Synthesis of Phenolic Glycosides: Glycosylation of Sugar Lactols with

J. Org. Chem. , 2018, 83 (21), pp 13325–13334. DOI: 10.1021/acs.joc.8b02129. Publication Date (Web): October 10, 2018. Copyright © 2018 American ...
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Synthesis of Phenolic Glycosides: Glycosylation of Sugar Lactols with Aryl Bromides via Dual Photoredox/Ni Catalysis Hui Ye,†,‡,# Cong Xiao,§,# Quan-Quan Zhou,† Peng George Wang,*,§ and Wen-Jing Xiao*,†,‡ †

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CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, China ‡ Hubei Key Laboratory for Processing and Application of Catalytic Materials, Huanggang Normal University, Huanggang 438000, China § Department of Chemistry, Georgia State University, Atlanta, Georgia 30302-4098, United States S Supporting Information *

ABSTRACT: Multifarious sugar lactols were efficiently transformed into the corresponding phenolic glycosides by treating with aryl bromides in acetonitrile with Ir[dF(CF3)ppy]2(dtbbpy)(PF6) as a photocatalyst under visible light irradiation. Both pyranoses and furanoses or even disaccharide could all suffer this glycosylation protocol under mild reaction conditions. A variety of phenyl glycosides can be produced in moderate to good yields (up to 93% yield), and a gram scale process of this protocol was also well-established.

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Scheme 1. Synthetic Methods for Phenolic Glycosidea

INTRODUCTION Phenolic glycosides are compounds with carbohydrate units attached to aryl units through the C−O bond linkage. It is a class of important organic compounds and encompasses a vast number of secondary metabolites, such as vancomycin and chromomycin.1 Since phenolic glycoside was first reported in 1879,2 a massive effort has been devoted toward their synthesis by varying different glycosyl donors (i.e., anomeric acetates, glycosyl halides, trichloroacetimidates, thioglycosides, et al.) and corresponding activation conditions3 because of their diverse biological activities and pharmaceutical potentials.4 The previous strategies of glycosylation were commonly built upon the electrophilic/cationic species by releasing a leaving group, such as bromides, trichloroacetimidates, thioglycosides, et al. (Scheme 1a). Lately, Ye and co-workers have also been dedicated to the continuous development of a highly efficient aromatic O-glycosylation with 1,2-anhydro-sugar and aryl boronic acids (Scheme 1b).5a In the same year, Olofsson et al. disclosed a novel methodology for O-functionalization of carbohydrate derivatives using bench-stable and easily prepared iodonium (III) reagents (Scheme 1c).5b,c However, because of the electron-withdrawing properties of aromatic rings, phenols are often difficult to glycosylate. The existing methods suffer from some drawbacks such as needing prepreparation of reactive substrates or reagents (Scheme 1a,c) or a limited substrate scope (Scheme 1b). Thus, the development of efficient and alternative protocols toward phenolic glycosides is still highly desired. Dual catalysis by merging visible light photoredox catalysis and transition-metal catalysis has enjoyed an increasing popularity in organic synthesis since the pioneering work of Osawa and Sanford et al.6 In 2015, the MacMillan group developed a highly efficient and general coupling reaction to forge the C−O bond through synergistic photoredox and © 2018 American Chemical Society

a

Pg = protecting group; L = leaving group.

nickel catalysis.7 In view of the appealing attributes of (i) the synthesis of phenolic glycosides via C−O coupling and (ii) the mild conditions of dual visible light photoredox/Ni catalysis via SET process, we recently decided to pursue the possibility that the two technologies could be merged to enable the synthesis of phenolic glycosides from readily available starting materials. Currently, only a few photoinduced reactions involving carbohydrates have been reported,8 maybe due to the complexity of the carbohydrate structures and the lack of Received: August 16, 2018 Published: October 10, 2018 13325

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry Table 1. Condition Optimization for the Model Reactiona

entry

[Ni] source

photocatalysts

amine reductants

yield [%]b

1c 2c 3c 4c 5c 6c 7c 8d 9d 10d 11d 12d,e 13d,f 14d,g 15d,h

NiCl2·glyme Ni(OTf)2 Ni(acac)2 NiCl2·glyme NiCl2·glyme NiCl2·glyme NiCl2·glyme NiCl2·glyme NiCl2·glyme NiCl2·glyme NiCl2·glyme

Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ru(bpy)3(PF6)2 Ir(ppy)2(dtbby)PF6 4CzIPN fac-Ir(ppy)3 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6

quinuclidine quinuclidine quinuclidine quinuclidine quinuclidine quinuclidine quinuclidine quinuclidine DABCO i-Pr2NEt DBU DABCO DABCO

42 15 trace NA NA trace NA 53 81 49 17 0 0 0 0

NiCl2·glyme NiCl2·glyme NiCl2·glyme

Ir[dF(CF3)ppy]2(dtbbpy)PF6 Ir[dF(CF3)ppy]2(dtbbpy)PF6

DABCO

a

Reaction conditions: 1a (0.20 mmol), 2a (0.40 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %), [Ni] (5 mol %), dtbbpy (5 mol %), amine reductant (10 mol %), and K2CO3 (0.20 mmol) in MeCN (2 mL) at 40 °C under an argon atmosphere and the irradiation of visible light for 48 h. b Isolated yield. c7 W blue LEDs. d2 × 3 W blue LEDs. eWithout [Ni] salt. fWithout Ir[dF(CF3)ppy]2(dtbbpy)PF6. gWithout amine reductants. h Without visible light irradiation; dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine.

photocatalyst, amine reductants, and visible light were all essential in this dual photoredox and nickel-catalyzed crosscoupling reaction (Table 1, entries 12−15). With the optimal conditions in hand, we probed the generality of this phenolic glycosidation protocol. As highlighted in Scheme 2, a variety of structurally diverse armed sugar lactols (Bn-protecting group) proved to be suitable for this reaction. Both pyranoses and furanoses 1a−i were welltolerated, and the corresponding products were obtained in moderate to good isolated yields (Scheme 2, 3aa−3ia, 54− 93% yield). The pyranoses of D-configuration 1a and 1c−1d were converted smoothly in good yields (81−93%) with a high α-stereoselectivity (3aa, α/β = 8:1; 3ca, α/β = 10:1; 3da, α only). The reaction of 1b and 4′-bromoacetophenone 2a gave the corresponding glycoside in 82% yield but a moderate αstereoselectivity (α/β = 2:1). In addition, the furanose of Dconfiguration D-ribose 1i could also participate in this coupling reaction under the optimized conditions (Scheme 2, 3ia, 60% yield, α only). It is worthy to note that variation of configuration of the sugar substrates has been proven feasible.10 Therefore, when the sugar substrates were changed to L-configuration, phenolic glycosides were given in acceptable yields (Scheme 2, 3ea 56% yield, β only; 3fa−3ha 54−65% yield, α only). Moreover, disaccharide substrate 1j was also examined and could be successfully transformed into phenolic glycoside products 3ja in modest yields and α-stereoselectivity (46%, α/β = 2:1). Meanwhile, armed sugar lactol 1k with a methyl-protecting group could also tolerate this glycosylation protocol, affording the desired product 3ka in a good yield (81%) and moderate α-stereoselectivity (α/β = 2:1). However, disarmed sugar lactol 1l with an Ac-protecting group was ineffective under our standard conditions. Most of the products are mainly in α-configuration, probably because the anomeric effect and long reaction time (48 h) facilitate the formation of a more stable α-anomer.11

general synthetic methods. On the basis of the importance of phenolic glycoside, we developed a dual photoredox and nickel-catalyzed cross-coupling of sugar lactols and aryl bromides under mild conditions (Scheme 1d). This protocol provides a novel and straightforward method for the synthesis of phenyl glycoside.

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RESULTS AND DISCUSSION Initially, we chose 2,3,4,6-tetra-O-benzyl-D-glucopyranose 1a and 4′-bromoacetophenone 2a as model substrates and Ir[dF(CF 3)ppy]2(dtbbpy)PF6 as a photocatalyst (E1/2red [*Ir(III)/Ir(II) = 1.21 V vs SCE in MeCN) to test the glycosylation reaction under the irradiation of a 7 W blue LED. As depicted in Table 1, this reaction did indeed proceed with Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %) and NiCl2·glyme (5 mol %)/dtbbpy (5 mol %) in MeCN at 40 °C, affording the desired phenolic glycoside 3aa in 42% yield (Table 1, entry 1). Other nickel catalysts were then examined to improve the reaction efficiency (Table 1, entries 1−3). NiCl2·glyme was still determined to be the most suitable catalyst (Table 1, entry 1). A further study revealed that Ir[dF(CF3)ppy]2(dtbbpy)PF6 was superior than others, such as Ru(bpy)3(PF6)2, Ir(ppy)2(dtbby)PF6, 4CzIPN, and fac-Ir(ppy)3 (Table 1, entries 4−7). The yield was promoted to 53% when the reaction was irradiated by 2 × 3 W blue LEDs (Table 1, entry 8). Screening of light sources, solvents, bases, and ligands did not further improve the reaction yield. (For more details, see the Supporting Information.) It has been reported in the literature that amines, such as DABCO, i-Pr2NEt, etc., can be used as reductive reagents to participate in the single-electron transfer process.9 So, other amine reductants (Table 1, entries 9−11) were tested for this reaction. A significant improvement was reached (Table 1, entry 9:81% yield) when using DABCO (1,4-diazabicyclo[2.2.2]octane) as the amine reductant. Control experiments indicated that the nickel catalyst, 13326

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry Scheme 2. Variation of the Sugar Lactolsa,b

a Reaction conditions, unless otherwise noted: 1 (0.20 mmol), 2a (0.40 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %), NiCl2·glyme (5 mol %), dtbbpy (5 mol %), DABCO (10 mol %), and K2CO3 (0.20 mmol) in MeCN (2 mL) at 40 °C under an argon atmosphere and the irradiation of 2 × 3 W blue LEDs for 48 h. bIsolated yield and the α/β ratio were determined by 1H NMR analysis.

Next, we investigated the photochemical glycosylation reactions of sugar lactol 1 with a variety of aryl bromides. As summarized in Scheme 3, this dual catalytic system exhibited a certain substrate scope with respect to sugar lactols. In addition to 1, a set of representative aryl bromides with diverse electron-withdrawing substituents (e.g., CN, MeSO2, CO2Et) on the phenyl ring proved to be suitable for the reaction; and the expected products 3ab, 3cb, 3fb, 3ac, 3bc, and 3ad were obtained in 32−71% yields and moderate to good αstereoselectivities (3ab, 55%, α/β = 1:0.6; 3cb, 45%, α/β = 5:1; 3fb, 32%, α only; 3ac, 71%, α/β = 1:0.4; 3bc, 43%, α/β = 1:0.3; 3ad, 35%, α/β = 1:0.75). The moderate yield of 3ae resulted from the low conversion of 2e, which contained a disubstituted phenyl ring (3ae, 53%, α/β = 3:1). Moreover, as shown in the synthesis of 3af and 3bf, nitrogen-containing aromatic rings such as pyridine could also be wellaccommodated (3af, 35%, α/β = 1:0.3; 3bf, 39%, α/β >

10:1). Note that aryl bromides with electron-neutral substituents (bromobenzene 2g and 2-bromonaphthalene 2h) could also suffer this glycosylation protocol in acceptable yields and good α-stereoselectivities (3ag, 33%, α/β = 5:1; 3ah, 26%, α/β = 2:1). Unfortunately, this reaction could not occur when we replaced 2a with 4-bromotoluene (2i), which contained an electron-donating group. To further demonstrate the synthetic potential of this protocol, we performed a gram scale process to the model reaction of 1a and 2a under standard conditions (Scheme 4). Delightedly, the reaction proceeded well to afford phenolic glycoside 3aa in a good yield with a high α-stereoselectivity (82%, α/β = 8:1). On the basis of our observations and related literatures,7 a plausible mechanism for this glycosylation reaction was proposed in Scheme 5. Initially, the aryl bromides 2 underwent an oxidative addition to chiral Ni(0) catalyst and generated a 13327

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

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The Journal of Organic Chemistry Scheme 3. Variation of the Aryl Bromide Scopea,b

Reaction conditions, unless otherwise noted: 1 (0.20 mmol), 2 (0.40 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %), NiCl2·glyme (5 mol %), dtbbpy (5 mol %), DABCO (10 mol %), and K2CO3 (0.20 mmol) in MeCN (2 mL) at 40 °C under an argon atmosphere and the irradiation of 2 × 3 W blue LEDs for 48 h. bIsolated yield and the α/β ratio were determined by 1H NMR analysis. a

Scheme 4. Gram Scale Reaction

final product 3 and Ni(I) complex E. Finally, reduction of Ni(I) to Ni(0) by Ir(II) species completed the catalytic cycles.

Ni(II) aryl complex B. At this stage, ligand exchange (displacement of the aryl bromide ion with the sugar lactols) would produce the Ni(II) aryl alkoxide (C). In addition, visible light irradiation of iridium(III) photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 could produce the long-lived photoexcited *IrIII species. At this juncture, the nickel and photoredox cycles would merge via SET process between the Ni(II) complex C and the excited state of Ir(III) photocatalyst, generating Ni(III) aryl alkoxide D and the reduced state of Ir(II) photocatalyst. Intermediate D then undergoes a reductive elimination to forge the desired C−O bond and provides the

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CONCLUSIONS In conclusion, a novel glycosylation reaction for phenolic glycosides has been developed via dual photoredox/Ni catalysis using multifarious sugar lactols and aryl bromides as starting materials. Through this method, a wide range of significant phenolic glycosides can be efficiently synthesized under mild reaction conditions. It is believed that this method represents a valuable addition to the existing modern synthetic 13328

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

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The Journal of Organic Chemistry

was stirred vigorously for 5 h at room temperature until consumption of 5 was observed by TLC. The mixture was then diluted with Et2O (20 mL), filtered through Celite, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc = 20:1 → 5:1) to afford 1. 2,3,4-Tri-O-benzyl-α/β-D-xylopyranose (1d): colorless oil, α/β = 1 1:0.3; [α]20 D +19.1 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.36−7.27 (m, 23H), 5.10 (t, J = 3.4 Hz, 1H), 4.90−4.83 (m, 3.3H), 4.75 (t, J = 8.0 Hz, 2H), 4.69 (d, J = 8.0 Hz, 2H), 4.66−4.60 (m, 2H), 3.94 (dd, J = 11.6, 4.4 Hz, 0.3H), 3.86 (t, J = 8.0 Hz, 2H), 3.79 (t, J = 8.0 Hz, 2H), 3.66 (dd, J = 12.0, 4.0 Hz, 2H), 3.63−3.51 (m, 2H), 3.48 (dd, J = 8.0, 4.0 Hz, 1H), 3.40 (d, J = 5.6 Hz, 0.3H), 3.33−3.23 (m, 0.6H), 3.05 (d, J = 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 138.8, 138.3, 137.9, 128.6, 128.6, 128.6, 128.5, 128.2, 128.2, 128.1, 128.1, 127.9, 127.9, 127.8, 97.9, 91.6, 83.3, 82.4, 79.6, 77.7, 77.6, 75.6, 74.9, 73.6, 73.4, 73.3, 63.9, 60.5; IR (in KBr) 3445, 3129, 3014, 1637, 1542, 1400, 1093 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H28O5Na 443.1829, found 443.1824. 2,3,4-Tri-O-benzyl-α/β-L-rhamnose (1f): colorless oil, α/β = 1:1; 1 [α]20 D −13.3 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.38−7.27 (m, 30H), 5.16−5.09 (m, 2H), 4.94 (dd, J = 11.2, 5.9 Hz, 2H), 4.79−4.51 (m, 10H), 3.92 (d, J = 11.7 Hz, 2H), 3.83 (d, J = 11.7 Hz, 2H), 3.66−3.56 (m, 4H), 3.36 (s, 1H), 2.73 (s, 1H), 1.33 (t, J = 7.5 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ (ppm) 138.7, 138.7, 138.4, 138.4, 138.2, 138.1, 128.8, 128.7, 128.5, 128.5, 128.4, 128.2, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 93.5, 93.1, 83.2, 80.6, 80.1, 79.8, 77.4, 76.7, 75.6, 75.5, 75.1, 75.0, 73.0, 72.4, 71.7, 68.3, 18.2, 18.1; IR (in KBr) 3445, 3129, 3030, 2928, 2361, 2341, 1453, 1400, 1094, 747, 695 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H30O5Na 457.1985, found 457.1980. 2,3,4-Tri-O-benzyl-α/β-L-fucose (1g): colorless oil, α/β = 2.5:1; 1 [α]20 D −24.0 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.40−7.27 (m, 21H), 5.26 (d, J = 3.4 Hz, 1H), 5.00−4.91 (m, 2H), 4.83−4.61 (m, 7.6H), 4.10 (dd, J = 12.0, 8.0 Hz, 1H), 3.89 (dd, J = 10.0, 2.4 Hz, 1H), 3.74 (t, J = 8.6 Hz, 0.5H), 3.66 (s, 1H), 3.58−3.51 (m, 1.3H), 3.27 (d, J = 7.1 Hz, 0.4H), 2.99 (s, 1H), 1.19 (d, J = 6.4 Hz, 1.3H), 1.14 (d, J = 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 138.8, 138.6, 138.3, 128.5, 128.5, 128.3, 128.3, 128.1, 128.0, 127.8, 127.8, 127.7, 127.7, 127.6, 97.8, 92.0, 82.6, 80.9, 79.2, 77.4, 77.4, 76.6, 76.5, 75.2, 74.9, 74.8, 73.6, 73.2, 73.1, 70.9, 66.8, 17.1, 16.9; IR (in KBr) 3367, 3131, 3032, 2935, 2361, 2340, 1453, 1400, 1365, 1140, 1106, 1054, 731, 696 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H30O5Na 457.1985, found 457.1985. General Procedure for the Preparation of Disaccharide Substrates 1j.10b 1,2,3,6,2′,3′,4′,6′-Octa-O-acetyl-D-maltose (6). D(+)-Maltose monohydrate (2.1 g, 5.8 mmol) was suspended in dry pyridine (7.5 mL, 93.4 mmol) and acetic anhydride (6.6 mL, 70.1 mmol), and a catalytic amount of 4-dimethylaminopyridine was added. The solution was stirred at ambient temperature for 16 h. The reaction mixture was diluted with ethyl acetate and washed successively with 1 N HCl (20 mL) and saturated aq NaHCO3 (20 mL). The resulting organic phase was dried (anhydrous Na2SO4) and filtered, and the filtrate was concentrated under reduced pressure to afford 6 (3.9 g, 98%) as a white solid. Allyl 2,3,6,2′,3′,4′,6′-Hepta-O-acetyl-D-maltose (7). Compound 6 (3.9 g, 5.7 mmol) was dissolved in dichloromethane (30 mL), and allyl alcohol (1.2 mL, 17.2 mmol) and boron trifluoride diethyl etherate (2.2 mL, 17.2 mmol) were added to the solution at 0 °C. The resulting solution was stirred at ambient temperature under a nitrogen atmosphere. The reaction was monitored by TLC and appeared to be complete after 6 h. The reaction mixture was diluted with dichloromethane (20 mL) and successively washed with saturated aq NaHCO3 (100 mL), 10% aq NaCl (30 mL), and water (30 mL). The resulting organic phase was dried (anhydrous Na2SO4) and filtered, and the filtrate was concentrated under reduced pressure to afford 7 (2.5 g, 65%) as a colorless oil. Allyl 4-O-α-D-Glucopyranosyl-α/β-D-glucopyranose (8). Compound 7 (2.5 g, 3.7 mmol) was dissolved in dry methanol (25 mL) followed by the addition of MeONa (20 mg, 0.37 mmol) until the

Scheme 5. Proposed Mechanism

arsenal to phenolic glycosides of interests, thereby facilitating their potential applications in carbohydrate synthesis.

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EXPERIMENTAL SECTION

General Information. Unless otherwise noted, substrates 2 and other materials were purchased from commercial suppliers and used without further purification. All solvents were treated using known methods. Substrates 1a−1c were commercially available, and the other substrates (1d−1l) were prepared according to the procedures in the literature.10,12−14 NMR spectra were measured at 400 MHz with CDCl3 as a solvent. The chemical shifts (δ) are reported in parts per million (ppm) using the solvent resonance as the internal standard (CDCl3 7.26 ppm). The data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet), coupling constants (Hz), and integration. The 13C NMR spectra were recorded at 400 (100 MHz) with complete proton decoupling spectrophotometers (CDCl3 77.0 ppm). High-resolution mass spectra (HRMS) were equipped with an ESI source and a TOF detector. The IR spectra were determined by an IR instrument. The melting points were measured with a digital melting point detector. General Procedure for the Preparation of Monosaccharide Substrates. Allyl Saccharide (4). Unprotected monosaccharide (6.7 mmol) was dissolved in allyl alcohol (8 mL), and Amberlite IR 120 (H+) (0.6 g) was added at room temperature. Then, the mixture was stirred at 90 °C for 4 h. The ion exchanger was filtered off, and the excess of allyl alcohol was removed by vacuum distillation. The crude product was purified by flash column chromatography (CH2Cl2/ MeOH = 20:1) to give 4 as a white solid. Fully Protected Saccharide (5). NaH (60% in oil, 29.2 mmol) was added in small portions at 0 °C to a solution of 4 (5.8 mmol) in anhydrous DMF (15 mL). After that, the mixture was stirred at 0 °C for 30 min. Then BnBr (29.2 mmol) was added dropwise, and the mixture was stirred at ambient temperature overnight. The reaction mixture was carefully quenched with H2O at 0 °C, diluted with Et2O (50 mL), and then washed with water (20 mL × 3). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (petroleum/EtOAc = 10:1) to afford 5 as a colorless oil. Sugar Lactol (1). To a mixture of 5 (3.3 mmol) in anhydrous MeOH (20 mL) was added PdCl2 (0.65 mmol), and then the mixture 13329

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry

127.7, 127.6, 116.5, 96.1, 79.0, 77.4, 76.1, 75.1, 74.8, 73.8, 73.5, 73.4, 70.5, 68.6, 26.6; IR (in KBr) 3447, 3128, 3030, 2920, 2866, 2361, 1679, 1600, 1400, 1240, 1100, 1063, 737, 698 cm−1; HRMS (ESITOF) m/z [M + Na]+ calcd for C42H42O7Na 681.2823, found 681.2818. Compound 3ba-β: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.94−7.84 (m, 2H), 7.44−7.21 (m, 20H), 7.13− 7.00 (m, 2H), 5.06 (d, J = 7.7 Hz, 1H), 4.97 (dd, J = 11.2, 9.8 Hz, 2H), 4.87 (d, J = 10.8 Hz, 1H), 4.77 (dd, J = 12.0, 12.0 Hz, 2H), 4.65 (d, J = 11.7 Hz, 1H), 4.42 (dd, J = 24.0, 11.6 Hz, 2H), 4.14 (dd, J = 9.7, 7.6 Hz, 1H), 3.96 (d, J = 2.8 Hz, 1H), 3.71 (t, J = 6.2 Hz, 1H), 3.68−3.52 (m, 3H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 161.1, 138.4, 138.3, 138.3, 137.9, 131.7, 130.6, 128.6, 128.5, 128.5, 128.4, 128.4, 128.0, 127.9, 127.9, 127.9, 127.7, 116.3, 101.1, 82.1, 79.1, 77.4, 75.7, 74.7, 74.3, 73.8, 73.2, 73.2, 69.0, 26.6; IR (in KBr) 3463, 3129, 3030, 2362, 2340, 1672, 1604, 1400, 1236, 1070, 736, 695 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C42H42O7Na 681.2823, found 681.2815. 4-Acetylphenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-mannopyranoside (3ca): 115 mg, 88% yield, α/β = 10:1. Compound 3ca-α: white 1 solid, mp 106−107 °C; [α]20 D +65.7 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.88 (d, J = 8.5 Hz, 2H), 7.42−7.22 (m, 19H), 7.20−7.14 (m, 2H), 7.06 (d, J = 8.6 Hz, 2H), 5.65 (d, J = 1.9 Hz, 1H), 4.89 (d, J = 10.7 Hz, 1H), 4.80 (dd, J = 24.0, 12.4 Hz, 2H), 4.71 (dd, J = 24.0, 12.4 Hz, 2H), 4.62 (d, J = 11.9 Hz, 1H), 4.53 (d, J = 10.7 Hz, 1H), 4.44 (d, J = 11.9 Hz, 1H), 4.18−4.06 (m, 2H), 3.97 (t, J = 2.5 Hz, 1H), 3.78 (m, 2H), 3.65 (d, J = 9.7 Hz, 1H), 2.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 196.9, 160.0, 138.4, 138.4, 138.3, 138.1, 131.6, 130.6, 128.5, 128.5, 128.4, 128.1, 128.0, 127.9, 127.8, 127.8, 127.8, 127.6, 116.1, 96.3, 79.9, 77.4, 75.3, 74.6, 74.5, 73.4, 73.1, 72.8, 72.6, 68.9, 26.5; IR (in KBr) 3420, 3131, 3030, 2361, 1671, 1596, 1400, 1247, 1102, 749, 697 cm−1; HRMS (ESITOF) m/z [M + Na]+ calcd for C42H42O7Na 681.2823, found 681.2828. 4-Acetylphenyl 2,3,4-Tri-O-benzyl-α-D-xylopyranoside (3da): 100 1 mg, 93% yield, α only, colorless oil; [α]20 D +45.7 (c 0.33, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.93 (d, J = 8.4 Hz, 2H), 7.46− 7.22 (m, 16H), 7.08 (d, J = 8.5 Hz, 2H), 5.40 (d, J = 3.4 Hz, 1H), 4.97 (d, J = 20.0, 12.0 Hz, 1H), 4.84 (d, J = 12.0 Hz, 1H), 4.76 (d, J = 11.6 Hz, 1H), 4.64 (t, J = 12.3 Hz, 2H), 4.11 (t, J = 8.8 Hz, 1H), 3.64 (m, 3H), 3.54 (m, 1H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 160.5, 138.8, 138.2, 138.0, 131.7, 130.5, 128.6, 128.6, 128.5, 128.1, 128.1, 128.0, 128.0, 127.8, 116.3, 95.3, 81.3, 79.4, 77.8, 76.0, 73.8, 73.8, 61.0, 26.6; IR (in KBr) 3480, 3124, 3031, 3005, 2869, 2360, 2341, 1679, 1600, 1401, 1239, 1092, 1028, 739, 699, 647 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C34H34O6Na 561.2248, found 561.2245. 4-Acetylphenyl 2,3,4-Tri-O-benzyl-β-L-arabinpyranoside (3ea): 60 mg, 56% yield, β only, white solid, mp 82−83 °C; [α]20 D −8.3 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.92 (d, J = 8.7 Hz, 2H), 7.42−7.27 (m, 15H), 7.06 (d, J = 8.8 Hz, 2H), 5.09 (d, J = 6.5 Hz, 1H), 4.85 (dd, J = 20.0, 11.0 Hz, 2H), 4.76 (d, J = 12.5 Hz, 1H), 4.70−4.67 (m, 3H), 4.13−4.07 (m, 2H), 3.80 (s, 1H), 3.65 (dd, J = 8.6, 3.2 Hz, 1H), 3.44 (dd, J = 12.5, 1.7 Hz, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 161.0, 138.2, 138.2, 138.0, 131.6, 130.5, 128.5, 128.5, 128.2, 128.1, 127.9, 127.9, 127.8, 127.8, 116.2, 100.4, 79.0, 78.2, 77.2, 75.2, 72.4, 71.9, 71.4, 62.8, 26.5; IR (in KBr) 3447, 3133, 3031, 2860, 2797, 2361, 2339, 1675, 1603, 1401, 1240, 1080, 736, 694 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C34H34O6Na 561.2248, found 561.2244. 4-Acetylphenyl 2,3,4-Tri-O-benzyl-α-L-rhampyranoside (3fa): 65 mg, 59% yield, α only, white solid, mp 91−92 °C; [α]20 D −54.1 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.90 (d, J = 8.0 Hz, 2H), 7.41−7.27 (m, 15H), 7.01 (d, J = 8.0 Hz, 2H), 5.54 (d, J = 2.0 Hz, 1H), 4.96 (d, J = 10.7 Hz, 1H), 4.85 (d, J = 12.0 Hz, 1H), 4.77 (d, J = 12.0 Hz, 1H), 4.72 (d, J = 4.0 Hz, 1H), 4.66 (d, J = 8.0 Hz, 1H), 4.07−4.04 (m, 1H), 3.96 (dd, J = 3.1, 2.1 Hz, 1H), 3.81−3.64 (m, 2H), 2.55 (s, 3H), 1.29 (d, J = 5.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 196.9, 160.0, 138.4, 138.0, 131.5, 130.6, 128.6, 128.6, 128.5, 128.1, 128.1, 128.0, 127.9, 127.8, 127.8, 115.9, 96.1, 80.3, 79.8, 75.6, 74.5, 73.3, 72.6, 69.2, 26.5, 18.1; IR (in KBr)

solution reached pH 9. The reaction was monitored for completion using TLC. The reaction was neutralized by adding Amberlite IR 120 H+ resin until the pH reached 7. Then resin was filtered away, and the filtrate was concentrated under reduced pressure to afford 8 (1.4 g, quantitative yield) as a white solid. Allyl 2,3,6-tri-O-benzyl-4-O-(2′,3′,4′,6′-tetra-O-benzyl-α-D-glucopyranosyl)-α/β-D-glucopyranoside 9 and disaccharide substrate 1j were prepared by following the general procedure for the preparation of monosaccharide substrates. 2,3,6-Tri-O-benzyl-4-O-(2′,3′,4′,6′-tetra-O-benzyl-α-D-glucopyranosyl)-α/β-D-glucopyranoside (1j): α/β = 2:1, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.29−7.20 (m, 27H), 7.19−7.16 (m, 5H), 7.14−7.10 (m, 2H), 5.62 (d, J = 3.6 Hz, 1H), 5.22 (d, J = 3.6 Hz, 0.7H), 4.96−4.84 (m, 3H), 4.81−4.74 (m, 3H), 4.67−4.63 (m, 1H), 4.60−4.48 (m, 5.7H), 4.43 (dd, J = 10.8, 2.8 Hz, 1H), 4.32 (t, J = 12.4 Hz, 1H), 4.12 (d, J = 8.0 Hz,1H), 4.08−3.99 (m, 1.7H), 3.89 (dd, J = 16.0, 8.0 Hz, 1H), 3.84−3.71 (m, 2.7H), 3.69−3.61 (m, 3H), 3.57−3.39 (m, 3.7H), 3.09 (br, 0.7H); 13C NMR (100 MHz, CDCl3) δ (ppm) 138.8, 138.7, 138.7, 138.4, 138.1, 138.0, 137.9, 137.9, 137.6, 128.5, 128.4, 128.4, 128.3, 128.3, 128.2, 128.2, 128.2, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.8, 127.7, 127.7, 127.6, 127.6, 127.6, 127.5, 127.5, 127.2, 126.7, 126.6, 97.4, 97.0, 96.9, 90.8, 84.4, 83.1, 82.0, 81.4, 80.0, 79.4, 79.2, 77.6, 77.3, 75.6, 75.0, 75.0, 74.6, 74.3, 74.3, 73.9, 73.5, 73.3, 73.3, 73.2, 73.1, 72.9, 72.7, 71.2, 71.0, 69.8, 69.4, 69.1, 68.1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C61H64O11Na 995.4341, found 995.4346. General Procedure for the Synthesis of Product 3. NiCl2· glyme (2.2 mg, 0.01 mmol) and 4,4′-di-tert-butyl-2,2′-bipyridine (dtbbpy, 2.7 mg, 0.01 mmol) were dissolved in MeCN (2.0 mL), and the mixture was stirred at room temperature for 10 min. Then aryl bromide 2 (0.4 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (2.2 mg, 0.002 mmol), 1,4-diazabicyclo[2.2.2]octane (DABCO, 2.2 mg, 0.02 mmol), K2CO3 (27.6 mg, 0.2 mmol), and sugar lactol 1 (0.2 mmol) were added, and the resulting mixture was degassed via the “freeze−pump− thaw” procedure (3 times) under an argon atmosphere. After that, the solution was stirred at a distance of ∼3 cm from 2 × 3 W blue LEDs (30 mW/cm2) at 40 °C for about 48 h until the reaction was completed, as monitored by TLC analysis. After the solvent MeCN was removed under reduced pressure, the crude product was purified by flash chromatography on silica gel (petroleum ether/EtOAc = 20:1 → 5:1) to give the desired product 3. 4-Acetylphenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-glucopyranoside (3aa): 107 mg, 81% yield, α/β = 8:1, white solid, mp 108−109 °C; 1 [α]20 D +96.6 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.96−7.87 (m, 2H), 7.44−7.21 (m, 21H), 7.15−7.05 (m, 4H), 5.49 (d, J = 3.5 Hz, 1H), 5.06 (d, J = 10.7 Hz, 1H), 4.96−4.77 (m, 4H), 4.65 (d, J = 12.1 Hz, 1H), 4.58 (d, J = 12.0 Hz, 1H), 4.47 (d, J = 10.7 Hz, 1H), 4.39 (d, J = 12.0 Hz, 1H), 4.20 (ddd, J = 9.1, 7.2, 1.5 Hz, 1H), 3.86−3.64 (m, 5H), 3.53 (dd, J = 10.7, 1.5 Hz, 1H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 196.9, 196.9, 161.0, 160.4, 138.7, 138.4, 138.1, 138.0, 138.0, 137.9, 137.7, 131.9, 131.6, 130.6, 130.5, 128.6, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.1, 128.1, 128.0, 128.0, 128.0, 128.0, 127.9, 127.8, 127.8, 127.8, 116.2, 100.8, 95.2, 84.6, 81.9, 81.9, 79.6, 77.6, 77.4, 76.0, 75.9, 75.3, 75.3, 75.2, 73.7, 73.6, 73.5, 71.2, 68.7, 68.0, 26.5; IR (in KBr) 3062, 3027, 2928, 1669, 1598, 1451, 1358, 1240, 1083, 736, 696 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C42H42O7Na 681.2823, found 681.2809. 4-Acetylphenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-galactopyranoside (3ba): 108 mg, 82% yield, α/β = 2:1. Compound 3ba-α: white solid, 1 mp 105−106 °C; [α]20 D +33.2 (c 0.33, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.95−7.85 (m, 2H), 7.48−7.20 (m, 18H), 7.16 (dd, J = 7.4, 2.2 Hz, 2H), 7.13−7.05 (m, 2H), 5.53 (d, J = 3.6 Hz, 1H), 4.98 (d, J = 11.3 Hz, 1H), 4.94−4.76 (m, 3H), 4.68 (d, J = 12.0 Hz, 1H), 4.59 (d, J = 11.3 Hz, 1H), 4.33 (dd, J = 24.0, 11.6 Hz, 2H), 4.22 (dd, J = 10.0, 3.6 Hz, 1H), 4.14 (dd, J = 10.1, 2.7 Hz, 1H), 4.05 (d, J = 2.7 Hz, 1H), 4.00 (t, J = 6.5 Hz, 1H), 3.56 (dd, J = 9.3, 6.5 Hz, 1H), 3.46 (dd, J = 9.3, 6.5 Hz, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 160.9, 138.7, 138.6, 138.3, 137.8, 131.6, 130.5, 128.6, 128.5, 128.5, 128.4, 128.4, 128.1, 128.0, 127.9, 127.8, 13330

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry

2H), 3.83−3.74 (m, 5H), 3.66 (t, J = 9.3 Hz, 1H), 3.58 (dd, J = 9.9, 3.6 Hz, 1H), 3.52 (dd, J = 9.9, 3.6 Hz, 1H), 3.46 (d, J = 10.4 Hz, 1H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 161.0, 138.7, 138.6, 138.3, 138.2, 137.9, 137.9, 137.8, 131.9, 130.7, 128.5, 128.5, 128.5, 128.4, 128.4, 128.3, 128.2, 128.2, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 127.6, 127.3, 126.7, 116.3, 100.8, 97.2, 84.7, 82.1, 81.9, 79.3, 77.7, 77.4, 75.7, 75.2, 75.1, 75.1, 74.3, 73.6, 73.5, 73.4, 73.0, 71.3, 69.1, 68.2, 26.6; IR (in KBr) 3463, 3127, 3030, 2925, 2864, 2361, 2340, 1680, 1600, 1454, 1400, 1239, 1099, 735, 697 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C69H70O12Na 1113.4759, found 1113.4761. 4-Acetylphenyl 2,3,4,6-Tetra-O-methyl-α/β-D-glucopyranoside (3ka): 58 mg, 82% yield, α/β = 2:1. Compound 3ka-α: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.93 (d, J = 8.9 Hz, 2H), 7.17 (d, J = 8.9 Hz, 2H), 5.71 (d, J = 3.5 Hz, 1H), 3.75−3.68 (m, 4H), 3.64−3.58 (m, 2H), 3.57 (s, 3H), 3.54−3.52 (m, 4H), 3.46 (dd, J = 10.7, 2.1 Hz, 1H), 3.42−3.34 (m, 5H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 160.4, 131.8, 130.6, 116.3, 94.7, 83.4, 81.4, 78.9, 71.2, 70.6, 61.1, 60.7, 59.3, 59.3, 26.6; IR (in KBr) 3128, 3030, 2928, 1669, 1600, 1454, 1400, 1239, 1099, 735, 697 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C18H26O7Na 377.1571, found 377.1566. Compound 3ka-β: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.97−7.85 (m, 2H), 7.08−6.97 (m, 2H), 4.91 (d, J = 7.4 Hz, 1H), 3.67−3.63 (m, 7H), 3.61−3.56 (m, 1H), 3.55 (s, 3H), 3.46−3.42 (m, 1H), 3.37 (s, 3H), 3.34−3.28 (m, 1H), 3.28−3.23 (m, 2H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 196.9, 161.1, 131.9, 130.6, 116.2, 100.7, 86.4, 83.5, 79.1, 75.1, 71.2, 61.1, 60.8, 60.6, 59.5, 26.5; IR (in KBr) 3129, 3030, 2925, 1672, 1600, 1454, 1400, 1236, 1099, 736, 695 cm−1; HRMS (ESI-TOF) m/ z [M + Na]+ calcd for C18H26O7Na 377.1571, found 377.1569. 4-Cyanophenyl 2,3,4,6-Tetra-O-benzyl-α-D-glucopyranoside (3ab): 71 mg, 55% yield, α/β = 1:0.6, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.56 (d, J = 8.6 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1.2H), 7.39−7.24 (m, 32H), 7.19−7.17 (m, 1.2H), 7.13−7.06 (m, 4H), 5.41 (d, J = 3.5 Hz, 1H), 5.04 (d, J = 10.7 Hz, 1.6H), 4.96−4.80 (m, 6H), 4.60 (d, J = 12.0 Hz, 1H), 4.57 (dd, J = 23.2, 12.0 Hz, 2H), 4.51−4.46 (m, 1.6H), 4.40 (d, J = 11.3 Hz, 1H), 4.16 (t, J = 9.1 Hz, 1H), 3.80−3.64 (m, 8H), 3.52 (d, J = 10.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 160.3, 159.8, 138.6, 138.3, 138.0, 137.8, 137.6, 134.0, 134.0, 128.6, 128.5, 128.4, 128.1, 128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 118.9, 117.2, 105.9, 105.6, 100.7, 95.4, 84.5, 81.8, 79.6, 77.2, 77.1, 75.9, 75.8, 75.3, 75.2, 75.1, 73.7, 73.5, 73.4, 71.3, 68.6, 68.0; IR (in KBr) 3447, 3123, 3030, 2922, 2865, 2361, 2341, 2226, 1722, 1604, 1505, 1400, 1244, 1101, 1073, 738, 698, 548 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C41H39NO6Na 664.2670, found 664.2676. 4-Cyanophenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-mannopyranoside (3cb): 58 mg, 45% yield, α/β = 5:1, colorless oil; [α]20 D +47.8 (c 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.54 (d, J = 8.5 Hz, 2.4H), 7.40−7.27 (m, 22H), 7.15 (dd, J = 7.0, 2.5 Hz, 2.4H), 7.06 (d, J = 8.6 Hz, 2H), 5.61 (s, 1H), 4.89 (d, J = 10.6 Hz, 1H), 4.80 (dd, J = 24.0, 12.4 Hz, 2.2H), 4.70 (dd, J = 20.0, 12.4 Hz, 2.2H), 4.63 (d, J = 12.0 Hz, 1.2H), 4.51 (d, J = 10.7 Hz, 1.2H), 4.45 (d, J = 11.9 Hz, 1.2H), 4.13 (t, J = 9.4 Hz, 1.2H), 4.06 (dd, J = 9.2, 2.7 Hz, 1H), 3.95 (s, 1H), 3.79−3.73 (m, 2.4H), 3.64 (d, J = 9.6 Hz, 1.2H), 3.21−3.17 (m, 0.2H), 3.14 (d, J = 15.2 Hz, 0.2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 159.3, 138.3, 138.2, 138.1, 138.0, 134.1, 128.6, 128.5, 128.5, 128.4, 128.4, 128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 127.8, 127.7, 119.0, 117.1, 105.6, 96.4, 79.7, 77.4, 75.3, 74.4, 74.2, 73.4, 73.1, 72.9, 72.6, 68.7; IR (in KBr) 3111, 3089, 3064, 3031, 2913, 2865, 2361, 2340, 2226, 1725, 1604, 1505, 1454, 1400, 1245, 1098, 984, 837, 737, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C41H39NO6Na 664.2670, found 664.2670. 4-Cyanophenyl 2,3,4-Tri-O-benzyl-α-L-rhampyranoside (3fb): 34 1 mg, 32% yield, α only, colorless oil; [α]20 D −33.8 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.55 (d, J = 8.6 Hz, 2H), 7.41− 7.29 (m, 15H), 7.02 (d, J = 8.6 Hz, 2H), 5.49 (d, J = 2.0 Hz, 1H), 4.96 (d, J = 10.7 Hz, 1H), 4.85 (d, J = 12.3 Hz, 1H), 4.76 (d, J = 12.0 Hz, 1H), 4.68 (dd, J = 22.0, 10.0 Hz, 3H), 4.02 (dd, J = 8.0, 2.0 Hz, 1H), 3.94 (t, J = 2.6 Hz, 1H), 3.74−3.64 (m, 2H), 1.29 (d, J = 5.2 Hz,

3485, 3117, 3032, 2918, 2362, 2341, 1672, 1600, 1399, 1271, 991, 735, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C35H36O6Na 575.2404, found 575.2409. 4-Acetylphenyl 2,3,4-Tri-O-benzyl-α-L-fucopyranoside (3ga): 60 mg, 54% yield, α only, white solid, mp 74−75 °C; [α]20 D −46.9 (c 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.93−7.91 (m, 2H), 7.49−7.20 (m, 15H), 7.14−7.04 (m, 2H), 5.52 (d, J = 3.6 Hz, 1H), 5.03 (d, J = 11.4 Hz, 1H), 4.95 (d, J = 11.7 Hz, 1H), 4.85 (dd, J = 16.0, 12.0 Hz, 1H), 4.68 (dd, J = 11.8, 3.6 Hz, 2H), 4.22 (dd, J = 10.1, 3.6 Hz, 1H), 4.14 (dd, J = 10.1, 2.8 Hz, 1H), 3.91 (dd, J = 12.0, 6.5 Hz, 1H), 3.73 (dd, J = 2.9, 1.2 Hz, 1H), 2.56 (s, 3H), 1.07 (d, J = 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 161.1, 138.8, 138.5, 138.3, 131.4, 130.5, 128.6, 128.5, 128.5, 128.4, 128.1, 127.9, 127.8, 127.7, 127.6, 116.3, 96.1, 79.2, 76.0, 75.1, 73.7, 73.5, 67.7, 26.6, 16.7; IR (in KBr) 3466, 3127, 3030, 2900, 2360, 2339, 1678, 1600, 1400, 1242, 1103, 738, 697 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C35H36O6Na 575.2404, found 575.2411. 4-Acetylphenyl 2,3,4,6-Tetra-O-benzyl-α- L -gulopyranoside (3ha): 85 mg, 65% yield, α only, colorless oil; [α]20 D +10.9 (c 0.50, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.90−7.87 (m, 2H), 7.43−7.26 (m, 18H), 7.11−7.08 (m, 4H), 5.55 (dd, J = 8.1, 2.4 Hz, 1H), 4.85 (dd, J = 12.1, 1.9 Hz, 1H), 4.68 (ddd, J = 16.9, 12.1, 1.9 Hz, 2H), 4.60−4.49 (m, 2H), 4.45 (dd, J = 11.8, 1.8 Hz, 1H), 4.39−4.23 (m, 3H), 3.91−3.88 (m, 1H), 3.83−3.81 (m, 1H), 3.67−3.57 (m, 2H), 3.53−3.51 (m, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 161.3, 138.4, 138.2, 138.1, 137.7, 131.5, 130.5, 128.5, 128.5, 128.5, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 116.3, 98.4, 75.8, 74.7, 74.6, 73.6, 73.6, 72.8, 72.8, 69.0, 26.6; IR (in KBr) 3063, 3030, 2914, 2871, 2361, 2338, 1678, 1601, 1504, 1454, 1399, 1359, 1243, 1080, 837, 737, 699 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C42H42O7Na 681.2823, found 681.2827. 4-Acetylphenyl 2,3,5-Tri-O-benzyl-α-D-ribofuranoside (3ia): 65 1 mg, 60% yield, α only, colorless oil; [α]20 D +1.6 (c 0.50, CHCl3); H NMR (600 MHz, CDCl3) δ (ppm) 7.92 (d, J = 8.7 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.35−7.24 (m, 13H), 7.06 (d, J = 8.5 Hz, 2H), 5.56 (d, J = 6.9 Hz, 1H), 4.84 (d, J = 8.9 Hz, 3H), 4.73 (d, J = 12.1 Hz, 1H), 4.58 (dd, J = 20.0, 12.0 Hz, 2H), 4.17 (s, 1H), 4.00 (t, J = 10.2 Hz, 1H), 3.84 (dd, J = 11.0, 4.5 Hz, 1H), 3.65−3.61 (m, 1H), 3.56 (dd, J = 8.0, 4.0 Hz, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 160.9, 138.7, 138.3, 138.0, 131.7, 130.6, 128.6, 128.5, 128.4, 128.0, 127.9, 127.9, 127.8, 127.7, 116.1, 98.4, 77.7, 75.2, 74.7, 74.1, 73.1, 71.7, 62.5, 26.6; IR (in KBr) 3112, 3030, 3005, 2880, 2361, 2340, 1718, 1601, 1505, 1400, 1358, 1249, 1072, 958, 837, 735, 698, 592 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C34H34O6Na 561.2248, found 561.2250. 4-Acetylphenyl O-(2′,3′,4′,6′-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-α/β-D-glucopyranoside (3ja): 100 mg, 46% yield, α/β = 2:1. Compound 3ja-α: colorless oil; [α]20 D +25.8 (c 0.33, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.92 (d, J = 8.3 Hz, 2H), 7.30−7.18 (m, 33H), 7.12 (d, J = 8.3 Hz, 2H), 7.07 (t, J = 4.0 Hz, 2H), 5.68 (d, J = 3.5 Hz, 1H), 5.45 (d, J = 3.4 Hz, 1H), 5.09 (d, J = 11.4 Hz, 1H), 4.90 (t, J = 10.0 Hz, 2H), 4.81−4.69 (m, 3H), 4.63−4.47 (m, 4H), 4.45−4.36 (m, 3H), 4.32−4.23 (m, 2H), 4.18 (t, J = 9.3 Hz, 1H), 3.91 (t, J = 9.4 Hz, 2H), 3.86−3.69 (m, 3H), 3.66 (d, J = 9.1 Hz, 1H), 3.57−3.45 (m, 3H), 3.38 (d, J = 10.6 Hz, 1H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.0, 160.6, 138.9, 138.8, 138.4, 138.1, 138.0, 137.9, 137.8, 131.7, 130.6, 128.6, 128.5, 128.5, 128.4, 128.4, 128.3, 128.2, 128.2, 128.0, 127.9, 127.8, 127.8, 127.7, 127.6, 127.3, 127.3, 126.9, 116.4, 97.1, 95.0, 82.1, 81.8, 80.0, 79.4, 77.7, 77.4, 75.7, 75.1, 74.7, 73.7, 73.6, 73.5, 73.1, 72.5, 71.1, 70.8, 68.7, 68.2, 26.6; IR (in KBr) 3463, 3127, 3030, 2925, 2864, 2361, 2340, 1680, 1600, 1454, 1400, 1239, 1099, 735, 697 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C69H70O12Na 1113.4759, found 1113.4769. Compound 3ja-β: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.91 (d, J = 8.4 Hz, 2H), 7.36− 7.13 (m, 33H), 7.13−7.03 (m, 4H), 5.65 (d, J = 3.6 Hz, 1H), 5.11 (d, J = 7.3 Hz, 1H), 4.95 (dd, J = 11.3, 6.6 Hz, 2H), 4.89 (d, J = 10.7 Hz, 1H), 4.85−4.76 (m, 3H), 4.72 (d, J = 10.8 Hz, 1H), 4.64−4.56 (m, 2H), 4.54 (s, 1H), 4.50 (s, 2H), 4.44 (d, J = 10.3 Hz, 1H), 4.35 (d, J = 12.2 Hz, 1H), 4.10 (t, J = 8.2 Hz, 1H), 3.89 (dd, J = 16.0, 9.2 Hz, 13331

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 159.4, 138.3, 138.3, 137.9, 134.1, 128.6, 128.6, 128.5, 128.1, 128.1, 128.0, 127.9, 127.9, 127.8, 119.1, 116.8, 105.4, 96.3, 80.1, 79.6, 75.6, 74.4, 73.3, 72.6, 69.4, 18.1; IR (in KBr) 3111, 3089, 3064, 3031, 2913, 2865, 2361, 2340, 2226, 1725, 1604, 1505, 1454, 1400, 1245, 1098, 984, 837, 737, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C34H33NO5Na 558.2251, found 558.2263. 4-Methylsulfonylphenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-glucopyranoside (3ac): 98 mg, 71% yield, α/β = 1:0.4, colorless oil; [α]20 D +27.8 (c 0.33, CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.85 (d, J = 8.6 Hz, 2.8H), 7.41−7.23 (m, 28H), 7.21−7.17 (m, 3.4H), 7.14−7.11 (m, 2.8H), 5.46 (d, J = 3.4 Hz, 1H), 5.06 (t, J = 10.9 Hz, 1.4H), 4.98−4.92 (m, 1.2H), 4.89−4.82 (m, 3.6H), 4.60−4.54 (m, 1.6H), 4.49 (t, J = 11.8 Hz, 1.4H), 4.40 (d, J = 12.0 Hz, 1H), 4.18 (t, J = 9.1 Hz, 1H), 3.83−3.66 (m, 6.4H), 3.53 (d, J = 10.7 Hz, 1H), 3.02 (s, 3H), 3.01 (s, 1.2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 160.7, 138.6, 138.0, 137.9, 137.9, 137.8, 137.6, 133.9, 129.6, 129.5, 128.6, 128.6, 128.5, 128.5, 128.5, 128.3, 128.2, 128.2, 128.1, 128.0, 128.0, 128.0, 127.9, 127.9, 127.9, 127.8, 127.8, 117.0, 117.0, 100.8, 95.5, 84.6, 81.8, 81.8, 79.5, 77.4, 77.0, 76.0, 75.9, 75.3, 75.2, 73.8, 73.5, 71.3, 68.6, 67.9, 44.8, 44.8; IR (in KBr) 3125, 3030, 2924, 2865, 2360, 1634, 1594, 1541, 1496, 1454, 1401, 1316, 1242, 1148, 738, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C41H42O8SNa 717.2493, found 717.2496. 4-Methylsulfonylphenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-galactopyranoside (3bc): 60 mg, 43% yield, α/β = 1:0.3, colorless oil; 1 [α]20 D +34.8 (c 0.67, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.83 (d, J = 8.0 Hz, 2.4H), 7.44−7.23 (m, 28H), 7.20−7.17 (m, 5H), 5.51 (d, J = 3.5 Hz, 1H), 5.05 (d, J = 7.6 Hz, 0.2H), 4.98 (d, J = 11.3 Hz, 1.4H), 4.90 (d, J = 12.0 Hz, 1H), 4.82 (dd, J = 24.0, 11.7 Hz, 2.2H), 4.68 (d, J = 11.3 Hz, 1.2H), 4.59 (d, J = 8.0 Hz, 1.2H), 4.41− 4.30 (m, 2.8H), 4.23 (dd, J = 10.0, 3.5 Hz, 1.2H), 4.17−4.11 (m, 1.4H), 4.06 (s, 1.2H), 3.97 (t, J = 6.3 Hz, 1.2H), 3.72 (t, J = 6.3 Hz, 0.2H), 3.66−3.59 (m, 0.4H), 3.55 (dd, J = 9.2, 7.1 Hz, 1.4H), 3.45 (dd, J = 9.3, 5.9 Hz, 1H), 2.99 (s, 4H); 13C NMR (100 MHz, CDCl3) δ (ppm) 161.2, 161.1, 138.6, 138.4, 138.3, 138.2, 138.2, 138.2, 137.7, 133.9, 133.7, 129.5, 129.5, 128.6, 128.6, 128.5, 128.5, 128.5, 128.5, 128.4, 128.4, 128.4, 128.3, 128.3, 128.1, 128.0, 128.0, 128.0, 127.9, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 117.3, 117.0, 101.0, 96.4, 82.0, 78.9, 78.8, 77.4, 76.0, 75.7, 75.0, 74.7, 74.6, 74.2, 73.9, 73.7, 73.5, 73.3, 73.1, 73.0, 70.7, 68.8, 44.9, 44.8; IR (in KBr) 3125, 3030, 2923, 2867, 2361, 2340, 1720, 1593, 1495, 1454, 1400, 1314, 1243, 1148, 1096, 738, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C41H42O8SNa 717.2493, found 717.2492. 4-Ethyl 2,3,4,6-Tetra-O-benzyl-α/β-D-glucopyranosyl Phenylacetate (3ad): 48 mg, 35% yield, α/β = 1:0.75, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.01−7.98 (m, 3.5H), 7.41−7.24 (m, 40H), 7.13−7.06 (m, 6H), 5.47 (d, J = 3.4 Hz, 1H), 5.08−5.04 (m, 1.5H), 4.99 (t, J = 8.0 Hz, 0.75H), 4.93 (d, J = 12.0 Hz, 1H), 4.89− 4.82 (m, 4.2H), 4.72−4.45 (m, 7.5H), 4.42−4.33 (m, 5H), 4.20 (t, J = 8.6 Hz, 1H), 3.88−3.66 (m, 8.5H), 3.52 (d, J = 10.7 Hz, 1H), 1.41−1.37 (m, 5.25H); 13C NMR (100 MHz, CDCl3) δ (ppm) 166.4, 166.3, 160.8, 160.2, 138.8, 138.4, 138.1, 138.1, 138.0, 137.9, 137.7, 131.7, 131.5, 128.7, 128.7, 128.6, 128.6, 128.5, 128.5, 128.4, 128.3, 128.3, 128.2, 128.2, 128.1, 128.1, 128.1, 128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 124.8, 124.5, 116.1, 100.9, 95.2, 84.7, 82.0, 79.7, 77.6, 77.4, 76.0, 75.3, 73.7, 71.1, 68.7, 68.0, 60.9, 60.9, 14.5; IR (in KBr) 3447, 3125, 3030, 2924, 2360, 2339, 1634, 1594, 1496, 1454, 1401, 1316, 1242, 1148, 955, 738, 698, 541, 521 cm−1; HRMS (ESITOF) m/z [M + Na]+ calcd for C43H44O8Na 711.2928, found 711.2924. 5-(1′-Fluoro-3′-trifluorophenyl) 2,3,4,6-Tetra-O-benzyl-α/β-Dglucopyranoside (3ae): 74 mg, 53% yield, α/β = 3:1, white solid, 1 mp 49−50 °C; [α]20 D +68.9 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ (ppm) 7.40−7.22 (m, 25H), 7.18−7.11 (m, 4H), 7.02− 6.93 (m, 2.5H), 5.35 (d, J = 3.5 Hz, 1H), 5.04 (d, J = 10.8 Hz, 1H), 4.99−4.83 (m, 5H), 4.61 (t, J = 12.0 Hz, 2H), 4.59−4.52 (m, 1H), 4.48 (d, J = 10.5 Hz, 1H), 4.41 (d, J = 12.0 Hz, 1H), 4.15 (t, J = 8.7 Hz, 1H), 3.82−3.64 (m, 6H), 3.55 (d, J = 10.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 163.2 (d, J = 240.0 Hz), 158.8 (d, J =

10.0 Hz), 158.3 (d, J = 10.0 Hz), 138.7, 138.4, 138.1, 138.1, 138.0, 137.9, 137.7, 133.0 (dq, J = 70, 40, 10.0 Hz), 129.7, 128.7, 128.6, 128.6, 128.5, 128.5, 128.3, 128.2, 128.2, 128.2, 128.1, 128.0, 128.0, 128.0, 127.9, 127.9, 127.9, 127.9, 127.8, 123.3 (d, J = 270, 10.0 Hz), 110.2 (m), 109.9 (m), 107.8 (d, J = 30.0 Hz), 107.7 (d, J = 30.0 Hz), 106.8 (d, J = 10.0 Hz), 106.5 (d, J = 10.0 Hz), 101.4, 96.1, 84.7, 81.9, 81.9, 79.7, 77.4, 77.2, 76.0, 75.9, 75.3, 75.2, 73.9, 73.6, 71.5, 68.5, 68.0; IR (in KBr) 3113, 3067, 3032, 2921, 2867, 2361, 2340, 1731, 1605, 1497, 1454, 1400, 1349, 1132, 1096, 895, 859, 737, 697 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C41H38O6F4Na 725.2497, found 725.2515. 5-(2′-Cyanopyridyl) 2,3,4,6-Tetra-O-pyridyl-α/β-D-glucopyranoside (3af): 48 mg, 35% yield, α/β = 1:0.3, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.48 (d, J = 4.0 Hz, 1H), 8.39 (d, J = 1.0 Hz, 0.3H), 7.59 (d, J = 13.1, 8.6 Hz, 1H), 7.55 (d, J = 8.6 Hz, 1H), 7.45−7.22 (m, 28H), 7.2−7.15 (m, 1H), 7.15−7.05 (m, 2H), 5.37 (d, J = 3.4 Hz, 1H), 5.04 (d, J = 10.7 Hz, 1H), 4.96−4.83 (m, 5H), 4.62 (d, J = 10.7 Hz, 1H), 4.58−4.53 (m, 1.6H), 4.49−4.46 (m, 1.3H), 4.40 (d, J = 12.0 Hz, 1H), 4.15 (t, J = 9.3 Hz, 1H), 3.82−3.64 (m, 6.3H), 3.51 (d, J = 10.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.5, 155.1, 153.3, 141.6, 141.5, 140.7, 138.5, 138.2, 137.9, 137.8, 137.8, 137.7, 137.5, 129.7, 129.6, 128.7, 128.6, 128.6, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.2, 128.1, 128.1, 128.0, 128.0, 128.0, 127.9, 127.9, 127.1, 126.9, 123.2, 123.0, 117.4, 100.8, 96.2, 84.6, 81.7, 79.5, 77.4, 76.1, 76.0, 75.5, 75.4, 75.3, 74.1, 73.6, 71.8, 68.5, 67.9; IR (in KBr) 3445, 3130, 3030, 2919, 2865, 2361, 2339, 2233, 1719, 1636, 1455, 1400, 1245, 1088, 738, 698 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for C40H39N2O6 643.2803, found 643.2798. 5-(2′-Cyanopyridyl) 2,3,4,6-Tetra-O-pyridyl-α/β-D-galactopyranoside (3bf): 50 mg, 39% yield, α/β > 10:1, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.48 (d, J = 2.6 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.44−7.29 (m, 19H), 7.16 (d, J = 7.2 Hz, 2H), 5.43 (d, J = 2.8 Hz, 1H), 4.98 (d, J = 11.2 Hz, 1H), 4.90 (d, J = 11.8 Hz, 2H), 4.81 (d, J = 11.7 Hz, 1H), 4.65 (d, J = 12.0 Hz, 1H), 4.58 (d, J = 11.3 Hz, 1H), 4.34 (dd, J = 20.0, 11.3 Hz, 2H), 4.23 (dd, J = 10.0, 3.2 Hz, 1H), 4.09 (dd, J = 10.0, 3.2 Hz, 1H), 4.04 (s, 1H), 3.90 (d, J = 12.5 Hz, 1H), 3.52−3.41 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.6, 141.7, 138.2, 138.0, 137.7, 129.6, 128.6, 128.6, 128.5, 128.5, 128.3, 128.1, 128.1, 128.0, 127.8, 126.9, 123.2, 117.4, 101.1, 82.0, 78.6, 77.4, 75.8, 74.7, 74.5, 73.8, 73.2, 72.9, 68.8; IR (in KBr) 3129, 3030, 2919, 2867, 2361, 2340, 2233, 1574, 1454, 1400, 1249, 1102, 737, 698 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C40H38N2O6Na 665.2622, found 665.2629. 4-Phenyl 2,3,4,6-Tetra-O-benzyl-α/β-D-glucopyranoside (3ag). 41 mg, 33% yield, α/β = 5:1, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.41−7.21 (m, 24H), 7.13 (dd, J = 7.4, 2.2 Hz, 2H), 7.11−7.06 (m, 2H), 7.01 (t, J = 8.0, 1H), 5.48 (d, J = 3.5 Hz, 1H), 5.05 (d, J = 10.8 Hz, 1H), 5.01 (d, J = 7.4 Hz, 0.2H), 4.95 (d, J = 11.0 Hz, 0.2H), 4.92−4.83 (m, 2H), 4.79 (d, J = 12.2 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.58 (d, J = 12.0 Hz, 1H), 4.49 (d, J = 10.7 Hz, 1H), 4.39 (d, J = 12.0 Hz, 1H), 4.21 (t, J = 9.3 Hz, 1H), 3.92−3.85 (m, 1H), 3.78 (dd, J = 10.1, 8.8 Hz, 1H), 3.75−3.69 (m, 2H), 3.56 (dd, J = 10.8, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 157.5, 156.8, 138.9, 138.6, 138.3, 138.2, 138.1, 137.9, 129.8, 129.6, 129.5, 128.6, 128.5, 128.5, 128.5, 128.4, 128.4, 128.4, 128.3, 128.3, 128.1, 128.1, 128.0, 128.0, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 126.1, 122.8, 122.4, 117.0, 116.9, 101.8, 95.6, 84.8, 82.1, 79.9, 77.8, 77.5, 77.4, 75.9, 75.9, 75.3, 75.2, 75.2, 75.1, 73.6, 73.5, 73.4, 70.9, 69.0, 68.4; IR (in KBr) 3062, 3027, 1598, 1451, 1358, 1240, 1083, 738, 695 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C40H40O6Na 639.2717, found 639.2710. 4-(2′-Naphthyl) 2,3,4,6-Tetra-O-benzyl-α/β-D-glucopyranoside (3ah): 35 mg, 26% yield, α/β = 2:1, colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.77 (t, J = 8.0 Hz, 3H), 7.70 (d, J = 8.1 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.48−7.18 (m, 35H), 7.13 (dd, J = 7.2, 2.2 Hz, 2H), 5.62 (d, J = 3.5 Hz, 1H), 5.15 (d, J = 7.0 Hz, 0.5H), 5.09 (dd, J = 10.8, 2.2 Hz, 1.5H), 5.00−4.76 (m, 5.5H), 4.69 (d, J = 12.1 Hz, 1H), 4.59 (d, J = 12.6 Hz, 1.5H), 4.58 (t, J = 12.0 Hz, 1H), 4.50 (d, J = 10.7 Hz, 1H), 4.39 (d, J = 12.0 Hz, 1H), 4.26 (t, J = 9.2 Hz, 13332

DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

The Journal of Organic Chemistry

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1H), 3.95−3.88 (m, 1H), 3.86−3.75 (m, 3.5H), 3.74−3.69 (m, 2.5H), 3.58 (dd, J = 10.7, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.3, 154.5, 138.9, 138.6, 138.3, 138.2, 138.1, 137.9, 134.5, 130.0, 129.8, 129.6, 129.5, 128.6, 128.6, 128.5, 128.5, 128.5, 128.4, 128.2, 128.1, 128.1, 128.0, 128.0, 127.9, 127.9, 127.9, 127.8, 127.8, 127.8, 127.7, 127.7, 127.4, 127.3, 126.5, 124.5, 124.4, 119.3, 119.2, 111.6, 110.9, 102.0, 95.6, 84.9, 82.2, 82.2, 82.2, 79.9, 77.9, 76.0, 75.4, 75.3, 75.2, 73.7, 73.6, 73.5, 71.0, 69.1, 68.4; IR (in KBr) 3060, 3025, 1600, 1450, 1358, 1240, 1083, 736, 696 cm−1; HRMS (ESI-TOF) m/ z [M + Na]+ calcd for C44H42O6Na 689.2874, found 689.2861. Gram Scale Reaction of Product 3. NiCl2·glyme (44 mg, 0.2 mmol) and dtbbpy (54 mg, 0.2 mmol) were dissolved in MeCN (30 mL), and the mixture was stirred at room temperature for 10 min. Then 2a (1.58 g, 8 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (45 mg, 0.04 mmol), DABCO (45 mg, 0.4 mmol), K2CO3 (553 mg, 4 mmol), and 1a (2.16 g, 4 mmol) were added, and the resulting mixture was degassed via the “freeze−pump−thaw” procedure (3 times) under an argon atmosphere. After that, the solution was stirred at a distance of ∼3 cm from 2 × 3 W blue LEDs (30 mW/cm2) at 40 °C for about 48 h until the reaction was completed, as monitored by TLC analysis. The crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate 10:1) directly to give the desired product 3aa (2.17g, 82%) as a white solid.

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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.8b02129. Preparation of sugar substrates, optimization and control experiments, and spectroscopic data of 1 and 3 (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Peng George Wang: 0000-0003-3335-6794 Wen-Jing Xiao: 0000-0002-9318-6021 Author Contributions #

H.Y. and C.X. contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (21772053 and 21472057), Natural Science Foundation of Hubei Province (2017AHB047), and Huanggang Normal University (2015001703 and 201615503) for financial support.

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REFERENCES

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DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334

Article

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DOI: 10.1021/acs.joc.8b02129 J. Org. Chem. 2018, 83, 13325−13334