Synthesis of pyrrolidine-fused 1,3-dithiolane oligomers by the cycloaddition of polycyclic dithiolethiones to maleimides and evaluation as mercury(II) indicators

Article abstract of DOI:10.1021/jo500076c

The scandium triflate-catalyzed cycloaddition reaction of polycyclic 1,2-dithiolethiones to maleimides is described. The reaction constitutes an easy approach to linear as well as branched oligomeric cis-fused dihydro[1,3]dithiolo[4,5-c]pyrrole-4,6-dione

Full text of DOI:10.1021/jo500076c

Article
pubs.acs.org/joc
Synthesis of Pyrrolidine-Fused 1,3-Dithiolane Oligomers by the
Cycloaddition of Polycyclic Dithiolethiones to Maleimides and
Evaluation as Mercury(II) Indicators
Pedro Fuertes, María García-Valverde, Jose V. Cuevas, Borja Díaz de Grenu, Teresa Rodríguez,
́
̃
Josefa Rojo, and Tomas Torroba*
́
Department of Chemistry, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain
S
* Supporting Information
ABSTRACT: The scandium triflate-catalyzed cycloaddition reaction
of polycyclic 1,2-dithiolethiones to maleimides is described. The
reaction constitutes an easy approach to linear as well as branched
oligomeric cis-fused dihydro[1,3]dithiolo[4,5-c]pyrrole-4,6-dione
rings interconnected by 3,5-diylidenethiomorpholine-2,6-dithione or
ylidene-6-thioxo[1,2]dithiolo[3,4-b][1,4]thiazin-3-one groups. The
presence of highly colored, highly polarized push−pull α,β-
unsaturated thione groups in their structures make these compounds
sensitive to the presence of mercury(II) cation in organic or mixed
organic/aqueous solvents.
the 2-methylene-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione
system, an almost unknown system14 that could be potentially
useful in the search for new materials and pharmacological leads.
Therefore, in this paper we describe the scandium triflate-
catalyzed cycloaddition of polycyclic dithiolethiones to mal-
eimides as an unprecedented approach to branched oligomeric
polyheterocyclic 1,3-dithiolanes.
INTRODUCTION
■
Polyheterocyclic compounds bearing 1,3-dithiole1 and 1,3-
dithiolane2 moieties are important donor units in new electronic
materials and molecular devices such as extended tetrathiafulva-
lene derivatives,3 organic superconductors,4 push−pull chromo-
phores,5 switchable organic materials,6 receptors,7 shape-
persistent macrocycles, and conducting polymer wires.8 Despite
the enormous synthetic efforts in the search for these new
materials, the number of methods currently used for this
chemistry is surprisingly low, being conserved unchanged for a
long time.9 Less common synthetic methods for the preparation
of 1,3-dithiole derivatives include 1,3-dipolar cycloadditions of
1,2-dithiole-3-thiones and activated triple bonds, which permit
multiple cycloadditions in one pot, thereby giving rise to
extended TTF derivatives by very short reaction pathways.10
Despite the rich chemistry shown by these reactions, related
alternatives are scarce. Thus, the photochemical reactions of 1,2-
dithiole-3-thiones and nonactivated alkenes are known to give
unstable adducts that can be trapped by dienophiles such as N-
phenylmaleimide.11 Notwithstanding the extensive chemistry
developed in the field of 1,2-dithiole-3-thiones,12 their cyclo-
addition reactions with classical activated double bonds such as
maleimides are not known. The only loosely related known
reaction is a single example of a thermal cycloaddition of 2,4-
diphenylisothiazoline-5-thione and N-phenylmaleimide that was
reported long time ago by McKinnon and co-workers.13
Apparently, the thermal reaction of N-substituted maleimides
and 1,2-dithiole-3-thiones does not work under heating in high-
boiling-point solvents. Such a reaction, if it should be possible,
would constitute a very good approach to dihydro derivatives of
RESULTS AND DISCUSSION
■
We selected a suitable catalyst, scandium triflate, which was very
effective for the 1,3-cycloaddition reactions of polyheterocyclic
dithiolethiones and activated alkynes,15 to study the cyclo-
addition reaction of the most reactive dithiolethiones we had in
hand and commercial or easily synthesized maleimides. Our
starting materials, 4-alkylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]-
thiazin-3-oxo-5-thiones and -3,5-dithiones can be prepared in
one-pot reactions from Hunig’s base or N,N-(diisopropyl)-
̈
benzylamine in a selective fashion and therefore are fast entries to
complex heterocyclic chemistry.10a We first selected to use 4-
ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-5-thione16
(1) in catalyzed reactions with commercial maleimides 2a−j. In
this way, 1 and 2a−j reacted equimolecularly in refluxing
dichloromethane for 1 h in the presence of scandium triflate
(25% mol) to give, after workup and column chromatography,
the corresponding orange solid adducts, 5-substituted 2-(4-ethyl-
3-oxo-6-thioxo[1,2]dithiolo[3,4-b][1,4]thiazin-5-ylidene)-
Received: January 13, 2014
Published: February 11, 2014
© 2014 American Chemical Society
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dihydro[1,3]dithiolo[4,5-c]pyrrole-4,6-diones 3a−j, in yields of
up to 88% (Scheme 1).
Scheme 2. Mechanism of the Reaction between
Bisdithioloketothione 1 and Maleimides and Nitrogen
Inversion of the 1,4-Thiazine Ring
Scheme 1. Reaction of Bisdithioloketothione 1 and
Maleimides 2a−j
a
formation can be explained as an inversion of the configuration of
the amine nitrogen atom. In order to avoid complications arising
from the simultaneous inversion on the nitrogen atom and the
rotation of the C−C bond in the ethyl group, this ethyl group was
simplified to a methyl group. In these theoretical calculations, we
found that for this simplified model of 3a−j the SYN and ANTI
conformers have similar stabilities, with a free energy difference
of 0.319 kcal·mol−1. This small difference is in good agreement
with the experimental observation of both conformers in
solution, and on the basis of the calculated free energy difference
between the conformers, the statistical distribution of the
population at 298 K is 63.2% for the ANTI conformer and
36.8% for the SYN conformer (Figure 1). The estimated barrier
for the SYN/ANTI transformation in the simplified model is 17.6
kcal/mol, which is high enough to allow the observation of both
Isolated yields.
All of the obtained compounds showed a single spot on the
TLC silica plates, but their 1H NMR spectra clearly showed two
sets of signals, each composed of two doublets at δ 4.5−6.0,
corresponding the C3a and C6a protons (the pair of cis-
bridgehead protons in the dithiolopyrrole system) for every
compound, in a roughly equimolecular amount, and two
complex multiplets for the signals of the methylene protons of
the ethyl group. Therefore, the complex 1H NMR spectra are due
to the slow inversion of the pyramidal nitrogen in the 1,4-thiazine
ring and consequently to the presence of nitrogen inversion
conformers. Two chiral centers at the C3a and C6a positions are
generated by the 1,3-dipolar cycloaddition reaction with the
maleimide, causing the α-methylene hydrogen atoms of the N-
substituent of the starting substrate 1 to become diastereotopic
in the cycloadduct and thus to show magnetic nonequivalence in
the 1H NMR spectra. Therefore, the two protons of the
dithiolopyrrole system (H3a and H6a) are structurally non-
equivalent. Indeed both the endo- and exo-1,3-dipolar cyclo-
addition reactions lead to enantiomeric dithiolopyrrole rings
(Scheme 2). In a characteristic example, compound 3f showed a
set of two partially superposed sextets centered at δ 3.24 (ddq, J =
25.9, 14.2, 6.9 Hz) for one methylene proton and another set of
two partially superposed sextets centered at δ 3.56 (ddq, J = 24.7,
14.6, 7.3 Hz) for the other methylene proton along with four
doublets, two at δ 5.28 and 5.02 (J = 8.5 Hz) for the pair of
dithiolopyrrole protons of one conformer and two at δ 5.18 and
4.81 (J = 9.0 Hz) for the pair of dithiolopyrrole protons of the
other conformer.
17
1
isomers in the H NMR experiments at room temperature.
Similar calculations performed on a nonsimplified structure of
compound 3a afforded populations of 62.7% for ANTI-3a and
37.3% for SYN-3a (61/39 experimental), in good agreement
with the experimental results (Figure 2).
All of these compounds decomposed at the melting point in a
cycloreversion reaction followed by thermal desulfuration, giving
rise to 4-ethylbis[1,2]dithiolo[4,3-b:3′,4′-d]pyrrole-3-oxo-5-thi-
one (4), a known product of thermal desulfuration of 116b
(Scheme 3). As a characteristic example, upon slow melting of 3c
in a heating chamber under a microscope, yellow crystals of 4
were formed by sublimation as 3c melted. Compound 4 was
characterized by mass spectrometry and compared to a synthetic
sample.
In the same way, 4-benzylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]-
thiazin-3-oxo-5-thione18 (5) and commercial maleimides 2a−
c,e−g reacted equimolecularly in refluxing dichloromethane for
2−4 h in the presence of scandium triflate (25% mol) to give,
after workup and column chromatography, the corresponding
The transformation among the conformational isomers SYN
and ANTI was studied by DFT calculations performed on a
simplified model of compounds 3a−j. The SYN/ANTI trans-
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Scheme 4. Reaction of Bisdithioloketothione 5 and
Maleimides 2a−c,e−g
Figure 1. DFT-calculated structures of the SYN and ANTI conformers
and of the transition state (TS) for the SYN/ANTI transformation of a
model compound.
a
Isolated yields.
dithioxothiomorpholine-3,5-diylidene)bis(5-methyl{or aryl}-
dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6-dione)s 8b,f,g, in
yields of up to 67% (Scheme 5). In this case, several conformers
Scheme 5. Reaction of Bisdithiolodithione 7 and Maleimides
2b,f,g
Figure 2. DFT-calculated structures of the ANTI and SYN conformers
of 3a.
Scheme 3. Thermal Decomposition of 3c
orange solid adducts, 5-substituted 2-(4-benzyl-3-oxo-6-thioxo-
[1,2]dithiolo[3,4-b][1,4]thiazin-5-ylidene)dihydro[1,3]-
dithiolo[4,5-c]pyrrole-4,6-diones 6a−c,e−g, in yields of up to
74% (Scheme 4). In this case, the inversion of the pyramidal
nitrogen in the 1,4-thiazine ring was evidenced in the 1H NMR
spectra by the presence of two pairs of doublets, one for each of
the benzyl methylene protons, and two sets of signals, each
composed of two doublets at δ 4.5−6.0, corresponding to the
pair of cis-dithiolopyrrole protons for every compound, in
amounts from equimolecular to 2:1. In a characteristic example,
the 1H NMR spectrum of 6f showed two pairs of doublets at δ
4.40/4.12 (J = 14.1 Hz) and δ 4.37/4.19 (J = 14.1 Hz) in a 2:1
proportion for the two benzyl methylene protons and two pairs
of doublets at δ 5.83/5.58 (J = 8.9 Hz) and δ 5.66/5.35 (J = 9.2
Hz) in a 2:1 proportion for the two pairs of dithiolopyrrole
protons.
a
Isolated yields.
1
are expected, therefore complicating the otherwise simple H
NMR spectrum of every compound. In this way, the H NMR
1
spectrum of 8b showed four sets of signals (eight doublets) for
the dithiolopyrrole protons (δ 5.0−6.0) in different proportions,
whereas 8f showed only two main equimolecular conformers and
traces of two others and 8g showed only one main conformer and
traces of two others in the same region of the 1H NMR spectrum,
probably for steric reasons.
On the other hand, 4-ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]-
thiazin-3,5-dithione16 (7) and 2 equiv of commercial maleimides
2b,f,g reacted in refluxing dichloromethane for 1−2 h in the
presence of scandium triflate (25% mol with respect to 2b,f,g) to
give, after workup and column chromatography, the correspond-
ing orange solid adducts, 5,5′-disubstituted 2,2′-(4-ethyl-2,6-
Moreover, bisdithioloketothione16 1 reacted with commercial
bismaleimides 9a and 9b and the synthesized bismaleimide 9c19
in refluxing dichloromethane for 1 h in the presence of scandium
triflate (25% mol) to give, after workup and column
chromatography, the corresponding orange solid monoadducts
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10a and 10b or the diadducts 11a−c in yields of up to 55%
(Scheme 6). The structures of compounds 10a−b and 11a−c are
Scheme 6. Reaction of Bisdithioloketothione 1 and
Bismaleimides 9a−c
a
Isolated yields.
Figure 3. Structures of 10a−b and 11a−c.
represented in Figure 3. The expected compound 10c was not
isolated, probably because of a lack of stability; therefore, in this
case only compound 11c was obtained. The presence of two
Furthermore, 1, 2, or 3 equiv of bisdithioloketothione16 1 and
trismaleimide 1320 reacted in refluxing dichloromethane for 4 h
in the presence of scandium triflate (25% mol with respect to 1)
to give, after workup and column chromatography, the
corresponding orange solid monoadduct 14, diadduct 15, or
triadduct 16, respectively, in yields of up to 41% (Scheme 8).
Variable amounts of the starting materials and adduct were
recovered in each case, and the yields given in Scheme 8 are only
for the main product obtained in each reaction. In this case, the
yields were lower because of the lack of selectivity, but the
compounds were reasonably stable and could be characterized by
spectroscopy and microanalysis as in the previous cases.
All of these compounds were obtained within a small window
between the reactivity of the starting materials and the stability of
the products; this series of reactions was possible because of the
presence of scandium triflate as the catalyst of the hitherto
unknown 1,3-cycloaddition reaction between dithiolethiones
and maleimides. The catalysis permitted the reaction to be
performed at a suitable temperature to allow the formation and
recovery of the obtained products in almost all cases. These new
compounds are thermally sensitive, undergoing a cycloreversion
1
dithiolopyrrole heterocycles in 11a−c was evidenced in the H
NMR spectra by again the presence of four sets of signals (eight
doublets) for the heterocyclic protons (δ 4.5−5.5). In contrast,
the presence of only one dithiolopyrrole system in 10a and 10b
was evidenced in their 1H NMR spectra by the presence of only
two sets of signals (four doublets) for the heterocyclic protons (δ
4.5−5.5).
In the case of monoadducts 10, the presence of a maleimide
nucleus makes the products suitable for a second cycloaddition
reaction. Therefore, bisdithiolodithione16 7 and 2 equiv of
maleimide 10a reacted in refluxing dichloromethane for 6 h in
the presence of scandium triflate (25% mol) to give, after workup
and column chromatography, the corresponding orange solid
adduct 12 in 74% yield (Scheme 7). Some traces of the
corresponding monoadduct were also recovered from the
column, but the compound was not sufficiently stable for a
correct characterization. Compound 12 possesses a remarkable
stable structure in which all of the spectroscopic characteristics
found in the 1H NMR spectra of compounds 3f−h and 8f−g are
preserved, showing a complex mixture of conformers.
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Scheme 7. Synthesis and Structure of 12
Scheme 8. Reaction of Bisdithioloketothione 1 and
Trismaleimide 13
reaction followed by thermal desulfuration at the melting point.
All of these compounds hold in their structure at least one α,β-
unsaturated thione group, which is a well-known heterodiene
system that is frequently used for hetero-Diels−Alder cyclo-
addition reactions with activated alkynes.15 In the present case,
all of the attempted reactions under uncatalyzed or catalyzed
conditions gave the product of sequential 1,3-dipolar cyclo-
reversion (presumably to give the starting material 1) followed
by the 1,3-dipolar cycloaddition of dithiolethione 1 and the new
dipolarophile. In a characteristic example, compound 3f was
subjected to reaction with dibenzoylacetylene (17) under diverse
conditions15b but only the known compound 1815b was obtained
with no traces of the expected compound 19 (Scheme 9).
On the other hand, the highly polarized push−pull α,β-
unsaturated thione group is responsible for the color exhibited by
these compounds. Compounds 3a−j display an orange color in
solution that may undergo changes in the presence of the most
common cations or anions. All of them behaved similarly when
tested with the same cations or anions, independently of the N-
alkyl or N-aryl group, and therefore, the behavior of two of the
most representative examples, 3f and 8f, is reported. Addition of
1 equiv or more of Hg2+ to 10−4 M solutions of 3f (λmax = 394 nm,
ε = 10 946 M−1 cm−1) in MeCN resulted in a dramatic change of
color from yellow to maroon. This response was selective for
Hg2+, and addition of several equivalents of other cations (Ag+,
Ni2+, Sn2+, Cd2+, Zn2+, Pb2+, Cu2+, Fe3+, Sc3+, and Al3+) as their
perchlorate or triflate salts resulted in no appreciable changes
(Figure 4).
a
Isolated yields.
A quantitative UV−vis titration of a 10−4 M solution of 3f in
MeCN with Hg2+ (added as the perchlorate salt in MeCN)
showed that as Hg2+ was added (up to 2 equiv), the original
absorption maximum bands centered at 394 and 345 nm
decreased and some new bands appeared at 550, 430, and 310
nm, generating isosbestic points at 290, 333, and 402 nm (Figure
5a). After the addition of more than 2 equiv of Hg2+, the new
bands slowly decreased with the disappearance of the isosbestic
point at 402 nm. The titration profile fitted nicely to a 1:1 binding
model (Figure 5b),21 and the association constant was calculated
as log K = 4.94 0.09. The Job’s plot analysis of the UV−vis
titration carried out in MeCN revealed a maximum at a mole
fraction of 50% (Figure 5c), in accordance with the proposed 1:1
binding stoichiometry. The Hg2+ detection limit of a 10−4
M
solution of 3f in MeCN, calculated in UV−vis absorption by the
blank variability method,22 was 3.69 × 10−6 M.
The selective sensing action of a 10−4 M solution of 8f in
MeCN and 1 equiv or more of Hg2+ in MeCN or water was also
very effective, in contrast to the lack of effect of adding 1 equiv or
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Scheme 9. 1,3-Dipolar Cycloreversion/Cycloaddition of 3f
Figure 4. Color changes of 10−4 M samples of 3f in MeCN in the
presence of 1 equiv of various cations.
more of other cations (Ag+, Ni2+, Sn2+, Cd2+, Zn2+, Pb2+, Cu2+,
Fe3+, Sc3+, and Al3+) in MeCN. In this case, a striking color
change from yellow to maroon only in the presence of Hg2+ was
observed (Figure 6).
A quantitative UV−vis titration of a 10−4 M solution of 8f in
MeCN with Hg2+ (added as the perchlorate salt in MeCN)
showed that addition of Hg2+ resulted in the decrease of the
original absorption maximum bands centered at 390 and 417 nm
and the appearance of a large absorption band from 300 to 600
nm (responsible for the observed color) with no appearance of
isosbestic points (Figure 7a). Related titrations performed in
acetonitrile/water mixtures showed a similar tendency, but a
clear isosbestic point at 365 nm was observed (Figure 7b), thus
confirming the appearance of a unique equilibrium complex. The
titration profile fitted nicely to a 2:1 binding model (Figure 7c),21
and the association constants were calculated as log K1 = 3.42
0.14 and log K2 = 4.56 0.17. The Job’s plot analysis of the UV−
vis titration carried out in MeCN revealed a maximum between
mole fractions of 0.60 and 0.70 (Figure 7d), in accordance with
the proposed 2:1 binding stoichiometry. The Hg2+ detection
limit of a 10−4 M solution of 8f in MeCN, calculated in UV−vis
absorption by the blank variability method,22 was 3.16 × 10−7 M,
so 8f showed better performance than 3f.
Figure 5. (a) UV−vis titration curves, (b) titration profile (λmax = 312
nm), and (c) Job’s plot (λmax = 393 nm) for a 10−4 M solution of 3f in
MeCN titrated with Hg2+.
In agreement with previous related chromogenic probes for
mercury(II) cation, we assumed that in both cases complexation
was probably effected through the thione group, leading to the
formation of complexes in which Hg2+ extends the conjugation
between the 1,3-dithiolane and thione groups, causing in both
cases bathochromic shifts of the main UV−vis absorption band in
UV−visible. As a representative example, the structure of the
complex 3f[Hg2+]·MeCN was obtained by DFT calculations
(Figure 8). The model found with ligand 3f and a mercury(II)
cation showed a preference for coordination of the mercury
cation to the thione sulfur and a preferred orientation through
the sulfur atom of the thiomorpholine moiety.
Figure 6. Color changes of 10−4 M samples of 8f in MeCN in the
presence of 2 equiv of various cations.
Comparison of the HOMOs and LUMOs of 3f and 3f[Hg2+]·
MeCN showed that the HOMO of 3f is a nonbonding orbital
spread through the 5-(1,3-dithiolan-2-ylidene)[1,2]dithiolo[3,4-
b][1,4]thiazin-3-oxo-6-thione moiety and the LUMO is an
antibonding orbital spread through the 2-(1,3-dithiolan-2-
ylidene)dithiocarboxylate moiety. In contrast, the HOMO of
3f[Hg2+]·MeCN is a nonbonding orbital on the N-phenyl-
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Figure 9. HOMOs and LUMOs of 3f and the 3f[Hg2+]·MeCN complex.
CONCLUSION
■
We have described the scandium triflate-catalyzed cycloaddition
of polycyclic dithiolethiones to maleimides. The reaction
constitutes an unprecedented approach to linear as well as
branched oligomeric cis-fused [1,3]dithiolo[4,5-c]pyrrole rings
interconnected by 3,5-diylidenethiomorpholine-2,6-dithione or
ylidene-6-thioxo[1,2]dithiolo[3,4-b][1,4]thiazin-3-one groups.
Both the 1,4-thiazine core and the cis-fused [1,3]dithiolo[4,5-
c]pyrrole ring are nonplanar nonaromatic rings that display the
presence of inversion conformers of the 1,4-thiazine nitrogen.
The presence of highly colored, highly polarized push−pull α,β-
unsaturated thione groups in their structures make these
compounds sensitive to the presence of mercury(II) cation in
organic or mixed organic/aqueous solvents with remarkable
selectivity, as shown for two simple derivatives. Therefore, the
more structurally complex compounds are good candidates in
mercury removal schemes, as absorbants for mercury(II) salts,
and as selective indicators. This is due to the enormous number
of sulfur heteroatoms (in either acceptor or donor positions) that
these new molecular systems display, such as the 1,3-dithiolanes
and the conjugated thione groups.
EXPERIMENTAL SECTION
■
General. The reactions were conducted under dry nitrogen. The
solvents were previously distilled under nitrogen over phosphorus
pentoxide, calcium hydride, or sodium filaments. Melting points were
not corrected. Infrared spectra were registered in potassium bromide
tablets. NMR spectra were recorded in DMSO-d6, CDCl3, CD3CN, or
CD3OD. Chemical shifts are reported in parts per million with respect to
residual solvent protons,23 and coupling constants (JX−X′) are reported
in hertz. DEPT experiments from selected samples permitted the
assignment of 13C NMR chemical shifts. Elemental analyses of C, H, and
N were performed for all new products. High-resolution mass spectra
were taken in a quadrupole mass spectrometer by electron impact, FAB,
or LSIMS. 4-Ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-5-
thione16 (1), 4-benzylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-
5-thione18 (5), 4-ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3,5-
dithione16 (7), bismaleimide 9c,19 and trismaleimide 1320 were
prepared following the reported methodologies. Analytical TLC was
performed on silica gel 60 plates. Flash column chromatography was
carried out on silica gel (0.040−0.063 mm).
General Procedure for the Catalytic Cycloaddition of 4-
Ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-5-thione
(1) and Maleimides 2a−j. Maleimide 2a−j (1 equiv) and Sc(OTf)3
(19 mg, 0.038 mmol) were added under nitrogen to 1 (50 mg, 0.15
mmol) dissolved in dry dichloromethane (10 mL), and the mixture was
refluxed for 1 h. Then the solvent was evaporated under reduced
pressure, and the residue was purified by column chromatography (silica
230−400 mesh, eluting with light petroleum/dichloromethane 60/40 to
dichoromethane/ethyl acetate mixtures) to get 3a−j. Analytical samples
Figure 7. (a, b) Hg2+ UV−vis titration curves of (a) 10−4 M 8f in MeCN
and (b) 5 × 10−4 M 8f in MeCN/water. (c) Titration profile (λmax = 390
nm). (d) Job’s plot (λmax = 295 nm).
Figure 8. DFT-calculated structure of the complex 3f[Hg2+]·MeCN.
pyrrolidine-2,5-dione moiety and the LUMO of 3f[Hg2+]·
MeCN is an σ antibonding orbital spread through the 2-(1,3-
dithiolan-2-ylidene)dithiocarboxylate−Hg2+ moiety (Figure 9),
thus proving that the extension of the conjugation between the
1,3-dithiolane group and the complexed thione group is
responsible for the bathochromic shift in the UV titration.
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were obtained by thin-layer chromatography (glass plates, silica 20 cm ×
20 cm × 0.1 cm, eluting with dichloromethane/ethyl acetate mixtures).
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3a). 44 mg (68%), orange
solid, mp 119−120 °C (dec.) (DCM/EtOAc 1:1), 61/39 ratio of
400 MHz): δ 5.11 (d, J = 8.6 Hz, 0.52H, CH conformer A), 5.03 (d, J =
8.9 Hz, 0.48H, CH conformer B), 4.86 (d, J = 8.6 Hz, 0.52H, CH
conformer A), 4.62 (d, J = 8.9 Hz, 0.48H, CH conformer B), 3.62−3.48
(m, 3H), 3.28−3.15 (m, 1H, CH2 conformer A/B), 1.67−1.52 (m, 2H),
1.37−1.24 (m, 2H), 1.13 (t, J = 7.1 Hz, 1.44H, CH 3 conformer B), 1.12 (t,
J = 7.1 Hz, 1.56H, CH3 conformer A), 0.93 (t, J = 7.3 Hz, 1.44H, CH3
conformer B), 0.90 (t, J = 7.4 Hz, 1.56H, CH3 conformer A). 13C NMR
and DEPT (CDCl3, 100 MHz): δ 200.9, 200.5, 184.7, 184.5, 172.8,
172.5, 172.2, 172.0, 165.3, 163.2, 151.1, 150.3, 133.3, 132.5 (Cq
conformer A/B), 59.8 (CH conformer A), 58.6 (CH conformer B), 51.31
(CH conformer A), 50.1 (CH conformer B), 48.7 (CH2 conformer A),
48.6 (CH2 conformer B), 39.9, 29.4, 19.9 (CH2 conformer A/B), 13.5
(CH3 conformer B), 13.4 (CH3 conformer A), 13.3 (CH3 conformer A),
13.2 (CH3 conformer B). MS (FAB+): m/z (%) 477 (M+ + 1, 4), 338
conformers. IR (KBr): ν
̃
= 3460, 2853, 1721, 1712, 1631, 1283 cm−1. 1H
NMR (CD3COCD3, 300 MHz): δ 10.86 (br s, 0.39H, NH conformer B),
10.73 (br s, 0.61H, NH conformer A), 5.63 (d, J = 8.6 Hz, 0.61H, CH
conformer A), 5.46 (d, J = 9.0 Hz, 0.39H, CH conformer B), 5.32 (d, J =
8.6 Hz, 0.61H, CH conformer A), 5.12 (d, J = 9.0 Hz, 0.39H, CH
conformer B), 3.59−3.48 (m, 1H, CH2 conformer A/B), 3.34−3.19 (m,
1H, CH2 conformer A/B), 1.14 (t, J = 7.2 Hz, 1.83H, CH3 conformer A),
1.13 (t, J = 7.2 Hz, 1.17H, CH3 conformer B). 13C NMR (CDCl3, 75
MHz): δ 201.2, 201.1, 184.9, 184.8, 172.8, 172.5, 172.2, 172.1, 171.1,
165.1, 163.2, 150.9, 150.7, 133.6, 133.1, 132.7 (Cq conformer A/B),
60.8 (CH conformer A), 59.9 (CH conformer B), 52.6 (CH conformer
A), 51.3 (CH conformer B), 48.8 (CH2 conformer A), 48.7 (CH2
conformer B), 13.3 (CH3 conformer A), 13.2 (CH3 conformer B). MS
(FAB+): m/z (%) 421 (M+ + 1, 28), 391 (18), 323 (34). HRMS
+
(10). HRMS (LSIMS): m/z 475.9502; calcd for C16H16N2O3S6 ,
475.9485. Anal. Calcd for C16H16N2O3S6: C 40.31, H 3.38, N 5.88.
Found: C 40.32, H 3.51, N 5.92.
(3aR,6aS)(Z/E)-5-Benzyl-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-
[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3e). 41 mg (52%), orange
solid, mp 105−106 °C (dec.) (DCM), 52/48 ratio of conformers. IR
+
(LSIMS): m/z 419.8860; calcd for C12H8N2O3S6 , 419.8859. Anal.
(KBr): ν
̃
= 2961, 2924, 1783, 1710, 1666, 1640 cm−1. 1H NMR (CDCl3,
Calcd for C12H8N2O3S6: C 34.27, H 1.92, N 6.66. Found: C 34.15, H
2.01, N 6.51.
400 MHz): δ 7.39−7.27 (m, 5H, HAr), 5.07 (d, J = 8.8 Hz, 0.52H, CH
conformer A), 4.98 (d, J = 9.0 Hz, 0.48H, CH conformer B), 4.82 (d, J =
8.8 Hz, 0.52H, CH conformer A), 4.73 (s, 0.96H, CH2 conformer B), 4.66
(s, 1.04H, CH2 conformer A), 4.55 (d, J = 9.0 Hz, 0.48H, CH conformer
B), 3.62−3.47 (m, 1H, CH2 conformer A/B), 3.26−3.14 (m, 1H, CH2
conformer A/B), 1.13 (t, J = 7.0 Hz, 1.56H, CH3 conformer A), 1.12 (t, J
= 7.00 Hz, 1.44H, CH3 conformer B). 13C NMR (CDCl3, 100 MHz): δ
201.1, 200.6, 184.7, 184.5, 172.5, 172.1, 171.8, 171.7, 163.0, 151.0, 150.2,
134.4, 133.4, 132.5 (Cq conformer A/B), 129.0, 128.9, 128.8, 128.8,
128.4 (CHAr), 59.8 (CH conformer A), 58.7 (CH conformer B), 51.3
(CH conformer A), 50.1 (CH conformer B), 48.7 (CH2 conformer A),
48.6 (CH2 conformer B), 43.8 (CH2 conformer A/B), 13.3 (CH3
conformer A), 13.2 (CH3 conformer B). MS (FAB+): m/z (%) 511
(M+ + 1, 8), 494 (6), 323 (100). HRMS (LSIMS): m/z 509.9323; calcd
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-methyldihydro-4H-
[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3b). 52 mg (77%),
orange solid, mp 88−89 °C (dec.) (DCM/EtOAc 98:2), 57/43 ratio
of conformers. IR (KBr): ν
̃
= 2923, 1783, 1704, 1677, 1639, 1614 cm−1.
1H NMR (CDCl3, 400 MHz): δ 5.13 (d, J = 8.4 Hz, 0.57H, CH
conformer A), 5.05 (d, J = 9.2 Hz, 0.43H, CH conformer B), 4.88 (d, J =
8.4 Hz, 0.57H, CH conformer A), 4.63 (d, J = 9.2 Hz, 0.43H, CH
conformer B), 3.63−3.48 (m, 1H, CH2 conformer A/B), 3.29−3.14 (m,
1H, CH2 conformer A/B), 3.11 (s, 1.29H, CH 3 conformer B), 3.05 (s,
1.71H, CH3 conformer A), 1.13 (t, J = 7.2 Hz, 3H, CH3 conformer A/B).
13C NMR and DEPT (CDCl3, 100 MHz): δ 201.1, 200.7, 184.7, 184.5,
172.9, 172.6, 172.2, 172.1, 171.1, 165.2, 163.0, 151.1, 150.2, 133.4, 133.3,
132.5 (Cq conformer A/B), 59.7 (CH conformer A), 58.6 (CH
conformer B), 51.3 (CH conformer A), 50.1 (CH conformer B), 48.7
(CH2 conformer A), 48.6 (CH2 conformer B), 26.1 (CH3 conformer B),
26.0 (CH3 conformer A), 13.3 (CH3 conformer A), 13.2 (CH3 conformer
B). MS (FAB+): m/z (%) 434 (M+, 9), 391 (11), 323 (11). HRMS
+
for C19H14N2O3S6 , 509.9329. Anal. Calcd for C19H14N2O3S6: C 44.69,
H 2.76, N 5.49. Found: C 44.58, H 2.84, N 5.38.
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-phenyldihydro-4H-
[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3f). 49 mg (64%),
orange solid, mp 119−120 °C (dec.) (DCM/EtOAc 50:50), 53/47
+
(LSIMS): m/z 433.9016; calcd for C13H10N2O3S6 , 433.9016. Anal.
̃
ratio of conformers. IR (KBr): ν = 2960, 2923, 1783, 1704, 1677, 1666,
Calcd for C13H10N2O3S6: C 35.92, H 2.32, N 6.45. Found: C 35.98, H
1639, 1614, 1536 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.52−7.29 (m,
5H, HAr), 5.28 (d, J = 8.6 Hz, 0.53H, CH conformer A), 5.18 (d, J = 9.0
Hz, 0.47H, CH conformer B), 5.03 (d, J = 8.6 Hz, 0.53H, CH conformer
A), 4.81 (d, J = 9.0 Hz, 0.47H, CH conformer B), 3.64−3.49 (m, 1H, CH2
conformer A/B), 3.32−3.17 (m, 1H, CH2 conformer A/B), 1.14 (t, J =
6.9 Hz, 3H, conformer A/B). 13C NMR (CDCl3, 100 MHz): δ 201.1,
200.6, 184.8, 184.5, 171.9, 171.7, 171.1, 164.9, 162.9 151.2, 150.2, 133.5,
132.4, 130.7 (Cq conformer A/B), 129.3, 129.2, 126.1, 126.0 (CHAr),
59.9 (CH conformer A), 58.7(CH conformer B), 51.5 (CH conformer
A), 50.0 (CH conformer B), 48.7 (CH2 conformer A), 48.6 (CH2
conformer B), 13.3 (CH3 conformer A), 13.2 (CH3 conformer B). MS
(FAB+): m/z (%) 496 (M+ + 1, 9), 338 (27). HRMS (LSIMS): m/z
496.9239; calcd for [C18H12N2O3S6 + H]+, 496.9245. Anal. Calcd for
C18H12N2O3S6: C 43.53, H 2.44, N 5.64. Found: C 43.40, H 2.56, N
5.72.
2.36, N 6.39.
(3aR,6aS)(Z/E)-5-(tert-Butyl)-2-(4-ethyl-3-oxo-6-thioxo-
3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-
4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3c). 60 mg (81%),
orange solid, mp 94−95 °C (dec.) (DCM), 52/48 ratio of conformers.
IR (KBr): ν
̃
= 2922, 1704, 1667, 1658, 1642, 1632, 1310, 1190 cm−1. 1H
NMR (CDCl3, 400 MHz): δ 4.98 (d, J = 8.8 Hz, 0.52H, CH conformer
A), 4.85 (d, J = 9.0 Hz, 0.48H, CH conformer B), 4.73 (d, J = 8.8 Hz,
0.52H, CH conformer A), 4.44 (d, J = 9.0 Hz, 0.48H, CH conformer B),
3.63−3.52 (m, 1H, CH2 conformer A/B), 3.30−3.19 (m, 1H, CH2
conformer A/B), 1.62 (s, 4.68H, CH3 conformer A), 1.58 (s, 4.32H, CH3
conformer B), 1.15 (t, J = 7.2 Hz, 1.44H, CH3 conformer B), 1.14 (t, J = 7.2
Hz, 1.56H, CH3 conformer A). 13C NMR (CDCl3, 100 MHz): δ 200.7,
200.6, 184.7, 184.5, 173.5, 173.3, 172.8, 172.7, 165.6, 164.1, 151.0, 150.3,
133.4, 133.1, 132.5, 130.9, 60.4 (Cq conformer A/B), 60.2 (CH
conformer A), 58.7 (CH conformer B), 51.8 (CH conformer A), 50.4
(CH conformer B), 48.7 (CH2 conformer A), 48.6 (CH2 conformer B)
29.7 (3 × CH3 conformer B), 28.1 (3 × CH3 conformer A), 13.3 (CH3
conformer A), 13.2 (CH3 conformer B). MS (FAB+): m/z (%) 477 (M+ +
1, 6), 391 (15), 323 (11). HRMS (LSIMS): m/z 475.9485; calcd for
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-iodophenyl)-
dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3g). 69
mg (72%), orange solid, mp 144−145 °C (dec.) (DCM), 55/45 ratio
of conformers. IR (KBr): ν
̃
= 3289, 2922, 1716, 1644, 1285, 1163 cm−1.
1H NMR (CDCl3, 400 MHz): δ 7.85−7.79 (m, 2H, HAr), 7.15−7.09 (m,
2H, HAr), 5.25 (d, J = 8.4 Hz, 0.55H, CH conformer A), 5.14 (d, J = 9.0
Hz, 0.45H, CH conformer B), 5.00 (d, J = 8.4 Hz, 0.55H, CH conformer
A), 4.73 (d, J = 9.0 Hz, 0.45H, CH conformer B), 3.67−3.53 (m, 1H, CH2
conformer A/B), 3.33−3.18 (m, 1H, CH2 conformer A/B), 1.16 (t, J =
7.0 Hz, 3H, CH3 conformer A/B). 13C NMR (CDCl3, 100 MHz): δ
201.3, 201.1, 184.7, 184.5, 171.4, 171.2, 170.6, 170.6, 164.2, 162.3, 151.0,
+
C16H16N2O3S6 , 475.9482. Anal. Calcd for C16H16N2O3S6: C 40.32, H
3.38, N 5.88. Found: C 40.26, H 3.46, N 5.92.
(3aR,6aS)(Z/E)-5-Butyl-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-
[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3d). 65 mg (88%), orange
solid, mp 92−93 °C (dec.) (DCM), 52/48 ratio of conformers. IR
(KBr): ν
̃
= 2955, 2927, 1782, 1705, 1666, 1639 cm−1. 1H NMR (CDCl3,
2220
dx.doi.org/10.1021/jo500076c | J. Org. Chem. 2014, 79, 2213−2225

The Journal of Organic Chemistry
Article
150.2 (Cq conformer A/B), 138.6, 138.5 (CHAr), 132.5, 132.4, 130.6,
(Cq), 127.68 (CHAr), 94.9, 94.8 (Cq conformer A/B), 59.9 (CH
conformer A), 58.6 (CH conformer B), 51.5 (CH conformer A), 50.4
(CH conformer B), 48.9 (CH2 conformer A), 48.7 (CH2 conformer B),
13.3 (CH3 conformer A/B). MS (FAB +): m/z (%) 623 (M+ + 1, 10),
410 (10), 340 (52). HRMS (LSIMS): m/z 622.8204; calcd for
[C18H11IN2O3S6 + H]+, 622.8212. Anal. Calcd for C18H11IN2O3S6: C
34.73, H 1.78, N 4.50. Found: C 34.64, H 1.86, N 4.41.
C24H16N4O3S6: C 47.98, H 2.68, N 9.33. Found: C 48.11, H 2.73, N
9.22.
General Procedure for the Catalytic Cycloaddition of 4-
Benzylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-5-thione
(5) and Maleimides 2a−c,e−g. Maleimide 2a−c,e−g (1 equiv) and
Sc(OTf)3 (19 mg, 0.039 mmol) were added under nitrogen to 5 (60 mg,
0.16 mmol) dissolved in dry dichloromethane (10 mL), and the mixture
was refluxed for 2 h (for 2a,c), 3 h (for 2b,e,f), or 4 h (for 2g). Then the
solvent was evaporated under reduced pressure, and the residue was
purified by column chromatography [silica 230−400 mesh, eluting with
light petroleum to dichoromethane (or a dichloromethane/ethyl acetate
95:5 mixture for 6a,g)] to get 6a−c,e−g. Analytical samples were
obtained by thin-layer chromatography (glass plates, silica 20 cm × 20
cm × 0.1 cm, eluting with dichloromethane or dichloromethane/ethyl
acetate mixtures).
(3aR,6aS)(Z/E)-5-(4-Acetylphenyl)-2-(4-ethyl-3-oxo-6-thioxo-
3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-
4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (3h). 49 mg (59%),
orange solid, mp 139−140 °C (dec.) (DCM/EtOAc 90:10), 55/45 ratio
̃
of conformers. IR (KBr): ν = 2922, 1790, 1721, 1682, 1602, 1558, 1538,
1378, 1263, 1180 cm−1. 1H NMR (CDCl3, 300 MHz): δ 8.08−8.01 (m,
2H, HAr), 7.53−7.44 (m, 2H, HAr), 5.32 (d, J = 8.6 Hz, 0.55H, CH
conformer A), 5.21 (d, J = 9.0 Hz, 0.45H, CH conformer B), 5.07 (d, J =
8.6 Hz, 0.55H, CH conformer A), 4.85 (d, J = 9.0 Hz, 0.45H, CH
conformer B), 3.65−3.48 (m, 1H, CH2 conformer A/B), 3.33−3.16 (m,
1H, CH2 conformer A/B), 2.61 (s, 1.35H, CH 3 conformer B), 2.60 (s,
1.65H, CH3 conformer A), 1.14 (t, J = 7.2 Hz, 1.35H, CH3 conformer B),
1.13 (t, J = 7.1 Hz, 1.65H, CH3 conformer A/B). 13C NMR (CDCl3, 75
MHz): δ 201.2, 200.9, 196.8, 184.8, 171.5, 171.3, 170.7, 170.6, 168.9,
164.3, 162.4, 151.1, 150.2, 137.1, 137.0, 134.8, 134.7, 134.4, 133.6, 132.4
(Cq conformer A/B), 129.2, 129.1, 126.0, 125.3 (CHAr), 60.0 (CH
conformer A), 58.6 (CH conformer B), 51.5 (CH conformer A), 50.4
(CH conformer B), 48.8 (CH2 conformer A), 48.7 (CH2 conformer B),
26.7 (CH3 conformer A), 26.6 (CH3 conformer B), 13.3 (CH3 conformer
A), 13.2 (CH3 conformer B). MS (FAB+): m/z (%) 539 (M+ + 1, 10), 215
(3aR,6aS)(Z/E)-2-(4-Benzyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6a). 50 mg (67%), orange
solid, mp 142−144 °C (dec.) (DCM/EtOAc 95:5), 66/34 ratio of
conformers. IR (KBr): ν
̃
= 3435, 1790, 1715, 1648, 1264 cm−1. 1H NMR
(CDCl3, 300 MHz): δ 9.22 (br s, 1H, NH), 7.33−7.19 (m, 3H, HAr),
7.06−7.04 (m, 2H, HAr), 5.18 (d, J = 8.5 Hz, 0.66H, CH conformer A),
5.08 (d, J = 9.0 Hz, 0.34H, CH conformer B), 4.94 (d, J = 8.5 Hz, 0.66H,
CH conformer A), 4.57 (d, J = 9.0 Hz, 0.34H, CH conformer B), 4.52 (d, J
= 14.2 Hz, 0.66H, CH2 conformer A), 4.49 (d, J = 13.6 Hz, 0.34H, CH2
conformer B), 4.20−4.08 (m, 1H, CH2 conformer A/B). 13C NMR
(CDCl3, 75 MHz): δ 200.9, 200.4, 184.8, 184.7, 173.2, 172.8, 172.6,
172.4, 165.0, 162.8, 151.9, 151.4 (Cq conformer A/B), 135.2, 135.1
(CHAr conformer A/B), 133.2, 133.1, 132.9, 131.7, 131.6 (Cq
conformer A/B), 129.6, 129.5, 128.5, 128.4 (CHAr conformer A/B),
127.9, 127.5 (Cq conformer A/B), 61.0 (CH conformer A), 60.0 (CH
conformer B), 57.4 (CH2), 52.7 (CH conformer A), 51.4 (CH conformer
B). MS (FAB+): m/z (%) 483 (M+ + 1, 6), 391 (20), 274 (60). HRMS
(LSIMS): m/z 482.9096; calcd for [C17H10N2O3S6 + H]+, 482.9089.
Anal. Calcd for C17H10N2O3S6: C 42.31, H 2.09, N 5.80. Found: C
42.22, H 2.21, N 5.69.
+
(100). HRMS (LSIMS): m/z 537.9283; calcd for C20H14N2O4S6 ,
537.9278. Anal. Calcd for C20H14N2O4S6: C 44.59, H 2.62, N 5.20.
Found: C 44.67, H 2.55, N 5.14.
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-4,6-dioxotetrahydro-
5H-[1,3]dithiolo[4,5-c]pyrrole-5-carboxamide (3i). 27 mg (38%),
orange solid, mp 114−115 °C (dec.) (EtOAc), 58/42 ratio of
̃
conformers. IR (KBr): ν = 3432, 2923, 1790, 1716, 1635, 1261, 1096
(3aR,6aS)(Z/E)-2-(4-Benzyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-methyldihydro-4H-
[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6b). 54 mg (70%),
orange solid, mp 200−203 °C (dec.) (DCM). IR (KBr): ν = 1706,
̃
cm−1. 1H NMR (CDCl3, 300 MHz): δ 8.59 (br s, 2H, NH2), 5.15 (d, J =
8.5 Hz, 0.58H, CH conformer A), 5.05 (d, J = 8.9 Hz, 0.42H, CH
conformer B), 4.90 (d, J = 8.5 Hz, 0.58H, CH conformer A), 4.66 (d, J =
8.9 Hz, 0.42H, CH conformer B), 3.64−3.51 (m, 1H, CH2 conformer A/
B), 3.31−3.16 (m, 1H, CH2 conformer A/B), 1.15 (t, J = 6.9 Hz, 1.26H,
1660, 1432, 1283 cm−1. 1H NMR (CDCl3, 300 MHz): δ 7.32−7.04 (m,
5H, HAr), 5.15 (d, J = 8.6 Hz, 0.59H, CH conformer A), 5.07 (d, J = 9.0
Hz, 0.41H, CH conformer B), 4.92 (d, J = 8.6 Hz, 0.59H, CH conformer
A), 4.67 (d, J = 9.0 Hz, 0.41H, CH conformer B), 4.56 (d, J = 14.3 Hz,
0.59H, CH2 conformer A), 4.50 (d, J = 14.7 Hz, 0.41H, CH2 conformer
B), 4.17−4.12 (m, 1H, CH2 conformer A/B), 3.15 (s, 1.23H, CH3
conformer B), 3.06 (s, 1.77H, CH3 conformer A). 13C NMR (CDCl3, 75
MHz): δ 201.0, 200.6, 184.5, 184.3, 172.9, 172.5, 172.2, 172.1, 171.1,
164.8, 162.4, 151.8, 150.9 (Cq conformer A/B), 135.1, 135.2 (CHAr
conformer A/B), 133.1, 132.9, 131.6 (Cq conformer A/B), 129.6, 129.5,
128.5, 128.4 (CHAr conformer A/B), 59.8 (CH conformer A), 58.7 (CH
conformer B), 57.4 (CH2 conformer B), 57.3 (CH2 conformer A), 51.4
(CH conformer A), 50.3 (CH conformer B), 26.1 (CH3 conformer B),
25.9 (CH3 conformer A). MS (FAB+): m/z (%) 497 (M+ + 1, 10), 464
(15), 405 (60), 301 (100). HRMS (LSIMS): m/z 495.9181; calcd for
CH3 conformer B), 1.14 (t, J = 6.9 Hz, 1.74H, CH3 conformer A). 13
C
NMR (CDCl3, 75 MHz): δ 201.3, 200.9, 184.8, 172.3, 171.5, 171.4,
151.1, 150.4, 133.6, 132.5, 125.0 (Cq conformer A/B), 60.7 (CH
conformer A), 59.7 (CH conformer B), 52.5 (CH conformer A), 51.2
(CH conformer B), 48.8 (CH2 conformer A), 48.7 (CH2 conformer B),
13.3 (CH3 conformer A), 13.2 (CH3 conformer B). MS (FAB+): m/z (%)
464 (M+ + 1, 20), 391 (100), 340 (55), 177 (82). HRMS (LSIMS): m/z
463.8984; calcd for [C13H9N3O4S6 + H]+, 463.8991. Anal. Calcd for
C13H9N3O4S6: C 33.68, H 1.96, N 9.06. Found: C 33.56, H 2.08, N 8.97.
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-((E)-
phenyldiazenyl)phenyl)dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-
4,6(5H)-dione (3j). 47 mg (51%), orange solid, mp 175−176 °C (dec.)
̃
(EtOAc/MeOH 95:5), 55/45 ratio of conformers. IR (KBr): ν = 3010,
+
C18H12N2O3S6 , 495.9172. Anal. Calcd for C18H12N2O3S6: C 43.53, H
2957, 1789, 1718, 1667, 1380, 1189 cm−1. 1H NMR (CDCl3, 400 MHz):
δ 8.05−7.99 (m, 2H, HAr), 7.94−7.91 (m, 2H, HAr), 7.55−7.50 (m, 5H,
HAr), 5.32 (d, J = 8.6 Hz, 0.55H, CH conformer A), 5.22 (d, J = 9.0 Hz,
0.45H, CH conformer B), 5.06 (d, J = 8.6 Hz, 0.55H, CH conformer A),
4.85 (d, J = 9.0 Hz, 0.45H, CH conformer B), 3.66−3.51 (m, 1H, CH2
conformer A/B), 3.35−3.18 (m, 1H, CH2 conformer A/B), 1.16 (t, J =
7.1 Hz, 1.35H, CH3 conformer B), 1.15 (t, J = 7.1 Hz, 1.65H, CH3
conformer A). 13C NMR (CDCl3, 100 MHz): δ 201.2, 200.8, 184.8,
184.6, 171.7, 171.5, 165.9, 163.8, 152.4, 152.2, 152.1, 150.2, 133.6, 132.7,
132.6, 132.4 (Cq conformer A/B), 131.5, 129.1, 126.7, 123.6, 123.5,
123.0 (CHAr), 60.0 (CH conformer A), 58.6 (CH conformer B), 51.5
(CH conformer A), 50.5 (CH conformer B), 48.8 (CH2 conformer A),
48.7 (CH2 conformer B), 13.3 (CH3 conformer A/B). MS (FAB+): m/z
(%) 601 (M+ + 1, 10), 600 (M+, 10). HRMS (LSIMS): m/z 600.9616;
calcd for [C24H16N4O3S6 + H]+, 600.9625. Anal. Calcd for
2.44, N 5.64. Found: C 43.64, H 2.35, N 5.52.
(3aR,6aS)(Z/E)-2-(4-Benzyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(tert-butyl)-
dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6c). 62
mg (74%), orange solid, mp 185−186 °C (dec.) (DCM), 55/45 ratio
of conformers. IR (KBr): ν
̃
= 1706, 1650, 1331, 1159 cm−1. 1H NMR
(CDCl3, 300 MHz): δ 7.31−7.04 (m, 5H, HAr), 5.02 (d, J = 8.8 Hz,
0.55H, conformer A), 4.89 (d, J = 9.1 Hz, 0.45H, conformer B), 4.79 (d, J
= 8.8 Hz, 0.55H, conformer A), 4.58−4.49 (m, 1.45H, CH conformer B
and CH2 conformer A/B), 4.20−4.11 (m, 1H, CH2 conformer A/B),
1.64 (s, 4.05H, (CH3)3 conformer B), 1.58 (s, 4.95 H (CH3)3 conformer
A). 13C NMR (CDCl3, 75 MHz): δ 200.6, 200.2, 184.4, 184.1, 172.9,
172.5, 172.3, 172.4, 164.7, 162.4, 151.5, 151.0 (Cq conformer A/B),
135.0, 134.8 (CHAr conformer A/B), 132.8, 132.7, 132.5, 131.3, 131.2
(Cq conformer A/B), 129.2, 129.0, 128.1, 127.9 (CHAr conformer A/
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B), 127.4, 127.1 (Cq conformer A/B), 60.5 (CH conformer A), 60.4
(Cq conformer A/B), 59.9 (CH conformer B), 58.5 (CH2), 52.3 (CH
conformer A), 51.0 (CH conformer B), 29.7 (3 × CH3 conformer B), 28.1
(3 × CH3 conformer A). MS (FAB+): m/z (%) 539 (M+ + 1, 30), 447
(70), 391 (70), 349 (90). HRMS (LSIMS): m/z 537.9635; calcd for
C23H13IN2O3S6: C 40.35, H 1.91, N 4.09. Found: C 40.44, H 1.83, N,
3.98.
General Procedure for the Catalytic Cycloaddition of 4-
Ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3,5-dithione (7)
and Maleimides 2b,f,g. Maleimide 2b,f,g (2 equiv) and Sc(OTf)3
(37 mg, 0.075 mmol) were added under nitrogen to 7 (50 mg, 0.15
mmol) dissolved in dry dichloromethane (10 mL), and the mixture was
refluxed for 1 h (for 2b,g) or 2 h (for 2c). Then the solvent was
evaporated under reduced pressure, and the residue was purified by
column chromatography [silica 230−400 mesh, eluting with light
petroleum to dichloromethane/ethyl acetate mixtures (95:5 for 8b,g,
90:10 for 8f)] to get 8b,f,g. Analytical samples were obtained by thin-
layer chromatography (glass plates, silica 20 cm × 20 cm × 0.1 cm,
eluting with dichloromethane/ethyl acetate mixtures).
+
C21H18N2O3S6 , 537.9642. Anal. Calcd for C21H18N2O3S6: C 46.82, H
3.37, N 5.20. Found: C 46.69, H 3.46, N 5.12.
(3aR,6aS)(Z/E)-5-Benzyl-2-(4-benzyl-3-oxo-6-thioxo-3H,4H-
[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6e). 59 mg (66%), orange
solid, mp 116−117 °C (dec.) (DCM), 62/38 ratio of conformers. IR
(KBr): ν
̃
= 3024, 2924, 1709, 1649, 1387, 1276, 1064 cm−1. 1H NMR
(CDCl3, 300 MHz): δ 7.43−7.20 (m, 8H, HAr), 7.06−7.01 (m, 2H,
HAr), 5.11 (d, J = 8.6 Hz, 0.62H, CH conformer A), 5.02 (d, J = 9.0 Hz,
0.38H, CH conformer B), 4.91 (d, J = 8.6 Hz, 0.62H, CH conformer A),
4.77 (s, 0.76H, CH2 conformer B), 4.67 (s, 1.24H, CH2 conformer A),
4.64 (d, J = 9.0 Hz, 0.38H, CH conformer B), 4.59 (d, J = 14.3 Hz, 0.62H,
CH2 conformer A), 4.52 (d, J = 14.2 Hz, 0.38H, CH2 conformer B), 4.12
(d, J = 14.2 Hz, 0.38H, CH2 conformer B), 4.11 (d, J = 14.3 Hz, 0.62H,
CH2 conformer A). 13C NMR (CDCl3, 75 MHz): δ 201.1, 200.6, 184.5,
184.4, 172.5, 172.1, 171.9, 171.8, 164.5, 162.4, 151.7, 150.9, 135.3, 135.1,
134.5, 134.4, 133.1, 132.9, 131.7, 131.6 (Cq conformer A/B), 129.6,
129.5, 129.1, 128.9, 128.8, 128.5, 128.4 (CHAr conformer A/B), 59.9
(CH conformer A), 58.8 (CH conformer B), 57.4 (CH2 conformer A/B),
51.4 (CH conformer A), 50.2 (CH conformer B), 43.7 (CH2 conformer
A/B). MS (FAB+): m/z (%) 573 (M+ + 1, 50), 481 (100), 386 (85), 296
(69), 214 (71). HRMS (LSIMS): m/z 572.9564; calcd for
[C24H16N2O3S6 + H]+, 572.9558. Anal. Calcd for C24H16N2O3S6: C
50.33, H 2.82, N 4.89. Found: C 50.41, H 2.75, N 4.83.
(2Z/E,2′E/Z,3aR,3a′R,6aS,6a′S)-2,2′-(4-Ethyl-2,6-dithioxothio-
morpholine-3,5-diylidene)bis(5-methyldihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione) (8b). 54 mg (65%), light-
brown solid, mp 144−145 °C (dec.) (DCM/EtOAc 95:5), 60/24/13/3
1
ratio of conformers. IR (KBr): ν
̃
= 1708, 1650, 1420, 1365 cm−1. H
NMR (DMSO-d6, 400 MHz): δ 5.66−5.51 (m, 2H, 2 × CH conformer
A/B/C), 5.36−5.22 (m, 2H, 2 × CH conformer A/B/C), 3.30−3.20 (m,
2H, CH2), 2.95 (s, 1.49H, 2 × CH3 conformer B), 2.94 (s, 1.83H, CH3
conformer A), 2.90 (s, 1.83H, CH3 conformer A), 2.89 (s, 0.85H, 2 ×
CH3 conformer C), 1.14−1.03 (m, CH3). 13C NMR (DMSO-d6, 100
MHz): δ 201.1, 199.8, 199.7, 198.4, 173.9, 173.8, 173.6, 173.5, 173.4,
173.3, 173.1, 172.0, 171.9, 171.3, 170.8, 135.0, 134.3, 134.0, 133.2 (Cq
conformer A/B/C), 60.4, 60.3, 59.8, 59.6, 51.0, 50.9, 50.4 (CH
conformer A/B/C), 50.3 (CH2), 50.0 (CH conformer A/B/C), 25.6,
25.5, 25.4 (CH3 conformer A/B/C), 13.0, 12.9 (CH3 conformer A/B/
C). MS (FAB+): m/z (%) 562 (M+ + 1, 12), 392 (30), 281 (36), 167
(100). HRMS (LSIMS): m/z 561.9175; calcd for [C18H15N3O4S7 +
H]+, 561.9181. Anal. Calcd for C18H 15N3O4S7: C 38.49, H 2.69, N 7.48.
Found: C 38.36, H 2.77, N 7.40.
(3aR,6aS)(Z/E)-2-(4-Benzyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-phenyldihydro-4H-
[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6f). 44 mg (51%),
orange solid, mp 210−211 °C (dec.) (DCM), 65/35 ratio of
conformers. IR (KBr): ν
̃
= 3024, 1705, 1654, 1623, 1383, 1184 cm−1.
(2Z/E,2′E/Z,3aR,3a′R,6aS,6a′S)-2,2′-(4-Ethyl-2,6-dithioxothio-
morpholine-3,5-diylidene)bis(5-phenyldihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione) (8f). 68 mg (67%), light-
1H NMR (DMSO-d6, 400 MHz): δ 7.56−6.99 (m, 10H, HAr), 5.83 (d, J
= 8.9 Hz, 0.65H, CH conformer A), 5.66 (d, J = 9.2 Hz, 0.35H, CH
conformer B), 5.58 (d, J = 8.9 Hz, 0.65H, CH conformer A), 5.35 (d, J =
9.2 Hz, 0.35H, CH conformer B), 4.40 (d, J = 14.4 Hz, 0.65H, CH2
conformer A), 4.37 (d, J = 14.1 Hz, 0.35H, CH2 conformer B) 4.19 (d, J =
14.1 Hz, 0.35H, CH2 conformer B), 4.12 (d, J = 14.4 Hz, 0.65H, CH2
conformer A). 13C NMR (DMSO-d6, 100 MHz): δ 200.6, 199.9, 184.9,
173.1, 172.8, 172.6, 168.4, 166.6, 152.0, 151.7, 135.5, 132.0, 131.7, 131.6,
131.5 (Cq conformer A/B), 129.4, 129.3, 129.1, 129.0, 128.9, 128.3,
128.2, 127.0, 126.9 (CHAr), 60.7 (CH conformer A), 59.5 (CH
conformer B), 56.6 (CH2 conformer A), 56.5 (CH2 conformer B), 51.8
(CH conformer A), 50.6 (CH conformer B). MS (FAB+): m/z (%) 559
(M+ + 1, 15), 467 (62), 386 (50), 295 (40), 237 (100). HRMS
brown solid, mp 104−105 °C (dec.) (DCM/EtOAc 90:10), 45/45/7/3
1
ratio of conformers. IR (KBr): ν
̃
= 1717, 1633, 1378 cm−1. H NMR
(DMSO-d6, 400 MHz): δ (for the main conformer) 7.52−7.33 (m, 10H,
HAr), 5.81 (d, J = 8.8 Hz, 1H, CH), 5.68 (d, J = 9.0 Hz, 1H, CH), 5.54 (d,
J = 8.8 Hz, 1H, CH), 4.45 (d, J = 9.0 Hz, 1H, CH), 3.35 (q, J = 7.0 Hz,
2H, CH2), 1.12 (t, J = 7.0 Hz, 3H, CH3). 13C NMR (DMSO-d6, 100
MHz): δ (for the main conformer) 201.0, 198.7, 173.0, 172.9, 172.6,
172.5, 172.1, 171.0, 135.0, 133.6 (Cq), 131.6, 131.5, 129.2, 129.1, 127.0,
126.9 (CHAr), 60.7, 60.1, 51.5, 50.7 (CH), 50.5 (CH2), 13.0 (CH3). MS
(FAB+): m/z (%) 686 (M+ + 1, 40), 513 (58). HRMS (LSIMS): m/z
685.9485; calcd for [C28H19N3O4S7 + H]+, 685.9494. Anal. Calcd for
C28H19N3O4S7: C 49.03, H 2.79, N 6.13. Found: C, 49.12, H 2.68, N
6.05.
+
(LSIMS): m/z 557.9322; calcd for C23H14N2O3S6 , 557.9329. Anal.
Calcd for C23H14N2O3S6: C 49.44, H 2.53, N 5.01. Found: C 49.33, H
2.61, N 4.92.
(2Z/E,2′E/Z,3aR,3a′R,6aS,6a′S)-2,2′-(4-Ethyl-2,6-dithioxothio-
morpholine-3,5-diylidene)bis(5-(4-iodophenyl)dihydro-4H-
[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione) (8g). 21 mg (15%),
light-brown solid, mp 184−185 °C (dec.) (DCM/EtOAc 95:5), 75/
(3aR,6aS)(Z/E)-2-(4-Benzyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-iodophenyl)-
dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-dione (6g). 51
mg (48%), orange solid, mp 155−156 °C (dec.) (DCM/EtOAc
12/11/2 ratio of conformers. IR (KBr): ν
̃
= 1710, 1640, 1375 cm−1. 1H
NMR (DMSO-d6, 400 MHz): δ (for the main conformer) 7.92−7.85
(m, 2H, HAr), 7.70−7.65 (m, 2H, HAr), 7.21−7.17 (m, 2H, HAr), 7.10−
7.07 (m, 2H, HAr), 5.78 (d, J = 8.7 Hz, 2H, 2 × CH), 5.47 (d, J = 8.7 Hz,
2H, 2 × CH), 3.32 (q, J = 7.2 Hz, 2H, CH2), 1.24 (t, J = 7.2 Hz, 3H,
CH3). 13C NMR (DMSO-d6, 100 MHz): δ (for the main conformer)
199.9, 172.7, 172.2, 172.0 (Cq), 137.8 (CHAr), 134.4, 131.1 (Cq), 129.0
(CHAr), 95.2 (Cq), 60.5 (CH), 51.5 (CH), 34.31 (CH2), 13.0 (CH3).
MS (FAB+): m/z (%) 938 (M+ + 1, 1). Anal. Calcd for C28H17I2N3O4S7:
C 35.87, H 1.83, N 4.48. Found: C 35.96, H 1.75, N 4.36.
̃
95:5), 55/45 ratio of conformers. IR (KBr): ν = 3022, 1707, 1654, 1380,
1182 cm−1. 1H NMR (CDCl3, 300 MHz): δ 7.87−7.77 (m, 2H, HAr),
7.37−7.05 (m, 7H, HAr), 5.31 (d, J = 8.4 Hz, 0.55H, CH conformer A),
5.19 (d, J = 8.9 Hz, 0.45H, CH conformer B), 5.08 (d, J = 8.4 Hz, 0.55H,
CH conformer A), 4.83 (d, J = 8.9 Hz, 0.45H, CH conformer B), 4.58 (d, J
= 14.2 Hz, 0.55H, CH2 conformer A), 4.54 (d, J = 14.2 Hz, 0.45H, CH2
conformer B), 4.19 (d, J = 14.2 Hz, 0.45H, CH2 conformer B), 4.15 (d, J =
14.2 Hz, 0.55H, CH2 conformer A). 13C NMR (CDCl3, 75 MHz): δ
201.3, 201.0, 184.4, 171.4, 171.1, 170.6, 170.5, 151.7, 150.8 (Cq
conformer A/B), 138.6, 138.5 (CHAr conformer A/B), 135.2, 135.0,
133.4, 131.6 (Cq conformer A/B), 129.7, 129.6, 128.8, 128.5, 127.7,
127.6 (CHAr conformer A/B), 94.9, 94.8 (Cq conformer A/B), 59.9
(CH conformer A), 58.6 (CH conformer B), 57.4 (CH2), 51.6 (CH
conformer A), 50.4 (CH conformer B). MS (FAB+): m/z (%) 685 (M+ +
1, 10), 593 (30), 410 (28), 340 (80), 177 (100). HRMS (LSIMS): m/z
684.8374; calcd for [C23H13IN2O3S6 + H]+, 684.8368. Anal. Calcd for
General Procedure for the Catalytic Cycloaddition of 4-
Ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3-oxo-5-thione 1
and Bismaleimides 9a−c. Bismaleimide 9a−c (1 equiv) and
Sc(OTf)3 (19 mg, 0.038 mmol or 37 mg, 0.075 mmol) were added
under nitrogen to 1 equiv (50 mg, 0.15 mmol, method A) or 2 equiv
(100 mg, 0.30 mmol, method B) of 1 dissolved in dry dichloromethane
(10 mL), and the mixture was refluxed for 1 h. Then the solvent was
evaporated under reduced pressure, and the residue was purified by
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column chromatography (silica 230−400 mesh, eluting with light
petroleum/dichloromethane 60:40 to dichloromethane/ethyl acetate
90:10) to get 10a−b and 11a−c. Analytical samples were obtained by
thin-layer chromatography (glass plates, silica 20 cm × 20 cm × 0.1 cm,
eluting with dichloromethane/ethyl acetate mixtures).
(CHAr), 60.2, 58.9, 51.8, 50.6 (CH conformers A/B/C/D), 49.0, 48.9
(CH2 conformers A/B/C/D), 41.3 (CH2), 13.6 (CH3 conformers A/B/
C/D). MS (FAB+): m/z (%) 1006 (M+ + 2, 14), 880 (15), 599 (32).
HRMS (LSIMS): m/z 1005.8487; calcd for [C37H24N4O6S12 + 2H]+,
1005.8501. Anal. Calcd for C37H24N4O6S12: C 44.20, H 2.41, N 5.57.
Found: C 44.14, H 2.35, N 5.45.
(3aR,6aS)(Z/E)-5-(4-(4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-
yl)benzyl)phenyl)-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (10a). 59 mg (56%) by
method A or 26 mg (25%) by method B, orange solid, mp 285−286
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-((3aR,6aS)(E/Z)-
2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]-
thiazin-5(6H)-ylidene)-4,6-dioxotetrahydro-5H-[1,3]dithiolo-
[4,5-c]pyrrol-5-yl)phenyl)dihydro-4H-[1,3]dithiolo[4,5-c]-
pyrrole-4,6(5H)-dione (11b). 24 mg (17%) by method A or 34 mg
(24%) by method B, orange solid, mp 214−215 °C (dec.) (DCM/
°C (dec.) (DCM/EtOAc 90:10), 53/47 ratio of conformers. IR (KBr): ν
̃
1
= 1788, 1712, 1666, 1639, 1536, 1376 cm−1. H NMR (CDCl3, 400
MHz): δ 7.32−7.21 (m, 8H, HAr), 6.83 (s, 0.94H, CHvin conformer B),
6.82 (s, 1.06H, CHvin conformer A), 5.24 (d, J = 8.4 Hz, 0.53H, CH
conformer A), 5.12 (d, J = 9.2 Hz, 0.47H, CH conformer B), 4.98 (d, J =
8.4 Hz, 0.53H, CH conformer A), 4.74 (d, J = 9.2 Hz, 0.47H, CH
conformer B), 4.04 (s, 0.94H, CH2 conformer B), 4.01 (s, 1.06H, CH2
conformer A), 3.63−3.49 (m, 1H, CH2 conformer A/B), 3.31−3.16 (m,
1H, CH2 conformer A/B), 1.13 (t, J = 7.2 Hz, 1.59H, CH3 conformer A),
1.12 (t, J= 7.2 Hz, 1.41H, CH3 conformer B). 13C NMR and DEPT
(CDCl3, 100 MHz): δ 201.1, 200.7, 184.7, 184.5, 171.8, 171.7, 171.1,
169.5, 165.0, 162.9, 151.1, 150.2, 141.8, 141.7, 140.0 (Cq conformer A/
B), 134.2 (CH conformer A/B), 133.5, 133.4, 132.4 (Cq conformer A/
B), 129.8, 129.7, 129.6 (CH conformer A/B), 129.4, 126.3, 129.0, 128.9
(Cq conformer A/B), 126.2, 126.1 (CH conformer A/B), 59.9, 58.6,
51.5, 50.4 (CH conformer A/B), 48.8, 48.6 (CH2 conformer A/B), 41.1,
41.0 (CH2 conformer A/B), 13.3, 13.2 (CH3 conformer A/B). MS
(FAB+): m/z (%) 684 (M+ + 2, 9), 487 (22), 391 (45). HRMS (LSIMS):
m/z 682.9813; calcd for [C29H19N3O5S6 + 2H]+, 682.9805. Anal. Calcd
for C29H19N3O5S6: C 51.08, H 2.81, N 6.16. Found: C 51.21, H 2.90, N
6.17.
̃
EtOAc 90:10), mixture of conformers. IR (KBr): ν = 1788, 1720, 1666,
1633, 1536, 1361 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.53−7.46 (m,
4H, HAr), 5.28−5.25 (m, 1.11H, mixture of conformers), 5.18−5.14 (m,
0.89H, mixture of conformers), 5.04−5.00 (m, 1.11H, mixture of
conformers), 4.79−4.75 (m, 0.89H, mixture of conformers), 3.65−3.51
(m, 2H, CH2), 3.36−3.17 (m, 2H, CH2), 1.17−1.12 (m, 6H, CH3). 13
C
NMR and DEPT (CDCl3, 100 MHz): δ 201.5, 201.4, 184.7, 171.5,
171.3, 171.2, 170.7, 170.6, 150.1, 146.5, 134.3, 133.7, 132.5 (Cq), 126.9
and 126.8 (CHAr), 59.9, 58.6, 51.5, 50.4 (CH, mixture of conformers),
48.8, 48.7 (CH2, mixture of conformers), 13.3 (CH3, mixture of
conformers). MS (FAB+): m/z (%) 915 (M+ + 1, 12), 391 (18), 338
(21). HRMS (LSIMS): m/z 914.7964; calcd for [C30H18N4O6S12 + H]+,
914.7953. Anal. Calcd for C30H18N4O6S12: C 39.37, H 1.98, N 6.12.
Found: C 39.49, H 1.89, N 6.02.
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(2-(2-(2-((3aR,6aS)-
(E/Z)-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]-
thiazin-5(6H)-ylidene)-4,6-dioxotetrahydro-5H-[1,3]dithiolo-
[4,5-c]pyrrol-5-yl)ethoxy)ethoxy)ethyl)dihydro-4H-[1,3]-
dithiolo[4,5-c]pyrrole-4,6(5H)-dione (11c). 31 mg (21%) by
method B, orange solid, mp 145−146 °C (dec) (DCM/EtOAc
(3aR,6aS)(Z/E)-5-(4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)-
phenyl)-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b]-
[1,4]thiazin-5(6H)-ylidene)dihydro-4H-[1,3]dithiolo[4,5-c]-
pyrrole-4,6(5H)-dione (10b). 25 mg (27%) by method A or 24 mg
(26%) by method B, orange solid, mp >300 °C (dec.) (DCM/EtOAc
̃
90:10), mixture of conformers. IR (KBr): ν = 1783, 1709, 1651, 1393
1
cm−1. H NMR (CDCl3, 400 MHz): δ 5.31−4.71 (m, 4H), 3.79 (m,
14H), 3.29−3.18 (m, 2H), 1.18−1.12 (m, 6H). 13C NMR (CDCl3, 100
MHz): δ 200.9, 200.6, 184.5, 173.3, 173.2, 172.4, 163.8, 150.4, 133.4,
132.6, 132.5, 130.9, 128.8, 125.0 (Cq, mixture of conformers), 70.0, 66.7
(CH2, mixture of conformers), 59.8, 58.8, 51.6, 50.1 (CH, mixture of
conformers), 48.8, 48.7, 39.4, 39.2 (CH2, mixture of conformers), 13.3,
13.2 (CH3, mixture of conformers). MS (FAB+): m/z (%) 956 (M+ + 2,
1). Anal. Calcd for C30H26N4O8S12: C 37.72, H 2.74, N 5.87. Found: C
37.85, H 2.84, N 5.74.
̃
90:10), 55/45 ratio of conformers. IR (KBr): ν = 1789, 1715, 1666,
1634, 1536, 1367 cm−1. 1H NMR (CDCl3, 200 MHz): δ 7.57−7.42 (m,
4H, HAr), 6.88 (s, 0.9H, CHvin conformer B), 6.86 (s, 1.1H, CHvin
conformer A), 5.29 (d, J = 8.6 Hz, 0.55H, CH conformer A), 5.18 (d, J =
8.9 Hz, 0.45H, CH conformer B), 5.04 (d, J = 8.6 Hz, 0.55H, CH
conformer A), 4.79 (d, J = 8.9 Hz, 0.45H, CH conformer B), 3.70−3.47
(m, 1H, CH2 conformer A/B), 3.37−3.13 (m, 1H, CH2 conformer A/
B), 1.15 (t, J = 7.1 Hz, 3H, CH3 conformer A/B). 13C NMR and DEPT
(CDCl3, 50 MHz): δ 201.4, 176.5, 171.9, 169.0 (Cq conformer A/B),
134.3 (CH conformer A/B), 132.5 (Cq conformer A/B), 126.9, 126.8,
126.7, 126.3 (CH conformer A/B), 59.9, 58.6, 51.5, 50.4 (CH
conformer A/B), 48.8, 48.7 (CH2 conformer A/B), 13.3 (CH3
conformer A/B). MS (FAB+): m/z (%) 593 (M+ + 2, 1). Anal. Calcd
for C22H13N3O5S6: C 44.65, H 2.21, N 7.10. Found: C 44.51, H 2.28, N
7.03.
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-(4-((3aR,6aS)(E/
Z)-2-((Z/E)-4-ethyl-5-((3aR,6aS)-5-(4-(4-((3aR,6aS)(E/Z)-2-(4-
ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-
5(6H)-ylidene)-4,6-dioxotetrahydro-5H-[1,3]dithiolo[4,5-c]-
pyrrol-5-yl)benzyl)phenyl)-4,6-dioxotetrahydro-4H-[1,3]-
dithiolo[4,5-c]pyrrol-2-ylidene)-2,6-dithioxothiomorpholin-3-
ylidene)-4,6-dioxotetrahydro-5H-[1,3]dithiolo[4,5-c]pyrrol-5-
yl)benzyl)phenyl)dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-
4,6(5H)-dione (12). Maleimide 10a (60 mg, 0.088 mmol) and
Sc(OTf)3 (9 mg, 0.018 mmol) were added under nitrogen to 4-
ethylbis[1,2]dithiolo[3,4-b:4′,3′-e][1,4]thiazin-3,5-dithione (7) (15
mg, 0.044 mmol) dissolved in dry dichloromethane (10 mL), and the
mixture was refluxed for 6 hours. Then the solvent was evaporated under
reduced pressure, and the residue was purified by column chromatog-
raphy (silica 230−400 mesh, eluting with light petroleum to
dichoromethane/ethyl acetate 50:50) to get 12 (56 mg, 74% yield).
An analytical sample of 12 was obtained by thin-layer chromatography
(glass plates, silica 20 cm × 20 cm × 0.1 cm, eluting with
dichloromethane/ethyl acetate 50:50). Yellow solid, mp 238−239 °C
(3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-[1,2]-
dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-5-(4-(4-((3aR,6aS)(E/
Z)-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]-
thiazin-5(6H)-ylidene)-4,6-dioxotetrahydro-5H-[1,3]dithiolo-
[4,5-c]pyrrol-5-yl)benzyl)phenyl)dihydro-4H-[1,3]dithiolo[4,5-
c]pyrrole-4,6(5H)-dione (11a). 10 mg (13%) by method A or 86 mg
(55%) by method B, orange solid, mp 179−180 °C (dec.) (DCM/
̃
EtOAc 90:10), 25/28/23/24 ratio of conformers. IR (KBr): ν = 1788,
1719, 1665, 1657, 1633, 1510, 1376 cm−1. 1H NMR (CDCl3, 400 MHz):
δ 7.31−7.20 (m, 8H, HAr), 5.25 (d, J = 8.6 Hz, 0.50H, conformer A), 5.24
(d, J = 8.6 Hz, 0.52H, conformer B), 5.14 (d, J = 9.0 Hz, 0.48H, conformer
C), 5.13 (d, J = 8.9 Hz, 0.50H, conformer D), 4.99 (d, J = 8.6 Hz, 0.50H,
conformer A), 4.98 (d, J = 8.6 Hz, 0.52H, conformer B), 4.74 (d, J = 9.0
Hz, 0.48H, conformer C), 4.73 (d, J = 8.9 Hz, 0.50H, conformer D), 4.04
(d, J = 10.5 Hz, 1H, CH2), 4.01 (d, J = 10.5 Hz, 1H, CH2), 3.64−3.49 (m,
2H), 3.32−3.17 (m, 2H), 1.14 (t, J = 7.0 Hz, 6H, CH3). 13C NMR
(CDCl3, 100 MHz): δ 201.5, 201.1, 200.1, 185.0, 184.8, 172.1, 172.0,
171.9, 171.4, 171.3, 171.2, 165.0, 163.0, 151.3, 150.4, 141.8, 141.7, 141.6,
133.8, 133.7, 132.7 (Cq conformers A/B/C/D), 130.2, 130.1, 130.0
(CHAr), 129.4, 129.3, 129.2 (Cq conformers A/B/C/D), 126.5, 126.4
̃
(dec.) (DCM/EtOAc 50:50). IR (KBr): ν = 1790, 1715, 1664, 1635,
1537, 1378 cm−1. 1H NMR (CD2Cl2, 400 MHz): δ 7.37−7.19 (m, 16H,
HAr), 5.23−4.78 (m, 8H, 8 × CH), 4.11−4.06 (m, 4H, 2 × CH2), 3.61−
3.49 (m, 3H), 3.31−3.18 (m, 3H), 1.16−1.12 (m, 9H, CH3). 13C NMR
(CD2Cl2, 100 MHz): δ 201.9, 201,4, 184.8, 172.2, 171.9, 171.6, 171.5,
163.5, 151.3, 150.5, 142.1, 142.0 (Cq), 135.4 (CHAr), 134.4, 133.8,
133.7, 132.7 (Cq), 130.0, 126.6, 125.2 (CHAr), 60.3, 59.1, 51.8, 50.7
(CH), 49.0, 48.9, 41.2 (CH2), 13.3, 13.2 (CH3). MS (FAB+): m/z (%)
2223
dx.doi.org/10.1021/jo500076c | J. Org. Chem. 2014, 79, 2213−2225

The Journal of Organic Chemistry
Article
1702 (M+ + 1, 58), 1552 (70), 1389 (78), 1341 (100). HRMS (LSIMS):
m/z 1701.7826; calcd for [C66H43N7O10S19 + H]+, 1701.7838. Anal.
Calcd for C66H43N7O10S19: C 46.54, H 2.54, N 5.76. Found: C 46.54, H
2.54, N 5.76.
H]+, 1355.7385. Anal. Calcd for C42H33N7O9S18: C 37.18, H 2.45, N
7.23. Found: C 37.07, H 2.55, N 7.16.
Calculations. DFT calculations were performed with the hybrid
method known as B3LYP, in which the Becke three-parameter exchange
functional24 and the Lee−Yang−Parr correlation functional25 are used,
as implemented in the Gaussian 03 (revision C.02) program suite.26
Geometry optimizations and the nitrogen inversion barrier for the
simplified model 3 and geometry optimizations for compounds 3a, 3b,
and 3f were calculated using the 6-31G(d) basis for all the atoms,
whereas for the complex 3f[Hg]2+·MeCN the effective core potentials
(ECPs) of Hay and Wadt with a double-ζ valence basis set
(LANL2DZ)27 were used to describe Hg and the 6-31G(d) basis set
was used for the rest of the atoms. Energy values for structures related to
model 3 and compounds 3a and 3b were calculated by punctual
calculations on the obtained geometries using the same functional and
the 6-311+G(2d,p) basis set for all atoms. The transition state of the
simplified model for 3 was confirmed by a vibrational analysis (one
imaginary frequency) and an IRC calculation.28
Catalytic Cycloaddition of 4-Ethylbis[1,2]dithiolo[3,4-b:4′,3′-
e][1,4]thiazin-3-oxo-5-thione (1) and Trismaleimide 13. Trisma-
leimide 13 (60 mg, 0.15 mmol) and Sc(OTf)3 [19 mg, 0.038 mmol
(method A)/37 mg, 0.075 mmol (method B)/56 mg, 0.11 mmol
(method C)] were added under nitrogen to 1 [50 mg, 0.15 mmol
(method A)/100 mg, 0.30 mmol (method B)/150 mg, 0.45 mmol
(method C)] dissolved in dry dichloromethane (10 mL), and the
mixture was refluxed for 4 h. Then the solvent was evaporated under
reduced pressure, and the residue was purified by column chromatog-
raphy (silica 230−400 mesh, eluting with light petroleum to
dichloromethane/ethyl acetate 50:50) to get monoadduct 14, diadduct
15, or triadduct 16. Analytical samples were obtained by thin-layer
chromatography (glass plates, silica 20 cm × 20 cm × 0.1 cm, eluting
with dichloromethane/ethyl acetate mixtures).
1,1′-(((2-((3aR,6aS)(Z/E)-2-(4-Ethyl-3-oxo-6-thioxo-3H,4H-
[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-4,6-dioxotetra-
hydro-5H-[1,3]dithiolo[4,5-c]pyrrol-5-yl)ethyl)azanediyl)bis-
(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (14). 46 mg (42%) by
method A or 15 mg (14%) by method B or 12 mg (11%) by method C,
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra of the products and
coordinates of all stationary points for the calculated structures.
This material is available free of charge via the Internet at http://
pubs.acs.org.
orange solid, mp 255−256 °C (dec.) (DCM/EtOAc 50:50), 57/43 ratio
1
of conformers. IR (KBr): ν
̃
= 3099, 1782, 1711, 1404, 1332 cm−1. H
NMR (CDCl3, 400 MHz): δ 6.65 (s, 4H), 5.33 (d, J = 8.5 Hz, 0.57H, CH
adduct A), 5.22 (d, J = 9.0 Hz, 0.43H, CH adduct B), 5.03 (d, J = 8.5 Hz,
0.57H, CH adduct A), 4.84 (d, J = 9.0 Hz, 0.43H, CH adduct B), 3.59−
3.52 (m, 1H), 3.48 (t, J = 6.6 Hz, 4H), 3.41−3.34 (m, 2H), 3.26−3.12
(m, 1H), 2.67 (t, J = 6.6 Hz, 4H), 2.61−2.47 (m, 2H), 1.11−1.08 (m,
3H). 13C NMR (CDCl3, 100 MHz): δ 200.8, 200.3, 185.0, 184.9, 184.7,
173.3, 172.9, 171.0, 170.7, 166.8, 164.6, 151.5, 150.4, 134.3, 134.2, 133.3,
133.2, 132.7, 132.6, 125.1, 60.4, 59.4, 52.7, 51.7, 51.4, 50.6, 48.9, 48.8,
37.9, 35.8, 35.7, 13.5, 13.4. MS (FAB+): m/z (%) 711 (M+ + 2, 2). Anal.
Calcd for C26H23N5O7S6: C 43.99, H 3.27, N 9.87. Found: C 43.86, H
3.38, N 9.78.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ttorroba@ubu.es.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the Ministerio
́
(3aR,6aS)(Z/E)-5-(2-((2-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-
yl)ethyl)(2-((3aR,6aS)(E/Z)-2-(4-ethyl-3-oxo-6-thioxo-3H,4H-
[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-4,6-dioxotetra-
hydro-5H-[1,3]dithiolo[4,5-c]pyrrol-5-yl)ethyl)amino)ethyl)-2-
(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-
5(6H)-ylidene)dihydro-4H-[1,3]dithiolo[4,5-c]pyrrole-4,6(5H)-
dione (15). 15 mg (19%) by method A or 61 mg (38%) by method B or
32 mg (20%) by method C, orange solid, mp 240−241 °C (dec.)
de Economia y Competitividad, Spain (Project CTQ2012-
́
́ ́
31611), Junta de Castilla y Leon, Consejeria de Educacion y
Cultura y Fondo Social Europeo (Project BU246A12-1), and the
European Commission Seventh Framework Programme (Proj-
ect SNIFFER FP7-SEC-2012-312411).
DEDICATION
■
̃
(DCM/EtOAc 50:50), mixture of conformers. IR (KBr): ν = 1783,
This paper is dedicated to Dr. Stefano Marcaccini, who passed
away on October 1, 2012.
1
1706, 1655, 1532, 1404, 1342 cm−1. H NMR (CDCl3, 400 MHz): δ
6.65 (s, 2H), 5.49−4.79 (m, 4H), 3.56−3.13 (m, 10H), 2.68−2.45 (m,
6H), 1.12−1.08 (m, 6H). 13C NMR (CDCl3, 100 MHz): δ 200.5, 199.9,
184.8, 184.7, 184.5, 173.7, 173.4, 172.8, 172.7, 171.3, 171.2, 170.8, 170.7,
170.5, 166.6, 164.5, 164.4, 151.3, 150.5, 150.2, 135.0, 133.9, 133.0, 132.7,
132.4, 132.3, 124.8, 60.3, 60.2, 59.5, 59.2, 52.0, 51.2, 48.6, 37.7, 35.6,
35.5, 13.2, 13.1, 13.0. MS (FAB+): m/z (%) 1033 (M+ + 1, 49), 923 (25),
586 (38), 445 (18). HRMS (LSIMS): m/z 1032.8699; calcd for
[C34H28N6O8S12 + H]+, 1032.8690. Anal. Calcd for C34H28N6O8S12: C
39.52, H 2.73, N 8.13. Found: C 39.64, H 2.82, N 8.02.
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(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-
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(16). 7 mg (10%) by method A or 28 mg (20%) by method B or 90 mg
(43%) by method C, orange solid, mp 197−198 °C (dec.) (DCM/
̃
EtOAc 50:50), mixture of conformers. IR (KBr): ν = 1781, 1710, 1670,
1540, 1404, 1340 cm−1. 1H NMR (CDCl3, 400 MHz): δ 5.73−4.72 (m,
6H), 3.67−3.07 (m, 12H), 3.07−2.16 (m, 6H), 1.16−1.05 (m, 9H). 13C
NMR (CDCl3, 100 MHz): δ 199.2, 185.1, 174.3, 164.4, 151.3, 133.4,
132.4, 60.7, 59.9, 52.3, 51.8, 51.6, 50.8, 49.0, 37.3, 13.3, 13.2. MS
(FAB+): m/z (%) 1356 (M+ + 1, 24), 1005 (27), 923 (41), 682 (34), 433
(22). HRMS (LSIMS): m/z 1355.7396; calcd for [C42H33N7O9S18
+
2224
dx.doi.org/10.1021/jo500076c | J. Org. Chem. 2014, 79, 2213−2225

The Journal of Organic Chemistry
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