2-Alkylidene-4-oxothiazolidine S-oxides: Synthesis and stereochemistry

Article abstract of DOI:10.1016/j.tet.2013.05.087

A series of 5-unsubstituted and 5-substituted 2-alkylidene-4- oxothiazolidine-S-oxides were synthesized by the sulfur-oxidation with m-CPBA. The stereochemistry of 5-substituted sulfoxides was determined by means of NMR spectroscopy and DFT theoretical ca

Full text of DOI:10.1016/j.tet.2013.05.087

Tetrahedron xxx (2013) 1e12
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
2-Alkylidene-4-oxothiazolidine S-oxides: synthesis
and stereochemistry
a
,
b
,
c
,
,
*
ꢀ
ꢁ a
Zdravko Dzambaski , Rade Markovic y, Erich Kleinpeter b
,
,c,
ꢁ a
*
Marija Baranac-Stojanovic
a Center for Chemistry ICTM, University of Belgrade, P.O. Box 473, 11000 Belgrade, Serbia
b
€
Chemisches Institut der Universitat Potsdam, Karl-Liebknecht Str. 24-25, D-14476 Potsdam (Golm), Germany
c Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 158, 11000 Belgrade, Serbia
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of 5-unsubstituted and 5-substituted 2-alkylidene-4-oxothiazolidine-S-oxides were synthesized
by the sulfur-oxidation with m-CPBA. The stereochemistry of 5-substituted sulfoxides was determined by
means of NMR spectroscopy and DFT theoretical calculations. It was found that the thermodynamically
less stable anti-isomer was initially formed in the course of the oxidation, but it underwent epimeri-
zation to the mixture enriched in the more stable syn-isomer, during the work-up process. The higher
Received 23 March 2013
Received in revised form 9 May 2013
Accepted 20 May 2013
Available online xxx
stability of syn-isomers is ascribed to the stronger hyperconjugative sCeH
weaker sCeC SeO delocalization in their anti-counterparts and to the existence of intramolecular 1,5-
CH/O hydrogen bonds.
/s*SeO interaction versus the
Keywords:
2-Alkylidene-4-oxothiazolidine
Sulfoxide
Diastereoselectivity
Density functional calculations
CH/O hydrogen bonds
/s*
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
In addition, sulfoxides are important synthetic intermediates and
can be employed for further functionalization of thiazolidines 1.
The 4-oxothiazolidine core is an important structural motif of
biologically active compounds.1 A wide range of pharmacological
activities, such as antibacterial,2 antiviral,3 anti-inflammatory,4
antifungal,5 analgesic,6 or anticancer7 have been reported. A sub-
class constitutes 4-oxothiazolidine derivatives possessing an exo-
cyclic double bond at the C-2 position of the ring, with some of
them registered as nontoxic, active substances in treatment of
neurological diseases (Ralitolinedan antiepileptic),8 liver diseases
(Piprozolineda choleretic), or for treatment of hypertension
(Etozolinda diuretic) (Fig. 1).
2. Results and discussion
The sulfoxide functional group is common in pharmaceutically
important compounds and many sulfoxides are known to have high
biological activity. Sulfur-oxidation of 4-oxothiazolidine ring may
result in more potent compounds.9 Having this in mind, we in-
The starting 4-oxothiazolidines 4 were prepared by the base-
catalyzed reaction of
a-mercapto esters 2 and a-substituted ni-
triles 3, as already described10 (Scheme 1). N-Alkylation was ach-
ieved with MeI, BnBr, Br(CH2)3Br or BrCH2CO2Et in moderate to
high yields (53e97%), under mild reaction conditions (Table 1 and
Scheme 1). After an initial screening of different agents, meta-
chloroperbenzoic acid (m-CPBA) was chosen for the oxidation step
(Table 2). When used in reagent/substrate 1.5e2/1 molar ratio,
sulfone formation was minimized11 and sulfoxides 5 were isolated
in good yields (65e95%, Table 1). All the products 1, 4 and 5 were
obtained exclusively as Z isomers, concerning the configuration
around the C]C double bond.12 5-Substituted substrates 1jer were
oxidized with moderate to good diastereoselectivity, as evidenced
vestigated the oxidation of
a
series of 2-alkylidene-4-
oxothiazolidines 1 into sulfoxides and analyzed the origin of dia-
stereoselectivity observed in the case of 5-substituted derivatives.
* Corresponding authors. Tel.: þ381113336740; fax: þ381112636061 (M.B.-S.); tel.:
þ49 331977 5210/5211; fax:þ49 331977 5064/5057 (E.K.); e-mail addresses: ekleinp@
ꢁ
uni-potsdam.de (E. Kleinpeter), mbaranac@chem.bg.ac.rs (M. Baranac-Stojanovic).
y
1946e2012.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.087
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2
Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
Fig. 1. Thiazolidine derivatives registered as drugs.
Scheme 1. Reagents and conditions: (i) K2CO3 cat., EtOH, reflux; (ii) MeI, BnBr, Br(CH2)3Br, or BrCH2CO2Et (1.1e1.5 equiv), K2CO3 (1 equiv), DMF, rt; (iii) m-CPBA (1.5e2 equiv),
CH2Cl2, 0 ꢀC.
Table 1
Yieldsa of N-alkylated products 1, sulfoxides 5, experimental and calculatedb syn/anti ratio for 5-substituted derivatives 5 and their relative free energy
R
R1
EWG
1 (%)
5 (%)
Ratio syn/anti
Relative free energy
exp (calcd)
(kcal/mol) syn/anti
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Bn
Bn
Bn
(CH2)3Br
CH2CO2Et
Me
Me
Me
Me
Bn
Bn
(CH2)3Br
Bn
CONHPh
CONH(CH2)2Ph
CO2Et
COPh
CONHPh
CO2Et
COPh
CO2Et
CO2Et
CONHPh
CONH(CH2)2Ph
CO2Et
COPh
CONHPh
CO2Et
CO2Et
CONHPh
COPh
1a (97)
1b (95)
1c (73)
1d (95)
1e (64)
1f (82)
1g (89)
1h (94)
1i (93)
1j (89)
1k (87)
1l (79)
1m (53)
1n (66)
1o (92)
1p (72)
1q (77)
1r (93)
5a (75)
5b (85)
5c (80)
5d (74)
5e (72)
5f (95)
5g (69)
5h (84)
5i (84)
5j (71)
5k (65)
5l (93)
5m (73)
5n (76)
5o (85)
5p (85)
5q (79)
5r (71)
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
85/15 (87/13)
86/14 (81/19)
86/14 (85/15)
85/15 (87/13)
87/13 (93/7)
86/14 (91/9)
87/13 (83/17)
79/21c (94/6)
77/23c (90/10)
0/1.15
0/0.87
0/1.01
0/1.13
0/1.58
0/1.41
0/0.93
0/1.60
0/1.27
CH2CO2Et
CH2CO2Et
Bn
a
Yields of isolated products.
At the B3LYP/6-31G* level, based on the relative free energy of diastereomers.
Not completely equilibrated.
b
c
from the NMR spectroscopic data of isolated products where two
sets of signals appeared, one prevailing. On the basis of 1H NMR
data, diastereomeric ratio was calculated to range from w79/21 for
5q,r to w87/13 for 5jep. It was necessary to identify whether the
syn or anti diastereomer was the major product.
Table 2
Screening of oxidizing agents
Having a sulfoxide in hand, it is often a challenge to determine
its configuration. Apart from an X-ray analysis requiring well-
defined single crystals, general and reliable methods for configu-
rational assignments are lacking. An assessment of stereochemistry
directly from NMR spectroscopic data is not possible since coupling
constants or NOE contacts with oxygen are inaccessible. Some re-
lations between chemical shifts of neighbouring hydrogen and
carbon atoms and the configuration of the sulfoxide group have
been observed,13 but are applicable only to specific cases. Although
magnetic anisotropy of the sulfoxide group has been predicted to
be acetylene-like,14 it is weak due to the single bond character of
the SO bond.15 Unfortunately, in the synthesized compounds 5jer
the 1H NMR chemical shift difference of C5eH and C5eCH3
Oxidant
Solvent
Temp (ꢀ)/Time (h)
Yielda
5c
6c
H2O2 (7.5 equiv)
H2O2 (7.5 equiv)
H2O2 (7.5 equiv)
NaIO4 (1.2 equiv)
Oxone (1.2 equiv)
m-CPBA (1.125 equiv)
CHCl3/MeOH 2/1 v/v
CHCl3/MeOH 2/1 v/v
CHCl3/MeOH 2/1 v/v
MeOH/H2O 3/1 v/v
MeOH/H2O 1/1 v/v
CH2Cl2
0/1
0
0
0
0
0
0
25/20
Reflux/6
25/72
0/1
21
27
80
0
19
1
0/1
a
Yields of isolated products.
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Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
3
ꢀ
ꢁ
between the two diastereomers is too small (0.1e0.3 ppm, Table 3)
to be of use for structure determination. In addition, all attempts to
obtain a single crystal suitable for an X-ray analysis resulted in
a mixture of isomers. So, we turned our attention to computational
methods, the use of which is now widespread among experimental
chemists to solve various stereochemical problems.16 Using quan-
tum chemical calculations it is possible to accurately predict NMR
chemical shifts,17 which then allows one to distinguish between
stereoisomers by comparing calculated and experimental values.
documented
g
-gauche effect. It has been suggested by Dracínsky
et al.16a,b to employ 13C NMR chemical shift changes (Dd) induced by
sulfur-oxidation as a means to differentiate between stereoisomeric
sulfoxides in which the sulfoxide group is contained in various five-
and six-membered rings. The corresponding experimental and
theoretically calculated values for the synthesized sulfoxides 5jer
are listed in Table 3 and they proved useful in the present case, as
well. These differences obviously arise from the above mentioned
steric and electric field effects and go in the following direction:
Table 3
Selected experimentala and calculatedb 1H NMR and 13C NMR chemical shifts, and the 13C NMR chemical shifts changes (Dd) induced by the oxidation
Compound
1H NMR (ppm)
13C NMR (ppm)
C5
Ddc (ppm)
C5
Exp CDCl3/DMSO-d6
C5eCH3
C5eCH3
C5eH
C5eCH3
Exp
Calcd
Exp
Calcd
Exp
Calcd
Exp
Calcd
5j
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
e/3.89
e/3.65
e/1.36
e/1.40
52.5
59.5
53.2
59.6
53.3
59.9
53.1
59.7
52.6
59.2
53.5
59.6
53.5
59.6
C5
57.1
63.0
56.9
65.5
57.4
63.5
57.0
62.9
58.0
63.1
58.4
63.5
57.1
63.2
6.6
11.7
6.8
12.4
6.7
12.3
6.9
12.4
6.6
11.7
6.7
12.4
6.6
12.2
C5eCH2
27.4
31.8
27.3
32.3
8.6
14.4
8.6
13.6
8.4
14.6
8.6
14.6
8.7
13.3
8.5
13.2
8.4
12.7
19.7
12.7
19.2
12.8
19.3
12.9
19.5
13.0
19.6
13.2
19.2
13.1
19.2
C5
12.5
18.3
12.3
20.9
12.3
18.4
12.4
18.3
13.7
18.8
13.7
18.7
12.4
18.5
ꢁ12.3
ꢁ7.2
ꢁ11.4
ꢁ5.5
5k
5l
3.31/3.82
3.50/3.56
3.42/3.95
3.63/3.74
3.44/3.98
3.67/3.78
e/4.11
1.57/1.33
1.49/1.35
1.63/1.36
1.56/1.44
1.65/1.38
1.59/1.48
e/1.42
ꢁ12.2
ꢁ6.6
ꢁ11.6
ꢁ6.6
ꢁ12.3
ꢁ6.7
ꢁ11.6
ꢁ5.4
5m
5n
5o
5p
ꢁ11.6
ꢁ6.2
ꢁ11.1
ꢁ5.1
ꢁ12.5
ꢁ7.4
ꢁ11.8
ꢁ7.2
e/3.80
e/1.46
3.48/4.16
3.71/3.90
3.39/e
3.63/e
C5eH
e/4.47
e/3.93
4.01/4.48
3.75/3.97
1.67/1.42
1.58/1.48
1.62/e
1.54/e
C5eCH2
e/2.94, 3.09
e/3.23, 3.54
3.23, 3.27/2.95; 3.10
3.41, 3.44/e
ꢁ12.6
ꢁ7.0
ꢁ12.0
ꢁ7.3
ꢁ12.4
ꢁ6.8
ꢁ11.6
ꢁ5.6
14.4
C5eCH2
ꢁ9.4
5q
5r
syn
anti
syn
anti
53.8
61.6
54.6
62.1
59.5
66.6
59.4
66.6
27.5
33.5
27.6
32.8
12.8
20.6
13.3
20.8
13.6
20.7
13.3
20.8
ꢁ12.8
ꢁ6.8
ꢁ4.9
ꢁ9.9
ꢁ12.5
ꢁ7.3
ꢁ5.0
a
Data are from DMSO-d6 solution for 5j, 5n and 5q, and from CDCl3 solution for all others.
At the B3LYP/6-31G* theory level, in the gas phase, relative to TMS.
Difference between chemical shift values of sulfoxides 5 and thiazolidines 1.
b
c
For this purpose the structures 5jer were optimized in the gas
paramagnetic shift for the
whereas diamagnetic shift for the
a
-carbon is higher for anti-isomers,
-carbon (CH3/CH2 group) is
phase at the B3LYP/6-31G* level.18 NMR chemical shifts were cal-
culated at the same level using the GIAO method19 and were
plotted against the experimental values (Fig. 2).20 An excellent
correlation gave evidence for reliable calculated structures and
allowed the stereochemistry determination: the major isomer
proved to be syn. The most diagnostic chemical shift values are
b
larger for syn-isomers. Interestingly, the C5eCH3 and C5eH signals
in the proton NMR spectra exchange their relative position upon
shifting from the non-polar solvent to the polar one. Thus, the
C5eCH3 (C5eH) protons of syn-isomers resonate at lower (higher)
field with respect to anti-isomers in chloroform solution, but at
higher (lower) field in DMSO solution (Table 3, Fig. S1 in the
Supplementary data).
those for carbon atoms at the a- (C5) and b-positions (C5eCH3),
which differ by w6 ppm between the two isomers (Table 3). A
diamagnetic shift observed for syn-isomers arises from steric and
electric field effects, in the case of the C5eCH3 being the well
Almost no change in the 13C NMR chemical shifts of the C2
atoms experimentally observed after the sulfur-oxidation (Table 4)
results from the two opposing effects: paramagnetic shift due to
the ꢁI effect of the sulfoxide group and diamagnetic shift coming
from the decrease in the pushepull effect of the C]C double bond.
This latter effect is the reason for the observed paramagnetic
movement of the C20 carbon resonances. The overall result is the
decrease in the 13C NMR chemical shift difference between the two
carbons of the double bond, DdC]C, in the oxidized products (Table
4). Namely, all thiazolidine derivatives 1aer and 5aer belong to the
class of the so-called pushepull alkenes, possessing one or two
electron-donating substituents at one end of the double bond and
one or two electron-accepting groups at the other. Electronic in-
teractions between the donor and acceptor groups via the C]C
double bond reduces its
p-bond order and strongly influences its
dynamic behaviour and chemical reactivity.
Among several parameters, such as the restricted rotation about
the partial C]C double bond,21 bond length22 and the occupation
quotient p*/p,
21d,23 this pushepull effect can also be quantified by
the 13C NMR chemical shift difference between the two carbons of
the double bond, which increase with increasing pushepull
Fig. 2. Computed 13C NMR chemical shifts against the experimental ones.
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Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
4
Table 4
Experimentala 13C NMR chemical shifts for the two carbons of the C]C double bond and their difference (DdC]C)
13C NMR (ppm)
13C NMR (ppm)
C2
C2
C20
DdC]
C20
DdC]
C
C
1a
1b
1c
1d
1e
1f
1g
1h
1i
155.3
152.9
158.6
161.8
154.5
158.6
160.6
157.6
157.3
153.5
93.7
93.6
90.7
95.7
94.4
90.3
97.0
90.6
90.7
93.5
61.6
59.3
67.9
66.1
60.1
68.3
63.6
67.0
66.6
60.0
5a
5b
5c
5d
5e
5f
5g
5h
5i
156.5
155.2
158.4
159.2
155.7
159.4
157.7
157.5
157.2
154.7
154.7
153.5
153.5
157.1
157.1
157.8
158.0
153.8
153.8
155.9
156.0
156.1
156.1
154.2
154.8
156.4
157.6
102.4
102.8
100.2
102.7
102.8
98.93
104.3
100.5
100.7
103.2
103.8
103.8
104.1
100.6
100.9
103.1
103.3
103.8
104.6
101.7
102.1
100.8
101.1
103.9
102.8
105.4
103.3
54.1
52.4
58.2
56.5
52.9
60.5
53.4
57.0
56.5
51.5
50.8
49.6
49.4
56.5
56.2
54.7
54.7
50.0
49.2
54.2
53.9
55.3
55.0
50.3
52.0
51.0
54.3
1j
5j
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
1k
1l
153.6
157.3
160.4
152.5
156.2
156.3
153.2
159.3
92.3
90.2
95.3
94.1
91.4
90.1
94.3
97.0
61.4
67.1
65.1
58.4
64.8
66.2
58.9
62.3
5k
5l
1m
1n
1o
1p
1q
1r
5m
5n
5o
5p
5q
5r
a
Data are from DMSO-d6 solution for 1a/5a, 1b/5b, 1e/5e, 1f/5f, 1j/5j, 1n/5n and 1q/5q, and from CDCl3 solution for all others.
character.21b,23a,24 The experimental chemical shifts for the C2 and
C20 atoms and their differences, DdC]C, for compounds 1aer and
5aer are given in Table 4. The observed decrease in the pushepull
activity results from the substitution of a good electron donor, the
sulfide, by a poor donor, the sulfoxide. The stabilization energies of
ratios are in good agreement and they point to a thermodynamic
control of the oxidation reactions. This was corroborated when the
oxidation of 1l was monitored by NMR spectroscopy in CDCl3, at
0 ꢀC: anti-5l was initially formed as the major product, as a result of
steric approach control (attack of the oxidizing agent from the less
hindered side) (Fig. S2 in the Supplementary data). The initial syn/
anti ratio of 28/72 did not change during the reaction time. How-
the sulfur lone pair conjugative interaction with the
p*-antibond-
ing orbital of the C]C double bond drastically decrease upon oxi-
dation. For example, this energy, obtained from the second order
perturbation theory analysis of Fock matrix in the NBO basis,25 for
1c amounts 24.4 kcal/mol, but only 0.7 kcal/mol for 5c. Though
ever, due to the facile isomerization of sulfoxides having an
a-
hydrogen,13b,27 the anti-5l underwent epimerization to the equi-
librium mixture (syn/anti 86/14, Table 1) during the work-up pro-
cess. In order to learn why syn-isomers are more stable than their
anti-counterparts donoreacceptor interactions and their stabiliza-
tion energies have been examined. The main difference in the
hyperconjugative interactions between the two isomers comes
significantly reduced, the sulfur lone pair n/p*C]C donation in
sulfoxides still exists and it has already been shown that the sulf-
oxide group can act as an electron donor.26 However, its net effect
on the double bond of compounds 5 is electron attraction: the
p-
electron density is attracted into the * SeO orbital, as evidenced
s
from the sC5eH
/s
*
SeO
existing in the syn-isomers (E2 values:
from the corresponding stabilization energy of 2.6 kcal/mol for 5c.
The reduction in the sulfur lone pair donation to the C]C double
bond is mainly caused by the presence of the electronegative ox-
ygen at the sulfur atom, but also by stereoelectronic factors: while
one of the sulfur’s lone pairs in compounds 1 is p-like and is in
1.42e1.6 kcal/mol; dihedral HeC5eSeO angles: from ꢁ161.2 to
ꢁ167.7ꢀ), but replaced by the weaker sC5eC5
/s*SeO interaction in
0
the anti-isomers (E2 values: 0.63e0.79 kcal/mol; dihedral
H3CeC5eSeO angles: from ꢁ109.5 to ꢁ158.2ꢀ) (Fig. 4 and Table 5).
plane with the
nificant nS/ *C]C delocalization, this is not the case for sulfoxides
with the sp3 hybridization of the sulfur (Fig. 3). The difference in
the DdC values between the syn- and anti-isomers is, however,
p* orbital of the double bond, which allows a sig-
p
]
C
too small and not regular to be of use for stereochemistry
determination.
The free energies, predicted at the same theory level employed
for the structure optimizations, favour syn-isomers by 0.9e1.6 kcal/
mol (Table 1). Experimentally observed and computed syn/anti
Fig. 3. Orbitals in the parent compounds 1 and sulfoxides 5.
Fig. 4. Hyperconjugative interactions in syn- and anti-sulfoxides 5.
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5
Table 5
3. Conclusion
Calculated dihedral angles and energies (E2)a of sCeH
interactions for syn- and anti-5, respectively
/s
*
and sCeC/s*
SeO SeO
A series of 5-unsubstituted and 5-substituted 2-alkylidene-4-
oxothiazolidine-S-oxides 5 were synthesized by the sulfur-oxida-
tion of the parent sulfides 1 with m-CPBA. The products were ob-
tained in good yields, 65e95%, and with moderate to good
diastereoselectivity in the case of 5-substituted derivatives (de
54e74%). The stereochemistry of 5-substituted products was elu-
cidated by means of NMR spectroscopy and theoretical calculations.
While the stereochemistry of the oxidation step is controlled by the
reagent (m-CPBA) approach from the less hindered side, the final
stereochemical outcome is governed by the relative stability of the
Compound
syn-isomer
anti-isomer
CeC5eSeO (ꢀ)
sHeC5eSeO (ꢀ)
sCeH
(kcal/mol)
/
s
*
s
sCeC/s*
SeO
(kcal/mol)
SeO
5j
5k
5l
5m
5n
5o
5p
5q
5r
ꢁ161.6
ꢁ161.2
ꢁ161.3
ꢁ161.4
ꢁ167.7
ꢁ167.4
ꢁ162.2
ꢁ163.4
ꢁ162.7
1.56
1.55
1.56
1.55
1.55
1.60
1.57
1.44
1.42
ꢁ145.1
ꢁ109.5
ꢁ141.4
ꢁ143.6
ꢁ158.2
ꢁ157.5
ꢁ144.1
ꢁ119.4
ꢁ113.3
0.67
d
0.63
0.65
0.79
0.79
0.67
d
isomers and is the result of the facile epimerization at the
a-carbon.
d
The greater stability of syn-isomers arises from intramolecular 1,5-
a
Obtained from the second order perturbation theory analysis of Fock matrix in
CH/O hydrogen bonding stabilization and stronger sCeH
hyperconjugative interaction versus the weaker sCeC
overlap in the anti-isomers.
/
s
*
*
SeO
SeO
the NBO basis.
/s
In addition, the syn-isomers are also preferred by the electro-
static effects, the so-called CH/O hydrogen bonds28 occurring
between the positively charged methyl/methylene hydrogens and
the negatively charged sulfoxide oxygen atom (Fig. 5; optimized
structures of syn-5l and syn-5q are shown). The calculated partial
charge of the hydrogen atom of syn-5l (0.20e; 1e¼1.602ꢂ10ꢁ19 C)
that interacts with the oxygen (ꢁ0.60e) is larger than the charges
4. Computational details
All calculations were done using Gaussian 03 program package.30
Geometries were optimized at the B3LYP/6-31G* level of theory,18
followed by frequency calculations to verify the nature of station-
ary points and to obtain thermochemical parameters. Magnetic
Fig. 5. Optimized structures (B3LYP/6-31G*) of syn-5l and syn-5q.
of the other hydrogen atoms (0.16 and 0.18e) and the H/O dis-
shieldings were computed at the same level using the GIAO
method.19 NMR chemical shifts were calculated relative to TMS.
Solvent effects on chemical shift values were modelled as IEF-PCM.31
ꢂ
tance of 2.56 A is shorter than the expected van der Waals sepa-
ꢂ
ration of 2.72 A. In the case of syn-5q the H/O distance is even
ꢂ
shorter and amounts 2.47 A. Here, another methylene hydrogen is
involved in hydrogen bonding with the carbonyl oxygen atom and
the calculated partial charges of the two H atoms are very similar
(0.224 and 0.215e, Fig. 5). Now, the above mentioned puzzling
reversal of position of the C5eCH3 signals in the 1H NMR spectra of
syn- and anti-isomers in the two solvents of different polarity
(Table 3) can be rationalized. Intramolecularly hydrogen bonded
CH3 in syn-isomers resonates at lower field in the chloroform so-
lution with respect to the CH3 in anti-isomers. In DMSO solution
the intermolecular hydrogen bonds formed between the CH3 and
the solvent molecules become stronger with the anti-isomers,
resulting in paramagnetic shift of their signals. The downfield
movement of proton chemical shift of hydrogen bonded CH pro-
tons has already been observed.28d,29 In the same manner, the 1H
NMR chemical shift position reversal observed for the C5eH sig-
nals can be accounted for by the formation of a hydrogen bond
between the C5eH and sulfoxide oxygen in the anti-isomers. This
hydrogen bond is weaker than that of the CH3 group (the CH/O
5. Experimental
5.1. General
Melting points were determined on a Stuart SMP10 apparatus.
The IR spectra were recorded on a PerkineElmer FT-IR 1725X
spectrophotometer and are reported as wave numbers (cmꢁ1). The
NMR spectra were recorded on a Varian Gemini 2000 spectrometer
(1H at 200 MHz, 13C at 50.3 MHz) and on a Bruker Ultrashield Ad-
vance III (1H at 500.26 MHz, 13C at 125.79 MHz) in DMSO-d6 or
CDCl3. Chemical shifts are given in parts per million downfield from
TMS as an internal standard. 13C NMR resonance assignments were
aided by the use of the DEPT technique to determine the number of
attached hydrogens. Elemental analyses were performed at the
microanalysis laboratory at the Centre for Chemistry ICTM. HRMS
was carried out on 6210 Time-of-Flight LC/MS (G1969A, Agilent
Technologies) coupled with 1200 Series HPLC system (Agilent
Technologies). Thin-layer chromatography (TLC) was carried out on
Kieselgel G nach Stahl and spots were visualized by iodine or by
50% H2SO4. Column chromatography was carried out on SiO2 (silica
ꢂ
distance for anti-5l amounts 2.64 A). Substituents attached at the
N3 and C20 positions do not affect the relative stability of isomers
and diastereoselectivity of the reaction.
ꢀ
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ꢀ
Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
6
ꢂ
gel 60 A, 12e26, ICN Biomedicals). All solvents were distilled before
(DMSO-d6, 200 MHz):
3H, NCH3), 3.85 (s, 2H, CH2S), 4.10 (q, J¼7.2 Hz, 2H, CH2O), 5.57 (s,1H,
]CH); 13C NMR (DMSO-d6, 50.3 MHz):
14.5 (CH3CH2), 29.9 (NCH3),
31.6 (CH2S), 59.4 (CH2O), 89.6(]CH),159.7 (C]),167.2 (COester),172.7
(COlactam); 1H NMR (CDCl3, 200 MHz):
1.30 (t, J¼7.2 Hz, 3H, CH3CH2),
3.17 (s, 3H, NCH3), 3.72 (s, 2H, CH2S), 4.22 (q, J¼7.2 Hz, 2H, CH2O), 5.49
(s, 1H, ]CH); 13C NMR (CDCl3, 50.3 MHz):
14.3 (CH3CH2), 29.9
(NCH3), 31.8 (CH2S), 60.0 (CH2O), 90.7 (]CH), 158.6 (C]), 167.6
(COester), 172.3 (COlactam); HRMS: calcd for C8H12NO3S [MþH]þ
202.0532, found 202.0525; Anal. Calcd for C8H11NO3S: C, 47.75; H,
5.51; N, 6.96; S, 15.93; found: C, 47.71; H, 5.40; N, 7.04; S, 16.12.
d
1.20 (t, J¼7.2 Hz, 3H, CH3CH2), 3.08 (s,
use. DMF was distilled over CaH2.
d
5.2. General procedure for the preparation of N-methyl de-
rivatives 1aed and 1jem
d
Methyl iodide (1.1e1.5 mmol) was added to a stirred mixture of
4-oxothiazolidine 4 (1 mmol) and K2CO3 (1 mmol) in DMF
(2e5 mL) and stirring was continued at rt until the disappearance
of the starting material (TLC). The products were precipitated by
pouring a threefold quantity of water onto the reaction mixture,
filtrated and air-dried. In the case of 1k and 1m the precipitate was
not suitable for filtration and the aqueous phase was extracted with
ethyl acetate (1k) or CH2Cl2 (1m) and the organic layer was washed
with water (3ꢂ8 mL), brine solution (1ꢂ8 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure and the
crude product was purified by column chromatography (gradient
toluene/ethyl acetate).
d
5.2.4. (Z)-(3-Methyl-4-oxothiazolidin-2-ylidene)-1-phenylethanone
(1d). Compound 1d was obtained from 4 (1.64 g; 7.50 mmol; R¼H,
EWG¼COPh), K2CO3 (1.04 g; 7.50 mmol), CH3I (1.17 g; 8.25 mmol;
1.1 equiv) in DMF (15 mL) according to the general procedure (re-
action time 1.5 h) as a pale yellow solid (1.67 g; 95%); mp
173e174 ꢀC; Rf¼0.39 (toluene/ethyl acetate 4/1); IR (ATR):
¼3062,
n
3032, 2974, 2921,1724,1614,1573,1513,1419,1345,1266,1206,1111,
5.2.1. (Z)-(3-Methyl-4-oxothiazolidin-2-ylidene)-N-phenylethanamide
(1a). Compound 1a was obtained from 4 (1.76 g; 7.50 mmol; R¼H,
EWG¼CONHPh), K2CO3 (1.04 g; 7.50 mmol), CH3I (1.60 g;
11.25 mmol; 1.5 equiv) in DMF (20 mL) according to the general
procedure (reaction time 2 h) as a white solid (1.80 g; 97%); mp
1053, 909, 888, 745, 697 cmꢁ1
3.25 (s, 3H, CH3), 3.85 (s, 2H, CH2S), 6.92 (s, 1H, ]CH), 7.47e7.63
(m, 3H, m- and p-Ph), 8.01e8.06 (m, 2H, o-Ph); 13C NMR (DMSO-d6,
50.3 MHz): 30.3 (CH3), 31.5 (CH2S), 95.5 (]CH), 127.7 (o-Ph),128.8
(m-Ph), 132.4 (p-Ph), 138.4 (C1ePh), 162.68 (C]), 172.2 (COlactam),
187.5 (COketone); 1H NMR (CDCl3, 200 MHz):
3.30 (s, 3H, CH3), 3.70
(s, 2H, CH2S), 6.68 (s, 1H, ]CH), 7.42e7.58 (m, 3H, m- and p-Ph),
7.92e7.97 (m, 2H, o-Ph); 13C NMR (CDCl3, 50.3 MHz):
30.2 (CH3),
;
1H NMR (DMSO-d6, 200 MHz):
d
d
205e208 ꢀC; Rf¼0.32 (toluene/ethyl acetate 3/2); IR (ATR):
n¼3544,
d
3457, 3296, 2964,1712,1649,1594,1560,1540,1489,1441,1344,1307,
1195, 1118, 795, 754, 690 cmꢁ1; 1H NMR (DMSO-d6, 200 MHz):
d
3.09
d
(s, 3H, CH3), 3.78 (s, 2H, CH2S), 5.79 (s,1H, ]CH), 6.70 (t, J¼7.3 Hz,1H,
p-Ph), 7.28 (m, 2H, m-Ph), 7.59 (d, J¼7.8 Hz, 2H, o-Ph), 9.90 (s, 1H,
NHamide), 11.53 (broad s, 1H, NHlactam); 13C NMR (DMSO-d6,
31.7 (CH2S), 95.7 (]CH), 127.5 (o-Ph), 128.5 (m-Ph), 132.2 (p-Ph),
138.3 (C1ePh), 161.8 (C]), 172.7 (COlactam), 188.6 (COketone); HRMS:
calcd for C12H12NO2S [MþH]þ 234.0583, found 234.0572; Anal.
Calcd for C12H11NO2S: C, 61.78; H, 4.75; N, 6.00; S, 13.74; found: C,
61.44; H, 4.75; N, 5.94; S, 14.01.
50.3 MHz): d 29.9 (CH3), 31.4 (CH2S), 93.7 (]CH), 118.8 (o-Ph), 122.9
(p-Ph), 129.0 (m-Ph), 140.0 (C1ePh), 155.3 (C]), 165.3 (COamide),
172.5 (COlactam); HRMS: calcd for C12H13N2O2S [MþH]þ 249.0692,
found 249.0696; Anal. Calcd for C12H12N2O2S: C, 58.05; H, 4.87; N,
11.28; S, 12.91; found: C, 58.01; H, 4.92; N, 10.98; S, 12.63.
5.2.5. (Z)-(3,5-Dimethyl-4-oxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (1j). Compound 1j was obtained from 4 (248 mg;
1.00 mmol; R¼Me, EWG¼CONHPh), K2CO3 (138 mg; 1.00 mmol),
CH3I (213 mg; 1.50 mmol; 1.5 equiv) in DMF (5 mL) according to the
general procedure (reaction time 2.5 h) as a white solid (0.234 g;
89%); mp 168e170 ꢀC; Rf¼0.30 (toluene/ethyl acetate 7/3); IR
5.2.2. (Z)-(3-Methyl-4-oxothiazolidin-2-ylidene)-N-(2-phenylethyl)
ethanamide (1b). Compound 1b was obtained from 4 (1.31 g;
5.00 mmol; R¼H, EWG¼CONH(CH2)2Ph), K2CO3 (0.69 g; 5.00 mmol),
CH3I (0.85 g; 6.00 mmol; 1.2 equiv) in DMF (15 mL) according to the
general procedure (reaction time 1.5 h) as a white solid (1.31 g; 95%);
(ATR):
n
¼3341, 1697, 1658, 1567, 1492, 1440, 1337, 1302, 1175, 1130,
1054, 761, 692 cmꢁ1
;
1H NMR (DMSO-d6, 200 MHz):
d
1.46 (d,
mp 177e179 ꢀC; Rf¼0.52 (toluene/acetone 7/3); IR (ATR):
n
¼3260,
J¼7.3 Hz, 3H, CH3CH), 3.11 (s, 3H, NCH3), 4.02 (q, J¼7.3 Hz, 1H, CHS),
5.80 (s, 1H, ]CH), 7.00 (t, J¼7.3 Hz, 1H, p-Ph), 7.28 (m, 2H, m-Ph),
7.59 (d, J¼7.2 Hz, 2H, o-Ph), 9.88 (s, 1H, NHamide); 13C NMR (DMSO-
3066, 2968, 2934,1712,1629,1569,1550,1451,1338,1286,1216,1121,
863, 803, 752, 701 cmꢁ1 1H NMR (DMSO-d6, 200 MHz):
; d 2.72 (t,
J¼7.3 Hz, 2H, CH2Ph), 3.02 (s, 3H, CH3), 3.28e3.38 (m, 2H, NCH2), 3.72
d6, 50,3 MHz): d 18.9 (CH3CH), 29.6 (NCH3), 39.8 (CHS), 93.5 (]CH),
(s, 2H, CH2S), 5.59 (s, 1H, ]CH), 7.16e7.34 (m, 5H, Ph), 7.84 (t,
118.7 (o-Ph), 122.8 (p-Ph), 128.9 (m-Ph), 139.9 (C1ePh), 153.5 (C]),
165.1 (COamide), 175.2 (COlactam); HRMS: calcd for C13H15N2O2S
[MþH]þ 263.0849, found 263.0855.
J¼5.6 Hz,1H, NHamide); 13C NMR (DMSO-d6, 50.3 MHz):
d 29.7 (CH3),
31.3 (CH2S), 35.6 (CH2Ph), 40.3 (NCH2), 93.6 (]CH), 126.3 (p-Ph),
128.6 (o-Ph), 128.8 (m-Ph), 139.8 (C1ePh), 152.9 (C]), 166.5 (COa-
mide), 172.4 (COlactam); 1H NMR (CDCl3, 200 MHz):
d
2.86 (t, J¼6.8 Hz,
5.2.6. (Z)-(3,5-Dimethyl-4-oxothiazolidin-2-ylidene)-N-(2-phenylethyl)
ethanamide (1k). Compound 1k was obtained from 4 (275 mg;
1.00 mmol; R¼Me, EWG¼CONH(CH2)2Ph), K2CO3 (138 mg;
1.00 mmol), CH3I (170 mg; 1.20 mmol; 1.2 equiv) in DMF (4 mL)
according to the general procedure (reaction time 1.5 h). Column
chromatography (eluent: gradient toluene/ethyl acetate 100/0 to 60/
40) gave pure 1k as a colourless oil (234 mg; 87%). Crystallization from
ethanol/water mixture 2/1 (v/v) gave a white solid, mp 87e89 ꢀC;
2H, CH2Ph), 3.11 (s, 3H, CH3), 3.55e3.66 (m, 2H, NCH2), 3.66 (s, 2H,
CH2S), 5.31 (s, 1H, ]CH), 5.42 (broad t, 1H, NHamide), 7.19e7.34 (m,
5H, Ph); 13C NMR (CDCl3, 50.3 MHz):
d 29.8 (CH3), 31.8 (CH2S), 35.8
(CH2Ph), 40.5 (NCH2), 92.7 (]CH), 126.5 (p-Ph), 128.6 (o-Ph), 128.8
(m-Ph), 139.0 (C1ePh), 155.2 (C]), 166.8 (COamide), 172.4 (COlactam);
HRMS: calcd for C14H17N2O2S [MþH]þ 277.1005, found 277.1005;
Anal. Calcd for C14H16N2O2S: C, 60.85; H, 5.84; N, 10.14; S, 11.60;
found: C, 61.15; H, 6.06; N, 10.13; S, 11.33.
Rf¼0.33 (toluene/ethyl acetate 3/2); IR (ATR):
2933, 1712, 1644, 1575, 1285, 1202, 1132, 1054, 794, 736, 702 cmꢁ1; 1H
NMR (DMSO-d6, 200 MHz):
n¼3313, 3058, 2979,
5.2.3. (Z)-Ethyl
(3-methyl-4-oxothiazolidin-2-ylidene)ethanoate
d
1.42 (d, J¼7.2 Hz, 3H, CH3CH), 2.72 (t,
(1c). Compound 1c was obtained from 4 (1.17 g; 6.25 mmol; R¼H,
EWG¼CO2Et), K2CO3 (0.86 g; 6.25 mmol), CH3I (0.98 g; 6.88 mmol;
1.1 equiv) in DMF (15 mL) according to the general procedure (re-
action time 1.5 h) as a white solid (0.94 g; 73%); mp 99e100 ꢀC;
J¼7.3 Hz, 2H, CH2Ph), 3.03 (s, 3H, NCH3), 3.28e3.38 (m, 2H, NCH2), 3.94
(q, J¼7.2 Hz, 1H, CHS), 5.59 (s, 1H, ]CH), 7.17e7.33 (m, 5H, Ph), 7.82 (t,
J¼5.6 Hz,1H, NH); 13C NMR (DMSO-d6, 50.3 MHz):
d 19.1 (CH3CH), 29.8
(NCH3), 35.6 (CH2Ph), 39.6 (NCH2), 40.2 (CHS), 93.4 (]CH), 126.3 (p-
Ph), 128.6 (o-Ph), 128.8 (m-Ph), 139.8 (C1ePh), 151.2 (C]), 166.4
Rf¼0.57 (toluene/ethyl acetate 7/3); IR (KBr): ¼2982, 2942, 1708,
n
1676, 1562, 1427, 1366, 1340, 1275, 1180, 1118, 805 cmꢁ1
;
1H NMR
(COamide), 175.2 (COlactam); 1H NMR (CDCl3, 200 MHz):
d 1.58 (d,
ꢀ
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Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
7
J¼7.1 Hz, 3H, CH3CH), 2.85 (t, J¼7.0 Hz, 2H, CH2Ph), 3.10 (s, 3H, NCH3),
3.53e3.63 (m, 2H, NCH2), 3.83 (q, J¼7.1 Hz,1H, CHS), 5.32 (s,1H, ]CH),
5.58 (broad t, 1H, NH), 7.18e7.36 (m, 5H, Ph); 13C NMR (CDCl3,
R¼H, EWG¼CO2Et), K2CO3 (138.2 mg; 1.00 mmol), benzyl bromide
(205.3 mg, 1.20 mmol) in DMF (5 mL) according to the general
procedure (reaction time 2.5 h). Column chromatography (eluent:
gradient toluene/ethyl acetate 100/0 to 85/15) gave pure 1f as
a white solid (227.4 mg; 82%); mp 89e91 ꢀC; Rf¼0.52 (toluene/ethyl
50,3 MHz):
d 19.0 (CH3CH), 29.9 (NCH3), 35.8 (CH2Ph), 40.2 (NCH2),
40.5 (CHS), 92.3 (]CH), 126.4 (p-Ph), 128.6 (o-Ph), 128.7 (m-Ph), 138.9
(C1ePh), 153.6 (C]),166.8 (COamide), 175.5 (COlactam); HRMS: calcd for
acetate 4/1); IR (KBr):
n
¼2981, 2930, 1718, 1681, 1560, 1289, 1159,
C
15H19N2O2S [MþH]þ 291.1162, found 291.1167.
1039, 967, 788, 691 cmꢁ1
;
1H NMR (DMSO-d6, 200 MHz):
d
1.15 (t,
J¼7.1 Hz, 3H, CH3), 4.01 (s, 2H, CH2S), 4.03 (q, J¼7.1 Hz, 2H, CH2O),
5.2.7. (Z)-Ethyl (3,5-dimethyl-4-oxothiazolidin-2-ylidene)ethanoate
(1l). Compound 1l was obtained from 4 (R¼Me, EWG¼CO2Et) as
already described.32
4.90 (s, 2H, CH2Ph), 5.47 (s, 1H, ]CH), 7.23e7.41 (m, 5H, Ph); 13C
NMR (DMSO-d6, 50.3 MHz): d 14.4 (CH3), 31.4 (CH2S), 45.8 (CH2Ph),
59.5 (CH2O), 90.3 (]CH), 126.9 (o-Ph), 127.8 (p-Ph), 128.9 (m-Ph),
135.2 (C1ePh), 158.6 (C]), 167.0 (COester), 173.1 (COlactam); 1H NMR
5.2.8. (Z)-(3,5-Dimethyl-4-oxothiazolidin-2-ylidene)-1-phenylethanone
(1m). Compound 1m was obtained from 4 (350 mg; 1.50 mmol; R¼H,
EWG¼COPh), K2CO3 (207 mg; 1.50 mmol), CH3I (245 mg; 1.725 mmol;
1.15 equiv) in DMF (6 mL) according to the general procedure (reaction
time 1.5 h). Column chromatography (eluent: gradient toluene/ethyl
acetate 100/0 to 80/20) gave pure 1m as a white solid (196 mg; 53%);
(CDCl3, 200 MHz):
4.15 (q, J¼7.3 Hz, 2H, CH2O), 4.88 (s, 2H, CH2Ph), 5.47 (s, 1H, ]CH),
7.20e7.36 (m, 5H, Ph); 13C NMR (CDCl3, 50.3 MHz):
14.3 (CH3),
31.6 (CH2S), 46.8 (CH2Ph), 60.0 (CH2O), 91.8 (]CH), 126.8 (o-Ph),
128.0 (p-Ph), 128.9 (m-Ph), 134.0 (C1ePh), 157.5 (C]), 167.6 (COes-
ter), 172.6 (COlactam); HRMS: calcd for C14H16NO3S [MþH]þ
278.0845, found 278.0854; Anal. Calcd for C14H15NO3S: C, 60.63; H,
5.45; N, 5.05; S, 11.56; found: C, 60.36; H, 5.42; N, 5.04; S, 11.65.
d
1.25 (t, J¼7.3 Hz, 3H, CH3), 3.81 (s, 2H, CH2S),
d
mp 130e132 ꢀC; Rf¼0.52 (toluene/ethyl acetate 4/1); IR (ATR):
¼3394,
n
3061, 2980, 2938,1711, 1624, 1516,1347,1224, 1052, 756, 704 cmꢁ1; 1H
NMR (DMSO-d6, 200 MHz):
d
1.49 (d, J¼7.2 Hz, 3H, CH3CH), 3.27 (s, 3H,
NCH3), 4.08 (q, J¼7.2 Hz,1H, CHS), 6.93 (s,1H, ]CH), 7.47e7.63 (m, 3H,
5.3.3. (Z)-(3-Benzyl-4-oxothiazolidin-2-ylidene)-1-phenylethanone
(1g). Compound 1g was obtained from 4 (328.9 mg; 1.50 mmol;
R¼H, EWG¼COPh), K2CO3 (207.4 mg; 1.50 mmol), benzyl bromide
(307.8 g, 1.80 mmol) in DMF (7 mL) according to the general pro-
cedure (reaction time 1 h). Column chromatography (eluent: gra-
dient toluene/ethyl acetate 100/0 to 90/10) gave pure 1g as a white
solid (412.3 mg; 89%); mp 169e170 ꢀC; Rf¼0.51 (toluene/ethyl ac-
m- and p-Ph), 8.01e8.06 (m, 2H, o-Ph); 13C NMR (DMSO-d6, 50.3 MHz):
d
18.4 (CH3CH), 30.5 (NCH3), 39.8 (CHS), 95.4 (]CH),127.7 (o-Ph),128.8
(m-Ph), 132.4 (p-Ph), 138.4 (C1ePh), 160.9 (C]), 176.1 (COlactam), 187.6
(COketone); 1H NMR (CDCl3, 200 MHz):
d
1.63 (d, J¼7.3 Hz, 3H, CH3CH),
3.31 (s, 3H, NCH3), 3.88 (q, J¼7.3 Hz, 1H, CHS), 6.67 (s, 1H, ]CH),
7.42e7.57 (m, 3H, m- and p-Ph), 7.92e7.98 (m, 2H, o-Ph); 13C
NMR (CDCl3, 50.3 MHz):
d
18.6 (CH3CH), 30.3 (NCH3), 40.2 (CHS), 95.3
etate 4/1); IR:
n
¼3059, 3031, 2968, 2930, 1708, 1633, 1575, 1515,
(]CH), 127.5 (o-Ph), 128.5 (m-Ph), 132.2 (p-Ph), 138.4 (C1ePh), 160.4
(C]), 176.0 (COlactam), 188.6 (COketone); HRMS: calcd for C13H14NO2S
[MþH]þ 248.0740, found 248.0746.
1348, 1216, 1176, 915, 883, 764, 695 cmꢁ1
;
1H NMR (DMSO-d6,
200 MHz): d 4.02 (s, 2H, CH2S), 5.11 (s, 2H, CH2Ph), 6.90 (s,1H, ]CH),
7.24e7.91 (m, 10H, 2ꢂ Ph); 13C NMR (DMSO-d6, 50.3 MHz):
d 31.4
(CH2S), 46.0 (CH2Ph), 96.1 (]CH), 127.3, 127.5, 127.8, 128.9, 128.9,
5.3. General procedure for the preparation of N-benzyl
derivatives 1eeg, 1n,o and 1q,r
132.4, 135.6, 138.8, 161.7 (C]), 173.7 (COlactam), 187.4 (COketone); 1H
NMR (CDCl3, 200 MHz): d 3.81 (s, 2H, CH2S), 5.01 (s, 2H, CH2Ph), 6.67
(s, 1H, ]CH), 7.26e7.79 (m, 10H, 2ꢂ Ph); 13C NMR (CDCl3,
Benzyl bromide (1.2 mmol) was added to a stirred mixture of
4-oxothiazolidine 4 (1 mmol) and K2CO3 (1e1.05 mmol) in DMF
(2e10 mL) and stirring was continued at rt until the disappearance
of the starting material (TLC). The reaction mixture was neutralized
with satd NH4Cl solution. The aqueous phase was extracted with
ethyl acetate (3ꢂ2e5 mL) and the organic layer was washed with
water (3ꢂ2e5 mL), brine solution (1ꢂ2e5 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure and the
crude product was purified by column chromatography (gradient
toluene/ethyl acetate).
50.3 MHz): d 31.6 (CH2S), 47.2 (CH2Ph), 97.0 (]CH), 126.9, 127.4,
128.2, 128.5, 129.1, 132.2, 134.2, 138.3, 160.6 (C]), 173.1 (COlactam),
188.6 (COketone); HRMS: calcd for C18H16NO2S [MþH]þ 310.0896,
found 310.0890; Anal. Calcd for C18H15NO2S: C, 69.88; H, 4.89; N,
4.53; S, 10.36; found: C, 70.15; H, 4.94; N, 4.40; S, 10.28.
5.3.4. (Z)-(3-Benzyl-5-methyl-4-oxothiazolidin-2-ylidene)-N-phe-
nylethanamide (1n). Compound 1n was obtained from 4 (124.2 mg;
0.50 mmol; R¼Me, EWG¼CONHPh), K2CO3 (69.1 mg; 0.50 mmol),
benzyl bromide (102.6 mg, 0.60 mmol) in DMF (5 mL) according to
general procedure (reaction time 2 h). Column chromatography
(eluent: gradient toluene/ethyl acetate 100/0 to 80/20) gave pure
1n as a white solid (111.6 mg; 66%); mp 166e167 ꢀC; Rf¼0.47 (tol-
5.3.1. (Z)-(3-Benzyl-4-oxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (1e). Compound was 1e obtained from 4 (234.3 mg;
1.00 mmol; R¼H, EWG¼CONHPh), K2CO3 (138.2 mg; 1.00 mmol),
benzyl bromide (205.3 mg, 1.20 mmol) in DMF (5 mL) according to
the general procedure (reaction time 2.5 h). Column chromatog-
raphy (eluent: gradient toluene/ethyl acetate 100/0 to 70/30) gave
pure 1e as a white solid (208.9 mg; 64%); mp 216e218 ꢀC; Rf¼0.64
uene/ethyl acetate 4/1); IR (ATR):
1717,1644,1560,1493,1440,1317,1159, 975, 731, 691 cmꢁ1; 1H NMR
(DMSO-d6, 200 MHz):
n
¼3291, 3056, 3030, 2976, 2932,
d
1.52 (d, J¼7.2 Hz, 3H, CH3CH), 4.17 (q,
J¼7.2 Hz, 1H, CHS), 4.86 (s, 2H, CH2Ph), 5.77 (s, 1H, ]CH), 6.98 (t,
J¼7.3 Hz, 1H, p-Ph), 7.22e7.43 (m, 7H, Ph), 7.53 (d, J¼7.8 Hz, 2H, o-
(toluene/ethyl acetate 3/2); IR:
n
¼3283, 3244, 3142, 1712, 1595,
Ph), 9.84 (s, 1H, NHamide); 13C NMR (DMSO-d6, 50.3 MHz):
d 19.1
1547, 1489, 1440, 1317, 1243, 1156, 861, 792, 752, 691 cmꢁ1; 1H NMR
(CH3), 39.5 (CHS), 46.2 (CH2Ph), 94.1 (]CH), 118.8, 122.9, 126.7,
127.7, 128.9, 135.1 (C1ePh), 139.6 (C1ePh), 152.6 (C]), 164.9 (COa-
mide), 175.8 (COlactam); HRMS: calcd for C19H19N2O2S [MþH]þ
339.1162, found 339.1157.
(DMSO-d6, 200 MHz): d 3.92 (s, 2H, CH2S), 4.85 (s, 2H, CH2Ph), 5.78
(s, 1H, ]CH), 6.95e7.56 (m, 10H, 2ꢂ Ph), 9.82 (s, 1H, NH); 13C NMR
(DMSO-d6, 50.3 MHz):
d 31.4 (CH2S), 46.3 (CH2Ph), 94.4 (]CH),
119.0, 123.0, 127.0, 127.9, 129.1, 135.2, 139.8, 154.5 (C]), 165.3
(COamide), 173.2 (COlactam); HRMS: calcd for C18H17N2O2S [MþH]þ
325.1005, found 325.1008; Anal. Calcd for C18H16N2O2S: C, 66.64; H,
4.97; N, 8.64; S, 9.88; found: C, 66.25; H, 5.07; N, 8.61; S, 9.72.
5.3.5. (Z)-Ethyl (3-benzyl-5-methyl-4-oxothiazolidin-2-ylidene)etha-
noate (1o). Compound 1o was obtained from
4 (150.9 mg;
0.75 mmol; R¼Me, EWG¼CO2Et), K2CO3 (103.6 mg; 0.75 mmol),
benzyl bromide (153.9 mg, 0.90 mmol) in DMF (6 mL) according to
the general procedure (reaction time 2.5 h). Column chromatog-
raphy (eluent: gradient toluene/ethyl acetate 100/0 to 90/10) gave
5.3.2. (Z)-Ethyl
(3-benzyl-4-oxothiazolidin-2-ylidene)ethanoate
(1f). Compound 1f was obtained from 4 (187.2 mg; 1.00 mmol;
ꢀ
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ꢀ
Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
8
pure 1o as a white solid (200.8 mg; 92%); mp 96e97 ꢀC; Rf¼0.48
5.5. (Z)-Ethyl (3-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)ethanoate (1i)
(toluene/ethyl acetate 9/1); IR (KBr):
n
¼3028, 2976, 2936, 1714,
1686, 1568, 1372, 1342, 1290, 1156, 1041, 969, 784, 693 cmꢁ1
;
1H
NMR (DMSO-d6, 200 MHz):
d
1.14 (t, J¼7.0 Hz, 3H, CH3CH2), 1.54 (d,
Compound 1i was obtained from 4 (187.2 mg; 1.00 mmol; R¼H,
EWG¼CO2Et), K2CO3 (145.1 mg; 1.05 mmol), ethyl 2-bromoacetate
(200.4 mg, 1.20 mmol, 0.14 mL) in DMF (2 mL) at rt (reaction time
1 h). The reaction mixture was then diluted with CHCl3 (3 mL) and
water (3 mL) was added. The organic layer was separated and the
water layer extracted with CHCl3 (3ꢂ2 mL). The chloroform extracts
were combined, washed with water (3ꢂ3 mL), brine (1ꢂ3 mL) and
dried over Na2SO4. The solvent was evaporated under reduced
pressure. Thus obtained product was stirred with n-hexane for 2 h
and filtered to give pure 1i as a white solid (111.6 mg; 93%); mp
J¼7.1 Hz, 3H, CH3CH), 4.03 (q, J¼7.0 Hz, 1H, CH2O), 4.27 (q, J¼7.1 Hz,
2H, CHS), 4.91 (s, 2H, CH2Ph), 5.86 (s, 1H, ]CH), 7.21e7.41 (m, 5H,
Ph); 13C NMR (DMSO-d6, 50.3 MHz):
d 14.4 (CH3CH2), 19.0 (CH3CH),
40.1 (CHS), 45.9 (CH2Ph), 59.5 (CH2O), 90.3 (]CH), 126.8 (o-Ph),
127.8 (p-Ph), 129.0 (m-Ph), 135.2 (C1ePh), 156.8 (C]), 166.9
(COester), 176.1 (COlactam); 1H NMR (CDCl3, 200 MHz):
d 1.24 (t,
J¼7.2 Hz, 3H, CH3CH2), 1.68 (d, J¼7.2 Hz, 3H, CH3CH), 4.00 (q,
J¼7.2 Hz, 1H, CHS), 4.15 (q, J¼7.2 Hz, 2H, CH2O), 4.85 (d, J¼15.8 Hz,
1H, CHAHBPh), 4.90 (d, J¼15.8 Hz, 1H, CHAHBPh), 5.44 (s, 1H, ]CH),
7.17e7.40 (m, 5H, Ph); 13C NMR (CDCl3, 50.3 MHz):
d
14.3 (CH3CH2),
103e104 ꢀC; Rf¼0.65 (toluene/ethyl acetate 7/3); IR (ATR):
n
¼2985,
19.3 (CH3CH), 40.4 (CHS), 46.8 (CH2Ph), 60.0 (CH2O), 91.4 (]CH),
126.7 (o-Ph), 127.9 (p-Ph), 128.9 (m-Ph), 134.2 (C1ePh), 156.2 (C]),
167.6 (COester), 175.9 (COlactam); HRMS: calcd for C15H18NO3S
[MþH]þ 292.1002, found 292.1001; Anal. Calcd for C15H17NO3S: C,
61.83; H, 5.88; N, 4.81; S, 11.01; found: C, 61.50; H, 5.64; N, 4.90;
S, 10.83.
1746, 1687, 1571, 1301, 1219, 1167, 1047, 1026, 976, 794 cmꢁ1 1H
;
NMR (CDCl3, 200 MHz):
d
1.19 (t, J¼7.2 Hz, 6H, 2ꢂ CH3), 3.79 (s, 2H,
CH2S), 4.20 (q, J¼7.2 Hz, 2H, CH2O), 4.24 (q, J¼7.2 Hz, 2H, CH2O),
4.40 (s, 2H, NCH2), 5.33 (s, 1H, ]CH); 13C NMR (CDCl3, 50.3 MHz):
d
14.0 (CH3), 14.3 (CH3), 31.4 (CH2S), 44.2 (NCH2), 60.1 (CH2O), 62.1
(CH2O), 90.7 (]CH), 157.3 (C]), 166.0 (COester), 167.3 (COester), 172.1
(COlactam); HRMS: calcd for C11H16NO5S [MþH]þ 274.0744, found
274.0735.
5.3.6. (Z)-(3-Benzyl-5-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)-N-phenylethanamide (1q). Compound 1q was obtained
from 4 (160.2 mg; 0.50 mmol; R¼CH2CO2Et, EWG¼CONHPh),
K2CO3 (69.1 mg; 0.50 mmol), benzyl bromide (102.6 mg,
0.60 mmol) in DMF (5 mL) according to the general procedure
(reaction time 2.5 h). Column chromatography (eluent: gradient
toluene/ethyl acetate 100/0 to 75/25) gave pure 1q as a white solid
(157.3 mg; 77%); Rf¼0.36 (toluene/ethyl acetate 4/1); mp
5.6. General procedure for the oxidation of thiazolidine
derivatives 1
A solution of m-CPBA (1.5e2.0 mmol) in CH2Cl2 was added
dropwise within 5 min to a solution of thiazolidine 1 (1.0 mmol)
in CH2Cl2 at 0 ꢀC. The mixture was stirred at 0 ꢀC for additional
30e60 min until the disappearance of the starting material (TLC).
After the addition of 10% aq Na2S2O3 (5e15 mL), the solution was
extracted with CH2Cl2 (3ꢂ2e5 mL). The combined organic
layers were washed with 10% K2CO3 (2ꢂ2e5 mL), water
(2ꢂ2e5 mL) and finally with brine (1ꢂ2e5 mL). The organic layer
was dried over Na2SO4 and solvent was removed under reduced
pressure. Thus obtained crude product was purified by column
chromatography.
209e211 ꢀC; IR (ATR):
n
¼3307, 3137, 2985, 2927, 1715, 1648, 1598,
1569, 1497, 1444, 1326, 1164, 1030, 765, 697 cmꢁ1; 1H NMR (DMSO-
d6, 200 MHz):
d
1.18 (t, J¼7.2 Hz, 3H, CH3), 3.02 (dd, JAB¼17.4 Hz,
JAX¼7.2 Hz, 1H, CHAHBCO2Et), 3.14 (dd, JAB¼17.4 Hz, JBX¼4.6 Hz, 1H,
CHAHBCO2Et), 4.11 (q, J¼7.2 Hz, 2H, CH2O), 4.42 (dd, JAX¼7.2 Hz,
JBX¼4.6 Hz,1H, CHXS), 4.87 (s, 2H, CH2Ph), 5.75 (s, 1H, ]CH), 6.98 (t,
J¼7.3 Hz, 1H, p-Ph), 7.22e7.43 (m, 7H, Ph), 7.53 (d, J¼7.8 Hz, 2H, o-
Ph), 9.82 (s, 1H, NHamide); 13C NMR (DMSO-d6, 50.3 MHz):
d 14.2
(CH3), 36.8 (CH2CO2Et), 40.9 (CHS), 46.5 (CH2Ph), 60.8 (CH2O), 94.3
(]CH), 118.8, 122.9, 126.9, 127.7, 128.9, 135.1, 139.7, 153.2 (C]),
165.0 (COamide), 170.3 (COester), 174.2 (COlactam); HRMS: calcd for
5.6.1. (Z)-(3-Methyl-1,4-dioxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (5a). Compound 5a was obtained from 1a (300 mg;
1.20 mmol; 18 mL CH2Cl2) and m-CPBA (428 mg; 2.48 mmol; 24 mL
CH2Cl2) according to the general procedure (reaction time 30 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 30/70) gave pure 5a as a white solid (248 mg; 75%);mp
228e231 ꢀC (decomposes); Rf¼0.39 (toluene/acetone 1/1); IR (KBr):
C
22H22N2NaO4S [MþNa]þ 433.1192, found 433.1177.
5.3.7. (Z)-(3-Benzyl-5-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)-1-phenylethanone (1r). Compound 1r was obtained from 4
(305.4 mg; 1.00 mmol; R¼CH2CO2Et, EWG¼COPh), K2CO3
(138.2 mg; 1.00 mmol), benzyl bromide (205.3 mg, 1.20 mmol) in
DMF (7 mL) according to the general procedure (reaction time 1 h).
Column chromatography (eluent: gradient toluene/ethyl acetate
100/0 to 80/20) gave pure 1r as a white solid (367.1 mg; 93%); mp
n
¼3303, 3263, 3198, 3097, 3054, 2931, 1711, 1677, 1625, 1552, 1493,
1439, 1339, 1108, 1041, 845, 771, 696 cmꢁ1 1H NMR (DMSO-d6,
200 MHz):
;
d
3.11 (s, 3H, CH3), 3.50 (d, J¼17.4 Hz, 1H, CHaHbS), 4.10
(d, J¼17.4 Hz, 1H, CHaHbS), 6.04 (s, 1H, ]CH), 7.08 (t, J¼7.3 Hz,1H, p-
105e106 ꢀC; Rf¼0.57 (toluene/ethyl acetate 4/1); IR:
¼3422, 3063,
n
Ph), 7.35 (m, 2H, m-Ph), 7.66 (d, J¼7.4 Hz, 2H, o-Ph), 10.35 (s, 1H,
2990, 1715, 1609, 1573, 1501, 1486, 1371, 1214, 1172, 915, 763,
NHamide); 13C NMR (DMSO-d6, 50.3 MHz):
d 29.3 (CH3), 52.1 (CH2S),
694 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
1.26 (t, J¼7.3 Hz, 3H, CH3),
102.6 (]CH), 119.3 (o-Ph), 123.8 (p-Ph), 129.2 (m-Ph), 139.2
(C1ePh), 156.8 (C]), 162.3 (COamide), 170.1 (COlactam); HRMS: calcd
for C12H13N2O3S [MþH]þ 265.0641, found 265.0637.
3.02 (dd, JAB¼14.4 Hz, JAX¼8.4 Hz, 1H, CHAHBCO2Et), 3.21 (dd,
JAB¼14.4 Hz, JBX¼4.0 Hz, 1H, CHAHBCO2Et), 4.19 (q, J¼7.3 Hz, 2H,
CH2O), 4.26 (dd, JAX¼8.4 Hz, JBX¼4.0 Hz, 1H, CHXS), 5.03 (s, 2H,
CH2Ph), 6.66 (s, 1H, ]CH), 7.26e7.78 (m, 10H, 2ꢂ Ph); 13C NMR
5.6.2. (Z)-(3-Methyl-1,4-dioxothiazolidin-2-ylidene)-N-(2-phenylethyl)
ethanamide (5b). Compound 5b was obtained from 1b (156 mg;
0.60 mmol; 15 mL CH2Cl2) and m-CPBA (214 mg; 0.90 mmol; 20 mL
CH2Cl2) according to the general procedure (reaction time 30 min).
Column chromatography (eluent: gradient toluene/acetone 100/0 to
30/70) gave pure 5b as a white solid (149 mg; 85%);mp 139e141 ꢀC
(CDCl3, 50.3 MHz):
d 14.1 (CH3), 37.2 (CH2CO2Et), 41.3 (CHS), 47.4
(CH2Ph), 61.4 (CH2O), 97.0 (]CH), 126.9, 127.4, 128.1, 128.5, 129.0,
132.2, 134.2, 138.3, 159.3 (C]), 169.7 (COester), 174.7 (COlactam), 186.6
(COketone); HRMS: calcd for C22H22NO4S [MþH]þ 396.1264, found
396.1272; Anal. Calcd for C22H21NO4S: C, 66.82; H, 5.35; N, 3.54; S,
8.11; found: C, 66.90; H, 5.46; N, 5.37; S, 8.30.
(decomposes); Rf¼0.27 (toluene/acetone 1/1); IR (KBr):
3239, 3072, 2934, 1724, 1652, 1605, 1286, 1124, 1040, 850, 705 cmꢁ1
1H NMR (DMSO-d6, 200 MHz):
3H, CH3), 3.36e3.46 (m, 3H, NCH2 and CHAHBS), 4.03 (d, J¼17.4 Hz,
1H, CHAHBS), 5.86 (s, 1H, ]CH), 7.17e7.35 (m, 5H, Ph), 8.33 (t,
n
¼3519, 3421,
;
5.4. Synthesis of N-bromoalkyl derivatives 1h and 1p
d
2.77 (t, J¼7.3 Hz, 2H, CH2Ph), 3.03 (s,
Compounds 1h and 1p were obtained as already described.33
ꢀ
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Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
9
J¼5.3 Hz, 1H, NHamide); 13C NMR (DMSO-d6, 50.3 MHz):
d
29.2 (CH3),
(COlactam); HRMS: calcd for C18H16N2NaO3S [MþNa]þ 363.0774,
35.3 (CH2Ph), NCH2 is covered by DMSO, 52.1 (CH2S), 102.8 (]CH),
126.4 (p-Ph), 128.7 (o-Ph), 128.9 (m-Ph), 139.6 (C1ePh), 155.2 (C]),
163.6 (COamide), 170.0 (COlactam); HRMS: calcd for C14H17N2O3S
[MþH]þ 293.0954, found 293.0960.
found 363.0775.
5.6.6. (Z)-Ethyl (3-benzyl-1,4-dioxothiazolidin-2-ylidene)ethanoate
(5f). Compound 5f was obtained from 1f (69.3 mg; 0.25 mmol;
3 mL CH2Cl2) and m-CPBA (76.0 mg; 0.35 mmol; 4 mL CH2Cl2)
according to the general procedure (reaction time 30 min). Column
chromatography (eluent: gradient toluene/acetone 100/0 to 80/20)
gave pure 5f as a white solid (69.6 mg; 95%);mp 128e129 ꢀC;
5.6.3. (Z)-Ethyl (3-methyl-1,4-dioxothiazolidin-2-ylidene)ethanoate
(5c). Compound 5c was obtained from 1c (151 mg; 0.75 mmol;
6 mL CH2Cl2) and m-CPBA (267 mg; 1.125 mmol; 10 mL CH2Cl2)
according to the general procedure (reaction time 60 min). Column
chromatography (eluent: gradient toluene/acetone 100/0 to 70/30)
gave pure 5c as a pale yellow solid (128 mg; 80%);mp 128e129 ꢀC;
Rf¼0.30 (toluene/acetone 4/1); IR (ATR):
1292, 1156, 1048, 834, 733, 698 cmꢁ1
200 MHz):
n
¼2985, 2933, 1706, 1616,
;
1H NMR (DMSO-d6,
d
1.20 (t, J¼7.1 Hz, 3H, CH3), 3.68 (d, J¼17.4 Hz, 1H,
Rf¼0.36 (toluene/acetone 7/3); IR (KBr):
1276, 1185, 1116, 1040, 847 cmꢁ1 1H NMR (DMSO-d6, 200 MHz):
1.25 (t, J¼7.1 Hz, 3H, CH3CH2), 3.09 (s, 3H, NCH3) 3.54 (d, J¼17.4 Hz,
1H, CHAHBS), 4.12 (d, J¼17.4 Hz, 1H, CHAHBS), 4.20 (q, J¼7.2 Hz, 2H,
CH2O), 5.87 (s, 1H, ]CH); 13C NMR (DMSO-d6, 50.3 MHz):
14.4
n
¼3046, 2924, 1711, 1619,
CHAHBS), 4.14 (q, J¼7.1 Hz, 2H, CH2O), 4.29 (d, J¼17.4 Hz, 1H,
CHAHBS), 4.93 (m, 2H, CH2Ph), 5.78 (s, 1H, ]CH), 7.25e7.40 (m, 5H,
;
d
Ph); 13C NMR (DMSO-d6, 50.3 MHz):
d 14.2 (CH3), 45.0 (CH2Ph), 52.1
(CH2S), 60.6 (CH2O), 98.9 (]CH), 127.0 (o-Ph), 127.9 (p-Ph), 128.9
(m-Ph), 134.5 (C1ePh), 159.4 (C]), 164.7 (COester), 170.9 (COlactam);
d
(CH3CH2), 29.4 (NCH3), 52.2 (CH2S), 60.6 (CH2O), 98.3 (]CH), 160.6
1H NMR (CDCl3, 200 MHz):
d
1.28 (t, J¼7.3 Hz, 3H, CH3), 3.65 (d,
(C]), 164.9 (COester), 170.3 (COlactam); 1H NMR (CDCl3, 200 MHz):
J¼17.5 Hz, 1H, CHAHBS), 3.89 (d, J¼17.5 Hz, 1H, CHAHBS), 4.23 (q,
J¼7.3 Hz, 2H, CH2O), 4.87 (m, 2H, CH2Ph), 5.66 (s, 1H, ]CH),
d
1.34 (t, J¼7.2 Hz, 3H, CH3CH2), 3.19 (s, 3H, NCH3) 3.60 (d, J¼17.7 Hz,
1H, CHAHBS), 3.86 (d, J¼17.7 Hz, 1H, CHAHBS), 4.31 (q, J¼7.2 Hz, 2H,
CH2O), 5.72 (s, 1H, ]CH); 13C NMR (CDCl3, 50.3 MHz):
14.0
7.19e7.36 (m, 5H, Ph); 13C NMR (CDCl3, 50.3 MHz):
d 14.0 (CH3),
d
46.4 (CH2Ph), 51.4 (CH2S), 61.3 (CH2O), 101.2 (]CH), 126.8 (o-Ph),
128.2 (p-Ph), 129.1 (m-Ph), 132.8 (C1ePh), 157.3 (C]), 164.5 (COes-
ter), 169.2 (COlactam); HRMS: calcd for C14H16NO4S [MþH]þ
294.0795, found 294.0786.
(CH3CH2), 29.4 (NCH3), 51.5 (CH2S), 61.3 (CH2O), 100.2 (]CH), 158.4
(C]), 164.6 (COester), 168.6 (COlactam); HRMS: calcd for C8H12NO4S
[MþH]þ 218.0418, found 218.0486; Anal. Calcd for C8H11NO4S: C,
44.23; H, 5.10; N, 6.45; S, 14.76; found: C, 44.33; H, 5.19; N, 6.43;
S, 14.48.
5.6.7. (Z)-(3-Benzyl-1,4-dioxothiazolidin-2-ylidene)-1-phenylethanone
(5g). Compound 5g was obtained from 1g (77.3 mg; 0.25 mmol;
3 mL CH2Cl2) and m-CPBA (76.3 mg; 0.375 mmol; 4 mL CH2Cl2)
according to the general procedure (reaction time 40 min). Column
chromatography (eluent: gradient toluene/acetone 100/0 to 90/10)
gave pure 5g as a yellow solid (55.8 mg; 69%);mp 173e175 ꢀC (de-
5.6.4. (Z)-(3-Methyl-1,4-dioxothiazolidin-2-ylidene)-1-phenylethanone
(5d). Compound 5d was obtained from 1d (175 mg; 0.75 mmol;
12 mL CH2Cl2) and m-CPBA (269 mg; 1.13 mmol; 20 mL CH2Cl2)
according to the general procedure (reaction time 40 min). Column
chromatography (eluent: gradient toluene/acetone 100/0 to 70/30)
gave pure 5d as a pale yellow solid (187 mg; 74%);mp 177e178 ꢀC
composes); Rf¼0.30 (toluene/acetone 4/1); IR (KBr):
2932, 1723, 1649, 1563, 1322, 1176, 1038, 1018, 892, 780, 740,
697 cmꢁ1 1H NMR (CDCl3, 200 MHz):
n¼3062, 3006,
(decomposes); Rf¼0.32 (toluene/acetone 4/1); IR (ATR):
3004, 2941, 1729, 1645, 1565, 1279, 1220, 1119, 1042, 907, 776,
697 cmꢁ1 1H NMR (DMSO-d6, 200 MHz):
3.35 (s, 3H, CH3), 3.56
(d, J¼17.4 Hz, 1H, CHaHbS), 4.17 (d, J¼17.4 Hz, 1H, CHaHbS), 7.09 (s, 1H,
]CH), 7.54e7.73 (m, 3H, m- and p-Ph), 8.13e8.17 (m, 2H, o-Ph); 13
NMR (DMSO-d6, 50.3 MHz): 29.8 (CH3), 51.9 (CH2S), 101.9 (]CH),
n¼3064,
;
d
3.71 (d, J¼17.5 Hz, 1H,
CHaHbS), 3.93 (d, J¼17.5 Hz, 1H, CHaHbS), 4.94 (d, J¼15.7 Hz, 1H,
;
d
CHaHbPh), 5.06 (d, J¼15.7 Hz, 1H, CHaHbPh), 6.75 (s, 1H, ]CH),
7.28e7.77 (m, 10H, 2ꢂ Ph); 13C NMR (CDCl3, 50.3 MHz):
d 46.9
C
(CH2Ph), 51.4 (CH2S), 104.3 (]CH), 127.0, 128.2, 128.5, 128.8, 129.3,
133.1, 133.5, 137.2, 157.7 (C]), 169.5 (COlactam), 187.6 (COketone);
HRMS: calcd for C18H16NO3S [MþH]þ 326.0845, found 326.0845;
Anal. Calcd for C18H15NO3S: C, 66.44; H, 4.65; N, 4.30; S, 9.85; found:
C, 66.12; H, 4.80; N, 4.28; S, 9.48.
d
128.6 and 129.1 (o- and m-Ph), 133.6 (p-Ph), 137.6 (C1ePh), 161.1
(C]), 170.6 (COlactam), 187.7 (COketone); 1H NMR (CDCl3, 200 MHz):
d
3.31 (s, 3H, CH3), 3.66 (d, J¼17.7 Hz, 1H, CHaHbS), 3.87 (d, J¼17.6 Hz,
1H, CHaHbS), 6.81 (s, 1H, ]CH), 7.48e7.68 (m, 3H, m- and p-Ph),
8.00e8.06 (m, 2H, o-Ph); 13C NMR (CDCl3, 50.3 MHz):
29.8 (CH3),
d
5.6.8. (Z)-Ethyl (3-(3-bromopropyl)-1,4-dioxothiazolidin-2-ylidene)
ethanoate (5h). Compound 5h was obtained from 1h (77.0 mg;
0.25 mmol; 3 mL CH2Cl2) and m-CPBA (89.2 mg; 0.375 mmol; 4 mL
CH2Cl2) according to the general procedure (reaction time 60 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 75/25) gave pure 5h as a colourless oil (67.7 mg; 84%); Rf¼0.47
51.4 (CH2S), 102.7 (]CH), 128.4 and 128.6 (o- and m-Ph), 133.6 (p-Ph),
137.3 (C1ePh), 159.2 (C]), 169.0 (COlactam), 187.6 (COketone) HRMS:
calcd for C12H12NO3S [MþH]þ 250.0532, found 250.0542; Anal. Calcd
for C12H11NO3S: C, 57.82; H, 4.45; N, 5.62; S, 12.86; found: C, 57.58; H,
4.53; N, 5.54; S, 12.41.
(toluene/acetone 7/3); IR (ATR):
n
¼2985, 1708, 1614, 1306, 1237,
5.6.5. (Z)-(3-Benzyl-1,4-dioxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (5e). Compound 5e was obtained from 1e (97.3 mg;
0.30 mmol; 4 mL CH2Cl2) and m-CPBA (107.1 mg; 0.45 mmol; 5 mL
CH2Cl2) according to the general procedure (reaction time 60 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 70/30) gave pure 5e as a white solid (73.1 mg; 72%);mp
142e144 ꢀC (decomposes); Rf¼0.33 (toluene/acetone 7/3); IR
1181, 1144, 1048, 836, 735 cmꢁ1; 1H NMR (CDCl3, 500 MHz):
d
1.35
(t, J¼7.2 Hz, 3H, CH3), 2.17e2.24 (m, 2H, CH2), 3.40e3.48 (m, 3H,
CH2Br), 3.61 (d, J¼18.0 Hz, 1H, CHAHBS), 3.80 (d, J¼18.0 Hz, 1H,
CHAHBS), 3.77e3.83 (m, 1H, NCHaHb), 3.87e3.93 (m, 1H, NCHaHb),
4.32 (q, J¼7.2 Hz, 2H, CH2O), 5.84 (s, 1H, ]CH); 13C NMR (CDCl3,
125.8 MHz):
d 14.1 (CH3), 28.8 (CH2CH2CH2), 29.5 (CH2Br), 41.8
(NCH2), 51.5 (CH2S), 61.5 (CH2O), 100.5 (]CH), 157.5 (C]), 164.6
(COester), 168.9 (COlactam); HRMS: calcd for C10H15BrNO4S [MþH]þ
323.9900, found 323.9901.
(ATR):
n
¼3036, 1722, 1671, 1613, 1548, 1311, 1495, 1446, 1164, 1018,
758, 696 cmꢁ1; 1H NMR (DMSO-d6, 500 MHz):
d
3.61 (d, J¼17.2 Hz,
1H, CHaHbS), 4.26 (d, J¼17.2 Hz, 1H, CHaHbS), 4.83 (d, J¼16.0 Hz, 1H,
CHaHbPh), 4.91 (d, J¼16.0 Hz, 1H, CHaHbPh), 6.00 (s, 1H, ]CH), 7.07
(t, J¼5.5 Hz, 1H, p-Ph), 7.30e7.40 (m, 7H, 2ꢂ Ph), 7.61 (d, J¼8.0 Hz,
2H, o-Ph), 10.25 (s, 1H, NHamide); 13C NMR (DMSO-d6, 125.8 MHz):
5.6.9. (Z)-Ethyl-(3-ethoxycarbonylmethyl-1,4-dioxothiazolidin-2-
ylidene)ethanoate (5i). Compound 5i was obtained from 1i
(82.0 mg; 0.30 mmol; 5 mL CH2Cl2) and m-CPBA (107.0 mg;
0.45 mmol; 6 mL CH2Cl2) according to the general procedure (re-
action time 40 min). Column chromatography (eluent: gradient
d
45.4 (CH2Ph), 51.7 (CH2S), 102.8 (]CH), 119.2, 123.6, 126.6, 127.6,
128.7, 128.8, 134.2, 138.8, 155.7 (C]), 161.9 (COamide), 170.4
ꢀ
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ꢀ
Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
10
toluene/acetone 100/0 to 80/20) gave pure 5i as a white solid
(73.0 mg; 84%);mp 87e89 ꢀC; Rf¼0.32 (toluene/acetone 4/1); IR
(CH3CH), 29.7 (NCH3), 35.4 (CH2Ph), 40.9 (NCH2), 53.2 (CHS), 103.8
(]CH), 126.5 (p-Ph), 128.6 and 128.7 (o- and m-Ph), 138.6
(C1ePh), 153.5 (C]), 163.6 (COamide), 171.7 (COlactam); anti-5k
(ATR):
n
¼3065, 2985, 2938, 1739, 1708, 1620, 1359, 1293, 1213, 1162,
1052, 971, 841 cmꢁ1; 1H NMR (CDCl3, 500 MHz):
d
1.30 (t, J¼7.2 Hz,
d 12.4 (CH3CH), 29.6 (NCH3), 35.4 (CH2Ph), 40.9 (NCH2), 59.6
3H, CH3), 1.34 (t, J¼7.2 Hz, 3H, CH3), 3.65 (d, J¼17.8 Hz, 1H, CHAHBS),
3.91 (d, J¼17.8 Hz,1H, CHAHBS), 4.25 (q, J¼7.2 Hz, 2H, CH2O), 4.31 (q,
J¼7.2 Hz, 2H, CH2O), 4.12 (d, J¼17.2 Hz, 1H, NCHaHb), 4.72 (d,
J¼17.2 Hz, 1H, NCHaHb), 5.58 (s, 1H, ]CH); 13C NMR (CDCl3,
(CHS), 104.1 (]CH), 126.5 (p-Ph), 128.6 and 128.7 (o- and m-Ph),
138.6 (C1ePh), 153.5 (C]), 163.6 (COamide), 171.7 (COlactam);
HRMS: calcd for
329.09304.
C
15H18N2NaO3S [MþNa]þ 329.0930, found
125.8 MHz):
d 13.9 (CH3), 14.0 (CH3), 44.0 (NCH2), 51.4 (CH2S), 61.5
(CH2O), 62.4 (CH2O), 100.7 (]CH), 157.2 (C]), 164.3 (COester), 165.5
(COester), 168.6 (COlactam); HRMS: calcd for C11H16NO6S [MþH]þ
290.0693, found 290.0696; Anal. Calcd for C11H15NO6S: C, 45.67; H,
5.23; N, 4.84; S, 11.08; found: C, 45.84; H, 5.11; N, 4.82; S, 10.77.
5.6.12. (Z)-Ethyl (3,5-dimethyl-1,4-dioxothiazolidin-2-ylidene)etha-
noate (5l). Compound 5l was obtained from 1l (150.7 mg;
0.70 mmol; 12 mL CH2Cl2) and m-CPBA (333.3 mg; 1.40 mmol;
10 mL CH2Cl2) according to the general procedure (reaction time
40 min). Column chromatography (eluent: gradient toluene/ace-
tone 100/0 to 80/20) gave pure 5l as a white solid (150.6 mg; 93%;
syn/anti 86/14);mp 97e99 ꢀC; Rf¼0.37 (toluene/acetone 4/1); IR
5.6.10. (Z)-(3,5-Dimethyl-1,4-dioxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (5j). Compound 5j was obtained from 1j (98.4 g;
0.375 mmol; 8 mL CH2Cl2) and m-CPBA (178.6 mg; 0.75 mmol; 6 mL
CH2Cl2) according to the general procedure (reaction time 60 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 60/40) gave pure 5j as a pale yellow solid (74.3 mg; 71%; syn/
anti 85/15);mp 204e207 ꢀC (decomposes); Rf¼0.42 and 0.47 (tol-
(KBr):
n
¼2983, 2937, 1705, 1614, 1262, 1183, 1131, 1056, 839, 732,
688 cmꢁ1; 1H NMR (DMSO-d6, 500 MHz): syn-5l
d
1.26 (t, J¼7.0 Hz,
3H, CH3CH2), 1.36 (d, J¼7.5 Hz, 3H, CH3CH), 3.10 (s, 3H,
NCH3), 3.95 (q, J¼7.5 Hz, 1H, CHS), 4.22 (q, J¼7.0 Hz, 2H, CH2O),
5.93 (s, 1H, ]CH); anti-5l
d
1.26 (t, J¼7.0 Hz, 3H, CH3CH2), 1.44 (d,
uene/acetone 3/2); IR (ATR):
1311, 1039, 820, 758, 697 cmꢁ1; 1H NMR (DMSO-d6, 500 MHz): syn-
5j
n
¼3330, 2914, 1722, 1673, 1606, 1538,
J¼7.5 Hz, 3H, CH3CH), 3.10 (s, 3H, NCH3), 3.74 (q, J¼7.5 Hz, 1H, CHS),
4.20 (q, J¼7.0 Hz, 2H, CH2O), 5.94 (s, 1H, ]CH); 13C NMR (DMSO-d6,
d
1.36 (d, J¼7.5 Hz, 3H, CH3CH), 3.12 (s, 3H, NCH3), 3.89 (q,
125.8 MHz): syn-5l d 6.6 (CH3CH), 14.1 (CH3CH2), 29.5 (NCH3), 52.5
J¼7.5 Hz, 1H, CHS), 6.11 (s, 1H, ]CH), 7.09 (t, J¼7.2 Hz, 1H, p-Ph),
(CHS), 60.4 (CH2O), 98.9 (]CH), 158.4 (C]), 164.6 (COester), 172.9
(COlactam); anti-5l 11.5 (CH3CH), 14.1 (CH3CH2), 29.5 (NCH3), 59.9
(CHS), 60.4 (CH2O), 99.3 (]CH), 158.6 (C]), 164.5 (COester), 172.1
(COlactam); 1H NMR (CDCl3, 500 MHz): syn-5l
7.35 (m, 2H, m-Ph), 7.66 (d, J¼8.0 Hz, 2H, o-Ph), 10.34 (s, 1H, NH);
d
anti-5j
d
1.40 (d, J¼8.0 Hz, 3H, CH3CH), 3.12 (s, 3H, NCH3), 3.65 (q,
J¼8.0 Hz, 1H, CHS), 6.13 (s, 1H, ]CH), 7.09 (t, J¼7.2 Hz, 1H, p-Ph),
7.35 (m, 2H, m-Ph), 7.66 (d, J¼8.0 Hz, 2H, o-Ph), 10.34 (s, 1H, NH);
d
1.35 (t, J¼7.1 Hz, 3H,
CH3CH2), 1.63 (d, J¼7.4 Hz, 3H, CH3CH), 3.18 (s, 3H, NCH3), 3.42 (q,
13C NMR (DMSO-d6, 125.8 MHz): syn-5j
d 6.6 (CH3CH), 29.4 (NCH3),
J¼7.4 Hz, 1H, CHS), 4.32 (q, J¼7.1 Hz, 2H, CH2O), 5.73 (s, 1H, ]CH);
52.5 (CHS), 103.2 (]CH), 119.1 (o-Ph), 123.6 (p-Ph), 128.9 (m-Ph),
138.9 (C1ePh), 154.7 (C]), 162.0 (COamide), 172.5 (COlactam); anti-5j
anti-5l
d
1.35 (t, J¼7.1 Hz, 3H, CH3CH2), 1.56 (d, J¼7.9 Hz, 3H,
CH3CH), 3.18 (s, 3H, NCH3), 3.63 (q, J¼7.9 Hz, 1H, CHS), 4.32 (q,
d
11.7 (CH3CH), 29.4 (NCH3), 59.5 (CHS), 103.8 (]CH), 119.1 (o-Ph),
J¼7.1 Hz, 2H, CH2O), 5.76 (s, 1H, ]CH); 13C NMR (CDCl3,
123.6 (p-Ph), 128.9 (m-Ph), 138.9 (C1ePh), 154.7 (C]), 162.0 (COa-
mide), 172.5 (COlactam); HRMS: calcd for C13H14N2NaO3S [MþNa]þ
301.0617, found 301.0624.
125.8 MHz): syn-5l d 6.7 (CH3CH), 14.1 (CH3CH2), 29.7 (NCH3), 53.3
(CHS), 61.3 (CH2O), 100.6 (]CH), 157.1 (C]), 164.6 (COester), 172.0
(COlactam); anti-5l 12.3 (CH3CH), 14.1 (CH3CH2), 29.8 (NCH3), 59.9
d
(CHS), 61.3 (CH2O), 100.9 (]CH), 157.1 (C]), 164.6 (COester), 172.0
(COlactam); HRMS: calcd for C9H14NO4S [MþH]þ 232.0638, found
232.0635.
5.6.11. (Z)-(3,5-Dimethyl-1,4-dioxothiazolidin-2-ylidene)-N-(2-
phenylethyl)ethanamide (5k). Compound 5k was obtained from 1k
(147.5 mg; 0.51 mmol; 8 mL CH2Cl2) and m-CPBA (241.8 mg;
1.01 mmol; 7 mL CH2Cl2) according to the general procedure
(reaction time 60 min). Column chromatography (eluent: gradient
toluene/acetone 100/0 to 60/40) gave pure 5k as a colourless oil
(100.8 mg; 65%; syn/anti 86/14); Rf¼0.28 (toluene/acetone 3/2); IR
5.6.13. (Z)-(3,5-Dimethyl-1,4-dioxothiazolidin-2-ylidene)-1-phenyle
thanone (5m). Compound 5m was obtained from 1m (74.2 mg;
0.30 mmol; 4 mL CH2Cl2) and m-CPBA (142.8 mg; 0.60 mmol; 7 mL
CH2Cl2) according to the general procedure (reaction time 45 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 75/25) gave pure 5m as a white solid (57.8 mg; 73%; syn/anti
85/15); mp 132e134 ꢀC (decomposes); Rf¼0.30 and 0.40 (toluene/
(ATR):
n
¼3299, 3066, 2937, 1721, 1660, 1610, 1288, 1046, 848, 735,
700 cmꢁ1
;
1H NMR (DMSO-d6, 500 MHz): syn-5k
d
1.33 (d,
J¼7.5 Hz, 3H, CH3), 2.79 (t, J¼7.3 Hz, 2H, CH2Ph), 3.04 (s, 1H,
NCH3), 3.40e3.46 (m, 2H, NCH2), 3.82 (q, J¼7.5 Hz, 1H, CHS), 5.93
(s, 1H, ]CH), 7.20e7.32 (m, 5H, Ph), 8.33 (t, J¼5.7 Hz, 1H, NH);
acetone 4/1); IR (ATR):
n
¼3065, 2915, 1729, 1644, 1558, 1348, 1224,
1038, 780, 702 cmꢁ1; 1H NMR (DMSO-d6, 500 MHz): syn-5m
d
1.38
anti-5k
d
1.35 (d, J¼7.5 Hz, 3H, CH3), 2.79 (t, J¼7.3 Hz, 2H, CH2Ph),
(d, J¼7.5 Hz, 3H, CH3), 3.27 (s, 1H, NCH3), 3.98 (q, J¼7.5 Hz, 1H, CHS),
7.15 (s, 1H, ]CH), 7.59 (m, 2H, m-Ph), 7.69 (t, J¼7.5 Hz, 1H, p-Ph),
3.04 (s, 1H, NCH3), 3.40e3.46 (m, 2H, NCH2), 3.56 (q, J¼7.5 Hz, 1H,
CHS), 5.96 (s, 1H, ]CH), 7.20e7.32 (m, 5H, Ph), 8.33 (t, J¼5.7 Hz,
8.16 (d, J¼8.2 Hz, 2H, o-Ph); anti-5m
d
1.48 (d, J¼7.7 Hz, 3H, CH3),
1H, NH); 13C NMR (DMSO-d6, 125.8 MHz): syn-5k
d
6.5 (CH3CH),
3.25 (s,1H, NCH3), 3.78 (q, J¼7.7 Hz,1H, CHS), 7.14 (s,1H, ]CH), 7.59
(m, 2H, m-Ph), 7.69 (t, J¼7.5 Hz, 1H, p-Ph), 8.16 (d, J¼8.2 Hz, 2H, o-
29.3 (NCH3), 35.0 (CH2Ph), 40.3 (NCH2), 52.5 (CHS), 103.4 (]CH),
126.2 (p-Ph), 128.4 and 128.6 (o- and m-Ph), 139.3 (C1ePh), 153.2
Ph); 13C NMR (DMSO-d6, 125.8 MHz): syn-5m
d 6.8 (CH3CH), 29.9
(C]), 163.3 (COamide), 172.4 (COlactam); anti-5k
d
11.7 (CH3CH),
(NCH3), 52.1 (CHS), 102.6 (]CH), 128.3 (o-Ph), 128.8 (m-Ph), 133.4
(p-Ph), 137.3 (C1ePh), 158.8 (C]), 173.3 (COlactam), 187.5 (COketone);
anti-5m d 11.5 (CH3CH), 29.9 (NCH3), 59.7 (CHS), 102.9 (]CH), 128.3
29.3 (NCH3), 40.0 (CH2Ph), 40.3 (NCH2), 59.3 (CHS), 104.1 (]CH),
126.5 (p-Ph), 128.6 and 128.7 (o- and m-Ph), 138.6 (C1ePh), 153.2
(C]), 163.6 (COamide), 172.4 (COlactam); 1H NMR (CDCl3, 500 MHz):
(o-Ph), 128.8 (m-Ph), 133.4 (p-Ph), 137.4 (C1ePh), 159.4 (C]), 172.2
syn-5k
d
1.57 (d, J¼7.5 Hz, 3H, CH3), 2.85 (t, J¼7.2 Hz, 2H, CH2Ph),
(COlactam), 187.5 (COketone); 1H NMR (CDCl3, 500 MHz): syn-5m
3.11 (s, 1H, NCH3), 3.31 (q, J¼7.5 Hz, 1H, CHS), 3.50e3.68 (m, 2H,
NCH2), 5.76 (s, 1H, ]CH), 6.54 (t, J¼5.7 Hz, 1H, NH), 7.18e7.30 (m,
d
1.65 (d, J¼7.5 Hz, 3H, CH3), 3.28 (s, 1H, NCH3), 3.44 (q, J¼7.5 Hz,1H,
CHS), 6.80 (s, 1H, ]CH), 7.51 (m, 2H, m-Ph), 7.61 (t, J¼7.2 Hz, 1H, p-
5H, Ph); anti-5k
d
1.49 (d, J¼7.5 Hz, 3H, CH3), 2.85 (t, J¼7.2 Hz, 2H,
Ph), 8.01 (d, J¼8.5 Hz, 2H, o-Ph); anti-5m
d
1.59 (d, J¼7.5 Hz,
CH2Ph), 3.11 (s, 1H, NCH3), 3.50 (q, J¼7.5 Hz, 1H, CHS), 3.50e3.68
3H, CH3), 3.30 (s, 1H, NCH3), 3.67 (q, J¼7.5 Hz, 1H, CHS), 6.84 (s,
1H, ]CH), 7.51 (m, 2H, m-Ph), 7.61 (t, J¼7.2 Hz, 1H, p-Ph), 8.01
(m, 2H, NCH2), 5.78 (s, 1H, ]CH), 6.54 (t, J¼5.7 Hz, 1H, NH),
7.18e7.30 (m, 5H, Ph); 13C NMR (CDCl3, 125.8 MHz): syn-5k
d
6.8
(d, J¼8.5 Hz, 2H, o-Ph); 13C NMR (CDCl3, 125.8 MHz): syn-5m
d 7.0
ꢀ
Please cite this article in press as: Dzambaski, Z.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.05.087

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Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
11
(CH3CH), 30.0 (NCH3), 53.1 (CHS), 103.1 (]CH), 128.3 and 128.8 (o-
and m-Ph), 133.5 (p-Ph), 137.5 (C1ePh), 157.8 (C]), 172.5 (COlactam),
(COlactam); HRMS: calcd for C15H18NO4S [MþH]þ 308.0951, found
308.0963.
187.6 (COketone); anti-5m
d 12.4 (CH3CH), 30.0 (NCH3), 59.7 (CHS),
103.3 (]CH), 128.3 and 128.8 (o- and m-Ph), 133.5 (p-Ph), 137.5
(C1ePh), 158.0 (C]), 172.3 (COlactam), 187.6 (COketone); HRMS: calcd
for C13H13NNaO3S [MþNa]þ 286.0508, found 286.0514.
5.6.16. (Z)-Ethyl (3-(3-bromopropyl)-5-methyl-1,4-dioxothiazolidin-
2-ylidene)ethanoate (5p). Compound 5p was obtained from 1p
(64.4 mg; 0.20 mmol; 4 mL CH2Cl2) and m-CPBA (95.1 mg;
0.40 mmol; 4 mL CH2Cl2) according to the general procedure (re-
action time 35 min). Column chromatography (eluent: gradient
toluene/acetone 100/0 to 85/15) gave pure 5p as a colourless oil
(57.5 mg; 85%; syn/anti 87/13); Rf¼0.39 (toluene/acetone 4/1); IR
5.6.14. (Z)-(3-Benzyl-5-methyl-1,4-dioxothiazolidin-2-ylidene)-N-
phenylethanamide (5n). Compound 5n was obtained from 1n
(67.7 mg; 0.20 mmol; 6 mL CH2Cl2) and m-CPBA (95.2 mg;
0.40 mmol; 5 mL CH2Cl2) according to the general procedure (re-
action time 30 min). Column chromatography (eluent: gradient
toluene/acetone 100/0 to 75/25) gave pure 5n as a colourless oil
(53.9 mg; 76%; syn/anti 87/13); Rf¼0.36 and 0.42 (toluene/acetone
(ATR):
n
¼2983, 2939, 1709, 1615, 1306, 1236, 1182, 1145, 1059,
838 cmꢁ1; 1H NMR (CDCl3, 500 MHz): syn-5p
CH3CH2), 1.62 (d, J¼7.0 Hz, 3H, CH3CH), 2.16e2.21 (m, 2H,
CH2CH2CH2), 3.39 (q, J¼7.0 Hz, 1H, CHS), 3.37e3.44 (m, 2H, CH2Br),
3.76e3.82 (m, 1H, NCHaHb), 3.85e3.91 (m, 1H, NCHaHb), 4.32 (q,
d
1.35 (t, J¼7.0 Hz, 3H,
7/3); IR (ATR):
1549, 1467, 1445, 1322, 1163, 1040, 1010, 735, 697 cmꢁ1
(DMSO-d6, 500 MHz): syn-5n
n
¼3300, 3198, 3173, 3060, 2931, 1726, 1671, 1613,
;
1H NMR
J¼7.0 Hz, 2H, CH2O), 5.85 (s,1H, ]CH); anti-5p 1.35 (t, J¼7.0 Hz, 3H,
d
d
1.42 (d, J¼7.5 Hz, 3H, CH3), 4.11 (q,
CH3CH2), 1.54 (d, J¼8.0 Hz, 3H, CH3CH), 2.16e2.21 (m, 2H,
CH2CH2CH2), 3.37e3.44 (m, 2H, CH2Br), 3.63 (q, J¼8.0 Hz, 1H, CHS),
3.76e3.82 (m, 1H, NCHaHb), 3.85e3.91 (m, 1H, NCHaHb), 4.32 (q,
J¼7.0 Hz, 2H, CH2O), 5.88 (s,1H, ]CH); 13C NMR (CDCl3,125.8 MHz):
J¼7.5 Hz, 1H, CHS), 4.84 (d, J¼16.5 Hz, 1H, CHAHBPh), 4.90 (d,
J¼16.5 Hz, 1H, CHAHBPh), 6.07 (s, 1H, ]CH), 7.06e7.62 (m, 10H, 2ꢂ
Ph), 10.28 (s, 1H, NH); anti-5n
d
1.46 (d, J¼8.0 Hz, 3H, CH3), 3.80 (q,
J¼8.0 Hz, 1H, CHS), 4.76 (d, J¼16.3 Hz, 1H, CHAHBPh), 4.96 (d,
syn-5p d 6.6 (CH3CH), 14.2 (CH3CH2), 28.9 (CH2CH2CH2), 29.5
J¼16.3 Hz, 1H, CHAHBPh), 6.12 (s, 1H, ]CH), 7.06e7.62 (m, 10H, 2ꢂ
(CH2Br), 41.9 (NCH2), 53.5 (CHS), 61.4 (CH2O), 100.8 (]CH), 156.1
(C]), 164.6 (COester), 172.3 (COlactam); anti-5p 12.2 (CH3CH), 14.2
Ph), 10.28 (s, 1H, NH); 13C NMR (DMSO-d6, 125.8 MHz): syn-5n
d
6.6
d
(CH3), 45.7 (CH2Ph), 52.6 (CHS), 103.8 (]CH), 119.3, 123.7, 126.6,
127.6, 128.8, 128.9, 134.2, 138.8, 153.8 (C]), 161.9 (COamide),
173.1 (COlactam); anti-5n d 11.7 (CH3), 45.7 (CH2Ph), 59.2 (CHS),104.6
(]CH), 119.2, 125.3, 126.7, 128.2, 134.2, 137.4, 153.8 (C]), 161.9
(COamide), 173.1 (COlactam); HRMS: calcd for C19H19N2O2S [MþH]þ
355.1116, found 355.1120.
(CH3CH2), 28.9 (CH2CH2CH2), 29.5 (CH2Br), 41.9 (NCH2), 59.6 (CHS),
61.4 (CH2O),101.1 (]CH),156.1 (C]),164.6 (COester),172.3 (COlactam);
HRMS: calcd for C11H17BrNO4S [MþNa]þ 338.0056, found 338.0041.
5.6.17. (Z)-(3-Benzyl-5-ethoxycarbonylmethyl-1,4-dioxothiazolidin-
2-ylidene)-N-phenylethanamide (5q). Compound 5q was obtained
from 1q (102.6 mg; 0.25 mmol; 5 mL CH2Cl2) and m-CPBA
(119.0 mg; 0.50 mmol; 8 mL CH2Cl2) according to the general
procedure (reaction time 45 min). Column chromatography (elu-
ent: gradient toluene/acetone 100/0 to 70/30) gave pure 5q as
a colourless oil (88.4 mg; 83%; syn/anti 79/21); Rf¼0.42 and 0.61
5.6.15. (Z)-Ethyl (3-benzyl-5-methyl-1,4-dioxothiazolidin-2-ylidene)
ethanoate (5o). Compound 5o was obtained from 1o (58.3 mg;
0.20 mmol; 3 mL CH2Cl2) and m-CPBA (81.2 mg; 0.40 mmol; 4 mL
CH2Cl2) according to the general procedure (reaction time 30 min).
Column chromatography (eluent: gradient toluene/acetone 100/
0 to 85/15) gave pure 5o as a colourless oil (52.3 mg; 85%; syn/anti
(toluene/acetone 7/3); IR (KBr):
1723, 1673, 1602, 1549, 1323, 1165, 1018, 839, 756, 695 cmꢁ1
NMR (DMSO-d6, 500 MHz): syn-5q
n
¼3259, 3196, 3061, 2981, 2930,
1H
1.23 (t, J¼7.0 Hz, 3H, CH3), 2.94
;
86/14); Rf¼0.30 (toluene/acetone 9/1); IR (ATR):
2937, 1727, 1707, 1616, 1293, 1154, 1056, 836, 734, 698 cmꢁ1
NMR (DMSO-d6, 500 MHz): syn-5o
n
¼3063, 2983,
1H
1.21 (t, J¼7.3 Hz, 3H, CH3CH2),
d
;
(dd, JAB¼17.8 Hz, JAX¼10.5 Hz, 1H, CHAHBCO2Et), 3.09 (dd,
JAB¼17.8 Hz, JBX¼4.0 Hz, 1H, CHAHBCO2Et), 4.16 (q, J¼7.0 Hz, 2H,
CH2O), 4.47 (dd, JAX¼10.5 Hz, JBX¼4.0 Hz, 1H, CHXS), 4.86 (d,
J¼16.2 Hz, 1H, CHAHBPh), 4.90 (d, J¼16.2 Hz, 1H, CHAHBPh), 6.08 (s,
1H, ]CH), 7.06e7.64 (m, 10H, 2ꢂ Ph), 10.29 (s, 1H, NH); anti-5q
d
1.42 (d, J¼7.0 Hz. 3H, CH3CH), 4.12e4.19 (m, 3H, CHS and CH2O),
4.92 (d, J¼16.0 Hz, 1H, CHAHBPh), 4.94 (d, J¼16.0 Hz, 1H, CHAHBPh),
5.85 (s, 1H, ]CH), 7.25 (d, J¼7.0 Hz, 2H, o-Ph), 7.29 (t, J¼7.3 Hz, 1H,
p-Ph), 7.35 (m, 2H, m-Ph); anti-5o
d
1.20 (t, J¼7.3 Hz, 3H, CH3CH2),
d
1.15 (t, J¼7.2 Hz, 3H, CH3), 3.23 (dd, JAB¼18.4 Hz, JAX¼5.5 Hz, 1H,
1.48 (d, J¼7.5 Hz, 3H, CH3CH), 3.90 (q, J¼7.5 Hz, 1H, CHS), CH2O is
covered by syn-5o, 4.82 (d, J¼16.0 Hz, 1H, CHAHBPh), 4.99 (d,
J¼16.0 Hz, 1H, CHAHBPh), 5.88 (s, 1H, ]CH), 7.24e7.37 (m, 5H, Ph);
CHAHBCO2Et), 3.54 (dd, JAB¼18.4 Hz, JBX¼4.2 Hz, 1H, CHAHBCO2Et),
3.93 (m, JAX¼5.5 Hz, JBX¼4.2 Hz, 1H, CHXS), 4.03e4.11 (q, J¼7.2 Hz,
2H, CH2O), CHAHBPh are covered by syn-5q, 6.08 (s, 1H, ]CH),
7.06e7.64 (m, 10H, 2ꢂ Ph), 10.26 (s, 1H, NH); 13C NMR (DMSO-d6,
13C NMR (DMSO-d6, 125.8 MHz): syn-5o
d 6.6 (CH3CH), 14.0
(CH3CH2), 45.1 (CH2Ph), 52.7 (CHS), 60.5 (CH2O), 99.6 (]CH), 126.7
(o-Ph), 127.6 (p-Ph), 128.7 (m-Ph), 134.3 (C1ePh), 157.2 (C]), 164.5
125.8 MHz): syn-5q d 14.0 (CH3), 27.4 (CH2CO2Et), 45.7 (CH2Ph),
53.8 (CHS), 60.8 (CH2O), 103.9 (]CH), 119.2, 123.7, 126.6, 127.6,
128.7, 128.8, 134.0, 138.8, 154.2 (C]), 161.9 (COamide), 170.2 and
(COester), 173.4 (COlactam); anti-5o
d 11.5 (CH3CH), 14.0 (CH3CH2),
45.2 (CH2Ph), 59.6 (CHS), 60.5 (CH2O), 100.3 (]CH), 126.8 (o-Ph),
127.7 (p-Ph), 128.7 (m-Ph), 134.3 (C1ePh), 157.3 (C]), 164.3 (COes-
171.6 (COlactam and COester); anti-5q d 13.8 (CH3), 31.8 (CH2CO2Et),
45.7 (CH2Ph), 61.2 (CH2O), 61.6 (CHS), 102.8 (]CH), 119.2, 123.6,
125.3, 126.8, 127.7, 128.2, 134.1, 138.8, 154.8 (C]), 161.8 (COamide),
170.7 and 171.3 (COlactam and COester); HRMS: calcd for C22H23N2O5S
[MþH]þ 427.1322, found 427.1313.
ter), 173.0 (COlactam); 1H NMR (CDCl3, 500 MHz): syn-5o
d 1.29 (t,
J¼7.3 Hz, 3H, CH3CH2), 1.67 (d, J¼7.5 Hz, 3H, CH3CH), 3.48 (q,
J¼7.5 Hz, 1H, CHS), 4.24 (q, J¼7.3 Hz, 2H, CH2O), 4.79 (d, J¼15.5 Hz,
1H, CHAHBPh), 4.94 (d, J¼15.5 Hz, 1H, CHAHBPh), 5.67 (s, 1H, ]CH),
7.18e7.39 (m, 5H, Ph); anti-5o
d
1.29 (t, J¼7.3 Hz, 3H, CH3CH2), 1.58
5.6.18. (Z)-(3-Benzyl-5-ethoxycarbonylmethyl-1,4-dioxothiazolidin-
2-ylidene)-1-phenylethanone (5r). Compound 5r was obtained from
1r (79.1 mg; 0.20 mmol; 3 mL CH2Cl2) and m-CPBA (81.2 mg;
0.40 mmol; 4 mL CH2Cl2) according tothegeneralprocedure (reaction
time 90 min). Column chromatography (eluent: gradient toluene/
acetone 100/0 to 60/40) gave pure 5r as a colourless oil (58.7 mg; 71%;
(d, J¼7.5 Hz, 3H, CH3CH), 3.71 (q, J¼7.5 Hz, 1H, CHS), 4.24 (q,
J¼7.3 Hz, 2H, OCH2), 4.81 (d, J¼15.5 Hz, 1H, CHAHBPh), 4.91 (d,
J¼15.5 Hz, 1H, CHAHBPh), 5.70 (s, 1H, ]CH), 7.18e7.39 (m, 5H, Ph);
13C NMR (CDCl3, 125.8 MHz): syn-5o
d 6.7 (CH3CH), 14.0 (CH3CH2),
46.8 (CH2Ph), 53.5 (CHS), 61.3 (CH2O), 101.7 (]CH), 126.7 (o-Ph),
128.2 (p-Ph), 129.1 (m-Ph), 133.1 (C1ePh), 155.9 (C]), 164.5
syn/anti 77/23); Rf¼0.30 (toluene/acetone 7/3); IR (KBr):
3032, 2980, 2930, 1720, 1650, 1575, 1320, 1292, 1175, 1042, 1019, 778,
740, 699 cmꢁ1; 1H NMR (CDCl3, 500 MHz): syn-5r
1.30 (t, J¼7.0 Hz,
3H, CH3), 3.23 (dd, JAB¼18.5 Hz, JAX¼9.5 Hz, 1H, CHAHBCO2Et), 3.27
n¼3063,
(COester), 172.4 (COlactam); anti-5o
d 12.4 (CH3CH), 14.0 (CH3CH2),
46.6 (CH2Ph), 59.6 (CHS), 61.3 (CH2O), 102.1 (]CH), assignation for
Ph is not certain, 133.0 (C1ePh), 156.0 (C]), 164.5 (COester), 172.8
d
ꢀ
Please cite this article in press as: Dzambaski, Z.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.05.087

ꢀ
12
Z. Dzambaski et al. / Tetrahedron xxx (2013) 1e12
ꢁ
ꢁ
ꢁ
Baranac, M.; Juranic, N.; Macura, S.; Cekic, I.; Minic, D. J. Mol. Struct. 2006, 800,
(dd, JAB¼18.5 Hz, JBX¼4.3 Hz, 1H, CHAHBCO2Et), 4.01 (dd, JAX¼9.5 Hz,
JBX¼4.3 Hz,1H, CHXS), 4.23 (q, J¼7.0 Hz, 2H, CH2O), 4.86 (d, J¼15.5 Hz,
1H, CHAHBPh), 5.11 (d, J¼15.5 Hz, 1H, CHAHBPh), 6.78 (s, 1H, ]CH),
ꢁ
ꢀ
ꢁ
85; (b) Markovic, R.; Shirazi, A.; Dzambaski, Z.; Baranac, M.; Minic, D. J. Phys.
Org. Chem. 2004, 17, 118; (c) Markovic, R.; Dzambaski, Z.; Baranac, M. Tetrahe-
dron 2001, 57, 5833; (d) Markovic, R.; Baranac, M. Heterocycles 1998, 48, 893
and Ref 10 in the present paper.
ꢁ
ꢀ
ꢁ
7.26e7.74 (m, 10H, 2ꢂ Ph); anti-5r
d
1.21 (t, J¼7.0 Hz, 3H, CH3), 3.41
13. (a) Buchanan, G. W.; Durst, T. Tetrahedron Lett. 1975, 1683; (b) Harrison, C. R.;
Hodge, P. J. Chem. Soc., Perkin Trans. 1 1976, 1772; (c) Cook, M. J.; Tonge, A. P. J.
Chem. Soc., Perkin Trans. 2 1974, 767.
14. (a) Green, C. H.; Hellier, D. G. J. Chem. Soc., Perkin Trans. 2 1972, 458; (b) Buck, K.
W.; Foster, A. B.; Pardoe, W. D.; Qadir, M. H.; Webber, J. M. J. Chem. Soc., Chem.
Commun. 1966, 759.
(dd, JAB¼18.5 Hz, JAX¼4.3 Hz,1H, CHAHBCO2Et), 3.44 (dd, JAB¼18.5 Hz,
JBX¼4.3 Hz, 1H, CHAHBCO2Et), 3.75 (t, JAX¼JBX¼4.3 Hz, 1H, CHXS),
4.07e4.14 (m, 2H, CH2O), 4.90 (d, J¼16.0 Hz, 1H, CHAHBPh), 5.16 (d,
J¼16.0 Hz, 1H, CHAHBPh), 6.75 (s, 1H, ]CH), 7.26e7.74 (m, 10H, 2ꢂ
Ph); 13C NMR (CDCl3,125.8 MHz): syn-5r
d 14.1 (CH3), 27.3 (CH2CO2Et),
15. Abraham, R. J.; Byrne, J. J.; Griffiths, L. Magn. Reson. Chem. 2008, 46, 667.
47.1 (CH2Ph), 54.6 (CHS), 61.6 (CH2O),105.4 (]CH),126.9,128.2,128.7,
129.2, 133.2, 133.4, 137.2, 156.4 (C]), 170.3 and 171.5 (COlactam and
16. For the application of theoretical methods for stereochemical determinations of
ꢀ
ꢁ
ꢀ
ꢁ
sulfoxide-containing compounds, see: (a) Dracínsky, M.; Pohl, R.; Slavetínska,
ꢂ
ꢁ
ꢀꢀ
ꢁ
L.; Janku, J.; Budesínsky, M. Tetrahedron: Asymmetry 2011, 22, 356; (b)
COester), 187.4 (COketone); anti-5r
d 13.9 (CH3), 32.3 (CH2CO2Et), 47.4
ꢀ
ꢀ
ꢁ
ꢀ
ꢁ
ꢀꢀ
ꢁ
Dracínsky, M.; Pohl, R.; Slavetínska, L.; Hrebabecky, H.; Budesínsky, M. Tetra-
(CH2Ph), 62.1 and 62.2 (CH2O and CHS), 103.3 (]CH), 127.0, 128.4,
128.6, 129.1, 133.1, 133.2, 137.4, 157.6 (C]), 170.4 and 171.3 (COlactam
and COester), 187.4 (COketone); 1H NMR (DMSO-d6, 500 MHz): syn-5r
ꢁ
hedron: Asymmetry 2011, 22, 1797; (c) Pihlaja, K.; Sinkkonen, J.; Stajer, G.; Koch,
A.; Kleinpeter, E. Magn. Reson. Chem. 2011, 49, 443; (d) Kovacs, J.; Toth, G.; Si-
mon, A.; Levai, A.; Koch, A.; Kleinpeter, E. Magn. Reson. Chem. 2003, 41, 193; (e)
ꢁ
ꢁ
ꢁ
Li, W.; Hwang, D. J.; Cremer, D.; Joo, H.; Kraka, E.; Kim, J.; Ross, C. R., II; Nguyen,
V. Q.; Dalton, J. T.; Miller, D. D. Chirality 2009, 21, 578.
17. For the calculation of 1H NMR chemical shifts, see: Jain, R.; Bally, T.; Rablen, P. R.
J. Org. Chem. 2009, 74, 4017.
18. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648; (b) Lee, C.; Yang, W.; Parr, R. G.
Phys. Rev. B 1988, 37, 785.
d
1.22 (t, J¼7.0 Hz, 3H, CH3), 2.95 (dd, JAB¼17.8 Hz, JAX¼10.5 Hz, 1H,
CHAHBCO2Et), 3.10 (dd, JAB¼17.8 Hz, JBX¼4.0 Hz,1H, CHAHBCO2Et), 4.14
(q, J¼7.0 Hz, 2H, CH2O), 4.48 (dd, JAX¼10.5 Hz, JBX¼4.0 Hz, 1H, CHXS),
5.10 (s, 2H, CH2Ph), 7.10 (s, 1H, ]CH), 7.27e7.97 (m, 10H, 2ꢂ Ph); 13
C
19. (a) Ditchfield, R. Mol. Phys. 1974, 27, 789; (b) Wolinski, K.; Hinton, J. F.; Pulay, P. J.
Am. Chem. Soc. 1990, 112, 8251.
NMR (DMSO-d6, 125.8 MHz): syn-5r
d 14.1 (CH3), 27.7 (CH2CO2Et),
44.6 (CH2Ph), 53.7 (CHS), 61.0 (CH2O),103.6 (]CH),127.2,128.2,128.8,
129.0, 133.7, 134.5, 137.3, 158.1 (C]), 170.3 and 172.4 (COlactam and
20. Inclusion of solvent in the chemical shift calculations gave similar correlation
with R2¼0.997.
€
21. (a) Sandstrom, J. Top. Stereochem. 1983, 14, 83; (b) Fischer, G.; Rudorf, W.-D.;
COester), 187.6 (COketone); anti-5r
d 13.5 (CH3), 31.8 (CH2CO2Et), 45.4
Kleinpeter, E. Magn. Reson. Chem. 1991, 29, 212; (c) Benassi, R.; Bertarini, C.;
Kleinpeter, E.; Taddei, F. THEOCHEM 2000, 498, 217; (d) Kleinpeter, E.; Klod, S.;
Rudorf, W.-D. J. Org. Chem. 2004, 69, 4317; (e) Rattananakin, P.; Pittman, C. R.,
Jr.; Collier, W. E.; Saebø, S. Struct. Chem. 2007, 18, 399.
(CH2Ph), 61.3 and 61.5 (CH2O and CHS), 102.6 (]CH), assignation for
Ph is not certain, 158.7 (C]), 170.9 and 171.7 (COlactam and COester),
187.2 (COketone); HRMS: calcd for C22H22NO5S [MþH]þ 412.1213,
found 412.1211.
22. Ye, G.; Chatterjee, S.; Li, M.; Zhou, A.; Song, Y.; Barker, B. L.; Chen, C.; Beard,
D. J.; Henry, W. P.; Pittman, C. U. Tetrahedron 2010, 66, 2919 and references
therein.
23. (a) Kleinpeter, E. J. Serb. Chem. Soc. 2006, 71, 1; (b) Kleinpeter, E.; Schulenburg,
Acknowledgements
ꢁ
€
A. Tetrahedron Lett. 2005, 46, 5995; (c) Baranac-Stojanovic, M.; Klaumunzer, U.;
ꢁ
Markovic, R.; Kleinpeter, E. Tetrahedron 2010, 66, 8958.
This work was supported by the Ministry of Education, Science
and Technological Development of the Republic of Serbia, Grant No.
172020 and Deutscher Akademischer Austauschdienst (DAAD)d
project ID: 504 252 70.
24. (a) Kleinpeter, E.; Thomas, St.; Uhlig, G.; Rudorf, W.-D. Magn. Reson. Chem. 1993,
31, 714; (b) Kleinpeter, E.; Heydenreich, M.; Chatterjee, S. K.; Rudorf, W.-D.
Magn. Reson. Chem. 1994, 32, 473; (c) Kleinpeter, E.; Koch, A.; Heydenreich, M.;
Chatterjee, S. K.; Rudorf, W.-D. J. Mol. Struct. 1995, 356, 25; (d) Mueller, J. L.;
ꢁ
Gibson, M. S.; Hartman, J. S. Can. J. Chem. 1996, 74, 1329; (e) Chiara, J. L.; Gomez-
ꢁ
Sanchez, A.; Bellanato, J. J. Chem. Soc., Perkin Trans. 2 1998, 1797; (f) Kleinpeter,
E.; Heydenreich, M.; Woller, J.; Wolf, G.; Koch, A.; Kempter, G. J. Chem. Soc.,
Perkin Trans. 2 1998, 1877; (g) Meier, H.; Muhling, B.; Gerold, J.; Jacob, D.;
Supplementary data
€
Oehlhof, A. Eur. J. Org. Chem. 2007, 625.
1H NMR spectra for syn- and anti-5l, absolute energies and x, y, z
coordinates of the optimized structures. Supplementary data re-
lated to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.05.087.
25. (a) Glendening, E. D.; Landis, C. R.; Weinhold, F. WIREs Comput. Mol. Sci. 2012, 2,
1; (b) Weinhold, F.; Landis, C. R. Discovering Chemistry with Natural Bond Or-
bitals; John Wiley & Sons: Hoboken, NJ, 2012.
26. Rosini, C.; Donnoli, M. I.; Superchi, S. Chem.dEur. J. 2001, 7, 72.
27. (a) Rozwadowska, M. D.; Sulima, A. Tetrahedron 2003, 59, 1173; (b) Clay, M. P.;
Hanssen, B. R.; Surapaneni, S. S.; Lindstrom, T. D. Chirality 1999, 11, 233.
28. For the literature about the CH/O hydrogen bonds, see: (a) Koch, U.; Popelier,
P. L. A. J. Phys. Chem. 1995, 99, 9747; (b) Yoshida, H.; Harada, T.; Ohno, K.;
Matsuura, H. Chem. Commun. 1997, 2213; (c) Tsuzuki, S.; Houjou, H.; Nagawa, Y.;
Hiratani, K. J. Chem. Soc., Perkin Trans. 2 2001, 1951; (d) Scheiner, S. Int. J.
Quantum Chem. 2010, 110, 2775 For the literature about the hydrogen bonds,
see; (e) Desiraju, G. R. Acc. Chem. Res. 2002, 35, 565.
29. (a) Yates, J. R.; Pham, T. N.; Pickard, C. J.; Mauri, F.; Amado, A. M.; Gil, A. M.;
Brown, S. P. J. Am. Chem. Soc. 2005, 127, 10216; (b) Wang, B.; Hinton, J. F.; Pulay,
P. J. Phys. Chem. A 2003, 107, 4683; (c) Scheiner, S.; Gu, Y.; Kar, T. J. Mol. Struct.
(Theochem) 2000, 500, 441.
References and notes
1. (a) Jain, A. K.; Vaidya, A.; Ravichandran, V.; Kashaw, S. K.; Agrawal, R. K. Bioorg.
Med. Chem. 2012, 20, 3378; (b) Prabhakar, Y. S.; Solomon, V. R.; Gupta, M. K.;
Katti, S. B. Top. Heterocycl. Chem. 2006, 4, 161.
€
2. (a) Vintonyak, V. V.; Warburg, K.; Kruse, H.; Grimme, S.; Hubel, K.; Rauh, D.;
€ €
€
Waldmann, H. Angew. Chem., Int. Ed. 2010, 49, 5902; (b) Kuc¸ ukguzel, S¸ . G.; Oruc¸ ,
€
E. E.; Rollas, S.; S¸ ahin, F.; Ozbek, A. Eur. J. Med. Chem. 2002, 37, 197.
3. (a) Rawal, R. K.; Katti, S. B.; Kaushik-Basu, N.; Arora, P.; Pan, Z. Bioorg. Med. Chem.
Lett. 2008, 18, 6110; (b) Hoye, T. R.; Ayyad, S.-E. N.; Eklov, B. M.; Hashish, N. E.;
Shier, W. T.; El Sayed, K. A.; Hamann, M. T. J. Am. Chem. Soc. 2002, 124, 7405.
4. Allen, S.; Newhouse, B.; Anderson, A. S.; Fauber, B.; Allen, A.; Chantry, D.;
Eberhardt, C.; Odingo, J.; Burgess, L. E. Bioorg. Med. Chem. Lett. 2004, 14, 1619.
5. Ahmed, S. A.; Odde, S.; Daga, P. R.; Bowling, J. J.; Mesbah, M. K.; Youssef, D. T.;
Khalifa, S. I.; Doerksen, R. J.; Hamann, M. T. Org. Lett. 2007, 9, 4773.
6. Knutsen, L. J. S.; Hobbs, C. J.; Earnshaw, C. G.; Fiumana, A.; Gilbert, J.; Mellor, S.
L.; Radford, F.; Smith, N. J.; Birch, P. J.; Burley, J. R.; Ward, S. D. C.; James, I. F.
Bioorg. Med. Chem. Lett. 2007, 17, 662.
7. Zhou, H.; Wu, S.; Zhai, S.; Liu, A.; Sun, Y.; Li, R.; Zhang, Y.; Ekins, S.; Swaan, P. W.;
Fang, B.; Zhang, B.; Yan, B. J. Med. Chem. 2008, 51, 1242.
8. Rock, D. M.; McLean, M. J.; Macdonald, R. L.; Catterall, W. A.; Taylor, C. P. Epilepsy
Res. 1991, 8, 197.
9. Gududuru, V.; Hurh, E.; Dalton, J. T.; Miller, D. D. Bioorg. Med. Chem. Lett. 2004,
14, 5289.
30. 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.; Mennuci, 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.; 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.; Babuol, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; 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 C.02); Gaussian: Wallingford CT, 2004.
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ꢁ
ꢁ
ꢀ
31. (a) Cances, E.; Mennucci, B.; Tomasi, J. J. Chem. Phys. 1997, 107, 3032; (b)
10. (a) Markovic, R.; Baranac, M.; Jovanovic, V.; Dzambaski, Z. J. Chem. Educ. 2004,
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ꢁ
ꢀ
ꢁ
Mennucci, B.; Cances, E.; Tomasi, J. J. Phys. Chem. B 1997, 101, 10506.
81, 1026; (b) Markovic, R.; Baranac, M.; Dzambaski, Z.; Stojanovic, M.; Steel, P. J.
Tetrahedron 2003, 59, 7803.
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32. Stojanovic, M.; Markovic, R.; Kleinpeter, E.; Baranac-Stojanovic, M. Org. Biomol.
Chem. 2012, 10, 575.
11. In all oxidation reactions, sulfones were formed in less than 3%.
12. For the determination of configuration around the CdbndC double bond in
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33. Stojanovic, M.; Markovic, R.; Kleinpeter, E.; Baranac-Stojanovic, M. Tetrahedron
2011, 67, 9541.
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these and similar compounds, and isomerization studies, see: (a) Markovic, R.;
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Please cite this article in press as: Dzambaski, Z.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.05.087