Stereospecific synthesis of functionalized C5-unsaturated hydantoin derivatives via a three-component reaction

Article abstract of DOI:10.1055/s-2008-1066993

An effective route to functionalized C5-unsaturated hydantoin derivatives is described. This involves the reaction of a urea derivative, derived from the addition of a primary amine to an aryl-sulfonyl isocyanate, and a dialkyl acetylenedicarboxylate in the presence of isoquinoline. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1066993

PAPER
A
Stereospecific Synthesis of Functionalized C5-Unsaturated Hydantoin
Derivatives via a Three-Component Reaction
S
tereospecific Syn
b
thesis of Fun
d
ctionalized
H
o
ydantoin D
e
l
rivativ
a
es li Alizadeh,* Ehsan Sheikhi
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Fax +98(21)88006544; E-mail: abdol_alizad@yahoo.com; E-mail: aalizadeh@modares.ac.ir
Received 5 December 2007; revised 1 January 2008
R1
O
Abstract: An effective route to functionalized C5-unsaturated hy-
dantoin derivatives is described. This involves the reaction of a urea
derivative, derived from the addition of a primary amine to an aryl-
sulfonyl isocyanate, and a dialkyl acetylenedicarboxylate in the
presence of isoquinoline.
R3
SO2Ar
Ph3P
R3 NH2
N
N
+
+
Ar SO2NCO
r.t., CH2Cl2
CO2R2
O
R1
Key words: primary amine, arylsulfonyl isocyanate, dialkyl acet-
ylenedicarboxylate, hydantoin, isoquinoline, multicomponent reac-
tion
Scheme 1
sibility of trapping the 1:1 intermediate formed between
dialkyl acetylenedicarboxylate and isoquinoline with a
urea derivative appeared attractive from the viewpoint of
devising a novel MCR. In view of the success of the above
reaction, we explored the use of isoquinoline as the cata-
lyst in this reaction. In this paper, we present the results of
an extended investigation of the reactivity of the interme-
diate zwitterions with a urea derivative in dichlo-
romethane. To our surprise, the products of the two
reactions (Scheme 1 and Table 1) are geometrical isomers
(Figure 1).
Hydantoins (imidazolidine-2,4-diones), and their bi- and
tricyclic derivatives, represent an important class of bio-
logically active molecules that have broad medical1 (anti-
cancer, anticonvulsant, antimuscrinic, antiulcer, and
antiarrhytmic) and agrochemical2 (herbicidal and fungi-
cidal) application.
From the point of view of organic synthesis, hydantoins
have been frequently used as precursors of unnatural a-
amino acids.3,4
C5-Unsaturated hydantoins are important as biological
and pharmacological intermediates as precursors to C5-
substituted hydantoins and their subsequent a-amino
acids.5,6 Classic methods for the preparation of C5-substi-
tuted hydantoins are (i) base- and acid-catalyzed conden-
sations of 5-unsubstituted hydantoins with aldehydes and
unhindered or activated ketones5 and (ii) reactions of al-
dehydes, certain ketones, and a-dicarbonyl compounds in
the presence of a base with diethyl (2,5-dioxoimidazoli-
din-4-yl)phosphonates, which are obtained from 5-bro-
mohydantoin, triethyl phosphite, and acetic acid.6
Synthesis of C5 functionally substituted hydantoins, how-
ever, has been limited.6,7
O
O
Ar1
SO2Ar2
CO2R
R3
SO2Ar
H
N
N
N
N
O
O
R1
H
E-isomer
Z-isomer
Figure 1
Herein, we wish to report a simple one-pot reaction be-
tween a urea derivative, derived from the addition of a pri-
mary amine to an arylsulfonyl isocyanate, and a dialkyl
acetylenedicarboxylate in the presence of isoquinoline
leading to alkyl (E)-[1-alkyl-3-(arylsulfonyl)-2,5-dioxo-
imidazolidin-4-ylidene]acetate derivatives 4. The reaction
proceeds in dichloromethane at ambient temperature, and
produces hydantoin derivatives 4 in 80–90% yields
(Table 1).
We have recently reported a multicomponent reaction me-
diated by zwitterionic intermediates.8 Treatment of a pri-
mary amine, an arylsulfonyl isocyanate, and a dialkyl
acetylenedicarboxylate in the presence of triphenylphos-
phine in anhydrous dichloromethane at room temperature
leads to the formation of alkyl (E)-[1-alkyl-3-(arylsulfo-
nyl)-2,5-dioxoimidazolidin-4-ylidene]acetate derivatives
(Scheme 1).8
The structure of compounds 4a–g was deduced from their
elemental analysis and IR and high-field 1H and 13C NMR
spectra. The mass spectrum of 4a displayed a molecular
ion peak at m/z = 414, which was consistent with the 1:1:1
adduct of benzyl amine, tosyl isocyanate, and dimethyl
In the context of our ongoing studies on heterocyclic con-
struction mediated by zwitterionic intermediates, the pos-
1
acetylenedicarboxylate minus methanol. The H NMR
spectrum of 4a exhibited four single sharp lines readily
recognized as arising from methyl (d = 2.47), methoxy
(d = 3.87), and methylene (d = 4.61) protons along with a
vinylic CH (d = 7.01) and phenyl moieties, which give
SYNTHESIS 2008, No. x, pp 000A–000D
Advanced online publication: xx.xx.2008
DOI: 10.1055/s-2008-1066993; Art ID: Z28107SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
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B
A. Alizadeh, E. Sheikhi
PAPER
tic signals with appropriate chemical shifts and coupling
constants.
Table 1 Reaction of Primary Amines 1 with Arylsulfonyl Isocyan-
ates 2 and Dialkyl Acetylenedicarboxylates 3 in the Presence of Iso-
quinoline
Although we have not established the mechanism of the
reaction between dialkyl acetylenedicarboxylates 3 and
urea derivative 5, which derived from the addition of a
primary amine 1 to an arylsulfonyl isocyanate 2, in the
presence of isoquinoline in an experimental manner, a
possible explanation is proposed in Scheme 2. On the ba-
sis of the well-established chemistry of the isocyanates9–11
and isoquinoline as a nucleophile,12–16 it is reasonable to
assume that functionalized hydantoin 4 results from the
deprotonation and cyclization of intermediate 9, which
can be generated by two paths A or B. At first the reaction
between a primary amine and arylsulfonyl isocyanate
leads to the urea derivative 5, which is an NH-acid. Fol-
lowing path A, compound 5 is deprotonated by the iso-
quinoline and leads to intermediate 6, which reacts with
dialkyl acetylenedicarboxylate and generates intermedi-
ate 9. Following path B, the reactive 1:1 intermediate ob-
tained from the addition of isoquinoline to a dialkyl
acetylenedicarboxylate is trapped by an NH-acid such as
compound 5 to produce intermediate 8. Then, the posi-
tively charged ion 8 might be attacked by the conjugate
base of the NH-acid 6 to form intermediate 9, which in
turn is converted into intermediate 10 in the presence of
isoquinoline. Cyclization of the intermediate 10 leads to
compound 4 (Scheme 2).
O
Ar1
CO2R
SO2Ar2
isoquinoline
r.t., CH2Cl2
N
N
+
Ar2 SO2NCO +
Ar1CH2 NH2
CO2R
O
CO2R
1
2
3
4
Product Ar1
Ar2
R
Yield (%)
4a
4b
4c
4d
4e
4f
Ph
4-MeC6H4
4-MeC6H4
Ph
Me
Me
Me
Et
89
85
80
89
90
85
80
2-ClC6H4
2-ClC6H4
Ph
4-MeC6H4
4-MeC6H4
Ph
2-ClC6H4
Ph
Et
Et
4g
2-ClC6H4
Ph
Et
characteristic signals in the aromatic region of the spec-
trum. The 1H decoupled 13C NMR spectrum of 4a showed
14 distinct resonances in agreement with the methyl (1-
benzyl-2,5-dioxo-3-tosylimidazolidin-4-ylidene)acetate
structure.
The 1H and 13C NMR spectra of compounds 4b–g are sim-
ilar to those of 4a, except for the alkyl group of the esters
moiety and the aromatic rings, which exhibit characteris-
In summary, we have found a simple, efficient, and ste-
reospecific method for the preparation of stabilized hy-
dantoins. The present method has the advantages that, not
O
Ar1
SO2Ar2
+
1
2
N
H
N
H
5
3
5
Path A isoquinoline
Path B isoquinoline
O
Ar1
CO2R
SO2Ar2
+
N
N
N
NH
H
6
7
CO2R
3
5
O
Ar1
SO2Ar2
N OR
O
Ar1
CO2R
H
N
SO2Ar2
H
O
N
H
N
N
O
CO2R
OR
9
8
6
Ar1
O
isoquinoline
SO2Ar2
N OR
4
N
O
O
OR
10
Scheme 2
Synthesis 2008, No. x, A–D © Thieme Stuttgart · New York

PAPER
Stereospecific Synthesis of Functionalized Hydantoin Derivatives
C
MS: m/z (%) = 448 (1) [M+], 413 (68), 293 (6), 155 (98), 91 (100),
77 (6), 65 (26).
only is the reaction performed under neutral conditions,
but the substances can be mixed without any activation or
modification. The simplicity of the present procedure Anal. Calcd for C20H17ClN2O6S (448.87): C, 53.52; H, 3.82; N,
6.24. Found: C, 53.70; H, 3.90; N, 6.30.
makes it an interesting alternative to complex multistep
approaches.
Methyl (Z)-[1-(2-Chlorobenzyl)-2,5-dioxo-3-(phenylsulfo-
nyl)imidazolidin-4-ylidene]acetate (4c)
White crystals; yield: 0.35 g (80%); mp 156–159 °C.
Amines, arylsulfonyl isocyanates, and dialkyl acetylenedicarboxy-
lates were obtained from Merck (Germany) and Fluka (Switzer-
land) and were used without further purification. Melting points
were measured on an Electrothermal 9100 apparatus. Elemental
analyses for C, H, and N were performed using a Heraeus CHN-O-
Rapid analyzer. Mass spectra were recorded on a Finnigan-Matt
8430 mass spectrometer operating at an ionization potential of 20
eV. 1H and 13C NMR spectra were measured (CDCl3) with a Bruker
DRX-500 Avance spectrometer at 500.1 and 125.8 MHz, respec-
tively. IR spectra were recorded on a Shimadzu IR-460 spectropho-
tometer. Chromatography columns were prepared from Merck
silica gel 230–240 mesh.
IR (KBr): 1792 and 1732 (2 C=O, hydantoin), 1661 (CO2Me), 1573
(C=C), 1562 and 1463 (Ar), 1338 and 1170 (SO2), 1267 (C–O,
ester) cm–1.
1H NMR (500.13 MHz, CDCl3): d = 3.86 (s, 3 H, OMe), 4.77 (s, 2
3
H, CH2Ph), 7.06 (s, 1 H, C=CH), 7.10 (d, JHH = 7.3 Hz, 1 Harom),
7.17 (t, 3JHH = 7.2 Hz, 1 Harom), 7.22 (t, 3JHH = 7.5 Hz, 1 Harom), 7.32
(d, 3JHH = 7.7 Hz, 1 Harom), 7.61 (t, 3JHH = 7.55 Hz, 2 Harom), 7.75 (t,
3JHH = 7.29 Hz, 1 Harom), 8.02 (d, 3JHH = 7.67 Hz, 2 Harom).
13C NMR (125.7 MHz, CDCl3): d = 40.84 (CH2Ph), 52.87 (OMe),
111.70 (C=CH), 127.07 (CHarom), 128.34 (2 CHarom), 129.54
(CHarom), 129.57 (3 CHarom), 129.79 (Cipso-SO2), 129.83 (CHarom),
131.22 (Cipso-Cl), 133.27 (Cipso-CH2), 135.31 (CHarom), 137.24
(C=CH), 149.77 (NCON), 158.34 (NC=O), 164.50 (CO2Me).
Methyl (Z)-(1-Benzyl-2,5-dioxo-3-tosylimidazolidin-4-ylid-
ene)acetate (4a); Typical Procedure
To a soln of BnNH2 (0.11 g, 1 mmol) and TsNCO (0.18 g, 1 mmol)
in anhyd CH2Cl2 (5 mL) was magnetically stirred for 30 min and
then isoquinoline (0.13 g, 1 mmol) was added followed by the drop-
wise addition of a soln of DMAD (0.14 g, 1 mmol) in anhyd CH2Cl2
(3 mL) at r.t. over 10 min. The mixture was then allowed to stir for
2 h. The solvent was removed under reduced pressure, and the res-
idue was separated by column chromatography (silica gel, Merck
230–240 mesh, hexane–EtOAc) as a white powder; yield: 0.37 g
(89%); mp 149–150 °C.
MS: m/z (%) = 435 (1) [M+], 399 (92), 293 (7), 141 (58), 91 (7), 77
(100), 65 (11).
Anal. Calcd for C19H15ClN2O6S (434.85): C, 52.48; H, 3.48; N,
6.44. Found: C, 52.60; H, 3.55; N, 6.52.
Ethyl (Z)-(1-Benzyl-2,5-dioxo-3-tosylimidazolidin-4-ylid-
ene)acetate (4d)
White crystals; yield: 0.37 g (89%); mp 130–131 °C.
IR (KBr): 1790 and 1728 (2 C=O, hydantoin), 1659 (CO2Me), 1585
(C=C), 1580 and 1482 (Ar), 1326 and 1178 (SO2), 1255 (C–O,
ester) cm–1.
IR (KBr): 1796 and 1756 (2 C=O, hydantoin), 1701 (CO2Me), 1651
(C=C), 1555 and 1453 (Ar), 1325 and 1170 (SO2), 1257 (C–O,
ester) cm–1.
3
1H NMR (500.13 MHz, CDCl3): d = 1.35 (t, JHH = 7.1 Hz, 3 H,
1H NMR (500.13 MHz, CDCl3): d = 2.47 (s, 3 H, CH3), 3.87 (s, 3
H, OMe), 4.61 (s, 2 H, CH2Ph), 7.01 (s, 1 H, C=CH), 7.29 (5 Harom),
7.38 (d, 3JHH = 8.1 Hz, 2 Harom), 7.94 (d, 3JHH = 8.3 Hz, 2 Harom).
13C NMR (125.7 MHz, CDCl3): d = 21.78 (CH3), 43.10 (CH2Ph),
52.82 (OMe), 111.38 (C=CH), 128.36 (2 CHarom), 128.47 (CHarom),
128.83 (2 CHarom), 128.88 (2 CHarom), 129.99 (Cipso-SO2), 130.15 (2
CHarom), 134.15 (Cipso-CH2), 134.35 (C=CH), 146.75 (Cipso-CH3),
150.06 (NCON), 158.46 (NC=O), 164.64 (CO2Me).
3
OCH2CH3), 2.46 (s, 3 H, CH3), 4.34 (q, JHH = 7.1 Hz, 2 H,
OCH2CH3), 4.61 (s, 2 H, CH2Ph), 7.00 (s, 1 H, C=CH), 7.29 (5
Harom), 7.38 (d, JHH = 8.0 Hz, 2 Harom), 7.94 (d, JHH = 8.0 Hz, 2
arom).
13C NMR (125.7 MHz, CDCl3): d = 13.93 (OCH2CH3), 21.78
(CH3), 43.06 (CH2Ph), 62.10 (OCH2CH3), 111.86 (C=CH), 128.38
(2 CHarom), 128.44 (CHarom), 128.82 (2 CHarom), 128.90 (2 CHarom),
129.75 (Cipso-SO2), 130.14 (2 CHarom), 134.23 (Cipso-CH2), 134.38
(C=CH), 146.72 (Cipso-CH3), 150.11 (NCON), 158.45 (NC=O),
164.17 (CO2Me).
3
3
H
MS: m/z (%) = 414 (2) [M+], 383 (4), 259 (32), 155 (94), 121 (3),
104 (5), 91 (100), 77 (8), 65 (29).
Anal. Calcd for C20H18N2O6S (414.43): C, 57.96; H, 4.38; N, 6.76.
Found: C, 58.00; H, 4.31; N, 6.80.
MS: m/z (%) = 428 (2) [M+], 383 (7), 273 (20), 155 (86), 104 (6), 91
(100), 77 (6), 65 (25).
Anal. Calcd for C21H20N2O6S (428.45): C, 58.87; H, 4.70; N, 6.54.
Found: C, 58.95; H, 4.82; N, 6.70.
Methyl (Z)-[1-(2-Chlorobenzyl)-2,5-dioxo-3-tosylimidazolidin-
4-ylidene]acetate (4b)
White crystals; yield: 0.38 g (85%); mp 127–130 °C.
Ethyl (Z)-[1-(2-Chlorobenzyl)-2,5-dioxo-3-tosylimidazolidin-4-
ylidene]acetate (4e)
White crystals; yield: 0.42 g (90%); mp 144–146 °C.
IR (KBr): 1789 and 1727 (2 C=O, hydantoin), 1657 (CO2Me), 1585
(C=C), 1555 and 1433 (Ar), 1334 and 1172 (SO2), 1268 (C–O,
ester) cm–1.
IR (KBr): 1790 and 1728 (2 C=O, hydantoin), 1660 (CO2Me), 1585
(C=C), 1555 and 1453 (Ar), 1326 and 1178 (SO2), 1255 (C–O,
ester) cm–1.
1H NMR (500.13 MHz, CDCl3): d = 2.48 (s, 3 H, CH3), 3.86 (s, 3
H, OMe), 4.77 (s, 2 H, CH2Ph), 7.17 (s, 1 H, C=CH), 7.11 (d,
3
3JHH = 7.6 Hz, 1 Harom), 7.17 (t, JHH = 7.3 Hz, 1 Harom), 7.22 (t,
3
1H NMR (500.13 MHz, CDCl3): d = 1.34 (t, JHH = 7.1 Hz, 3 H,
3
3JHH = 7.6 Hz, 1 Harom), 7.33 (d, JHH = 7.9 Hz, 1 Harom), 7.39 (d,
3
3JHH = 8.3 Hz, 2 Harom), 7.95 (d, 3JHH = 8.3 Hz, 2 Harom).
OCH2CH3), 2.48 (s, 3 H, CH3), 4.34 (q, JHH = 7.1 Hz, 2 H,
OCH2CH3), 4.77 (s, 2 H, CH2Ph), 7.05 (s, 1 H, C=CH), 7.10 (d,
13C NMR (125.7 MHz, CDCl3): d = 21.79 (CH3), 40.77 (CH2Ph),
52.85 (OMe), 111.61 (C=CH), 127.05 (CHarom), 128.40 (2 CHarom),
3
3JHH = 7.4 Hz, 1 Harom), 7.17 (t, JHH = 7.4 Hz, 1 Harom), 7.22 (t,
3
3JHH = 7.7 Hz, 1 Harom), 7.33 (d, JHH = 7.8 Hz, 1 Harom), 7.39 (d,
129.49 (CHarom), 129.54 (CHarom), 129.82 (CHarom), 129.85 (Cipso
-
3JHH = 7.9 Hz, 2 Harom), 7.95 (d, 3JHH = 8.0 Hz, 2 Harom).
SO2), 130.17 (2 CHarom), 131.29 (Cipso-Cl), 133.29 (Cipso-CH2),
134.28 (C=CH), 146.82 (Cipso-CH3), 149.85 (NCON), 158.41
(NC=O), 164.58 (CO2Me).
13C NMR (125.7 MHz, CDCl3): d = 13.89 (OCH2CH3), 21.79
(CH3), 40.73 (CH2Ph), 62.19 (OCH2CH3), 112.12 (C=CH), 127.03
Synthesis 2008, No. x, A–D © Thieme Stuttgart · New York

D
A. Alizadeh, E. Sheikhi
PAPER
(CHarom), 128.42 (2 CHarom), 129.46 (CHarom), 129.51 (CHarom),
129.63 (Cipso-SO2), 129.81 (CHarom), 130.15 (2 CHarom), 131.34
(Cipso-Cl), 133.27 (Cipso-CH2), 134.34 (C=CH), 146.77 (Cipso-CH3),
149.89 (NCON), 158.39 (NC=O), 164.11 (CO2Me).
MS: m/z (%) = 447 (3) [M+], 413 (83), 417 (7), 407(4), 227(32), 141
(53), 77 (100), 65 (6).
Anal. Calcd for C20H17ClN2O6S (448.87): C, 53.52; H, 3.82; N,
6.24. Found: C, 53.60; H, 3.91; N, 6.35.
MS: m/z (%) = 462 (1) [M+], 427 (68), 417 (7), 307(6), 155 (96), 91
(100), 77 (6), 65 (24).
References
Anal. Calcd for C21H19ClN2O6S (462.90): C, 54.49; H, 4.14; N,
6.05. Found: C, 54.70; H, 4.21; N, 6.10.
(1) (a) Ware, E. Chem. Rev. 1950, 403. (b) Spinks, A.; Waring,
W. S. Prog. Med. Chem. 1963, 3, 313. (c) Brouillete, W. J.;
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(d) Nefazi Giulianotti, M.; Truong, L.; Rattan, S.; Ostresh, J.
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Ethyl (Z)-[1-Benzyl-2,5-dioxo-3-(phenylsulfonyl)imidazolidin-
4-ylidene]acetate (4f)
White crystals; yield: 0.35 g (85%); mp 119–121 °C.
IR (KBr): 1780 and 1736 (2 C=O, hydantoin), 1661 (CO2Me), 1585
(C=C), 1574 and 1463 (Ar), 1334 and 1167 (SO2), 1246 (C–O,
ester) cm–1.
3
1H NMR (500.13 MHz, CDCl3): d = 1.35 (t, JHH = 7.0 Hz, 3 H,
3
OCH2CH3), 4.35 (q, JHH = 7.0 Hz, 2 H, OCH2CH3), 4.61 (s, 2 H,
CH2Ph), 7.02 (s, 1 H, C=CH), 7.29 (5 Harom), 7.60 (t, 3JHH = 7.5 Hz,
3
3
2 Harom), 7.73 (t, JHH = 7.2 Hz, 1 Harom), 8.07 (d, JHH = 7.6 Hz, 2
Harom).
13C NMR (125.7 MHz, CDCl3): d = 13.91 (OCH2CH3), 43.11
(CH2Ph), 62.13 (OCH2CH3), 111.98 (C=CH), 128.34 (2 CHarom),
128.48 (CHarom), 128.83 (2 CHarom), 128.87 (2 CHarom), 129.53 (2
CHarom), 129.70 (Cipso-SO2), 134.17 (Cipso-CH2), 135.21 (CHarom),
137.38 (C=CH), 150.04 (NCON), 158.37 (NC=O), 164.08
(CO2Me).
(5) (a) Avendano, C.; Menendez, J. C. Kirk-Othmer
Encyclopedia of Chemical Technology, Vol. 13; Wiley-
Interscience: New York, 1995, 512. (b) Guella, G.;
Mancini, I.; Zibrowius, H.; Pietra, F. Helv. Chim. Acta 1988,
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MS: m/z (%) = 414 (3) [M+], 383 (1), 273 (57), 141 (73), 91 (83), 77
(100), 65 (11).
Anal. Calcd for C20H18N2O6S (414.43): C, 57.96; H, 4.38; N, 6.76.
Found: C, 58.00; H, 4.52; N, 6.80.
Ethyl (Z)-[1-(2-Chlorobenzyl)-2,5-dioxo-3-(phenylsulfonyl)imi-
dazol-4-ylidene]acetate (4g)
White crystals; yield: 0.33 g (80%); mp 144–146 °C.
(8) Alizadeh, A.; Sheikhi, E. Tetrahedron Lett. 2007, 48, 4887.
(9) Ulrich, H. Chem. Rev. 1962, 2, 186.
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2004, 45, 1803.
IR (KBr): 1783 and 1727 (2 C=O, hydantoin), 1716 (CO2Me), 1655
(C=C), 1556 and 1462 (Ar), 1323 and 1170 (SO2), 1257 (C–O,
ester) cm–1.
(11) Ozaki, Sh. Chem. Rev. 1972, 72, 457.
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Kennedy, V. O. J. Org. Chem. 1991, 56, 5893. (d) Garner,
P.; Ho, W. B.; Shin, C. J. Am. Chem. Soc. 1993, 115, 10742.
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(f) Fiswick, C. W. G.; Foster, R. J.; Carr, R. E. Tetrahedron
Lett. 1996, 37, 3915.
3
1H NMR (500.13 MHz, CDCl3): d = 1.34 (t, JHH = 7.1 Hz, 3 H,
3
OCH2CH3), 4.34 (q, JHH = 7.1 Hz, 2 H, OCH2CH3), 4.77 (s, 2 H,
CH2Ph), 7.06 (s, 1 H, C=CH), 7.10 (d, 3JHH = 7.4 Hz, 1 Harom), 7.17
(t, 3JHH = 7.4 Hz, 1 Harom), 7.22 (t, 3JHH = 7.7 Hz, 1 Harom), 7.33 (d,
3
3JHH = 7.8 Hz, 1 Harom), 7.61 (t, JHH = 7.7 Hz, 2 Harom), 7.75 (t,
3JHH = 7.3 Hz, 1 Harom), 8.08 (d, 3JHH = 7.8 Hz, 2 Harom).
13C NMR (125.7 MHz, CDCl3): d = 13.89 (OCH2CH3), 40.80
(CH2Ph), 62.18 (OCH2CH3), 112.21 (C=CH), 127.06 (CHarom),
128.37 (2 CHarom), 129.51 (CHarom), 129.56 (3 CHarom), 129.70 (Cip-
so-SO2), 129.82 (CHarom), 131.27 (Cipso-Cl), 133.27 (Cipso-CH2),
135.28 (CHarom), 137.29 (C=CH), 149.82 (NCON), 158.32
(NC=O), 164.04 (CO2Me).
(13) (a) Huisgen, R. Top. Heterocycl. Chem. 1969, 223.
(b) Huisgen, R. Z. Chem. 1968, 8, 290.
(14) Huisgen, R.; Morikawa, M.; Herbig, K.; Brunn, E. Chem.
Ber. 1967, 100, 1094.
(15) Nair, V.; Sreekanth, A. R.; Abhilash, N.; Bhadbhade, M. M.;
Gonnade, R. C. Org. Lett. 2002, 4, 3575.
(16) Nair, V.; Sreekanth, A. R.; Biju, A. T.; Nigam, P. R.
Tetrahedron Lett. 2003, 44, 729.
Synthesis 2008, No. x, A–D © Thieme Stuttgart · New York