, the increased concentration of Ph2SO would increase the concentration of β-oxosulfonium salt at the expense of αtriflate (as it was observed for 1, Figure S3), and βoxosulfonium salt will dominate in the reaction mixture after preactivation. The increase in Ph2SO loading from 1.3 to 3.0 equiv resulted in a drop in β-selectivity from α/β 1:5 to 1:1.6. We interpret this result as indicating that β-oxosulfonium triflate undergoes SN2 substitution but its contribution to overall stereoselectivity under given conditions is minor compared to α-triflate; otherwise, we would have observed reversal from β-selectivity to α-selectivity. High α-selectivity observed for glycosylation of acceptor C with both galactosazide donors emphasizes that for a given donor and conditions, factors other than acceptor nucleophilicity may

Figure 3. Relative energies of geometry-optimized conformers of the oxocarbenium ion derived from 1.40

greater stability of the D-gluco-configured α-triflate compared to D-galacto-configured α-triflate (with respect to the corresponding separated ion pair, see also Table S4 in Supporting Information) may suppress its full dissociation, and the glycosylation mechanism remains at the interface between SN1 and SN2 pathways even for weak acceptors. Good α-selectivity was reported for D-gluco donor phenyl 2-azido-3O-benzyl-4,6-O-benzylidene-2-deoxy-1-thio-β-D-glucopyranoside in preactivation-based glycosylation with weak acceptors G and I.16 In this case, α-selectivity results from conformational restriction imposed by benzylidene acetal. It forces the oxocarbenium ion to adopt 3E/3H4-like conformation, and it is attacked by the nucleophile from the bottom face to give αdisaccharides via an energetically favorable chair-like transition state.16 Application in Glycoside Synthesis. With the prospect of preparing multivalent deoxofluorinated glycoconjugates in mind, and also to illustrate application of our donors, we prepared benzylated spacer-armed 4F-GalNAc derivative 23 ready for conjugation by click chemistry (Scheme 3). D


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The Journal of Organic Chemistry Scheme 3. Synthesis of Spacer-Armed 23 and Protected α-D-GalpN3-(1,3)-D-GalpN3 Disaccharide 26

particle size 15 μm, containing 12−13.5% CaSO4·0.5 H2O and fluorescent indicator). Maximum loading used was ca. 65 mg per one plate. If necessary, the plates were developed repeatedly. The solutions were concentrated using a vacuum rotary evaporator at less than 45 °C. Anhydrous sodium sulfate was used to dry solutions after aqueous workup. The 1H (400.1 MHz), 13C (100.6 MHz), and 19 F (376.4 MHz) NMR spectra were measured on a Bruker AVANCE 400 spectrometer at 25 °C. The 1H and 13C NMR spectra were referenced to the line of the solvent (δ/ppm; δH/δC: CDCl3, 7.26/ 77.16). The 19F spectra were referenced to the line of internal standard hexafluorobenzene (δ/ppm; −163.00). High-resolution mass spectrometry (HRMS) analyses were done using Bruker MicrOTOFQIII, using APCI ionization in positive mode; general settings: 100− 2000m/z, capillary 4000 V, end plate −500 V, corona 3000 nA, collision cell RF 350 Vpp, nebulizer (N2) 3 bar, dry heater 350 °C, dry gas (N2) 3 L/min, calibration Tuning mix APCI-TOF (pos). The m/z value of the [M − N2 + H]+ adduct is reported for 2-azido sugars because the molecular ion adducts were undetectable or extremely weak in abundance. The optical rotation was measured at 589 nm in a 10 cm cell; concentration is given in g/100 mL. Starting compounds 6,20 12,20 and 1620 and carbohydrate glycosyl acceptors B,45 C,11 E,46 G,46 H,47 I,48 and 2443 were prepared by published procedures, D was prepared as described below, and F was commercially available. To simplify numbering, symbol α or β placed after a compound number indicates the anomeric configuration of the newly formed glycosidic bond in glycosylation of model acceptors A−I (e.g., 1C-α, 1C-β). EtOAc stands for ethyl acetate, PE for petroleum ether, and TBAI for tetrabutylammonium iodide. General Procedure for Reaction of 1,6-Anhydropyranoses with Phenyl Trimethylsilyl Sulfide. To a solution of starting deoxofluorinated 1,6-anhydrohexopyranose in dry 1,2-dichloroethane (c 0.3 M), trimethyl(phenylthio)silane (3.0−3.3 equiv) and ZnI2 (1.5−1.8 equiv) were added sequentially under argon atmosphere, and the reaction was stirred vigorously and protected from light at rt for 16−72 h until TLC indicated full consumption of the starting compound. It was diluted with dichloromethane, the organic layer was washed with water, and the water phase was extracted with dichloromethane (3×). The organic extracts were combined, dried, and concentrated. The crude product was then stirred in methanol acidified by AcOH (ca. 0.5 mL) at rt (2−4 h) to remove the 6-Otrimethylsilyl group, concentrated, and purified by column chromatography. General Procedure for 6-O-Benzylation of Compounds 7, 10, 14, and 19. Sodium hydride (60% suspension in oil) was added to a cooled (−25 °C) solution of the starting alcohol in the specified volume of dry THF under argon atmosphere. The reaction mixture was stirred for about 30 min, and then benzyl bromide and catalytic amount of TBAI were added. The reaction was allowed to warm up to room temperature and stirred overnight protected from moisture. It was then cooled by ice water bath, quenched by dropwise addition of methanol (0.5−1 mL), and diluted with dichloromethane. The organic layer was washed with water, and the water phase was neutralized by 5% HCl if thick emulsion formed and then extracted

Glycosylation of 2-[2-(chloroethoxy)-ethoxy]ethanol with 4 proceeded with moderate β-selectivity as anticipated on the basis of model glycosylations. Although the β-linkage is generally better constructed with N-acylated donors than azides, such an approach would require extra synthetic steps in the case of our fluorinated donors: azide reduction and acylation before a glycosylation step, and then removal of the acyl group and acetylation. Finally, to further illustrate the synthetic utility of the obtained knowledge, we synthesized protected C-3′-deoxofluorinated analog of disaccharide α-D-GalpN3-(1,3)-D-GalpN3, whose N-acetyl form (α-D-GalpNAc-(1,3)-D-GalpNAc) is commonly found in pathogenic bacteria.42 It also forms the terminal nonreducing end motif in the Forssman antigen.42 We anticipated that glycosylation of C-3 hydroxyl in acceptor 2443 with β-3 would provide α-linked disaccharide because this C-3 axial hydroxyl is very weakly nucleophilic (Scheme 3).44 This was indeed the case and product 25 was obtained with exclusive α-selectivity. Acetolysis of the 1,6-anhydro bridge, somewhat surprisingly accompanied by acetolytic cleavage of the benzyl ether at O-6′, yielded the target disaccharide 26 (Scheme 3). In summary, we prepared C-3 and C-4 deoxofluorinated glucosazide and galactosazide phenyl 1-thioglycosides and examined their anomeric stereoselectivity using the preactivation-based glycosylation protocol. We demonstrated that preactivation with a Ph2SO/Tf2O promoter system led to formation of covalent α-triflate and both anomers of oxosulfonium triflate. Glycosylation with the galactosazide donors was very sensitive to the acceptor structure and exhibited a selectivity reversal with decreasing acceptor reactivity, whereas glycosylation with glucosazide donors showed gradual loss of β-selectivity.

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EXPERIMENTAL SECTION

General Methods. Reagents and reactants were purchased from commercial suppliers and used as obtained. Tetrahydrofuran (THF) and toluene were dried by distillation from sodium, CH2Cl2, and (CH2Cl)2 were dried by distillation from CaH2 and stored over molecular sieves 3 Å. Pyridine was dried by standing over NaOH. Dry DMF was purchased from a commercial supplier. Ethyl acetate and petroleum ether (fraction with boiling point 40−65 °C) were distilled before use. Thin-layer chromatography (TLC) was carried out with Merck DC Alufolien with Kiesegel F254, and spots were detected with an anisaldehyde solution in EtOH/AcOH/H2SO4. UV detection at 254 nm was also used where appropriate. Column chromatography was performed with silica gel 60 (70−230 mesh, Material Harvest). Preparative TLC chromatography was performed using 20 cm × 20 cm glass plates covered with TLC-Silica gel 60 GF254 (20 g, mean E


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(2CHarom), 130.9 (Cq), 129.4 (2CHarom), 128.9 (CHarom), 128.7 (2CHarom), 128.3 (3CHarom), 97.9 (d, 1J(C−F) = 189.0 Hz, C-3), 85.5 (d, 3J(C−F) = 7.3 Hz, C-1), 78.5 (d, 3J(C−F) = 8.4 Hz, C-5), 74.9 (d, 2 J(C−F) = 16.7 Hz, C-4), 74.7 (d, 4J(C−F) = 2.9 Hz, CH2 Bn), 63.6 (d, 2 J(C−F) = 18.0 Hz, C-2), 61.9 (d, 4J(C−F) = 1.4 Hz, C-6). 19F NMR (CDCl3, 376 MHz): δ −184.62 (dt, 2J(H−F) = 51.6 Hz, 3J(H−F) = 12.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1219. Phenyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-1thio-α-D-glucopyranoside (α-1). Compound α-1 was prepared according to the general procedure by reaction of α-7 (1.000 g, 2.568 mmol) with sodium hydride (60% in oil, 154 mg, 3.850 mmol) and benzyl bromide (0.49 mL, 4.12 mmol) in dry THF (10 mL). Chromatography in EtOAc/petroleum ether 1:10 afforded α-1 as a colorless syrup (995 mg, 81%), Rf 0.22 (EtOAc/heptane 1:10), [α]20 D +208 (c 0.41, CHCl3). 1H NMR (CDCl3, 400 MHz, H−H COSY, HSQC, HMBC): δ 7.50−7.46 (m, 2H, CHarom), 7.36−7.23 (m, 13H, CHarom), 5.60 (dd, 1H, J = 5.7, 3.3 Hz, H-1), 4.87 (ddd, 1H, J = 52.8, 10.1, 8.4 Hz, H-3), 4.87 (dd, 1H, J = 11.0, 1.2 Hz, CHH O-4Bn), 4.60 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.53 (d, 1H, J = 11.0 Hz, CHH O4Bn), 4.44 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.35 (ddd, 1H, J = 10.0, 3.8, 2.1 Hz, H-5), 4.06 (ddd, 1H, J = 11.5, 10.1, 5.7 Hz, H-2), 3.86 (ddd, 1H, J = 14.4, 10.0, 8.4 Hz, H-4), 3.80 (dd, 1H, J = 10.8, 3.8 Hz, H-6), 3.64 (dt, 1H, J = 10.8, 2.1 Hz, H-6). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6Bn), 137.6 (Cq O-4Bn), 133.0 (Cq), 132.4, 129.3, 128.59, 128.55, 128.23 (5× 2CHarom), 128.15 (CHarom), 128.1 (3CHarom), 128.0 (CHarom), 95.7 (d, 1J(C−F) = 186.1 Hz, C-3), 86.7 (d, 3J(C−F) = 8.1 Hz, C-1), 75.9 (d, 2 J(C−F) = 16.6 Hz, C-4), 74.8 (d, 4J(C−F) = 2.4 Hz, CH2 O-4Bn), 76.6 (CH2 O-6Bn), 71.1 (d, 3J(C−F) = 8.4 Hz, C-5), 68.1 (C-6), 62.4 (d, 2 J(C−F) = 17.3 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −189.38 (dddd, 2J(H−F) = 53.2 Hz, 3J(H−F) = 14.4, 11.5, 4J(H−F) = 3.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1695; found, 452.1701. Phenyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-1thio-β-D-glucopyranoside (β-1). Compound β-1 was prepared according to the general procedure by reaction of β-7 (155 mg, 0.398 mmol) with sodium hydride (60% in oil, 21 mg, 0.525 mmol) and benzyl bromide (76 μL, 0.64 mmol) in dry THF (2 mL). Chromatography in EtOAc/petroleum ether 1:10 afforded β-1 as a colorless syrup (180 mg, 81%) which crystallized on standing in a refrigerator, mp 51−54 °C (heptane/MTBE), [α]20 D +0.5 (c 1.59, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.60 (dd, 2H, J = 8.1, 1.6 Hz, CHarom), 7.38−7.24 (m, 13H, CHarom), 4.80 (dd, 1H, J = 11.1, 0.8 Hz, CHH O-4Bn), 4.61 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.56 (d, 1H, J = 11.1 Hz, CHH O4Bn), 4.54 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.53 (ddd, 1H, J = 51.6, 9.0, 8.8 Hz, H-3), 4.40 (dd, 1H, J = 10.2, 0.9 Hz, H-1), 3.79 (dt, 1H, J = 11.0, 1.9 Hz, H-6), 3.73 (dd, 1H, J = 11.0, 4.3 Hz, H-6), 3.71 (ddd, 1H, J = 12.9, 9.8, 8.8 Hz, H-4), 3.47 (ddd, 1H, J = 12.9, 10.2, 9.0 Hz, H-2), 3.44 (ddd, 1H, J = 9.8, 4.3, 1.9 Hz, H-5). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.2 (Cq O-6Bn), 137.6 (Cq O-4Bn), 133.8 (2CHarom), 131.1 (Cq), 129.2 (2CHarom), 128.7 (CHarom), 128.58, 128.55, 128.22 (3× 2CHarom), 128.15, 127.84 (2× 1CHarom), 127.79 (2CHarom), 97.9 (d, 1J(C−F) = 188.9 Hz, C-3), 85.4 (d, 3J(C−F) = 7.2 Hz, C-1), 78.3 (d, 3J(C−F) = 8.7 Hz, C-5), 75.2 (d, 2J(C−F) = 16.7 Hz, C-4), 74.7 (d, 4J(C−F) = 2.6 Hz, CH2 O-4Bn), 73.6 (CH2 O-6Bn), 68.6 (d, 4J(C−F) = 1.6 Hz, C-6), 63.5 (d, 2J(C−F) = 17.8 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −184.66 (dt, 2J(H−F) = 51.6 Hz, 3J(H−F) = 12.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1695; found, 452.1693. 1,6-Anhydro-2-azido-2,3-dideoxy-3-fluoro-β-D-galactopyranose (8). Compound 8 was prepared using a minor modification of the procedure from lit.20 A solution of NaBrO3 (2.998 g, 19.869 mmol) in water (61 mL) was added to a solution of 620 (1.839 g, 6.585 mmol) in EtOAc (93 mL). The resulting mixture was stirred vigorously and a solution of Na2S2O4 (3.469 g, 19.92 mmol) in water (134 mL) was added dropwise. The reaction mixture turned orange. Stirring continued at rt until TLC (EtOAc/petroleum ether 1:2) indicated the absence of the starting compound 6 (2.5 h). The

with dichloromethane (3×). The organic extracts were combined, dried, and concentrated to afford crude benzylated phenyl 1thioglycopyranoside which was purified by column chromatography. General Glycosylation Procedure. The procedure was adapted from ref 16. A mixture of thioglycoside donor (48 mg, 0.100 mmol), diphenyl sulfoxide (1.3 equiv, 0.129 mmol, 26 mg), and tri-tertbutylpyrimidine (2.5 equiv, 0.250 mmol, 62 mg) was codistilled with dry toluene (3×) and then dried for 20 min in the vacuum of an oil pump. Dry dichloromethane (2 mL) and 3 Å molecular sieves were added, and the resulting suspension was stirred for 1.5 h at room temperature under argon and then cooled to −78 °C. Triflic anhydride (1.3 equiv, 0.13 mmol, 22 μL) was added dropwise, and the reaction was allowed to warm up to −60 °C and then recooled to −78 °C. A solution of glycosyl acceptor (2.0 equiv, 0.200 mmol) in dry dichloromethane (1 mL) was added dropwise. The reaction mixture was allowed to warm up to −40 °C in about 60−90 min and stirred for additional 2−4 h. The reaction mixture was quenched with Et3N (0.1 mL, 0.7 mmol) at −40 °C and left at −20 °C overnight. It was then diluted with dichloromethane, filtered, and washed with water. The water phase was extracted with dichloromethane (3×). Organic extracts were combined, dried, and concentrated to afford the crude glycosylation product. 1H NMR and 19F NMR spectra were recorded, and the crude product was purified by column chromatography. Fractions from column chromatography were further purified by preparative TLC chromatography when needed. Whenever possible, separation of anomers was attempted to facilitate NMR assignment. Phenyl 2-Azido-4-O-benzyl-2,3-dideoxy-3-fluoro-1-thio-αD-glucopyranoside (α-7) and Phenyl 2-Azido-4-O-benzyl-2,3dideoxy-3-fluoro-1-thio-β- D-glucopyranoside (β-7). Compounds α-7 and β-7 were prepared according to the general procedure by reaction of 1,6-anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-fluoro-β-D-glucopyranose20 (6, 1.300 g, 4.655 mmol) with PhSTMS (2.86 mL, 15.10 mmol) and ZnI2 (2.5 g, 7.8 mmol) in dichloroethane (14 mL). The reaction was completed in 30 h, and TLC (EtOAc/petroleum ether 1:5) showed the absence of 6 and the presence of one major product (Rf 0.56). The residue after workup was dissolved in MeOH (70 mL), AcOH (7 drops) was added, and the solution was stirred at rt for 2 h until TLC (EtOAc/petroleum ether 1:5) showed the absence of the product with Rf 0.56 and formation of two slower-moving compounds. Methanolic solution was concentrated, and the residue was chromatographed in EtOAc/ petroleum ether 1:3 to afford first β-7 (373 mg, 21%) as a crystalline compound. Continued elution afforded α-7 (1.009 g, 56%) as a colorless syrup that crystallized in a refrigerator after 2 months. Data for α-7: mp 55−57 °C (MTBE/heptane), [α]20 D +237 (c 0.36, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.48−7.45 (m, 2H, CHarom), 7.39−7.30 (m, 8H, CHarom), 5.56 (ddd, 1H, J = 5.7, 3.2, 0.6 Hz, H-1), 4.91 (ddd, 1H, J = 52.5, 10.2, 8.4 Hz, H-3), 4.91 (dd, 1H, J = 11.2, 1.2 Hz, CHH Bn), 4.67 (d, 1H, J = 11.2 Hz, CHH Bn), 4.23 (dddd, 1H, J = 10.0, 3.4, 3.2, 0.9 Hz, H-5), 4.02 (ddd, 1H, J = 11.5, 10.0, 5.7 Hz, H-2), 3.81−3.73 (m, 3H, H-4, H-6), 1.48 (br s, 1H, OH). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC): δ 137.5 (Cq), 132.7 (2CHarom), 132.6 (Cq), 129.4, 128.7, 128.43 (3× 2CHarom), 128.37, 128.3 (2× 1CHarom), 95.6 (d, 1 J(C−F) = 186.3 Hz, C-3), 86.6 (d, 3J(C−F) = 8.1 Hz, C-1), 75.3 (d, 2 J(C−F) = 16.5 Hz, C-4), 74.8 (d, 4J(C−F) = 2.9 Hz, CH2 Bn), 71.7 (d, 3 J(C−F) = 8.0 Hz, C-5), 62.5 (d, 2J(C−F) = 17.5 Hz, C-2), 61.4 (C-6). 19 F NMR (CDCl3, 376 MHz): δ −189.58 (dddd, 2J(H−F) = 52.8 Hz, 3 J(H−F) = 14.2, 11.5, 4J(H−F) = 3.2 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1225. Data for β-7: mp 77−79 °C (heptane/EtOAc), [α]20 D −1 (c 1.14, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.56−7.53 (m, 2H, CHarom), 7.38−7.31 (m, 8H, CHarom), 4.85 (dd, 1H, J = 11.3, 1.2 Hz, CHH Bn), 4.62 (d, 1H, J = 11.3 Hz, CHH Bn), 4.57 (ddd, 1H, J = 51.6, 9.1, 8.6 Hz, H-3), 4.44 (dd, 1H, J = 10.2, 0.9 Hz, H-1), 3.90 (ddd, 1H, J = 12.2, 6.0, 2.6 Hz, H-6), 3.72 (ddd, 1H, J = 12.2, 7.7, 4.4 Hz, H-6), 3.64 (ddd, 1H, J = 12.6, 9.8, 8.6 Hz, H-4), 3.45 (ddd, 1H, J = 12.9, 10.2, 9.1 Hz, H-2), 3.36 (dddd, 1H, J = 9.7, 4.2, 2.6, 1.3 Hz, H-5), 1.78 (dd, 1H, J = 7.7, 6.0 Hz, OH). 13 C{1H} APT NMR (CDCl3, 101 MHz, HSQC): δ 137.4 (Cq), 133.7 F


Article


Data for α-10: Rf 0.27 (toluene/Et2O/PE 1:1:1.7), mp 69−73 °C 1 (heptane/MTBE), [α]20 D +200 (c 0.21, CHCl3). H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.49−7.47 (m, 2H, CHarom), 7.41−7.28 (m, 8H, CHarom), 5.67 (dd, 1H, J = 5.7, 4.3 Hz, H-1), 4.92 (d, 1H, J = 11.6 Hz, CHH Bn), 4.86 (ddd, 1H, J = 48.0, 10.4, 3.2 Hz, H-3), 4.60 (d, 1H, J = 11.6 Hz, CHH Bn), 4.53 (ddd, 1H, J = 10.4, 10.0, 5.7 Hz, H-2), 4.31 (ddd, 1H, J = 6.6, 5.2, 1.3 Hz, H-5), 4.08 (ddd, 1H, J = 6.5, 3.2, 1.3 Hz, H-4), 3.73 (dd, 1H, J = 11.4, 6.6 Hz, H-6), 3.53 (dd, 1H, J = 11.4, 5.2 Hz, H-6), 1.37 (br s, 1H, OH). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.4 (Cq Bn), 132.8 (2CHarom), 132.6 (Cq), 129.3, 128.8, 128.7 (3× 2CHarom), 128.5, 128.2 (2× 1CHarom), 92.2 (d, 1J(C−F) = 190.6 Hz, C-3), 87.0 (d, 3J(C−F) = 7.7 Hz, C-1), 75.0 (d, 4J(C−F) = 4.4 Hz, CH2 Bn), 73.9 (d, 2J(C−F) = 15.1 Hz, C-4), 71.3 (d, 3J(C−F) = 6.4 Hz, C-5), 61.8 (d, 4J(C−F) = 2.5 Hz, C-6), 59.7 (d, 2J(C−F) = 18.0 Hz, C-2). 19 F NMR (CDCl3, 376 MHz): δ −196.76 (dddd, 2J(H−F) = 48.0 Hz, 3 J(H−F) = 10.0, 6.5, 4J(H−F) = 4.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1222. Data for β-10: Rf 0.17 (toluene/Et2O/PE 1:1:1.7), mp 102−104 1 °C (heptane/MTBE), [α]20 D +1 (c 0.61, CHCl3). H NMR (CDCl3, 400 MHz, H−H COSY, HSQC): δ 7.59−7.56 (m, 2H, CHarom), 7.39−7.27 (m, 8H, CHarom), 4.87, 4.56 (2× d, 2× 1H, J = 11.6 Hz, CHH Bn), 4.48 (ddd, 1H, J = 47.5, 9.6, 3.1 Hz, H-3), 4.41 (dd, 1H, J = 10.0, 0.9 Hz, H-1), 3.95 (ddd, 1H, J = 6.1, 3.1, 1.1 Hz, H-4), 3.93 (ddd, 1H, J = 11.0, 10.0, 9.6 Hz, H-2), 3.85 (ddd, 1H, J = 11.3, 6.8, 0.9 Hz, H-6), 3.57 (dd, 1H, J = 11.3, 5.4 Hz, H-6), 3.46 (dddd, 1H, J = 6.8, 5.4, 1.9, 1.1 Hz, H-5), 1.59 (br s, 1H, OH). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC): δ 137.6 (Cq), 133.1 (2CHarom), 131.5 (Cq), 129.2, 128.7 (2× 2CHarom), 128.4 (CHarom), 128.32 (2CHarom), 128.27 (CHarom), 94.8 (d, 1J(C−F) = 193.1 Hz, C-3), 86.1 (d, 3J(C−F) = 6.8 Hz, C-1), 78.0 (d, 3J(C−F) = 6.9 Hz, C-5), 74.6 (d, 4 J(C−F) = 4.2 Hz, CH2 Bn), 72.7 (d, 2J(C−F) = 15.2 Hz, C-4), 61.9 (d, 4 J(C−F) = 2.6 Hz, C-6), 60.9 (d, 2J(C−F) = 18.2 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −189.94 (ddd, 2J(H−F) = 47.5 Hz, 3J(H−F) = 11.0, 6.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1220. Phenyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-1thio-α-D-galactopyranoside (α-3). Compound α-3 was prepared according to the general procedure by reaction of α-10 (243 mg, 0.624 mmol) with sodium hydride (60% in oil, 38 mg, 0.950 mmol) and benzyl bromide (0.13 mL, 1.09 mmol) in dry THF (4 mL). Chromatography in EtOAc/PE 1:15 afforded α-3 (253 mg, 85%) as a colorless syrup, Rf 0.19 (EtOAc/heptane 1:15), [α]20 D +186 (c 0.42, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.51−7.48 (m, 2H, CHarom), 7.35−7.24 (m, 13H, CHarom), 5.63 (dd, 1H, J = 5.7, 4.3 Hz, H-1), 4.89 (d, 1H, J = 11.3 Hz, CHH O4Bn), 4.84 (ddd, 1H, J = 48.4, 10.5, 3.2 Hz, H-3), 4.57 (d, 1H, J = 11.3 Hz, CHH O-4Bn), 4.56−4.48 (m, 2H, H-2, H-5), 4.46, 4.41 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6Bn), 4.14 (ddd, 1H, J = 6.7, 3.2, 1.3 Hz, H-4), 3.63 (dd, 1H, J = 9.5, 6.8 Hz, H-6), 3.56 (ddd, 1H, J = 9.5, 6.2, 1.5 Hz, H-6). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 137.89, 137.86, 133.0 (3× Cq), 132.6, 129.2 (2× 2CHarom), 128.6 (4CHarom), 128.3 (2CHarom), 128.1, 128.0, 127.9 (3× 1CHarom), 127.8 (2CHarom), 92.0 (d, 1J(C−F) = 190.3 Hz, C-3), 87.2 (d, 3J(C−F) = 7.6 Hz, C-1), 75.3 (d, 4J(C−F) = 3.8 Hz, CH2 O-4Bn), 74.4 (d, 2J(C−F) = 15.1 Hz, C-4), 73.6 (CH2 O-6Bn), 70.0 (d, 3J(C−F) = 6.7 Hz, C-5), 68.3 (d, 4J(C−F) = 2.3 Hz, C-6), 59.7 (d, 2J(C−F) = 17.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −196.40 (m). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1690; found, 452.1688. Phenyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-1thio-β-D-galactopyranoside (β-3). Compound β-3 was prepared according to the general procedure by reaction of β-10 (297 mg, 0.763 mmol) with sodium hydride (60% in oil, 46 mg, 1.150 mmol) and benzyl bromide (155 μL, 1.300 mmol) in dry THF (4 mL). Chromatography in EtOAc/PE 7:1 afforded β-3 (340 mg, 93%) as a colorless syrup, Rf 0.29 (EtOAc/heptane 1:7), [α]20 D +1 (c 0.72, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.58−7.56 (m, 2H, CHarom), 7.35−7.23 (m, 13H, CHarom), 4.84 (d, 1H, J = 11.4 Hz, CHH O-4Bn), 4.54−4.38 (m, 3H, H-3, CH2 O-6Bn), 4.53 (d, 1H, J = 11.4 Hz, CHH O-4Bn), 4.40 from 1H{19F}

organic phase was separated, and the water phase was extracted with EtOAc (3×). EtOAc solutions were combined and washed with NaHCO3, and the water phase was extracted with dichloromethane. Organic phases were combined, dried, and concentrated. Chromatography in EtOAc/petroleum ether 1:2 afforded de-O-benzylated product (1.060 g) contaminated with traces of aromatics (TLC) which was used without additional purification. Triflic anhydride (2.1 mL, 12.5 mmol) was added dropwise under cooling (−40 °C) and stirring to a solution of the de-O-benzylated product (1.06 g, 5.60 mmol) in dry dichloromethane (12 mL) and dry pyridine (4 mL). The reaction was allowed to warm up to −3 °C when TLC (EtOAc/ PE 1:2) indicated consumption of the starting material. The reaction mixture was poured onto ice, extracted with dichloromethane (3×), dried, concentrated, and co-evaporated with toluene (3×). The residue was dissolved in dry DMF (8 mL), KNO2 (2.0 g, 23.5 mmol) was immediately added, and the resulting suspension was stirred for 24 h when TLC (EtOAc/PE 1:2 and 1:1) showed completion of the reaction. The reaction mixture was diluted with dichloromethane, filtered through silica gel, and concentrated. Chromatography of the residue in EtOAc/PE 1:2 afforded 8 (659 mg, 53% over 2 steps) as a colorless syrup which crystallized on inoculation with an authentic sample. NMR data are in agreement with those reported.20 1,6-Anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-fluoro-β-Dgalactopyranose (9). Sodium hydride (60% suspension in oil, 130 mg, 3.250 mmol) was added to a solution of 8 (477 mg, 2.522 mmol) in dry THF/DMF 10:1 (6.6 mL) under cooling (−25 °C). The reaction was stirred for 10 min, and then benzyl bromide (0.35 mL, 2.94 mmol) was added. The temperature was allowed to reach rt, and the reaction mixture was stirred for 6 h until TLC (EtOAc/PE 1:2) indicated the absence of the starting compound. Methanol (0.7 mL) was added under cooling (ice-water) to quench the reaction. After 1 h of stirring, the reaction mixture was diluted with dichloromethane and washed with water, the water phase was extracted with dichloromethane (3×), and the combined organic phases were dried and concentrated. Chromatography of the residue in EtOAc/PE 1:7 afforded 9 (647 mg, 92%) as a colorless syrup which crystallized after about a month in a refrigerator, Rf (0.35 EtOAc/heptane 1:5) mp 1 46−47 °C (Et2O/heptane), [α]20 D +6 (c 0.20, CHCl3). H NMR (CDCl3, 400 MHz, H−H COSY, HSQC): δ 7.40−7.31 (m, 5H, CHarom), 5.48 (t, 1H, J = 1.6 Hz, H-1), 4.83 (ddq, 1H, J = 48.1, 4.2, 1.6 Hz, H-3), 4.76, 4.61 (2× d, 2× 1H, J = 11.7 Hz, CHH Bn), 4.49 (dddd, 1H, J = 4.9, 4.1, 1.6, 0.9 Hz, H-5), 4.37 (d, 1H, J = 7.4 Hz, H6en), 3.80 (dtt, 1H, J = 26.9, 4.1, 0.9 Hz, H-4), 3.73−3.67 (m, 2H, H2, H-6ex). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC): δ 137.2 (Cq), 128.8 (2CHarom), 128.5 (CHarom), 128.0 (2CHarom), 99.8 (C-1), 86.7 (d, 1J(C−F) = 189.7 Hz, C-3), 73.0 (d, 3J(C−F) = 0.9 Hz, C-5), 71.4 (CH2 Bn), 71.3 (d, 2J(C−F) = 16.5 Hz, C-4), 64.9 (d, 4J(C−F) = 3.7 Hz, C-6), 61.5 (d, 2J(C−F) = 24.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −198.21 (ddd, 2J(H−F) = 48.2 Hz, 3J(H−F) = 26.9, 14.7 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C13H15FNO3, 252.1030; found, 252.1027. Phenyl 2-Azido-4-O-benzyl-2,3-dideoxy-3-fluoro-1-thio-αD-galactopyranoside (α-10) and Phenyl 2-Azido-4-O-benzyl2,3-dideoxy-3-fluoro-1-thio-β-D-galactopyranoside (β-10). Compounds α-10 and β-10 were prepared according to the general procedure by reaction of 1,6-anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-fluoro-β-D-galactopyranose (9, 619 mg, 2.216 mmol) with PhSTMS (1.36 mL, 7.18 mmol) and ZnI2 (1.20 g, 3.76 mmol) in dichloroethane (7 mL). The reaction was completed in 24 h and TLC (EtOAc/PE 1:5) showed the absence of 9 and the presence of one major product (Rf ≈ 0.6). The residue after workup was dissolved in MeOH (30 mL), AcOH (7 drops) was added, and the solution was stirred at rt for 4 h when TLC (EtOAc/petroleum ether 1:5 and toluene/Et2O/PE 1:1:1.5) showed the absence of the product with Rf 0.6 and formation of two slow-moving compounds. Methanolic solution was concentrated, and the residue was chromatographed in toluene/Et2O/PE 1:1:1.7 to afford first α-10 (314 mg, 36%) as a colorless syrup, which crystallized overnight. Continued elution afforded β-10 (376 mg, 43%) as crystalline material. G


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6). 19F NMR (CDCl3, 376 MHz): δ −195.67 (dd, 2J(H−F) = 50.2 Hz, J(H−F) = 13.2). NMR data for β-anomer (β-14): 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.54−7.51 (m, 2H, CHarom), 7.38−7.31 (m, 8H, CHarom), 4.87 (dd, 1H, J = 10.9, 1.0 Hz, CHH Bn), 4.77 (d, 1H, J = 10.9 Hz, CHH Bn), 4.47 (ddd, 1H, J = 50.4, 9.8, 8.6 Hz, H-4), 4.45 (d, 1H, J = 10.3 Hz, H-1), 3.79−3.73 (m, 2H, H-6), 3.63 (ddd, 1H, J = 14.6, 9.3, 8.6 Hz, H-3), 3.50 (ddt, 1H, J = 9.8, 5.2, 2.5 Hz, H-5), 3.32 (ddd, 1H, J = 10.3, 9.3, 0.8 Hz, H-2), 1.88 (t, 1H, J = 6.8 Hz, OH). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.3 (Cq Bn), 133.8 (2CHarom), 130.7 (Cq), 129.4 (2CHarom), 128.9 (CHarom), 128.6, 128.5 (2× 2CHarom), 128.3 (CHarom), 89.6 (d, 1J(C−F) = 183.4 Hz, C-4), 86.0 (d, 4J(C−F) = 1.5 Hz, C-1), 82.2 (d, 2J(C−F) = 17.6 Hz, C-3), 77.8 (d, 2J(C−F) = 24.4 Hz, C5), 75.2 (d, 4J(C−F) = 2.5 Hz, CH2 Bn), 64.2 (d, 3J(C−F) = 9.1 Hz, C-2), 61.6 (C-6). 19F NMR (CDCl3, 376 MHz): δ −197.08 (dd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 14.6 Hz). Phenyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-1thio-α,β-D-glucopyranoside (2). Compound 2 was prepared according to the general procedure by reaction of 14 (973 mg, 2.498 mmol) with sodium hydride (60% in oil, 160 mg, 4.00 mmol) and benzyl bromide (0.48 mL, 4.03 mmol) in dry THF (20 mL). Chromatography in EtOAc/petroleum ether 1:15 afforded 2 (1.036 g, 86%) as a colorless syrup which solidified after a few months in a refrigerator. Rf 0.6 (EtOAc/heptane 1:2), HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1690; found, 452.1694. NMR data for α-anomer (α-2): 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.53−7.50 (m, 2H, CHarom), 7.44−7.25 (m, 13H, CHarom), 4.93 (dd, 1H, J = 10.7, 0.9 Hz, CHH O-3Bn), 4.82 (d, 1H, J = 10.7 Hz, CHH O-3Bn), 4.61, 4.53 (2× d, 2× 1H, J = 12.0 Hz, CHH O-6Bn), Strong coupled spin system was resolved by simulation in Mnova, with the following shifts and coupling constants: 5.56 (dddd, 1H, J = 5.3, 3.1, −0.5, −0.4 Hz, H-1), 4.67 (ddd, 1H, J = 50.1, 9.9, 8.2 Hz, H-4), 4.52 (ddddd, 1H, J = 9.9, 4.3, 3.5, 2.5, −0.4 Hz, H-5), 3.91 (ddd, 1H, J = 10.0, 5.3, 0.4 Hz, H-2), 3.91 (dddd, 1H, J = 13.8, 10.0, 8.2, −0.5 Hz, H-3), 3.76 (ddd, 1H, J = −11.4, 4.3, 1.4 Hz, H-6), 3.73 (ddd, 1H, J = −11.4, 3.5, 2.5 Hz, H-6). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.9 (Cq O-6Bn), 137.5 (Cq O-3Bn), 133.0 (Cq), 132.4, 129.3, 128.6, 128.5, 128.4 (5× 2CHarom), 128.2, 128.0, 127.9 (3× 1CHarom), 127.7 (2CHarom), 90.6 (d, 1J(C−F) = 184.1 Hz, C-4), 87.1 (d, 4J(C−F) = 1.4 Hz, C-1), 79.3 (d, 2J(C−F) = 17.9 Hz, C-3), 75.2 (d, 4J(C−F) = 2.9 Hz, CH2 O-3Bn), 73.7 (CH2 O-6Bn), 70.0 (d, 2J(C−F) = 25.0 Hz, C5), 68.1 (C-6), 62.9 (d, 3J(C−F) = 8.7 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −195.32 (strong coupled spin system was resolved by simulation in Mnova, with the following coupling constants: 2J(H−F) = 50.1 Hz, 3J(H−F) = 13.8, 3.5, 4J(H−F) = 3.5, 1.4, 0.4, 5J(H−F) = 3.1 Hz). NMR data for β-anomer (β-2): 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.59−7.57 (m, 2H, CHarom), 7.44−7.24 (m, 13H, CHarom), 4.86 (dd, 1H, J = 10.9, 1.0 Hz, CHH O-3Bn), 4.76 (d, 1H, J = 10.9 Hz, CHH O-3Bn), 4.63, 4.60 (2× d, 2× 1H, J = 12.0 Hz, CHH O-6Bn), 4.50 (ddd, 1H, J = 50.3, 9.9, 8.5 Hz, H-4), 4.42 (d, 1H, J = 10.2 Hz, H-1), 3.83 (dt, 1H, J = 11.2, 2.3 Hz, H-6), 3.72 (ddd, 1H, J = 11.2, 5.2, 2.1 Hz, H-6), Strong coupled spin system for H-5 and H-3 was resolved by simulation in Mnova, with the following shifts and coupling constants: 3.60 (ddd, 1H, J = 14.6, 9.3, 8.5 Hz, H-3), 3.60 (dddd, 1H, J = 9.9, 5.2, 3.5, 2.3 Hz, H-5), 3.34 (ddd, 1H, J = 10.2, 9.3, 0.8 H-2). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (Cq O-6Bn), 137.4 (Cq O-3Bn), 133.8 (2CHarom), 131.0 (Cq), 129.2 (2CHarom), 128.7 (CHarom), 128.6, 128.5, 128.4 (3× 2CHarom), 128.3, 127.8 (2× 1CHarom), 127.7 (2CHarom), 89.8 (d, 1J(C−F) = 184.0 Hz, C-4), 86.0 (d, 4J(C−F) = 1.5 Hz, C-1), 82.4 (d, 2J(C−F) = 17.7 Hz, C-3), 77.5 (d, 2 J(C−F) = 23.1 Hz, C-5), 75.1 (d, 4J(C−F) = 2.9 Hz, CH2 O-3Bn), 73.7 (CH2 O-6Bn), 68.6 (C-6), 64.1 (d, 3J(C−F) = 8.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −196.40 (ddd, 2J(H−F) = 50.3 Hz, 3J(H−F) = 14.6, 3.5 Hz). 1,6-Anhydro-2-azido-3-O-benzyl-2,4-dideoxy-4-fluoro-β-Dgalactopyranose (17). Sodium hydride (60% suspension in oil, 400 mg, 10.00 mmol) was added to a solution of 1,6-anhydro-2-azido-2,4-

(d, 1H, J = 10.1 Hz, H-1), 4.04 (dd, 1H, J = 6.7, 3.0 Hz, H-4), 3.92 (ddd, 1H, J = 11.2, 10.1, 9.9 Hz, H-2), 3.69−3.59 (m, 3H, H-5, H-6). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (Cq O4Bn), 137.8 (Cq O-6Bn), 133.1 (2CHarom), 131.6 (Cq), 129.1, 128.6, 128.4 (3× 2CHarom), 128.3, 128.04 (2× 1CHarom), 127.98, 127.89 (2× 2CHarom), 127.86 (CHarom), 94.6 (d, 1J(C−F) = 192.8 Hz, C-3), 86.1 (d, 3J(C−F) = 6.7 Hz, C-1), 76.6 (d, 3J(C−F) = 7.3 Hz, C-5), 74.8 (d, 4J(C−F) = 3.6 Hz, CH2 O-4Bn), 73.7 (CH2 O-6Bn), 73.2 (d, 2J(C−F) = 15.4 Hz, C-4), 68.1 (d, 4J(C−F) = 2.5 Hz, C-6), 60.8 (d, 2J(C−F) = 18.1 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −189.80 (ddd, 2J(H−F) = 47.9 Hz, 3J(H−F) = 11.2, 6.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1690; found, 452.1695. 1,6-Anhydro-2-azido-3-O-benzyl-2,4-dideoxy-4-fluoro-β-Dglucopyranose (13). Benzyl bromide (1.2 mL, 10.1 mmol) was added to a solution of 1,6-anhydro-2-azido-2,4-dideoxy-4-fluoro-β-Dglucopyranose20 12 (568 mg, 3.002 mmol) in dry DMF (12 mL) under cooling (−25 °C). The reaction was stirred for 1 min, and then sodium hydride (60% suspension in oil, 323 mg, 8.075 mmol) was added. The temperature was allowed to reach rt, and the reaction mixture was stirred for 30 min until TLC (EtOAc/PE 1:2) indicated the absence of the starting compound. The reaction mixture was then cooled to 0 °C, and methanol (1.0 mL) was added. The suspension was then diluted with dichloromethane and washed with water, the water phase was extracted with dichloromethane (3×), and the combined organic phases were dried and concentrated. Chromatography of the residue in EtOAc/PE 1:7 afforded 13 (769 mg, 91%) as a colorless syrup. Rf 0.48 (EtOAc/heptane 1:3), [α]20 D +28 (c 1.09, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.40−7.31 (m, 5H, CHarom), 5.51 (t, 1H, J = 1.3 Hz, H-1), 4.73 (ddddd, 1H, J = 13.0, 5.9, 1.6, 1.3, 1.2 Hz, H-5), 4.69, 4.65 (2× d, 2× 1H, J = 11.8 Hz, CHH Bn), 4.50 (dddd, 1H, J = 46.4, 2.6, 1.6, 0.8 Hz, H-4), 4.05 (dt, 1H, J = 7.6, 1.2 Hz, H-6en), 3.79 from 1H{19F} (dd, 1H, J = 7.6, 5.9 Hz, H-6ex), 3.75 (dtt, 1H, J = 17.5, 2.6, 1.3 Hz, H-3), 3.29 (dd, 1H, J = 2.6, 1.3 H-2). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 136.9 (Cq), 128.8 (2CHarom), 128.4, 127.3 (2CHarom), 100.9 (C-1), 89.3 (d, 1J(C−F) = 182.2 Hz, C-4), 76.5 (d, 2J(C−F) = 28.8 Hz, C-3), 74.4 (d, 2J(C−F) = 22.1 Hz, C-5), 73.0 (CH2 Bn), 64.6 (d, 3J(C−F) = 9.6 Hz, C-6), 59.9 (d, 3J(C−F) = 4.8 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −181.92 (dddd, 2J(H−F) = 46.3 Hz, 3J(H−F) = 17.5, 13.0 Hz, 4J(H−F) = 4.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C13H15FNO3, 252.1030; found, 252.1032. Phenyl 2-Azido-3-O-benzyl-2,4-dideoxy-4-fluoro-1-thio-α,βD-glucopyranoside (14). Compound 14 was prepared according to the general procedure by reaction of 1,6-anhydro-2-azido-3-O-benzyl2,4-dideoxy-4-fluoro-β-D-glucopyranose (13, 1.69 g, 6.05 mmol) with PhSTMS (3.7 mL, 19.5 mmol) and ZnI2 (3.22 g, 10.09 mmol) in dichloroethane (15 mL). The reaction was completed in 48 h, and TLC (EtOAc/PE 1:3) showed the absence of 13 and one major product (Rf 0.7). The residue after workup was dissolved in MeOH (50 mL), AcOH (0.5 mL) was added, and the solution was stirred at rt for 1 h when TLC (EtOAc/PE 1:3) showed the absence of the product with Rf 0.7 and formation of a more polar compound (Rf 0.25). Methanolic solution was concentrated, and the residue chromatographed in EtOAc/PE 1:3 to afford colorless syrupy 14 (1.786 g, 76%). Rf 0.25 (EtOAc/heptane 1:3), HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1219. NMR data for α-anomer (α-14): 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.51−7.49 (m, 2H, CHarom), 7.44−7.31 (m, 8H, CHarom), 5.54 (dd, 1H, J = 5.3, 2.9 Hz, H-1), 4.93 (dd, 1H, J = 11.9, 1.2 Hz, CHH Bn), 4.82 (d, 1H, J = 11.9 Hz, CHH Bn), 4.61 (ddd, 1H, J = 50.6, 9.9, 8.0 Hz, H-4), 4.38 (ddd, 1H, J = 9.9, 4.4, 2.4 Hz, H-5), 3.94 (ddd, 1H, J = 13.2, 10.2, 8.0 Hz, H-3), 3.87 (dd, 1H, J = 10.2, 5.3 Hz, H-2), 3.84−3.78 (m, 2H, H-6), 1.64 (dd, 1H, J = 7.2, 5.9 Hz, OH). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.4 (Cq Bn), 132.7 (2CHarom), 132.7 (Cq), 129.4, 128.6, 128.4 (3× 2CHarom), 128.3, 128.2 (2× 1CHarom), 90.4 (d, 1J(C−F) = 183.5 Hz, C-4), 87.0 (d, 4J(C−F) = 1.5 Hz, C-1), 79.2 (d, 2J(C−F) = 17.9 Hz, C-3), 75.2 (d, 4J(C−F) = 2.9 Hz, CH2 Bn), 70.6 (d, 2J(C−F) = 26.0 Hz, C-5), 62.8 (d, 3J(C−F) = 8.8 Hz, C-2), 61.1 (C-

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APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 136.9 (Cq Bn), 133.5 (2CHarom), 131.0 (Cq), 129.3, 128.8 (2× 2CHarom), 128.7, 128.4 (2× 1CHarom), 128.1 (2CHarom), 86.3 (C-1), 84.5 (d, 1J(C−F) = 184.8 Hz, C-4), 79.5 (d, 2J(C−F) = 18.1 Hz, C-3), 77.8 (d, 2J(C−F) = 18.0 Hz, C-5), 72.2 (CH2 Bn), 61.4 (d, 3J(C−F) = 5.0 Hz, C-6), 61.1 (C-2). 19F NMR (CDCl3, 376 MHz): δ −218.14 (ddd, 2J(H−F) = 50.1 Hz, 3J(H−F) = 27.7, 27.0 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1226. Phenyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-1thio-α-D-galactopyranoside (α-4). Compound α-4 was prepared according to the general procedure by reaction of α-19 (489 mg, 1.256 mmol) with sodium hydride (60% in oil, 96 mg, 2.400 mmol) and benzyl bromide (0.30 mL, 2.52 mmol) in dry THF (12 mL containing 0.5 mL of dry DMF). Chromatography in EtOAc/ petroleum ether 1:7 afforded α-4 as a colorless syrup (494 mg, 82%) which crystallized in a refrigerator, mp 63−65 °C, [α]20 D −50 (c 0.264, CHCl3), Rf 0.34 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC): δ 7.51−7.44 (m, 2H, CHarom), 7.39− 7.24 (m, 13H, CHarom), 5.60 (d, 1H, J = 5.4 Hz, H-1), 4.94 (dd, 1H, J = 50.2, 2.5 Hz, H-4), 4.79, 4.74 (2× d, 2× 1H, J = 11.5 Hz, CHH O3Bn), 4.53 (br s, 2H, CH2 O-6Bn), 4.52 (ddd, 1H, J = 29.8, 6.9, 6.3 Hz, H-5), 4.29 (dd, 1H, J = 10.6, 5.4 Hz, H-2), 3.75 (ddd, 1H, J = 26.3, 10.6, 2.5 Hz, H-3), 3.74 (dd, 1H, J = 9.7, 6.9 Hz, H-6), 3.61 (ddd, 1H, J = 9.7, 6.3, 1.4 Hz, H-6). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC): δ 137.9, 137.1, 132.9 (Cq), 132.7, 129.2, 128.8, 128.6 (4× 2CHarom), 128.3 (CHarom), 128.1 (2CHarom), 128.08, 128.06 (2× 1CHarom), 127.8 (2CHarom), 87.4 (C-1), 85.5 (d, 1J(C−F) = 185.5 Hz, C-4), 76.3 (d, 2J(C−F) = 18.0 Hz, C-3), 73.7, 72.0 (CH2 Bn), 69.3 (d, 2 J(C−F) = 18.1 Hz, C-5), 67.9 (d, 3J(C−F) = 5.4 Hz, C-6), 59.8 (d, 3 J(C−F) = 1.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −218.42 (ddd, 2J(H−F) = 50.1 Hz, 3J(H−F) = 29.8, 26.4 Hz). HRMS-APCI (m/ z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1690; found, 452.1693. Phenyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-1thio-β-D-galactopyranoside (β-4). Compound β-4 was prepared according to the general procedure by reaction of β-19 (535 mg, 1.374 mmol) with sodium hydride (60% in oil, 106 mg, 2.650 mmol) and benzyl bromide (0.32 mL, 2.69 mmol) in dry THF (12 mL containing 0.5 mL of dry DMF). Chromatography in EtOAc/ petroleum ether 1:7 afforded β-4 as a colorless syrup (628 mg, 95%) which crystallized in a refrigerator, mp 58−59 °C, [α]20 D +162 (c 0.468, CHCl3), Rf 0.26 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.57−7.55 (m, 2H, CHarom), 7.37−7.29 (m, 13H, CHarom), 4.85 (dd, 1H, J = 49.7, 2.5 Hz, H-4), 4.76, 4.67 (2× d, 2× 1H, J = 11.7 Hz, CHH O-3Bn), 4.56 (br s, 2H, CH2 O-6Bn), 4.38 (dd, 1H, J = 10.2, 0.8 Hz, H-1), 3.73−3.71 (m, 2H, H-6), 3.66 (dd, 1H, J = 10.2, 9.7 Hz, H-2), 3.59 (ddd, 1H, J = 26.7, 7.1, 6.2 Hz, H-5), 3.40 (ddd, 1H, J = 27.7, 9.7, 2.5 Hz, H-3). 13 C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6Bn), 137.0 (Cq O-3Bn), 133.6 (2CHarom), 131.2 (Cq), 129.2, 128.8, 128.7 (3× 2CHarom), 128.6, 128.4 (2× 1CHarom), 128.14 (2CHarom), 128.10 (CHarom), 128.0 (2CHarom), 86.4 (C-1), 84.3 (d, 1 J(C−F) = 184.9 Hz, C-4), 79.6 (d, 2J(C−F) = 18.2 Hz, C-3), 76.2 (d, 2 J(C−F) = 18.3 Hz, C-5), 73.9 (CH2 O-6Bn), 72.1 (CH2 O-3Bn), 67.7 (d, 3J(C−F) = 5.0 Hz, C-6), 61.1 (C-2). 19F NMR (CDCl3, 376 MHz): δ −219.44 (dt, 2J(H−F) = 49.8 Hz, 3J(H−F) = 27.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H27FNO3S, 452.1690; found, 452.1690. Methyl 2,4,6-Tri-O-methyl-α-D-galactopyranoside (D). Sodium hydride (60% suspension in oil, 200 mg, 5.00 mmol) was added

dideoxy-4-fluoro-β-D-galactopyranose20 (16, 1.15 g, 6.08 mmol) in dry THF (12 mL) under cooling (−25 °C). The reaction was stirred for 2 min, and then benzyl bromide (1.1 mL, 9.2 mmol) was added. A catalytic amount of TBAI was added subsequently. The temperature was allowed to reach rt, and the reaction mixture was stirred for 48 h until TLC (EtOAc/PE 1:2) indicated the absence of the starting compound. The reaction mixture was than cooled to 0 °C and quenched by methanol (2 mL). The reaction was then diluted with chloroform and washed with brine, the water phase was extracted with chloroform (3×), and the combined organic phases were dried and concentrated. Chromatography of the residue in EtOAc/PE 1:10 afforded 17 (1.292 g, 79%) as a colorless syrup, Rf 0.26 (EtOAc/ 1 heptane 1:10), [α]20 D +102 (c 0.27, CHCl3). H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.37−7.29 (m, 5H, CHarom), 5.42 (dt, 1H, J = 4.8, 1.2 Hz, H-1), 4.84 (dddt, 1H, J = 45.2, 5.1, 4.3, 0.8 Hz, H-4), 4.78, 4.63 (2× d, 2× 1H, J = 12.0 Hz, CHH Bn), 4.64−4.61 (m, 1H, H-5), 4.60−4.57 (m, 1H, H-6en), 3.96 (ddq, 1H, J = 5.1, 2.5, 1.4 Hz, H-3), 3.74 (dddd, 1H, J = 7.3, 5.1, 0.8, 0.5 Hz, H-6ex), 3.61 (dtd, 1H, J = 3.8, 1.4, 0.8 Hz, H-2). 13C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.5 (Cq), 128.7 (2CHarom), 128.2 (CHarom), 127.9 (2CHarom), 100.4 (d, 4J(C−F) = 1.4 Hz, C-1), 84.7 (d, 1J(C−F) = 192.2 Hz, C-4), 75.0 (d, 2J(C−F) = 15.1 Hz, C-3), 74.4 (d, 4J(C−F) = 3.0 Hz, CH2 Bn), 72.5 (d, 2J(C−F) = 27.7 Hz, C-5), 64.5 (C-6), 63.3 (d, 3J(C−F) = 2.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −205.93 (dddd, 2J(H−F) = 45.2 Hz, 3J(H−F) = 2.5 Hz, 4 J(H−F) = 3.8 Hz, 5J(H−F) = 4.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C13H15FNO3, 252.1030; found, 252.1035. Phenyl 2-Azido-3-O-benzyl-2,4-dideoxy-4-fluoro-1-thio-αD-galactopyranoside (α-19) and Phenyl 2-Azido-3-O-benzyl2,4-dideoxy-4-fluoro-1-thio-β-D-galactopyranoside (β-19). Compounds α-19 and β-19 were prepared according to the general procedure by reaction of 1,6-anhydro-2-azido-3-O-benzyl-2,4-dideoxy-4-fluoro-β-D-galactopyranose (17, 1.29 g, 4.62 mmol) with PhSTMS (2.95 mL, 15.58 mmol) and ZnI2 (2.64 g, 8.27 mmol) in dichloroethane (15 mL). The reaction was completed in 72 h, and TLC (EtOAc/PE 1:5) showed the absence of 17 and the presence of two major products (Rf 0.6 and 0.7). The residue after workup was dissolved in MeOH (50 mL), AcOH (0.4 mL) was added, and the solution was stirred at rt for 1 h when TLC (EtOAc/PE 1:5) showed absence of the products (Rf 0.6, 0.7) and formation of more polar compounds. Methanolic solution was concentrated, and the residue was chromatographed in EtOAc/PE 1:2 to afford sequentially α-19 (676 mg, 35%) and β-19 (696 mg, 37%) as a crystalline and amorphous solid, respectively. Data for α-19: Rf 0.31 (EtOAc/heptane 1:2), mp 82−86 °C 1 (heptane/EtOAc), [α]20 D +170 (c 0.21, CHCl3). H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.52−7.49 (m, 2H, CHarom), 7.44−7.30 (m, 8H, CHarom), 5.64 (d, 1H, J = 5.4 Hz, H1), 4.88 (dd, 1H, J = 50.6, 2.7 Hz, H-4), 4.79, 4.75 (2× d, 2× 1H, J = 11.6 Hz, CHH Bn), 4.38 (ddd, 1H, J = 30.0, 7.5, 5.3 Hz, H-5), 4.30 (dd, 1H, J = 10.6, 5.4 Hz, H-2), 3.84 (dddd, 1H, J = 11.4, 7.4, 3.8, 1.1 Hz, H-6), 3.77 (ddd, 1H, J = 26.4, 10.6, 2.7 Hz, H-3), 3.76 (ddd, 1H, J = 11.4, 8.4, 5.3 Hz, H-6), 1.54 (dd, 1H, J = 8.4, 3.8 Hz, OH). 13 C{1H} APT NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.0 (Cq Bn), 133.0 (2CHarom), 132.5 (Cq), 129.4, 128.8 (2× 2CHarom), 128.4, 128.3 (2× 1CHarom), 128.1 (2CHarom), 87.1 (C-1), 85.7 (d, 1 J(C−F) = 185.2 Hz, C-4), 76.2 (d, 2J(C−F) = 17.8 Hz, C-3), 72.0 (CH2 Bn), 70.8 (d, 2J(C−F) = 17.8 Hz, C-5), 61.4 (d, 3J(C−F) = 5.6 Hz, C-6), 59.8 (d, 3J(C−F) = 1.9 Hz, C-2). 19F NMR (CDCl3, 376 MHz): δ −217.42 (ddd, 2J(H−F) = 50.6 Hz, 3J(H−F) = 30.0, 26.4 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C19H21FNO3S, 362.1220; found, 362.1224. Data for β-19: Rf 0.17 (EtOAc/heptane 1:2), [α]20 D −27 (c 0.23, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.58−7.55 (m, 2H, CHarom), 7.38−7.32 (m, 8H, CHarom), 4.76 (dd, 1H, J = 50.1, 2.5 Hz, H-4), 4.76, 4.70 (2× d, 2× 1H, J = 11.7 Hz, CHH Bn), 4.40 (dd, 1H, J = 10.1, 0.8 Hz, H-1), 3.94 (dd, 1H, J = 11.4, 7.5 Hz, H-6), 3.76−3.73 (m, 1H, H-6), 3.67 (ddd, 1H, J = 10.1, 9.9, 0.9 Hz, H-2), 3.52 (ddd, 1H, J = 27.0, 7.5, 5.4 Hz, H-5), 3.42 (ddd, 1H, J = 27.7, 3.8, 2.5 Hz, H-3), 1.81 (br s, 1H, OH). 13C{1H}

to a solution of methyl 3-O-allyl-α-D-galactopyranoside49 (300 mg, 1.281 mmol) in THF/DMF 2:1 (6 mL) under cooling (−25 °C) and stirring. The reaction was allowed to warm up to −10 °C in 30 min I


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Hz, H-1), 5.01 (ddd, 1H, J = 54.1, 10.0, 7.9 Hz, H-3), 3.31 (dd, 1H, J = 10.6, 3.7 Hz, H-2). 19F NMR (CDCl3, 376 MHz): δ −193.23 (m). Methyl 6-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroβ-D-glucopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (1B-β). Compound 1B-β was prepared by glycosylation of methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside45 (B) with α-1 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:4 afforded 1B-β as a colorless crystalline solid (73 mg, 87%), Rf 0.15 (EtOAc/PE 1:5), mp 114 °C (heptane). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.36− 7.21 (m, 25H, CHarom), 4.99 (d, 1H, J = 10.9 Hz, CHH O-3Bn), 4.94 (d, 1H, J = 11.2 Hz, CHH O-2/4Bn), 4.82 (d, 1H, J = 10.9 Hz, CHH O-3Bn), 4.80 (d, 1H, J = 11.0 Hz, CHH O-4′Bn), 4.78, 4.65 (2× d, 2× 1H, J = 12.1 Hz, CHH O-2/4Bn), 4.64 (d, 1H, J = 11.2 Hz, CHH O-2/4Bn), 4.60 (d, 1H, J = 3.8 Hz, H-1), 4.58 (d, 1H, J = 12.2 Hz, CHH O-6′Bn), 4.53 (d, 1H, J = 11.0 Hz, CHH O-4′Bn), 4.51 (d, 1H, J = 12.2 Hz, CHH O-6′Bn), 4.41 (ddd, 1H, J = 51.5, 9.6, 8.4 Hz, H3′), 4.13 (d, 1H, J = 8.2 Hz, H-1′), 4.11 (dd, 1H, J = 11.2, 1.9 Hz, H6), 4.01 (t, 1H, J = 9.3 Hz, H-3), 3.81 (ddd, 1H, J = 10.1, 4.7, 1.9 Hz, H-5), 3.73−3.65 (m, 4H, H-6, H-4′, H-6′), 3.59−3.52 (m, 3H, H-2, H-4, H-2′), 3.39 (s, 3H, MeO), 3.34 (m, 1H, H-5′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.9, 138.5, 138.3, 138.1, 137.6 (Cq), 128.60 (4CHarom), 128.56 (2CHarom), 128.5 (4CHarom), 128.3, 128.2 (2× 2CHarom), 128.14 (CHarom), 128.13 (2CHarom), 128.07 (CHarom), 127.9 (2CHarom), 127.85, 127.8 (2× 2CHarom), 127.7 (CHarom), 101.4 (d, 3J(C−F) = 10.8 Hz, C-1′), 98.3 (C-1), 96.4 (d, 1J(C−F) = 186.6 Hz, C-3′), 82.2 (C-3), 79.9, 77.8 (C-2/4), 75.9 (CH2 O-3Bn), 75.6 (d, 2 J(C−F) = 16.8 Hz, C-4′), 75.0 (CH2 O-2/4Bn), 74.7 (d, 4J(C−F) = 2.5 Hz, CH2 O-4′Bn), 73.9 (d, 3J(C−F) = 9.5 Hz, C-5′), 73.62, 73.59 (CH2 O-2/4/6′Bn), 69.8 (C-5), 68.7 (C-6), 68.5 (d, 4J(C−F) = 1.5 Hz, C-6′), 64.7 (d, 2J(C−F) = 17.6 Hz, C-2′), 55.4 (MeO). 19F NMR (CDCl3, 376 MHz): δ −188.28 (dt, 2J(H−F) = 51.5 Hz, 3J(H−F) = 13.4 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3682. Selected resonances were tentatively assigned as 1B-α: 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 5.03 (dd, 1H, J = 3.6. 3.5 Hz, H-1′). 19F NMR (CDCl3, 376 MHz): δ −193.17 (m). Methyl 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-glucopyranosyl)-2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside (1C-α) and Methyl 3-O-(2-azido-4,6-di-O-benzyl2,3-dideoxy-3-fluoro-β-D-glucopyranosyl)-2-O-benzyl-4,6-Obenzylidene-α-D-galactopyranoside (1C-β). Compounds 1C-α and 1C-β were prepared by glycosylation of methyl 2-O-benzyl-4,6-Obenzylidene-α-D-galactopyranoside11 (C) with α-1 according to the general procedure. Chromatography in toluene/PE/Et2O 1:1:1 gave the product in two fractions. Preparative TLC of the faster moving fraction in Et2O/cyclohexane 20:3 afforded 1C-β as a colorless syrup (45 mg, 58%). Preparative TLC of the slower moving fraction in Et2O/PE 2:1 afforded 1C-α as a colorless syrup (8 mg, 11%), and the combined yield was 69%. Data for β-anomer 1C-β: Rf 0.25 (toluene/heptane/Et2O 1:1:1). 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.52 (dd, 2H, J = 7.4, 2.0 Hz, CHarom), 7.42−7.22 (m, 18H, CHarom), 5.58 (s, 1H, CHPh), 4.86 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.81 (dd, 1H, J = 10.6, 0.7 Hz, CHH O-4′Bn), 4.76 (dd, 1H, J = 8.1, 0.7 Hz, H-1′), 4.71 (d, 1H, J = 3.4 Hz, H-1), 4.60 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.58, 4.49 (2× d, 2× 1H, J = 12.1 Hz, CHH O-6′Bn), 4.39 (ddd, 1H, J = 51.5, 9.6, 8.5 Hz, H-3′), 4.32 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.32 (dd, 1H, J = 3.3, 1.1 Hz, H-4), 4.23 (dd, 1H, J = 10.0, 3.3 Hz, H-3), 4.20 (dd, 1H, J = 12.5, 1.7 Hz, H-6), 4.14 (dd, 1H, J = 10.0, 3.4 Hz, H-2), 3.97 (dd, 1H, J = 12.5, 1.7 Hz, H-6), 3.75 (ddd, 1H, J = 13.3, 9.9, 8.5 Hz, H-4′), 3.70 (m, 2H, H-6′), 3.64 (ddd, 1H, J = 13.3, 9.6, 8.1 Hz, H-2′), 3.60 (br s, 1H, H-5), 3.40 (dt, 1H, J = 9.9, 3.2 Hz, H-5′), 3.35 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.2 (Cq O-6′Bn), 138.1 (Cq O-2Bn), 138.0 (Cq), 137.6 (Cq O-4′Bn), 128.8 (CHarom), 128.64, 128.58, 128.56, 128.5, 128.3 (5× 2CHarom), 128.16 (3CHarom), 128.15 (CHarom), 127.9 (3CHarom), 126.3 (2CHarom), 102.2 (d, 3J(C−F) = 10.8 Hz, C-1′), 100.5 (CHPh), 99.0 (C-1), 96.1 (d, 1J(C−F) = 186.8 Hz, C3′), 76.6 (C-4), 76.4 (C-2), 75.7 (d, 2J(C−F) = 16.8 Hz, C-4′), 74.7 (C-

under stirring, and methyl iodide (0.36 mL, 5.78 mmol) was added. The reaction mixture was allowed to warm up to rt, and stirring continued overnight. The mixture was diluted with THF, and methanol (0.5 mL) was added under cooling (ice-water) to quench the reaction. The mixture was diluted with dichloromethane and washed with water, the water phase was extracted with dichloromethane, and combined organic phases were dried and concentrated. Chromatography in EtOAc/PE 1:1 afforded methyl 3-O-allyl-2,4,6-triO-methyl-α-D-galactopyranoside (S1) which was used in the next step. A sample was taken for NMR characterization: 1H NMR (CDCl3, 400 MHz, H−H COSY, HSQC): δ 5.94 (dddd, 1H, J = 17.2, 10.4, 5.7, 5.3 Hz, CH), 5.31 (dq, 1H, J = 17.2, 1.5 Hz, CHH), 5.16 (dq, 1H, J = 10.4, 1.5 Hz, CHH), 4.86 (d, 1H, J = 3.4 Hz, H1), 4.22 (ddt, 1H, J = 13.0, 5.3, 1.5 Hz, OCHHCH2), 4.16 (ddt, 1H, J = 13.0, 5.7, 1.5 Hz, OCHHCH2), 3.84 (td, 1H, J = 6.6, 1.1 Hz, H-5), 3.70 (dd, 1H, J = 10.0, 2.8 Hz, H-3), 3.65 (dd, 1H, J = 10.0, 3.4 Hz, H-2), 3.62 (dd, 1H, J = 2.8, 1.1 Hz, H-4), 3.55−3.49 (m, 2H, H-6), 3.57, 3.52 (2× s, 2× 3H, MeO), 3.40 (s, 6H, 2× MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 135.2 (CH), 116.8 (CH2), 98.3 (C-1), 78.4, 78.3 (C-2/3), 77.5 (C-4), 71.8 (OCH2CH2), 71.4 (C-6), 69.1 (C-5), 61.5, 59.5, 59.4, 55.5 (OMe). The product S1 was dissolved in MeOH (30 mL), PdCl2 (55 mg, 0.310 mmol) was added, and the resulting suspension was stirred vigorously overnight until TLC (EtOAc) indicated consumption of the starting S1 and formation of one major product. The reaction mixture was diluted with EtOAc, filtered through Celite and silica gel, and concentrated. The brown residue was chromatographed in EtOAc to afford D with traces of side products (TLC in EtOAc). The product was dissolved in hot heptane and decanted, and the heptane solution was concentrated. Recrystallization of the residue from hot heptane afforded D (199 mg, 72%) as colorless needles, Rf 0.3 (EtOAc), mp 1 67−69 °C (heptane), [α]20 D +136 (c 0.64, CHCl3). H NMR (CDCl3, 400 MHz, H−H COSY, HSQC): δ 4.92 (dd, 1H, J = 3.6, 0.6 Hz, H1), 3.96 (ddd, 1H, J = 10.1, 5.5, 3.4 Hz, H-3), 3.91 (tdd, 1H, J = 6.5, 1.3, 0.6 Hz, H-5), 3.61 (dd, 1H, J = 3.4, 1.3 Hz, H-4), 3.50 (dd, 1H, J = 10.1, 3.6 Hz, H-2), 3.57−3.53 (m, 2H, H-6), 3.58, 3.50, 3.42, 3.40 (4× s, 4× 3H, MeO), 2.34 (d, 1H, J = 5.5 Hz, OH). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 97.3 (C-1), 79.1 (C-4), 79.0 (C-2), 71.4 (C-6), 70.3 (C-3), 69.1 (C-5), 61.9, 59.4, 58.4, 55.6 (OMe). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C10H21O6, 237.1332; found, 237.1336. Cyclohexyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-βD-glucopyranoside (1A-β). Compound 1A-β was prepared by glycosylation of cyclohexanol with α-1 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:8 afforded 1A-β (41 mg, 88%) as crystalline material containing 5% (19F NMR) of the chromatographically inseparable α-anomer 1A-α, Rf 0.42 (EtOAc/PE 1:7), mp 77−78 °C (heptane). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.34−7.29 (m, 8H, CHarom), 7.25−7.23 (m, 2H, CHarom), 4.81 (dd, 1H, J = 11.0, 1.2 Hz, CHH O-4Bn), 4.61, 4.55 (2× d, 2× 1H, J = 12.2 Hz, CHH O6Bn), 4.54 (d, 1H, J = 11.0 Hz, CHH O-4Bn), 4.38 (dd, 1H, J = 8.1, 0.8 Hz, H-1), 4.37 (ddd, 1H, J = 51.5, 9.7, 8.4 Hz, H-3), 3.76−3.65 (m, 4H, H-4, H-6, CH cyclohexyl), 3.52 (ddd, 1H, J = 13.6, 9.7, 8.1 Hz, H-2), 3.39 (dddd, 1H, J = 9.9, 4.7, 2.0, 1.5 Hz, H-5), 1.97−1.90 (m, 2H, CH2 cyclohexyl), 1.78−1.75 (m, 2H, CH2 cyclohexyl), 1.55− 1.40 (m, 3H, CH2 cyclohexyl), 1.35−1.22 (m, 3H, CH2 cyclohexyl). 13 C{1H NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.2 (Cq O6Bn), 137.7 (Cq O-4Bn), 128.6, 128.5, 128.3 (3× 2CHarom), 128.1 (CHarom), 127.9 (2CHarom), 127.8 (CHarom), 100.0 (d, 3J(C−F) = 10.8 Hz, C-1), 98.1 (d, 1J(C−F) = 187.0 Hz, C-3), 78.4 (CH cyclohexyl), 75.8 (d, 2J(C−F) = 16.7 Hz, C-4), 74.7 (d, 4J(C−F) = 2.7 Hz, CH2 O4Bn), 73.7 (d, 3J(C−F) = 9.5 Hz, C-5), 73.6 (CH2 O-6Bn), 68.6 (d, 4 J(C−F) = 1.8 Hz, C-6), 64.7 (d, 2J(C−F) = 16.9 Hz, C-2), 33.6, 31.8, 25.7, 24.1, 23.9 (5× CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −187.63 (dt, 2J(H−F) = 51.5 Hz, 3J(H−F) = 13.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2391. Selected NMR data for 1A-α: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 5.09 (dd, 1H, J = 3.7, 3.5 J


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Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3698. Data for α-anomer 1E-α: Rf 0.41 (toluene/Et2O/heptane 1:1:2), 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.34−7.18 (m, 25H, CHarom), 5.77 (dd, 1H, J = 3.9, 3.7 Hz, H-1′), 5.11 (d, 1H, J = 10.7 Hz, CHH O-3Bn), 4.88 (ddd, 1H, J = 53.8, 10.3, 8.4 Hz, H-3′), 4.83 (d, 1H, J = 10.7 Hz, CHH O-3Bn), 4.78 (d, 1H, J = 10.7 Hz, CHH O-4′Bn), 4.75, 4.62 (2× d, 2× 1H, J = 11.9 Hz, CHH O-2/6Bn), 4.61 (d, 1H, J = 3.6 Hz, H-1), 4.49 (d, 1H, J = 12.2 Hz, CHH O-6′Bn), 4.48, 4.45 (2× d, 2× 1H, J = 12.4 Hz, CHH O-2/6Bn), 4.45 (d, 1H, J = 10.7 Hz, CHH O-4′Bn), 4.24 (d, 1H, J = 12.2 Hz, CHH O-6′Bn), 4.07 (dd, 1H, J = 9.6, 8.7 Hz, H-3), 3.91 (dd, 1H, J = 9.8, 8.7 Hz, H-4), 3.80 (ddd, 1H, J = 13.9, 10.1, 8.4 Hz, H-4′), 3.74 (ddd 1H, J = 9.8, 4.0, 1.9 Hz, H-5), 3.69−3.63 (m, 2H, H-6, H-5′), 3.59 (dd, 1H, J = 11.0, 1.9 Hz, H-6), 3.57 (dd, 1H, J = 9.6, 3.6 Hz, H-2), 3.49 (dd, 1H, J = 10.8, 2.7 Hz, H-6′), 3.38 (s, 3H, MeO), 3.33 (ddd, 1H, J = 10.8, 10.3, 3.9 Hz, H-2′), 3.30 (dt, 1H, J = 10.8, 2.2 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7, 138.2, 138.0, 137.93, 137.87 (Cq), 128.7, 128.51, 128.50, 128.46, 128.4, 128.3, 128.21 (7× 2CHarom), 128.15 (CHarom), 128.1 (2CHarom), 128.0, 127.9 (2× 1CHarom), 127.7 (2CHarom), 127.64, 127.63 (2× 1CHarom), 127.4 (2CHarom), 97.9 (d, 3J(C−F) = 9.0 Hz, C-1′), 97.8 (C-1), 94.0 (d, 1J(C−F) = 184.4 Hz, C-3′), 82.1 (C-3), 80.6 (C-2), 75.7 (d, 2J(C−F) = 16.5 Hz, C-4′), 75.1 (CH2 O-3Bn), 74.8 (d, 4J(C−F) = 2.3 Hz, CH2 O-4′Bn), 73.7 (CH2 O-6′Bn), 73.5, 73.4 (CH2 O-2/6Bn), 73.2 (C-4), 70.6 (d, 3J(C−F) = 8.2 Hz, C-5′), 69.5 (C-5), 69.2 (C-6), 67.5 (C-6′), 61.6 (d, 2J(C−F) = 16.6 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −193.48 (ddd 2J(H−F) = 53.8 Hz, 3J(H−F) = 13.9, 10.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3695. 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-β-D-glucopyranosyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (1F-β) and 3-O-(2-azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-glucopyranosyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (1F-α). Compounds 1F-β and 1F-α were prepared by glycosylation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (F) with α-1 according to the general procedure. Chromatography in EtOAc/PE 1:5 resulted in poor separation. Second chromatography in toluene/Et2O/PE 1:1:2 gave the product in two fractions. The faster moving fraction afforded α-anomer 1F-α as a colorless syrup which crystallized on standing (17 mg, 27%). The slower moving fraction afforded β-anomer 1F-β containing about 6% of 1F-α as a colorless syrup (35 mg, 55%). The combined yield was 82%. Data for β-anomer 1F-β: Rf 0.25 (EtOAc/PE 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.37−7.24 (m, 10H, CHarom), 5.97 (d, 1H, J = 3.7 Hz, H-1), 4.81 (dd, 1H, J = 11.0, 1.2 Hz, CHH O-4′Bn), 4.62−4.52 (m, 4H, H-2, CHH O-4′Bn, CH2 O-6′Bn), 4.50−4.31 (m, 5H, H-3, H-4, H-5, H-1′, H-3′), 4.08−4.02 (m, 2H, H-6), 3.77 (ddd, 1H, J = 13.4, 9.9, 8.5 Hz, H-4′), 3.71 (m, 2H, H-6′), 3.50 (ddd, 1H, J = 13.4, 9.6, 8.1 Hz, H-2′), 3.38 from 1 H{19F} (dt, 1H, J = 9.9, 3.1 Hz, H-5′), 1.51, 1.41, 1.33, 1.30 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.1, 137.5 (Cq), 128.61, 128.59, 128.3 (3× 2CHarom), 128.2 (CHarom), 127.96 (2CHarom), 127.95 (CHarom), 112.3, 108.9 (2× CMe2), 105.4 (C-1), 99.8 (d, 3J(C−F) = 10.9 Hz, C-1′), 96.0 (d, 1J(C−F) = 187.7 Hz, C-3′), 82.9 (C-2), 81.1, 80.5 (C-3/4), 75.3 (d, 2J(C−F) = 17.0 Hz, C4′), 74.8 (d, 4J(C−F) = 2.6 Hz, CH2 O-4′Bn), 74.4 (d, 3J(C−F) = 9.2 Hz, C-5′), 73.9 (CH2 O-6′Bn), 73.2 (C-5), 68.2 (C-6′), 66.3 (C-6), 64.6 (d, 2J(C−F) = 17.7 Hz, C-2′), 26.9, 26.8, 26.4, 25.5 (Me). 19F NMR (CDCl3, 376 MHz): δ −188.41 (dt, 2J(H−F) = 51.4 Hz, 3J(H−F) = 13.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2754. Data for α-anomer 1F-α: Rf 0.33 (EtOAc/PE 1:5), mp 85−89 °C (heptane/MTBE). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.35−7.29 (m, 8H, CHarom), 7.22 (dd, 2H, J = 7.6, 2.0 Hz, CHarom), 5.83 (d, 1H, J = 3.6 Hz, H-1), 5.32 (dd, 1H, J = 3.8, 3.6 Hz, H-1′), 4.90 (ddd, 1H, J = 53.4, 10.1, 8.0 Hz, H-3′), 4.83 (d, 1H, J = 11.0 Hz, CHH O-4′Bn), 4.63 (d, 1H, J = 12.1 Hz, CHH O-6′Bn), 4.54 (d, 1H, J = 3.6 Hz, H-2), 4.50 (d, 1H, J = 11.0 Hz, CHH O-4′Bn), 4.50 (d, 1H, J = 12.1 Hz, CHH O-6′Bn), 4.42 (ddd,

3), 74.7 (d, 4J(C−F) = 2.4 Hz, CH2 O-4′Bn), 73.8 (CH2 O-2Bn), 73.6 (CH2 O-6′Bn), 73.3 (d, 3J(C−F) = 9.4 Hz, C-5′), 69.3 (C-6), 68.5 (C6′), 64.7 (d, 2J(C−F) = 17.3 Hz, C-2′), 62.7 (C-5), 55.7 (MeO). 19F NMR (CDCl3, 376 MHz): δ −188.38 (dt, 2J(H−F) = 51.5 Hz, 3J(H−F) = 13.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3061. Data for α-anomer 1C-α: Rf 0.18 (toluene/heptane/Et2O 1:1:1). 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.52 (dd, 2H, J = 7.6, 1.8 Hz, CHarom), 7.38−7.28 (m, 13H, CHarom), 7.20−7.15 (m, 5H, CHarom), 5.58 (s, 1H, CHPh), 5.22 (dd, 1H, J = 3.6, 3.5 Hz, H-1′), 5.04 (ddd, 1H, J = 53.7, 10.1, 8.3 Hz, H-3′), 4.83 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.78 (d, 1H, J = 3.5 Hz, H-1), 4.69 (d, 1H, J = 11.5 Hz, CHH O-2Bn), 4.58 (d, 1H, J = 12.0 Hz, CHH O-6′Bn), 4.54 (d, 1H, J = 11.5 Hz, CHH O-2Bn), 4.49 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.37 (m, 2H, H-4, CHH O6′Bn), 4.28 (dd, 1H, J = 12.5, 1.6 Hz, H-6), 4.20 (dd, 1H, J = 10.0, 3.6 Hz, H-3), 4.11 (ddd, 1H, J = 10.0, 2.6, 2.3 Hz, H-5′), 4.08 (dd, 1H, J = 12.5, 1.9 Hz, H-6), 4.03 (dd, 1H, J = 10.1, 3.5 Hz, H-2), 3.88 (ddd, 1H, J = 14.3, 10.0, 8.3 Hz, H-4′), 3.66 (dd, 1H, J = 11.0, 2.6 Hz, H6′), 3.63 (m, 1H, H-5), 3.58 (dt, 1H, J = 11.0, 2.3 Hz, H-6′), 3.38 (td, 1H, J = 10.1, 3.6 Hz, H-2′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1, 137.92, 137.90, 137.7 (Cq), 128.9 (CHarom), 128.6, 128.53, 128.51, 128.4, 128.23, 128.19 (6× 2CHarom), 128.02 (CHarom), 127.96 (2CHarom), 127.9, 127.8 (2× 1CHarom), 126.1 (2CHarom), 100.9 (CHPh), 99.0 (C-1), 94.0 (d, 3 J(C−F) = 9.7 Hz, C-1′), 93.4 (d, 1J(C−F) = 184.4 Hz, C-3′), 75.9 (d, 2 J(C−F) = 16.8 Hz, C-4′), 74.6 (d, 4J(C−F) = 2.4 Hz, CH2 O-4′Bn), 74.5 (C-2), 73.9 (CH2 O-2Bn), 73.6 (CH2 O-6′Bn), 72.1 (C-4), 71.7 (C3), 69.9 (d, 3J(C−F) = 8.3 Hz, C-5′), 69.6 (C-6), 67.9 (C-6′), 62.2 (C5), 61.0 (d, 2J(C−F) = 17.1 Hz, C-2′), 55.7 (MeO). 19F NMR (CDCl3, 376 MHz): δ −193.23 (dddd, 2J(H−F) = 53.7 Hz, 3J(H−F) = 10.1, 14.3, 4 J(H−F) = 3.5 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3075. Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-glucopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (1E-α) and Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy3-fluoro-β-D-glucopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (1E-β). Compounds 1E-α and 1E-β were prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside46 (E) with α-1 according to the general procedure. Chromatography in toluene/Et2O/PE 1:1:3 afforded first α-anomer 1E-α as a colorless syrup (13 mg, 16%). Continued elution gave β-anomer 1E-β as a colorless syrup (34 mg, 41%), and the combined yield was 57%. Data for β-anomer 1E-β: Rf 0.30 (toluene/Et2O/heptane 1:1:2), 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.21 (m, 25H, CHarom), 5.00, 4.78 (2× d, 2× 1H, J = 11.4 Hz, CHH O-3Bn), 4.78 (d, 1H, J = 11.1 Hz, CHH O-4′Bn), 4.74 (d, 1H, J = 12.2 Hz, CHH O-2Bn), 4.68 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.59 (d, 1H, J = 3.7 Hz, H-1), 4.58 (d, 1H, J = 12.2 Hz, CHH O-2Bn), 4.51 (d, 1H, J = 11.1 Hz, CHH O-4′Bn), 4.43 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.38 (br s, 2H, CH2 O-6′Bn), 4.20 (ddd, 1H, J = 51.7, 9.5, 8.4 Hz, H-3′), 4.18 (d, 1H, J = 8.2 Hz, H-1′), 3.94 (dd, 1H, J = 9.9, 8.4 Hz, H-4), 3.91 (dd, 1H, J = 11.0, 2.5 Hz, H6), 3.88 (dd, 1H, J = 9.6, 8.4 Hz, H-3), 3.76 (dt, 1H, J = 9.9, 2.5 Hz, H-5), 3.73−3.65 (m, 2H, H-6, H-4′), 3.62 (dt, 1H, J = 11.0, 1.8 Hz, H-6′), 3.50 (dd, 1H, J = 11.0, 4.3 Hz, H-6′), 3.48 (dd, 1H, J = 9.6, 3.7 Hz, H-2), 3.38 (ddd, 1H, J = 13.7, 9.5, 8.2 Hz, H-2′), 3.38 (s, 3H, MeO), 3.10 (ddd, 1H, J = 9.9, 4.3, 1.8 Hz, H-5′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.6, 138.39, 138.38, 137.9, 137.8 (Cq), 128.7, 128.52, 128.51, 128.45, 128.3, 128.24, 128.18 (7× 2CHarom), 128.09 (CHarom), 128.07 (2CHarom), 128.0, 127.94 (2× 1CHarom), 127.89, 127.8 (2× 2CHarom), 127.7, 127.3 (2× 1CHarom), 100.3 (d, 3J(C−F) = 10.9 Hz, C-1′), 98.4 (C-1), 96.6 (d, 1J(C−F) = 186.2 Hz, C-3′), 80.4 (C-3), 79.2 (C-2), 77.1 (C-4), 75.5 (d, 2J(C−F) = 14.8 Hz, C-4′), 75.5 (CH2 O-3Bn), 74.5 (d, 4J(C−F) = 2.4 Hz, CH2 O4′Bn), 74.0 (d, 3J(C−F) = 9.4 Hz, C-5′), 73.69, 73.65 (CH2 O-2/6Bn), 73.5 (CH2 O-6′Bn), 69.7 (C-5), 68.3 (d, 4J(C−F) = 1.6 Hz, C-6′), 68.2 (C-6), 65.2 (d, 2J(C−F) = 17.2 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −187.83 (dt, 2J(H−F) = 51.4 Hz, 3J(H−F) = 13.7 K


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55.6 (MeO). 19F NMR (CDCl3, 376 MHz): δ −193.31 (dt, 2J(H−F) = 53.8 Hz, 3J(H−F) = 12.5 Hz). 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-α,β-Dglucopyranosyl)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-βD -glucopyranoside (1H). Compound 1H was prepared by glycosylation of 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranoside47 (H) with α-1 according to the general procedure. Chromatography in EtOAc/PE 1:2 followed by chromatography in toluene/Et2O/PE 1:1:2 afforded the product in two fractions. The faster moving fraction was a colorless syrup enriched in α-anomer (16 mg, 25%, α/β ca. 5:1), HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2559. The slower moving fraction was a colorless syrup enriched in β-anomer (26 mg, 40%, α/β ca. 1:5), HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2568. Combined yield was 65%. NMR data for the α-anomer of 1H: Rf 0.25 (EtOAc/heptane 1:3). 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.28 (m, 13H, CHarom), 7.25−7.22 (m, 2H, CHarom), 5.50 (t, 1H, J = 1.6 Hz, H-1), 5.10 (ddd, 1H, J = 53.4, 10.1, 8.3 Hz, H-3′), 4.91 (dd, 1H, J = 3.8, 3.6 Hz, H-1′), 4.84 (dd, 1H, J = 11.2, 1.0 Hz, CHH O-4′Bn), 4.75 (ddd, 1H, J = 6.0, 2.7, 1.2 Hz, H-5), 4.69 (d, 1H, J = 11.8 Hz, CHH O-3Bn), 4.57 (d, 2× 1H, J = 11.8 Hz, CHH O-3Bn, O-6′Bn), 4.52 (d, 1H, J = 11.2 Hz, CHH O4′Bn), 4.45 (d, 1H, J = 11.9 Hz, CHH O-6′Bn), 4.12 (ddd, 1H, J = 10.3, 4.1, 2.7 Hz, H-5′), 4.04 (dd, 1H, J = 7.4, 1.2 Hz, H-6en), 3.74− 3.69 (m, 4H, H-3, H-4′, H-6′), 3.61 (dd, 1H, J = 7.4, 6.0 Hz, H-6ex), 3.51 (dd, 1H, J = 2.7, 1.6 Hz, H-4), 3.41 (ddd, 1H, J = 11.4, 10.1, 3.8 Hz, H-2′), 3.16 (dd, 1H, J = 1.8, 1.6 Hz, H-2). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8, 137.7, 137.1 (Cq), 128.8, 128.6, 128.5 (3× 2CHarom), 128.4 (CHarom), 128.2, 128.1 (2× 2CHarom), 128.03 (CHarom), 127.99 (3CHarom), 100.9 (C-1), 100.1 (d, 3 J(C−F) = 9.8 Hz, C-1′), 93.7 (d, 1J(C−F) = 184.1 Hz, C-3′), 78.7 (C-4), 75.9 (C-3), 75.8 (d, 2J(C−F) = 16.6 Hz, C-4′), 74.8 (C-5), 74.5 (d, 4 J(C−F) = 3.0 Hz, CH2 O-4′Bn), 73.7 (CH2 O-6′Bn), 73.0 (CH2 O3Bn), 70.5 (d, 3J(C−F) = 8.3 Hz, C-5′), 68.5 (C-6′), 65.1 (C-6), 61.7 (d, 2J(C−F) = 17.4 Hz, C-2′), 59.2 (C-2). 19F NMR (CDCl3, 376 MHz): δ −192.50 (dddd, 2J(H−F) = 53.4 Hz, 3J(H−F) = 12.7, 11.4 Hz, 4 J(H−F) = 3.6 Hz). NMR data for the β-anomer of 1H: Rf 0.25 (EtOAc/heptane 1:3). 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.36−7.24 (m, 15H, CHarom), 5.51 (t, 1H, J = 1.6 Hz, H-1), 4.82 (dd, 1H, J = 10.9, 1.2 Hz, CHH O-4′Bn), 4.68 (m, 1H, H5), 4.59−4.46 (m, 4H, CH2 C-3/O-6′Bn), 4.55 (d, 1H, J = 10.9 Hz, CHH O-4′Bn), 4.39 (ddd, 1H, J = 51.3, 9.6, 8.5 Hz, H-3′), 4.33 (d, 1H, J = 8.0 Hz, H-1′), 4.12 (dd, 1H, J = 7.3, 1.1 Hz, H-6en), 3.99 (q, 1H, J = 1.6 Hz, H-3), 3.75−3.57 (m, 5H, H-4, H-2′, H-4′, H-6′), 3.77 (dd, 1H, J = 7.3, 5.9 Hz, H-6ex), 3.34 (ddt, 1H, J = 9.8, 5.0, 1.7 Hz, H5′), 3.21 (t, 1H, J = 1.6 Hz, H-2). 13C{1H} NMR (CDCl3, 100 MHz, HSQC, HMBC): δ 137.9, 137.7, 137.5 (Cq), 128.7, 128.62, 128.59, 128.3 (4× 2CHarom), 128.2, 128.1, 128.0 (3× 1CHarom), 127.9, 127.8 (2× 2CHarom), 101.8 (d, 3J(C−F) = 10.9 Hz, C-1′), 100.7 (C-1), 96.1 (d, 1J(C−F) = 187.6 Hz, C-3′), 77.4 (C-4), 77.0 (C-3), 75.4 (d, 2J(C−F) = 16.7 Hz, C-4′), 74.7 (m, CH2 O-4′Bn, C-5), 74.0 (d, 3J(C−F) = 9.3 Hz, C-5′), 73.7 (CH2 O-6′Bn), 72.7 (CH2 O-3Bn), 68.7 (d, 4J(C−F) = 1.5 Hz, C-6′), 65.1 (C-6), 64.3 (d, 2J(C−F) = 17.9 Hz, C-2′), 59.5 (C2). 19F NMR (CDCl3, 376 MHz): δ −188.45 (dt, 2J(H−F) = 51.3 Hz, 3 J(H−F) = 13.3 Hz). Methyl 2-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-glucopyranosyl)-3-O-benzyl-4,6-O-benzylidene-α-D-mannopyranoside (1I-α) and Methyl 2-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-β-D-glucopyranosyl)-3-O-benzyl-4,6O-benzylidene-α-D-mannopyranoside (1I-β). Compounds 1I-α and 1I-β were prepared by glycosylation of methyl 3-O-benzyl-4,6-Obenzylidene-α-D-mannopyranoside48 (I) with α-1 according to the general procedure. Chromatography in EtOAc/PE 1:3 followed by preparative TLC in EtOAc/PE 1:4 gave two fractions. The faster moving fraction afforded α-anomer 1I-α as colorless syrup (18 mg, 24%). The slower moving fraction afforded β-anomer 1I-β as crystalline solid (22 mg, 30%), combined yield was 54%.

1H, J = 8.9, 6.2, 5.4 Hz, H-5), 4.26 (d, 1H, J = 2.7 Hz, H-3), 4.17 (dd, 1H, J = 8.6, 6.2 Hz, H-6), 4.03 (dd, 1H, J = 8.9, 2.7 Hz, H-4), 3.96 (dd, 1H, J = 8.6, 5.4 Hz, H-6), 3.80−3.71 (m, 3H, H-5′, H-6′), 3.83 from 1H{19F} (dd, 1H, J = 9.2, 8.0 Hz, H-4′), 3.58 (ddd, 1H, J = 11.3, 10.1, 3.8 Hz, H-2′), 1.47, 1.41, 1.35, 1.23 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6′Bn), 137.5 (Cq O-4′Bn), 128.7, 128.6, 128.4 (3× 2CHarom), 128.3 (CHarom), 128.14 (2CHarom), 128.07 (CHarom), 112.2, 109.5 (2× CMe2), 105.3 (C-1), 98.2 (d, 3J(C−F) = 9.6 Hz, C-1′), 94.3 (d, 1J(C−F) = 184.3 Hz, C-3′), 83.8 (C-2), 81.6 (C-4), 80.3 (C-3), 75.7 (d, 2J(C−F) = 16.8 Hz, C-4′), 75.0 (d, 4J(C−F) = 2.8 Hz, CH2 O-4′Bn), 73.8 (CH2 O-6′Bn), 71.9 (C-5), 70.8 (d, 3J(C−F) = 8.3 Hz, C-5′), 68.03, 67.99 (C-6/6′), 62.1 (d, 2J(C−F) = 17.0 Hz, C-2′), 27.0, 26.9, 26.3, 25.4 (Me). 19F NMR (CDCl3, 376 MHz): δ −193.07 (ddd, 2J(H−F) = 53.4 Hz, 3J(H−F) = 14.5, 11.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2761. Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα,β-D-glucopyranosyl)-2,3,6-tri-O-benzyl-α-D-galactopyranoside (1G). Compound 1G was prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside46 (G) with α-1 according to the general procedure. Column chromatography in Et2O/PE 9:7 followed by preparative TLC in Et2O/PE 9:7 afforded 1G as a colorless syrupy mixture of anomers (56 mg, 67%) Rf 0.43 (Et2O/ heptane 9:7). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3694. NMR data for the α-anomer of 1G: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.37−7.18 (m, 25H, CHarom), 4.97 (dd, 1H, J = 3.8, 3.6 Hz, H-1′), 4.89 (ddd, 1H, J = 53.8, 10.0, 8.6 Hz, H-3′), 4.83 (d, 1H, J = 12.3 Hz, CHH Bn), 4.77 (d, 1H, J = 10.4 Hz, CHH Bn), 4.75 (d, 1H, J = 11.6 Hz, CHH Bn), 4.88− 4.64 (m, overlapped with β-anomer, 2H, H-1, CHH Bn), 4.54−4.51 (m, overlapped with β-anomer, 4H, CHH Bn), 4.47 (d, 1H, J = 11.6 Hz, CHH Bn), 4.43 (d, 1H, J = 10.8 Hz, CHH Bn), 4.23 (t, 1H, J = 2.1 Hz, H-5′), 4.17 (m, H-4), 3.87−3.80 (m, 5H, H-2, H-5, H-3, H-6, H-4′), 3.56−3.52 (m, overlapped with β-anomer, 1H, H-6), 3.43 (ddd, 1H, J = 12.5, 10.0, 3.8 Hz, H-2′), 3.35 (s, 3H, MeO), 3.26 (dd, 1H, J = 11.0, 2.2 Hz, H-6′), 2.98 (dd, 1H, J = 11.0, 2.4 Hz, H-6′). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7, 138.2, 138.1, 138.0, 137.7 (Cq), 128.6, 128.57, 128.56, 128.47, 128.42, 128.2 (6× 2CHarom), 128.13 (CHarom), 128.12, 128.08 (2× 2CHarom), 128.0, 127.89, 127.87 (3× 1CHarom) 127.7, 127.64 (2× 2CHarom), 127.59 (CHarom), 98.8 (d, 3J(C−F) = 10.2 Hz, C-1′), 98.7 (C-1), 94.3 (d, 1 J(C−F) = 183.8 Hz, C-3′), 77.1 (C-2), 75.8 (d, 2J(C−F) = 17.6 Hz, C4′), 75.6 (C-3), 75.4 (C-4), 74.7 (d, 4J(C−F) = 2.3 Hz, CH2 O-4′Bn), 73.9, 73.8, 73.6 (CH2 Bn), 73.5 (d, 3J(C−F) = 10.3 Hz, C-5′), 73.4 (CH2 Bn), 70.1 (C-6), 69.3 (C-5), 68.6 (d, 4J(C−F) = 1.6 Hz, C-6′), 64.8 (d, 2J(C−F) = 17.3 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −188.20 (dt, 2J(H−F) = 51.4 Hz, 3J(H−F) = 13.5 Hz). NMR data for the β-anomer of 1G: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.37−7.18 (m, 25H, CHarom), 4.93 (d, 1H, J = 12.2 Hz, CHH Bn), 4.83 (d, 1H, J = 12.3 Hz, CHH Bn), 4.77 (d, 1H, J = 10.4 Hz, CHH Bn), 4.71 (d, 1H, J = 8.1 Hz, H-1′), 4.88−4.64 (m, overlapped with α-anomer, 2H, CHH Bn), 4.63 (d, 1H, J = 3.7 Hz, H-1), 4.54−4.51 (m, overlapped with αanomer, 2H, CHH Bn), 4.44 (d, 1H, J = 11.8 Hz, CHH Bn), 4.35 (d, 1H, J = 12.1 Hz, CHH Bn), 4.32 (ddd, 1H, J = 51.4, 9.4, 8.4 Hz, H3′), 4.18 (d, 1H, J = 12.0 Hz, CHH Bn), 4.15 (dd, 1H, J = 2.8, 1.2 Hz, H-4), 4.10 (dd, 1H, J = 10.0, 3.7 Hz, H-2), 3.96−3.94 (m, 1H, H-5), 3.91 (dd, 1H, J = 10.0, 2.8 Hz, H-3), 3.76−3.68 (m, 2H, H-6, H-4′), 3.65−3.58 (m, 3H, H-6, H-6′), 3.49 (ddd, 1H, J = 13.5, 9.5, 8.1 Hz, H-2′), 3.38 (s, 3H, MeO), 3.27−3.20 (m, overlapped with α-anomer, 1H, H-5′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.0 (Cq), 138.6 (2× Cq), 138.0, 137.7 (Cq), 128.57, 128.56, 128.49, 128.48, 128.45, 128.3, 128.25 (7× 2CHarom), 128.2 (CHarom), 127.9 (3CHarom), 127.8 (2CHarom), 128.6 (CHarom), 127.5, 127.3 (2× 2CHarom), 101.1 (d, 3J(C−F) = 10.7 Hz, C-1′), 98.9 (C-1), 96.0 (d, 1 J(C−F) = 186.7 Hz, C-3′), 78.4 (C-3), 76.6 (C-2), 75.6 (d, 2J(C−F) = 17.0 Hz, C-4′), 74.9 (C-4), 74.6 (d, 4J(C−F) = 2.5 Hz, CH2 O-4′Bn), 73.7, 73.6, 73.49, 73.45 (CH2 Bn), 70.0 (d, 3J(C−F) = 8.1 Hz, C-5′), 68.7 (C-5), 67.3 (C-6), 67.1 (C-6′), 62.5 (d, 2J(C−F) = 16.9 Hz, C-2′), L


Article

The Journal of Organic Chemistry Data for 1I-α: Rf 0.33 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.49 (dd, 2H, J = 7.6, 2.0 Hz, CHarom), 7.37−7.27 (m, 16H, CHarom), 7.27−7.25 (m, 2H, CHarom), 5.64 (s, 1H, CHPh), 5.39 (dd, 1H, J = 3.8, 3.6 Hz, H1′), 5.05 (ddd, 1H, J = 53.7, 10.3, 7.9 Hz, H-3′), 4.89 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.86 (dd, 1H, J = 10.8, 1.1 Hz, CHH O-4′Bn), 4.68 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.67 (d, 1H, J = 1.7 Hz, H1), 4.62 (d, 1H, J = 12.0 Hz, CHH O-6′Bn), 4.52 (d, 1H, J = 10.8 Hz, CHH O-4′Bn), 4.50 (d, 1H, J = 12.0 Hz, CHH O-6′Bn), 4.26−4.21 (m, 2H, H-4, H-6), 4.05 (dd, 1H, J = 3.2, 1.7 Hz, H-2), 3.97 (dd, 1H, J = 9.9, 3.2 Hz, H-3), 3.87−3.73 (m, 5H, H-5, H-6, H-4′, H-5′, H-6′), 3.68 (dt, 1H, J = 10.7, 1.9 Hz, H-6′), 3.38 (ddd, 1H, J = 10.6, 10.3, 3.8 Hz, H-2′), 3.25 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7 (Cq O-3Bn), 137.8 (Cq O-6′Bn), 137.7 (Cq), 137.6 (Cq O-4′Bn), 129.0 (CHarom), 128.61, 128.58, 128.4, 128.33, 128.29 (5× 2CHarom), 128.2 (CHarom), 128.1 (2CHarom), 128.0, 127.6 (2× 1CHarom), 127.5, 126.2 (2× 2CHarom), 101.7 (CHPh), 100.7 (C-1), 99.6 (d, 3J(C−F) = 9.3 Hz, C-1′), 93.2 (d, 1J(C−F) = 184.6 Hz, C-3′), 79.5 (C-4), 76.3 (C-2), 76.1 (d, 2J(C−F) = 16.5 Hz, C-4′), 75.7 (C-3), 74.9 (d, 4J(C−F) = 2.8 Hz, CH2 O-4′Bn), 73.7 (CH2 O-6′Bn), 73.4 (CH2 O-3Bn), 70.5 (d, 3J(C−F) = 8.1 Hz, C-5′), 69.0 (C-6), 68.2 (C-6′), 64.0 (C-5), 61.6 (d, 2J(C−F) = 17.0 Hz, C-2′), 54.9 (MeO). 19F NMR (CDCl3, 376 MHz): δ −193.64 (m). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3073. Data for 1I-β: Rf 0.20 (EtOAc/heptane 1:3), mp 94−99 °C (MTBE/heptane). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.50 (dd, 2H, J = 7.6, 2.0 Hz, CHarom), 7.40−7.35 (m, 5H, CHarom), 7.33−7.29 (m, 3H, CHarom), 7.29−7.22 (m, 10H, CHarom), 5.60 (s, 1H, CHPh), 4.83 (d, 1H, J = 11.0 Hz, CHH O-4′Bn), 4.82 (d, 1H, J = 2.1 Hz, H-1), 4.80, 4.66 (2× d, 2× 1H, J = 11.7 Hz, CHH O-3Bn), 4.55 (d, 1H, J = 11.0 Hz, CHH O4′Bn), 4.54, 4.49 (2× d, 2× 1H, J = 12.0 Hz, CHH O-6′Bn), 4.38 (d, 1H, J = 8.1 Hz, H-1′), 4.38 (ddd, 1H, J = 51.3, 9.7, 8.5 Hz, H-3′), 4.28−4.24 (m, 2H, H-2, H-6), 4.16 (dd, 1H, J = 10.1, 9.1 Hz, H-4), 3.95 (dd, 1H, J = 10.1, 3.4 Hz, H-3), 3.85 (t, 1H, J = 10.1 Hz, H-6), 3.80−3.68 (m, 5H, H-5, H-2′, H-4′, H-6′), 3.45 (ddd, 1H, J = 9.9, 5.2, 1.9 Hz, H-5′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.5, 138.0, 137.8, 137.5 (Cq), 128.9 (CHarom), 128.60, 128.55, 128.4, 128.34, 128.29 (5× 2CHarom), 128.2, 127.87 (2× 1CHarom), 127.86, 127.8, 127.6 (3× 2CHarom), 126.2 (CHarom), 101.7 (CHPh), 100.3 (d, 3J(C−F) = 11.0 Hz, C-1′), 99.3 (C-1), 95.7 (d, 1J(C−F) = 187.6 Hz, C-3′), 78.3 (C-4), 75.7 (d, 2J(C−F) = 16.7 Hz, C-4′), 75.1 (C-2), 74.8 (d, 4J(C−F) = 2.5 Hz, CH2 O-4′Bn), 74.2 (d, 3 J(C−F) = 9.2 Hz, C-5′), 73.9 (C-3), 73.8 (CH2 O-6′Bn), 71.5 (CH2 O-3Bn), 69.1 (C-6′), 69.0 (C-6), 64.6 (d, 2J(C−F) = 17.5 Hz, C-2′), 64.3 (C-5), 55.1 (MeO). 19F NMR (CDCl3, 376 MHz): δ −188.15 (dt, 2J(H−F) = 51.5 Hz, 3J(H−F) = 13.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3073. Cyclohexyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-βD-glucopyranoside (2A-β). Compound 2A-β was prepared by glycosylation of cyclohexanol with 2 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:20 afforded 2A-β (35 mg, 77%) as a colorless crystalline solid, Rf 0.48 (EtOAc/heptane 1:5), mp 57−59 °C (EtOH/H2O). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.42− 7.29 (m, 10H, CHarom), 4.84, 4.76 (2× d, 2× 1H, J = 11.3 Hz, CHH O-3Bn), 4.59, 4.62 (2× d, 2× 1H, J = 12.1 Hz, CHH O-6Bn), 4.47 (ddd, 1H, J = 50.4, 9.9, 8.0 Hz, H-4), 4.40 (d, 1H, J = 7.6 Hz, H-1), 3.78 (dt, 1H, J = 11.0, 2.3 Hz, H-6), 3.72 (dt, 1H, J = 8.0, 3.9 Hz, CH cyclohexyl), 3.66 (ddd, 1H, J = 11.0, 5.6, 2.1 Hz, H-6), 3.54 (ddt, 1H, J = 9.9, 5.6, 2.4 Hz, H-5), 3.47−3.37 (m, 2H, H-2, H-3), 1.97−1.90 (m, 2H, CH2 cyclohexyl), 1.78−1.75 (m, 2H, CH2 cyclohexyl), 1.50− 1.39 (m, 2H, CH2 cyclohexyl), 1.35−1.25 (m, 4H, CH2 cyclohexyl). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (Cq O6Bn), 137.8 (Cq O-3Bn), 128.5 (4CHarom), 128.3 (2CHarom), 128.12, 127.8 (2× 1CHarom), 127.7 (2CHarom), 100.5 (d, 4J(C−F) = 1.1 Hz, C1), 90.3 (d, 1J(C−F) = 183.7 Hz, C-4), 80.3 (d, 2J(C−F) = 18.3 Hz, C-3), 78.4 (CH cyclohexyl), 74.8 (d, 4J(C−F) = 2.4 Hz, CH2 O-3Bn), 73.7 (CH2 O-6Bn), 73.3 (d, 2J(C−F) = 23.8 Hz, C-5), 68.7 (C-6), 65.5 (d,

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J(C−F) = 9.2 Hz, C-2), 33.6, 31.8, 25.7, 24.1, 23.9 (5× CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −197.72 (dd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 14.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2389. Selected NMR data for 2A-α: 1H NMR (CDCl3, 400 MHz, H−H COSY, HSQC): δ 5.05 (dd, 1H, J = 3.6, 3.5 Hz, H-1), 4.91 (dd, 1H, J = 11.0, 1.1 Hz, CHH O-3Bn), 4.61 (ddd, 1H, J = 50.7, 10.0, 8.6 Hz, H-4), 4.13−4.01 (m, 2H, H-3, H-5), 3.71 (s, 2H, H-6), 3.26 (ddd, 1H, J = 10.4, 3.6, 1.1 Hz, H-2). 19F NMR (CDCl3, 376 MHz): δ −195.42 (dd, 1H, J = 50.7, 14.4 Hz). Methyl 6-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα,β-D-glucopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (2B). Compound 2B was prepared by glycosylation of methyl 2,3,4tri-O-benzyl-α-D-glucopyranoside45 (B) with 2 according to the general procedure. Chromatography of the crude product in EtOAc/ PE 1:5 yielded 2B (62 mg, 75%, α/β ca. 1:10) as a colorless syrup. HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3690. Data for β-anomer 2B-β: Rf 0.46 (toluene/Et2O/heptane 1:1:1), 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.40−7.26 (m, 25H, CHarom), 4.99 (d, 1H, J = 11.0 Hz, CHH O-3Bn), 4.94 (d, 1H, J = 11.2 Hz, CHH O-4Bn), 4.85 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.82 (d, 1H, J = 11.0 Hz, CHH O-3Bn), 4.79 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.75 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.65 (d, 1H, J = 11.2 Hz, CHH O-4Bn), 4.65 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.61 (d, 1H, J = 3.6 Hz, H-1), 4.57 (m, 2H, CH2 O-6′Bn), 4.47 (ddd, 1H, J = 50.1, 9.7, 8.0 Hz, H-4′), 4.15 (d, 1H, J = 7.8 Hz, H-1′), 4.11 (dd, 1H, J = 10.8, 1.9 Hz, H-6), 4.00 (dd, 1H, J = 9.7, 9.3 Hz, H-3), 3.79 (ddd, 1H, J = 10.0, 4.4, 1.9 Hz, H5), 3.75 (dt, 1H, J = 11.1, 2.0 Hz, H-6′), 3.70 (dd, 1H, J = 10.8, 4.4 Hz, H-6), 3.65 (ddd, 1H, J = 11.1, 5.5, 2.0 Hz, H-6′), 3.57 (dd, 1H, J = 10.0, 9.3 Hz, H-4), 3.54 (dd, 1H, J = 9.7, 3.6 Hz, H-2), 3.50−3.43 (m, 3H, H-2′, H-3′, H-5′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.9 (Cq O-3Bn), 138.6 (Cq O-4Bn), 138.3 (Cq O-2Bn), 138.0 (Cq O-6′Bn), 137.6 (Cq O-3′Bn), 128.60, 128.59, 128.58 (3× 2CHarom), 128.54 (4CHarom), 128.34, 128.31 (2× 2CHarom), 128.16 (CHarom), 128.14 (2CHarom), 128.06 (CHarom), 127.9 (2CHarom), 127.84, 127.83, 127.74 (3× 1CHarom), 127.69 (2CHarom), 102.0 (d, 4J(C−F) = 1.1 Hz, C-1′), 98.4 (C-1), 90.2 (d, 1J(C−F) = 183.9 Hz, C-4′), 82.2 (C-3), 80.5 (d, 2J(C−F) = 18.4 Hz, C-3′), 79.9 (C-2), 77.7 (C-4), 75.9 (CH2 O-3Bn), 75.0 (CH2 O4Bn), 74.9 (d, 4J(C−F) = 2.5 Hz, CH2 O-3′Bn), 73.8 (CH2 O-6′Bn), 73.6 (CH2 O-2Bn), 73.4 (d, 2J(C−F) = 24.2 Hz, C-5′), 69.8 (C-5), 68.7 (C-6), 68.6 (d, 3J(C−F) = 9.7 Hz, C-6′), 65.3 (d, 3J(C−F) = 9.2 Hz, C2′), 55.4 (MeO). 19F NMR (CDCl3, 376 MHz): δ −197.66 (dd, 2 J(H−F) = 50.4 Hz, 3J(H−F) = 13.5 Hz). Selected NMR resonances for α-anomer 2B-α: 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): 4.97 (overlapped with β-anomer, H-1′), 4.58 (overlapped with β-anomer, H-1), 3.30 (dd, 1H, J = 10.8, 3.4 Hz, H-2′), 3.35 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): 138.8, 138.4, 137.9, 137.7 (Cq), 98.1 (C-1), 98.0 (C-1′), 62.2 (d, 3J(C−F) = 8.5 Hz, C-2′), 55.3 (MeO). 19 F NMR (CDCl3, 376 MHz): δ −195.46 (dd, 2J(H−F) = 50.5 Hz, 3 J(H−F) = 14.9 Hz). Methyl 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-glucopyranosyl)-2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside (2C-α) and Methyl 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-β-D-glucopyranosyl)-2-O-benzyl-4,6O-benzylidene-α-D-galactopyranoside (2C-β). Compounds 2C-β and 2C-α were prepared by glycosylation of methyl 2-O-benzyl-4,6-Obenzylidene-α-D-galactopyranoside11 (C) with 2 according to the general procedure. Chromatography in EtOAc/PE 1:3 followed by preparative TLC in Et2O/PE 7:5 gave the product in two fractions. The faster moving fraction afforded β-anomer 2C-β as a colorless gum (38 mg, 51%). The slower moving fraction afforded α-anomer 2C-α as a colorless syrup (6 mg, 8%). The combined yield was 59%. Data for 2C-β: Rf 0.21 (Et2O/heptane 7:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.51 (dd, 2H, J = 7.3, 2.4 Hz, CHarom), 7.42−7.29 (m, 18H, CHarom), 5.51 (s, 1H, CHPh), 4.89 (d, 1H, J = 11.8 Hz, CHH O-2Bn), 4.82, 4.79 (2× d, 2× M


Article

The Journal of Organic Chemistry 1H, J = 11.3 Hz, CHH O-3′Bn), 4.76 (d, 1H, J = 7.8 Hz, H-1′), 4.68 (d, 1H, J = 3.4 Hz, H-1), 4.62 (d, 1H, J = 12.0 Hz, CHH O-6′Bn), 4.58 (d, 1H, J = 11.8 Hz, CHH O-2Bn), 4.55 (d, 1H, J = 12.0 Hz, CHH O-6′Bn), 4.54 (ddd, 1H, J = 50.3, 9.9, 8.2 Hz, H-4′), 4.32 (dd, 1H, J = 3.1, 1.5 Hz, H-4), 4.22 (dd, 1H, J = 10.2, 3.1 Hz, H-3), 4.19 (dd, 1H, J = 12.4, 1.2 Hz, H-6), 4.12 (dd, 1H, J = 10.2, 3.4 Hz, H-2), 3.95 (dd, 1H, J = 12.4, 1.7 Hz, H-6), 3.76 (dt, 1H, J = 11.0, 2.3 Hz, H6′), 3.67 (ddd, 1H, J = 11.0, 5.2, 1.9 Hz, H-6′), 3.60 (dd, 1H, J = 1.7, 1.5 Hz, H-5), 3.58−3.42 (m, 3H, H-2′, H-3′, H-5′), 3.35 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.4, 137.97, 138.04, 137.8 (Cq), 128.8 (CHarom), 128.6 (2CHarom), 128.53 (4CHarom), 128.48, 128.2, 128.13 (3× 2CHarom), 128.07, 128.05, 127.9 (3× 1CHarom), 127.7, 126.3 (2× 2CHarom), 102.9 (C-1′), 100.5 (CHPh), 99.1 (C-1), 90.1 (d, 1J(C−F) = 183.6 Hz, C-4′), 80.5 (d, 2 J(C−F) = 18.2 Hz, C-3′), 76.7 (C-4), 76.3 (C-2), 75.1 (C-3), 74.9 (d, 4 J(C−F) = 2.1 Hz, CH2 O-3′Bn), 73.9 (CH2 O-2Bn), 73.7 (CH2 O6′Bn), 72.8 (d, 2J(C−F) = 24.3 Hz, C-5′), 69.3 (C-6), 68.5 (C-6′), 65.4 (d, 3J(C−F) = 9.1 Hz, C-2′), 62.7 (C-5), 57.6 (MeO). 19F NMR (CDCl3, 376 MHz): δ −197.78 (dd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 13.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3079. Data for 2C-α: Rf 0.15 (Et2O/heptane 7:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.56 (dd, 2H, J = 7.3, 2.4 Hz, CHarom), 7.42−7.26 (m, 18H, CHarom), 5.58 (s, 1H, CHPh), 5.17 (dd, 1H, J = 3.5, 3.4 Hz, H-1′), 4.90 (d, 1H, J = 11.1 Hz, CHH O-3′Bn), 4.78 (d, 1H, J = 3.3 Hz, H-1), 4.77 (d, 1H, J = 11.1 Hz, CHH O-3′Bn), 4.73 (ddd, 1H, J = 50.2, 10.0, 8.4 Hz, H-4′), 4.69 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.61 (d, 1H, J = 12.1 Hz, CHH O6′Bn), 4.55 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.47 (d, 1H, J = 12.1 Hz, CHH O-6′Bn), 4.28 (dd, 1H, J = 3.6, 1.2 Hz, H-4), 4.28 (dd, 1H, J = 12.5, 1.6 Hz, H-6), 4.24−4.21 (m, 1H, H-5′), 4.22 (dd, 1H, J = 9.9, 3.6 Hz, H-3), 4.16−4.06 (m, 2H, H-6, H-3′), 4.05 (dd, 1H, J = 9.9, 3.3 Hz, H-2), 3.64−3.56 (m, 3H, H-5, H-6′), 3.38 (s, 3H, MeO), 3.29 (ddd, 1H, J = 10.4, 3.5, 1.1 Hz, H-2′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1, 138.0 (Cq), 137.7 (2Cq), 128.9 (CHarom), 128.6 (4CHarom), 128.5, 128.40, 128.38, 128.2 (4× 2CHarom), 128.13, 128.11 (2× 1CHarom), 127.9 (2CHarom), 127.8 (CHarom), 126.2 (2CHarom), 100.9 (CHPh), 99.0 (C-1), 93.5 (C-1′), 90.5 (d, 1J(C−F) = 183.3 Hz, C-4′), overlapped with CDCl3 (C-3′), 74.8 (d, 4J(C−F) = 2.9 Hz, CH2 O-3′Bn), 74.5 (C-2), 73.7, 73.6 (CH2 Bn), 72.1 (C-4), 71.5 (C-3), 69.6 (C-6), 68.7 (d, 2J(C−F) = 25.0 Hz, C5′), 67.7 (C-6′), 62.2 (C-5), 61.7 (d, 3J(C−F) = 8.1 Hz, C-2′), 57.7 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.81 (dd, 2J(H−F) = 50.3 Hz, 3J(H−F) = 14.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3079. Methyl 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα,β-D-glucopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (2E). Compound 2E was prepared by glycosylation of methyl 2,3,6tri-O-benzyl-α-D-glucopyranoside46 (E) with 2 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:5 afforded first the fraction enriched in α-anomer 2Eα (25 mg, 30%, α/β ca. 4:1) as a colorless syrup, HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3698. Continued elution gave the second fraction enriched in β-anomer 2Eβ (33 mg, 40%, β/α ca. 9:1) as a colorless syrup, HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3697. The combined yield was 70%. NMR data for 2E-α: Rf 0.43 (EtOAc/heptane 1:3), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.41−7.23 (m, 25H, CHarom), 5.71 (dd, 1H, J = 3.9, 3.6 Hz, H-1′), 5.10 (d, 1H, J = 10.7 Hz, CHH Bn), 4.88 (dd, 1H, J = 11.0, 1.1 Hz, CHH O-3′Bn), 4.83 (d, 1H, J = 10.7 Hz, CHH Bn), 4.75 (d, 1H, J = 11.8 Hz, CHH Bn), 4.74 (d, 1H, J = 11.0 Hz, CHH O-3′Bn), 4.63 (ddd, 1H, J = 50.6, 9.9, 8.4 Hz, H-4′), 4.62 (d, 1H, J = 11.8 Hz, CHH Bn), 4.61 (d, 1H, J = 3.6 Hz, H-1), 4.50 (m, 2H, CH2 Bn), 4.49, 4.36 (2× d, 2× 1H, J = 12.3 Hz, CHH Bn), 4.07 (dd, 1H, J = 9.6, 8.5 Hz, H-3), 3.92 from 1 H{19F} (dd, 1H, J = 10.4, 8.4 Hz, H-3′), 3.88 (dd, 1H, J = 9.9, 8.5 Hz, H-4), 3.80 (ddd, 1H, J = 9.9, 4.1, 2.1 Hz, H-5), 3.75 from 1H{19F} (ddd, 1H, J = 10.0, 3.1, 2.6 Hz, H-5′), 3.69 (dd, 1H, J = 11.1, 4.2 Hz, H-6), 3.64 (dd, 1H, J = 11.1, 2.2 Hz, H-6), 3.57 (dd, 1H, J = 9.6, 3.6

Hz, H-2), 3.44 (dd, 1H, J = 10.9, 3.1 Hz, H-6′), 3.39 (s, 3H, MeO), 3.36 (dd, 1H, J = 10.9, 2.6 Hz, H-6′), 3.23 (ddd, 1H, J = 10.3, 3.9, 1.1 Hz, H-2′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.7, 138.13, 138.05, 138.0, 137.8 (Cq), 128.7, 128.6, 128.52, 128.49, 128.48, 128.32, 128.26 (7× 2CHarom), 128.2, 128.1, 127.78, 127.75 (4× 1CHarom), 127.71, 127.70 (2× 2CHarom), 127.6 (CHarom), 127.5 (2CHarom), 97.9 (C-1), 97.4 (d, 4J(C−F) = 1.2 Hz, C-1′), 90.4 (d, 1 J(C−F) = 183.3 Hz, C-4′), 82.1 (C-3), 80.6 (C-2), 77.7 (d, 2J(C−F) = 17.5 Hz, C-3′), 75.2 (CH2 Bn), 74.9 (d, 4J(C−F) = 2.9 Hz, CH2 O3′Bn), 73.7 (CH2 Bn), 73.6 (C-4), 73.54, 73.45 (CH2 Bn), 69.51 (C6), 69.45 (d, 2J(C−F) = 24.4 Hz, C-5′), 69.42 (C-5), 67.5 (C-6′), 62.1 (d, 3J(C−F) = 8.3 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.34 (br dd, 2J(H−F) = 50.7 Hz, 3J(H−F) = 14.0 Hz). NMR data for 2E-β: Rf 0.38 (EtOAc/heptane 1:3), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.43− 7.21 (m, 25H, CHarom), 4.95 (d, 1H, J = 11.3 Hz, CHH O-3Bn), 4.85 (dd, 1H, J = 11.2, 1.0 Hz, CHH O-3′Bn), 4.78 (d, 1H, J = 11.3 Hz, CHH O-3Bn), 4.77 (d, 1H, J = 11.9 Hz, CHH O-6Bn), 4.73 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.73, 4.60 (2× d, 2× 1H, J = 12.2 Hz, CHH O-2Bn), 4.60 (d, 1H, J = 3.7 Hz, H-1), 4.49 (d, 1H, J = 12.2 Hz, CHH O-6′Bn), 4.46 (ddd, 1H, J = 49.7, 9.9, 8.5 Hz, H-4′), 4.41 (d, 1H, J = 11.9 Hz, CHH O-6Bn), 4.36 (d, 1H, J = 12.2 Hz, CHH O6′Bn), 4.16 (d, 1H, J = 7.9 Hz, H-1′), 3.94 (dd, 1H, J = 9.7, 8.7 Hz, H-4), 3.94 (dd, 1H, J = 10.8, 2.5 Hz, H-6), 3.87 (dd, 1H, J = 9.3, 8.7 Hz, H-3), 3.76 (ddd, 1H, J = 9.7, 2.5, 1.9 Hz, H-5), 3.69 (dd, 1H, J = 10.8, 1.9 Hz, H-6), 3.65 (ddd, 1H, J = 11.4, 2.2, 2.0 Hz, H-6′), 3.48 (dd, 1H, J = 9.3, 3.7 Hz, H-2), 3.41 (ddd, 1H, J = 11.4, 5.1, 1.8 Hz, H6′), 3.39 (s, 3H, MeO), 3.30−3.20 (m, 2H, H-2′, H-3′), 3.18 (ddd, 1H, J = 9.9, 5.1, 2.0 Hz, H-5′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.5, 138.5, 138.4, 137.9, 137.7 (Cq), 128.7, 128.6 (2× 2CHarom), 128.5 (4CHarom), 128.43, 128.3, 128.23, 128.15 (4× 2CHarom), 128.13, 128.12 (2× 1CHarom), 128.0 (2CHarom), 127.9, 127.6 (2× 1CHarom), 127.5 (2CHarom), 127.3 (CHarom), 100.7 (d, 4 J(C−F) = 1.2 Hz, C-1′), 98.5 (C-1), 90.3 (d, 1J(C−F) = 183.7 Hz, C-4′), 80.5 (d, 2J(C−F) = 18.1 Hz, C-3′), 80.3 (C-3), 79.2 (C-2), 76.8 (C-4), 75.5 (CH2 Bn), 74.7 (d, 4J(C−F) = 2.6 Hz, CH2 O-3′Bn), 73.71, 73.65, 73.66 (CH2 Bn), 73.4 (d, 2J(C−F) = 24.2 Hz, C-5′), 69.7 (C-5), 68.4 (C-6′), 68.2 (C-6), 65.7 (d, 3J(C−F) = 9.1 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −197.60 (dd, 2J(H−F) = 49.7 Hz, 3J(H−F) = 13.7 Hz). 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-D-glucopyranosyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2F-α) and 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroβ-D-glucopyranosyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2F-β). Compounds 2F-α and 2F-β were prepared by glycosylation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (F) with 2 according to the general procedure. Chromatography in EtOAc/PE 1:5 gave two fractions. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 1:1:2 afforded α-anomer 2F-α as a colorless syrup (17 mg, 27%). Preparative TLC of the slower moving fraction in toluene/Et2O/PE 1:1:3 afforded β-anomer 2F-β as a colorless syrup (26 mg, 41%), and the combined yield was 68%. Data for 2F-α: Rf 0.27 (EtOAc/PE 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.42−7.29 (m, 10H, CHarom), 5.91 (d, 1H, J = 3.6 Hz, H-1), 5.25 (dd, 1H, J = 3.7, 3.5 Hz, H-1′), 4.89 (dd, 1H, J = 10.9, 1.3 Hz, CHH O-3′Bn), 4.77 (d, 1H, J = 10.9 Hz, CHH O-3′Bn), 4.66 (d, 1H, J = 3.6 Hz, H-2), 4.63 (d, 1H, J = 12.1 Hz, CHH O-6′Bn), 4.60 (ddd, 1H, J = 50.5, 10.0, 8.4 Hz, H4′), 4.58 (d, 1H, J = 12.1 Hz, CHH O-6′Bn), 4.45 (ddd, 1H, J = 8.5, 6.2, 5.8 Hz, H-5), 4.28 (d, 1H, J = 2.7 Hz, H-3), 4.16 (dd, 1H, J = 8.5, 6.2 Hz, H-6), 4.08 (dd, 1H, J = 8.5, 2.7 Hz, H-4), 4.01−3.90 (m, 3H, H-6, H-3′, H-5′), 3.78 (dt, 1H, J = 10.9, 2.3 Hz, H-6′), 3.71 (ddd, 1H, J = 10.9, 4.9, 2.0 Hz, H-6′), 3.47 (ddd, 1H, J = 10.3, 3.7, 1.1 Hz, H2′), 1.49, 1.42, 1.35, 1.23 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6′Bn), 137.6 (Cq O4′Bn), 128.62, 128.58, 128.3 (3× 2CHarom), 128.2, 127.9 (2× 1CHarom), 127.8 (2CHarom), 112.2, 109.5 (CMe2), 105.3 (C-1), 98.1 (C-1′), 90.6 (d, 1J(C−F) = 183.9 Hz, C-4′), 83.7 (C-2), 81.6 (C-4), 81.0 (C-3), 77.8 (d, 2J(C−F) = 17.8 Hz, C-3′), 75.1 (d, 4J(C−F) = 2.8 Hz, CH2 O-3′Bn), 73.9 (CH2 O-6′Bn), 72.0 (C-5), 69.7 (d, 2J(C−F) = 24.2 N


Article

The Journal of Organic Chemistry Hz, C-5′), 68.2 (C-6′), 67.9 (C-6), 62.7 (d, 3J(C−F) = 8.4 Hz, C-2′), 27.0, 26.9, 26.3, 25.4 (Me). 19F NMR (CDCl3, 376 MHz): δ −195.12 (dd, 2J(H−F) = 50.6 Hz, 3J(H−F) = 14.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2747. Data for 2F-β: Rf 0.21 (EtOAc/PE 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.29 (m, 10H, CHarom), 5.97 (d, 1H, J = 3.8 Hz, H-1), 4.86, 4.76 (2× d, 2× 1H, J = 11.3 Hz, CHH O-3′Bn), 4.61−4.56 (m, 2H, CH2 O-6′Bn), 5.57 (d, 1H, J = 3.8 Hz, H-2), 4.55 (ddd, 1H, J = 50.0, 9.9, 8.3 Hz, H-4′), 4.42−4.37 (m, 1H, H-5), 4.38 (d, 1H, J = 8.1 Hz, H-1′), 4.35−4.31 (m, 2H, H-3, H-4), 4.07−4.00 (m, 2H, H-6), 3.76 (dt, 2H, J = 11.4, 2.3 Hz, H-6′), 3.68 (ddd, 1H, J = 11.4, 5.0, 2.0 Hz, H-6′), 3.53 from 1 H{19F} (ddd, 1H, J = 9.9, 5.0, 2.3 Hz, H-5′), 3.50 from 1H{19F} (dd, 1H, J = 9.9, 8.3 Hz, H-3′), 3.37 (ddd, 1H, J = 9.9, 8.1, 0.7 Hz, H-2′), 1.51, 1.40, 1.33, 1.30 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.0 (Cq O-6′Bn), 137.5 (Cq O-4′Bn), 128.6 (4CHarom), 128.3 (2CHarom), 128.2, 127.9 (2× 1CHarom), 127.8 (2CHarom), 112.2, 108.8 (CMe2), 105.4 (C-1), 100.3 (C-1′), 90.0 (d, 1 J(C−F) = 183.6 Hz, C-4′), 82.9 (C-2), 81.1 (C-3), 80.4 (C-4), 80.1 (d, 2 J(C−F) = 18.4 Hz, C-3′), 74.8 (d, 4J(C−F) = 2.5 Hz, CH2 O-3′Bn), 74.0 (CH2 O-6′Bn), 73.8 (d, 2J(C−F) = 24.5 Hz, C-5′), 73.2 (C-5), 68.2 (C6′), 66.3 (C-6), 65.2 (d, 3J(C−F) = 9.3 Hz, C-2′), 26.9, 26.8, 26.4, 25.5 (Me). 19F NMR (CDCl3, 376 MHz): δ −197.83 (ddd, 2J(H−F) = 49.5 Hz, 3J(H−F) = 14.9, 2.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2760. Methyl 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα,β-D-glucopyranosyl)-2,3,6-tri-O-benzyl-α-D-galactopyranoside (2G). Compound 2G was prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside46 (G) with 2 according to the general procedure. Column chromatography in EtOAc/PE 1:3 followed by preparative TLC in Et2O/PE 1:1 afforded the product as a syrupy mixture of anomers inseparable under given conditions (55 mg, 66%). Rf 0.32 (EtOAc/heptane 1:3), HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3694. NMR data for the α-anomer of 2G: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.23 (m, 25H, CHarom), 4.95−4.41 (m, 11H, H-1, H-4′, CH2 Bn), 4.91 (dd, 1H, J = 3.7, 3.3 Hz, H-1′), 4.31 (m, 2H, CHH Bn, H-5′), 4.19 (d, 1H, J = 2.6 Hz, H-4), 3.97−3.84 (m, 5H, H-2, H-3, H-5, H-6, H-3′), 3.55 (dd, 1H, J = 12.0, 2.4 Hz, H-6), 3.38 (s, 3H, MeO), 3.31 (dd, 1H, J = 10.4, 3.7 Hz, H-2′), 3.20 (dt, 1H, J = 11.3, 2.4 Hz, H-6′), 3.03 (ddd, 1H, J = 11.3, 2.0, 2.1 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.6, 138.2, 138.1, 137.9, 137.6 (Cq), 128.63, 128.61, 128.56, 128.5, 128.46, 128.4, 128.3 (7× 2CHarom), 128.2, 128.06, 128.04 (3× 1CHarom), 127.88 (2CHarom), 128.85, 127.71 (2× 1CHarom), 127.67, 127.6, (2× 2CHarom), 98.7 (C-1), 98.3 (d, 4J(C−F) = 1.4 Hz, C-1′), 90.3 (d, 1J(C−F) = 182.4 Hz, C-4′), 78.3 (d, 2J(C−F) = 17.5 Hz, C-3′), 77.3 (C-3), 75.3 (C-4), 75.2 (C-2), 75.0 (d, 4J(C−F) = 3.0 Hz, CH2 O-3′Bn), 75.7, 73.52, 73.50, 73.3 (CH2 Bn), 68.9 (C-5), 68.8 (d, 2J(C−F) = 25.1 Hz, C-5′), 65.7 (C-6), 66.8 (C-6′), 62.9 (d, 3 J(C−F) = 8.5 Hz, C-2′), 55.6 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.74 (dd, 2J(H−F) = 50.9 Hz, 3J(H−F) = 14.8 Hz). NMR data for the β-anomer of 2G: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.21 (m, 25H, CHarom), 4.95−4.40 (m, 11H, H-4′, CH2 Bn), 4.75 (d, 1H, J = 8.0 Hz, H-1′), 4.64 (d, 1H, J = 3.7 Hz, H-1), 4.17 (dd, 1H, J = 3.0, 1.2 Hz, H4), 3.96−3.87 (m, 2H, H-3, H-5), 4.10 (dd, 1H, J = 10.1, 3.7 Hz, H2), 3.71−3.65 (m, 2H, H-6, H-6′), 3.61−3.53 (m, 2H, H-6, H-6′), 3.43−3.34 (m, 3H, H-2′, H-3′, H-5′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.1, 138.64, 138.62, 138.0, 137.8 (Cq), 128.54 (4CHarom), 128.52, 128.49, 128.4, 128.3, 128.22 (5× 2CHarom), 128.21, 128.1, 127.8, 127.7, 127.6 (5× 1CHarom), 127.58, 127.5, 127.3 (3× 2CHarom), 101.5 (d, 4J(C−F) = 1.1 Hz, C-1′), 98.9 (C-1), 90.1 (d, 1J(C−F) = 183.4 Hz, C-4′), 80.3 (d, 2 J(C−F) = 18.4 Hz, C-3′), 78.5 (C-3), 76.5 (C-2), 74.9 (d, 4J(C−F) = 2.2 Hz, CH2 O-3′Bn), 74.5 (C-4), 73.9, 73.7, 73.6, 73.4 (CH2 Bn), 73.0 (d, 2J(C−F) = 24.3 Hz, C-5′), 70.1 (C-6), 69.4 (C-5), 68.6 (C-6′), 65.6 (d, 3J(C−F) = 9.2 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −197.81 (dd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 13.1 Hz).

4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-D-glucopyranosyl)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-Dglucopyranose (2H-α) and 4-O-(2-Azido-3,6-di-O-benzyl-2,4dideoxy-4-fluoro-β-D-glucopyranosyl)-1,6-anhydro-2-azido-3O-benzyl-2-deoxy-β-D-glucopyranose (2H-β). Compounds 2H-α and 2H-β were prepared by glycosylation of 1,6-anhydro-2-azido-3-Obenzyl-2-deoxy-β-D-glucopyranoside47 (H) with 2 according to the general procedure. Chromatography of the crude product in PE/ toluene/Et2O 2:1:1 afforded a fraction containing 2H-α, which was purified by preparative TLC in PE/toluene/Et2O 3:1:1 to give 2H-α (20 mg, 31%) as a colorless syrup. Continued elution gave a fraction containing 2H-β, which was purified in the same manner to afford 2H-β (25 mg, 40%) as a colorless syrup. The combined yield was 71%. Data for 2H-α: Rf 0.31 (toluene/Et2O/heptane 1:1:2), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41− 7.28 (m, 15H, CHarom), 5.55 (t, 1H, J = 1.5 Hz, H-1), 4.88 (dd, 1H, J = 11.0, 1.2 Hz, CHH O-3′Bn), 4.86 (d, 1H, J = 3.7 Hz, H-1′), 4.83 (ddd, 1H, J = 6.0, 1.5, 1.2 Hz, H-5), 4.76 (d, 1H, J = 11.0 Hz, CHH O-3′Bn), 4.69 (d, 1H, J = 11.8 Hz, CHH O-3Bn), 4.62 (d, 1H, J = 11.9 Hz, CHH O-6′Bn), 4.57 (d, 1H, J = 11.8 Hz, CHH O-3Bn), 4.54 (d, 1H, J = 11.9 Hz, CHH O-6′Bn), 4.53 (ddd, 1H, J = 50.4, 10.0, 8.3 Hz, H-4′), 4.11 (ddd, 1H, J = 13.8, 10.4, 8.3 Hz, H-3′), 4.30 (ddd, 1H, J = 10.0, 3.3, 2.1 Hz, H-5′), 4.07 (dd, 1H, J = 7.4, 1.2 Hz, H-6en), 3.79−3.74 (m, 2H, H-3, H-6′), 3.70 (ddd, 1H, J = 11.0, 5.4, 2.0 Hz, H-6′), 3.62 (dd, 1H, J = 7.4, 6.0 Hz, H-6ex), 3.52 (q, 1H, J = 1.5 Hz, H-4), 3.29 (ddd, 1H, J = 10.4, 3.7, 1.1 Hz, H-2′), 3.14 (br s, H-2). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.9 (Cq O6′Bn), 137.7 (Cq O-3′Bn), 137.1 (Cq O-3Bn), 128.8, 128.6, 128.5, 128.4 (4× 2CHarom), 128.12 (CHarom), 128.09, 127.9, 127.7 (3× 2CHarom), 100.9 (s, C-1), 101.2 (d, 4J(C−F) = 1.4 Hz, C-1′), 90.7 (d, 1 J(C−F) = 184.7 Hz, C-4′), 78.7 (C-4), 77.7 (C-3), overlapped with CDCl3 (C-3′), 75.1 (d, 4J(C−F) = 2.8 Hz, CH2 O-3′Bn), 74.8 (C-5), 73.8 (CH2 O-6′Bn), 73.0 (CH2 O-3Bn), 69.5 (d, 2J(C−F) = 24.5 Hz, C-5′), 68.4 (C-6′), 65.0 (C-6), 62.3 (d, 3J(C−F) = 8.4 Hz, C-2′), 58.9 (C-2). 19F NMR (CDCl3, 376 MHz): δ −196.14 (dd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 14.0 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2566. Data for 2H-β: Rf 0.25 (toluene/Et2O/heptane 1:1:2), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41− 7.24 (m, 15H, CHarom), 5.50 (t, 1H, J = 1.6 Hz, H-1), 4.86, 4.77 (2× d, 2× 1H, J = 11.2 Hz, CHH O-3′Bn), 4.67 (m, 1H, H-5), 4.58 (d, 1H, J = 11.9 Hz, CHH O-3Bn), 4.54 (m, 2H, CH2 O-6′Bn), 4.51 (d, 1H, J = 11.9 Hz, CHH O-3Bn), 4.50 (ddd, 1H, J = 50.0, 9.9, 8.1 Hz, H-4′), 4.35 (d, 1H, J = 7.7 Hz, H-1′), 4.09 (dd, 1H, J = 7.4, 1.2 Hz, H-6en), 3.98 (q, 1H, J = 1.6 Hz, H-3), 3.78−3.73 (m, 3H, H-4, H-6ex, H-6′), 3.68−3.66 (m, 1H, H-6′), 3.54−3.43 (m, 3H, H-2′, H-3′, H5′), 3.20 (q, 1H, J = 1.6 Hz, H-2). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6′Bn), 137.7 (Cq O-3′Bn), 137.6 (Cq O-3Bn), 128.64, 128.59, 128.58, 128.3 (4× 2CHarom), 128.2, 128.1, 128.0 (3× 1CHarom), 127.84, 127.81 (2× 2CHarom), 102.1 (d, 4 J(C−F) = 1.5 Hz, C-1′), 100.8 (s, C-1), 90.0 (d, 1J(C−F) = 183.7 Hz, C4′), 80.2 (d, 2J(C−F) = 18.3 Hz, C-3′), 77.4 (C-4), 77.3 (C-3), 74.9 (d, 4 J(C−F) = 2.5 Hz, CH2 O-3′Bn), 74.7 (C-5), 73.8 (CH2 O-6′Bn), 73.4 (d, 2J(C−F) = 24.4 Hz, C-5′), 72.7 (CH2 O-3Bn), 69.4 (C-6′), 65.1 (C6), 65.0 (d, 3J(C−F) = 8.9 Hz, C-2′), 59.6 (C-2). 19F NMR (CDCl3, 376 MHz): δ −197.66 (ddd, 2J(H−F) = 50.0 Hz, 3J(H−F) = 13.4, 1.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2568. Methyl 2-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-glucopyranosyl)-4,6-O-benzylidene-3-O-benzyl-α-D-mannopyranoside (2I-α) and Methyl 2-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-β-D-glucopyranosyl)-4,6-O-benzylidene-3-O-benzyl-α-D-mannopyranoside (2I-β). Compounds 2Iα and 2I-β were prepared by glycosylation of methyl 4,6-Obenzylidene-3-O-benzyl-α-D-manopyranoside48 (I) with 2 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:5 afforded a fraction containing 2I-α, which was purified by preparative TLC in PE/toluene/Et2O 3:1:1 to give 2I-α (22 mg, 30%) as a colorless syrup. Continued elution gave a fraction O


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1H, J = 5.9, 3.2, 1.1 Hz, H-4), 3.89 (ddd, 1H, J = 11.2, 10.2, 8.1 Hz, H-2), 3.68 (tt, 1H, J = 9.3, 3.9 Hz, CH cyclohexyl), 3.61−3.59 (m, 2H, H-6), 3.51 (ddd, 1H, J = 7.0, 5.6, 1.1 Hz, H-5), 1.93−1.89 (m, 2H, CH2 cyclohexyl), 1.78−1.72 (m, 2H, CH2 cyclohexyl), 1.52−1.39 (m, 3H, CH2 cyclohexyl), 1.31−1.21 (m, 3H, CH2 cyclohexyl). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.94, 137.90 (Cq), 128.6 (4CHarom), 128.4 (2CHarom), 128.00, 127.98 (2× 1CHarom), 127.9 (2CHarom), 100.4 (d, 3J(C−F) = 10.5 Hz, C-1), 92.9 (d, 1J(C−F) = 191.3 Hz, C-3), 78.3 (CH cyclohexyl), 74.9 (d, 4J(C−F) = 4.0 Hz, CH2 O-4Bn), 73.7 (CH2 O-6Bn), 73.0 (d, 2J(C−F) = 15.0 Hz, C-4), 72.4 (d, 3J(C−F) = 7.8 Hz, C-5), 68.4 (d, 4J(C−F) = 2.9 Hz, C-6), 62.5 (d, 2J(C−F) = 17.0 Hz, C-2), 33.5, 31.7, 25.7, 24.1, 23.9 (5× CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −194.40 (ddd, 2J(H−F) = 47.7 Hz, 3J(H−F) = 11.2, 5.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2381. Data for 3A-α: Rf 0.36 (EtOAc/heptane 1:7), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.35−7.26 (m, 10H, CHarom), 5.08 (dd, 1H, J = 4.9, 3.7 Hz, H-1), 5.01 (ddd, 1H, J = 49.6, 10.5, 3.2 Hz, H-3), 4.86, 4.54 (2× d, 2× 1H, J = 11.4 Hz, CHH O4Bn), 4.50, 4.43 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6Bn), 4.12 (ddd, 1H, J = 4.8, 3.2, 1.3 Hz, H-4), 4.07 (ddd, 1H, J = 7.2, 5.8, 1.3 Hz, H5), 3.79 (ddd, 1H, J = 10.5, 8.9, 3.7 Hz, H-2), 3.63−3.54 (m, 3H, H-6, CH cyclohexyl), 1.90−1.82 (m, 2H, CH2 cyclohexyl), 1.76−1.69 (m, 2H, CH2 cyclohexyl), 1.49−1.52 (m, 1H, CH2 cyclohexyl), 1.43−1.39 (m, 2H, CH2 cyclohexyl), 1.29−1.23 (m, 3H, CH2 cyclohexyl). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.03, 137.98 (Cq), 128.6, 128.5, 128.4 (3× 2CHarom), 128.0, 127.9 (2× 1CHarom), 127.8 (2CHarom), 97.1 (d, 3J(C−F) = 9.1 Hz, C-1), 90.2 (d, 1J(C−F) = 187.9 Hz, C-3), 77.4 (CH cyclohexyl), 75.2 (d, 4J(C−F) = 3.9 Hz, CH2 O-4Bn), 74.7 (d, 2J(C−F) = 15.3 Hz, C-4), 73.6 (CH2 O-6Bn), 69.1 (d, 3 J(C−F) = 6.8 Hz, C-5), 68.5 (d, 4J(C−F) = 2.4 Hz, C-6), 58.8 (d, 2J(C−F) = 17.2 Hz, C-2), 33.4, 31.5, 25.7, 24.1, 23.9 (5× CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −199.62 (dddd, 2J(H−F) = 49.6 Hz, 3 J(H−F) = 8.9, 6.8 Hz, 4J(H−F) = 4.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2388. Methyl 6-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (3B-α) and Methyl 6-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy3-fluoro-β-D-galactopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (3B-β). Compounds 3B-β and 3B-α were prepared by glycosylation of methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside45 (B) with β-3 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:4 gave the product in two fractions. The slower moving fraction afforded β-anomer 3B-β (44 mg, 53%) as a crystalline compound. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 1:1:2 gave syrupy 3B-α (13 mg, 16%) as the less polar component and crystalline β-anomer 3B-β (15 mg, 18%, combined yield of 3B-β 71%) as the more polar component. The combined yield of both anomers was 87%. Data for 3B-β: Rf 0.16 (EtOAc/heptane 1:5), mp 116−118 °C (heptane). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.36−7.24 (m, 25H, CHarom), 4.98 (d, 1H, J = 11.0 Hz, CHH Bn), 4.91 (d, 1H, J = 11.1 Hz, CHH O-4′Bn), 4.84 (d, 1H, J = 11.4 Hz, CHH Bn), 4.81 (d, 1H, J = 11.0 Hz, CHH Bn), 4.78, 4.64 (2× d, 2× 1H, J = 11.9 Hz, CHH Bn), 4.62 (d, 1H, J = 11.1 Hz, CHH O-4′Bn), 4.59 (d, 1H, J = 3.6 Hz, H-1), 4.52 (d, 1H, J = 11.4 Hz, CHH Bn), 4.43, 4.39 (2× d, 2× 1H, J = 11.9 Hz, CHH Bn), 4.34 (ddd, 1H, J = 47.6, 10.1, 3.2 Hz, H-3′), 4.12 (d, 1H, J = 8.0 Hz, H-1′), 4.08 (dd, 1H, J = 10.9, 2.0 Hz, H-6), 3.97−4.01 (m, 2H, H-3, H-4′), 3.94 (ddd, 1H, J = 11.1, 10.1, 8.0 Hz, H-2′), 3.80 (ddd, 1H, J = 10.1, 5.1, 2.0 Hz, H-5), 3.64 (dd, 1H, J = 10.9, 5.1 Hz, H-6), 3.63 (dd, 1H, J = 7.4, 1.7 Hz, H-6′), 3.60−3.45 (m, 4H, H-2, H-4, H-5′, H-6′), 3.37 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.9, 138.5, 138.3, 138.0, 137.8 (Cq), 128.60, 128.59, 128.55, 128.5, 128.4, 128.32, 128.30, 128.1 (8× 2CHarom), 128.04, 128.03, 127.96 (3× 1CHarom), 127.95, 127.9 (2× 2CHarom), 127.8, 127.7 (2× 1CHarom), 102.0 (d, 3J(C−F) = 10.5 Hz, C-1′), 98.2 (C-1), 93.2 (d, 1J(C−F) = 190.9 Hz, C-3′), 82.2 (C-3), 80.0 (C-2), 78.0 (C-4), 75.9 (CH2 Bn), 75.0 (d, 4J(C−F) = 3.6 Hz, CH2 O-4′Bn), 74.96, 73.7, 73.6 (CH2 Bn), 73.2 (d, 2J(C−F) = 15.0 Hz, C-4′), 72.4 (d, 3J(C−F) = 7.7 Hz, C-5′), 69.9 (C-

containing 2I-β, which was purified on Sephadex LH20 in dichloromethane/methanol 1:1 to give 2I-β (31 mg, 42%) as a colorless syrup. The combined yield was 72%. Data for 2I-α: Rf 0.46 (EtOAc/heptane 1:3), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.49 (dd, 2H, J = 7.7, 2.1 Hz, CHarom), 7.44−7.27 (m, 18H, CHarom), 5.65 (s, 1H, CHPh), 5.30 (dd, 1H, J = 3.8, 3.5 Hz, H-1′), 4.92 (dd, 1H, J = 10.9, 0.9 Hz, CHH O-3′Bn), 4.89 (d, 1H, J = 12.0 Hz, CHH O-3Bn), 4.82 (d, 1H, J = 10.9 Hz, CHH O-3′Bn), 4.78 (d, 1H, J = 1.7 Hz, H-1), 4.69 (d, 1H, J = 12.0 Hz, CHH O-3Bn), 4.62, 4.57 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6′Bn), 4.57 (ddd, 1H, J = 50.6, 10.7, 8.4 Hz, H-4′), 4.28−4.22 (m, 2H, H-4, H-6), 4.11 (ddd, 1H, J = 14.4, 10.4, 8.4 Hz, H-3′), 4.07 (dd, 1H, J = 3.3, 1.7 Hz, H-2), 4.04−3.97 (m, 2H, H-3, H5′), 3.88 (t, 1H, J = 10.2 Hz, H-6), 3.81−3.73 (m, 1H, H-5), 3.75 from 1H{19F} (dd, 1H, J = 10.8, 1.9 Hz, H-6′), 3.69 from 1H{19F} (dd, 1H, J = 10.8, 5.1 Hz, H-6′), 3.30 (ddd, 1H, J = 10.4, 3.8, 0.9 Hz, H-2′), 3.25 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.7, 137.9, 137.8, 137.7 (Cq), 129.0 (CHarom), 128.61, 128.55, 128.5, 128.3, 128.2 (5× 2CHarom), 128.1, 127.9 (2× 1CHarom), 127.8 (2CHarom), 127.6 (CHarom), 127.5, 126.2 (2× 2CHarom), 101.7 (CHPh), 100.8 (C-1), 99.4 (C-1′), 90.8 (d, 1J(C−F) = 184.0 Hz, C-4′), 79.5 (C-4), 77.3 (d, 2J(C−F) = 19.7 Hz, C-3′), 76.7 (C-2), 75.6 (C-3), 75.0 (d, 4J(C−F) = 2.9 Hz, CH2 O-3′Bn), 73.8 (CH2 O-6′Bn), 73.3 (CH2 O-3Bn), 69.5 (d, 2J(C−F) = 24.2 Hz, C-5′), 69.1 (C-6), 68.3 (C-6′), 64.1 (C-5), 62.4 (d, 3J(C−F) = 8.1 Hz, C-2′), 55.0 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.15 (dd, 2J(H−F) = 50.7 Hz, 3J(H−F) = 14.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3071. Data for 2I-β: Rf 0.33 (EtOAc/heptane 1:3), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC. HMBC): δ 7.49 (dd, 2H, J = 7.6, 2.0 Hz, CHarom), 7.42−7.22 (m, 18H, CHarom), 5.60 (s, 1H, CHPh), 4.85 (d, 1H, J = 11.4 Hz, CHH O-3′Bn), 4.81 (d, 1H, J = 1.6 Hz, H-1), 4.79 (d, 1H, J = 12.0 Hz, CHH O-3Bn), 4.78 (d, 1H, J = 11.4 Hz, CHH O-3′Bn), 4.66 (d, 1H, J = 12.0 Hz, CHH O-3Bn), 4.54 (br s, 2H, CH2 O-6′Bn), 4.47 (ddd, 1H, J = 49.8, 9.8, 8.3 Hz, H-4′), 4.39 (d, 1H, J = 8.0 Hz, H-1′), 4.26 (dd, 1H, J = 3.4, 1.6 Hz, H-2), 4.25 (dd, 1H, J = 10.2, 4.3 Hz, H-6), 4.15 (dd, 1H, J = 10.1, 9.2 Hz, H-4), 3.94 (dd, 1H, J = 10.1, 3.4 Hz, H-3), 3.85 (t, 1H, J = 10.2, Hz, H-6), 3.78 from 1H{19F} (dd, 1H, J = 10.9, 1.8 Hz, H-6′), 3.77 (ddd, 1H, J = 10.2, 9.2, 4.3 Hz, H-5), 3.68 (ddd, 1H, J = 10.9, 6.0, 1.9 Hz, H-6′), 3.59 from 1H{19F} (ddd, 1H, J = 9.8, 6.0, 1.8 Hz, H-5′), 3.57 (dd, 1H, J = 10.0, 8.0 Hz, H-2′), 3.45 (ddd, 1H, J = 14.9, 10.0, 8.3 Hz, H-3′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.5 (Cq O-3Bn), 137.9 (Cq O-6′Bn), 137.8 (Cq), 137.7 (Cq O-3′Bn), 128.9 (CHarom), 128.56, 128.55, 128.34, 128.28, 128.26 (5× 2CHarom), 128.1, 127.9 (2× 1CHarom), 127.82, 127.78 (2× 2CHarom), 127.5 (CHarom), 126.2 (2CHarom), 101.6 (CHPh), 101.0 (C-1′), 99.5 (C-1), 90.2 (d, 1J(C−F) = 184.1 Hz, C-4′), 79.9 (d, 2J(C−F) = 18.2 Hz, C-3′), 78.2 (C-4), 75.3 (C-2), 74.8 (d, 4J(C−F) = 2.2 Hz, CH2 O-3′Bn), 73.92 (CH2 O-6′Bn), 73.89 (C-3), 73.7 (d, 2J(C−F) = 24.2 Hz, C-5′), 71.5 (CH2 O-3Bn), 69.2 (C-6′), 69.0 (C-6), 65.4 (d, 3 J(C−F) = 9.4 Hz, C-2′), 64.3 (C-5), 55.1 (MeO). 19F NMR (CDCl3, 376 MHz): δ −197.82 (ddd, 2J(H−F) = 49.8 Hz, 3J(H−F) = 14.9, 2.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3068. Cyclohexyl 2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-αD-galactopyranoside (3A-α) and Cyclohexyl 2-Azido-4,6-di-Obenzyl-2,3-dideoxy-3-fluoro-β-D-galactopyranoside (3A-β). Compounds 3A-α and 3A-β were prepared by glycosylation of cyclohexanol with β-3 according to the general procedure. Column chromatography in toluene/Et2O/PE 1:1:5 gave two fractions. The faster moving fraction afforded α-anomer 3A-α as a colorless syrup (5 mg, 10%). Preparative TLC of the slower moving fraction in toluene/ Et2O/PE 1:1:6 afforded β-anomer 3A-β as a colorless syrup (28 mg, 59%). The combined yield was 69%. Data for 3A-β: Rf 0.25 (EtOAc/heptane 1:7), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.35−7.25 (m, 10H, CHarom), 4.86, 4.55 (2× d, 2× 1H, J = 11.5 Hz, CHH O-4Bn), 4.45, 4.41 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6Bn), 4.34 (d, 1H, J = 8.1 Hz, H-1), 4.32 (ddd, 1H, J = 47.7, 10.2, 3.2 Hz, H-3), 3.96 (ddd, P


Article


APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3056. Selected NMR resonances for 3C-β: 1H NMR (CDCl3, 400 MHz, 1 H{19F}, H−H COSY, HSQC): δ 5.52 (s, 1H, CHPh), 4.75 (d, 1H, J = 8.1 Hz, H-1′), 4.69 (d, 1H, J = 3.6 Hz, H-1), 4.31 (ddd, 1H, J = 47.7, 10.3, 3.3 Hz, H-3′), 4.15 (dd, 1H, J = 10.1, 3.6 Hz, H-2), 4.02 (ddd, 1H, J = 10.7, 10.5, 8.1 Hz, H-2′), 3.59 (br s, 1H, H-5), 3.34 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 102.6 (d, 3 J(C−F) = 10.5 Hz, C-1′), 100.4 (CHPh), 99.0 (C-1), 76.9 (overlapped with CDCl3 C-2), 76.5 (C-4), 69.3 (C-6), 62.4 (d, 2J(C−F) = 17.3 Hz, C-2′), 62.8 (C-5), 55.6 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.40 (ddd, 2J(H−F) = 47.7 Hz, 3J(H−F) = 10.7, 5.7 Hz). Methyl 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-2,4,6-tri-O-methyl-α-D-galactopyranoside (3D-α) and Methyl 3-O-(2-Azido-4,6-di-O-benzyl-2,3dideoxy-3-fluoro-β-D-galactopyranosyl)-2,4,6-tri-O-methyl-αD-galactopyranoside (3D-β). Compounds 3D-α and 3D-β were prepared by glycosylation of methyl 2,4,6-tri-O-methyl-α-D-galactopyranoside (D) with β-3 according to the general procedure. Column chromatography in EtOAc/PE 1:2 gave the product in two fractions. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 1:2:1 afforded 3D-α (15 mg, 24%) as a colorless gum. Preparative TLC of the slower moving fraction in toluene/Et2O/PE 1:2:1 afforded 3D-β (24 mg, 39%) as a colorless syrup. The combined yield was 63%. Data for 3D-α: Rf 0.14 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.33−7.27 (m, 10H, CHarom), 5.13 (dd, 1H, J = 4.5, 3.6 Hz, H-1′), 5.05 (ddd, 1H, J = 49.7, 10.5, 3.1 Hz, H-3′), 4.88 (d, 1H, J = 3.7 Hz, H-1), 4.85, 4.56 (2× d, 2× 1H, J = 11.2 Hz, CHH O-4′Bn), 4.49, 4.43 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6′Bn), 4.32 (dddd, 1H, J = 7.8, 6.0, 1.5, 1.3 Hz, H-5′), 4.18 (ddd, 1H, J = 7.2, 3.1, 1.4 Hz, H-4′), 4.00 from 1H{19F} (dd, 1H, J = 10.2, 2.9 Hz, H-3), 4.00 from 1H{19F} (dd, 1H, J = 10.5, 3.6 Hz, H-2′), 3.83 (dd, 1H, J = 7.1, 6.3 Hz, H-5), 3.67−3.59 (m, 4H, H-2, H-4, H-6′), 3.62 (s, 3H, MeO), 3.56 (dd, 1H, J = 9.3, 7.1 Hz, H6), 3.51 (dd, 1H, J = 9.3, 6.3 Hz, H-6), 3.43, 3.40, 3.37 (3× s, 3× 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (2× Cq), 128.49, 128.48, 128.4 (3× 2CHarom), 127.99 (CHarom), 127.98 (2CHarom), 127.8 (CHarom), 97.7 (C-1), 95.6 (d, 3J(C−F) = 9.2 Hz, C-1′), 90.7 (d, 1J(C−F) = 188.0 Hz, C-3′), 77.2 (C-2), 75.8 (C-4), 75.3 (d, 4J(C−F) = 3.5 Hz, CH2 O-4′Bn), 74.69 (d, 2J(C−F) = 15.1 Hz, C-4′), 74.69 (C-3), 73.3 (CH2 O-6′Bn), 71.2 (C-6), 68.9 (C-5), 68.7 (d, 3J(C−F) = 6.6 Hz, C-5′), 67.8 (d, 4J(C−F) = 2.3 Hz, C-6′), 61.4, 59.33 (MeO), 59.31 (d, 2J(C−F) = 17.5 Hz, C-2′), 59.1, 55.4 (MeO). 19 F NMR (CDCl3, 376 MHz): δ −199.67 (dddd, 2J(H−F) = 49.7 Hz, 3 J(H−F) = 8.8, 7.2 Hz, 4J(H−F) = 4.5 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C30H41FNO9, 578.2759; found, 578.2761. Data for 3D-β: Rf 0.10 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.36−7.26 (m, 10H, CHarom), 4.92 (d, 1H, J = 3.6 Hz, H-1), 4.86 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.64 (dd, 1H, J = 7.9, 0.7 Hz, H-1′), 4.56 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.43 (s, 2H, CH2 O-6′Bn), 4.31 (ddd, 1H, J = 47.6, 10.3, 3.3 Hz, H-3′), 4.05 (dd, 1H, J = 10.2, 3.0 Hz, H-3), 3.98 (dd, 1H, J = 5.7, 3.3 Hz, H-4′), 3.89−3.86 (m, 2H, H-5, H-2′), 3.79 (dd, 1H, J = 10.2, 3.6 Hz, H-2), 3.65 (dd, 1H, J = 3.0, 1.2 Hz, H-4), 3.63−3.50 (m, 5H, H-6, H-5′, H-6′), 3.56, 3.52, 3.42, 3.37 (4× s, 4× 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (Cq O-4′Bn), 137.9 (Cq O-6′Bn), 128.6, 128.4, 128.3 (3× 2CHarom), 128.0, 127.9 (2× 1CHarom), 127.8 (2CHarom), 102.6 (d, 3 J(C−F) = 10.6 Hz, C-1′), 97.4 (C-1), 92.6 (d, 1J(C−F) = 191.2 Hz, C3′), 79.2 (C-4), 78.7 (C-2), 77.1 (C-3), 75.0 (d, 4J(C−F) = 3.8 Hz, CH2 O-4′Bn), 73.6 (CH2 O-6′Bn), 73.2 (d, 2J(C−F) = 15.1 Hz, C-4′), 72.0 (d, 3J(C−F) = 7.5 Hz, C-5′), 71.5 (C-6), 69.3 (C-5), 67.8 (d, 4J(C−F) = 2.7 Hz, C-6′), 62.7 (d, 2J(C−F) = 17.4 Hz, C-2′), 61.5, 59.4, 58.4, 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.32 (ddd, 2J(H−F) = 47.5 Hz, 3J(H−F) = 10.8, 5.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C30H41FNO9, 578.2759; found, 578.2762. Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (3E-α) and Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-

5), 68.7 (C-6), 67.9 (d, 4J(C−F) = 2.2 Hz, C-6′), 62.5 (d, 2J(C−F) = 17.8 Hz, C-2′), 55.4 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.12 (ddd, 2J(H−F) = 47.6 Hz, 3J(H−F) = 11.1, 5.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3692. Data for 3B-α: Rf 0.21 (EtOAc/heptane 1:5), 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.37−7.27 (m, 25H, CHarom), 5.01 (dd, 1H, J = 4.7, 3.6 Hz, H-1′), 4.98 (d, 1H, J = 10.9 Hz, CHH Bn), 4.90, 4.85 (2× d, 2× 1H, J = 11.1 Hz, CHH O-4′Bn), 4.83 (ddd, 1H, J = 49.4, 10.5, 3.1 Hz, H-3′), 4.80 (d, 1H, J = 10.9 Hz, CHH Bn), 4.78, 4.65 (2× d, 2× 1H, J = 12.0 Hz, CHH Bn), 4.58 (d, 1H, J = 11.3 Hz, CHH Bn), 4.57 (d, 1H, J = 3.1 Hz, H-1), 4.52 (d, 1H, J = 11.3 Hz, CHH Bn), 4.44, 4.37 (2× d, 2× 1H, J = 11.8 Hz, CHH Bn), 4.07 (ddd, 1H, J = 6.9, 3.1, 1.3 Hz, H-4′), 4.03 (t, 1H, J = 9.1 Hz, H-3), 3.93 (tdd, 1H, J = 6.9, 1.8, 1.3 Hz, H-5′), 3.86 (ddd, 1H, J = 10.5, 9.0, 3.6 Hz, H-2′), 3.79 (dd, 1H, J = 9.9, 4.5 Hz, H-6), 3.75 (ddd, 1H, J = 10.1, 4.5, 1.9 Hz, H-5), 3.67 (dd, 1H, J = 9.9, 1.9 Hz, H-6), 3.58−3.49 (m, 4H, H-2, H-4, H-6′), 3.36 (s, 3H, MeO). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.9, 138.34, 138.25, 137.94, 137.90 (Cq), 128.59, 128.56, 128.55, 128.54, 128.50, 128.4, 128.3, 128.13 (8× 2CHarom), 128.05, 128.04 (2× 1CHarom), 127.98 (2CHarom), 127.93, 127.88 (2× 1CHarom), 127.81 (2CHarom), 127.75 (CHarom), 98.9 (d, 3J(C−F) = 9.1 Hz, C-1′), 98.1 (C-1), 90.1 (d, 1J(C−F) = 188.5 Hz, C-3′), 82.1 (C-3), 80.2 (C-2), 77.8 (C-4), 75.9 (CH2 Bn), 75.2 (d, 4J(C−F) = 4.1 Hz, CH2 O-4′Bn), 75.1 (CH2 Bn), 74.5 (d, 2 J(C−F) = 15.3 Hz, C-4′), 73.58, 73.55 (CH2 Bn), 70.1 (C-5), 69.1 (d, 3 J(C−F) = 6.9 Hz, C-5′), 68.2 (d, 4J(C−F) = 1.6 Hz, C-6′), 66.9 (C-6), 59.0 (d, 2J(C−F) = 17.4 Hz, C-2′), 55.3 (MeO). 19F NMR (CDCl3, 376 MHz): δ −198.45 (dddd, 2J(H−F) = 49.4 Hz, 3J(H−F) = 8.7, 6.7 Hz, 4 J(H−F) = 4.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3699. In another experiment, 60 mg (0.297 mmol, 3 equiv) of Ph2SO was used, while other conditions remained identical as before. The anomeric ratio determined after workup was α/β 1:1.6. The products were not isolated. Methyl 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside (3C-α). Compound 3C-α was prepared by glycosylation of methyl 2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside11 (C) with β-3 according to the general procedure. Column chromatography in Et2O/PE 2:1 followed by preparative TLC in EtOAc/PE 2:5 gave 3C-α as a faster moving fraction which crystallized on standing (55 mg, 74%). The slower moving fraction contained both anomers of 3C and impurities (5 mg, α/β 10:7); this fraction was used to obtain NMR data for β-anomer 3C-β. Data for 3C-α: Rf 0.25 (EtOAc/heptane 1:2), mp 152−155 °C (heptane/EtOAc). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.56 (dd, 2H, J = 7.6, 1.8 Hz, CHarom), 7.39−7.27 (m, 18H, CHarom), 5.57 (s, 1H, CHPh), 5.22 (dd, 1H, J = 4.1, 3.6 Hz, H-1′), 4.89 (ddd, 1H, J = 49.1, 10.5, 3.1 Hz, H-3′), 4.83 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.74 (d, 1H, J = 3.5 Hz, H-1), 4.72, 4.62 (2× d, 2× 1H, J = 12.0 Hz, CHH O-2Bn), 4.52 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.43, 4.39 (2× d, 2× 1H, J = 12.2 Hz, CHH O-6′Bn), 4.37 (dd, 1H, J = 3.6, 1.3 Hz, H-4), 4.28−4.25 (m, 2H, H-6, H-5′), 4.21 (dd, 1H, J = 10.1, 3.6 Hz, H-3), 4.10−4.00 (m, 2H, H-2, H-6), 4.02 (ddd, 1H, J = 6.9, 3.1, 1.3 Hz, H-4′), 3.81 (ddd, 1H, J = 10.5, 8.7, 3.6 Hz, H-2′), 3.62 (p, 1H, J = 1.3 Hz, H-5), 3.61−3.52 (m, 2H, H-6′), 3.37 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.5 (Cq O-2Bn), 138.1 (Cq O-6′Bn), 138.0 (Cq O-4′Bn), 137.7 (Cq), 128.9 (CHarom), 128.6, 128.48, 128.46, 128.4, 128.22, 128.19 (6× 2CHarom), 128.1, 128.0 (2× 1CHarom), 127.9 (2CHarom), 127.8 (CHarom), 126.1 (2CHarom), 100.8 (CHPh), 99.2 (C-1), 94.4 (d, 3J(C−F) = 9.2 Hz, C-1′), 89.7 (d, 1J(C−F) = 188.2 Hz, C3′), 75.3 (d, 4J(C−F) = 3.7 Hz, CH2 O-4′Bn), 74.9 (C-2), 74.7 (d, 2 J(C−F) = 15.2 Hz, C-4′), 73.8 (CH2 O-2Bn), 73.2 (CH2 O-6′Bn), 72.1 (C-4), 71.5 (C-3), 69.6 (C-6), 68.9 (d, 3J(C−F) = 6.7 Hz, C-5′), 67.9 (d, 4J(C−F) = 2.3 Hz, C-6′), 62.2 (C-5), 58.3 (d, 2J(C−F) = 17.5 Hz, C-2′), 55.7 (MeO). 19F NMR (CDCl3, 376 MHz): δ −199.93 (dddd, 2 J(H−F) = 49.3 Hz, 3J(H−F) = 8.7, 6.9 Hz, 4J(H−F) = 4.1 Hz). HRMSQ


Article

The Journal of Organic Chemistry 3-fluoro-β-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (3E-β). Compounds 3E-α and 3E-β were prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside46 (E) with β-3 according to the general procedure. Column chromatography in Et2O/PE 2:3 followed by preparative TLC in Et2O/PE 5:9 afforded colorless syrupy α-anomer 3E-α (27 mg. 32%) as the faster moving fraction and colorless syrupy β-anomer 3E-β (32 mg, 38%) as the slower moving fraction. The combined yield was 70%. Data for 3E-α: Rf 0.40 (Et2O/heptane 1:1). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.35−7.18 (m, 25H, CHarom), 5.74 (dd, 1H, J = 4.3, 4.0 Hz, H-1′), 5.09, 4.85 (2× d, 2× 1H, J = 10.6 Hz, CHH O-3Bn), 4.81 (ddd, 1H, J = 49.7, 10.7, 3.1 Hz, H-3′), 4.80 (d, 1H, J = 11.3 Hz, CHH O-4′Bn), 4.74, 4.61 (2× d, 2× 1H, J = 12.0 Hz, CHH O-2Bn), 4.59 (d, 1H, J = 3.5 Hz, H-1), 4.55 (d, 1H, J = 12.2 Hz, CHH O-6Bn), 4.49 (d, 1H, J = 11.3 Hz, CHH O4′Bn), 4.42 (d, 1H, J = 12.2 Hz, CHH O-6Bn), 4.28, 4.20 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6′Bn), 4.06 (dd, 1H, J = 9.6, 8.4 Hz, H-3), 3.98 (ddd, 1H, J = 7.2, 3.1, 1.3 Hz, H-4′), 3.85−3.74 (m, 4H, H-4, H5, H-2′, H-5′), 3.61 (m, 2H, H-6), 3.55 (dd, 1H, J = 9.6, 3.5 Hz, H-2), 3.45 (dd, 1H, J = 8.9, 7.7 Hz, H-6′), 3.39 (s, 3H, MeO), 3.37 from 1 H{19F} (dd, 1H, J = 8.9, 5.3 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7, 138.4, 138.0, 137.90, 137.85 (Cq), 128.6, 128.53 (2× 2CHarom), 128.50 (6CHarom), 128.4, 128.3 (2× 2CHarom), 128.15, 128.09 (2× 1CHarom), 127.9 (3CHarom), 127.7 (2CHarom), 127.62, 127.59 (2× 1CHarom), 127.48 (2CHarom), 98.4 (d, 3 J(C−F) = 9.0 Hz, C-1′), 97.8 (C-1), 90.2 (d, 1J(C−F) = 188.6 Hz, C-3′), 80.0 (C-3), 80.6 (C-2), 75.1 (d, 4J(C−F) = 4.3 Hz, CH2 O-4′Bn), 75.1 (CH2 O-3Bn), 74.3 (d, 2J(C−F) = 15.2 Hz, C-4′), 73.7 (C-4), 73.5 (CH2 O-6′Bn), 73.4 (CH2 O-2Bn), 73.2 (CH2 O-6Bn), 69.6 (d, 3 J(C−F) = 7.2 Hz, C-5′), 69.49, 69.47 (C-5/6), 68.1 (d, 4J(C−F) = 2.0 Hz, C-6′), 58.8 (d, 2J(C−F) = 17.0 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −199.43 (m). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3692. Data for 3E-β: Rf 0.30 (Et2O/heptane 1:1). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.34−7.12 (m, 25H, CHarom), 4.92 (d, 1H, J = 10.6 Hz, CHH O-3Bn), 4.86 (d, 1H, J = 11.3 Hz, CHH O-4′Bn), 4.81 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.70 (d, 1H, J = 12.1 Hz, CHH O-6Bn), 4.75 (d, 1H, J = 10.6 Hz, CHH O3Bn), 4.63 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.59 (d, 1H, J = 3.7 Hz, H-1), 4.51 (d, 1H, J = 11.9 Hz, CHH O-4′Bn), 4.43 (d, 1H, J = 12.1 Hz, CHH O-6Bn), 4.34, 4.22 (2× d, 2× 1H, J = 11.2 Hz, CHH O-6′Bn), 4.13 (d, 1H, J = 7.7 Hz, H-1′), 4.11 (ddd, 1H, J = 48.0, 10.1, 3.1 Hz, H-3′), 3.96−3.91 (m, 3H, H-4, H-6, H-4′), 3.87−3.81 (m, 2H, H-3, H-2′), 3.76 (ddd, 1H, J = 10.0, 2.6, 1.8 Hz, H-5), 3.70 (dd, 1H, J = 10.8, 1.8 Hz, H-6), 3.51−3.47 (m, 2H, H-2, H-6′), 3.32 (ddd, 1H, J = 9.1, 5.2, 1.8 Hz, H-6′), 3.21 (dd, 1H, J = 8.4, 5.2 Hz, H-5′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.4 (Cq O-3Bn), 138.5 (Cq O-2Bn), 138.3 (Cq O4′Bn), 138.1 (Cq O-6Bn), 138.0 (Cq O-6′Bn), 128.6, 128.54, 128.52, 128.4 (4× 2CHarom), 128.2 (6CHarom), 128.1, 128.0 (2× 2CHarom), 127.95, 127.93, 127.87, 127.86 (4× 1CHarom), 127.85 (2CHarom), 127.2 (CHarom), 100.7 (d, 3J(C−F) = 10.6 Hz, C-1′), 98.5 (C-1), 93.4 (d, 1J(C−F) = 190.4 Hz, C-3′), 80.2 (C-3), 79.2 (C-2), 76.9 (C-4), 75.6 (CH2 O-3Bn), 75.1 (d, 4J(C−F) = 3.6 Hz, CH2 O-4′Bn), 73.8 (CH2 O6′Bn), 73.5 (2× CH2 O-2, O-6Bn), 73.4 (d, 2J(C−F) = 15.1 Hz, C-4′), 72.1 (d, 3J(C−F) = 7.7 Hz, C-5′), 69.8 (C-5), 68.2 (C-6), 67.4 (d, 4 J(C−F) = 2.5 Hz, C-6′), 63.0 (d, 2J(C−F) = 17.6 Hz, C-2′), 55.5 (MeO). 19 F NMR (CDCl3, 376 MHz): δ −194.91 (ddd, 2J(H−F) = 47.8 Hz, 3 J(H−F) = 11.2, 6.0 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3700. 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-α-D-galactopyranosyl)-1,2:5,6-di-O-isopropylidene-α-D -glucofuranose (3F-α) and 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3fluoro-β-D-galactopyranosyl)-1,2:5,6-di-O-isopropylidene-α-Dglucofuranose (3F-β). Compounds 3F-α and 3F-β were prepared by glycosylation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (F) with β-3 according to the general procedure. Column chromatography in EtOAc/PE 1:5 gave the product in two fractions. The faster moving fraction provided 3F-α (24 mg, 38%) as a yellow syrup. Preparative TLC of the slower moving fraction in toluene/Et2O/PE

1:1:2 afforded 3F-β (23 mg, 36%) as a colorless syrup. The combined yield was 74%. Data for 3F-α: Rf 0.26 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.36−7.27 (m, 10H, CHarom), 5.85 (d, 1H, J = 3.6 Hz, H-1), 5.28 (dd, 1H, J = 4.2, 3.8 Hz, H-1′), 4.88 (ddd, 1H, J = 49.1, 10.5, 3.1 Hz, H-3′), 4.86 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.62 (d, 1H, J = 3.6 Hz, H-2), 4.54 (d, 1H, J = 11.2 Hz, CHH O-4′Bn), 4.51, 4.43 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6′Bn), 4.43 (ddd, 1H, J = 8.6, 6.2, 5.9 Hz, H-5), 4.23 (d, 1H, J = 2.7 Hz, H-3), 4.16 (dd, 1H, J = 8.5, 6.2 Hz, H-6), 4.10−4.02 (m, 2H, H-4, H-2′), 4.09 from 1H{19F} (dd, 1H, J = 3.1, 1.3 Hz, H4′), 3.97−3.94 (m, 2H, H-5′, H-6), 3.62 (ddd, 1H, J = 9.5, 6.2, 1.3 Hz, H-6′), 3.56 (dd, 1H, J = 9.5, 6.4 Hz, H-6′), 1.48, 1.41, 1.25, 1.21 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.77, 137.75 (Cq), 128.61, 128.56, 128.4 (3× 2CHarom), 128.2, 128.0 (2× 1CHarom), 127.9 (2CHarom), 112.1, 109.4 (CMe2), 105.3 (C-1), 99.0 (d, 3J(C−F) = 9.2 Hz, C-1′), 90.5 (d, 1J(C−F) = 188.7 Hz, C-3′), 83.6 (C-2), 81.5 (C-4), 81.1 (C-3), 75.1 (d, 4J(C−F) = 3.8 Hz, CH2 O-4′Bn), 74.4 (d, 2J(C−F) = 15.4 Hz, C-4′), 74.4 (CH2 O6′Bn), 72.0 (C-5), 70.0 (d, 3J(C−F) = 6.8 Hz, C-5′), 68.8 (d, 4J(C−F) = 2.5 Hz, C-6′), 67.9 (C-6), 59.5 (d, 2J(C−F) = 17.6 Hz, C-2′), 27.0, 26.9, 26.3, 25.3 (Me). 19F NMR (CDCl3, 376 MHz): δ −199.22 (m). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2758. Data for 3F-β: Rf 0.13 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.35−7.24 (m, 10H, CHarom), 5.96 (d, 1H, J = 3.7 Hz, H-1), 4.86 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.57 (d, 1H, J = 3.7 Hz, H-2), 4.55 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.44, 4.41 (2× d, 2× 1H, J = 12.0 Hz, CHH O6′Bn), 4.35 (ddd, 1H, J = 47.5, 10.1, 3.2 Hz, H-3′), 4.32 (d, 1H, J = 7.9 Hz, H-1′), 4.58−4.36 (m, 1H, H-5), 4.31 (br s, 2H, H-3, H-4), 4.05−4.01 (m, 2H, H-6), 3.99 (ddd, 1H, J = 5.9, 3.2, 1.5 Hz, H-4′), 3.85 (ddd, 1H, J = 10.9, 10.1, 7.9 Hz, H-2′), 3.62−3.53 (m, 2H, H6′), 3.52 (ddd, 1H, J = 7.6, 5.1, 1.5 Hz, H-5′), 1.49 (s, 6H, 2× Me), 1.41, 1.32 (2× s, 2× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.9, 137.7 (Cq), 128.6, 128.5, 128.3 (3× 2CHarom), 128.07, 128.05 (2× 1CHarom), 128.0 (2CHarom), 112.2, 108.7 (CMe2), 105.3 (C-1), 100.4 (d, 3J(C−F) = 10.6 Hz, C-1′), 92.9 (d, 1J(C−F) = 191.7 Hz, C-3′), 83.0 (C-2), 81.3 (C-4), 80.5 (C-3), 75.0 (d, 4J(C−F) = 3.8 Hz, CH2 O-4′Bn), 73.7 (CH2 O-6′Bn), 73.3 (C-5), 73.0 (d, 2J(C−F) = 15.3 Hz, C-4′), 72.8 (d, 3J(C−F) = 7.7 Hz, C-5′), 67.8 (d, 4J(C−F) = 2.7 Hz, C-6′), 66.2 (C-6), 62.5 (d, 2J(C−F) = 17.9 Hz, C2′), 25.5, 26.4, 26.7, 26.9 (Me). 19F NMR (CDCl3, 376 MHz): δ −195.18 (ddd, 2J(H−F) = 47.5 Hz, 3J(H−F) = 10.9, 5.8 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2764. Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-galactopyranoside (3G-α) and Methyl 4-O-(2-Azido-4,6-di-O-benzyl-2,3dideoxy-3-fluoro-β-D-galactopyranosyl)-2,3,6-tri-O-benzyl-αD-galactopyranoside (3G-β). Compounds 3G-α and 3G-β were prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside46 (G) with β-3 according to the general procedure. Column chromatography in EtOAc/PE 1:3 followed by preparative TLC in EtOAc/PE 2:7 gave the product in two fractions. The faster moving fraction afforded 3G-α (48 mg, 57%) as a colorless syrup. The slower moving fraction was further purified by preparative TLC in toluene/ Et2O/PE 1:1:1 to afford 3G-β (9 mg, 11%) as a colorless syrup. The combined yield was 68%. Data for 3G-α: Rf 0.40 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.40−7.23 (m, 23H, CHarom), 7.17 (dd, 2H, J = 7.5, 2.0 Hz, CHarom), 4.97 (dd, 1H, J = 4.2, 3.7 Hz, H-1′), 4.88 (ddd, 1H, J = 49.6, 10.4, 3.1 Hz, H-3′), 4.84 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.81 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.80 (d, 1H, J = 12.5 Hz, CHH O-2Bn), 4.72 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.72 (dd, 1H, J = 3.9, 2.3 Hz, H-1), 4.63 (d, 1H, J = 12.5 Hz, CHH O-2Bn), 4.54 (d, 1H, J = 11.5 Hz, CHH O4′Bn), 4.53 (br s, 2H, CH2 O-6Bn), 4.44 from 1H{19F} (ddd, 1H, J = 9.3, 4.8, 1.3 Hz, H-5′), 4.16−4.09 (m, 4H, H-4, H-4′, CH2 O-6′Bn), 3.91 from 1H{19F} (dd, 1H, J = 10.4, 3.7 Hz, H-2′), 3.91−3.83 (m, R


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(Cq), 128.8, 128.6 (2× 2CHarom), 128.5 (4CHarom), 128.4, 128.2 (2× 1CHarom), 128.1 (2CHarom), 127.9 (1CHarom), 127.7 (2CHarom), 101.2 (d, 3J(C−F) = 9.3 Hz, C-1′), 100.9 (C-1), 90.0 (d, 1J(C−F) = 187.9 Hz, C-3′), 78.7 (C-4), 78.0 (C-3), 75.1 (d, 4J(C−F) = 4.1 Hz, CH2 O4′Bn), 74.8 (C-5), 74.6 (d, 2J(C−F) = 15.5 Hz, C-4′), 73.5 (CH2 O6′Bn), 73.0 (CH2 O-3Bn), 69.9 (d, 3J(C−F) = 6.9 Hz, C-5′), 69.4 (d, 4 J(C−F) = 2.4 Hz, C-6′), 65.0 (C-6), 58.9 (C-2), 58.9 (d, 2J(C−F) = 17.9 Hz, C-2′). 19F NMR (CDCl3, 376 MHz): δ −199.28 (dddd, 2J(H−F) = 48.9 Hz, 3J(H−F) = 9.2, 6.5 Hz, 4J(H−F) = 4.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2566. Data for 3H-β: Rf 0.14 (toluene/Et2O/PE 1:1:1). 1H NMR (CDCl3, 500 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.34− 7.28 (m, 13H, CHarom), 7.24−7.22 (m, 2H, CHarom), 5.48 (t, 1H, J = 1.6 Hz, H-1), 4.88 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.69−4.67 (m, 1H, H-5), 4.62, 4.55 (2× d, 2× 1H, J = 11.9 Hz, CHH O-3Bn), 4.54 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.40, 4.36 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6′Bn), 4.33 (ddd, 1H, J = 47.5, 10.2, 3.3 Hz, H-3′), 4.29 (dd, 1H, J = 7.9, 0.7 Hz, H-1′), 4.08 (dd, 1H, J = 7.3, 1.2 Hz, H-6en), 4.00 (ddd, 1H, J = 11.2, 10.2, 7.9 Hz, H-2′), 3.97 (ddd, 1H, J = 5.8, 3.3, 1.3 Hz, H-4′), 3.91 (p, 1H, J = 1.6 Hz, H-3), 3.78−3.75 (m, 2H, H-4, H-6ex), 3.54 (dd, 1H, J = 8.9, 7.0 Hz, H-6′), 3.49 (ddd, 1H, J = 8.9, 5.6, 1.4 Hz, H-6′), 3.44 (dddd, 1H, J = 7.0, 5.6, 1.5, 1.3 Hz, H-5′), 3.25 (q, 1H, J = 1.6 Hz, H-2). 13C{1H} APT NMR (CDCl3, 126 MHz, HSQC, HMBC): δ 137.9, 137.63, 137.57 (Cq), 128.64, 128.63, 128.5, 128.3 (4× 2CHarom), 128.11, 128.10, 128.02 (3× 1CHarom), 128.00, 127.9 (2× 2CHarom), 101.6 (d, 3J(C−F) = 10.6 Hz, C-1′), 100.8 (C-1), 92.9 (d, 1J(C−F) = 191.6 Hz, C-3′), 77.0 (C-4, C-3), 74.9 (d, 4 J(C−F) = 4.0 Hz, CH2 O-4′Bn), 74.5 (C-5), 73.7 (CH2 O-6′Bn), 72.9 (d, 2J(C−F) = 15.2 Hz, C-4′), 72.64 (CH2 O-3Bn), 72.64 (d, 3J(C−F) = 8.6 Hz, C-5′), 68.2 (d, 4J(C−F) = 2.6 Hz, C-6′), 65.3 (C-6), 62.1 (d, 2 J(C−F) = 17.8 Hz, C-2′), 59.8 (C-2). 19F NMR (CDCl3, 376 MHz): δ −194.97 (ddd, 2J(H−F) = 47.5 Hz, 3J(H−F) = 11.2, 5.8 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2563. Preparative TLC of the slower moving fraction in Et2O 1:1 afforded in addition to 3H-β a trisaccharide S2 (5 mg) which was assigned structure S2 on the basis of NMR.

4H, H-2, H-3, H-5, H-6), 3.58−3.51 (m, 2H, H-6, H-6′), 3.36 (s, 3H, MeO), 3.24 (ddd, 1H, J = 8.3, 4.8, 2.2 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.8 (Cq O-2Bn), 138.32, 138.29 (Cq O-2/4′Bn), 138.0 (Cq O-6′Bn), 137.7 (Cq O-6Bn), 128.6, 128.50, 128.46 (3× 2CHarom), 128.4 (4CHarom), 128.3, 128.2, 128.12 (3× 2CHarom), 128.07, 127.92, 127.85 (3× 1CHarom), 127.83 (2CHarom), 127.76, 127.6 (2× 1CHarom), 127.5 (2CHarom), 99.2 (d, 3 J(C−F) = 9.1 Hz, C-1′), 98.7 (C-1), 90.6 (d, 1J(C−F) = 187.8 Hz, C-3′), 77.2 (C-2), 75.3 (C-3), 75.2 (d, 4J(C−F) = 3.4 Hz, CH2 O-4′Bn), 75.0 (C-4), 74.6 (d, 2J(C−F) = 15.2 Hz, C-4′), 73.6 (CH2 O-6Bn), 73.4 (CH2 O-3Bn), 73.3 (CH2 O-6′Bn), 72.9 (CH2 O-2Bn), 68.8 (C-5), 68.7 (d, 3J(C−F) = 6.4 Hz, C-5′), 67.4 (C-6), 67.3 (d, 4J(C−F) = 2.2 Hz, C-6′), 59.7 (d, 2J(C−F) = 17.2 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −199.25 (dtdd, 2J(H−F) = 49.6 Hz, 3J(H−F) = 7.2, 4J(H−F) = 4.8, 2.4 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3694. Data for 3G-β: Rf 0.30 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.25 (m, 23H, CHarom), 7.21 (dd, 2H, J = 7.7, 1.8 Hz, CHarom), 4.91 (d, 1H, J = 12.1 Hz, CHH O-3Bn), 4.86 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.82 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.66 (d, 1H, J = 8.3 Hz, H-1′), 4.66 (d, 2H, J = 12.1 Hz, CHH C-2, O-3Bn), 4.62 (d, 1H, J = 3.7 Hz, H-1), 4.55 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.52 (d, 1H, J = 11.5 Hz, CHH O-4′Bn), 4.46 (d, 1H, J = 12.0 Hz, CHH O-6Bn), 4.32 (br s, 2H, CH2 O-6′Bn), 4.23 (ddd, 1H, J = 47.5, 10.2, 3.3 Hz, H-3′), 4.16 (dd, 1H, J = 3.1, 1.2 Hz, H-4), 4.10 (dd, 1H, J = 10.1, 3.7 Hz, H-2), 3.94−3.88 (m, 3H, H-3, H-5, H-4′), 3.87 from 1H{19F} (dd, 1H, J = 10.2, 8.3 Hz, H-2′), 3.64 (dd, 1H, J = 10.2, 5.4 Hz, H-6), 3.56 (dd, 1H, J = 10.2, 6.5 Hz, H-6), 3.52 (dd, 1H, J = 8.7, 7.5 Hz, H-6′), 3.40− 3.32 (m, 2H, H-5′, H-6′), 3.37 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.1 (Cq O-3Bn), 138.7 (Cq O-2Bn), 138.6 (Cq O-6Bn), 138.3 (Cq O-4′Bn), 137.8 (Cq O-6′Bn), 128.6, 128.50, 128.48, 128.46, 128.4, 128.3, 128.1 (7× 2CHarom), 128.0, 127.90, 127.87 (3× 1CHarom), 127.8 (2CHarom), 127.58 (CHarom), 127.56 (3CHarom), 127.2 (2CHarom), 101.4 (d, 3J(C−F) = 10.4 Hz, C1′), 98.9 (C-1), 92.8 (d, 1J(C−F) = 191.1 Hz, C-3′), 78.6 (C-3), 76.6 (C-2), 75.0 (d, 4J(C−F) = 3.7 Hz, CH2 O-4′Bn), 74.2 (C-4), 73.9 (CH2 O-2Bn), 73.60, 73.56 (CH2 C3/6′Bn), 73.5 (CH2 O-6Bn), 73.3 (d, 2 J(C−F) = 15.2 Hz, C-4′), 72.1 (d, 3J(C−F) = 7.7 Hz, C-5′), 69.9 (C-6), 69.3 (C-5), 67.9 (d, 4J(C−F) = 2.8 Hz, C-6′), 62.6 (d, 2J(C−F) = 17.5 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.24 (ddd, 2 J(H−F) = 47.5 Hz, 3J(H−F) = 11.1, 5.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3695. 4-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-α-D-galactopyranosyl)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-Dglucopyranose (3H-α) and 4-O-(2-Azido-4,6-di-O-benzyl-2,3dideoxy-3-fluoro-β-D-galactopyranosyl)-1,6-anhydro-2-azido3-O-benzyl-2-deoxy-β-D-glucopyranose (3H-β). Compounds 3H-α and 3H-β were prepared by glycosylation of 1,6-anhydro-2azido-3-O-benzyl-2-deoxy-β-D-glucopyranoside5 (H) with β-3 according to the general procedure. Column chromatography in toluene/ Et2O/PE 1:1:1 followed by preparative TLC in toluene/Et2O/PE 1:1:2 gave the product in two fractions. The faster moving fraction afforded 3H-α as a colorless syrup (35 mg, 54%). The slower moving fraction was further purified by preparative TLC in Et2O/PE 1:1 to afford 3H-β as a colorless syrup (10 mg, 15%). The combined yield was 69%. Data for 3H-α: Rf 0.41 (toluene/Et2O/PE 1:1:1). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.39− 7.25 (m, 15H, CHarom), 5.55 (t, 1H, J = 1.5 Hz, H-1), 5.14 (ddd, 1H, J = 48.9, 10.6, 3.2 Hz, H-3′), 4.93 (dd, 1H, J = 4.1, 3.8 Hz, H-1′), 4.86 (d, 1H, J = 11.4 Hz, CHH O-4′Bn), 4.83 (ddd, 1H, J = 6.0, 1.6, 1.1 Hz, H-5), 4.68, 4.56 (2× d, 2× 1H, J = 11.8 Hz, CHH O-3Bn), 4.53 (d, 1H, J = 11.4 Hz, CHH O-4′Bn), 4.46 (s, 2H, CH2 O-6′Bn), 4.29 (ddd, 1H, J = 6.8, 5.1, 1.3 Hz, H-5′), 4.06 (ddd, 1H, J = 6.5, 3.2, 1.3 Hz, H-4′), 4.03 (dd, 1H, J = 7.4, 1.1 Hz, H-6en), 3.85 (ddd, 1H, J = 10.6, 9.3, 3.8 Hz, H-2′), 3.77 (q, 1H, J = 1.5 Hz, H-3), 3.63 (ddd, 1H, J = 10.0, 7.3, 0.8 Hz, H-6′), 3.52 (dd, 1H, J = 7.4, 6.0 Hz, H-6ex), 3.49−3.45 (m, 2H, H-4, H-6′), 3.10 (t, 1H, J = 1.5 Hz, H-2). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.0, 137.7, 137.1

Data for S2: 1H NMR (CDCl3, 500 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.39−7.28 (m, 18H, CHarom), 7.24−7.22 (m, 2H, CHarom), 5.55 (t, 1H, J = 1.7 Hz, H-1), 4.97 from 1H{19F} (d, 1H, J = 3.8 Hz, H-1″), 4.90 (ddd, 1H, J = 49.2, 10.4, 3.2 Hz, H-3″), 4.84 (d, 1H, J = 3.6 Hz, H-1′), 4.88 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.84 (d, 1H, J = 11.3 Hz, CHH O-4″Bn), 4.76 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.74 (m, 1H, H-5), 4.69, 4.57 (2× d, 2× 1H, J = 11.9 Hz, CHH O-3Bn), 4.50 (d, 1H, J = 11.3 Hz, CHH O-4″Bn), 4.48, 4.39 (2× d, 2× 1H, J = 12.0 Hz, CHH O-6″Bn), 4.12 (dd, 1H, J = 7.5, 1.2 Hz, H-6en), 4.03−4.00 (m, 2H, H5′, H4″), 3.97−3.91 (m, 4H, H3′, H-6′, H2″, H-5″), 3.78 (p, 1H, J = 1.7 Hz, H-3), 3.75 (dd, 1H, J = 7.5, 5.9 Hz, H-6ex), 3.66 (dd, 1H, J = 11.1, 2.6 Hz, H-6′), 3.60 (ddd, 1H, J = 9.4, 8.8, 4.0 Hz, H-4′), 3.54 (q, 1H, J = 1.7 Hz, H-4), 3.52 (ddd, 1H, J = 9.5, 6.4, 1.2 Hz, H-6″), 3.42 (ddd, 1H, J = 9.5, 6.0, 0.9 Hz, H6″), 3.27 (dd, 1H, J = 10.3, 3.6 Hz, H-2′), 3.15 (q, 1H, J = 1.7 Hz, H2), 2.68 (d, 1H, J = 4.0 Hz, OH). 13C{1H} APT NMR (CDCl3, 126 MHz, HSQC, HMBC): δ 138.1, 137.7, 137.4, 137.1 (Cq), 128.8 (4CHarom), 128.62, 128.55, 128.46, 128.40 (4× 2CHarom), 128.37, 128.3, 128.2, 128.09 (4× 1CHarom), 128.05, 128.0 (2× 2CHarom), 100.8 (C-1), 100.0 (C-1′), 98.3 (d, 3J(C−F) = 9.2 Hz, C-1″), 90.6 (d, 1 J(C−F) = 188.6 Hz, C-3″), 79.5 (C-3′), 74.7 (C-4), 77.3 (C-3), 75.3 (CH2 O-3′Bn), 75.0 (d, 4J(C−F) = 3.5 Hz, CH2 O-4″Bn), 75.0 (C-5), 74.2 (d, 2J(C−F) = 15.4 Hz, C-4″), 73.7 (CH2 O-6″Bn), 72.8 (CH2 O3Bn), 71.4 (C-5′), 70.8 (C-4′), 69.5 (d, 3J(C−F) = 6.9 Hz, C-5″), 68.7 (d, 4J(C−F) = 2.6 Hz, C-6″), 66.6 (C-6′), 65.0 (C-6), 63.1 (C-2′), 59.1 S


Article

The Journal of Organic Chemistry (d, 2J(C−F) = 17.6 Hz, C-2″), 58.7 (C-2). 19F NMR (CDCl3, 376 MHz): δ −199.24 (m). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C46H51FN7O11, 896.3625; found, 896.3628, [M − N2 − N2 + H]+ calcd for C46H51FN5O11, 868.3563; found 868.3578. Methyl 2-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoroα- D -galactopyranosyl)-3-O-benzyl-4,6-O-benzylidene-α- D mannopyranoside (3I-α). Compound 3I-α was prepared by glycosylation of methyl 3-O-benzyl-4,6-O-benzylidene-α-D-mannopyranoside48 (I) with β-3 according to the general procedure. Column chromatography in EtOAC/PE 1:3 gave the product in two fractions. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 1:1:2 afforded 3I-α (39 mg, 53%) as a colorless syrup. Preparative TLC of the slower moving fraction in toluene/Et2O/PE 1:1:2 afforded β-anomer 3I-β (9 mg) which was contaminated by aromatic impurities (NMR) inseparable under chromatographic conditions used. Data for 3I-α: Rf 0.37 (EtOAc/PE 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.49 (dd, 2H, J = 7.5, 2.2 Hz, CHarom), 7.37−7.23 (m, 18H, CHarom), 5.64 (s, 1H, CHPh), 5.37 (dd, 1H, J = 4.2, 3.8 Hz, H-1′), 5.04 (ddd, 1H, J = 49.2, 10.7, 3.1 Hz, H-3′), 4.88 (d, 1H, J = 11.4 Hz, CHH O-4′Bn), 4.88 (d, 1H, J = 12.3 Hz, CHH O-3Bn), 4.69 (d, 1H, J = 1.6 Hz, H-1), 4.67 (d, 1H, J = 12.3 Hz, CHH O-3Bn), 4.55 (d, 1H, J = 11.4 Hz, CHH O4′Bn), 4.49, 4.42 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6′Bn), 4.26− 4.21 (m, 2H, H-4, H-6), 4.10 (ddd, 1H, J = 6.8, 3.1, 2.9 Hz, H-4′), 4.03−4.00 (m, 2H, H-2, H-5′), 3.96 (dd, 1H, J = 9.9, 3.1 Hz, H-3), 3.89−3.82 (m, 2H, H-6, H-2′), 3.76 (ddd, 1H, J = 10.0, 9.8, 4.4 Hz, H-5), 3.60 (dd, 1H, J = 9.6, 6.6 Hz, H-6′), 3.51 (dd, 1H, J = 9.6, 5.9 Hz, H-6′), 3.20 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.8, 137.9, 137.8, 137.7 (Cq), 129.0 (CHarom), 128.56, 128.55, 128.5, 128.4, 128.3 (5× 2CHarom), 128.1, 128.0 (2× 1CHarom), 127.8 (2CHarom), 127.6 (CHarom), 127.5, 126.2 (2× CHarom), 101.7 (CHPh), 100.8 (C-1), 100.1 (d, 3J(C−F) = 9.0 Hz, C-1′), 89.6 (d, 1J(C−F) = 188.5 Hz, C-3′), 79.6 (C-4), 76.2 (C-2), 75.6 (C-3), 75.1 (d, 4J(C−F) = 4.0 Hz, CH2 O-4′Bn), 74.6 (d, 2J(C−F) = 15.4 Hz, C-4′), 73.7 (CH2 O-6′Bn), 73.3 (CH2 O-3Bn), 69.9 (d, 3J(C−F) = 6.9 Hz, C-5′), 69.12 (d, 4J(C−F) = 2.3 Hz, C-6′), 69.05 (C-6), 64.0 (C5), 58.8 (d, 2J(C−F) = 17.6 Hz, C-2′), 54.9 (MeO). 19F NMR (CDCl3, 376 MHz): δ −199.55 (dddd, 2J(H−F) = 49.2 Hz, 3J(H−F) = 8.2, 6.8 Hz, 4 J(H−F) = 4.2 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3067. Data for 3I-β: Rf 0.18 (EtOAc/PE 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.52 (m, 2H, CHarom), 7.37−7.17 (m, 18H, CHarom), 5.59 (s, 1H, CHPh), 4.88 (d, 1H, J = 13.3 Hz, CHH O-4′Bn), 4.82 (d, 1H, J = 1.6 Hz, H-1), 4.73, 4.62 (2× d, 2× 1H, J = 11.7 Hz, CHH O-3Bn), 4.54 (d, 1H, J = 13.3 Hz, CHH O-4′Bn), 4.41, 4.36 (2× d, 2× 1H, J = 11.8 Hz, CHH O6′Bn), 4.35 (d, 1H, J = 7.9 Hz, H-1′), 4.32 (ddd, 1H, J = 47.6, 10.1, 3.1 Hz, H-3′), 4.28−4.26 (m, 2H, H-2, H-6), 4.15 (dd, 1H, J = 10.1, 9.1 Hz, H-4), 4.08 (ddd, 1H, J = 10.9, 10.7, 7.9 Hz, H-2′), 4.00 (ddd, 1H, J = 5.8, 3.1, 0.9 Hz, H-4′), 3.93 (dd, 1H, J = 10.1, 3.4 Hz, H-3), 3.85 (t, 1H, J = 10.1 Hz, H-6), 3.78 (ddd, 1H, J = 10.1, 5.4, 4.3 Hz, H5), 3.65 (dd, 1H, J = 8.4, 6.8 Hz, H-6′), 3.61−3.54 (m, 2H, H-5′, H6′), 3.38 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.5, 138.0, 137.8, 137.7 (Cq), 128.9 (CHarom), 128.6, 128.5 (2× 2CHarom), 128.28, 128.26 (2× 3CHarom), 128.1 (CHarom), 127.98 (2CHarom), 127.95 (3CHarom), 127.5 (CHarom), 126.2 (2CHarom), 101.7 (CHPh), 100.7 (d, 3J(C−F) = 10.8 Hz, C-1′), 99.4 (C-1), 92.6 (d, 1J(C−F) = 191.6 Hz, C-3′), 78.2 (C-4), 75.2 (d, 4J(C−F) = 3.8 Hz, CH2 O-4′Bn), 74.6 (C-2), 74.2 (C-3), 73.7 (CH2 O-6′Bn), 73.4 (d, 2J(C−F) = 15.1 Hz, C-4′), 72.7 (d, 3J(C−F) = 7.7 Hz, C-5′), 71.5 (CH2 O-3Bn), 69.0 (C-6), 68.2 (d, 4J(C−F) = 2.5 Hz, C-6′), 64.2 (C5), 62.4 (d, 2J(C−F) = 17.8 Hz, C-2′), 55.1 (MeO). 19F NMR (CDCl3, 376 MHz): δ −195.17 (ddd, 2J(H−F) = 47.6 Hz, 3J(H−F) = 10.9, 5.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3075. Cyclohexyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-αD-galactopyranoside (4A-α) and Cyclohexyl 2-Azido-3,6-di-Obenzyl-2,4-dideoxy-4-fluoro-β-D-galactopyranoside (4A-β). Compounds 4A-α and 4A-β were prepared by glycosylation of

cyclohexanol with 4 according to the general procedure. Chromatography of the crude product in EtOAc/PE 2:25 afforded 4A-α (8 mg, 17%) as a colorless syrup. Continuous elution gave 4A-β (22 mg, 46%) as a colorless syrup. The combined yield was 63%. Data for 4A-α: Rf 0.61 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.43−7.29 (m, 10H, CHarom), 5.07 (d, 1H, J = 3.5 Hz, H-1), 4.94 (dd, 1H, J = 50.3, 2.5 Hz, H-4), 4.77, 4.70 (2× d, 2× 1H, J = 11.4 Hz, CHH O-3Bn), 4.58, 4.54 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6Bn), 4.05 (dt, 1H, J = 30.1, 6.8 Hz, H-5), 3.95 (ddd, 1H, J = 26.9, 10.8, 2.5 Hz, H-3), 3.72− 3.63 (m, 4H, H-2, H-6, CH cyclohexyl), 1.92−1.85 (m, 2H, CH2 cyclohexyl), 1.77−1.71 (m, 2H, CH2 cyclohexyl), 1.55−1.50 (m, 1H, CH2 cyclohexyl), 1.42−1.37 (m, 2H, CH2 cyclohexyl), 1.32−1.21 (m, 3H, CH2 cyclohexyl). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.9 (Cq O-6Bn), 137.5 (Cq O-3Bn), 128.7, 128.6 (2× 2CHarom), 128.1 (CHarom), 128.04 (2CHarom), 127.97 (CHarom), 127.8 (2CHarom), 96.6 (C-1), 85.8 (d, 1J(C−F) = 184.8 Hz, C-4), 76.8 (CH cyclohexyl), 74.4 (d, 2J(C−F) = 18.2 Hz, C-3), 73.8 (CH2 O-3Bn), 71.8 (CH2 O-6Bn), 68.4 (d, 2J(C−F) = 18.2 Hz, C-5), 68.0 (d, 3J(C−F) = 5.5 Hz, C-6), 59.2 (d, 3J(C−F) = 2.4 Hz, C-2), 33.4, 31.6, 25.7, 24.2, 24.0 (CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −221.27 (ddd, 2 J(H−F) = 50.2 Hz, 3J(H−F) = 30.1, 26.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2388. Data for 4A-β: Rf 0.48 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.31 (m, 10H, CHarom), 4.79 (dd, 1H, J = 49.6, 2.6 Hz, H-4), 4.77, 4.70 (2× d, 2× 1H, J = 12.0 Hz, CHH O-3Bn), 4.56, 4.54 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6Bn), 4.35 (d, 1H, J = 7.9 Hz, H-1), 3.76−3.64 (m, 4H, H-2, H-6, CH cyclohexyl), 3.53 (ddd, 1H, J = 26.8, 7.6, 5.8 Hz, H-5), 3.25 (ddd, 1H, J = 27.7, 10.4, 3.2 Hz, H-3), 1.93−1.90 (m, 2H, CH2 cyclohexyl), 1.75 (m, 2H, CH2 cyclohexyl), 1.39−1.37 (m, 3H, CH2 cyclohexyl), 1.32−1.22 (m, 3H, CH2 cyclohexyl). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6Bn), 137.4 (Cq O-3Bn), 128.7, 128.6 (2× 2CHarom), 128.2 (CHarom), 128.0 (3CHarom), 127.9, (2CHarom), 100.6 (C-1), 84.6 (d, 1J(C−F) = 185.1 Hz, C-4), 78.2 (CH cyclohexyl), 74.5 (d, 2J(C−F) = 18.0 Hz, C-3), 73.9 (CH2 O-3Bn), 72.3 (d, 2J(C−F) = 18.2 Hz, C-5), 72.0 (CH2 O-6Bn), 67.8 (d, 3J(C−F) = 5.3 Hz, C-6), 63.0 (C-2), 33.6, 31.8, 25.7, 24.1, 23.9 (CH2 cyclohexyl). 19F NMR (CDCl3, 376 MHz): δ −218.75 (ddd, 2 J(H−F) = 49.6 Hz, 3J(H−F) = 27.7, 26.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H33FNO4, 442.2388; found, 442.2388. Methyl 6-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-galactopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (4B-α) and Methyl 6-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy4-fluoro-β-D-galactopyranosyl)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (4B-β). Compounds 4B-α and 4B-β were prepared by glycosylation of methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside45 (B) with 4 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:5 afforded a fraction containing 4B-α. Continued elution gave a fraction containing 4B-β. The α-anomer was purified by preparative TLC in PE/toluene/Et2O 2.5:1:1, which gave 4B-α (16 mg, 19%) as a colorless syrup. The β-anomer was purified in the same manner to give 4B-β (43 mg, 52%) as a colorless syrup. The combined yield was 71%. Data for 4B-α: Rf 0.38 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.41−7.23 (m, 25H, CHarom), 5.00 (d, 1H, J = 3.3 Hz, H-1′), 4.99 (d, 1H, J = 10.8 Hz, CHH O-3Bn), 4.88 (d, 1H, J = 11.2 Hz, CHH O-4Bn), 4.87 (dd, 1H, J = 50.2, 2.4 Hz, H-4′), 4.80 (d, 1H, J = 10.8 Hz, CHH O-3Bn), 4.79 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.78, 4.66 (2× d, 2× 1H, J = 12.0 Hz, CHH O-3′Bn), 4.66 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.57 (d, 1H, J = 3.6 Hz, H-1),4.53 (d, 1H, J = 11.2 Hz, CHH O-4Bn), 4.53 (m, CH2 O-6′Bn), 3.99 (dd, 1H, J = 9.7, 9.3 Hz, H-3), 3.90 (ddd, 1H, J = 29.6, 7.5, 6.6 Hz, H-5′), 3.81 (ddd, 1H, J = 27.9, 10.7, 2.4 Hz, H3′), 3.76−3.70 (m, 3H, H-5, H-6), 3.72−3.66 (m, 1H, H-2′), 3.65 (dd, 1H, J = 9.4, 7.5 Hz, H-6′), 3.56 (ddd, 1H, J = 9.4, 6.6, 1.9 Hz, H6′), 3.52 (dd, 1H, J = 9.7, 3.6 Hz, H-2), 3.50 (dd, 1H, J = 10.0, 9.3 Hz, H-4), 3.32 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.9 (Cq O-3Bn), 138.4 (Cq O-4Bn), 138.3 (Cq O-2Bn), 137.9 (Cq O-6′Bn), 137.2 (Cq O-3′Bn), 128.7, 128.60, T


Article


2Bn), 73.5 (d, 2J(C−F) = 18.4 Hz, C-3′), 73.2 (CH2 O-6′Bn), 72.2 (C4), 71.46 (d, 4J(C−F) = 2.1 Hz, CH2 O-3′Bn), 71.45 (C-3), 69.6 (C-6), 68.1 (d, 2J(C−F) = 18.0 Hz, C-5′), 67.6 (d, 3J(C−F) = 5.9 Hz, C-6′), 62.3 (C-5), 58.7 (d, 3J(C−F) = 2.5 Hz, C-2′), 55.7 (MeO). 19F NMR (CDCl3, 376 MHz): δ −221.48 (ddd, 2J(H−F) = 50.3 Hz, 3J(H−F) = 29.7, 26.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3070. Data for 4C-β: Rf 0.26 (toluene/Et2O/PE 2:3:2). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.52 (dd, 2H, J = 7.6, 2.0 Hz, CHarom), 7.42−7.28 (m, 18H, CHarom), 5.53 (s, 1H, CHPh), 4.87 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.80 from 1 H{19F} (d, 1H, J = 2.6 Hz, H-4′), 4.77 (d, 1H, J = 12.0 Hz, CHH O3′Bn), 4.74 from 1H{19F} (d, 1H, J = 8.1 Hz, H-1′), 4.71 (d, 1H, J = 12.0 Hz, CHH O-3′Bn), 4.69 (d, 1H, J = 3.4 Hz, H-1), 4.58 (d, 1H, J = 11.6 Hz, CHH O-2Bn), 4.57, 4.52 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6′Bn), 4.28 (dd, 1H, J = 3.4, 0.9 Hz, H-4), 4.21 (dd, 1H, J = 10.2, 3.4 Hz, H-3), 4.20 (dd, 1H, J = 12.4, 1.5 Hz, H-6), 4.14 (dd, 1H, J = 10.2, 3.4 Hz, H-2), 3.99 (dd, 1H, J = 12.4, 1.8 Hz, H-6), 3.79 (dd, 1H, J = 11.4, 8.1 Hz, H-2′), 3.70 (dd, 1H, J = 9.3, 7.8 Hz, H-6′), 3.64− 3.57 (m, 1H, H-6′), 3.60 (br s, 1H, H-5), 3.55 from 1H{19F} (dd, 1H, J = 7.8, 5.7 Hz, H-5′), 3.35 (s, 3H, MeO), 3.26 (ddd, 1H, J = 27.7, 10.4, 2.6 Hz, H-3′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.4 (Cq O-2Bn), 138.0, 137.9 (Cq O-6′Bn/Ph), 137.4 (Cq O-3′Bn), 128.8 (CHarom), 128.68, 128.65, 128.60, 128.57 (4× 2CHarom), 128.2 (CHarom), 128.14 (2CHarom), 128.10, 128.04 (2× 1CHarom), 128.03, 127.8, 126.3 (3× 2CHarom), 102.9 (C-1′), 100.5 (CHPh), 99.1 (C-1), 84.7 (d, 1J(C−F) = 185.3 Hz, C-4′), overlapped with CDCl3 (C-3′), 76.7 (C-4), 76.6 (C-2), 74.2 (C-3), 73.9 (CH2 O2Bn), 73.7 (CH2 O-6′Bn), 72.14 (CH2 O-3′Bn), 72.05 (d, 2J(C−F) = 18.3 Hz, C-5′), 69.3 (C-6), 67.5 (d, 3J(C−F) = 5.4 Hz, C-6′), 62.83 (d, 3 J(C−F) = 3.6 Hz, C-2′), 62.81 (C-5), 57.6 (MeO). 19F NMR (CDCl3, 376 MHz): δ −218.67 (dt, 2J(H−F) = 49.6 Hz, 3J(H−F) = 27.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3071. Methyl 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-galactopyranosyl)-2,4,6-tri-O-methyl-α-D-galactopyranoside (4D-α) and Methyl 3-O-(2-Azido-3,6-di-O-benzyl-2,4dideoxy-4-fluoro-β-D-galactopyranosyl)-2,4,6-tri-O-methyl-αD-galactopyranoside (4D-β). Compounds 4D-α and 4D-β were prepared by glycosylation of methyl 2,4,6-tri-O-methyl-α-D-galactopyranoside (D) with 4 according to the general procedure. Column chromatography in EtOAc/PE 1:2 gave the product in two fractions. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 1:2:1 afforded 4D-α (25 mg, 41%) as a crystalline solid. Preparative TLC of the slower moving fraction in dichloromethane/EtOAc 20:3 afforded 4D-β (13 mg, 21%) as a colorless syrup which crystallized overnight. The combined yield was 62%. Data for 4D-α: Rf 0.20 (EtOAc/heptane 1:2), mp 95−99 °C (heptane/MTBE). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.43−7.41 (m, 2H, CHarom), 7.37−7.28 (m, 8H, CHarom), 5.10 (d, 1H, J = 3.4 Hz, H-1′), 4.99 (dd, 1H, J = 50.4, 2.4 Hz, H-4′), 4.88 (d, 1H, J = 3.6 Hz, H-1), 4.81, 4.69 (2× d, 2× 1H, J = 11.5 Hz, CHH O-3′Bn), 4.38 (s, 2H, CH2 O-6′Bn), 4.28 (dt, 1H, J = 30.1, 6.9 Hz, H-5′), 4.00 (dd, 1H, J = 10.2, 3.1 Hz, H-3), 3.97 (ddd, 1H, J = 26.6, 10.7, 2.4 Hz, H-3′), 3.85−3.81 (m, 2H, H-5, H-2′), 3.69−3.63 (m, 3H, H-4, H-6′), 3.63 (dd, 1H, J = 10.2, 3.6 Hz, H-2), 3.58 (s, 3H, MeO), 3.56−3.49 (m, 2H, H-6), 3.40, 3.37, 3.36 (3× s, 3× 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.1 (Cq O-6′Bn), 137.2 (Cq O-3′Bn), 128.7, 128.5, 128.20 (3× 2CHarom), 128.19 (CHarom), 127.9 (2CHarom), 127.8 (CHarom), 97.7 (C-1), 95.2 (C-1′), 85.5 (d, 1J(C−F) = 184.8 Hz, C-4′), 77.2 (C-2), 75.8 (C-4), 74.8 (C-3), 74.4 (d, 2J(C−F) = 18.2 Hz, C-3′), 73.4 (CH2 O-6′Bn), 71.4 (CH2 O-3′Bn), 71.1 (C-6), 68.9 (C-5), 67.9 (d, 2J(C−F) = 18.0 Hz, C-5′), 67.4 (d, 3J(C−F) = 5.7 Hz, C-6′), 61.4 (MeO), 59.4 (d, 3J(C−F) = 2.4 Hz, C-2′), 59.3, 58.9, 55.4 (MeO). 19F NMR (CDCl3, 376 MHz): δ −221.69 (ddd, 2J(H−F) = 50.4 Hz, 3J(H−F) = 30.1, 26.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C30H41FNO9, 578.2759; found, 578.2758. Data for 4D-β: Rf 0.12 (EtOAc/heptane 1:2), mp 102−105 °C (heptane/MTBE). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H

128.59 (3× 2CHarom), 128.56 (4CHarom), 128.3 (2CHarom), 128.22 (CHarom), 128.18, 128.12 (2× 2CHarom), 128.1, 120.0 (2× 1CHarom), 127.91 (2CHarom), 127.88 (CHarom), 127.8 (2CHarom), 127.79 (CHarom), 98.3 (C-1′), 98.1 (C-1), 85.6 (d, 1J(C−F) = 184.9 Hz, C4′), 82.1 (C-3), 80.2 (C-2), 77.9 (C-4), 75.9 (CH2 O-3Bn), 75.1 (CH2 O-4Bn), 73.7 (d, 2J(C−F) = 18.2 Hz, C-3′), 73.7 (CH2 O-6′Bn), 73.6 (CH2 O-2Bn), 71.5 (CH2 O-3′Bn), 70.1 (C-5), 68.4 (d, 2J(C−F) = 18.2 Hz, C-5′), 67.8 (d, 3J(C−F) = 5.8 Hz, C-6′), 66.8 (C-6), 59.3 (d, 3 J(C−F) = 2.5 Hz, C-2′), 55.2 (MeO). 19F NMR (CDCl3, 376 MHz): δ −221.36 (ddd, 2J(H−F) = 50.2 Hz, 3J(H−F) = 29.6, 27.9 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3692. Data for 4B-β: Rf 0.23 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.25 (m, 25H, CHarom), 4.98 (d, 1H, J = 10.9 Hz, CHH O-3Bn), 4.92 (d, 1H, J = 11.2 Hz, CHH O-2/4Bn), 4.81 (d, 1H, J = 10.9 Hz, CHH O-3Bn), 4.79 (d, 1H, J = 11.7 Hz, CHH O-2/4Bn), 4.78 (dd, 1H, J = 48.9, 2.6 Hz, H-4′), 4.76, 4.67 (2× d, 2× 1H, J = 11.5 Hz, CHH O-3′Bn), 4.64 (2× d, 2× 1H, J = 11.7/11.2 Hz, CHH O-2/4Bn), 4.61 (d, 1H, J = 3.6 Hz, H-1), 4.55, 4.51 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6′Bn), 4.11−4.08 (m, 1H, H-6), 4.10 (d, 1H, J = 8.3 Hz, H-1′), 3.99 (t, 1H, J = 9.3 Hz, H-3), 3.79 (ddd, 1H, J = 10.0, 4.6, 1.4 Hz, H-5), 3.70−3.67 (m, 3H, H-6, H-2′, H-6′), 3.62 (ddd, 1H, J = 9.3, 5.6, 1.2 Hz, H-6′), 3.56−3.53 (m, 2H, H-2, H-4), 3.47 (ddd, 1H, J = 26.8, 7.7, 5.6 Hz, H5′), 3.37 (s, 3H, MeO), 3.27 (ddd, 1H, J = 27.5, 10.3, 2.6 Hz, H-3′). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.9 (Cq O3Bn), 138.6, 138.3 (Cq O-2/4Bn), 137.8 (Cq O-6′Bn), 137.2 (Cq O3′Bn), 128.7, 128.64, 128.59, 128.54, 128.52, 128.3 (6× 2CHarom), 128.2 (CHarom), 128.12 (2CHarom), 128.08 (CHarom), 128.05 (3CHarom), 127.93, 127.89 (2× 2CHarom), 127.8, 127.7 (2× 1CHarom), 102.2 (C-1′), 98.3 (C-1), 84.2 (d, 1J(C−F) = 185.8 Hz, C-4′), 82.2 (C3), 80.0 (C-2/4), 77.9 (d, 2J(C−F) = 17.2 Hz, C-3′), 77.8 (C-2/4), 75.9 (CH2 O-3Bn), 75.0 (CH2 O-2/4Bn), 73.9 (CH2 O-6′Bn), 73.6 (CH2 O-2/4Bn), 72.4 (d, 2J(C−F) = 18.3 Hz, C-5′), 72.0 (CH2 O-3′Bn), 69.8 (C-5), 68.6 (C-6), 67.5 (d, 3J(C−F) = 5.3 Hz, C-6′), 62.6 (C-2′), 55.4 (MeO). 19F NMR (CDCl3, 376 MHz): δ −218.94 (ddd, 2J(H−F) = 49.8 Hz, 3J(H−F) = 27.5, 26.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3692. Methyl 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-galactopyranosyl)-2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside (4C-α) and Methyl 3-O-(2-Azido-3,6-di-Obenzyl-2,4-dideoxy-4-fluoro-β-D-galactopyranosyl)-2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside (4C-β). Compounds 4C-α and 4C-β were prepared by glycosylation of methyl 2-O-benzyl-4,6-O-benzylidene-α-D-galactopyranoside11 (C) with β-3 according to the general procedure. Column chromatography in EtOAc/PE 1:2.3 gave the product in two fractions. Preparative TLC of the faster moving fraction in EtOAc/PE 1:2 afforded 4C-α (49 mg, 66%) as a colorless crystalline solid. Preparative TLC of the slower moving fraction in toluene/Et2O/PE 2:3:2 afforded 4C-β (4 mg, 5%) as a colorless syrup with some contamination in the aliphatic region (NMR); 4C-β was therefore not included in yield calculation. Data for 4C-α: Rf 0.14 (EtOAc/heptane 1:3), mp 122−124 °C (heptane/EtOAc). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.57 (dd, 2H, J = 7.7, 1.9 Hz, CHarom), 7.41−7.25 (m, 18H, CHarom), 5.58 (s, 1H, CHPh), 5.22 (d, 1H, J = 3.4 Hz, H-1′), 4.86 (dd, 1H, J = 50.3, 2.4 Hz, H-4′), 4.74 (d, 1H, J = 3.6 Hz, H-1), 4.73 (d, 1H, J = 11.5 Hz, CHH O-3′Bn), 4.64 (d, 1H, J = 12.0 Hz, CHH O-2Bn), 4.63 (d, 1H, J = 11.5 Hz, CHH O-3′Bn), 4.52 (d, 1H, J = 12.0 Hz, CHH O-2Bn), 4.51, 4.46 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6′Bn), 4.40 (dd, 1H, J = 3.6, 1.2 Hz, H-4), 4.31− 4.20 (m, 3H, H-3, H-6, H-5′), 4.08 (dd, 1H, J = 12.6, 1.8 Hz, H-6), 4.03 (dd, 1H, J = 10.2, 3.6 Hz, H-2), 3.93 (ddd, 1H, J = 26.9, 10.7, 2.4 Hz, H-3′), 3.68−3.57 (m, 4H, H-5, H-2′, H-6′), 3.37 (s, 3H, MeO). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.5 (Cq O2Bn), 138.1 (Cq O-6′Bn), 137.7 (Cq), 137.2 (Cq O-3′Bn), 128.9 (CHarom), 128.7, 128.6, 128.5 (3× 2CHarom), 128.3 (CHarom), 128.18, 128.17, 128.1 (3× 2CHarom), 128.0 (CHarom), 127.81 (2CHarom), 127.77 (CHarom), 126.2 (2CHarom), 100.8 (CHPh), 99.2 (C-1), 93.9 (C-1′), 85.7 (d, 1J(C−F) = 184.9 Hz, C-4′), 74.7 (C-2), 73.6 (CH2 OU


Article

The Journal of Organic Chemistry COSY, HSQC, HMBC): δ 7.41−7.30 (m, 10H, CHarom), 4.91 (d, 1H, J = 3.6 Hz, H-1), 4.81 (dd, 1H, J = 49.7, 2.6 Hz, H-4′), 4.75, 4.70 (2× d, 2× 1H, J = 11.7 Hz, CHH O-3′Bn), 4.63 (dd, 1H, J = 8.0, 0.6 Hz, H-1′), 4.57, 4.53 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6′Bn), 4.04 (dd, 1H, J = 10.2, 3.2 Hz, H-3), 3.86 (t, 1H, J = 6.4 Hz, H-5), 3.77 (dd, 1H, J = 10.2, 3.6 Hz, H-2), 3.73−3.57 (m, 5H, H-4, H-2′, H-5′, H-6′), 3.55, 3.53 (2× s, 2× 3H, MeO), 3.52−3.48 (m, 2H, H-6), 3.42, 3.38 (2× s, 2× 3H, MeO), 3.27 (ddd, 1H, J = 27.7, 10.4, 2.7 Hz, H-3′). 13 C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O6′Bn), 137.4 (Cq O-3′Bn), 128.66, 128.65 (2× 2CHarom), 128.2, 128.04 (2× 1CHarom), 127.99, 127.8 (2× 2CHarom), 102.9 (C-1′), 97.6 (C-1), 84.6 (d, 1J(C−F) = 185.0 Hz, C-4′), 79.4 (C-4), 78.5 (C-2), 77.5 (d, 2J(C−F) = 16.6 Hz, C-3′), 77.4 (C-3), 73.8 (CH2 O-6′Bn), 72.2 (CH2 O-3′Bn), 72.0 (d, 2J(C−F) = 18.1 Hz, C-5′), 71.6 (C-6), 69.3 (C-5), 67.4 (d, 3J(C−F) = 5.3 Hz, C-6′), 63.2 (C-2′), 61.6, 59.4, 58.7, 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −219.34 (ddd, 2 J(H−F) = 49.7 Hz, 3J(H−F) = 27.7, 27.2 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C30H41FNO9, 578.2759; found, 578.2760. Methyl 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (4E-α) and Methyl 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy4-fluoro-β-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (4E-β). Compounds 4E-α and 4E-β were prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside46 (E) with 4 according to the general procedure. Chromatography of the crude product in EtOAc/PE 1:5 afforded 4E-α (26 mg, 31%) as a colorless syrup. Continued elution gave 4E-β (20 mg, 24%) as a colorless syrup. The combined yield was 55%. Data for 4E-α: Rf 0.40 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.24 (m, 25H, CHarom), 5.73 (d, 1H, J = 3.7 Hz, H-1′), 5.09 (d, 1H, J = 10.6 Hz, CHH O-3Bn), 4.85 (dd, 1H, J = 50.4, 2.3 Hz, H-4′), 4.87 (d, 1H, J = 10.6 Hz, CHH O-3Bn), 4.76 (d, 1H, J = 12.0 Hz, CHH O-2Bn), 4.70 (d, 1H, J = 11.4 Hz, CHH O-3′Bn), 4.63 (d, 1H, J = 12.0 Hz, CHH O-2Bn), 4.61 (d, 1H, J = 11.4 Hz, CHH O-3′Bn), 4.60 (d, 1H, J = 3.6 Hz, H-1), 4.56, 4.45 (2× d, 2× 1H, J = 12.2 Hz, CHH O-6Bn), 4.38 (s, 2H, CH2 O-6′Bn), 4.06 (dd, 1H, J = 9.6, 8.6 Hz, H-3), 3.87 (dd, 1H, J = 9.9, 8.6 Hz, H-4), 3.82−3.76 (m, 2H, H-5, H-5′), 3.76 from 1H{19F} (dd, 1H, J = 10.7, 2.3 Hz, H-3′), 3.67−3.63 (m, 3H, H6, H-2′), 3.56 (dd, 1H, J = 9.6, 3.6 Hz, H-2), 3.54 (dd, 1H, J = 9.1, 7.9 Hz, H-6′), 3.44 (ddd, 1H, J = 9.1, 5.7, 1.4 Hz, H-6′), 3.39 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7 (Cq O-3Bn), 138.3 (Cq O-6Bn), 138.0 (Cq O-2Bn), 137.9 (Cq O6′Bn), 137.3 (Cq O-3′Bn), 128.7, 128.6 (2× 2CHarom), 128.5 (4CHarom), 128.4, 128.3, 128.1 (3× 2CHarom), 127.93 (3CHarom), 127.85, 127.8 (2× 2CHarom), 127.64, 127.61 (2× 1CHarom), 127.55 (2CHarom), 97.9 (C-1), 97.7 (C-1′), 85.3 (d, 1J(C−F) = 185.3 Hz, C4′), 82.0 (C-3), 80.5 (C-2), 75.2 (CH2 O-3Bn), 74.5 (d, 2J(C−F) = 18.2 Hz, C-3′), 73.9 (C-4), 73.7 (CH2 O-6′Bn), 73.4 (CH2 O-2Bn), 73.3 (CH2 O-6Bn), 71.6 (CH2 O-3′Bn), 69.6 (C-6), 69.5 (C-5), 68.7 (d, 2J(C−F) = 18.3 Hz, C-5′), 67.7 (d, 3J(C−F) = 2.5 Hz, C-6′), 59.9 (d, 3 J(C−F) = 2.5 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −221.64 (ddd, 2J(H−F) = 50.2 Hz, 3J(H−F) = 29.7, 26.1 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3695. Data for 4E-β: Rf 0.28 (EtOAc/heptane 1:5). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.19 (m, 25H, CHarom), 4.88 (d, 1H, J = 10.7 Hz, CHH O-3Bn), 4.80 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.78 (d, 1H, J = 10.7 Hz, CHH O-3Bn), 4.75 (d, 1H, J = 11.9 Hz, CHH O-3′Bn), 4.75 (dd, 1H, J = 49.8, 2.6 Hz, H-4′), 4.69 (d, 1H, J = 12.1 Hz, CHH O-6Bn), 4.64 (d, 1H, J = 11.9 Hz, CHH O-3′Bn), 4.63 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.59 (d, 1H, J = 3.7 Hz, H-1), 4.41 (d, 1H, J = 11.9 Hz, CHH O-6′Bn), 4.39 (d, 1H, J = 12.1 Hz, CHH O-6Bn), 4.34 (d, 1H, J = 11.9 Hz, CHH O-6′Bn), 4.11 (dd, 1H, J = 8.2, 1.0 Hz, H-1′), 3.95 (dd, 1H, J = 10.8, 2.9 Hz, H-6), 3.92 (t, 1H, J = 9.4 Hz, H-4), 3.85 (dd, 1H, J = 9.4, 9.0 Hz, H-3), 3.77 (ddd, 1H, J = 9.4, 2.9, 1.9 Hz, H-5), 3.69 (dd, 1H, J = 10.8, 1.9 Hz, H-6), 3.61 (dd, 1H, J = 10.2, 8.2 Hz, H-2′), 3.48 (dd, 1H, J = 9.4, 8.5 Hz, H-6′), 3.47 (dd, 1H, J = 9.0, 3.7 Hz, H-2), 3.38 (s, 3H, MeO), 3.35 (ddd, 1H, J = 9.4, 5.3, 1.5 Hz, H-6′), 3.17

(ddd, 1H, J = 27.1, 8.5, 5.3 Hz, H-5′), 3.08 (ddd, 1H, J = 27.6, 10.2, 3.2 Hz, H-3′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.3 (Cq O-3Bn), 138.5 (Cq O-2Bn), 138.08, 138.06 (Cq O-6/ 6′Bn), 137.3 (Cq O-3′Bn), 128.7, 128.58, 128.56, 128.52 (4× 2CHarom), 128.24 (3CHarom), 128.21, 128.18, 128.15, 128.0 (4× 2CHarom), 127.94, 127.92, 127.91 (3× 1CHarom), 127.8 (2CHarom), 127.4 (CHarom), 100.8 (C-1′), 98.5 (C-1), 83.7 (d, 1J(C−F) = 185.2 Hz, C-4′), 80.2 (C-3), 79.3 (C-2), 78.1 (d, 2J(C−F) = 18.1 Hz, C-3′), 76.7 (C-4), 75.5 (CH2 O-3Bn), 73.73 (CH2 O-2Bn), 73.66 (CH2 O6′Bn), 73.5 (CH2 O-6Bn), 72.0 (d, 2J(C−F) = 18.2 Hz, C-5′), 71.7 (CH2 O-3′Bn), 69.8 (C-5), 68.3 (C-6), 67.0 (d, 3J(C−F) = 5.2 Hz, C6′), 63.2 (d, 3J(C−F) = 9.1 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −219.83 (dt, 2J(H−F) = 49.7 Hz, 3J(H−F) = 27.1 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3698. 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-D-galactopyranosyl)-1,2:5,6-di-O-isopropylidene-α- D-glucofuranose (4F-α) and 3-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4fluoro-β-D-galactopyranosyl)-1,2:5,6-di-O-isopropylidene-α-Dglucofuranose (4F-β). Compounds 4F-α and 4F-β were prepared by glycosylation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (F) with 4 according to the general procedure. Column chromatography in toluene/Et2O/PE 1:1:2 gave the product in two fractions. Preparative TLC of the faster moving fraction in toluene/Et2O/PE 9:15:20 afforded 4F-α (35 mg, 55%) as a colorless syrup. The slower moving fraction from column chromatography afforded 4F-β (13 mg, 21%) as a colorless syrup. The combined yield was 76%. Data for 4F-α: Rf 0.33 (toluene/Et2O/PE 3:5:6). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.42− 7.30 (m, 10H, CHarom), 5.86 (d, 1H, J = 3.6 Hz, H-1), 5.24 (d, 1H, J = 3.3 Hz, H-1′), 4.89 (dd, 1H, J = 50.2, 2.2 Hz, H-4′), 4.75, 4.70 (2× d, 2× 1H, J = 11.5 Hz, CHH O-3′Bn), 4.62 (d, 1H, J = 3.6 Hz, H-2), 4.59, 4.55 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6′Bn), 4.45 (ddd, 1H, J = 8.4, 5.6, 6.2 Hz, H-5), 4.25 (d, 1H, J = 2.7 Hz, H-3), 4.14 (dd, 1H, J = 8.5, 6.2 Hz, H-6), 4.08 (dd, 1H, J = 8.4, 2.7 Hz, H-4), 3.98−3.87 (m, 1H, H-5′), 3.95 (dd, 1H, J = 8.5, 5.6 Hz, H-6), 3.87 from 1H{19F} (dd, 1H, J = 10.7, 3.5 Hz, H-2′), 3.80 (ddd, 1H, J = 25.3, 10.7, 2.4 Hz, H-3′), 3.72−3.66 (m, 2H, H-6′), 1.49, 1.42, 1.36, 1.23 (4× s, 4× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.7 (Cq O-6′Bn), 137.2 (Cq O-4′Bn), 128.72, 128.65 (2× 2CHarom), 128.3, 128.1 (2× 1CHarom), 128.0, 127.9 (2× 2CHarom), 112.2, 109.4 (CMe2), 105.3 (C-1), 98.6 (C-1′), 85.6 (d, 1J(C−F) = 185.3 Hz, C-4′), 83.6 (C-2), 81.5 (C-4), 81.3 (C-3), 74.7 (d, 2J(C−F) = 18.1 Hz, C-3′), 73.9 (CH2 O-6′Bn), 72.0 (C-5), 71.9 (CH2 O-3′Bn), 69.2 (d, 2J(C−F) = 18.4 Hz, C-5′), 68.3 (d, 3J(C−F) = 5.2 Hz, C-6′), 67.8 (C-6), 59.7 (d, 3 J(C−F) = 2.4 Hz, C-2′), 27.0, 26.9, 26.3, 25.4 (Me). 19F NMR (CDCl3, 376 MHz): δ −220.64 (ddd, 2J(H−F) = 50.2 Hz, 3J(H−F) = 29.3, 25.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2754. Data for 4F-β: Rf 0.23 (toluene/Et2O/PE 3:5:6). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.39− 7.30 (m, 10H, CHarom), 5.96 (d, 1H, J = 3.7 Hz, H-1), 4.81 (dd, 1H, J = 49.5, 2.6 Hz, H-4′), 4.77, 4.67 (2× d, 2× 1H, J = 11.9 Hz, CHH O3′Bn), 4.59−4.52 (m, 3H, H-2, CH2 O-6′Bn), 4.37 (td, 1H, J = 6.2, 4.9 Hz, H-5), 4.33−4.29 (m, 2H, H-3, H-4), 4.31 from HSQC (d, 1H, J = 7.8 Hz, H-1′), 4.03 (d, 2H, J = 6.2 Hz, H-6), 3.71 (dd, 1H, J = 9.4, 7.8 Hz, H-6′), 3.66−3.61 (m, 2H, H-2′, H-6′), 3.53 (ddd, 1H, J = 26.5, 7.8, 5.6 Hz, H-5′), 3.29 (ddd, 1H, J = 27.4, 10.3, 2.6 Hz, H-3′), 1.49, 1.41 (2× s, 2× 3H, Me), 1.32 (s, 2× 3H, Me). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.7 (Cq O-6′Bn), 137.1 (Cq O-4′Bn), 128.74, 128.68 (2× 2CHarom), 128.3, 128.2 (2× 1CHarom), 128.1, 128.0 (2× 2CHarom), 112.2, 108.7 (CMe2), 105.3 (C-1), 100.6 (C-1′), 84.1 (d, 1J(C−F) = 185.9 Hz, C-4′), 83.0 (C-2), 81.2 (C-4), 80.5 (C-3), 77.5 (d, 2J(C−F) = 25.5 Hz, C-3′), 73.9 (CH2 O-6′Bn), 73.4 (C-5), 72.7 (d, 2J(C−F) = 18.3 Hz, C-5′), 72.0 (CH2 O-3′Bn), 67.4 (d, 3J(C−F) = 5.2 Hz, C-6′), 61.1 (C-6), 62.7 (C-2′), 26.9, 26.7, 26.5, 25.6 (Me). 19F NMR (CDCl3, 376 MHz): δ −219.19 (ddd, 2 J(H−F) = 49.5 Hz, 3J(H−F) = 27.4, 26.5 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H41FNO9, 602.2759; found, 602.2763. V


Article

The Journal of Organic Chemistry Methyl 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα-D-galactopyranosyl)-2,3,6-tri-O-benzyl-α-D-galactopyranoside (4G-α). Compound 4G-α was prepared by glycosylation of methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside46 (G) with 4 according to the general procedure. Column chromatography in EtOAc/PE 1:3 gave the product in two fractions. Preparative TLC of the faster moving fraction in PE/Et2O 7:6 afforded 4G-α (33 mg, 40%) as a colorless syrup. Preparative TLC of the slower moving fraction in PE/ Et2O 5:6 afforded colorless syrupy β-anomer 4G-β (20 mg) containing about 10% of an unknown carbohydrate inseparable under given chromatographic conditions. Data for 4G-α: Rf 0.37 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.43−7.21 (m, 25H, CHarom), 4.90 (dd, 1H, J = 50.0, 2.3 Hz, H-4′), 4.90 (d, 1H, J = 3.4 Hz, H-1′), 4.82−4.72 (m, 5H, H-1, CH2 O-2Bn, CHH O-3Bn, CHH O-3′Bn), 4.66 (d, 1H, J = 12.6 Hz, CHH O-3Bn), 4.60 (d, 1H, J = 11.2 Hz, CHH O-3′Bn), 4.57, 4.51 (2× d, 2× 1H, J = 11.8 Hz, CHH O-6Bn), 4.46 (ddd, 1H, J = 30.6, 9.2, 5.1 Hz, H-5′), 4.28, 4.23 (2× d, 2× 1H, J = 11.7 Hz, CHH O-6′Bn), 4.16 (d, 1H, J = 2.3 Hz, H-4), 3.93−3.82 (m, 4H, H-2, H-3, H-5, H-6), 3.78 (ddd, 1H, J = 25.9, 10.7, 2.3 Hz, H-3′), 3.70 (ddd, 1H, J = 10.7, 3.4, 1.5 Hz, H-2′), 3.56−3.50 (m, 2H, H-6, H-6′), 3.37 (s, 3H, MeO), 3.29 (ddd, 1H, J = 8.6, 5.1, 1.6 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 138.7 (Cq O-3Bn), 138.4 (Cq O-2Bn), 138.0 (Cq O6′Bn), 137.6 (Cq O-6Bn), 137.5 (Cq O-3′Bn), 128.63, 128.60, 128.50, 128.49, 128.4, 128.3, 128.23 (7× 2CHarom), 128.16, 128.1 (2× 1CHarom), 128.0 (2CHarom), 127.9 (CHarom), 127.8 (3CHarom), 127.6 (CHarom), 127.5 (2CHarom), 98.62, 98.60 (C-1/1′), 85.1 (d, 1J(C−F) = 184.5 Hz, C-4′), 77.2 (C-3), 75.3 (C-2), 75.1 (d, 2J(C−F) = 18.3 Hz, C3′), 74.9 (C-4), 73.7 (CH2 O-6Bn), 73.4 (CH2 O-6′Bn), 73.2 (CH2 O-2Bn), 72.9 (CH2 O-3Bn), 71.5 (CH2 O-3′Bn), 68.9 (C-5), 68.0 (d, 2 J(C−F) = 17.9 Hz, C-5′), 67.2 (C-6), 67.1 (d, 3J(C−F) = 6.0 Hz, C-6′), 59.8 (d, 3J(C−F) = 2.6 Hz, C-2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −221.97 (ddd, 2J(H−F) = 50.0 Hz, 3J(H−F) = 30.6, 25.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3694. Data for 4G-β: Rf 0.27 (EtOAc/heptane 1:3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.43−7.24 (m, 25H, CHarom), 4.92 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.83 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.76 (d, 1H, J = 11.9 Hz, CHH O-3′Bn), 4.73 (dd, 1H, J = 49.5, 2.6 Hz, H-4′), 4.70 (d, 1H, J = 11.9 Hz, CHH O-3′Bn), 4.69 (dd, 1H, J = 8.1, 1.0 Hz, H-1′), 4.67 (d, 1H, J = 12.1 Hz, CHH O-2Bn), 4.65 (d, 1H, J = 12.2 Hz, CHH O-3Bn), 4.64 (d, 1H, J = 3.7 Hz, H-1), 4.56, 4.41 (2× d, 2× 1H, J = 12.0 Hz, CHH O6Bn), 4.51−4.40 (m, 2H, CH2 O-6′Bn), 4.16 (dd, 1H, J = 3.0, 1.3 Hz, H-4), 4.12 (dd, 1H, J = 10.1, 3.7 Hz, H-2), 3.94−3.89 (m, 2H, H-3, H-5), 3.68−3.62 (m, 2H, H-6, H-2′), 3.59 (dd, 1H, J = 9.2, 8.0 Hz, H6′), 3.56 (dd, 1H, J = 10.2, 6.5 Hz, H-6), 3.43 (ddd, 1H, J = 9.2, 5.5, 1.5 Hz, H-6′), 3.38 (s, 3H, MeO), 3.33 (ddd, 1H, J = 26.9, 5.5, 8.0 Hz, H-5′), 3.17 (ddd, 1H, J = 27.9, 10.4, 2.6 Hz, H-3′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 139.1 (Cq O-3Bn), 138.7 (Cq O-2Bn), 138.6 (Cq O-6Bn), 137.8 (Cq O-6′Bn), 137.4 (Cq O-3′Bn), 128.68, 128.65, 128.49, 128.46, 128.45, 128.3 (6× 2CHarom), 128.2, 128.1 (2× 1CHarom), 128.0 (2CHarom), 127.9 (CHarom), 127.8 (2CHarom), 127.61 (CHarom), 127.54 (2CHarom), 127.51 (CHarom), 127.2 (2CHarom), 101.5 (C-1′), 98.9 (C-1), 84.6 (d, 1J(C−F) = 185.2 Hz, C-4′), 78.6 (C-3), overlapped with CDCl3 (C-3′), 76.5 (C-2), 73.90, 73.85 (C-4/CH2 O-2Bn), 73.7 (CH2 O-6′Bn), 73.51, 73.49 (CH2 O-3/6Bn), 72.1 (CH2 O-3′Bn), 72.0 (d, 2J(C−F) = 18.3 Hz, C5′), 69.9 (C-6), 69.3 (C-5), 67.4 (d, 3J(C−F) = 5.2 Hz, C-6′), 63.0 (C2′), 55.5 (MeO). 19F NMR (CDCl3, 376 MHz): δ −219.30 (ddd, 2 J(H−F) = 49.5 Hz, 3J(H−F) = 26.9, 27.9 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C48H53FNO9, 806.3698; found, 806.3694. 4-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-D-galactopyranosyl)-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-Dglucopyranose (4H-α). Compound 4H-α was prepared by glycosylation of 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-β-D-glucopyranose47 (H) with 4 according to the general procedure. Column chromatography of the crude product in EtOAc/PE 1:5 afforded a fraction containing 4H-α. This anomer was further purified by

preparative TLC in PE/toluene/Et2O 2:1:1 which gave 4H-α (28 mg, 44%) as a colorless syrup. The β-anomer 4H-β could not be separated by silica gel column chromatography because of its co-elution with the acceptor H and parallel decomposition (19F NMR). In a repeated experiment, the crude product 4H was separated from the acceptor H on Sephadex LH-20 in dichloromethane/MeOH 1:1 to give a mixture of both anomers, the NMR spectra of which were recorded. Selected NMR data for β-anomer 4H-β were extracted from these NMR spectra. Data for 4H-α: Rf 0.58 (EtOAc/heptane 1:1). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.27 (m, 15H, CHarom), 5.57 (t, 1H, J = 1.5 Hz, H-1), 4.92 (d, 1H, J = 3.6 Hz, H-1′), 4.85 (m, 1H, H-5), 4.83 (dd, 1H, J = 50.4, 2.5 Hz, H-4′), 4.73, 4.68 (2× d, 2× 1H, J = 11.5 Hz, CHH Bn), 4.68, 4.56 (2× d, 2× 1H, J = 12.2 Hz, CHH Bn), 4.55 (br s, 2H, CH2 Bn), 4.31 (dt, 1H, J = 30.2, 6.3 Hz, H-5′), 4.11 (ddd, 1H, J = 26.7, 10.9, 2.5 Hz, H-3′), 4.06 (dd, 1H, J = 7.4, 1.2 Hz, H-6en), 3.78 (q, 1H, J = 1.5 Hz, H-3), 3.69−3.66 (m, 3H, H-2′, H-6′), 3.57 (dd, 1H, J = 7.4, 6.0 Hz, H-6ex), 3.51 (dtd, 1H, J = 1.5, 0.9, 0.8 Hz, H-4), 3.09 (t, 1H, J = 1.5 Hz, H-2). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.9, 137.3, 137.1 (Cq), 128.8, 128.7, 128.5 (3× 2CHarom), 128.3, 128.18 (2× 1CHarom), 128.20, 128.06 (2× 2CHarom), 127.9 (CHarom), 127.6 (2CHarom), 100.9 (d, 4J(C−F) = 3.8 Hz, C-1′ overlapped with C-1), 86.2 (d, 1J(C−F) = 184.9 Hz, C-4′), 78.6 (C-4), 77.9 (C-3), 74.5 (C-5), 74.2 (d, 2J(C−F) = 18.0 Hz, C-3′), 73.6, 73.0, 72.0 (CH2 Bn), 69.3 (d, 2J(C−F) = 18.1 Hz, C-5′), 68.8 (d, 3J(C−F) = 5.3 Hz, C-6′), 65.0 (C-6), 59.2 (d, 3J(C−F) = 2.5 Hz, C-2′), 58.7 (C-2). 19F NMR (CDCl3, 376 MHz): δ −220.04 (ddd, 2J(H−F) = 50.3 Hz, 3J(H−F) = 30.2, 26.7 Hz). HRMSAPCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2563. Selected NMR data for 4H-β: 1H NMR (CDCl3, 400 MHz, HSQC): δ 5.48 (t, 1H, J = 1.5 Hz, H-1), 4.79 (d, J = 49,7 Hz, H-4′), 4.29 (d, 1H, J = 8 Hz, H-1′), 19F NMR (CDCl3, 376 MHz): δ −218.96 (dt, 2J(H−F) = 49.6 Hz, 3J(H−F) = 27.1 Hz). Methyl 2-O-(2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoroα- D -galactopyranosyl)-4,6-O-benzylidene-3-O-benzyl-α- D mannopyranoside (4I-α). Compound 4I-α was prepared by glycosylation of methyl 4,6-O-benzylidene-3-O-benzyl-α-D-manopyranoside 48 (I) with 4 according to the general procedure. Chromatography of the crude product in EtOAc/PE 3:10 afforded a fraction containing 4I-α. This anomer was purified by preparative TLC in EtOAc/PE 1:3 (Rf 0.26) which gave 4I-α (42 mg, 57%) as a colorless syrup. 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.50 (dd, 2H, J = 7.3, 2.4 Hz, CHarom), 7.44 (dd, 2H, J = 8.2, 1.5 Hz, CHarom), 7.39−7.25 (m, 16H, CHarom), 5.64 (s, 1H, CHPh), 5.34 (d, 1H, J = 3.6 Hz, H-1′), 4.94 (dd, 1H, J = 50.3, 2.4 Hz, H-4′), 4.88 (d, 1H, J = 12.3 Hz, CHH Bn), 4.80 (d, 1H, J = 11.3 Hz, CHH Bn), 4.75 (d, 1H, J = 3.1 Hz, H-1), 4.74 (d, 1H, J = 11.3 Hz, CHH Bn), 4.70 (d, 1H, J = 12.3 Hz, CHH Bn), 4.59, 4.55 (2× d, 2× 1H, J = 11.8 Hz, CHH Bn), 4.26 (dd, 1H, J = 9.5, 4.1 Hz, H-6), 4.21 (t, 1H, J = 9.4 Hz, H-4), 4.09−3.94 (m, 4H, H-2, H-3, H-3′, H-5′), 3.87−3.75 (m, 2H, H-5, H-6), 3.72−3.65 (m, 3H, H-2′, H-6′), 3.24 (s, 3H, MeO). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 138.8, 137.8, 137.7, 137.4 (Cq), 129.0 (CHarom), 128.7, 128.6, 128.4, 128.3 (4× 2CHarom), 128.2 (CHarom), 128.0 (3CHarom), 127.9 (2CHarom), 127.6 (CHarom), 127.5, 126.2 (2× 2CHarom), 101.7 (CHPh), 100.8 (C-1), 99.8 (C-1′), 85.9 (d, 1J(C−F) = 185.4 Hz, C-4′), 79.4 (C-4), 75.5 (C-2), 74.0 (C-3), 73.9 (d, 2J(C−F) = 18.5 Hz, C-3′), 73.8, 73.2, 71.7 (CH2 Bn), 69.1 (d, 2J(C−F) = 18.3 Hz, C-5′), 69.05 (C-6), 68.5 (d, 3J(C−F) = 5.0 Hz, C-6′), 64.0 (C-5), 59.2 (d, 3J(C−F) = 2.5 Hz, C2′), 54.9 (MeO). 19F NMR (CDCl3, 376 MHz): δ −220.46 (ddd, 2 J(H−F) = 50.3 Hz, 3J(H−F) = 29.8, 26.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C41H45FNO9, 714.3072; found, 714.3071. Selected resonances were tentatively assigned as 4I-β: 1H NMR (CDCl3, 400 MHz, HSQC, COSY): δ 4.57 (d, 1H, J = 7.7 Hz, H-1′). 19 F NMR (CDCl3, 376 MHz): δ −218.91 (m). 2-[2-(2-Chloroethoxy)ethoxy]ethyl 2-Azido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-D-galactopyranoside (α-22) and 2[2-(2-chloroethoxy)ethoxy]ethyl 2-Azido-3,6-di-O-benzyl-2,4dideoxy-4-fluoro-β-D-galactopyranoside (β-22). A mixture of 4 W


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The Journal of Organic Chemistry (200 mg, 0.417 mmol), diphenyl sulfoxide (104 mg, 0.514 mmol) and tri-tert-butylpyrimidine (248 mg, 0.998 mmol) was co-evaporated with dry toluene (3×) and then dried for 20 min at vacuum of an oil pump. Dry dichloromethane (8 mL) and 3 Å molecular sieves were added, and the resulting suspension was stirred for 1 h at room temperature under argon atmosphere and then cooled to −78 °C. Triflic anhydride (90 μL, 0.54 mmol) was added dropwise; the reaction was allowed to warm up to −60 °C and then recooled to −78 °C. A solution of 2-[2-(2-chloroethoxy)ethoxy]ethanol (169 mg, 1.002 mmol) in dry dichloromethane (2 mL) was added dropwise. The reaction mixture was allowed to warm up to −40 °C in 90 min and stirred for additional 3 h. The reaction mixture was quenched with Et3N (0.4 mL, 2.9 mmol) at −40 °C and left at −20 °C overnight. It was then diluted with dichloromethane, filtered, and washed with water. The water phase was extracted with dichloromethane (3×). The organic extracts were combined, dried, and concentrated. Column chromatography of the residue in EtOAc/PE 1:2 afforded α-22 as a colorless syrup (52 mg, 23%), and continued elution afforded β-22 as a colorless syrup (120 mg, 53%). Combined yield was 76%. Data for α-22: Rf 0.25 (EtOAc/heptane 1:3), [α]20 D +54 (c 0.71, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.42−7.31 (m, 10H, CHarom), 4.99 (dd, 1H, J = 3.6, 3.5 Hz, H-1), 4.94 (dd, 1H, J = 50.1, 2.5 Hz, H-4), 4.77, 4.69 (2× d, 2× 1H, J = 11.5 Hz, CHH O-3Bn), 4.58, 4.54 (2× d, 2× 1H, J = 11.9 Hz, CHH O-6Bn), 4.04 (dt, 1H, J = 29.8, 6.7 Hz, H-5), 3.94 (ddd, 1H, J = 26.8, 10.6, 2.5 Hz, H-3), 3.86−3.79 (m, 1H, CHH O-1), 3.74−3.67 (m, 7H, CHH O-1, 2× CH2, H-2, H-6), 3.65−3.58 (m, 5H, 2× CH2, H-6), 3.59 (t, 2H, J = 5.6 Hz, CH2Cl). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-6Bn), 137.3 (Cq O-3Bn), 128.6, 128.5 (2× 2CHarom), 128.01 (CHarom), 127.9 (2CHarom), 127.9 (CHarom), 127.8 (2CHarom), 98.1 (C-1), 85.6 (d, 1J(C−F) = 184.8 Hz, C-4), 74.3 (d, 2J(C−F) = 18.2 Hz, C-3), 73.7 (CH2 6-OBn), 71.6 (CH2 3-OBn), 71.4, 70.7, 70.6, 70.2 (CH2), 68.2 (d, 2J(C−F) = 18.3 Hz, C-5), 67.9 (d, 3J(C−F) = 5.7 Hz, C-6), 67.6 (CH2), 59.1 (d, 3J(C−F) = 2.5 Hz, C-2), 42.8 (CH2Cl). 19F NMR (CDCl3, 376 MHz): δ −221.28 (ddd, 2 J(H−F) = 50.1 Hz, 3J(H−F) = 29.8, 26.8 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H34ClFNO6, 510.2053; found, 510.2054. Data for β-22: Rf 0.18 (EtOAc/heptane 1:3), [α]20 D −22 (c 0.97, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC): δ 7.41−7.28 (m, 10H, CHarom), 4.79 (dd, 1H, J = 49.6, 2.6 Hz, H-4), 4.77, 4.69 (2× d, 2× 1H, J = 11.9 Hz, CHH OBn), 4.55 (s, 2H, CH2 OBn), 4.34 (dd, 1H, J = 8.1, 1.1 Hz, H-1), 3.99 (dt, 1H, J = 10.7, 4.1 Hz, CHH O-1), 3.80−3.60 (m, 14H, CHH O-1, 5× CH2, H2, H-6), 3.55 (ddd, 1H, J = 26.6, 7.6, 5.7 Hz, H-5), 3.29 (ddd, 1H, J = 27.6, 10.4, 2.6 Hz, H-3). 13C{1H} NMR (CDCl3, 101 MHz, HSQC): δ 137.8, 137.3 (Cq), 128.69, 128.65 (2× 2CHarom), 128.2, 128.08 (2× 1CHarom), 128.06, 127.95 (2× 2CHarom), 102.3 (C-1), 84.5 (d, 1J(C−F) = 185.4 Hz, C-4), 77.6 (d, 2J(C−F) = 15.0 Hz, C-3), 73.9 (CH2 OBn),72.3 (d, 2J(C−F) = 18.2 Hz, C-5), 72.1 (CH2 OBn), 71.5, 70.83, 70.81, 70.6, 69.3 (CH2), 67.6 (d, 3J(C−F) = 5.2 Hz, C-6), 62.7 (C-2), 42.9 (CH2Cl). 19F NMR (CDCl3, 376 MHz): δ −219.06 (ddd, 2 J(H−F) = 49.6 Hz, 3J(H−F) = 27.6, 26.6 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C26H34ClFNO6, 510.2053; found, 510.2054. 2-[2-(2-Azidoethoxy)ethoxy]ethyl 2-Acetamido-3,6-di-Obenzyl-2,4-dideoxy-4-fluoro-β-D-galactopyranoside (23). Compound β-22 (48 mg, 0.096 mmol) was dissolved in thioacetic acid (150 μL, 2.11 mmol), and the solution was stirred for 20 h under argon atmosphere. TLC EtOAc/PE 1:1 then revealed the absence of the starting compound and the presence of one major slow-moving product. Thioacetic acid was then evaporated under reduced pressure and column chromatography of the residue in dichloromethane/ MeOH 30:1 afforded the corresponding 2-acetamido-2-deoxy-β-Dgalactopyranoside (41 mg, 83%) which was immediately used in the next step. This product was dissolved in DMF (1.5 mL), and NaN3 (30 mg, 0.46 mmol) and TBAI (20 mg, 0.05 mmol) were added. The reaction mixture was stirred at 50 °C for 27 h. TLC in dichloromethane/MeOH 30:1 did not separate the product from the starting material, and the completion of the reaction was confirmed by HRMS. DMF was removed under reduced pressure, and

column chromatography in dichloromethane/MeOH 30:1 afforded product 23 as a white crystalline compound (35 mg, 70% over 2 steps). Recrystallization (EtOAc/heptane) afforded 10 mg of 23 for analysis, mp 93−96 °C (EtOAc/heptane), [α]20 D +5 (c 0.76, CHCl3), Rf 0.24 (dichloromethane/methanol 30:1). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.29 (m, 10H, CHarom), 5.90 (d, 1H, J = 7.3 Hz, NH), 5.06 (d, 1H, J = 8.3 Hz, H-1), 4.88 (dd, 1H, J = 50.0, 2.5 Hz, H-4), 4.72 (d, 1H, J = 11.7 Hz, CHH O-3Bn), 4.57 (s, 2H, CH2 O-6Bn), 4.54 (d, 1H, J = 11.7 Hz, CHH O3Bn), 4.31 (ddd, 1H, J = 28.4, 10.9, 2.5 Hz, H-3), 3.94 (dt, 1H, J = 11.5, 4.3 Hz, CHH O-1), 3.76−3.59 (m, 12H, CHH O-1, 4× CH2, H5, H-6), 3.46 (ddd, 1H, J = 10.9, 8.3, 7.3 Hz, H-2), 3.35 (t, 2H, J = 5.1 Hz, CH2N3), 1.94 (s, 3H, Me Ac). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 171.0 (CO), 138.0, 137.9 (Cq), 128.61 (4CHarom), 128.12 (2CHarom), 128.08, 128.0 (2× 1CHarom), 127.9 (2CHarom), 99.7 (C-1), 85.2 (d, 1J(C−F) = 184.5 Hz, C-4), 75.1 (d, 2 J(C−F) = 18.0 Hz, C-3), 73.8 (CH2 O-6Bn),72.2 (d, 2J(C−F) = 18.1 Hz, C-5), 71.9 (CH2 O-3Bn), 70.8, 70.7, 70.6, 70.1, 68.6 (CH2), 67.9 (d, 3 J(C−F) = 5.0 Hz, C-6), 54.8 (d, 3J(C−F) = 1.2 Hz, C-2), 50.8 (CH2N3), 23.8 (Me). 19F NMR (CDCl3, 376 MHz): δ −220.53 (dt, 2J(H−F) = 50.0 Hz, 3J(H−F) = 28.3 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C28H38FN2O7, 533.2657; found, 533.2660. 3-O-(2-Azido-4,6-di-O-benzyl-2,3-dideoxy-3-fluoro-α-D-galactopyranosyl)-1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-β-Dgalactopyranose (25). A mixture of β-3 (140 mg, 0.292 mmol), diphenyl sulfoxide (73 mg, 0.361 mmol), and tri-tert-butylpyrimidine (174 mg, 0.700 mmol) was co-evaporated with dry toluene (3×) and then dried for 20 min at vacuum of an oil pump. Dry dichloromethane (7 mL) and 3 Å molecular sieves were added, and the resulting suspension was stirred for 1.5 h at room temperature under argon atmosphere and then cooled to −78 °C. Triflic anhydride (62 μL, 0.37 mmol) was added dropwise; the reaction was allowed to warm up to −60 °C and then recooled to −78 °C. A solution of 1,6anhydro-2-azido-4-O-benzyl-2-deoxy-β-D-galactopyranose43 (24, 160 mg, 0.577 mmol) in dry dichloromethane (1.6 mL) was added dropwise. The reaction mixture was allowed to warm up to −40 °C in 90 min and stirred at −40 °C for additional 5 h. The reaction mixture was quenched with Et3N (0.3 mL, 2.2 mmol) at −40 °C and left at −20 °C overnight. It was then diluted with dichloromethane, filtered, and washed with water. The water phase was extracted with dichloromethane (3×). The organic extracts were combined, dried, and concentrated. Column chromatography of the residue in EtOAc/ PE 1:4 afforded 25 as a slightly yellow syrup (159 mg, 84%). Preparative TLC of a sample (35 mg) in EtOAc/PE 1:4 afforded 25 (32 mg) for analysis, Rf 0.21 (EtOAc/heptane 1:4), [α]20 D +65 (c 0.1.6, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.27 (m, 15H, CHarom), 5.27 (t, 1H, J = 1.5 Hz, H1), 5.13 (dd, 1H, J = 4.2, 3.8 Hz, H-1′), 4.93 (ddd, 1H, J = 49.2, 10.6, 3.1 Hz, H-3′), 4.88 (d, 1H, J = 11.6 Hz, CHH O-4′Bn), 4.71, 4.57 (2× d, 2× 1H, J = 11.8 Hz, CHH O-4Bn), 4.54 (d, 1H, J = 11.6 Hz, CHH O-4′Bn), 4.50 (d, 1H, J = 11.8 Hz, CHH O-6′Bn), 4.51 (d, 1H, J = 7.2 Hz, H-6en), 4.46 (t, 1H, J = 4.6 Hz, H-5), 4.42 (d, 1H, J = 11.8 Hz, CHH O-6′Bn), 4.16 (dddd, 1H, J = 7.1, 5.0, 1.5, 1.3 Hz, H-5′), 4.06 from 1H{19F} (dd, 1H, J = 3.1, 1.3 Hz, H-4′), 4.02 (ddd, 1H, J = 10.6, 10.4, 3.8 Hz, H-2′), 3.99 (dq, 1H, J = 4.6, 1.5 Hz, H-3), 3.83− 3.80 (m, 2H, H-2, H-4), 3.66 (dd, 1H, J = 7.2, 4.6, 1.1 Hz, H-6ex), 3.59 (ddd, 1H, J = 9.7, 7.1, 0.9 Hz, H-6′), 3.43 (dd, 1H, J = 9.7, 5.0 Hz, H-6′). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 137.8 (Cq O-4Bn), 137.7 (Cq O-4′Bn), 137.6 (Cq O-6′Bn), 128.7, 128.58, 128.56, 128.5 (4× 2CHarom), 128.23, 128.18, 128.0 (3× 1CHarom), 127.82, 127.81 (2× 2CHarom), 101.1 (d, 3J(C−F) = 9.2 Hz, C-1′), 100.0 (C-1), 90.4 (d, 1J(C−F) = 189.0 Hz, C-3′), 76.6 (C-3), 75.0 (d, 4J(C−F) = 4.0 Hz, CH2 O-4′Bn), 74.5 (d, 2J(C−F) = 15.4 Hz, C4′), 73.6 (CH2 O-6′Bn), 73.3 (C-5), 72.2 (C-4), 71.6 (CH2 O-4Bn), 70.1 (d, 3J(C−F) = 7.0 Hz, C-5′), 69.3 (d, 4J(C−F) = 2.6 Hz, C-6′), 65.1 (C-6), 61.9 (C-2), 59.3 (d, 2J(C−F) = 17.5 Hz, C-2′). 19F NMR (CDCl3, 376 MHz): δ −199.28 (dddd, 2J(H−F) = 49.2 Hz, 3J(H−F) = 10.4, 5.7 Hz, 4J(H−F) = 4.2 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C33H36FN4O7, 619.2562; found, 619.2558. X


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dispersion correction according to Grimme.54 The Gaussian16 program package was used throughout this study.55 The vibrational frequencies and free energies were calculated for all of the optimized structures, and the stationary-point character (a minimum or a firstorder saddle point) was thus confirmed.

3-O-(6-O-Acetyl-2-azido-4-O-benzyl-2,3-dideoxy-3-fluoroα-D-galactopyranosyl)-1,6-di-O-acetyl-2-azido-4-O-benzyl-2deoxy-α-D-galactopyranose (α-26) and 3-O-(6-O-Acetyl-2azido-4-O-benzyl-2,3-dideoxy-3-fluoro-α-D-galactopyranosyl)-1,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-β-D-galactopyranose (β-26). A mixture of A2O/AcOH/H2SO4/72:33:0.5 (2 mL) was added to the starting disaccharide 25 (73 mg, 0.113 mmol) under cooling (ice/water), and the resulting solution was stirred for 90 min at 0 °C. TLC in EtOAc/PE 1:2 indicated the absence of 25. Sodium acetate (70 mg, 0.853 mmol) was added, and the resulting suspension was stirred until all NaOAc dissolved (about 30 min). The reaction mixture was diluted with water and extracted with chloroform (3×). NaCl was added during extraction to break the formed emulsion. The extracts were combined, dried, and concentrated. Preparative TLC in Et2O/PE/EtOAc 15:10:8 gave the product in two fractions. The faster moving fraction afforded β-26 (20 mg, 25%) as a colorless syrup. The slower moving fraction afforded α-26 (49 mg, 62%) as a colorless syrup. The combined yield was 87%. Data for α-26: Rf 0.29 (EtOAc/PE 1:1), [α]20 D +118 (c 2.53, CHCl3). 1H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.38−7.30 (m, 10H, CHarom), 6.31 (d, 1H, J = 3.5 Hz, H1), 5.26 (dd, 1H, J = 4.7, 3.7 Hz, H-1′), 5.08 (d, 1H, J = 11.1 Hz, CHH O-4′Bn), 5.06 (ddd, 1H, J = 48.9, 10.5, 3.1 Hz, H-3′), 4.93 (d, 1H, J = 11.3 Hz, CHH O-4Bn), 4.65 (d, 1H, J = 11.1 Hz, CHH O4′Bn), 4.61 (d, 1H, J = 11.3 Hz, CHH O-4Bn), 4.24−3.97 (m, 11H, H-2, H-3, H-4, H-5, H-6, H-2′, H-4′, H-5′, H-6′), 2.11, 2.01, 2.00 (3× s, 3× 3H, Me OAc). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 170.53, 170.41 (CO OAc), 168.91 (CO O-1Ac), 137.7 (Cq O-4Bn), 137.3 (Cq O-4′Bn), 128.71, 128.68, 128.67 (3× 2CHarom), 128.4, 128.2 (2× 1CHarom), 128.1 (2CHarom), 96.2 (d, 3 J(C−F) = 9.4 Hz, C-1′), 90.91 (d, 1J(C−F) = 188.4 Hz, C-3′), 90.89 (C1), 75.13 (d, 4J(C−F) = 4.7 Hz, CH2 O-4′Bn), 75.06 (CH2 O-4Bn), 74.9 (C-3), 73.8 (d, 2J(C−F) = 15.5 Hz, C-4′), 72.2 (C-4), 70.9 (C-5), 69.2 (d, 3J(C−F) = 7.3 Hz, C-5′), 62.8 (d, 4J(C−F) = 2.6 Hz, C-6′), 62.5 (C-6), 59.1 (d, 2J(C−F) = 17.9 Hz, C-2′), 58.9 (C-2), 21.1 (Me O1Ac), 20.90, 20.86 (Me OAc). 19F NMR (CDCl3, 376 MHz): δ −199.81 (dddd, 2J(H−F) = 48.9 Hz, 3J(H−F) = 8.9, 6.9 Hz, 4J(H−F) = 4.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H38FN4O11, 673.2515; found, 673.2513; [M − N2 − N2 + H]+ calcd for C32H38FN2O11, 645.2454; found 645.2451. Data for β-26: Rf 0.33 (EtOAc/PE 1:1), [α]20 D +73 (c 1.00 CHCl3). 1 H NMR (CDCl3, 400 MHz, 1H{19F}, H−H COSY, HSQC, HMBC): δ 7.41−7.29 (m, 10H, CHarom), 5.43 (d, 1H, J = 8.4 Hz, H-1), 5.23 (dd, 1H, J = 4.7, 3.8 Hz, H-1′), 5.06 (ddd, 1H, J = 49.0, 10.4, 3.1 Hz, H-3′), 5.06 (d, 1H, J = 11.3 Hz, CHH O-4Bn), 4.93 (d, 1H, J = 11.4 Hz, CHH O-4′Bn), 4.66 (d, 1H, J = 11.3 Hz, CHH O4Bn), 4.60 (d, 1H, J = 11.4 Hz, CHH O-4′Bn), 4.25 from 1H{19F} (ddd, 1H, J = 6.8, 5.0, 1.2 Hz, H-5′), 4.20 from 1H{19F} (dd, 1H, J = 10.4, 3.8 Hz, H-2′), 4.22−4.05 (m, 5H, H-6, H-4′, H-6′), 3.98 (dd, 1H, J = 10.6, 8.4 Hz, H-2), 3.86 (dd, 1H, J = 2.6, 1.0 Hz, H-4), 3.66 (td, 1H, J = 6.4, 1.0 Hz, H-5), 3.62 (dd, 1H, J = 10.6, 2.6 Hz, H-3), 2.16, 2.00, 1.99 (3× s, 3× 3H, Me OAc). 13C{1H} NMR (CDCl3, 101 MHz, HSQC, HMBC): δ 170.6, 170.5 (CO OAc), 169.0 (CO O1Ac), 137.6 (Cq O-4Bn), 137.3 (Cq O-4′Bn), 128.74 (2CHarom), 128.68 (4CHarom), 128.44 (CHarom), 128.37 (2CHarom), 128.3 (CHarom), 95.3 (d, 3J(C−F) = 9.7 Hz, C-1′), 93.4 (C-1), 91.0 (d, 1 J(C−F) = 188.4 Hz, C-3′), 76.6 (C-3), 75.1 (d, 4J(C−F) = 4.4 Hz, CH2 O-4′Bn), 74.8 (CH2 O-4Bn), 73.9 (d, 2J(C−F) = 15.5 Hz, C-4′), 73.4 (C-5), 70.7 (C-4), 69.2 (d, 3J(C−F) = 7.4 Hz, C-5′), 63.2 (d, 4J(C−F) = 2.9 Hz, C-6′), 62.5 (C-6), 61.2 (C-2), 59.0 (d, 2J(C−F) = 17.8 Hz, C2′), 21.1 (Me O-1Ac), 20.92, 20.90 (Me OAc). 19F NMR (CDCl3, 376 MHz): δ −199.64 (dddd, 2J(H−F) = 49.0 Hz, 3J(H−F) = 10.2, 5.8 Hz, 4J(H−F) = 4.7 Hz). HRMS-APCI (m/z): [M − N2 + H]+ calcd for C32H38FN4O11, 673.2515; found, 673.2511; [M − N2 − N2 + H]+ calcd for C32H38FN2O11, 645.2454; found 645.2438. Computational Methods. The geometry of oxocarbenium ions was optimized at the DFT level of theory using the B3LYP functional,50,51 standard 6-31G(d,p) basis set, polarizable continuum model used for implicit dichloromethane solvation,52,53 and empirical

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b00705. Selected NMR data of unstable covalent intermediates, computational data, NMR spectra of new compounds, and variable-temperature 1H NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Martin Dračínský: 0000-0002-4495-0070 Jindřich Karban: 0000-0001-5360-1035 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Czech Science Foundation for support of our research (grant no. 17-18203S). REFERENCES

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