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Synthesis 2015; 47(02): 199-208
DOI: 10.1055/s-0034-1379473
paper
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Sugar-Derived Triazole- and Pyridine-Based Metal Complex Ligands

Jochen Kraft
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany   Fax: +49(7071)295244   Email: thomas.ziegler@uni-tuebingen.de
,
Daniel Schmollinger
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany   Fax: +49(7071)295244   Email: thomas.ziegler@uni-tuebingen.de
,
Jakob Maudrich
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany   Fax: +49(7071)295244   Email: thomas.ziegler@uni-tuebingen.de
,
Thomas Ziegler*
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany   Fax: +49(7071)295244   Email: thomas.ziegler@uni-tuebingen.de
› Author Affiliations
Further Information

Publication History

Received: 09 September 2014

Accepted after revision: 19 September 2014

Publication Date:
24 October 2014 (online)

 
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Abstract

A series of 30 bi- and tridentate ligands for metals were prepared by copper-catalyzed coupling (CLICK reaction) of 2-ethynylpridine, 2-ethynyl-5-nitropyridine, 2-ethynylquinoline, and 2,6-diethynylpyridine with 12 protected glycosyl azides in the gluco and galacto series and 2 benzyl azides. The 1,2,3-triazole-linked glycoconjugates prepared were used as ligands for the copper-catalyzed addition of phenylacetylene to N-benzylideneaniline to give chiral N-(1,3-diphenylprop-2-yn-1-yl)aniline.


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Key words

asymmetric catalysis - azides - carbohydrates - enantio­selectivity - glycoconjugates

Despite the fact that carbohydrates are the most abundant enantiomerically pure natural products and that a vast number of sugars can be easily obtained in bulk quantities and high purity from natural sources they were neglected badly, if not even spurned or scorned, as chiral reagents in asymmetric synthesis for a long time. This unduly dislike of sugar-derived reagents was often attributed to their structural complexity and difficulties to selectively modify and purify them although sugars had long and successfully been used as starting material for ex-chiral-pool syntheses of other natural products. In the past decades, however, carbohydrates have gained significant importance as chiral auxiliaries, chiral reagents, and organocatalysts, and, most notably, as chiral ligands for metal-catalyzed stereoselective reactions.[1] For example, Boysen recently introduced bisoxazoline (box) ligands A and B (Figure [1]), containing d-glucosamine-derived 1,2-oxazoline and 1,2-thiazoline moieties, respectively, which both gave high enantioselectivities in Cu-catalyzed asymmetric alkynylations of N-arylimines and cyclopropanations of olefins with azo esters.[2]

Recently, we communicated the synthesis of multidentate carbohydrate-containing ligands C (Figure [1]) in which the sugar moieties were linked through a 1,2,3-triazole group to isophthalic acid or pyridine-2,6-dicarboxylic acid, respectively.[3] Our original intention for the preparation of such ligands was to study their ability to complex metal ions, which may result in a change of the orientation of the sugar moieties. This was thought to enable us to modify the specific interaction of the ligand with sugar-binding proteins upon complexation with metal ions and thus, will give us a closer insight into the interactions of carbohydrates with proteins[4] or will result in novel analytical tools for studying such interactions.[5]

Zoom Image
Figure 1 Examples of known glycosyl-based ligands for metal ions

Inspired by the recent successful application of sugar-bearing ligands for metal-catalyzed stereoselective reactions, we anticipated to use the ligands we have previously prepared for binding studies with carbohydrate-binding proteins also as ligands for metal-catalyzed reactions. Therefore, we present here the straightforward synthesis of some novel bi- and tridentate ligands in which the sugar moiety is directly connected to the heteroaromatic backbone through a 1,2,3-triazole group which, in turn, can also participate in binding the metal ions.[3] [6]

For the preparation of the carbohydrate-bearing ligands four 2-ethynylpyridines 1a–d were coupled with a series of glycosyl azides 2a–l and two benzyl derivatives 2m and 2n by means of the CLICK reaction (Figure [2, ]Scheme [1]). All starting materials were known and were prepared according to literature procedures (see Scheme [1] and Figure [2] for references). In general, ethynylpyridines 1a,b,d were prepared via Sonogashira-coupling of the respective pyridine halogenides and trimethylsilylacetylene followed by desilylation according to known procedures.[7a] [b] [d] 2-Ethynylquinoline 1c was prepared via Sonogashira­-coupling of 2-chloroquinoline and 2-methylbut-3-yn-2-ol followed by treatment of the intermediate with NaOH.[7c]

Zoom Image
Figure 2 Azides 2 used for the preparation of ligands 3–6 via copper(I)-catalyzed 1,3-dipolar cycloaddition. The numbers in superscript refer to the references describing the preparation of 2.
Zoom Image
Scheme 1 Reagents and conditions: CuSO4·H2O (0.2 equiv), sodium ascorbate (0.4 equiv), t-BuOH–H2O, 48 h, 40 °C. The numbers in superscript refer to the references describing the preparation of 1. R = protective group.

Although the syntheses of glycosyl azides 2j and 2l were mentioned in the literature,[8h] [i] the compounds were never fully characterized. Thus, we prepared and fully characterized both the glycosyl azides as follows. Acetylation of 4,6-O-benzylidene-β-d-galactosyl azide[9] with acetic anhydride in pyridine gave 2j in 81% yield. Likewise, treatment of β-d-glucopyranosyl azide[8b] [10] with trityl chloride in pyridine followed by acetylation of the intermediate with acetic anhydride afforded 2l in 53% yield. For comparison reasons, the two benzyl azides 2m and 2n (Figure [2]) were also chosen in order to prepare ligands not containing sugars. (S)-(1-Azidoethyl)benzene (2m) was prepared in situ from commercial (S)-1-phenylethylamine by treatment with 1H-imidazole-1-sulfonyl azide and using the crude 2m directly for the following click reaction.[11]

Table 1 Compounds 3–6 Prepared

Entry

2

Yield (%) 3

Yield (%) 4

Yield (%) 5

Yield (%) 6

 1

2a

81 3a

67 4a

78 5a

60 6a

 2

2b

60 3b

–

73 5b

89 6b

 3

2c

–

–

84 5c

–

 4

2d

–

–

91 5d

–

 5

2e

95 3e

68 4e

68 5e

67 6e

 6

2f

85 3f

–

73 5f

–

 7

2g

52 3g

77 4g

71 5g

61 6g

 8

2h

87 3h

–

81 5h

–

 9

2i

23 3i

–

–  5i a

39 6i

10

2j

–

–

90 5j

76 6j

11

2k

–

–

71 5k

–

12

2l

86 3l

–

–

–

13

2m

–

–

67 5m

–

14

2n

–

–

70 5n

97 6n

a Separation of starting material and product was not possible.

As catalyst for the click reaction of alkynes 1 and azides 2 the copper(II)sulfate/sodium ascorbate protocol[12] was chosen, which gave the best yields in our hands. Thus, the copper-catalyzed 1,3-dipolar cycloadditions between 1 and 2 were performed in aqueous tert-butyl alcohol at 40 °C to afford bidentate ligands 3, 4, and 5 and tridentate ligands 6 in medium to good yields (Scheme [1, ]Table [1]). Compounds 3a (Table [1], entry 1), 3b (entry 2), 3e (entry 5), and 6n (entry 14) were previously prepared in a similar manner and used either for biological studies, as ligands for rhodium-catalyzed enantioselective hydrosilylations or for X-ray studies of metal complexes.[13] All products were isolated either by direct crystallization from the crude product mixture or by flash chromatography. In the case of ligand 5i (entry 9), all attempts to purify the ligand failed because separation from contaminant by-products was not possible. All ligands 3–6 were fully characterized.

With triazole ligands 3–6 on hand we then turned to some preliminary applications of these ligands for enantioselective metal-catalyzed reactions. As a model reaction the copper(I)-catalyzed addition of phenylacetylene to N-benzylideneaniline to give chiral N-(1,3-diphenylprop-2-yn-1-yl)aniline 7 was chosen (Scheme [2]). Similar enantioselective additions of alkynes to enamines were previously investigated in great detail.[2a] [14] In general, the benchmark conditions of Wei et al.[14k] was used (i.e., 10 mol% CuOTf and 10 mol% ligand) for a selection of ligands (Table [2]). In addition, the achiral ligands 5n and 6n were also used for evaluating the reaction conditions and for comparison reasons. The aniline derivative 7 was isolated by chromatography in all cases and its enantiomeric excess was determined via gas chromatography on a chiral stationary phase. The assignment of the absolute configuration was done by comparing the optical rotation with that of N-[1-(3-bromophenyl)-3-phenylprop-2-yn-1-yl]aniline for which the absolute configuration was unambiguously determined through X-ray crystallography.[14a] [b] Thus, a positive optical rotation refers to R-configuration while a negative optical rotation refers to the S-enantiomer. All ligands tested here resulted in an excess of R-enantiomer of 7.

Table 2 Enantioselective Alkynylation with Ligands 3–6 to Give 7

Entry

Ligand

Yield (%)a

ee (%)b,c

 1

A (X = O)d

69

99 (S)d

 2

5n

81

–

 3

6n

87

–

 4

5m

78

 5 (R)

 5

3a

48

17 (R)

 6

4a

78

22 (R)

 7

5a

99

24 (R)

 8

6a

80

31 (R)

 9

5e

92

63 (R)

10

6i

75

60 (R)

11

6j

85

56 (R)

a Isolated yield after chromatography.

b Determined by chiral GC.

c Absolute configuration was determined by comparison of the optical rotation to literature values.[14a] [b]

d Figure [1]; taken from ref. 2a; no unambiguous assignment of the absolute configuration was done.

Zoom Image
Scheme 2 Addition of phenylacetylene to N-benzylidenaniline

For tridentate ligands 6 and for bidentate ligands 4 and 5, preparative yields of 7 were in the range of 75–99% and thus, higher than for previously reported ligand A (Table [2], entry 1).[2a] Only bidentate ligand 3a showed a significantly lower yield (entry 5). The enantioselectivity of the reaction was poor for (S)-methylbenzyl-derived triazolylquinoline ligand 5m (entry 4) and bidentate ligand 3a (entry 5). Better selectivities were obtained with tridentate ligands 5 and 6 where the ligands contained pivaloyl­-protected sugar moieties (entry 9) or conformationally restricted 4,6-O-benzylidene sugar moieties (entries 10 and 11). Although the enantioselectivity achieved with ligands 3–6 shown in Table [2] are medium, these preliminary results show that the ligands described here can be useful for metal-catalyzed stereoselective reactions. Further optimizations and other examples are currently under investigation and will be published elsewhere.

All solvents were dried according to standard methods, distilled, and stored over molecular sieves 3 Å under an atmosphere of N2 prior to their use. Petroleum ether (PE) used refers to the fraction boiling­ in the 60–90 °C range. All nonaqueous reactions were performed in oven-dried glassware under an atmosphere of N2, unless otherwise stated. NMR spectra were recorded on a Bruker Avance 400 spectrometer and calibrated for the solvent signal (1H CDCl3: 7.26 ppm; 13C CDCl3: 77.16 ppm; 1H DMSO-d 6: 2.50 ppm; 13C DMSO-d 6: 39.52 ppm). ESI-HRMS were recorded on a Bruker Apex II FT-ICR-MS spectrometer, FAB-spectra on a Finnigan model TSQ 70. Elemental analysis was performed on a HEKAtech Euro 3000 CHN analyzer. IR-spectra were recorded on a Bruker Tensor 27 spectrophotometer. Optical rotations were measured with a Perkin-Elmer Polarimeter 341 in a 10 cm cuvette at 20 °C. Melting points were determined with a Büchi Melting Point M-560 apparatus. Reactions were monitored by TLC on Polygram Sil G/UV silica gel plates from Machery & Nagel. Detection of spots was effected by charring with H2SO4 (5% in EtOH), staining by spraying the plates with an alkaline aqueous solution of KMnO4 or by inspection of the TLC plates under UV light. Preparative chromatography was performed on silica gel (0.032–0.063 mm) from Machery & Nagel with different mixtures of solvents as eluent. The enantiomeric excess of 7 was determined by gas chromatography on a Hewlett Packard 5890 GC equipped with a MEGA-DEX DET-Beta column; carrier gas H2; injection temp 280 °C; column temp 160 °C constant. t R = 237.8 min for (S)-7, and t R = 243.4 min for enantiomer (R)-7. All yields given below are isolated yields determined after purification of the product either by silica gel column chromatography or crystallization and were not optimized, unless noted otherwise.


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2,3-O-Acetyl-4,6-O-benzylidene-β-d-galactopyranosyl Azide (2j)

Ac2O (3.2 mL, 33.8 mmol) was added to an ice-cold solution of 4,6-O-benzylidene-β-d-galactopyranosyl azide[9] (2.5 g, 8.5 mmol) in pyridine (20 mL). The resulting mixture was allowed to warm to r.t. and stirred at this temperature for 2 h. The mixture was diluted with H2O (50 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined organic phases were washed with 1 M aq HCl (100 mL), sat. aq NaHCO3 (100 mL) and H2O (100 mL), dried (Na2SO4), filtered, and concentrated. Recrystallization of the residue from EtOH gave 2j as colorless needles; yield: 2.6 g (81%); mp 157 °C (EtOH); Rf  = 0.38 (PE–EtOAc, 1:1); [α]D 20 +16.8 (c 1.00, CHCl3).

IR (KBr): 3415, 2114, 1750, 1638, 1617, 1455 cm–1.

1H NMR (CDCl3): δ = 2.07, 2.09 (2 s, 6 H, CH3), 3.61 (d, J 5,4 = 1.0 Hz, 1 H, H-5), 4.05 (dd, J 6b,5 = 1.7 Hz, 1 H, H-6b), 4.34 (dd, J 6a,5 = 1.5 Hz, J 6a,6b = 12.6 Hz, 1 H, H-6a), 4.40 (d, 1 H, H-4), 4.58 (d, J 1,2 = 8.8 Hz, 1 H, H-1), 4.97 (dd, J 3,4 = 3.5 Hz, 1 H, H-3), 5.35 (t, J 2,3 = 10.3 Hz, 1 H, H-2), 5.50 (s, 1 H, benzylidene-H), 7.37–7.51 (m, 5 H, phenyl-H).

13C NMR (CDCl3): δ = 20.8, 20.9 (CH3), 67.9 (C-2), 68.3 (C-5), 68.7 (C-6), 71.8 (C-3), 73.2 (C-4), 88.3 (C-1), 101.2 (benzylidene-C), 126.4, 128.4, 129.3, 137.4 (phenyl-C), 169.4, 170.7 (C=O).

MS (FAB): m/z = 335.1 (100%, [M – N3]+).

Anal. Calcd for C17H19N3O7 (377.4): C, 54.11; H, 5.08; N, 11.14. Found: C, 54.10; H, 4.96; N, 10.79.


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2,3,4-Tri-O-acetyl-6-O-trityl-β-d-glucopyranosyl Azide (2l)

A mixture of β-d-glucopyranosyl azide[10] (8.2 g, 39.9 mmol) and trityl­ chloride (14.4 g, 51.7 mmol) in pyridine (150 mL) was stirred at 40 °C for 72 h. The solution was cooled to 0 °C and Ac2O (33.8 mL, 0.36 mol) was added. After stirring for another 12 h at r.t., the reaction was quenched with EtOH (100 mL) and concentrated. Chromatography (PE–EtOAc, 2:1) of the residue and subsequent recrystallization from EtOH gave 2l as colorless crystals; yield: 12.1 g (53%); mp 130 °C (EtOH); Rf  = 0.46 (PE–EtOAc, 2:1); [α]D 20 +16.8 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.77, 2.03, 2.11 (3 s, 9 H, CH3), 3.11 (dd, J 6b,5 = 4.1 Hz, J 6b,6a = 10.6 Hz, 1 H, H-6b), 3.37 (dd, J 6a,5 = 2.1 Hz, 1 H, H-6a), 3.70 (m, 1 H, H-5), 4.67 (d, J 1,2 = 8.8 Hz, 1 H, H-1), 5.06 (t, J 2,3 = 9.1 Hz, 1 H, H-2), 5.19 (t, J 3,4 = 9.4 Hz, 1 H, H-3), 5.29 (t, J 4,5 = 9.4 Hz, 1 H, H-4), 7.24–7.28 (m, 3 H, trityl-H), 7.31–7.35 (m, 6 H, trityl-H), 7.47–7.49 (m, 6 H, trityl-H).

13C NMR (CDCl3): δ = 20.5, 20.7 (CH3), 61.7 (C-6), 68.3 (C-4), 71.1 (C-2), 73.1 (C-3), 75.7 (C-5), 86.8 (trityl-C), 87.6 (C-1), 127.2, 128.0, 128.8, 143.5 (phenyl-C), 168.9, 169.4, 170.4 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C31H31N3O8 + Na: 596.200340; found: 596.200047.

Anal. Calcd for C31H31N3O8 (573.6): C, 64.91; H, 5.45; N, 7.33: Found: C, 64.95; H, 5.57; N, 7.43.


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Click Reaction; General Procedure

To a stirred solution of the glycosyl azide 2 (1 mmol for alkynes 1a,b,c; 2 mmol for 1d) in t-BuOH–H2O (4:1, 100 mL) was added the alkynyl compound 1 (1 mmol), CuSO4·H2O (50 mg, 0.2 mmol for 1a,b,c; 100 mg, 0.4 mmol for 1d), and sodium ascorbate (80 mg, 0.4 mmol for 1a,b,c; 160 mg, 0.8 mmol for 1d). The resulting solution was stirred at 40 °C until TLC (eluent: see individual examples) showed complete consumption of the starting material (12–48 h). The reaction mixture was diluted with H2O (100 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined organic layers were washed with 1 M aq EDTA solution (50 mL) and H2O (50 mL), dried (Na2SO4), filtered, and concentrated. Flash chromatography or crystallization of the crude product gave compounds 3–6.


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2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3a)

Treatment of 2a (373 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by recrystallization from EtOH gave 3a; yield: 386 mg (81%); colorless crystals; mp 211 °C. Spectroscopic data were in accordance with the literature.[13a]


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2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3b)

Treatment of 2b (373 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by recrystallization from EtOH gave 3b; yield: 286 mg (60%); colorless needles; mp 182 °C. Spectroscopic data were in accordance with the literature.[13b]


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2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3e)

Treatment of 2e (542 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 2:1) gave 3e; yield: 613 mg (95%); white amorphous solid. Spectroscopic data were in accordance with the literature.[13c]


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2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3f)

Treatment of 2f (542 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 5:2) and recrystallization from EtOH gave 3f; yield: 550 mg (85%); colorless crystals; mp 199 °C (EtOH); Rf  = 0.33 (PE–EtOAc, 5:2); [α]D 20 –35.0 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 0.92, 1.10, 1.13, 1.31 (4 s, 36 H, CH3), 4.11 (m, 2 H, H-6a, H-6b), 4.31 (m, 1 H, H-5), 5.35 (dd, J 3,4 = 1.8 Hz, 1 H, H-3), 5.56 (s, 1 H, H-4), 5.70 (t, J 2,3 = 10.1 Hz, 1 H, H-2), 5.98 (d, J 1,2 = 9.1 Hz, 1 H, H-1), 7.22 (t, J = 7.2 Hz, 1 H, pyridine-H), 7.75 (t, J = 7.7 Hz, 1 H, pyridine-H), 8.12 (d, J = 8.1 Hz, 1 H, pyridine-H), 8.32 (s, 1 H, triazole-H), 8.59 (d, J = 3.5 Hz, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 27.0, 27.3, 27.3, 27.5 (CH3), 39.0, 39.1, 39.5 (pivaloyl-C), 61.1 (C-6), 66.8 (C-4), 68.1 (C-2), 71.3 (C-3), 74.6 (C-5), 86.8 (C-1), 120.4, 120.7, 123.4, 137.2, 149.2, 149.8, 150.0 (Carom), 176.6, 176.9, 177.4, 178.0 (C=O).

MS (FAB): m/z = 651.2 (100%, [M + Li]+).

Anal. Calcd for C33H48N4O9 (644.8): C, 61.47; H, 7.50; N, 8.69. Found: C, 61.23; H, 7.44; N, 8.71.


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2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-benzyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3g)

Treatment of 2g (566 mg, 1 mmol) and 1a (101 mL, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 3:1) and recrystallization from EtOH gave 3g; yield: 500 mg (75%); colorless crystals; mp 165 °C (EtOH); Rf  = 0.11 (PE–EtOAc, 3:1); [α]D 20 –39.3 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.75–3.79 (m, 3 H, H-5, H-6a, H-6b), 3.85–3.93 (m, 2 H, H-3, H-4), 4.09 (t, J 2,3 = 8.8 Hz, 1 H, H-2), 4.19 (m, 1 H, benzyl-CH2), 4.51–4.68 (m, 4 H, benzyl-CH2), 4.90–4.99 (m, 3 H, benzyl-CH2), 5.71 (d, J 1,2 = 9.0 Hz, 1 H, H-1), 7.01–7.03 (m, 2 H, phenyl-H), 7.10–7.37 (m, 19 H, phenyl-H, pyridine-H), 7.80–7.84 (m, 1 H, pyridine-H), 8.25 (d, J = 7.8 Hz, 1 H, pyridine-H), 8.32 (s, 1 H, triazole-H), 8.64 (m, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 68.5 (C-6), 73.7, 75.1, 75.3, 75.9, (benzyl-CH2), 77.4, 78.2, 85.5 (C-3, C-4, C-5), 81.1 (C-2), 87.8 (C-1), 120.5 (triazole-C), 121.3, 123.1, 127.8, 127.9, 127.9, 128.0, 128.0, 128.0, 128.1, 128.3, 128.4, 128.5, 128.6, 136.9, 137.0, 137.9, 137.9, 138.2 (Carom), 148.7 (triazole-C), 149.6, 150.1 (Carom).

HRMS-ESI: m/z [M + Na]+ calcd for C41H40N4O5 + Na: 691.289092; found: 691.289110.

Anal. Calcd for C41H40N4O5 (668.8): C, 73.63; H, 6.03; N, 8.38. Found: C, 73.63; H, 6.07; N, 8.49.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-benzyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3h)

Treatment of 2h (566 mg, 1 mmol) and 1a (101 mL, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 5:2) and recrystallization from EtOH gave 3h; yield: 580 mg (87%); colorless crystals; mp 148 °C (EtOH); Rf  = 0.15 (PE–EtOAc, 5:2); [α]D 20 –48.5 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.63 (m, 2 H, H-6a, H-6b), 3.80 (dd, J 3,4 = 2.8 Hz, H-3), 3.86 (m, 1 H, H-5), 4.08 (d, J 4,5 = 2.4 Hz, 1 H, H-4), 4.22 (d, J = 10.6 Hz, 1 H, benzyl-CH2), 4.38 (t, J 2,3 = 9.6 Hz, 1 H, H-2), 4.45 (dd, J = 11.8 Hz, 2 H, benzyl-CH2), 4.65 (m, 2 H, benzyl-CH2), 4.79 (m, 2 H, benzyl-CH2), 5.02 (d, J = 11.4 Hz, 1 H, benzyl-CH2), 5.71 (d, J 1,2 = 9.1 Hz, 1 H, H-1), 7.03–7.39 (m, 21 H, phenyl-H, pyridine-H), 7.78 (dt, J = 1.8, 7.8 Hz, 1 H, pyridine-H), 8.21 (m, 1 H, pyridine-H), 8.31 (s, 1 H, triazole-H), 8.60 (m, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 68.5 (C-6), 73.1 (benzyl-CH2), 73.6 (C-4), 73.9, 75.1, 76.6 (benzyl-CH2), 76.6 (C-5), 78.2 (C-2), 83.2 (C-3), 88.4 (C-1), 120.6, 121.0, 123.2, 127.9, 128.0, 128.1, 128.2, 128.2, 128.3, 128.5, 128.6, 128.6, 128.7, 128.8, 137.1 (Carom), 137.4, 137.9, 138.2, 138.7, 148.8, 149.7, 150.4 (Carom).

HRMS-ESI: m/z [M + Na]+ calcd for C41H40N4O5 + Na: 691.289092; found: 691.289406.


#

2-[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3i)

Treatment of 2i (377 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:1) gave 3i; yield: 110 mg (23%); white amorphous solid; Rf  = 0.23 (PE–EtOAc, 1:1); [α]D 20 –116.3 (c 1.00, DMSO).

1H NMR (DMSO-d 6): δ = 1.82, 2.02 (2 s, 6 H, CH3), 3.78–3.83 (m, 1 H, H-6b), 4.11 (m, 2 H, H-4, H-5), 4.29–4.33 (m, 1 H, H-6a), 5.57–5.77 (m, 3 H, benzylidene-H, H-2, H-3), 6.41 (d, J 1,2 = 9.0 Hz, 1 H, H-1), 7.36–7.42 (m, 6 H, phenyl-H, pyridine-H), 7.89–7.93 (m, 1 H, pyridine-H), 8.03–8.05 (m, 1 H, pyridine-H), 8.61–8.63 (m, 1 H, pyridine-H), 8.96 (s, 1 H, triazole-H).

13C NMR (DMSO-d 6): δ = 20.0, 20.6 (CH3), 67.4 (C-6), 68.2, 76.9 (C-4, C-5), 71.2 (C-2), 71.6 (C-3), 84.9 (C-1), 100.7 (benzylidene-C), 119.8, 122.6 (Carom), 123.6 (triazole-C), 126.3, 128.3, 129.2, 137.2, 137.5, 147.9, 149.3, 149.9 (Carom), 168.9, 169.8 (C=O).

HRMS-ESI: m/z [M + H]+ calcd for C24H24N4O7 + H: 481.171776; found: 481.172147.


#

2-[1′-(2′′,3′′,4′′-Tri-O-acetyl-6′′-O-trityl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (3l)

Treatment of 2l (574 mg, 1 mmol) and 1a (101 μL, 1 mmol) according to the general procedure followed by recrystallization from EtOH gave 3l; yield: 580 mg (86%); colorless crystals; mp 193 °C (EtOH); Rf  = 0.15 (PE–EtOAc, 2:1); [α]D 20 +15.7 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.78, 1.88, 2.01 (3 s, 9 H, CH3), 3.16 (dd, J 6a,6b = 10.9 Hz, 1 H, H-6b), 3.37 (dd, 1 H, H-6a), 3.89 (ddd, J 5,6a = 4.4 Hz, J 5,6b = 2.1 Hz, 1 H, H-5), 5.36–5.41 (m, 2 H, H-3, H-4), 5.44–5.49 (m, 1 H, H-2), 5.90 (d, J 1,2 = 9.2 Hz, 1 H, H-1), 7.17–7.27 (m, 10 H, trityl-H, pyridine-H), 7.35–7.41 (m, 6 H, trityl-H), 7.74–7.79 (m, 1 H, pyridine-H), 8.15 (d, J = 7.9 Hz, 1 H, pyridine-H), 8.44 (s, 1 H, triazole-H), 8.60 (d, J = 4.3 Hz, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 20.4, 20.5, 20.7 (CH3), 61.9 (C-6), 68.2, 73.1 (C-3, C-4), 71.0 (C-2), 77.3 (C-5), 86.3 (C-1), 87.0 (trityl-C), 120.4 (triazole-C), 120.4, 123.2, 127.3, 128.0, 128.8, 136.9, 143.4, 149.2, 149.8, 149.8 (Carom), 169.0, 169.0, 170.3 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C38H36N4O8 + Na: 699.242535; found: 699.241896.

Anal. Calcd for C38H36N4O8 (676.7): C, 67.44; H, 5.36; N, 8.28. Found: C, 67.50; H, 5.44; N, 8.30.


#

5-Nitro-2-[1′-(2′′,3′′,4′′,6′′-tetra-O-acetyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (4a)

Treatment of 2a (373 mg, 1 mmol) and 1b (148 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 2:1) and recrystallization from EtOH gave 4a; yield: 410 mg (79%); colorless needles; mp 258 °C (EtOH); Rf  = 0.45 (PE–EtOAc, 1:1); [α]D 20 –79.1 (c 1.00, CHCl3).

1H NMR (DMSO-d 6): δ = 1.82, 1.98, 2.00, 2.04 (4 s, 12 H, CH3), 4.09–4.18 (m, 2 H, H-6a, H-6b), 4.40–4.43 (m, 1 H, H-5), 5.24 (t, J 4,5 = 9.8 Hz, 1 H, H-4), 5.61 (t, J 3,4 = 9.5 Hz, 1 H, H-3), 5.80 (t, J 2,3 = 9.3 Hz, 1 H, H-2), 6.46 (d, J 1,2 = 9.1 Hz, 1 H, H-1), 8.28 (d, J = 8.7 Hz, 1 H, pyridine-H), 8.70 (dd, J = 2.3, 8.7 Hz, 1 H, pyridine-H), 9.25 (s, 1 H, triazole-H), 9.42 (d, J = 2.3 Hz, 1 H, pyridine-H).

13C NMR (DMSO-d 6): δ = 19.9, 20.3, 20.4, 20.5 (CH3), 61.9 (C-6), 67.5 (C-4), 70.3 (C-2), 71.9 (C-3), 73.4 (C-5), 84.2 (C-1), 119.9 (pyridine-C), 124.6 (triazole-C), 133.0 (pyridine-C), 143.3 (Carom), 145.4 (pyridine-C), 146.3, 154.1 (Carom), 168.7, 169.4, 169.6, 170.1 (C=O).

MS (FAB): m/z (%) = 522.1 (15, [M + H]+), 331.1 (100, [M – C7H4N5O2]+).

Anal. Calcd for C21H23N5O11 (521.1): C, 48.37; H, 4.45; N, 13.43. Found: C, 48.47; H, 4.43; N, 13.36.


#

5-Nitro-2-[1′-(2′′,3′′,4′′,6′′-tetra-O-pivaloyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (4e)

Treatment of 2e (542 mg, 1 mmol) and 1b (148 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 4:1) and recrystallization from EtOH gave 4e; yield: 470 mg (68%); pale yellow needles; mp 232 °C (EtOH); Rf  = 0.33 (PE–EtOAc, 4:1); [α]D 20 –47.5 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 0.93, 1.11, 1.17, 1.19 (4 s, 36 H, CH3), 4.05–4.10 (m, 1 H, H-5), 4.15–4.25 (m, 2 H, H-6a, H-6b), 5.35 (t, J = 9.6 Hz, 1 H, H-4), 5.49–5.58 (m, 2 H, H-2, H-3), 5.99 (d, J 1,2 = 8.9 Hz, 1 H, H-1), 8.31 (dd, J = 0.4, 8.8 Hz, 1 H, pyridine-H), 8.48 (s, 1 H, triazole-H), 8.54 (dd, J = 2.6, 8.7 Hz, 1 H, pyridine-H), 9.40 (dd, J = 0.5, 2.6 Hz, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 26.8, 27.1, 27.2, 27.2 (CH3), 38.8, 38.9, 38.9, 39.0 (pivaloyl-C), 61.3 (C-6), 67.1 (C-4), 70.6, 72.0 (C-2, C-3), 75.9 (C-5), 86.4 (C-1), 120.1 (pyridine-C), 122.6 (triazole-C), 132.2 (pyridine-C), 143.4 (triazole-C), 145.5 (pyridine-C), 147.4, 154.7 (pyridine-C), 176.4, 176.4, 177.0, 178.0 (C=O).

HRMS-ESITOF: m/z [M + Na]+ calcd for C33H47N5O11 + Na: 712.31643; found: 712.31750.

Anal. Calcd for C33H47N5O11 (689.3): C, 57.46; H, 6.87; N, 10.15. Found: C, 57.54; H, 6.87; N, 10.08.


#

5-Nitro-2-[1′-(2′′,3′′,4′′,6′′-tetra-O-benzyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (4g)

Treatment of 2g (566 mg, 1 mmol) and 1b (148 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 3:1) gave 4g; yield: 550 mg (77%); pale yellow amorphous solid; Rf  = 0.45 (PE–EtOAc, 2:1); [α]D 20 –49.8 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.78–3.81 (m, 3 H, H-5, H-6a, H-6b), 3.90–3.96 (m, 2 H, H-3, H-4), 4.11 (t, J 2,3 = 8.8 Hz, 1 H, H-2), 4.24 (d, J = 10.9 Hz, 1 H, benzyl-CH2), 4.50–4.68 (m, 4 H, benzyl-CH2), 4.90–4.98 (m, 3 H, benzyl-CH2), 5.75 (d, J 1,2 = 9.0 Hz, 1 H, H-1), 6.98–7.37 (m, 20 H, phenyl-H), 8.34–8.38 (m, 2 H, pyridine-H, triazole-H), 8.50 (dd, J = 2.6, 8.7 Hz, 1 H, pyridine-H), 9.42 (d, J = 2.5 Hz, 1 H, pyridine-H).

13C NMR (CDCl3): δ = 68.3 (C-6), 73.5, 74.9, 75.2, 75.8 (benzyl-CH2), 77.2, 85.4 (C-3, C-4), 78.1 (C-5), 80.6 (C-2), 87.7 (C-1), 119.9 (Carom), 123.4 (triazole-C), 127.7, 127.8, 127.8, 127.9, 128.0, 128.2, 128.3, 128.4, 128.5, 132.1 (Carom), 136.8, 137.7, 138.0, 143.1 (Carom), 145.3 (pyridine-C), 146.7 (Carom), 154.9 (CNO2).

HRMS-ESI: m/z [M + Na]+ calcd for C41H39N5O7 + Na: 736.274170; found: 736.273641.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5a)

Treatment of 2a (373 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:1) and recrystallization from EtOH gave 5a; yield: 410 mg (78%); colorless needles; mp 209 °C (EtOH); Rf  = 0.23 (PE–EtOAc, 1:1); [α]D 20 –94.4 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.88, 2.03, 2.07, 2.09 (4 s, 12 H, CH3), 4.02–4.06 (m, 1 H, H-5), 4.17 (dd, J 6b,6a = 12.6 Hz, J 6b,5 = 1.6 Hz, 1 H, H-6b), 4.33 (dd, J 6a,5 = 5.0 Hz, 1 H, H-6a), 5.28 (t, J 4,5 = 9.7 Hz, 1 H, H-4), 5.46 (t, J 3,4 = 9.4 Hz, 1 H, H-3), 5.56 (t, J 2,3 = 9.4 Hz, 1 H, H-2), 5.97 (d, J 1,2 = 9.3 Hz, 1 H, H-1), 7.51 (t, J = 7.4 Hz, 1 H, quinoline-H), 7.70 (t, J = 7.7 Hz, 1 H, quinoline-H), 7.80 (d, J = 8.0 Hz, 1 H, quinoline-H), 8.06 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.21–8.29 (m, 2 H, quinoline-H), 8.61 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 20.3, 20.6, 20.8 (CH3), 61.6 (C-6), 67.7 (C-4), 70.6 (C-2), 72.8 (C-3), 75.2 (C-5), 86.0 (C-1), 118.7 (quinoline-C), 121.5 (triazole-C), 126.6, 127.8 (quinoline-C), 128.0 (triazole-C), 129.2, 129.9, 137.0 (quinoline-C), 148.1, 149.4, 149.7 (quinoline-C), 169.0, 169.4, 170.1, 170.6 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C25H26N4O9 + Na: 549.159200; found: 549.159685.

Anal. Calcd for C25H26N4O9 (526.5): C, 57.03; H, 4.98; N, 10.64. Found: C, 57.38; H, 4.98; N, 10.62.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5b)

Treatment of 2b (373 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 3:4) and recrystallization from EtOH gave 5b; yield: 385 mg (73%); colorless crystals; mp 193 °C (EtOH); Rf  = 0.38 (PE–EtOAc, 3:4); [α]D 20 –78.0 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.89, 2.00, 2.02, 2.25 (4 s, 12 H, CH3), 4.13–4.23 (m, 2 H, H-6a, H-6b), 4.28 (t, J 5,6 = 6.2 Hz, 1 H, H-5), 5.30 (dd, J 3,4 = 3.2 Hz, 1 H, H-3), 5.66 (t, J 2,3 = 10.2 Hz, 1 H, H-2), 5.67 (d, J 4,5 = 2.7 Hz, 1 H, H-4), 5.94 (d, J 1,2 = 9.2 Hz, 1 H, H-1), 7.50 (t, J = 7.3 Hz, 1 H, quinoline-H), 7.69 (t, J = 7.5 Hz, 1 H, quinoline-H), 7.79 (t, J = 8.1 Hz, 1 H, quinoline-H), 8.06 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.21–8.31 (m, 2 H, quinoline-H), 8.64 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 20.3, 20.6, 20.7, 20.8 (CH3), 61.4 (C-6), 67.0 (C-4), 68.1 (C-2), 70.9 (C-3), 74.1 (C-5), 86.5 (C-1), 118.7 (Carom), 121.4 (triazole-C), 126.6, 127.8, 127.9, 129.1, 129.9, 137.0 (Carom), 148.1, 149.2, 149.9 (Carom), 169.1, 169.9, 170.1, 170.4 (C=O).

MS (FAB): m/z (%) = 527.1 (40, [M + H]+), 331.1 (35, [M – C11H7N4]+).

Anal. Calcd for C25H26N4O9 (526.2): C, 57.03; H, 4.98; N, 10.64. Found: C, 56.93; H, 5.01; N, 10.61.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-d-mannopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5c)

Treatment of 2c (373 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:1) gave 5c; yield: 440 mg (84%); pale yellow amorphous solid; Rf  = 0.29 (PE–EtOAc, 1:1); [α]D 20 –128.5 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 2.00, 2.09, 2.11 (3 s, 12 H, CH3), 4.01–4.06 (m, 1 H, H-5), 4.24 (dd, J 6b,5 = 2.1 Hz, J 6b,6a = 12.5 Hz, 1 H, H-6b), 4.36 (dd, J 6a,5 = 5.9 Hz, 1 H, H-6a), 5.33–5.43 (m, 2 H, H-3, H-4), 5.83 (d, J 2,3 = 1.4 Hz, 1 H, H-2), 6.27 (d, J 1,2 = 1.2 Hz, 1 H, H-1), 7.49–7.53 (m, 1 H, quinoline-H), 7.68–7.72 (m, 1 H, quinoline-H), 7.81 (d, J = 8.1 Hz, 1 H, quinoline-H), 8.05 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.22 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.30 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.61 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 20.6, 20.7, 20.8, 20.9 (CH3), 62.4 (C-6), 65.1 (C-4), 68.9 (C-2), 70.9 (C-3), 75.8 (C-5), 85.0 (C-1), 118.8 (quinoline-C), 122.0 (triazole-C), 126.6, 127.9, 128.0, 129.1, 129.9, 137.1 (Carom), 148.1, 148.7, 150.0 (Carom), 169.3, 169.7, 169.9, 170.7 (C=O).

HRMS-ESITOF: m/z [M + H]+ calcd for C25H26N4O9 + H: 527.17725; found: 527.17796.


#

2-[1′-(2′′-Acetamido-2′′-deoxy-3′′,4′′,6′′-tri-O-acetyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5d)

Treatment of 2d (372 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:2) and recrystallization from EtOH gave 5d; yield: 480 mg (91%); colorless crystals; mp >260 °C (EtOH, dec.); Rf  = 0.27 (PE–EtOAc, 1:2); [α]D 20 –112.9 (c 1.00, CHCl3).

1H NMR (DMSO-d 6): δ = 1.61, 1.97, 2.01, 2.04 (4 s, 12 H, CH3), 4.11 (dd, J 6b,5 = 1.8 Hz, J 6b,6a = 12.3 Hz, 1 H, H-6b), 4.19 (dd, J 6a,5 = 5.4 Hz, 1 H, H-6a), 4.27–4.31 (m, 1 H, H-5), 4.82 (q, J 2,3 = 9.8 Hz, 1 H, H-2), 5.21 (t, J 4,5 = 9.7 Hz, 1 H, H-4), 5.42 (t, J = 9.8 Hz, 1 H, H-3), 6.23 (d, J 1,2 = 9.9 Hz, 1 H, H-1), 7.61 (m, 1 H, quinoline-H), 7.80 (m, 1 H, quinoline-H), 8.02 (m, 2 H, quinoline-H), 8.16 (d, J NH,2 = 9.2 Hz, 1 H, NHAc), 8.22 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.49 (d, J = 8.6 Hz, 1 H, quinoline-H), 9.10 (s, 1 H, triazole-H).

13C NMR (DMSO-d 6): δ = 20.3, 20.4, 20.5, 22.3 (CH3), 52.2 (C-2), 62.0 (C-6), 68.1 (C-4), 72.3 (C-3), 73.5 (C-5), 85.1 (C-1), 118.2 (quinoline-C), 123.0 (triazole-C), 126.6 (quinoline-C), 127.4 (Carom­), 128.1, 128.5, 130.2, 137.3 (quinoline-C), 147.5, 147.6, 149.7 (Carom), 169.4, 169.5, 169.6, 170.1 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C25H27N5O8 + Na: 548.175184; found: 548.174921.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5e)

Treatment of 2e (542 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 4:1) and recrystallization from EtOH gave 5e; yield: 470 mg (68%); colorless needles; mp 199 °C (EtOH); Rf  = 0.32 (PE–EtOAc, 3:1); [α]D 20 –63.1 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 0.94, 1.13, 1.19, 1.22 (4 s, 36 H, CH3), 4.05–4.09 (m, 1 H, H-5), 4.17–4.25 (m, 2 H, H-6a, H-6b), 5.37 (t, J = 9.6 Hz, 1 H, H-4), 5.54–5.62 (m, 2 H, H-2, H-3), 6.02 (d, J 1,2 = 8.8 Hz, 1 H, H-1), 7.51–7.55 (m, 1 H, quinoline-H), 7.70–7.74 (m, 1 H, quinoline-H), 7.82 (d, J = 8.2 Hz, 1 H, quinoline-H), 8.08 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.26 (q, J = 8.4 Hz, 2 H, quinoline-H), 8.57 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 26.9, 27.2, 27.3, 27.3 (CH3), 38.9, 38.9, 39.0, 39.1 (pivaloyl-C), 61.5 (C-6), 67.3 (C-4), 70.6, 72.3 (C-2, C-3), 75.9 (C-5), 86.4 (C-1), 118.7 (quinoline-C), 121.3 (triazole-C), 126.7, 127.8 (quinoline-C), 128.0 (Carom), 129.5, 130.0, 137.0 (quinoline-C), 148.3, 149.5, 149.8 (Carom), 176.5, 177.2, 178.1 (C=O).

HRMS-ESITOF: m/z [M + H]+ calcd for C37H50N4O9 + H: 695.36506; found: 695.36462.

Anal. Calcd for C37H50N4O9 (694.4): C, 63.96; H, 7.25; N, 8.06. Found: C, 63.89; H, 7.27; N, 8.00.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5f)

Treatment of 2f (542 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 3:1) and recrystallization from EtOH gave 5f; yield: 510 mg (73%); pale yellow crystals; mp 197 °C (EtOH); Rf  = 0.41 (PE–EtOAc, 3:1); [α]D 20 –60.2 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 0.94, 1.13, 1.15, 1.36 (4 s, 36 H, CH3), 4.09–4.21 (m, 2 H, H-6a, H-6b), 4.34 (t, J 5,6 = 6.8 Hz, 1 H, H-5), 5.38 (dd, J 3,4 = 3.1 Hz, 1 H, H-3), 5.60 (d, J 4,5 = 3.0 Hz, 1 H, H-4), 5.77 (t, J 2,3 = 10.1 Hz, 1 H, H-2), 6.04 (d, J 1,2 = 9.4 Hz, 1 H, H-1), 7.50–7.53 (m, 1 H, quinoline-H), 7.69–7.73 (m, 1 H, quinoline-H), 7.81 (d, J = 8.3 Hz, 1 H, quinoline-H), 8.10 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.22–8.30 (m, 2 H, quinoline-H), 8.52 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 27.0, 27.3, 27.4, 27.6 (CH3), 39.0, 39.0, 39.1, 39.5 (pivaloyl-C), 61.1 (C-6), 66.9 (C-4), 68.1 (C-2), 71.4 (C-3), 74.6 (C-5), 86.9 (C-1), 119.0 (Carom), 121.2 (triazole-C), 126.9, 128.0, 128.2, 129.5, 130.1, 137.2 (Carom), 148.4, 149.5, 150.1 (Carom­), 176.8, 177.0, 177.4, 178.1 (C=O).

HRMS-ESI: m/z [M + H]+ calcd for C37H50N4O9 + H: 695.365056; found: 695.365597.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-benzyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5g)

Treatment of 2g (566 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 3:1) gave 5g; yield: 510 mg (71%); pale yellow amorphous solid; Rf  = 0.40 (PE–EtOAc, 2:1); [α]D 20 –55.7 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.75–3.81 (m, 3 H, H-5, H-6a, H-6b), 3.87–3.94 (m, 2 H, H-3, H-4), 4.13 (t, J 2,3 = 8.8 Hz, 1 H, H-2), 4.21–5.00 (m, 8 H, benzyl-CH2), 5.74 (d, J 1,2 = 9.0 Hz, 1 H, H-1), 7.01–7.37 (m, 20 H, phenyl-H), 7.53–7.57 (m, 1 H, quinoline-H), 7.72–7.77 (m, 1 H, quinoline-H), 7.86 (d, J = 7.5 Hz, 1 H, quinoline-H), 8.11 (d, J = 8.5 Hz, 1 H, quinoline-H), 8.27 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.39 (d, J = 8.5 Hz, 1 H, quinoline-H), 8.51 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 68.5 (C-6), 73.7, 75.0, 75.3, 75.9 (benzyl-CH2), 77.4 (C-4), 78.2 (C-5), 80.9 (C-2), 85.6 (C-3), 87.9 (C-1), 118.8 (Carom), 122.2 (triazole-C), 126.5, 127.8, 127.8, 127.9, 127.9, 127.9, 128.0, 128.0, 128.1, 128.3, 128.4, 128.5, 128.6, 129.2, 129.8, 136.9 (Carom), 136.9, 137.8, 137.9, 138.2 (benzyl-C), 148.2, 149.0, 150.2 (quinoline-C).

HRMS-ESI: m/z [M + Na]+ calcd for C45H42N4O5 + Na: 741.304742; found: 741.304567.


#

2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-benzyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5h)

Treatment of 2h (566 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 5:2) gave 5h; yield: 580 mg (81%); pale yellow amorphous solid; Rf  = 0.23 (PE–EtOAc, 5:2); [α]D 20 –69.3 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.62–3.70 (m, 2 H, H-6a, H-6b), 3.82 (dd, J 3,4 = 2.7 Hz, 1 H, H-3), 3.88 (t, J 5,6 = 6.4 Hz, 1 H, H-5), 4.11 (d, J 4,5 = 2.2 Hz, 1 H, H-4), 4.26 (d, J = 10.7 Hz, 1 H, benzyl-CH2), 4.42–4.51 (m, 3 H, H-2, benzyl-CH2), 4.68 (dd, J = 11.1, 24.9 Hz, 2 H, benzyl-CH2), 4.77–4.84 (m, 2 H, benzyl-CH2), 5.05 (d, J = 11.4 Hz, 1 H, benzyl-CH2), 5.77 (d, J 1,2 = 8.9 Hz, 1 H, H-1), 7.05–7.08 (m, 3 H, phenyl-H), 7.13–7.17 (m, 2 H, phenyl-H), 7.29–7.42 (m, 15 H, phenyl-H), 7.52–7.56 (m, 1 H, quinoline-H), 7.71–7.76 (m, 1 H, quinoline-H), 7.84 (d, J = 8.1 Hz, 1 H, quinoline-H), 8.10 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.25 (d, J = 8.5 Hz, 1 H, quinoline-H), 8.38 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.50 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 68.3 (C-6), 72.9 (benzyl-CH2), 73.5 (C-4), 73.7, 74.9, 75.3 (benzyl-CH2), 76.5 (C-5), 77.9 (C-2), 83.1 (C-3), 88.3 (C-1), 118.9 (Carom), 121.6 (triazole-C), 126.4, 127.7, 127.8, 127.9, 127.9, 128.0, 128.1, 128.2, 128.4, 128.4, 128.5, 128.6, 128.6, 129.2, 129.8, 136.8 (Carom), 137.2, 137.7, 138.0, 138.5 (benzyl-C), 148.2, 148.9, 150.4 (Carom).

HRMS-ESI: m/z [M + H]+ calcd for C45H42N4O5 + H: 719.322797; found: 719.322765.


#

2-[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5j)

Treatment of 2j (377 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:1) gave 5j; yield: 480 mg (90%); pale yellow amorphous solid; Rf  = 0.12 (PE–EtOAc, 1:1); [α]D 20 –117.5 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.93, 2.12 (2 s, 6 H, CH3), 3.89 (s, 1 H, H-5), 4.14 (dd, J 6b,5 = 1.6 Hz, J 6b,6a = 12.7 Hz, 1 H, H-6b), 4.38 (dd, J 6a,5 = 1.2 Hz, 1 H, H-6a), 4.59 (d, J 4,5 = 3.4 Hz, 1 H, H-4), 5.23 (dd, J 3,4 = 3.5 Hz, 1 H, H-3), 5.60 (s, 1 H, benzylidene-H), 5.81 (d, J 2,3 = 9.7 Hz, 1 H, H-2), 5.98 (d, J 1,2 = 9.2 Hz, 1 H, H-1), 7.44–7.73 (m, 7 H, phenyl-H, quinoline-H), 7.81 (d, J = 8.1 Hz, 1 H, quinoline-H), 8.10 (d, J = 8.5 Hz, 1 H, quinoline-H), 8.26 (m, 2 H, quinoline-H), 8.70 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 20.5, 21.0 (CH3), 68.1 (C-2), 68.7 (C-6), 69.4 (C-5), 72.0 (C-3), 73.2 (C-4), 86.8 (C-1), 101.3 (benzylidene-C), 118.8 (Carom), 121.5 (triazole-C), 126.4, 126.6, 127.8, 128.0, 128.5, 129.5, 129.9, 136.9, 137.3 (Carom), 148.3, 149.3, 150.0 (Carom), 169.1, 170.7 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C28H26N4O7 + Na: 553.169370; found: 553.169259.


#

2-[1′-(2′′,3′′,6′′,2′′′,3′′′,4′′′,6′′′-Hepta-O-acetyl-β-d-cellobiosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5k)

Treatment of 2k (662 mg, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:2) gave 5k; yield: 580 mg (71%); white amorphous solid; Rf  = 0.37 (PE–EtOAc, 1:2); [α]D 20 –65.2 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.88, 1.98, 2.01, 2.04, 2.10, 2.12 (6 s, 21 H, CH3), 3.69–3.72 (m, 1 H, H-5), 3.96–3.98 (m, 2 H, H-4′, H-5′), 4.07 (dd, J 6b,5 = 1.8 Hz, J 6b,6a = 12.4 Hz, 1 H, H-6b), 4.16 (dd, J 6b′,5′ = 4.4 Hz, J 6b′,6a′ = 12.2 Hz, 1 H, H-6b′), 4.39 (dd, J 6a,5 = 4.4 Hz, 1 H, H-6a), 4.52 (d, 1 H, H-6a′), 4.57 (d, J 1,2 = 7.9 Hz, 1 H, H-1), 4.96 (t, J 2,3 = 8.6 Hz, 1 H, H-2), 5.08 (t, J 4,5 = 9.6 Hz, 1 H, H-4), 5.17 (t, J 3,4 = 9.3 Hz, 1 H, H-3), 5.42 (t, J 3′,4′ = 8.8 Hz, 1 H, H-3′), 5.52 (t, J 2′,3′ = 9.4 Hz, 1 H, H-2′), 5.90 (d, J 1′,2′ = 9.2 Hz, 1 H, H-1′), 7.51 (t, J = 7.5 Hz, 1 H, quinoline-H), 7.70 (t, J = 7.7 Hz, 1 H, quinoline-H), 7.81 (d, J = 8.1 Hz, 1 H, quinoline-H), 8.04 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.23–8.30 (m, 2 H, quinoline-H), 8.53 (s, 1 H, triazole-H).

13C NMR (CDCl3): δ = 20.3, 20.6, 20.6, 20.8, 20.9 (CH3), 61.6 (C-6), 61.8 (C-6′), 67.8 (C-4), 70.7 (C-2′), 71.6 (C-2), 72.2 (C-5), 72.5 (C-3′), 72.9 (C-3), 75.9, 76.0 (C-4′, C-5′), 85.8 (C-1′), 100.9 (C-1), 118.7 (quinoline-C), 121.5 (triazole-C), 126.6, 127.9 (quinoline-C), 128.0 (Carom), 129.2, 129.9, 137.0 (quinoline-C), 148.1, 149.3, 149.8 (Carom), 169.2, 169.4, 169.7, 170.3, 170.6 (C = O).

HRMS-ESI: m/z [M + Na]+ calcd for C37H42N4O17 + Na: 837.243717; found: 837.243681.


#

2-[1′-(S-α-Methylbenzyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5m)

To a stirred solution of 1H-imidazole-1-sulfonyl azide hydrochloride[11c] (210 mg, 1 mmol) in MeOH (6 mL) was added in the following order: S-(–)-α-methylbenzylamine (0.129 mL, 1 mmol), 2-ethynylquinoline (153 mg, 1 mmol), CuSO4·H2O (25 mg, 0.1 mmol), sodium ascorbate (40 mg, 0.2 mmol), and Et3N (0.139 mL, 1 mmol) under an atmosphere of N2. The deep red mixture was stirred at r.t. for 24 h and concentrated. Flash chromatography (PE–EtOAc, 2:1) of the residue afforded 5m; yield: 200 mg (67%); orange amorphous solid; Rf  = 0.48 (PE–EtOAc, 1:1); [α]D 20 –103.1 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 2.06 (d, J = 7.1 Hz, 3 H, CH3), 5.94 (q, J = 7.1 Hz, 1 H, CH), 7.32–7.41 (m, 5 H, phenyl-H), 7.48–7.52 (m, 1 H, quinoline-H), 7.66–7.70 (m, 1 H, quinoline-H), 7.81 (d, J = 8.1 Hz, 1 H, quinoline-H), 8.00 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.22 (d, J = 8.6 Hz, 1 H, quinoline-H), 8.27 (s, 1 H, triazole-H), 8.35 (d, J = 8.6 Hz, 1 H, quinoline-H).

13C NMR (CDCl3): δ = 21.3 (CH3), 60.5 (CH), 118.7, 121.4, 126.3, 126.6, 127.8, 128.6, 128.9, 129.1, 129.7 (Carom), 139.6, 148.0, 148.6, 150.6 (Carom).

HRMS-ESI: m/z [M + Na]+ calcd for C19H16N4 + Na: 323.126718; found: 323.126428.

Anal. Calcd for C19H16N4 (300.1): C, 75.98; H, 5.37; N, 18.65. Found: C, 75.86; H, 5.42; N, 18.43.


#

2-[1′-Benzyl-1H-1′,2′,3′-triazo-4′-yl]quinoline (5n)

Treatment of 2n (125 μL, 1 mmol) and 1c (153 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 2:1) and recrystallization from EtOH gave 5n; yield: 200 mg (70%); colorless needles; mp 155 °C (EtOH); Rf  = 0.30 (PE–EtOAc, 1:1).

1H NMR (CDCl3): δ = 5.62 (s, 2 H, benzyl-CH2), 7.35–7.40 (m, 5 H, phenyl-H), 7.50 (m, 1 H, quinoline-H), 7.68 (m, 1 H, quinoline-H), 7.81 (dd, J = 1.0, 8.1 Hz, 1 H, quinoline-H), 8.00 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.22–8.26 (m, 2 H, triazole-H, quinoline-H), 8.34 (d, J = 8.6 Hz, 1 H, quinoline-H).

13C NMR (CDCl3): δ = 54.4 (benzyl-CH2), 118.7, 122.7, 126.3, 127.7, 128.3, 128.9, 128.9, 129.2, 129.7 (Carom), 134.4 (Carom), 136.9 (Carom), 148.0, 149.1, 150.4 (Carom).

HRMS-ESI: m/z [M + Na]+ calcd for C18H14N4 + Na: 287.129123; found: 287.129159.


#

2,6-Bis[1′-(2′′,3′′,4′′,6′′-tetra-O-acetyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6a)

Treatment of 2a (747 mg, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:2) and recrystallization from EtOH gave 6a; yield: 520 mg (60%); colorless crystals; mp 268 °C (EtOH); Rf  = 0.26 (PE–EtOAc, 1:2); [α]D 20 –81.1 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.90, 2.05, 2.09, 2.10 (4 s, 24 H, CH3), 4.03–4.07 (m, 2 H, H-5), 4.18 (dd, J 6b,5 = 1.9 Hz, 2 H, H-6b), 4.34 (dd, J 6a,5 = 5.3 Hz, J 6a,6b = 12.6 Hz, 2 H, H-6a), 5.30 (t, J 4,5 = 9.8 Hz, 2 H, H-4), 5.46 (t, J 3,4 = 9.4 Hz, 2 H, H-3), 5.60 (t, J 2,3 = 9.5 Hz, 2 H, H-2), 5.97 (d, J 1,2 = 9.4 Hz, 2 H, H-1), 7.87 (t, J = 7.8 Hz, 1 H, pyridine-H), 8.10 (d, J = 7.8 Hz, 2 H, pyridine-H), 8.45 (s, 2 H, triazole-H).

13C NMR (CDCl3): δ = 20.3, 20.7, 20.8 (CH3), 61.9 (C-6), 67.9 (C-4), 70.5 (C-2), 72.9 (C-3), 75.4 (C-5), 86.0 (C-1), 119.9 (pyridine-C), 120.8 (triazole-C), 137.9 (pyridine-C), 149.1 (triazole-C), 149.5 (pyridine-C), 169.1, 169.5, 170.1, 170.7 (C=O).

MS (FAB): m/z = 874.2 (100%, [M + H]+).

Anal. Calcd for C37H43N7O18 (873.2): C, 50.86; H, 4.96; N, 11.22. Found: C, 50.86; H, 4.96; N, 11.22.


#

2,6-Bis[1′-(2′′,3′′,4′′,6′′-tetra-O-acetyl-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6b)

Treatment of 2b (747 mg, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 1:7) gave 6b; yield: 780 mg (89%); white amorphous solid; Rf  = 0.53 (PE–EtOAc, 1:7); [α]D 20 –85.0 (c 1.00, CHCl3).

1H NMR (DMSO-d 6): δ = 1.85, 1.96, 1.99, 2.23 (4 s, 24 H, CH3), 4.06–4.20 (m, 4 H, H-6a, H-6b), 4.65 (t, J 5,6 = 5.7 Hz, 2 H, H-5), 5.47 (s, 2 H, H-4), 5.53 (dd, J 3,4 = 3.0 Hz, H-3), 5.69 (t, J 2,3 = 9.9 Hz, 2 H, H-2), 6.38 (d, J 1,2 = 9.1 Hz, 2 H, H-1), 8.04 (s, 3 H, pyridine-H), 8.99 (s, 2 H, triazole-H).

13C NMR (DMSO-d 6): δ = 20.1, 20.4, 20.5, 20.6 (CH3), 61.7 (C-6), 67.4 (C-4), 68.1 (C-2), 70.5 (C-3), 73.3 (C-5), 84.8 (C-1), 119.3 (pyridine-C), 123.0 (triazole-C), 138.7 (pyridine-C), 147.7, 149.4 (Carom), 168.9, 169.7, 170.2, 170.3 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C37H43N7O18 + Na: 896.255679; found: 896.255346.


#

2,6-Bis[1′-(2′′,3′′,4′′,6′′-tetra-O-pivaloyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6e)

Treatment of 2e (1.08 g, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 2:1) and recrystallization from EtOH gave 6e; yield: 810 mg (67%); colorless crystals; mp 267 °C (EtOH); Rf  = 0.43 (PE–EtOAc, 2:1); [α]D 20 –43.5 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 0.92, 1.13, 1.18, 1.20 (4 s, 72 H, CH3), 4.07 (m, 2 H, H-5), 4.15 (dd, J 6b,5 = 5.4 Hz, 2 H, H-6b), 4.24 (dd, J 6a,5 = 1.7 Hz, J 6a,6b = 12.6 Hz, 2 H, H-6a), 5.37 (t, J = 9.8 Hz, 2 H, H-4), 5.59 (m, 4 H, H-2, H-3), 6.00 (d, J 1,2 = 9.0 Hz, 2 H, H-1), 7.83 (t, J = 7.7 Hz, 1 H, pyridine-H), 8.08 (d, J = 7.8 Hz, 2 H, pyridine-H), 8.40 (s, 2 H, triazole-H).

13C NMR (CDCl3): δ = 26.8, 27.1, 27.2, 27.2 (CH3), 38.8, 38.9, 38.9, 39.0 (pivaloyl-C), 61.7 (C-6), 67.4 (C-4), 70.4 (C-2), 72.3 (C-3), 75.8 (C-5), 88.3 (C-1), 119.8 (pyridine-C), 120.5 (triazole-C), 137.7 (pyridine-C), 149.1, 149.5 (Carom), 176.4, 176.5, 177.1, 178.1 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C61H91N7O18 + Na: 1232.631280; found: 1232.632214.

Anal. Calcd for C61H91N7O18 (1210.4): C, 60.53; H, 7.58; N, 8.10. Found: C, 60.54; H, 7.57; N, 8.10.


#

2,6-Bis[1′-(2′′,3′′,4′′,6′′-tetra-O-benzyl-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6g)

Treatment of 2g (1.13 g, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (PE–EtOAc, 2:1) gave 6g; yield: 770 mg (61%); colorless oil; Rf  = 0.26 (PE–EtOAc, 2:1); [α]D 20 –60.2 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 3.72–3.75 (m, 6 H, H-5, H-6a, H-6b), 3.88–3.90 (m, 4 H, H-3, H-4), 4.09 (t, J = 8.8 Hz, 2 H, H-2), 4.18–4.95 (m, 16 H, benzyl-CH2), 5.71 (d, J 1,2 = 8.8 Hz, 2 H, H-1), 6.94–7.34 (m, 40 H, phenyl-H), 7.85 (t, J = 7.8 Hz, 1 H, pyridine-H), 8.14 (d, J = 7.8 Hz, 2 H, pyridine-H), 8.26 (s, 2 H, triazole-H).

13C NMR (CDCl3): δ = 68.4 (C-6), 73.6, 74.8, 75.2, 75.8 (benzyl-CH2), 77.3 (C-3/C-4), 78.1 (C-5), 80.5 (C-2), 85.6 (C-3/C-4), 87.8 (C-1), 119.4 (Carom), 121.5 (triazole-C), 127.7, 127.8, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5, 128.5 (Carom), 136.8, 137.7, 138.2 (Carom­), 137.7 (Carom), 148.6, 149.6 (Carom).

HRMS-ESITOF: m/z [M + H]+ calcd for C77H76N7O10 + H: 1258.56482; found: 1258.56378.


#

2,6-Bis[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-d-glucopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6i)

Treatment of 2i (755 mg, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by recrystallization from CHCl3 gave 6i; yield: 340 mg (39%); white solid; mp >300 °C (CHCl­3, dec.); Rf  = 0.17 (PE–EtOAc, 1:1); [α]D 20 –172.1 (c 1.00, DMSO).

1H NMR (DMSO-d 6): δ = 1.85, 2.04 (2 s, 12 H, CH3), 3.84 (t, J 6b,6a = 9.9 Hz, 2 H, H-6b), 4.12–4.20 (m, 4 H, H-4, H-5), 4.37 (dd, J 6a,5 = 4.6 Hz, 2 H, H-6a), 5.66 (t, J = 9.2 Hz, 2 H, H-3), 5.73–5.79 (m, 4 H, benzylidene-H, H-2), 6.50 (d, J 1,2 = 9.0 Hz, 2 H, H-1), 7.39–7.44 (m, 10 H, phenyl-H), 8.03 (s, 3 H, pyridine-H), 9.07 (s, 2 H, triazole-H).

13C NMR (DMSO-d 6): δ = 19.9, 20.4 (CH3), 67.3 (C-6), 68.1 (C-5), 71.1 (C-2), 71.4 (C-3), 77.0 (C-4), 84.9 (C-1), 100.6 (benzylidene-C), 119.1 (pyridine-C), 122.6 (triazole-C), 126.2, 128.2, 129.1 (phenyl-C), 137.1 (Carom), 138.5 (pyridine-C), 147.6, 149.3 (Carom), 168.8, 169.6 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C43H43N7O14 + Na: 904.276020; found: 904.276028.


#

2,6-Bis[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-d-galactopyranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6j)

Treatment of 2j (755 mg, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (CHCl3–MeOH, 60:1) gave 6j; yield: 670 mg (76%); pale yellow solid; Rf  = 0.33 (CHCl3–MeOH, 60:1); [α]D 20 –79.8 (c 1.00, CHCl3).

1H NMR (CDCl3): δ = 1.90, 2.10 (2 s, 12 H, CH3), 3.85 (s, 2 H, H-5), 4.11 (d, J 6b, 6a = 12.6 Hz, 2 H, H-6b), 4.34 (d, 2 H, H-6a), 4.56 (d, J = 3.3 Hz, 2 H, H-4), 5.21–5.24 (m, 2 H, H-3), 5.56 (s, 2 H, benzylidene-H), 5.91–5.92 (m, 4 H, H-1, H-2), 7.32–7.54 (m, 10 H, phenyl-H), 7.84 (t, J = 7.8 Hz, 1 H, pyridine-H), 8.06 (d, J = 7.8 Hz, 2 H, pyridine-H), 8.51 (s, 2 H, triazole-H).

13C NMR (CDCl3): δ = 20.5, 20.9 (CH3), 67.8 (C-2), 68.6 (C-6), 69.3 (C-5), 72.2 (C-3), 73.2 (C-4), 86.5 (C-1), 101.4 (benzylidene-C), 119.9 (pyridine-C), 121.4 (triazole-C), 126.4, 128.4, 129.3 (phenyl-C), 137.2 (Carom), 137.6 (pyridine-C), 148.7, 149.8 (Carom), 168.9, 170.6 (C=O).

HRMS-ESI: m/z [M + Na]+ calcd for C43H43N7O14 + Na: 904.276020; found: 904.276259.


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2,6-Bis[1′-benzyl-1H-1′,2′,3′-triazo-4′-yl]pyridine (6n)

Treatment of 2n (250 μL, 2 mmol) and 1d (127 mg, 1 mmol) according to the general procedure followed by column chromatography (CHCl3–MeOH, 40:1) gave 6n; yield: 380 mg (97%); white amorphous solid. Spectroscopic data were in accordance with the literature.[13d]


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Addition of Phenylacetylene to N-Benzylideneaniline; General Procedure

The respective ligand 3–6 (0.05 mmol; 10 mol% with respect to the imine) and (CuOTf)2·C6H6 (25 mg, 0.05 mmol; 10 mol%) were dissolved in CH2Cl2 (6 mL) and stirred for 30 min at r.t. Phenylacetylene (88 μL, 0.8 mmol) and N-benzylideneaniline (91 mg, 0.5 mmol) were added to the mixture and the resulting yellow to green solution was allowed to stir for 48 h at r.t. and concentrated. Chromatography (PE–EtOAc, 40:1) of the residue gave 7 as a pale yellow amorphous solid (for results, see Table [2]). Spectroscopic data were in accordance with the literature.[14a]


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Acknowledgment

We thank Dr. M. Kramer and Dr. D. Wistuba and their co-workers for measuring the NMR and mass spectra. We also thank P. Krüger for performing the elemental analyses.

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/products/ejournals/journal/ 10.1055/s-00000084. Included are the NMR spectra of all new compounds.


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Figure 1 Examples of known glycosyl-based ligands for metal ions
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Figure 2 Azides 2 used for the preparation of ligands 3–6 via copper(I)-catalyzed 1,3-dipolar cycloaddition. The numbers in superscript refer to the references describing the preparation of 2.
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Scheme 1 Reagents and conditions: CuSO4·H2O (0.2 equiv), sodium ascorbate (0.4 equiv), t-BuOH–H2O, 48 h, 40 °C. The numbers in superscript refer to the references describing the preparation of 1. R = protective group.
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Scheme 2 Addition of phenylacetylene to N-benzylidenaniline