An efficient copper-catalyzed three-component synthesis of 3-C-linked glycosyl iminocoumarins

Article abstract of DOI:10.1055/s-0031-1289763

An efficient general strategy was developed for the synthesis of previously unknown 3-C-linked glycosyl iminocoumarins. The strategy involves a copper-catalyzed multicomponent reaction of sugar-derived alkynes with tosyl azide and salicylaldehyde to give a diverse array of glycosyl iminocoumarins in good yields. These compounds can serve as appropriate precursors for the synthesis of the corresponding coumarin 3-C-glycosides. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289763

SPECIAL TOPIC
▌1841
sApencialEtopfifcicient Copper-Catalyzed Three-Component Synthesis of 3-C-Linked
Glycosyl Iminocoumarins
Synthesis of 3-C-Linked Glycosyl Iminocoumarins
Kalanidhi Palanichamy, Sankar R. Suravarapu, Krishna P. Kaliappan*
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India
Fax +91(22)25723480; E-mail: kpk@chem.iitb.ac.in
Received: 03.04.2012; Accepted: 10.04.2012
sensitive functional groups. Consequently, the develop-
Abstract: An efficient general strategy was developed for the syn-
ment of new and mild methods for constructing coumarin
thesis of previously unknown 3-C-linked glycosyl iminocoumarins.
and iminocoumarin frameworks is an attractive goal.
The strategy involves a copper-catalyzed multicomponent reaction
of sugar-derived alkynes with tosyl azide and salicylaldehyde to
Since the first syntheses of coumarin C-glycosides by
give a diverse array of glycosyl iminocoumarins in good yields. Mahling and Schmidt,16 many reports have appeared on
These compounds can serve as appropriate precursors for the syn-
thesis of the corresponding coumarin 3-C-glycosides.
the synthesis of C-glycosyl coumarin derivatives in which
the aromatic ring of the coumarin unit is attached to the
anomeric carbon of the sugar.4j,17 However, there are few
Key words: multicomponent reactions, copper, alkynes, azides,
glycosides, glycosylations, heterocycles
reports on the synthesis of coumarin 3- or 4-C-glycosides.
Dhavale and co-workers reported a Knoevenagel reac-
tion/lactonization-based approach to the synthesis of C-
The C-aryl glycosides1 are a group of compounds that in- glycosyl coumarins in which the coumarin ring is linked
cludes many natural products such as ravidomycin (1)2 to the C-5 carbon of the pyranose moiety with a free ano-
and gilvocarcin M (2)3 (Figure 1). Because the aromatic meric center (Scheme 1).18 Later, Roy and co-workers de-
ring is directly attached to the sugar unit at an anomeric veloped a one-pot Heck reaction and lactonization
center through a C–C bond, C-aryl glycosides show great- methodology for the synthesis of 3- and 4-C-linked man-
er stability to enzymatic or acidic hydrolysis than do O- or nopyranosyl coumarins (Scheme 1).19
N-glycosides.4 Glycosides in which the sugar unit is
Multicomponent reactions have become attractive tools,
linked to a coumarin5 pharmacophore constitute a novel
particularly in combinatorial organic synthesis, as they
class of glycosides, namely the coumarin glycosides. In
permit the construction of complex structures through the
accord with the intriguing biological profile of coumarins,
OH OMe
coumarin glycosides exhibit a broad spectrum of biologi-
cal activities, such as anti-inflammatory,6 anticoagulant,7
OMe
anticancer,8 and antibacterial activities,9 and they are also
useful as fluorescent probes for studies on ultrafast DNA
dynamics.10
O
O
OH
Although there are many naturally occurring O-glycosyl
coumarins11 [e.g., dauroside A (3),12], the only coumarin
C-glycoside that has been found in nature is dauroside D
(4),13 also known as mulberroside B,14 which exhibits
spasmolytic and hypotensive activities.
O
AcO
Me2N
OH OMe
ravidomycin (1)
OMe
HO
AcO
O
O
OH
OH
O
Whereas iminocoumarins have been shown to be inhibi-
tors of protein tyrosine kinase in cancer research,15 the
chemistry of glycosyl iminocoumarins, to the best of our
knowledge, remains unexplored. We therefore hypothe-
sized that linking of an iminocoumarin scaffold to a car-
bohydrate unit might lead to a new class of glycosides that
might have interesting biological profiles.
O
HO
OH
gilvocarcin M (2)
O
HO
O
HO
O
O
O
OH
HO
HO
dauroside A (3)
In view of the biological and other applications of couma-
rin and iminocoumarin derivatives, many methods have
been developed for the synthesis of these compounds.
However, most of these methods have severe shortcom-
ings, such as a lack of generality or a lack of tolerance to
O
OH
HO
HO
HO
O
O
dauroside D (4)
(also known as
mulberroside B)
SYNTHESIS 2012, 44, 1841–1848
Advanced online publication: 10.05.2012
DOI: 10.1055/s-0031-1289763; Art ID: SS-2012-C0331-ST
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Examples of C-aryl glycosides (ravidomycin and gilvocar-
cin M), a coumarin O-glycoside (dauroside A), and a coumarin C-gly-
coside (dauroside D)
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1842
K. Palanichamy et al.
SPECIAL TOPIC
Dhavale's approach
O
O
R2
R2
O
O
O
CHO
OH
O
piperidine
O
O
+
EtO
EtOH
70 °C
R3
O
O
R3
R1
O
R1
O
Roy's approach
RO
O
RO
I
Pd(0)
(a)
+
OH
O
O
CO2Me
R = Ac, Bn
OBn
BnO
BnO
BnO
O
OBn
O
BnO
BnO
BnO
I
Pd(0)
(b)
+
n
n
OH
O
O
MeO2C
n = 0, 1
Scheme 1 Previous approaches to coumarin 3- and 4-C-linked glycosides
formation of multiple covalent bonds in a one-pot pro- To test our hypothesis, we chose a suite of sugar-derived
cess.20 Several years ago, Chang and co-workers reported alkynes (Figure 2), which we prepared by the procedures
a copper-catalyzed multicomponent reaction of alkynes described in the literature.26,27 Having prepared these al-
and sulfonyl azides with amines, water, or alcohols to give kynes, we initially examined the copper-catalyzed multi-
N-sulfonylamidines, amides, and N-sulfonylimidates, re- component reaction of alkyne 5 (1 mmol) with tosyl azide
spectively.21 This methodology has been further (1 mmol) and salicylaldehyde 13 (1 mmol) in the presence
developed22 by Chang,23 Wang,24 and others25 to construct of copper(I) iodide (0.1 mmol) and triethylamine (2
a diverse array of interesting compounds. The technique mmol) in dichloromethane at room temperature (Table 1,
was used by Wang to synthesize iminocoumarins through entry 1). The reaction was sluggish and was incomplete
a copper-catalyzed multicomponent reaction of alkynes, even after 30 hours, giving the required product 14 in only
sulfonyl azides, and 2-hydroxybenzaldehydes or 2-hy- a 36% yield. To optimize the reaction, we screened sever-
droxyacetophenones (Scheme 2).24a
al conditions with various solvents and bases (Table 1).
Whereas 1,4-dioxane (entry 2) or toluene (entry 3) gave
the desired product 14 in 43% and 51% yield, respective-
ly, 14 was obtained in 60% yield when the reaction was
carried out in acetonitrile (entry 4). When the reaction was
performed in tetrahydrofuran (entry 5) for 24 hours, it
went nearly to completion, giving the desired glycosyl im-
inocoumarin 14 in 79% yield. When triethylamine was re-
placed with pyridine (entry 6) in tetrahydrofuran, the yield
of compound 14 was poor (22%). Furthermore, no reac-
tion was observed in the presence of 4-(N,N-dimethylami-
no)pyridine (entry 7) or potassium carbonate (entry 8).
However, the required glycosyl iminocoumarin was ob-
tained in a moderate yield (57%) when the reaction was
performed in the presence of N,N-diisopropylethylamine
(entry 9). We therefore concluded that triethylamine as
the base and tetrahydrofuran as the solvent provide the op-
timal conditions for this reaction.
In continuation of our interest in exploring the application
of sugar-derived alkynes,26 it occurred to us that copper-
catalyzed multicomponent reaction of sugar-derived al-
kynes with tosyl azide and 2-hydroxybenzaldehyde
should provide C-glycosyl iminocoumarins that might
serve as precursors of coumarin 3-C-glycosides. Here, we
report our efforts to synthesize several 3-C-linked glyco-
syl iminocoumarins.
previous work by Wang
R1O2SN
R2
O
R1SO2N3
CuI, Et3N
HO
R3
R2
R4
+
R4
R3
O
this work
O
HO
O
TsN
O
TsN3, CuI
Et3N
+
O
Next, we examined the scope of the reaction with various
sugar-derived alkyne templates under our optimized con-
ditions (Table 2). In all the cases, the multicomponent re-
action occurred smoothly to give the corresponding 3-C-
glycosyl iminocoumarin in 51–91% yield. In the case of
the sterically hindered alkynes 10 and 11 (entries 6 and 7,
H
Scheme 2 Wang’s multicomponent approach to the synthesis of
iminocoumarins, and our approach to glycosyl iminocoumarins
Synthesis 2012, 44, 1841–1848
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of 3-C-Linked Glycosyl Iminocoumarins
1843
As originally proposed by Chang21 and as postulated by
Wang,24a the reaction proceeds by a stepwise mechanism,
as outlined in Scheme 3. In the presence of copper(I) io-
dide and triethylamine, the sugar-derived terminal alkyne
and tosyl azide react to give the triazolyl copper species
A, which eliminates dinitrogen to give the reactive keten-
imine B. This undergoes addition with the phenolate C,
derived from salicylaldehyde 13. Subsequent intramolec-
ular cyclization leads to intermediate D, which is finally
dehydrated to give the required glycosyl iminocoumarin.
O
O
O
MeO
MeO
TBSO
O
O
O
O
O
O
5
6
7
O
OTBS
O
O
O
O
O
O
O
O
OBn
MeO
8
9
10
Cu
Ts
O
N
O
O
CuI, Et3N
– H+
O
O
TsN3
+
N
O
N
O
O
O
A
O
O
– Cu
– N2
O
H+
MeO
11
12
NTs
H
Figure 2 Selected sugar-derived alkynes for the multicomponent re-
action
O
O
HO
O
H
+
H
– H+
Table 1 Screening of Bases and Solvents To Optimize the Reaction
Conditions
O
13
C
B
MeO
O
O
O
TsN
O
O
TsN
O
O
5
TsN
O
TsN3, CuI
– H2O
+
OH
O
MeO
base (2 equiv)
solvent
HO
O
D
H
Scheme 3 Postulated mechanism for the multicomponent reaction
O
O
13
14
In summary, we have reported for the first time the syn-
thesis of a variety of 3-C-glycosyl iminocoumarins in
which the carbohydrate unit is directly attached to the C-
3 carbon of the iminocoumarin skeleton. The synthesis in-
volves a copper-catalyzed multicomponent reaction of a
sugar-derived alkyne, tosyl azide, and salicylaldehyde to
form the iminocoumarin framework. The resulting glyco-
syl iminocoumarins can serve as intermediates for the
synthesis of the corresponding coumarin 3-C-glycosides.
Our strategy therefore opens a path to the synthesis of a
series of 3-C-linked glycosyl iminocoumarins and couma-
rins that might have interesting biological profiles.
Entrya
Base
Solvent
CH2Cl2
Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
Et3N
30
24
24
24
24
30
24
24
24
36
43
51
60
79
22
−
Et3N
1,4-dioxane
Et3N
toluene
MeCN
THF
Et3N
Et3N
py
THF
DMAP
DIPEA
K2CO3
THF
Unless and otherwise noted, all starting materials and reagents were
obtained from commercial suppliers and used after further purifica-
tion. THF was distilled from sodium–benzophenone ketyl and tolu-
ene was distilled from Na. CH2Cl2, DMF, hexanes, and pyridine
were all freshly distilled from CaH2. All solvents for routine isola-
tion of products and chromatography were of reagent grade and
glass distilled. Reaction flasks were dried in an oven at 100 °C for
12 h. Air- and moisture-sensitive reactions were performed under
an argon/UHP N2 atmosphere. Chromatography was performed by
using silica gel (100–200 mesh; Acme) with the indicated solvents.
All reactions were monitored by TLC on 0.25-mm E. Merck silica
plates (60F-254) visualized with UV radiation, with a charring soln
[prepared by dropwise addition of concd H2SO4 (5 mL) to a soln of
THF
57
−
THF
a The reaction was carried out with alkyne 5 (1 mmol), TsN3 (1
mmol), and salicylaldehyde (1 mmol) in the presence of CuI (0.1
mmol) and base (2 mmol) in the appropriate solvent (5 mL) at r.t.
respectively), the reaction gave the corresponding prod-
ucts 19 and 20 in moderate yields.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1841–1848

1844
K. Palanichamy et al.
SPECIAL TOPIC
Table 2 Copper-Catalyzed Multicomponent Reaction of Various Sugar-Derived Alkynes and Tosyl Azide with Salicylaldehyde
Entrya
Alkyne
Product
Yield (%)
TsN
O
O
O
MeO
O
MeO
1
5
14
79
O
O
O
TsN
O
O
TBSO
O
TBSO
2
3
6
7
15
16
75
83
O
O
O
O
TsN
O
O
MeO
O
MeO
O
O
O
O
TsN
O
O
O
4
5
6
8
9
17
18
19
74
91
56
O
O
O
O
TsN
O
O
O
O
O
O
OBn
O
TBSO
OBn
TsN
O
OTBS
O
O
O
10
OMe
O
O
O
MeO
O
TsN
O
O
O
O
O
O
O
7
11
20
51
O
OMe
O
O
MeO
TsN
O
O
O
O
O
O
O
O
8
12
21
68
O
O
O
a Reaction conditions: Alkyne (1 mmol), TsN3 (1 mmol), salicylaldehyde (1 mmol), CuI (0.1 mmol), and Et3N (2 mmol) in THF (5 mL) at r.t.
for 24 h.
Synthesis 2012, 44, 1841–1848
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of 3-C-Linked Glycosyl Iminocoumarins
1845
20
phosphomolybdic acid (1 g) and Ce(SO4)2 (2 g) in H2O (95 mL)], or
with alkaline KMnO4 [prepared by dissolving KMnO4 (2 g) and
NaHCO3 (4 g) in H2O (100 mL)] with heat as a developing agent.
Optical rotations were recorded on Autopol IV automatic polarim-
eter. IR spectra were recorded on Thermo Nicolet Avater 320 FT-
IR and Nicolet Impact 400 spectrometers. Mass spectra were re-
corded on a Waters Micromass-Q-Tof microTM (YA105) spectrom-
eter. 1H and 13C NMR spectra were recorded on a Bruker 400-MHz
spectrometer and were processed by using MestReNova software.
(83%); mp 99–101 °C; Rf = 0.51 (EtOAc–hexanes, 1:1); [α]D
−37.0 (c 0.9, CHCl3).
IR (KBr): 3855, 3741, 3020, 2930, 1636, 1569, 1458, 1375, 1303,
1216, 1158, 1086, 837 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.3 Hz, 2 H), 7.89 (d,
J = 0.7 Hz, 1 H), 7.57 (td, J = 7.7, 1.2 Hz, 1 H), 7.52–7.49 (m, 2 H),
7.35 (td, J = 7.7, 1.2 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 2 H), 5.3 (s, 1 H),
5.15 (s, 1 H), 4.85 (dd, J = 6.0, 1.6 Hz, 1 H), 4.52 (d, J = 6.0 Hz, 1
H), 3.45 (s, 3 H), 2.42 (s, 3 H), 1.53 (s, 3 H), 1.31 (s, 3 H).
Copper-Catalyzed Multicomponent Reaction; General Proce-
dure
13C NMR (100 MHz, CDCl3): δ = 156.2, 152.4, 143.1, 139.6, 138.4,
132.2, 129.2, 128.6, 128.6, 127.3, 125.9, 119.2, 116.9, 112.9, 112.2,
85.2, 85.1, 84.4, 56.5, 26.9, 25.3, 21.7.
Et3N (2 mmol) was added dropwise to a suspension of TsN3 (1
mmol), the appropriate carbohydrate-derived alkyne (1 mmol), CuI
(0.1 mmol), and salicylaldehyde (1 mmol) in THF (5 mL) at r.t., and
the mixture was stirred at r.t. for 24 h under N2. The resulting mix-
ture was concentrated and the residue was diluted with CH2Cl2 (20
mL) and washed successively with H2O (10 mL) and brine (10 mL).
The organic layer was dried (Na2SO4) and concentrated. The result-
ing crude product was purified by column chromatography (silica
gel, hexanes–EtOAc) to give the corresponding glycosyl iminocou-
marin.
HRMS (ESI): m/z calcd for C24H25NO7S: 472.1430; found:
472.1425.
N-{3-[(3aS,4R,6aR)-2,2-Dimethyltetrahydrofuro[3,4-d][1,3]di-
oxol-4-yl]-2H-chromen-2-ylidene}-4-tolylsulfonamide (17)
By following the general procedure, the multicomponent reaction of
alkyne 8 (20 mg, 0.12 mmol) gave a white solid; yield: 39 mg
20
(74%); mp 136–137 °C; Rf = 0.45 (EtOAc–hexanes, 1:1); [α]D
−53.3 (c 0.8, CHCl3).
N-{3-[(3aS,4R,6S,6aS)-6-Methoxy-2,2-dimethyltetrahydrofu-
ro[3,4-d][1,3]dioxol-4-yl]-2H-chromen-2-ylidene}-4-tolylsul-
fonamide (14)
By following the general procedure, the multicomponent reaction of
alkyne 5 (30 mg, 0.15 mmol) gave a white solid; yield: 56 mg
(79%); mp 146–148 °C; Rf = 0.61 (EtOAc–hexanes, 1:1); [α]D
–19.3 (c 0.9, CHCl3).
IR (KBr): 2926, 2853, 2252, 2102, 1635, 1560, 1458, 1380, 1320,
1261, 1216, 1159, 1088, 913, 815, 736, 672, 611 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.2 Hz, 2 H), 7.87 (s,
1 H), 7.55–7.50 (m, 2 H), 7.39–7.33 (m, 2 H), 7.30 (d, J = 8.2 Hz, 2
H), 5.04 (dd, J = 6.0, 3.6 Hz, 1 H), 4.83 (dd, J = 6.0, 3.6 Hz, 1 H),
4.62 (d, J = 3.6 Hz, 1 H), 4.14 (d, J = 10.7 Hz, 1 H), 3.62 (dd,
J = 10.7, 3.6 Hz, 1 H), 2.41 (s, 3 H), 1.32 (s, 3 H), 1.26 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.4, 152.3, 143.5, 139.2, 139.1,
131.9, 129.4, 128.4, 127.7, 126.0, 125.6, 119.5, 116.6, 112.3, 81.1,
80.3, 79.2, 72.7, 26.1, 24.8, 21.7.
20
IR (KBr): 3020, 2933, 1635, 1561, 1375, 1216, 1158, 1086, 1028,
968, 909 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.3 Hz, 2 H), 7.87 (s,
1 H), 7.56–7.52 (m, 2 H), 7.41 (d, J = 8.2 Hz, 1 H), 7.36–7.27 (m, 3
H), 5.07–5.02 (m, 3 H), 4.61 (d, J = 5.3 Hz, 1 H), 3.34 (s, 3 H), 2.41
(s, 3 H), 1.29 (s, 3 H), 1.24 (s, 3 H).
HRMS (ESI): m/z calcd for C23H23NO6S: 442.1324; found:
442.1329.
13C NMR (100 MHz, CDCl3): δ = 156.3, 152.3, 143.4, 139.0, 131.9,
129.9, 129.4, 128.4, 127.6, 125.9, 125.6, 119.5, 116.7, 112.7, 107.0,
84.9, 79.7, 55.0, 26.2, 24.9, 21.8.
N-{3-[(3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyltetrahydro-
furo[2,3-d][1,3]dioxol-5-yl]-2H-chromen-2-ylidene}-4-tolylsul-
fonamide (18)
By following the general procedure, the multicomponent reaction of
alkyne 9 (50 mg, 0.18 mmol) gave a white solid; yield: 91 mg
(91%); mp 108–109 °C; Rf = 0.63 (EtOAc–hexanes, 1:1); [α]D
HRMS (ESI): m/z calcd for C24H25NO7S: 472.1430; found:
472.1433.
20
−74.8 (c 0.9, CHCl3).
N-{3-[(3aS,4R,6R,6aR)-6-({[tert-Butyl(dimethyl)silyl]oxy}meth-
yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2H-
chromen-2-ylidene}-4-tolylsulfonamide (15)
IR (KBr): 3020, 2928, 1629, 1564, 1216, 1159, 1086, 1020, 909
cm–1.
By following the general procedure, the multicomponent reaction of
alkyne 6 (30 mg, 0.096 mmol) gave a low-melting solid; yield: 42
1H NMR (400 MHz, CDCl3): δ = 7.97–7.95 (m, 3 H), 7.55 (td,
J = 7.5, 1.4 Hz, 1 H), 7.48 (dd, J = 7.5, 1.4 Hz, 1 H), 7.43 (d, J = 7.5
Hz, 1 H), 7.33 (td, J = 7.5, 1.4 Hz, 1 H), 7.25 (d, J = 7.5 Hz, 2 H),
7.12 (m, 3 H), 6.95 (m, 2 H), 6.03 (d, J = 3.7 Hz, 1 H), 5.27 (dd,
J = 3.3, 1.4 Hz, 1 H), 4.60 (d, J = 3.7 Hz, 1 H), 4.53 (d, J = 3.3 Hz,
1 H), 4.44, 4.32 (ABq, JAB = 11.6 Hz, 2 H), 2.36 (s, 3 H), 1.53 (s, 3
H), 1.34 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.2, 152.3, 143.5, 139.4, 139.2,
137.3, 131.9, 129.5, 128.5, 128.5, 127.9, 127.6, 127.6, 126.0, 125.6,
119.4, 116.5, 112.6, 104.8, 83.4, 82.5, 78.2, 73.3, 27.3, 26.6, 21.7.
20
mg (75%); Rf = 0.74 (EtOAc–hexanes, 1:1); [α]D −27.8 (c 0.54,
CHCl3).
IR (CHCl3): 2929, 2857, 2102, 1636, 1564, 1457, 1381, 1324, 1259,
1216, 1161, 1088, 911, 838, 761, 671, 609 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.2 Hz, 2 H), 7.87 (s,
1 H), 7.54–7.49 (m, 2 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.34–7.21 (m, 3
H), 5.17 (d, J = 3.4 Hz, 1 H), 5.04 (dd, J = 5.9, 3.4 Hz, 1 H), 4.83
(d, J = 5.9 Hz, 1 H), 4.25 (t, J = 3.4 Hz, 1 H), 3.78 (dd, J = 10.9, 3.5
Hz, 1 H), 3.73 (dd, J = 10.9, 3.5 Hz, 1 H), 2.41 (s, 3 H), 1.28 (s, 3
H), 1.27 (s, 3 H), 0.84 (s, 9 H), 0.00 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 156.5, 152.3, 143.2, 139.5, 138.2,
131.6, 129.4, 128.3, 127.5, 127.2, 125.8, 119.6, 116.7, 112.4, 84.6,
83.2, 81.7, 79.7, 65.1, 26.4, 26.0, 25.0, 21.7, 18.3, –5.4, –5.5.
HRMS (ESI): m/z calcd for C30H29NO7S: 548.1743; found:
548.1739.
N-{3-[(3aR,5R,6R,6aR)-5-({[tert-Butyl(dimethyl)si-
lyl]oxy}methyl)-6-methoxy-2,2-dimethyltetrahydrofuro[2,3-
d][1,3]dioxol-6-yl]-2H-chromen-2-ylidene}-4-tolylsulfonamide
(19)
By following the general procedure, the multicomponent reaction of
alkyne 10 (50 mg, 0.15 mmol) gave a low-melting solid; yield: 50
mg (56%); Rf = 0.70 (EtOAc–hexanes, 1:1); [α]D20 −110.9 (c 0.61,
CHCl3).
HRMS (ESI): m/z calcd for C30H39NO7SSi: 586.2295; found:
586.2311.
N-{3-[(3aR,4R,6S,6aR)-6-Methoxy-2,2-dimethyltetrahydrofu-
ro[3,4-d][1,3]dioxol-4-yl]-2H-chromen-2-ylidene}-4-tolylsul-
fonamide (16)
By following the general procedure, the multicomponent reaction of
alkyne 7 (50 mg, 0.25 mmol) gave a white solid; yield: 98 mg
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1841–1848

1846
K. Palanichamy et al.
SPECIAL TOPIC
IR (CHCl3): 2929, 1628, 1574, 1455, 1375, 1321, 1259, 1216, 1159,
1089, 1019, 911, 838, 759, 671, 623 cm–1.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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1H NMR (400 MHz, CDCl3): δ = 7.97 (s, 1 H), 7.94 (d, J = 8.2 Hz,
2 H), 7.58 (td, J = 7.7, 1.3 Hz, 1 H), 7.52 (dd, J = 7.7, 1.3 Hz, 1 H),
7.46 (d, J = 7.7 Hz, 1 H), 7.35 (td, J = 7.7, 1.3 Hz, 1 H), 7.31 (d,
J = 8.2 Hz, 2 H), 5.71 (d, J = 3.9 Hz, 1 H), 5.27 (d, J = 3.9 Hz, 1 H),
4.17 (t, J = 4.9 Hz, 1 H), 3.56 (dd, J = 11.6, 4.9 Hz, 1 H), 3.43 (dd,
J = 11.6, 4.9 Hz, 1 H), 3.30 (s, 3 H), 2.41 (s, 3 H), 1.56 (s, 3 H), 1.24
(s, 3 H), 0.71 (s, 9 H), –0.12 (s, 3 H), –0.19 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.5, 152.4, 143.6, 142.8, 139.1,
132.7, 129.6, 128.6, 127.3, 126.0, 125.7, 119.2, 116.5, 111.8, 106.5,
87.8, 83.8, 81.4, 61.6, 53.9, 26.8, 26.5, 25.9, 21.8, 18.4, –5.4, –5.4.
References
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616.2405.
N-(3-{(3aR,5R,6R,6aR)-5-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-
yl]-6-methoxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-
yl}-2H-chromen-2-ylidene)-4-tolylsulfonamide (20)
By following the general procedure, the multicomponent reaction of
alkyne 11 (50 mg, 0.17 mmol) gave a low-melting solid; yield: 49
20
mg (51%); Rf = 0.53 (EtOAc–hexanes, 1:1); [α]D −97.4 (c 0.32,
CHCl3).
IR (CHCl3): 3366, 2926, 2854, 2104, 1561, 1455, 1216, 1160, 1089,
1018, 911, 853, 760, 669 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.21 (s, 1 H), 7.93 (d, J = 8.3 Hz,
2 H), 7.61 (td, J = 7.7, 1.3 Hz, 1 H), 7.57 (dd, J = 7.7, 1.3 Hz, 1 H),
7.49 (d, J = 7.7 Hz, 1 H), 7.37 (td, J = 7.7, 1.3 Hz, 1 H), 7.32 (d,
J = 8.3 Hz, 2 H), 5.63 (d, J = 3.8 Hz, 1 H), 5.32 (d, J = 3.8 Hz, 1 H),
4.06 (d, J = 8.4 Hz, 1 H), 3.82 (dd, J = 8.3, 6.8 Hz, 1 H), 3.72 (dd,
J = 8.3, 6.8 Hz, 1 H), 3.49 (dt, J = 8.4, 6.8 Hz, 1 H), 3.30 (s, 3 H),
2.41 (s, 3 H), 1.56 (s, 3 H), 1.39 (s, 3 H), 1.21 (s, 3 H), 1.10 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.5, 152.5, 145.2, 143.8, 139.0,
133.1, 129.9, 128.8, 127.3, 126.7, 126.1, 119.1, 116.6, 111.8, 109.6,
106.8, 89.0, 84.0, 81.1, 74.1, 68.1, 53.9, 26.8, 26.8, 26.3, 25.8, 21.8.
HRMS (ESI): m/z calcd for C29H33NO9S: 572.1954; found:
572.1971.
N-{3-[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-Tetramethyltetrahydro-
3aH-bis[1,3]dioxolo[4,5-b:4',5'-d]pyran-5-yl]-2H-chromen-2-
ylidene}-4-tolylsulfonamide (21)
By following the general procedure, the multicomponent reaction of
alkyne 12 (30 mg, 0.12 mmol) gave a white solid; yield: 42 mg
(68%); mp 92–93 °C; Rf = 0.60 (EtOAc–hexanes, 1:1); [α]D20 −9.5
(c 0.8, CHCl3).
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IR (KBr): 3020, 2990, 2926, 1633, 1560, 1457, 1383, 1318, 1255,
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1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.2 Hz, 2 H), 7.84 (s,
1 H), 7.54–7.51 (m, 2 H), 7.40 (d, J = 8.2 Hz, 1 H), 7.34–7.28 (m, 3
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528.1689.
Acknowledgment
K.P.K. thanks the DST for the award of the Swarnajayanti fellow-
ship. K.P. thanks CSIR, New Delhi, for a fellowship.
Synthesis 2012, 44, 1841–1848
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of 3-C-Linked Glycosyl Iminocoumarins
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© Georg Thieme Verlag Stuttgart · New York
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Synthesis 2012, 44, 1841–1848
© Georg Thieme Verlag Stuttgart · New York