Expedient synthesis of coumarin-coupled triazoles via 'click chemistry' leading to the formation of coumarin-triazole-sugar hybrids

Article abstract of DOI:10.1016/j.carres.2010.07.037

Coumarin-based triazoles were synthesized from 3-azidomethylcoumarin and a terminal acetylenic compound. Uncatalysed thermal conditions result in a mixture of both 1,4- and 1,5-regioisomers or the thermodynamically more stable 1,4-regioisomer, whereas the Cu(I)-catalysed reaction affords only the favourable 1,4-regioisomer. B3LYP/6-31G(d) level of theory has been used to calculate geometry and frequency features of the reactants, transition states (TSs) and products. Computational studies further reveal that 1,4-regioisomeric products are more favourable and also thermodynamically more stable compared to the 1,5-regioisomers.

Full text of DOI:10.1016/j.carres.2010.07.037

Carbohydrate Research 345 (2010) 2297–2304
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Expedient synthesis of coumarin-coupled triazoles via ‘click chemistry’
leading to the formation of coumarin–triazole–sugar hybrids
K. Karthik Kumar a, R. Mahesh Kumar b, V. Subramanian b, T. Mohan Das a,
⇑
a Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
b Chemical Laboratory, Central Leather Research Institute (CSIR), Adyar, Chennai 600 020, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Coumarin-based triazoles were synthesized from 3-azidomethylcoumarin and a terminal acetylenic com-
pound. Uncatalysed thermal conditions result in a mixture of both 1,4- and 1,5-regioisomers or the ther-
modynamically more stable 1,4-regioisomer, whereas the Cu(I)-catalysed reaction affords only the
favourable 1,4-regioisomer. B3LYP/6-31G(d) level of theory has been used to calculate geometry and fre-
quency features of the reactants, transition states (TSs) and products. Computational studies further
reveal that 1,4-regioisomeric products are more favourable and also thermodynamically more stable
compared to the 1,5-regioisomers.
Received 13 April 2010
Received in revised form 20 July 2010
Accepted 23 July 2010
Available online 29 July 2010
Keywords:
Coumarin derivatives
Click chemistry
Ó 2010 Elsevier Ltd. All rights reserved.
Cu(I)-catalysed
B3LYP/6-31G(d)
Saccharide triazole derivative
1. Introduction
As a privileged scaffold, coumarin is an ubiquitous subunit in
many natural products with remarkable biological activities and
N-Heterocyclic compounds are broadly distributed in nature
and include amino acids, purines, pyrimidines and many other nat-
ural products. N-Heterocyclic compounds, such as [1,2,3]-triazoles,
benzimidazoles and benzothiazoles, display a wide range of biolog-
ical activities1 and have also found extensive industrial applica-
tions, such as dyes, corrosion inhibitors, photo stabilizers,
photographic materials and agrochemicals.2
Some of the heterocyclic glycoconjugates, such as nucleosides
and nucleotides, act as primary building blocks of nucleic acids
and are widespread in nature. Certain heterocyclic-based carbohy-
drates of natural and unnatural origins containing exocyclic nitro-
gen atoms exhibit valuable biological activities.3,4 In general the
carbohydrate derivatives reported in the literature5 are known to
possess good therapeutic profiles of solubility, in vivo stability, tar-
get-binding affinity and cell permeability. Due to an increasing
need to decipher the information contained in complex carbohy-
drates, simple and readily accessible methods for high-throughput
analysis must be developed. ‘Click chemistry’ has been reported to
be one of the most frequently used approaches in glycochemistry6
where libraries of compounds can be quickly synthesized. Ferrieres
and co-workers7 have employed a mild uncatalysed 1,3-DCR (1,3-
dipolar cycloaddition reaction) to generate a series of saccharidyl
1,4,5-trisubstituted-1,2,3-triazoles as heterocyclic analogues.
unique physical properties.8–10 Recently Wang and co-workers11
have synthesized a coumarin-containing triazole structure where
the triazole ring is directly linked to the third position of the cou-
marin moiety (Fig. 1).
It is to be noted that 1,2,3-triazoles, can be prepared through
two possible pathways in which the catalysed route affords 1,4-
disubstituted-1,2,3-triazoles, and the non-catalysed route affords
a mixture of 1,4- and 1,5-disubstituted-1,2,3-triazoles (Fig. 2). Reg-
ioselectivity is influenced in a complicated manner by the presence
of substituents on the acetylenic and azido compounds as well as
on the reaction conditions.
The present investigation focuses on the effect of the reaction
conditions, either the thermal or Cu(I)-catalysed pathway chosen
by alkyne moieties to synthesize 1,2,3-triazoles from 3-azidometh-
ylcoumarin. As a guide to the present work, we chose the alkyne
moieties in such a way that the regioselectivity is explained by
both experimental and DFT calculations. Thus, in this report we
N
N
N
R2
R1
O
O
R1 = H, OH, Et3N, Br, OCH3
R2 = C6H5, C7H7, C7H4F3, C6H4F, C6H4Cl, C6H4Br
⇑
Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494.
E-mail address: tmdas_72@yahoo.com (T.M. Das).
Figure 1. Coumarin triazole compounds known in the literature.11
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.07.037

2298
K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
R1
N
N N
N
N N
N
N N
R3
O
O
R2
Cu(I)
(7−9)
(4−6)
( ) R1 = R2 = H
4
(7) R3 = C6H5
(8) R3 = CH2OH
(9) R3 = CH2Br
( ) R1 = H, R2 = OCH3
5
( ) R1 = Br, R2 = H
6
N
N
N
N
N
N
Xylene
Yield 21−71%
R1
R3
Catalysed reaction
pathway
Non-catalysed reaction
pathway
N
N
N
O
O
R2
Figure 2. Two possible pathways in the synthesis of triazole compounds.
(10−18)
) R1 = R2 = H, R3 = 4-C6H5, 5-C6H5
) R1 = R2 = H, R3 = 4-CH2OH
10
(
(
11
R1
R1
(12) R1 = R2 = H, R3 = 5-CH2OH
NaN3
N N N
Cl
(13) R1 = R2 = H, R3 = 4-CH2Br
Acetone−H2O
Yield 85−93%
O
O
O
O
(14) R1 = H, R2 = OCH3, R3 = 4-C6H5, 5-C6H5
R2
R2
15
(
) R1 = H, R2 = OCH3, R3 = 4-CH2OH
) R1 = H, R2 = OCH3, R3 = 5-CH2OH
(1) R1 = R2 = H
(4) R1 = R2 = H
16
(
(5) R1 = H, R2 = OCH3
(6) R1 = Br, R2 = H
(17) R1 = H, R2 = OCH3, R3 = 4-CH2Br
(18) R1 = Br, R2 = H, R3 = 4-CH2Br
(2) R1 = H, R2 = OCH3
(3) R1 = Br, R2 = H
Scheme 1. Synthesis of 3-azidomethyl coumarin (4–6).
Scheme 2. Synthesis of coumarin-coupled triazole compounds (10–18).
The normal distance between the molecule and its (stacking)
translational equivalents (sym: Àx, Ày, 1 À z) are 3.463 (3) Å and
3.551 (3) Å (sym: 1 À x, 1 À y, 2 À z), respectively.
have demonstrated that the use of these conditions provides a
simple and general method for the synthesis of coumarin-coupled
triazole compounds. In order to obtain further insight into the
structure–function relationships among the triazoles, we have gen-
erated a library of triazole derivatives linked via a methylene group
to coumarin. Although there exist several reports on triazoles in
the recent literature,12 to our knowledge this is the first report
on sugar-containing coumarin-triazole derivatives substituted at
the 3-position of coumarin via a methylene group.
As shown in Scheme 2, reaction of 3-azidomethylcoumarin
derivatives (4–6) with propargyl bromide (9) in xylene under ther-
mal conditions furnishes primarily 1,4-disubstituted triazole prod-
ucts 13, 17 and 18 in 61–71% yields. Reaction of propargyl alcohol
(8) with 3-azidomethylcoumarins 4 and 5 affords 1,4- (11 and 15)
and 1,5-triazole (12 and 16) compounds that were separated
through column chromatography in 45–59% and 21–23% yields,
respectively. Reaction of phenylacetylene (7) with 3-azidomethyl-
coumarin derivatives 4 and 5 affords an inseparable mixture of
1,4- and 1,5-isomers 10 and 14 in a ratio of 1:0.8 and 1:0.25,
respectively, as determined from NMR studies. However, the ratio
of these isomers depends upon the electronic and steric effects as
has been reported with a similar kind of derivatives.14
2. Results and discussion
In this study we employed 3-azidomethyl coumarin and acetyl-
enic derivatives to prepare coumarin-coupled triazole compounds
linked via a methylene group. 3-Chloromethylcoumarins (1–3)
were synthesized and characterized by adopting the literature pro-
cedure.13 Reaction of 1–3 with sodium azide in acetone gave the
corresponding 3-azidomethyl coumarin derivatives (4–6) in 85–
93% yields (Scheme 1), and these compounds were characterized
by NMR spectroscopy, mass spectrometry and elemental analysis.
6-Bromo-3-azidomethylcoumarin (6) crystallizes from chloro-
form in an orthorhombic lattice in a monoclinic space group
P21/c. An ORTEP view and crystal packing diagram are shown in
Figure 3. The coumarin moiety is nearly planar with atom C10,
which shows only a minimal deviation (0.026(1) Å) from the mean
plane. The molecule and its centre of inversion along with (a + c)
Synthesis of compounds containing a coumarin triazole moiety
was further extended to carbohydrate derivatives. The propargyl
glycosides 19, 20, 21 and 22 were synthesized from readily
available sugars, viz.,
D
-glucose,
D
-galactose, 4.6-O-ethylidene-
-glucopyranose, from the
D-glucopyranose and 4,6-O-butylidene-
D
corresponding acetylated sugars by treatment with propargyl alco-
hol in the presence of borontrifluoride etherate.15
Attempts to couple 3-azidomethylcoumarins 4–6 with the
propargyl glycoside of D-glucose did not result in the expected
products under thermal conditions. Though few literature reports
are focussed on cycloaddition reactions of propargylglycosides
under thermal conditions,16 the same strategy seemed to be
translations form a one-dimensional
p–p stacking arrangement.
Figure 3. (a) Single-crystal XRD and (b) crystal-packing diagram of compound 6.

K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
2299
unappealing for our molecules, since these labile molecules do not
survive at elevated temperature. Therefore, an alternate strategy
has been chosen, and the present investigations revealed a mild
and efficient method for synthesizing [1,2,3]-triazoles using Cu(I)
as catalyst. To our expectations, Cu(I)-catalysed reaction condi-
tions resulted in the formation of the expected products 23–27
in 53–73% yield (Scheme 3). The Cu(I)-catalysed reaction results
in the thermodynamically more favourable 1,4-regioisomer and
not the 1,5-regioisomer.
and 14 reveal the presence of a mixture of both 1,4- and 1,5-iso-
mers in a ratio of 1:0.8 and 1:0.25, respectively. In contrast to
phenylacetylene 7 and propargyl alcohol 8, propargyl bromide 9
results only in the favourable 1,4-regioisomers 13, 17 and 18 as
confirmed by NMR studies.
Compounds 23–27 were shown to be in the b-anomeric form as
evidenced by a wide doublet for H-1 (d 4.6 ppm, J = 7.8 Hz). The 13
C
NMR spectra of triazole compounds 23–27 confirmed the presence
of conjugated products as the anomeric carbon was identified at
99.7–100.1 ppm. 13C NMR analyses of compounds 23–27 were also
In the 1H NMR spectra of both non-sugar (10–18) and sugar-hy-
brid (23–27) coumarin triazole derivatives, the triazole proton ap-
pears as singlet in the range 6.94–8.07 ppm, while the allylic
methylene resonances were observed at 3.9 ppm. In their 13C
NMR spectra the triazole carbons appear in the range 144.2–
151.7 and 122.8–124.6 ppm. The triazole proton in 1,4-regioiso-
meric compounds 11 and 15 was found at 7.05 and 7.88 ppm,
respectively, whereas in the case of 1,5-regioisomeric compounds
12 and 16, it was shifted upfield to 6.94 and 7.67 ppm, respectively.
Similar observations were reported in the literature for 1,4- and
carried out: the relatively large
D
(dC4 À dC5) values for the different
triazoles, ranging from 19.3 to 21.5 ppm, indicate that these com-
pounds are 1,4-regioisomers, since much smaller values would be
expected for 1,5-regioisomers.18 (Table 1)
2.1. Computational studies
Earlier studies reveal that the B3LYP hybrid functional in den-
sity functional theory (DFT)19,20 is a reliable method for studying
Diels–Alder reactions.21 Hence, geometry optimization and fre-
quency calculations were carried out on the reactants, transition
states (TSs) and products using the B3LYP/6-31G(d) level of theory.
All gas-phase-optimized stationary points were verified as minima
or first-order saddle points by the frequency calculations. All calcu-
lations were performed with the GAUSSIAN 0322 program package.
The geometries of the TS are depicted in Figure 4.
1,5-substituted triazoles.17 Moreover, the
compounds 11 and 15 were calculated as 25.7 and 27.1 ppm,
respectively, whereas for compounds 12 and 16 the
(dC4 À dC5
values were 22.3 and 23.2, respectively. These results further sup-
port our observations that
D
(dC4 À dC5) values of
D
)
D
(dC4 À dC5) values of 1,4-regioisomeric
compounds are comparatively larger than those for 1,5-regioisom-
ers, which is in accordance with the values reported in the litera-
ture.18 1H NMR spectra of coumarin triazole phenyl hybrids 10
R1
N
N
N
O
R3
O
O
R2
(19-22)
(4-5)
OAc
O
AcO
AcO
OAc
( ) R1 = R2 = H
3
3
O
4
5
(20) R3
=
19
21
(
(
) R
=
=
O
AcO
AcO
( ) R1 = H, R2 = OCH3
O
O
OAc
OAc
CH3
H3C
H
(22) R3
=
) R
O
O
O
O
O
O
AcO
H
O
OAc
AcO
OAc
Sodium ascorbate
CuSO4·5H2O
1:1 THF−H2O
Yield 53−73%
C5
R3
O
R1
N
N
N
O
O
C4
R2
(23−27)
OAc
OAc
O
O
O
O
(26) R1 = R2 = H, R3
=
H
AcO
AcO
(
) R1 = R2 = H, R3
23
=
AcO
OAc
OAc
OAc
AcO
O
(
) R1 = H, R2 = OCH3, R3
27
O
AcO
=
(
) R1 = R2 = H, R3
24
=
AcO
AcO
OAc
OAc
H3C
H
O
O
) R1 = R2 = H, R3
25
=
O
(
AcO
OAc
Scheme 3. Synthesis of coumarin-coupled triazole saccharide compounds (23–27).

2300
K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
Table 1
that of a recent study on the unsubstituted 1,3-dipolar compounds
13C NMR analysis of triazole compounds 23–27
with acetylene and ethylene carried out by Houk and co-workers. A
new distortion/interaction energy model has been proposed for the
1,3-dipolar cycloaddition reactivity. The qualitative comparison
of the present results with those of an earlier finding indicates that
the origin of regioselectivity in these systems is mainly due to the
substitution of various functional groups.
Compd No.
C-4
C-5
D
(dC4 À dC5) ppm
23
24
25
26
27
144.4
144.2
145.1
144.4
144.3
124.9
124.9
125
124.9
122.8
19.5
19.3
20.1
19.5
21.5
It can be noted from Figure 5 that the steric hindrance between
coumarin and substituent groups destabilizes the structure of 1,5-
TSs when compared to that of the 1,4-product. This effect is also
reflected in the corresponding energies. As a result, the exotherm-
icities of the 1,4-reactions are higher than those of the 1,5-reac-
tions as evidenced from the reaction energies. Therefore, the 1,4-
products are thermodynamically more favourable in comparison
with the 1,5-products, which are kinetically controlled. These
observations are also in accordance with the results of higher tem-
perature studies.23
1
2
1
3
1
3
3
4
1
2
3
4
4
2
4
2
3. Conclusion
In summary, the Cu(I)-catalysed reaction pathway is the more
efficient route for propargyl glycosides to undergo cycloaddition
with azidomethylcoumarin. The non-catalysed reaction pathway
chosen by the acetylenic derivatives seems to be unsuitable for
propargyl glycosides. Studies further suggest that 1,4-products
are thermodynamically controlled processes, and it is consistent
with experimental observations that 1,4-products are the major
products in all cases. However, the introduction of 1-methyltriaz-
ole is expected to result in analogues with improved bioactivity
and pharmacokinetic profiles. For future applications the present
results should provide caution on the use of thermal reaction con-
ditions in connection with propargyl glycosides. Alternatively
Cu(I)-catalysed reaction conditions offer a clear promise for the
synthesis of coumarin–triazole–sugar hybrids.
3
1
3
1
4
2
4
2
Figure 4. B3LYP/6-31G(d)-optimized geometries of concerted transition states of 3-
methylazidocoumarin with propargyl bromide (TS 1 and 2), propargyl alcohol (TS 3
and 4) and phenyl acetylene (TS 5 and 6) along with distances in Å.
All geometries of all transition states namely propargyl bromide
(TS 1 and 2), propargyl alcohol (TS 3 and 4) and phenyl acetylene
(TS 5 and 6) are depicted in Figure 4. Analysis of the geometries
of the TS reveals that all TSs are nearly synchronous and concerted
in nature. Calculated activation and reaction energies for various
reactions are presented in Table 2 along with the calculated dipole
moments. Examination of the results shows that the reaction free-
energy of 1,4-products is higher than that of the 1,5-products. Thus
1,4-products are thermodynamically favourable, whereas the for-
mation of 1,5-products is kinetically controlled. These findings
are in accordance with the experimental observations. It can be
noted from Table 2 that the substituent marginally influences the
formation of the products, and Figure 4 illustrates the effect of sub-
stitution on the reactivity of 1,3-dipolar compounds with acety-
lene. Upon substitution the synchronicity is lost, and the steric
hindrance from coumarin plays an important role in the regioselec-
tivity. Moreover, the substitution of various functional groups on
acetylene affects the bond lengths in TS. For example, the calcu-
lated distances (1–2 and 3–4) in TS5 are different due to substitu-
tion of the phenyl group. In the case of TS6 these distances are 2.05
and 2.34 Å, respectively. The trend obtained in this study is akin to
4. Experimental
4.1. General methods
1H and 13C NMR spectra were measured on a Bruker Avance 300
NMR spectrometer using tetramethylsilane (Me4Si) as the internal
standard. High-resolution mass spectra (HRMS) were carried out
on a Jeol GC mate mass spectrometer in the electrospray-ionization
(ESI) mode at IIT Madras (Chennai, India). Elemental analysis was
carried out using an Eager 300 C,H,N analyser at IIT Bombay
(Mumbai, India). Single-crystal XRD studies were performed using
a Bruker axs (kappa apex 2) analyser at IIT Madras (Chennai, India).
Thin-layer chromatography (TLC) was performed on manually
coated plates (Acme) with detection by UV light or iodine vapour.
Column chromatography was performed using SiO2 (Acme
100–200 mesh). Earlier studies reveal that B3LYP20,21 is a reliable
method for studying Diels–Alder reactions.22 Hence, geometry
optimization and frequency calculations were carried out on the
reactants, transition states (TSs) and products using B3LYP/
6-31G* level of theory. All gas-phase-optimized stationary points
Table 2
Activation enthalpies, free energies and reaction energies (given in the brackets) at 298 K for the addition of an azido compound to an acetylenic compounda
S. No.
1,4-Product
àG° [
Grxn]
1,5-Product
àG° [
Grxn]
D
àH° [
D
Hrxn]
D
D
Dipole moment(D)
D
àH° [
D
Hrxn]
D
D
Dipole moment (D)
1
2
3
15.19 (À71.57)
15.33 (À71.72)
18.87 (À69.38)
27.98 (À57.04)
28.00 (À57.63)
31.48 (À54.52)
7.30
5.63
5.94
14.73 (À70.60)
12.77 (À70.32)
16.98 (À66.03)
27.68 (À54.73)
25.6 (À55.82)
29.63 (À50.78)
3.89
5.74
4.06
a
Energies in kcal/mol at 298 K, B3LYP/6-31G* geometry and ZPVE corrections are included.

K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
2301
‡
‡
R'
R
R
N
N
R'
N
N
N
N
R'
R
R
N
N
NH
R'
N
N
N
R
N
N
R'
N
Figure 5. Energy profile of cycloaddition reaction.
were verified as minima or first-order saddle points by frequency
calculations. All calculations were performed with the GAUSSIAN
0323 program package. While assigning the spectral data, several
abbreviations were used and these include ‘Trz’ for triazole, ‘Cou’
for coumarin, ‘Phe’ for phenyl, ‘Sacc’ for saccharide, ‘Ace’ for acetyl,
‘Eth’ for 4,6-O-ethylidene, ‘But’ for 4,6-O-butylidene and ‘Ano’ for
anomeric.
compounds 11 and 12 on subsequent purification by column
chromatography.
4.2.1.1. Data for 11. White solid (0.29 g, 45%); mp 182–184 °C; 1H
NMR (300 MHz, CDCl3): dH 7.05 (s, 1H, Trz-H), 6.99 (s, 1H, Cou-H),
6.81–6.86 (m, 2H, Cou-H), 6.55–6.6 (m, 2H, Cou-H), 4.73 (s, 2H,
Cou-CH2), 3.92 (s, 2H, Trz-CH2), 1.84 (s, 1H, Trz-CH2–OH). 13C
NMR (75 MHz, CDCl3): dC 165.2 (1C, Cou-C@O), 158.3 (1C, Cou-C),
153.4 (1C, Trz-C), 147.2–128.2 (5C, Cou-C), 127.7 (1C, Trz-C),
123.5 (1C, Cou-C), 121.2 (1C, Cou-C), 60.5 (1C, Cou-CH2), 53.8
(1C, Trz-CH2): Anal. Calcd for C13H11N3O3 257.24: C, 60.70; H,
4.31; N, 16.33. Found: C, 61.12; H, 4.57; N, 16.64.
4.2. General procedure for the synthesis of coumarin-coupled
triazole compounds (10–18)
A mixture of 3-azidomethylcoumarin 4 (0.5 g, 2.5 mmol) and
phenylacetylene (7, 0.27 mL, 2.5 mmol) in xylene (5 mL) was stir-
red overnight, and then the reaction mixture was refluxed for 7–
9 h. The reaction mixture was cooled to room temperature, where-
by a solid separated. The crude product was then filtered off and
purified by column chromatography using a 1:9 MeOH–CHCl3 as
eluant, which afforded the expected compound 10. Yellow solid
(0.4 g, 53%); mp 148–150 °C; 1H NMR (300 MHz, CDCl3): dH 8.07
(s, 2 Â 1H, Trz-H), 7.85–7.73 (s, 2 Â 1H, Cou-H), 7.58–7.41 (m,
2 Â 4H, Cou-H), 7.4–7.27 (m, 2 Â 3H, Phe-H), 5.53–5.48 (s,
2 Â 2H, Cou-CH2). 13C NMR (75 MHz, CDCl3): dC 160–159.9
(2 Â 1C, Cou-C@O), 153.3–148.2 (2 Â 1C, Cou-C), 142.3–140.3
(2 Â 1C, Trz-C), 133.3–124.8 (2 Â 12C, Phe-C, Cou-C), 123.6–122.9
(2 Â 1C, Trz-C), 120.9–116.7 (2 Â 1C, Phe-C), 49.2–46.7 (2 Â 1C,
Cou-CH2). HRESIMS: calcd for C18H13N3O2 ([M+1]), 303.1008,
found: 303.1005. Anal. Calcd for C18H13N3O2: C, 71.28; H, 4.32, N,
13.85. Found: C, 71.51; H, 4.18, N, 13.25.
4.2.1.2. Data for 12. White solid (0.14 g, 21%); mp 176–178 °C; 1H
NMR (300 MHz, CDCl3): dH 6.94 (s, 1H, Trz-H), 6.89 (s, 1H, Cou-H),
6.88–6.83 (m, 2H, Cou-H), 6.64–6.57 (m, 2H, Cou-H), 4.78 (s, 2H,
Cou-CH2), 4.01 (s, 2H, Trz-CH2), 1.86 (s, 1H, Trz-CH2-OH). 13C
NMR (CDCl3, 75 MHz): dC 160.7 (1C, Cou-C@O), 153.7 (1C, Cou-C),
144.7 (1C, Trz-C), 142.8–124.2 (5C, Cou-C), 122.4 (1C, Trz-C),
118.5 (1C, Cou-C), 116.6 (1C, Cou-C), 49.3 (1C, Cou-CH2), 21.4
(1C, Trz-CH2): Anal. Calcd for C13H11N3O3 257.24: C, 60.70; H,
4.31; N, 16.33. Found: C, 60.45; H, 4.21; N, 16.64.
4.2.2. 3-((4-(Bromomethyl)-1H-1,2,3-triazol-1-yl)methyl)-
coumarin (13)
A mixture of 3-azidomethylcoumarin (4, 0.5 g, 2.5 mmol) and
propargyl bromide (9, 0.3 mL, 2.5 mmol) in xylene (5 mL) afforded
compound 13. Brown solid (0.5 g, 62%); mp 163–165 °C; 1H NMR
(300 MHz, CDCl3): dH 7.9 (s, 1H, Trz-H), 7.77 (s, 1H, Cou-H), 7.60–
7.48 (m, 2H, Cou-H), 7.37–7.29 (m, 2H, Cou-H), 5.46 (s, 2H, Cou-
CH2), 4.58 (s, 2H, Trz-CH2). 13C NMR (75 MHz, CDCl3): dC 160.7
(1C, Cou-C@O), 153.8 (1C, Cou-C), 144.9 (1C, Trz-C), 142.8–124.13
(5C, Cou-C), 122.5 (1C, Trz-C), 118.5 (1C, Cou-C), 116.8 (1C, Cou-
C), 49.3 (1C, Cou-CH2), 21.4 (1C, Trz-CH2): Anal. Calcd for
4.2.1. 3-((4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)cou-
marin (11) and 3-((5-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-
methyl)coumarin (12)
A mixture of 3-azidomethyl coumarin 4 (0.5 g, 2.5 mmol) and
propargyl alcohol 8 (0.14 mL, 2.5 mmol) in xylene (5 mL) afforded

2302
K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
C13H10BrN3O2 320.14: C, 48.77; H, 3.15; N, 13.13. Found: C, 48.21;
H, 2.87; N, 13.36.
4.2.6. 6-Bromo-3-((4-(bromomethyl)-1H-1,2,3-triazol-1-
yl)methyl)coumarin (18)
A
mixture of 6-bromo-3-azidomethylcoumarin (6, 0.7 g,
2.5 mmol) and propargyl bromide (9, 0.3 mL, 2.5 mmol) in xylene
(5 mL) afforded compound 18. White solid (0.53 g, 71%); mp
168–170 °C; 1H NMR (300 MHz, CDCl3): dH 7.89 (s, 1H, Trz-H),
7.69 (s, 1H, Cou-H), 7), 7.65 (s, 1H, Cou-H), 7.32–7.25 (m, 2H,
Cou-H), 5.47 (s, 2H, Cou-CH2), 4.59 (s, 2H, Trz-CH2). 13C NMR
(75 MHz, CDCl3): dC 160 (1C, Cou-C@O), 152.6 (1C, Cou-C), 145.02
(1C, Trz-C), 141.3–124.2 (4C, Cou-C), 123.7 (1C, Trz-C), 119.9 (1C,
Cou-C), 118.5–117.6 (2C, Cou-C), 49.2 (1C, Cou-CH2), 21.3 (1C,
Trz-CH2). Anal. Calcd for C13H9Br2N3O2 399.04: C, 39.13; H, 2.27;
N, 10.53. Found: C, 39.67; H, 2.59; N, 10.16.
4.2.3. 3-(4-(Phenyl-1H-1,2,3-triazol-1-yl)methyl)-8-methoxy-
coumarin (14)
A mixture of 8-methoxy-3-azidomethylcoumarin (5, 0.57 g,
2.5 mmol) and phenylacetylene (7, 0.3 mL, 2.5 mmol) in xylene
(5 mL) afforded compound 14. White solid (0.47 g, 66%); mp
156–158 °C; 1H NMR (300 MHz, CDCl3): dH 8.06 (s, 2 Â 1H, Trz-
H), 7.85–7.82 (s, 2 Â 1H, Cou-H), 7.68–7.17 (m, 2 Â 3H, Cou-H),
7.11–6.96 (m, 2 Â 3H, Phe-H), 5.53–4.86 (s, 2 Â 2H, Cou-CH2),
3.96 (s, 2 Â 3H, Cou-OCH3). 13C NMR (75 MHz, CDCl3): dC 160.2–
159.4 (2 Â 1C, Cou-C@O), 148.1–147.0 (2 Â 1C, Cou-C), 143.3–
142.9 (2 Â 1C, Trz-C), 142.4–124.8 (2 Â 10C, Phe-C, Cou-C),
123.8–123.1 (2 Â 1C, Trz-C), 121.0–113.9 (2 Â 3C, Phe-C), 49.2–
46.7 (2 Â 1C, Cou-CH2), 56.26 (2 Â 1C, Cou-OCH3). HRESIMS: calcd
for C19H15N3O3 ([M+1]), 333.3407, found: 333.3405. Anal. Calcd for
4.3. General procedure for the synthesis of coumarin-coupled
triazole compounds (23–27)
C19H15N3O3: C, 68.46; H, 4.54; N, 12.61. Found: C, 67.55; H, 4.17; N,
To a vigorously stirring suspension of 2-propyn-1-yl 2,3,4,6-
12.17.
tetra-O-acetyl-b-D-glucopyranoside (19, 0.21 g, 0.6 mmol) in 1:1
THF–H2O was added 3-azidomethylcoumarin (4, 0.11 g,
0.6 mmol). The reaction was initiated by the addition of Cu-
SO4Á5H2O (0.014 g, 0.05 mmol) and sodium ascorbate (0.022 g,
0.1 mmol). The suspension was stirred vigorously at 40 °C for
2 h. At this time TLC indicated completion of the reaction. Dis-
tilled water was added, and the aqueous layer was extracted with
CHCl3 (2 Â 25 mL). The combined extracts were dried, filtered and
evaporated to afford a brownish oily residue. The product was
then purified using column chromatography using 3:7 MeOH–
CHCl3 as eluant, which afforded the expected compound 23 as a
brownish oil.
4.2.4. 3-((4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)-8-
methoxycoumarin (15) and 3-((5-(hydroxymethyl)-1H-1,2,3-
triazol-1-yl)methyl)-8-methoxycoumarin (16)
A mixture of 8-methoxy-3-azidomethylcoumarin (5, 0.57 g,
2.5 mmol) and propargyl alcohol (8, 0.14 mL, 2.5 mmol) in xylene
(5 mL) afforded compounds 15 and 16 on subsequent purification
by column chromatography.
4.2.4.1. Data for 15. White solid (0.37 g, 59%); mp 163–165 °C; 1H
NMR (300 MHz, CDCl3): dH 7.88 (s, 1H, Trz-H), 7.66 (s, 1H, Cou-H),
7), 7.29–7.23 (m, 1H, Cou-H), 7.16–7.08 (m, 2H, Cou-H), 5.48 (s, 2H,
Cou-CH2), 4.73 (s, 2H, Trz-CH2), 3.97 (s, 3H, Cou-OCH3) 2.6 (s, 1H,
Trz-CH2–OH). 13C NMR (75 MHz, CDCl3): dC 164.7 (1C, Cou-C@O),
153.5 (1C, Cou-C), 151.7 (1C, Trz-C), 147.8–128 (5C, Cou-C), 124.6
(1C, Trz-C), 124.1–119.1 (2C, Cou-C), 61.1 (1C, Cou-OCH3), 60.6
(1C, Cou-CH2), 53.7 (1C, Trz-CH2): Anal. Calcd for C14H13N3O4
287.27: C, 58.53; H, 4.56; N, 14.63. Found: C, 59.21; H, 4.96; N,
14.84.
4.3.1. 3-((4-((2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-
methyl)-1H-1,2,3-triazol-1-yl)methyl)coumarin (23)
Brownish oily liquid (0.32 g, 68%); 1H NMR (300 MHz, CDCl3):
dH 7.84 (s, 1H, Trz-H), 7.73 (s, 1H, Cou-H), 7.6–7.5 (m, 2H, Cou-
H), 7.3–7.29 (m, 2H, Cou-H), 5.47 (s, 2H, Cou-CH2), 5.22–4.81 (m,
3H, Sacc-H), 4.67 (d, J = 7.8 Hz, 1H ano-H), 4.3–3.71 (m, 5H, Sacc-
H), 2.1–1.1 (m, 12H, Ace-H). 13C NMR (CDCl3, 75 MHz): dC 170.7–
170.2 (2C, Ace-C@O), 169.4 (2 Â 1C, Ace-C@O), 161.1 (1C, Cou-
C@O), 153.8 (1C, Cou-C), 144.4 (1C, Trz-C), 142.5–128.4 (3C, Cou-
C), 124.9 (1C, Trz-C), 124.3–116.7 (4C, Cou-C), 99.7 (1C, Ano-C),
72.8–68.3 (4C, Sacc-C), 62.7 (1C, Trz-CH2), 61.8 (1C, Sacc-C), 49.3
(1C, Cou-CH2), 29.6 (1C, Ace-C), 20.7–20.5 (3C, Ace-CH3). HRESIMS:
calcd for C27H29N3O12 ([M+1]), 587.5321, found: 587.5320. Anal.
Calcd for C27H29N3O12: C, 55.20; H, 4.98; N, 7.15. Found: C,
54.87; H, 4.59; N, 6.98.
4.2.4.2. Data for 16. White solid (0.15 g, 23%); mp 172–175 °C; 1H
NMR (300 MHz,CDCl3): dH 7.67 (s, 1H, Trz-H), 7.34 (s, 1H, Cou-H),
7.25–7.21 (m, 1H, Cou-H), 7.14–7.01 (m, 2H, Cou-H), 5.54 (s, 2H,
Cou-CH2), 4.75 (d, J = 4.5 Hz, 2H, Trz-CH2), 3.97 (s, 3H, Cou-OCH3),
2.6 (s, 1H, Trz-CH2-OH). 13C NMR (75 MHz, CDCl3): dC 164.5 (1C,
Cou-C@O), 151.7 (1C, Cou-C), 147.6 (1C, Trz-C), 145.8–128.3 (5C,
Cou-C), 124.4 (1C, Trz-C), 124.1–118.8 (2C, Cou-C), 61 (1C, Cou-
OCH3), 57.3 (1C, Cou-CH2), 51.58 (1C, Trz-CH2): Anal. Calcd for
4.3.2. 3-((4-((2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyloxy)-
methyl)-1H-1,2,3-triazol-1-yl)methyl)coumarin (24)
C14H13N3O4 287.27: C, 58.53; H, 4.56; N, 14.63. Found: C, 58.17;
H, 4.24; N, 14.15.
A mixture of 3-azidomethylcoumarin (4, 0.11 g, 0.6 mmol)
and 2-propyn-1-yl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside
4.2.5. 3-((4-(Bromomethyl)-1H-1,2,3-triazol-1-yl)methyl)-8-
methoxycoumarin (17)
(20, 0.21 g, 0.6 mmol) in 1:1 THF–H2O afforded compound 24
(0.30 g, 65%). Brownish oily liquid; 1H NMR (300 MHz, CDCl3):
dH 7.82 (s, 1H, Trz-H), 7.51 (s, 1H, Cou-H), 7.48–7.42 (m, 2H,
Cou-H), 7.29–7.19 (m, 2H, Cou-H), 5.41 (s, 2H, Cou-CH2), 5.32–
4.73 (m, 3H, Sacc-H), 4.61 (d, J = 7.8 Hz, 1H, Ano-H), 4.1–3.9
(m, 5H, Sacc-H), 2.1–1.89 (m, 12H, Ace-H). 13C NMR (75 MHz,
CDCl3): dC 170.4–169.6 (4C, Ace-C@O), 160.6 (1C, Cou-C@O),
157.5–153.6 (2C, Cou-C), 144.2 (1C, Trz-C), 142.6–128.4 (3C,
Cou-C), 124.9 (1C, Trz-C), 122.6–116.6 (3C, Cou-C), 100.1 (1C,
Ano-C), 70.7–62.5 (4C, Sacc-C), 61.3 (1C, Trz-CH2), 60.9 (1C,
Sacc-C), 49.2 (1C, Cou-CH2), 20.9–20.5 (4C-Ace-CH3). HRESIMS:
calcd for C27H29N3O12 ([M+1]), 587.5321, found: 587.5310. Anal.
Calcd for C27H29N3O12: C, 55.20; H, 4.98; N, 7.15. Found: C,
55.39; H, 4.58; N, 7.08.
A mixture of 8-methoxy-3-azidomethylcoumarin (5, 0.57 g,
2.5 mmol) and propargyl bromide (9, 0.3 mL, 2.5 mmol) in xylene
(5 mL) afforded compound 17. Brown solid (0.46 g, 61%); mp
160–163 °C; 1H NMR (300 MHz, CDCl3): dH 8.04 (s, 1H, Trz-H),
7.79 (s, 1H, Cou-H), 7.3–7.23 (m, 1H, Cou-H), 7.18–7.12 (m, 2H,
Cou-H), 5.5 (s, 2H, Cou-CH2), 4.62 (s, 2H, Trz-CH2), 3.98 (s, 3H,
Cou-OCH3). 13C NMR (75 MHz, CDCl3): d 164.8 (1C, Cou-C@O),
151.7 (1C, Cou-C), 149.1 (1C, Trz-C), 147.9–127.5 (5C, Cou-C),
124.6 (1C, Trz-C), 123.9–119.2 (2C, Cou-C), 61.03 (1C, Cou-OCH3),
54.01 (1C, Cou-CH2), 26.6 (1C, Trz-CH2). Anal. Calcd for
C14H12BrN3O3 350.17: C, 48.02; H, 3.45; N, 12.00. Found: C,
48.29; H, 3.58; N, 11.87.

K. K. Kumar et al. / Carbohydrate Research 345 (2010) 2297–2304
2303
4.3.3. 3-((4-((2,3-Di-O-acetyl-4,6-O-ethylidene-b-
syloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)coumarin (25)
A mixture of 3-azidomethylcoumarin (4, 0.11 g, 0.6 mmol) and
D
-glucopyrano-
Chemistry, University of Madras. K.K.K. thanks CSIR, New Delhi,
for a research fellowship.
2-propyn-1-yl 2,3-di-O-acetyl-4,6-O-ethylidene-b-D-glucopyranose
Supplementary data
(21, 0.18 g, 0.6 mmol) in 1:1 THF–H2O afforded compound 25.
White solid (0.30 g, 73%); mp 138–140 °C; 1H NMR (300 MHz,
CDCl3): dH 7.79 (s, 1H, Trz-H), 7.72 (s, 1H, Cou-H), 7.59–7.49 (m,
2H, Cou-H), 7.36–7.26 (m, 2H, Cou-H), 5.46 (s, 2H, Cou-CH2),
5.22–4.77 (m, 4H, Sacc-H), 4.67 (d, J = 7.8 Hz, 1H Ano-H), 4.23–
3.35 (m, 5H, Sacc-H), 2.04 (s, 3H, Ace-CH3), 1.989 (s, 3H, Ace-CH3),
1.32 (d, J = 5.1 Hz, 3H, Eth-CH3). 13C NMR (75 MHz, CDCl3): dC 170–
169.5 (2C, Ace-C@O), 168.9 (1C, Cou-C@O), 153.9 (1C, Cou-C),
145.1 (1C, Trz-C), 142.8–128.4 (3C, Cou-C), 124.99 (1C, Trz-C),
124.1–99.8 (5C, Cou-C), 92.15 (1C, Ano-C), 71.8–66.9 (5C, Sacc-C),
49.3 (1C, Trz-CH2), 29.9 (1C, Cou-CH2), 20.7–20.6 (2C, Ace-CH3),
20.1 (1C, Eth-CH3): Anal. Calcd for C25H27N3O10 529.50: C, 56.71;
H, 5.14; N, 7.94. Found: C, 57.24; H, 5.47; N, 7.66.
Full crystallographic details have been deposited with Cam-
bridge Crystallographic Data Centre for structure
6 (CCDC
723228). These data may be obtained, on request from The Direc-
tor, CCDC, 12 Union Road, Cambridge CBZ 1EZ, UK (Email: depos-
it@cdc.cam.ac.uk or http://www.ccdc.cam.ac.uk). Supplementary
data (NMR spectra) associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.07.037.
References
1. Alvarez, R.; Velazquez, S.; San, F.; Aquaro, S.; De, C.; Perno, C. F.; Karlsson, A.;
Balzarini, J.; Camarasa, M. J. J. Med. Chem. 1994, 37, 4185–4194.
2. Fan, W. Q.; Katritzky, A. R.. In Comprehensive Heterocyclic Chemistry II; Katritzky,
A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Science: Oxford, 1996; Vol. 4, pp
1–126.
4.3.4. 3-((4-((2,3-Di-O-acetyl-4,6-O-butylidene-b-D-glucopyrano-
syloxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)coumarin (26)
A mixture of 3-azidomethylcoumarin (4, 0.11 g, 0.6 mmol) and
3. Ichikawa, E.; Kato, K. Curr. Med. Chem. 2001, 8, 385–423.
4. (a) Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515–
554; (b) Rossi, L. L.; Basu, A. Bioorg. Med. Chem. Lett. 2005, 15, 3596–3599; (c)
Gallos, J. K.; Koumbis, A. E. Curr. Org. Chem. 2003, 7, 771–797.
2-propyn-1-yl
2,3-di-O-acetyl-4,6-O-butylidene-b-D-glucopyra-
nose (22, 0.21 g, 0.6 mmol) in 1:1 THF–H2O afforded compound
26. White solid (0.31 g, 71%); mp 148–150 °C; 1H NMR
(300 MHz, CDCl3): dH 7.80 (s, 1H, Trz-H), 7.73 (s, 1H, Cou-H),
7.59–7.49 (m, 2H, Cou-H), 7.36–7.29 (m, 2H, Cou-H), 5.46 (s,
2H, Cou-CH2), 5.22–4.77 (m, 4H, Sacc-H), 4.67 (d, J = 7.8 Hz, 1H
Ano-H), 4.51–3.37 (m, 5H, Sacc-H), 2.04 (s, 3H, Ace-H), 1.99 (s,
3H, Ace-H), 1.63–1.56 (m, 2H, But-CH2), 1.40–1.33 (m, 2H, But-
CH2), 0.92–0.87 (m, 3H, But-CH3). 13C NMR (75 MHz, CDCl3): dC
170.4–169.6 (2C, Ace-C@O), 160.6 (1C, Cou-C@O), 153.7 (1C,
Cou-C), 144.4 (1C, Trz-C), 142.5–128.4 (3C, Cou-C), 124.9 (1C,
Trz-C), 124.1–102.6 (5C, Cou-C), 100.1 (1C, Ano-C), 72.1–66.5
(5C, Sacc-C), 62.7 (1C, Trz-CH2), 49.2 (1C, Cou-CH2), 35.95 (1C,
But-CH2), 20.9–20.5 (2C, Ace-CH3), 17.7 (1C, But-CH3), 13.8 (1C,
But-CH2): Anal. Calcd for C27H31N3O10 557.55: C, 58.16; H, 5.60;
N, 7.54. Found: C, 59.23; H, 5.23; N, 7.86.
5. (a) Santoyo-Gonzalez, F.; Hernandez-Mateo, F. Top. Heterocycl. Chem. 2007, 7,
133–177; (b) Dedola, S.; Nepogodiev, S. A.; Feild, R. A. Org. Biomol. Chem. 2007,
5, 1006–1017; (c) Wilkinson, B. L.; Bornaghi, L. F.; Houston, T. A.; Poulsen, S.-A.
In Drug Des. Res. Perspectives; Kaplan, S. P., Ed.; Nova: New York, 2007; pp 57–
102.
6. (a) Dondoni, A. Chem. Asian J. 2007, 2, 700–708; (b) Hanson, S. R.; Greenberg, W.
A.; Wong, C.-H. QSAR Comb. Sci. 2007, 26, 1243–1252; (c) Pieters, R. J.; Rijkers,
D. T. S.; Liskamp, R. M. J. QSAR Comb. Sci. 2007, 26, 1181–1190; (d) Santoyo-
Gonzalez, F.; Hernandez-Meteo, F. Chem. Soc. Rev. 2009, 38, 3449–3462; (e)
Sawa, M.; Hsu, T. L.; Itoh, T.; Sugiyama, M.; Hanson, S. R.; Vogt, P. K.; Wong, C.
H. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12371–12376.
7. Perion, R.; Ferrieres, V.; Garcia Moreno, M. I.; Mellet, C. O.; Duval, R.; Garcia
Fernandez, J. M.; Plusquellec, D. Tetrahedron 2005, 61, 9118–9128.
8. Curir, P.; Galeotti, F.; Dolci, M.; Barile, E.; Lanzotti, V. J. Nat. Prod. 2007, 70,
1668–1671.
9. Kontogiorgis, C. A.; Hadjipavlou Litina, D. J. Med. Chem. 2005, 48, 6400–6408.
10. (a) Zhao, Y.; Zheng, Q.; Dakin, K.; Xu, K.; Martinez, M. L.; Li, W. H. J. Am. Chem.
Soc. 2004, 126, 4653–4663; (b) Zhou, Z.; Fahrni, C. J. J. Am. Chem. Soc. 2004, 126,
8862–8863; (c) Kwon, J. Y.; Singh, N. J.; Kim, H. N.; Kim, S. K.; Kim, K. S.; Yoon, J.
J. Am. Chem. Soc. 2004, 126, 8892–8893; (d) Wu, J.; Liao, Y.; Yang, Z. J. Org. Chem.
2001, 66, 3642–3645; (e) Schiedel, M. S.; Briehn, C. A.; Bauerle, P. Angew. Chem.,
Int. Ed. 2001, 40, 4677–4680; (f) Yee, D. J.; Balsanek, V.; Sames, D. J. Am. Chem.
Soc. 2004, 126, 2282–2283.
4.3.5. 3-((4-((2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-
methyl)-1H-1,2,3-triazol-1-yl)methyl)-8-methoxycoumarin (27)
A mixture of 8-methoxy-3-azidomethylcoumarin (5, 0.14 g,
11. Sivakumar, K.; Xie, F.; Cash, B. M.; Long, S.; Barnhill, H. N.; Wang, Q. Org. Lett.
2004, 6, 4603–4606.
0.6 mmol) and 2-propyn-1-yl 2,3,4,6-tetra-O-acetyl-b-D-glucopy-
12. (a) Ganesh, N. V.; Jayaraman, N. J. Org. Chem. 2009, 74, 739–746; (b) Shi, F.;
Waldo, J. P.; Chen, Y.; Larock, R. C. Org. Lett. 2008, 10, 2409–2412; (c) Zhang, J.;
Chang, C.-W. T. J. Org. Chem. 2009, 74, 4414–4417; (d) Sherman, R. W.; Robins,
E. Carbohydr. Res. 1968, 7, 184–192; (e) Baggett, N.; Marsden, B. J. Carbohydr.
Res. 1982, 110, 11–18; (f) Marino, C.; Cancio, M. J.; Varela, O.; de Lederkremer,
R. M. Carbohydr. Res. 1995, 276, 209–213; (g) Key, J. A.; Koh, S.; Timerghazin, Q.
K.; Brown, A.; Cairo, C. W. Dyes Pigments 2009, 82, 196–203.
ranoside (19, 0.21 g, 0.6 mmol) in 1:1 THF–H2O afforded com-
pound 27 (0.23 g, 53%). Brownish oily liquid; 1H NMR (300 MHz,
CDCl3): dH 7.84 (s, 1H, Trz-H), 7.69 (s, 1H, Cou-H), 7.23–7.1 (m,
3H, Cou-H), 5.47 (s, 2H, Cou-CH2), 5.22–4.81 (m, 3H, Sacc-H),
4.67 (d, J = 7.8 Hz, 1H Ano-H), 4.3–4.14 (m, 3H, Sacc-H), 3.96 (s,
3H, Cou-OCH3), 3.75–3.72 (m, 2H, Sacc-H), 2.18–1.99 (m, 12H,
Ace-H). 13C NMR (75 MHz, CDCl3): dC 170.7–170.2 (2C, Ace-C@O),
169.4 (2 Â 1C, Ace-C@O), 160.2 (1C, Cou-C@O), 147.2 (1C, Cou-C),
144.3 (1C, Trz-C), 142.7–124.3 (3C, Cou-C), 122.8 (1C, Trz-C),
119.7–114.4 (4C, Cou-C), 99.6 (1C, Ano-C), 72.8–68.3 (4C, Sacc-C),
62.6 (1C, Trz-CH2), 61.8 (1C, Sacc-C), 56.3 (1C, Cou-OCH3), 49.2
(1C, Cou-CH2), 30.8 (1C, Ace-CH3), 20.7–20.5 (3C, Ace-CH3).
13. Kaye, P. T.; Musa, M. A. Synthesis 2002, 18, 2701–2706.
14. Sustmann, R. Tetrahedron Lett. 1971, 29, 2717–2720.
15. Mereyala, H. B.; Gurrala, S. R. Carbohydr. Res. 1998, 307, 351–354.
16. Calvo-Flores, F. G.; Isac-Garcia, J.; Hernandez-Mateo, F.; Perez-Balderas, F.;
Calvo-Asin, J. A.; Sanchez-Vaquero, E.; Santoyo-Gonzalez, F. Org. Lett. 2000, 2,
2499–2502.
17. Torne, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064.
18. (a) Rodios, N. A. J. Heterocycl. Chem. 1984, 21, 1169–1173; (b) Gouin, S. G.;
Bultel, L.; Falentin, C.; Kovensky, J. Eur. J. Org. Chem. 2007, 1160–1167.
19. Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
HR-ESIMS: calcd for
C28H31N3O13 ([M+1]), 617.5580, found:
20. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B. 1988, 37, 785–789.
21. Singh, L.; Ishar, M. P. S.; Elango, M.; Subramanian, V.; Gupta, V.; Kanwal, P. J.
Org. Chem. 2008, 73, 2224–2233.
617.5578. Anal. Calcd for C28H31N3O13: C, 54.46; H, 5.06; N, 6.80.
Found: C, 54.12; H, 4.98; N, 6.98.
22. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Acknowledgements
Authors acknowledge CSIR, New Delhi, for financial support. We
also acknowledge Professor C. P. Rao, Department of Chemistry, IIT
Bombay, Mumbai, for his valuable suggestions and elemental anal-
ysis. T.M.D. thanks DST, New Delhi, for a 300 MHz NMR spectrom-
eter under the FIST scheme to the Department of Organic

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Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.;
23. (a) Ess, D. H.; Jones, G. O.; Houk, K. N. Org. Lett. 2008, 10, 1633–1636; (b) Ess, D.
H.; Houk, K. N. J. Am. Chem. Soc. 2008, 130, 10187–10193; (c) Ess, D. H.; Houk, K.
N. J. Am. Chem. Soc. 2007, 129, 10646–10647.
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,
M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
GAUSSIAN 03, Revision E.01; Gaussian, Inc.: Wallingford, CT, 2004.