Synthesis of sugar-derived triazole- and pyridine-based metal complex ligands

Article abstract of DOI:10.1055/s-0034-1379473

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 a

Full text of DOI:10.1055/s-0034-1379473

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 199–208
paper
199
J. Kraft et al.
Paper
Synthesis
Synthesis of Sugar-Derived Triazole- and Pyridine-Based Metal
Complex Ligands
Sugar-Based 1,2,3-Triazole-Linked Complex Ligands
Jochen Kraft
L*
Cu(I)
Ph
Ph
HN
Ph
N
Daniel Schmollinger
Jakob Maudrich
up to 99% yield
and 63% ee
+
Ph
O
Ph
Ph
R
Thomas Ziegler*
L* =
X
Institute of Organic Chemistry, University of Tuebingen,
Auf der Morgenstelle 18, 72076 Tuebingen, Germany
thomas.ziegler@uni-tuebingen.de
N
O
N
N
O
N
N
N
N
N
N
O
R
R
R
N
N
N
N
N
N
X = H, NO2
30 examples
R = protective group
Received: 09.09.2014
Accepted after revision: 19.09.2014
Published online: 24.10.2014
DOI: 10.1055/s-0034-1379473; Art ID: ss-2014-t0555-op
X
X
N
O
O
AcO
OAc
N
N
Abstract A series of 30 bi- and tridentate ligands for metals were pre-
pared by copper-catalyzed coupling (CLICK reaction) of 2-ethynylpyri-
dine, 2-ethynyl-5-nitropyridine, 2-ethynylquinoline, and 2,6-diethyn-
ylpyridine 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 phe-
nylacetylene to N-benzylideneaniline to give chiral N-(1,3-diphenyl-
prop-2-yn-1-yl)aniline.
AcO
OAc
A X = O, S
AcO
OAc
O
O
O
O
N
N
O
O
Key words asymmetric catalysis, azides, carbohydrates, enantioselec-
tivity, glycoconjugates
O
OCHO
OHCO
O
Ph
Ph
B
Despite the fact that carbohydrates are the most abun-
dant 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 struc-
tural 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, carbo-
hydrates have gained significant importance as chiral auxil-
iaries, chiral reagents, and organocatalysts, and, most nota-
bly, as chiral ligands for metal-catalyzed stereoselective re-
actions.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 moi-
eties, respectively, which both gave high enantioselectivi-
ties in Cu-catalyzed asymmetric alkynylations of N-aryl-
imines and cyclopropanations of olefins with azo esters.2
OAc
O
N
N
AcO
N
(CH2)n
AcO
O
H
OAc
N
X
H
N
OAc
O
O
AcO
AcO
(CH2)n
N
N
N
OAc
C X = N, CH; n = 0, 2
Figure 1 Examples of known glycosyl-based ligands for metal ions
Recently, we communicated the synthesis of multiden-
tate 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
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

200
J. Kraft et al.
Paper
Synthesis
AcO
sugar moieties. This was thought to enable us to modify the
specific interaction of the ligand with sugar-binding pro-
teins upon complexation with metal ions and thus, will give
us a closer insight into the interactions of carbohydrates
with proteins4 or will result in novel analytical tools for
studying such interactions.5
Inspired by the recent successful application of sugar-
bearing ligands for metal-catalyzed stereoselective reac-
tions, 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 back-
bone 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 accord-
ing to literature procedures (see Scheme 1 and Figure 2 for
references). In general, ethynylpyridines 1a,b,d were pre-
pared via Sonogashira-coupling of the respective pyridine
halogenides and trimethylsilylacetylene followed by desil-
ylation according to known procedures.7a,b,d 2-Ethynylquin-
oline 1c was prepared via Sonogashira-coupling of 2-chlo-
roquinoline and 2-methylbut-3-yn-2-ol followed by treat-
ment of the intermediate with NaOH.7c
OAc
O
AcO
AcO
OAc
O
OAc
O
AcO
AcO
AcO
AcO
N3
N3
N3
OAc
2a8a
OAc
2c8b
2b8a
OAc
O
PivO
PivO
OPiv
O
OPiv
O
AcO
AcO
PivO
PivO
N3
N3
N3
HNAc
2d8j
OPiv
2f8d
OPiv
2e8c
OBn
O
BnO
BnO
OBn
O
O
Ph
O
BnO
BnO
O
N3
N3
AcO
N3
OBn
2g8e
OAc
OBn
2i8g
2h8f
Ph
O
OAc
O
OAc
O
AcO
AcO
O
O
O
N3
N3
AcO
AcO
OAc
OAc
OAc
2j8h
2k8k
N3
OTrt
O
AcO
AcO
N3
N3
OAc
2l8i
2m11
2n
Figure 2 Azides 2 used for the preparation of ligands 3–6 via cop-
per(I)-catalyzed 1,3-dipolar cycloaddition. The numbers in superscript
refer to the references describing the preparation of 2.
X
X
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 character-
ized both the glycosyl azides as follows. Acetylation of 4,6-
O-benzylidene-β-D-galactosyl azide9 with acetic anhydride
in pyridine gave 2j in 81% yield. Likewise, treatment of β-D-
glucopyranosyl azide8b,10 with trityl chloride in pyridine fol-
lowed by acetylation of the intermediate with acetic anhy-
dride 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-Azi-
doethyl)benzene (2m) was prepared in situ from commer-
cial (S)-1-phenylethylamine by treatment with 1H-imidaz-
ole-1-sulfonyl azide and using the crude 2m directly for the
following click reaction.11
N
1a X = H7a
1b X = NO2
O
N
7b
N
R
N
N
3 X = H
4 X = NO2
N
1c7c
O
O
N
N
N3
R
R
N
CuSO4
Na ascorbate
t-BuOH, H2O
N
2
5
N
1d7d
N
N
N
N
N
As catalyst for the click reaction of alkynes 1 and azides
2 the copper(II)sulfate/sodium ascorbate protocol12 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 (en-
try 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
N
N
O
O
R
R
6
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 super-
script refer to the references describing the preparation of 1.
R = protective group.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

201
J. Kraft et al.
Paper
Synthesis
studies of metal complexes.13 All products were isolated ei-
ther by direct crystallization from the crude product mix-
ture 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.
3–6
(CuOTf)2⋅C6H6
Ph
Ph
HN
N
Ph
CH2Cl2
r.t., 48 h
Ph
Ph
Ph
7
Scheme 2 Addition of phenylacetylene to N-benzylidenaniline
Table 2 Enantioselective Alkynylation with Ligands 3–6 To Give 7
Table 1 Compounds 3–6 Prepared
Entry
Ligand
Yield (%)a
ee (%)b,c
Entry
2
Yield (%) 3
Yield (%) 4 Yield (%) 5 Yield (%) 6
1
A (X = O)d
69
81
87
78
48
78
99
80
92
75
85
99 (S)d
–
1
2a
2b
2c
2d
2e
2f
81 3a
60 3b
–
67 4a
78 5a
73 5b
84 5c
91 5d
68 5e
73 5f
71 5g
81 5h
– 5ia
60 6a
89 6b
–
2
5n
6n
5m
3a
4a
5a
6a
5e
6i
2
–
3
–
3
–
4
5 (R)
17 (R)
22 (R)
24 (R)
31 (R)
63 (R)
60 (R)
56 (R)
4
–
–
–
5
5
95 3e
85 3f
52 3g
87 3h
23 3i
–
68 4e
67 6e
–
6
6
–
7
7
2g
2h
2i
77 4g
61 6g
–
8
8
–
–
–
–
–
–
–
9
9
39 6i
76 6j
–
10
11
10
11
12
13
14
2j
90 5j
71 5k
–
6j
2k
2l
–
a Isolated yield after chromatography.
b Determined by chiral GC.
86 3l
–
–
c Absolute configuration was determined by comparison of the optical rota-
tion to literature values.14a,b
2m
2n
67 5m
70 5n
–
d Figure 1; taken from ref. 2a; no unambiguous assignment of the absolute
configuration was done.
–
97 6n
a Separation of starting material and product was not possible.
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). Bet-
ter 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 pub-
lished elsewhere.
With triazole ligands 3–6 on hand we then turned to
some preliminary applications of these ligands for enantio-
selective metal-catalyzed reactions. As a model reaction the
copper(I)-catalyzed addition of phenylacetylene to N-ben-
zylideneaniline to give chiral N-(1,3-diphenylprop-2-yn-1-
yl)aniline 7 was chosen (Scheme 2). Similar enantioselec-
tive additions of alkynes to enamines were previously in-
vestigated 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 addi-
tion, the achiral ligands 5n and 6n were also used for evalu-
ating 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 as-
signment of the absolute configuration was done by com-
paring the optical rotation with that of N-[1-(3-bromophe-
nyl)-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 re-
fers to R-configuration while a negative optical rotation re-
fers to the S-enantiomer. All ligands tested here resulted in
an excess of R-enantiomer of 7.
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 spectrom-
eter and calibrated for the solvent signal (1H CDCl3: 7.26 ppm; 13C
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

202
J. Kraft et al.
Paper
Synthesis
CDCl3: 77.16 ppm; 1H DMSO-d6: 2.50 ppm; 13C DMSO-d6: 39.52 ppm).
ESI-HRMS were recorded on a Bruker Apex II FT-ICR-MS spectrome-
ter, 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 cu-
vette at 20 °C. Melting points were determined with a Büchi Melting
Point M-560 apparatus. Reactions were monitored by TLC on Poly-
gram 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 chromatogra-
phy 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; car-
rier gas H2; injection temp 280 °C; column temp 160 °C constant.
tR = 237.8 min for (S)-7, and tR = 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 crystalliza-
tion and were not optimized, unless noted otherwise.
H-2), 5.19 (t, J3,4 = 9.4 Hz, 1 H, H-3), 5.29 (t, J4,5 = 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.
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 reac-
tion 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.
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 azide9 (2.5 g, 8.5 mmol) in pyri-
dine (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. Re-
crystallization of the residue from EtOH gave 2j as colorless needles;
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
20
yield: 2.6 g (81%); mp 157 °C (EtOH); Rf = 0.38 (PE–EtOAc, 1:1); [α]D
+16.8 (c 1.00, CHCl3).
IR (KBr): 3415, 2114, 1750, 1638, 1617, 1455 cm–1
.
2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-acetyl-β-D-galactopyranosyl)-1H-1′,2′,3′-
triazo-4′-yl]pyridine (3b)
1H NMR (CDCl3): δ = 2.07, 2.09 (2 s, 6 H, CH3), 3.61 (d, J5,4 = 1.0 Hz, 1 H,
H-5), 4.05 (dd, J6b,5 = 1.7 Hz, 1 H, H-6b), 4.34 (dd, J6a,5 = 1.5 Hz,
J6a,6b = 12.6 Hz, 1 H, H-6a), 4.40 (d, 1 H, H-4), 4.58 (d, J1,2 = 8.8 Hz, 1 H,
H-1), 4.97 (dd, J3,4 = 3.5 Hz, 1 H, H-3), 5.35 (t, J2,3 = 10.3 Hz, 1 H, H-2),
5.50 (s, 1 H, benzylidene-H), 7.37–7.51 (m, 5 H, phenyl-H).
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
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).
2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-D-glucopyranosyl)-1H-
1′,2′,3′-triazo-4′-yl]pyridine (3e)
MS (FAB): m/z = 335.1 (100%, [M – N3]+).
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
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.
2,3,4-Tri-O-acetyl-6-O-trityl-β-D-glucopyranosyl Azide (2l)
2-[1′-(2′′,3′′,4′′,6′′-Tetra-O-pivaloyl-β-D-galactopyranosyl)-1H-
1′,2′,3′-triazo-4′-yl]pyridine (3f)
A mixture of β-D-glucopyranosyl azide10 (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]D20 +16.8 (c 1.00, CHCl3).
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]D20 –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, J3,4 = 1.8 Hz, 1 H, H-3),
5.56 (s, 1 H, H-4), 5.70 (t, J2,3 = 10.1 Hz, 1 H, H-2), 5.98 (d, J1,2 = 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).
1H NMR (CDCl3): δ = 1.77, 2.03, 2.11 (3 s, 9 H, CH3), 3.11 (dd, J6b,5 = 4.1
Hz, J6b,6a = 10.6 Hz, 1 H, H-6b), 3.37 (dd, J6a,5 = 2.1 Hz, 1 H, H-6a), 3.70
(m, 1 H, H-5), 4.67 (d, J1,2 = 8.8 Hz, 1 H, H-1), 5.06 (t, J2,3 = 9.1 Hz, 1 H,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

203
J. Kraft et al.
Paper
Synthesis
13C NMR (CDCl3): δ = 27.0, 27.3, 27.3, 27.5 (CH3), 39.0, 39.1, 39.5 (piv-
aloyl-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).
2-[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-D-glucopyrano-
syl)-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]D20 –116.3 (c 1.00, DMSO).
1H NMR (DMSO-d6): 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, J1,2 = 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-d6): 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).
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.
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) accord-
ing 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]D20 –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, J2,3 = 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, J1,2 = 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 + 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]D20 +15.7 (c 1.00, CHCl3).
1H NMR (CDCl3): δ = 1.78, 1.88, 2.01 (3 s, 9 H, CH3), 3.16 (dd,
J6a,6b = 10.9 Hz, 1 H, H-6b), 3.37 (dd, 1 H, H-6a), 3.89 (ddd, J5,6a = 4.4
Hz, J5,6b = 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, J1,2 = 9.2 Hz, 1 H, H-1), 7.17–7.27 (m, 10 H, tri-
tyl-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).
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.
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.
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) accord-
ing 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]D20 –48.5 (c 1.00, CHCl3).
1H NMR (CDCl3): δ = 3.63 (m, 2 H, H-6a, H-6b), 3.80 (dd, J3,4 = 2.8 Hz,
H-3), 3.86 (m, 1 H, H-5), 4.08 (d, J4,5 = 2.4 Hz, 1 H, H-4), 4.22 (d,
J = 10.6 Hz, 1 H, benzyl-CH2), 4.38 (t, J2,3 = 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, J1,2 = 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.
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) accord-
ing 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]D20 –79.1 (c 1.00, CHCl3).
1H NMR (DMSO-d6): 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, J4,5 = 9.8 Hz,
1 H, H-4), 5.61 (t, J3,4 = 9.5 Hz, 1 H, H-3), 5.80 (t, J2,3 = 9.3 Hz, 1 H, H-2),
6.46 (d, J1,2 = 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-d6): 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]+).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

204
J. Kraft et al.
Paper
Synthesis
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.
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).
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) accord-
ing 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]D20 –47.5 (c 1.00, CHCl3).
HRMS-ESI: m/z [M + Na]+ calcd for C25H26N4O9 + Na: 549.159200;
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, J1,2 = 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).
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) accord-
ing 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]D20 –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, J5,6 = 6.2 Hz, 1 H, H-5), 5.30 (dd, J3,4 = 3.2
Hz, 1 H, H-3), 5.66 (t, J2,3 = 10.2 Hz, 1 H, H-2), 5.67 (d, J4,5 = 2.7 Hz, 1 H,
H-4), 5.94 (d, J1,2 = 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, quino-
line-H), 8.06 (d, J = 8.4 Hz, 1 H, quinoline-H), 8.21–8.31 (m, 2 H, quin-
oline-H), 8.64 (s, 1 H, triazole-H).
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)
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).
Treatment of 2g (566 mg, 1 mmol) and 1b (148 mg, 1 mmol) accord-
ing 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]D20 –49.8 (c 1.00, CHCl3).
MS (FAB): m/z (%) = 527.1 (40, [M + H]+), 331.1 (35, [M – C11H7N4]+).
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, J2,3 = 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, J1,2 = 9.0 Hz, 1 H, H-1), 6.98–7.37 (m, 20 H, phe-
nyl-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).
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) accord-
ing 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]D20 –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, J6b,5 = 2.1 Hz, J6b,6a = 12.5 Hz, 1 H, H-6b), 4.36 (dd,
J6a,5 = 5.9 Hz, 1 H, H-6a), 5.33–5.43 (m, 2 H, H-3, H-4), 5.83 (d, J2,3 = 1.4
Hz, 1 H, H-2), 6.27 (d, J1,2 = 1.2 Hz, 1 H, H-1), 7.49–7.53 (m, 1 H, quino-
line-H), 7.68–7.72 (m, 1 H, quinoline-H), 7.81 (d, J = 8.1 Hz, 1 H, quin-
oline-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, tri-
azole-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.
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) accord-
ing 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]D20 –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, J6b,6a = 12.6 Hz, J6b,5 = 1.6 Hz, 1 H, H-6b), 4.33
(dd, J6a,5 = 5.0 Hz, 1 H, H-6a), 5.28 (t, J4,5 = 9.7 Hz, 1 H, H-4), 5.46 (t,
J3,4 = 9.4 Hz, 1 H, H-3), 5.56 (t, J2,3 = 9.4 Hz, 1 H, H-2), 5.97 (d, J1,2 = 9.3
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

205
J. Kraft et al.
Paper
Synthesis
2-[1′-(2′′-Acetamido-2′′-deoxy-3′′,4′′,6′′-tri-O-acetyl-β-D-glucopy-
ranosyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5d)
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).
Treatment of 2d (372 mg, 1 mmol) and 1c (153 mg, 1 mmol) accord-
ing 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]D20 –112.9 (c 1.00, CHCl3).
1H NMR (DMSO-d6): δ = 1.61, 1.97, 2.01, 2.04 (4 s, 12 H, CH3), 4.11 (dd,
J6b,5 = 1.8 Hz, J6b,6a = 12.3 Hz, 1 H, H-6b), 4.19 (dd, J6a,5 = 5.4 Hz, 1 H, H-
6a), 4.27–4.31 (m, 1 H, H-5), 4.82 (q, J2,3 = 9.8 Hz, 1 H, H-2), 5.21 (t,
J4,5 = 9.7 Hz, 1 H, H-4), 5.42 (t, J = 9.8 Hz, 1 H, H-3), 6.23 (d, J1,2 = 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, JNH,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-d6): 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.
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) accord-
ing 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]D20 –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, J2,3 = 8.8 Hz, 1 H, H-2), 4.21–5.00 (m, 8 H,
benzyl-CH2), 5.74 (d, J1,2 = 9.0 Hz, 1 H, H-1), 7.01–7.37 (m, 20 H, phe-
nyl-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, quino-
line-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).
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) accord-
ing 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]D20 –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, J1,2 = 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 (quin-
oline-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-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) accord-
ing 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]D20 –69.3 (c 1.00, CHCl3).
1H NMR (CDCl3): δ = 3.62–3.70 (m, 2 H, H-6a, H-6b), 3.82 (dd, J3,4 = 2.7
Hz, 1 H, H-3), 3.88 (t, J5,6 = 6.4 Hz, 1 H, H-5), 4.11 (d, J4,5 = 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,
J1,2 = 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, quin-
oline-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-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) accord-
ing 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]D20 –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, J5,6 = 6.8 Hz, 1 H, H-5), 5.38 (dd, J3,4 = 3.1
Hz, 1 H, H-3), 5.60 (d, J4,5 = 3.0 Hz, 1 H, H-4), 5.77 (t, J2,3 = 10.1 Hz, 1 H,
H-2), 6.04 (d, J1,2 = 9.4 Hz, 1 H, H-1), 7.50–7.53 (m, 1 H, quinoline-H),
HRMS-ESI: m/z [M + H]+ calcd for C45H42N4O5 + H: 719.322797; found:
719.322765.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

206
J. Kraft et al.
Paper
Synthesis
2-[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-D-galactopyrano-
syl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5j)
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).
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 sol-
id; Rf = 0.12 (PE–EtOAc, 1:1); [α]D20 –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, J6b,5 = 1.6 Hz, J6b,6a = 12.7 Hz, 1 H, H-6b), 4.38 (dd, J6a,5 = 1.2 Hz, 1
H, H-6a), 4.59 (d, J4,5 = 3.4 Hz, 1 H, H-4), 5.23 (dd, J3,4 = 3.5 Hz, 1 H, H-
3), 5.60 (s, 1 H, benzylidene-H), 5.81 (d, J2,3 = 9.7 Hz, 1 H, H-2), 5.98 (d,
J1,2 = 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).
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.
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′-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, phe-
nyl-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, quino-
line-H), 8.22–8.26 (m, 2 H, triazole-H, quinoline-H), 8.34 (d, J = 8.6 Hz,
1 H, quinoline-H).
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) accord-
ing to the general procedure followed by column chromatography
(PE–EtOAc, 1:2) gave 5k; yield: 580 mg (71%); white amorphous sol-
id; Rf = 0.37 (PE–EtOAc, 1:2); [α]D20 –65.2 (c 1.00, CHCl3).
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.
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,
J6b,5 = 1.8 Hz, J6b,6a = 12.4 Hz, 1 H, H-6b), 4.16 (dd, J6b′,5′ = 4.4 Hz,
J6b′,6a′ = 12.2 Hz, 1 H, H-6b′), 4.39 (dd, J6a,5 = 4.4 Hz, 1 H, H-6a), 4.52 (d,
1 H, H-6a′), 4.57 (d, J1,2 = 7.9 Hz, 1 H, H-1), 4.96 (t, J2,3 = 8.6 Hz, 1 H, H-
2), 5.08 (t, J4,5 = 9.6 Hz, 1 H, H-4), 5.17 (t, J3,4 = 9.3 Hz, 1 H, H-3), 5.42 (t,
J3′,4′ = 8.8 Hz, 1 H, H-3′), 5.52 (t, J2′,3′ = 9.4 Hz, 1 H, H-2′), 5.90 (d,
J1′,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).
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) accord-
ing 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]D20 –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, J6b,5 = 1.9 Hz, 2 H, H-6b), 4.34 (dd, J6a,5 = 5.3 Hz,
J6a,6b = 12.6 Hz, 2 H, H-6a), 5.30 (t, J4,5 = 9.8 Hz, 2 H, H-4), 5.46 (t,
J3,4 = 9.4 Hz, 2 H, H-3), 5.60 (t, J2,3 = 9.5 Hz, 2 H, H-2), 5.97 (d, J1,2 = 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 (tri-
azole-C), 137.9 (pyridine-C), 149.1 (triazole-C), 149.5 (pyridine-C),
169.1, 169.5, 170.1, 170.7 (C=O).
HRMS-ESI: m/z [M + Na]+ calcd for C37H42N4O17 + Na: 837.243717;
found: 837.243681.
MS (FAB): m/z = 874.2 (100%, [M + H]+).
2-[1′-(S-α-Methylbenzyl)-1H-1′,2′,3′-triazo-4′-yl]quinoline (5m)
To a stirred solution of 1H-imidazole-1-sulfonyl azide hydrochlo-
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.
ride11c (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 sol-
id; Rf = 0.48 (PE–EtOAc, 1:1); [α]D20 –103.1 (c 1.00, CHCl3).
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) accord-
ing to the general procedure followed by column chromatography
(PE–EtOAc, 1:7) gave 6b; yield: 780 mg (89%); white amorphous sol-
id; Rf = 0.53 (PE–EtOAc, 1:7); [α]D20 –85.0 (c 1.00, CHCl3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

207
J. Kraft et al.
Paper
Synthesis
1H NMR (DMSO-d6): 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, J5,6 = 5.7 Hz, 2 H, H-5), 5.47 (s, 2 H,
H-4), 5.53 (dd, J3,4 = 3.0 Hz, H-3), 5.69 (t, J2,3 = 9.9 Hz, 2 H, H-2), 6.38
(d, J1,2 = 9.1 Hz, 2 H, H-1), 8.04 (s, 3 H, pyridine-H), 8.99 (s, 2 H, tri-
azole-H).
1H NMR (DMSO-d6): δ = 1.85, 2.04 (2 s, 12 H, CH3), 3.84 (t, J6b,6a = 9.9
Hz, 2 H, H-6b), 4.12–4.20 (m, 4 H, H-4, H-5), 4.37 (dd, J6a,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, J1,2 = 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-d6): 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).
13C NMR (DMSO-d6): 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 C37H43N7O18 + Na: 896.255679;
HRMS-ESI: m/z [M + Na]+ calcd for C43H43N7O14 + Na: 904.276020;
found: 896.255346.
found: 904.276028.
2,6-Bis[1′-(2′′,3′′,4′′,6′′-tetra-O-pivaloyl-β-D-glucopyranosyl)-1H-
1′,2′,3′-triazo-4′-yl]pyridine (6e)
2,6-Bis[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-D-galactopy-
ranosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6j)
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]D20 –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, J6b,5 = 5.4 Hz, 2 H, H-6b), 4.24 (dd, J6a,5 = 1.7 Hz,
J6a,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, J1,2 = 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).
Treatment of 2j (755 mg, 2 mmol) and 1d (127 mg, 1 mmol) accord-
ing 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]D20 –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, J6b, 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 = 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).
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 C61H91N7O18 + Na: 1232.631280;
HRMS-ESI: m/z [M + Na]+ calcd for C43H43N7O14 + Na: 904.276020;
found: 1232.632214.
found: 904.276259.
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′-benzyl-1H-1′,2′,3′-triazo-4′-yl]pyridine (6n)
Treatment of 2n (250 μL, 2 mmol) and 1d (127 mg, 1 mmol) accord-
ing 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
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]D20 –60.2 (c 1.00, CHCl3).
Addition of Phenylacetylene to N-Benzylideneaniline; General
Procedure
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, J1,2 = 8.8 Hz, 2 H, H-1), 6.94–7.34 (m, 40 H, phe-
nyl-H), 7.85 (t, J = 7.8 Hz, 1 H, pyridine-H), 8.14 (d, J = 7.8 Hz, 2 H, pyr-
idine-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).
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 dis-
solved 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
HRMS-ESITOF: m/z [M + H]+ calcd for C77H76N7O10 + H: 1258.56482;
found: 1258.56378.
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.
2,6-Bis[1′-(2′′,3′′-Di-O-acetyl-4′′,6′′-O-benzylidene-β-D-glucopyra-
nosyl)-1H-1′,2′,3′-triazo-4′-yl]pyridine (6i)
Treatment of 2i (755 mg, 2 mmol) and 1d (127 mg, 1 mmol) accord-
ing 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]D20 –172.1 (c 1.00, DMSO).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208

208
J. Kraft et al.
Paper
Synthesis
Supporting Information
(e) Ogawa, T.; Nakabayashi, S.; Shibata, S. Agric. Biol. Chem.
1983, 47, 281. (f) Bianchi, A.; Bernardi, A. J. Org. Chem. 2006, 71,
4565. (g) Kovacs, J.; Pinter, I.; Szego, F.; Toth, G.; Messmer, A.
Acta Chim. Acad. Sci. Hung. 1979, 101, 7. (h) Moinizadeh, N.;
Klemme, R.; Kansy, M.; Zimmer, R.; Reissig, H.-U. Synthesis
2013, 45, 2752. (i) El Meslouti, A.; Beaupere, D.; Demailly, G.;
Uzan, R. Tetrahedron Lett. 1994, 35, 3913. (j) Unverzagt, C.;
Kunz, H. J. Prakt. Chem. 1992, 334, 570. (k) Porwanski, S.;
Marsura, A. Eur. J. Org. Chem. 2009, 13, 2047.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379473. Included are the NMR
spectra of all new compounds.
S
u
p
p
ortioInfgrmoaitn
References
(1) (a) Carbohydrates – Tools for Stereoselective Synthesis; Boysen,
M. M. K., Ed.; Wiley-VCH: Weinheim, 2013. (b) Lehnert, T.;
Özüduru, G.; Gruel, H.; Albrecht, F.; Telligmann, S. M.; Boysen,
M. M. K. Synthesis 2011, 2685. (c) Diéguez, M.; Pàmies, O.;
Claver, C. Chem. Rev. 2004, 104, 3189. (d) Khiar, N.; Navas, R.;
Fernández, I. Tetrahedron Lett. 2012, 53, 395.
(2) (a) Irmak, M.; Boysen, M. M. K. Adv. Synth. Catal. 2008, 350, 403.
(b) Imrak, M.; Groschner, A.; Boysen, M. M. K. Chem. Commun.
2007, 177. (c) Minuth, T.; Boysen, M. M. K. Synthesis 2010, 2799.
(3) Ziegler, T.; Hermann, K. Tetrahedron Lett. 2008, 49, 2166.
(4) (a) Sakai, S.; Sasaki, T. J. Am. Chem. Soc. 1994, 116, 1587. (b) Roy,
R.; Kim, J. M. Tetrahedron 2003, 59, 3881. (c) Orlandi, S.;
Annuntiata, R.; Banaglia, M.; Cozzi, F.; Manzoni, L. Tetrahedron
2005, 61, 10048. (d) Yano, S.; Ohi, H.; Ashizaki, M.; Obata, M.;
Mikata, Y.; Tanaka, R.; Nishioka, T.; Kinoshita, I.; Sugai, Y.;
Okura, I.; Ogura, S.-i.; Czaplewska, J. A.; Gottschalk, M.;
Schubert, U. S.; Funabiki, T.; Morimoto, K.; Nakai, M. Chem. Bio-
divers. 2012, 9, 1903.
(5) (a) Hasegawa, T.; Yonemura, T.; Matsuura, K.; Kobayashi, K. Tet-
rahedron Lett. 2001, 42, 3989. (b) Kojima, S.; Hasegawa, T.;
Yonemura, T.; Sasaki, K.; Yamamoto, K.; Makimura, Y.;
Takahashi, T.; Suzuki, T.; Kobayashi, K. Chem. Commun. 2003,
1250.
(6) (a) Suijkerbuijk, B. M. J. M.; Aerts, B. N. H.; Dijkstra, H. P.; Lutz,
M.; Spek, A. L.; van Koten, G.; Gebbink, R. J. M. K. J. Chem. Soc.,
Dalton Trans. 2007, 1273. (b) Li, Y.; Huffman, J. C.; Flood, H. M.
Chem. Commun. 2007, 2692.
(7) (a) Röse, P.; Pünner, F.; Hilt, G.; Harms, K. Synlett 2013, 24, 1101.
(b) Sagitullina, G. P.; Vorontsova, M. A.; Garkushenko, A. K.;
Poendaev, N. V.; Sagitullin, R. S. Russian J. Org. Chem. 2010, 46,
1830. (c) Rodriguez, J. G.; de los Rios, C.; Lafuente, A. Tetrahe-
dron 2005, 61, 9042. (d) Dana, B. H.; Robinson, B. H.; Simpson, J.
J. Organomet. Chem. 2002, 648, 251.
(8) (a) Sabesan, S.; Neira, S. Carbohydrate Res. 1992, 223, 169.
(b) Farrell, M.; Zhou, J.; Murphy, P. V. Chem. Eur. J. 2013, 19,
14836. (c) Watt, J. A.; Gannon, C. T.; Loft, K. J.; Dinev, Z.;
Williams, S. J. Aust. J. Chem. 2008, 61, 837. (d) Kunz, H.; Sager,
W.; Schanzenbach, D.; Decker, M. Liebigs Ann. Chem. 1991, 649.
(9) (a) Marcaurelle, L. A.; Pratt, M. R.; Bertozzi, C. R. ChemBioChem
2003, 224. (b) Vicente, V.; Martin, J.; Jimenez-Barbero, J.; Chiara,
J. L.; Vicent, C. Chem. Eur. J. 2004, 10, 4240.
(10) Györgydeak, Z.; Szilagyi, L. Liebigs Ann. Chem. 1987, 235.
(11) (a) Smith, N. M.; Greaves, M. J.; Jewell, R.; Perry, M. W. D.;
Stocks, M. J.; Stonehouse, J. P. Synlett 2009, 1391. (b) de Oliveira
Freitas, L. B.; Eisenberger, P.; Crudden, C. M. Organometallics
2013, 32, 6635. (c) Goddard-Borger, E. D.; Stick, R. V. Org. Lett.
2007, 9, 3797.
(12) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596; Angew. Chem. 2002, 114,
2708. (b) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057. (c) Meldal, M.; Tornoe, C. W. Chem. Rev. 2008,
108, 2952.
(13) (a) Wilkinson, B. L.; Bornaghi, L. F.; Poulson, S.-A.; Houston, T. A.
Tetrahedron 2006, 62, 8115. (b) Carvallo, I.; Andrade, P.; Campo,
V. L.; Guedes, P. M. M.; Sesti-Costa, R.; Silva, J. S.; Schenkman, S.;
Dedola, S.; Hill, L.; Rejzek, M.; Nepogodiev, S. A.; Field, R. A.
Bioorg. Med. Chem. 2010, 18, 2412. (c) Shen, C.; Zhang, P.-F.;
Chen, X.-Z. Helv. Chim. Acta 2010, 93, 2433. (d) Crowley, J. D.;
Bandeen, P. H.; Hanton, L. R. Polyhedron 2010, 29, 70.
(14) (a) Wei, C.; Mague, J. T.; Li, C.-J. Proc. Natl. Acad. Sci. USA 2004,
101, 5749. (b) Lu, Y.; Johnstone, T. C.; Arndtsen, B. A. J. Am.
Chem. Soc. 2009, 131, 11284. (c) Balaraman, K.; Vasanthan, R.;
Kesavan, V. Tetrahedron Lett. 2013, 54, 3613. (d) Campbell, M. J.;
Toste, F. D. Chem. Sci. 2011, 2, 1369. (e) Zeng, T.; Yang, L.;
Hudson, R.; Song, G.; Moores, A. R.; Li, C.-J. Org. Lett. 2011, 13,
442. (f) Goyard, D.; Telligmann, S. M.; Goux-Henry, C.; Boysen,
M. M. K.; Framery, E.; Gueyrard, D.; Vidal, S. Tetrahedron Lett.
2010, 51, 374. (g) Drabina, P.; Funk, P.; Ruzicka, A.; Hanusek, J.;
Sedlak, M. Transition Met. Chem. 2010, 35, 363. (h) Panera, M.;
Diez, J.; Merino, I.; Rubio, E.; Gamasa, M. P. Inorg. Chem. 2009,
48, 11147. (i) Hatano, M.; Asai, T.; Ishihara, K. Tetrahedron Lett.
2008, 49, 379. (j) Weissberg, A.; Halak, B.; Portnoy, M. J. Org.
Chem. 2005, 70, 4556. (k) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002,
124, 5638.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 199–208