Dialkyl Dicyanofumarates as Oxidizing Reagents for the Conversion of Thiols into Disulfides and Selenols into Diselenides

Article abstract of DOI:10.1002/ejoc.201701066

Aliphatic and aromatic thiols react smoothly with dialkyl dicyanofumarates in CH₂Cl₂ at room temperature to give the corresponding disulfides in excellent yields. Aliphatic 1,2-, 1,3-, and 1,4-dithiols afford cyclic disulfides. Analogous reaction courses were observed for selenols, and the required diselenides also formed in nearly quantitative yields. In all of the reactions, dialkyl dicyanosuccinates formed as 1:1 mixtures of diastereoisomers as the only other product. Cysteamine (2-mercaptoethylamine) behaved differently; the Michael addition of the primary amine group led to the complete consumption of the dicyanofumarate, and the formation of the disulfide containing an enamine moiety occurred without the formation of dicyanosuccinate.

Full text of DOI:10.1002/ejoc.201701066

A Journal of
Accepted Article
Title: Dialkyl Dicyanofumarates as New Oxidizing Reagents for the
Conversion of Thiols into Disulfides and Selenols into Diselenides
Authors: Grzegorz Mloston, Antonella Capperucci, Damiano Tanini,
Róża Hamera-Fałdyga, and Heinz Heimgartner
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701066
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10.1002/ejoc.201701066
European Journal of Organic Chemistry
Dialkyl Dicyanofumarates as New Oxidizing Reagents
for the Conversion of Thiols into Disulfides and Selenols into Diselenides
Grzegorz Mlostoń,*[a] Antonella Capperucci,*[b] Damiano Tanini,[b] Róża Hamera-
Fałdyga,[a] and Heinz Heimgartner[c]
Dedicated ‘In Memoriam’ to Professor Jerzy Suwiński (1939-2017) (TU Gliwice,
Poland)
Abstract
Both aliphatic and aromatic thiols react smoothly with dialkyl dicyanofumarates in
CH2Cl2 at r.t. to give the corresponding disulfides in excellent yields. Aliphatic 1,2-,
1,3- and 1,4-dithiols afford cyclic disulfides. Analogous reaction courses were
observed starting with selenols and the required diselenides were also formed in
nearly quantitative yields. In all reactions, dialkyl dicyanosuccinates, formed as a 1:1-
mixture of diastereoisomers, were the only second product. Cysteamine (2-
mercaptoethylamine) behaved differently and the Michael addition of the primary
amino group led to complete consumption of the dicyanofumarate, and the formation
of the disulfide containing the enamine motive occurred without formation of
dicyanosuccinate.
[a] Prof. Dr. G. Mlostoń, Mgr. R. Hamera-Fałdyga
Department of Organic & Applied Chemistry, University of Łódź, Tamka 12,
PL-91-403 Łódż, Poland
[b] Prof. Dr. A. Capperucci, Dr. D. Tanini
Chemistry Department ‘Ugo Schiff’, University of Florence, I-50019 Sesto
Fiorentino, Italy
[c] Prof. Dr. H. Heimgartner
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-
8057 Zurich, Switzerland
KEYWORDS
1
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European Journal of Organic Chemistry
Disulfides, Diselenides, Dialkyl dicyanofumarates, SET mechanism, Michael addition
Introduction
Organic disulfides constitute a most relevant class of organic sulfur compounds with
great importance not only in organic synthesis, but also in biological, polymer and
materials chemistry.[1] Moreover, the formation and dissociation of the S–S bond is of
central importance in life sciences.[2] Disulfides play also an important role in
medicinal chemistry, especially in peptide-based therapeutics.[3] Different methods
are known for their preparation, but the most important is the oxidation of thiols by
treatment with diverse oxidizing agents, and the use of iodine offers the most popular
approach.[1b,4a] Other methods have to be applied to obtain non-symmetrical disulfides
and they have been summarized in a recent review.[4b] The formation of symmetrical
disulfides can also be achieved efficiently by using electron deficient reagents such as
azodicarboxylates[5] or 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione.[6] In these systems,
the addition of the thiol onto the activated N=N unit is proposed as the initial step of
the reaction. Subsequent nucleophilic attack of the second molecule of thiol on the
activated S-atom leads to the formation of the S–S bond.
Electron deficient ethenes were also used in reactions with thiols, and in some
instances the formation of disulfides was observed side by side with other products.
For example, the reaction of tetracyanoethene (TCNE) with a 3-mercapto-1,2,4-
triazine derivative gave, among other products, the corresponding disulfide in 46%
yield.[7] In another example, the disulfide derived from diethyl dithiophosphonate was
formed after treatment with TCNE. In this case, TCNE was reduced to 1,1,2,2-
tetracyanoethane without fragmentation.[8]
In a series of recent publications, reactions of electron deficient dialkyl
dicyanofumarates with primary amines[9] as well as with diverse dinucleophiles such
as 2-aminoalcohols[10] and 1,2-diamines[11] were described. In all studied reactions,
the initial step was the nucleophilic addition of the amino group, followed by
spontaneous elimination of HCN. The enamines formed thereby underwent secondary
conversions leading to cyclic products (heterocyclizations). For example, the reaction
of dimethyl dicyanofumarate (DCFM, 1a) with (S)-prolinamine (2a) afforded bicyclic
2
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piperazine derivatives 3[11] (Scheme 1). A similar reaction with 2-aminoethanol (4a)
led to the morpholinone derivative 5.[10]
Scheme 1. Reactions of DCFM (1a) with dinucleophiles 2a and 4a.
In the present study, reactions of 2-aminothiols as another class of dinucleophiles
should be examined in reactions with dialkyl dicyanofumarates 1. Thiols are known
as reactive nucleophiles[12] and Michael donors.[13] For that reason the comparison of
the reactivity of 2-aminothiols with 2-aminoalcohols and 1,2-diamines toward 1
would supplement the previous studies. It is also worth of mentioning that
aminothiols are important compounds from the biological point of view, and the
cytoprotective functions are of special interest.[14a,b] In addition, mercaptoalcohols and
mercaptoselenols are important building blocks for the preparation of sulfur and
selenium containing organic compounds with diverse functional groups.[14c]
Results and Discussion
Aniline (6a) reacts smoothly with diethyl dicyanofumarate (DCFE, 1b), and dimethyl
(Z)-2-cyano-3-phenylaminoethene-1,2-dicarboxylate (7a) was obtained as sole
1
product.[9] In the analogous experiment with 2-mercaptoaniline (6b), the H NMR
spectrum of the crude reaction mixture showed, along with the signals of aromatic H-
atoms and Et groups, two characteristic singlets at 4.24 and 4.18 ppm. After
chromatographic separation, two products were isolated, and the more polar one
showed these two singlets as well as two triplets and two quartets for two ethoxy
moieties. By comparison with original samples,[15] the isolated material was
indentified as 1:1-mixture of dl- and meso-diethyl 2,3-dicyanosuccinate (8b, Scheme
2).
3
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Scheme 2. Different pathways in reactions of DCFE (1b) with aniline (6a) and 2-
mercaptoaniline (6b).
o
The second product, isolated as yellow crystals (m.p. 88–90 C) from the less
polar fraction, was identified as 2,2’-diaminodiphenyldisulfide (9a).[16a] This
unexpected result prompted us to test 2-mercaptopyrimidine (10a) and 1-butyl-2-
mercapto-4,5-dimethylimidazole (10b)[16b] in the reaction with DCFM (1a). Whereas
in the case of 10a a slow formation of 8a and disulfide 9b[16c] (Scheme 3) was
observed at r.t., no disulfide was formed in the case of 10b, neither at r.t. nor in
boiling ClCH2CH2Cl (80 oC). In the latter case, a violet charge-transfer complex was
formed, which decomposed after evaporation of the solvent.
It is worth mentioning that 4-mercaptoaniline and other aromatic thiols are
reported to react at r.t. with DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone) in
CH2Cl2 solutions forming charge transfer complexes with absorption bands located
between 440 and 800 nm; in these systems no redox reactions leading to the formation
of the corresponding diaryl disulfides were observed.[16d]
4
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European Journal of Organic Chemistry
Scheme 3. Reactions of DCFM (1a) with 2-mercaptopyrimidine (10a) and 2-
mercaptoimidazole derivative 10b.
In our study, preliminary experiments were also performed with sterically
crowded thiols, but the attempted syntheses of disulfides starting either with tritylthiol
or tert-butylthiol and 1a (molar ratio 2:1) were unsuccessful, and after 24 h at r.t. only
1
non-converted substrates were detected in the H NMR spectra. These results point
out the influence of the steric hindrance on the studied redox processes.
In the next step of the study, selected binucleophiles such as β-amino thiols, β-
mercapto alcohols, and β-hydroxy selenols should be tested in reactions with dialkyl
dicyanofumarates. Firstly, the reactivity of cysteamine (11a) should be compared with
that of the aromatic analogue 6b. Equimolar amounts of 11a and DCFE (1b) were
reacted in CH2Cl2 at r.t. After 10 min, the reaction was complete, and the initially
formed blue color of the intermediate charge transfer complex practically vanished.
The 1H NMR spectrum of the crude mixture showed, unexpectedly, that in contrast to
the reaction with 6a no diethyl succinate 8b was formed. The chromatographic
separation gave one product only, which in the 1H NMR spectrum showed signals for
structural fragments of both 11a and 1b. The only new signal was a triplet at 9.64
ppm (J = 6.0 Hz), which could be attributed to a CH2-NH-C=C unit. Furthermore, the
13C NMR spectrum revealed three signals at low field for CN (116.0 ppm) and two
C=O groups (160.9 and 161.0 ppm). In addition, signals located at 167.9 and 72.2
ppm suggest the presence of an enamine of type 7. On the other hand, no indication of
1
a SH group could be found neither in the H NMR nor in the IR spectra. Finally, the
HRMS showed a peak at m/z = 565.1393, which corresponds with the molecular
formula C22H30N4NaO8S2 of disulfide 12b ([M+Na]+). An analogous reaction course
was observed in the reactions of 11a with DCFM (1a) and diisopropyl
dicyanofumarate (DCFP, (1c). In both cases, the corresponding disulfides 12a and
12c were obtained as the only products, and no formation of dicyanosuccinates was
observed.
5
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European Journal of Organic Chemistry
Scheme 4. Reactions of cysteamine (11a) and L-cysteine methyl ester (11b) with
dialkyl dicyanofumarates 1 leading to disulfides 12 with enamine units.
The reaction of freshly prepared L-cysteine methyl ester (11b), liberated from its
hydrochloride, with DCFM (1a) was performed using equimolar amounts of both
reagents. Also in this case, the reaction solution showed an intense blue coloration,
which disappeared after ca. 10 min. In analogy to the experiment with cysteamine
1
(11a), the H NMR analysis of the crude mixture did not reveal the presence of
dimethyl dicyanosuccinates. Chromatographic separation gave a product as an oily
fraction, formed side by side with minor admixtures of some non-identified
components. Based on spectroscopic data and comparison with the product 12a
obtained in the reaction of 1a with 11a, the isolated product was identified as the
analogous disulfide 12d containing the characteristic enamine moiety.
The absence of dicyanosuccinates in the reactions with cysteamine (11a) and L-
cysteine methyl ester (11b) points out that these reactions follow a different course.
The observed initial blue coloration of the reaction solution suggests that the first step
of the reaction with a β-aminothiol unit is the formation of a reactive charge-transfer
complex, which undergoes further transformations, e.g., the Michael addition of the
primary amino group followed by elimination of HCN to give enamine 7. Therefore,
6
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dicyanofumarate 1 is completely consumed, and the subsequent oxidation leading to
the disulfide 12 results from the presence of air oxygen or it is formed via an
unknown reaction mechanism. In contrast, the formation of disulfides 9 is governed
by a SET mechanism, and the initiating step is the electron transfer from the SH
group to the electron-deficient C=C bond of 1. Dicyanofumarates are well known as
powerful one-electron acceptors,[17a,b] and therefore they may act as oxidizing agents
for thiols via a SET mechanism.
The presented results obtained in reactions of 11a and 11b with dimethyl
dicyanofumarate (1a) differ drastically from those reported for 11a and typical
Michael acceptors, like α-methylidene lactones[17c,d] and α,β-unsaturated esters.[17e] In
all these cases, the –SH group reacted as Michael donor and the initial formation of
the corresponding sulfides was observed with no exception.
In our study, in an additional experiment, L-methionine methyl ester (11c) was
treated with dimethyl dicyanofumarate (1a) at room temperature, and after short
reaction time (5 min) the expected, stable enamine 7e was isolated in 52% yield
(Scheme 5).
Scheme 5. Reaction of L-methionine methyl ester (11c) with dimethyl
dicyanofumarate (1a) leading to enamine 7e.
Based on the results obtained with 2-mercaptoaniline (6a) and 2-
mercaptopyrimidine (10a), the study was extended by the involvement of thiophenol
(13a), octadecane-1-thiol (13b), propane-1,3-dithiol (13k) and ethane-1,2-dithiol
(13n, Table 1). All these thiols were efficiently oxidized with equimolar amounts of
DCFM (1a). The products obtained from 13a and 13b were identified as disulfides
14a and 14b, respectively (Scheme 6, Table 1). In the reactions with dithiols 13k and
13n, cyclic disulfides 14k and14n, respectively, were obtained in high yields.
Whereas 1,2-dithiolane 14k is formed via an intramolecuar oxidative ring closure of
7
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European Journal of Organic Chemistry
13k, 1,2,5,6-tetrathiocane (14n) is the product of an oxidative dimerization. In all
these reactions, the expected mixture of diastereoisomers of dimethyl
dicyanosuccinate (8a) was obtained in ca. equimolar amounts.
Scheme 6. Reactions of thiols 13 and selenols 15 with 1a to give disulfides 14 and
diselenides 16 (see Table 1 and 2).
Table 1. Reactions of methyl dicyanofumarate (DCFM, 1a) with thiols 13.
Yield
(%)a)
Entry
1
Thiol
PhSH
Disulfide
PhSSPh
13
a
14
a[18]
98
96
2
3
b[18]
b
c
c[18]
96
97
4
5
d[19]
d
e
95
94
e
6
f
f
8
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7
8
9
g[20]
h[21]
i[22]
92
94
98
g
h
i
10
j[22]
98
j
11
12
k[23]
89
98
k
l
l[24]
13
14
m[25]
96
82
m
n
n[26]
9
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a) Yield of isolated product.
Another group of thiols examined in reactions with DCFM (1a) involved
mercaptoalcohols 13c–f and 13l. Whereas substrates 13c–f delivered linear disulfides
14c–f, the latter afforded, in analogy to 13k, 4,5-dihydroxy-1,2-dithiane 14l via
intramolecular reaction. Another cyclic disulfide, 14m, was formed in excellent yield
from 3,3’-selenobis[1-(benzyloxy)propane]-2-thiol (13m, Table 1).
In two cases of enantiopure N-protected aminothiols, 13g and 13h, smooth
formation of the expected disulfides 14g and 14h, respectively, was observed. Finally,
cystein (13i) and the tripeptide glutathione (13j) were used as substrates for the
transformation into disulfides. In full agreement with the other thiols 13, the expected
products 14i and 14j were obtained in nearly quantitative yields (Table 1). In these
two cases, the primary amino groups exist as ammonium ions and therefore are
completely inactive toward the activated C=C bond of 1a.
In order to establish the scope of the application of the presented oxidative
disulfide formation, selected selenols were evaluated whether the diselenide bond can
be formed via a SET mechanism. Thus, the treatment of phenylselenol (15a) with
DCFM (1a, Scheme 6) was as efficient as in the case of 13a, and the known
diphenyldiselenide 16a was isolated in 98% yield (Table 2). Similar results were
obtained in three other experiments with aliphatic selenols 15b–d.
Table 2. Reactions of methyl dicyanofumarate (1a) with selenols 15.
Yield
(%)a)
Entry
1
Selenol
PhSeH
Diselenide
PhSeSePh
15
a
16
a[27]
98
2
3
b[28]
95
b
c
c[28]
96
10
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4
d[28]
97
d
a) Yield of isolated product.
Dialkyl dicyanofumarates and dicyanomaleates are known as prone one-electron
acceptors,[17a,b] and for that reason the presented conversions of thiols or selenols into
disulfides and diselenides, respectively, can be explained by the assumption that the
initiating step of the studied reactions is a single electron transfer (SET) leading to
pairs of elusive radical cations 17 and radical anions 18 (Scheme 7). Further
interaction of the radical cation 17 with the parent thiol 13 (or selenol 15) and transfer
of an H-atom leads to the ions 19 and 20 and via proton transfer to the respective
disulfide 14 (or diselenide 16) and succinates 8. No question, the reactions of
thiols/selenols with strongly electron deficient alkenes open a new field for
discussions about the reaction mechanisms involving chalcogens.
On the other hand, in a very recent publication by other authors, the mechanism
of the reaction of ethane-1,2-dithiol with the electron deficient TCNE was explained
via a stepwise ionic addition-cyclization-elimination route leading to a 1,4-dithiane
derivative.[29a]
11
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Scheme 7. Proposed SET mechanism for the formation of disulfides 14 and
diselenides 16 from thiols 13 and selenols 14, respectively, in the presence of dialkyl
dicyanofumarates 1.
However, the presence of the ‘free’ β-NH2 group in cysteamine (11a) or L-
cysteine methyl ester (11b) strongly modifies the behavior of the system. Very likely,
a fast irreversible Michael addition of the NH2 group onto the C=C bond of 1,
followed by the fast HCN elimination occurs, consuming the fumarate 1 completely.
The subsequent oxidation step occurs via H2 elimination or interaction with the air
oxygen without the involvement of dicyanofumarates 1 as oxidizing agents.
Conclusions
The presented studies showed that easily available electron-deficient dialkyl
dicyanofumarates can be applied for the efficient oxidation of thiols and selenols
leading to disulfides and diselenides, respectively. The reactions occur under mild
12
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conditions and, in general, the yields of the products are excellent. The only product
formed side-by-side with disulfides or diselenides is the corresponding dialkyl
dicyanosuccinate, obtained as a 1:1-mixture of diastereoisomers, which can easily be
separated from the target products by standard chromatographic methods. For all
these reasons, the described protocol can be recommended as a practically useful
approach to disulfides and diselenides. However, sterically bulky thiols such as
tritylthiol and tert-butylthiol do not undergo the oxidation reaction leading to the
desired disulfides. This is the first observation of an efficient application of fumaric
acid derivatives for the oxidative formation of disulfide and diselenide bonds. On the
other hand, it should be emphasized that fumaric acid and succinic acid form an
important red-ox system operating in biological systems.[30]
It seems likely that the SET mechanism formulated for the formation of dialkyl
dicyanosuccinates in the course of the oxidative conversion of thiols into disulfides
operates also in the reaction of dialkyl dicyanofumarates with diethyl phosphinate
described in our recent publication.[15]
However, the reactions with cysteamine and L-cysteine methyl ester deserve a
special comment as in these cases, in contrast to mercaptoalcohols and
hydroxyselenols, a competitive Michael addition of the primary amino group is
observed. The oxidation of the thiol function occurs without reduction of
dicyanofumarate. This amazing effect of the β-amino thiol motif cannot be explained
by the same interpretation formulated for all other cases studied and requires further
mechanistic investigation.
Acknowledgements: The authors (GM, RH-F, HH) thank the National Science
Center (Cracow, Poland) for a generous financial support within the Maestro-3
Project (Grant # Dec-2012/06/A/ST5/00219). We thank PD Dr. L. Bigler, University
of Zurich, for the registration of the HRMS and Ms M. Celeda, University of Łódź for
skillful help in performance of experiments with cysteamine.
Experimental Section
General
All reactions were carried out in oven-dried glassware under inert atmosphere (N2).
CH2Cl2 and MeOH were dried using a solvent purification system (Pure-Solv™). -
13
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Hydroxy- and -aminothiols were synthesized according to ref.[29b] Benzeneselenol is
commercially available. β-Substituted selenols were prepared through the procedure
developed in one of our groups.[31] L-Cysteine methyl ester hydrochloride, L-
methionine methyl ester hydrochloride, and cysteamine were purchased from Aldrich
and they were used without further purification. Flash column chromatography
purifications were performed with silica gel 60 (230-400 mesh). Thin layer
chromatography was carried out on TLC plates silica gel 60 F254. NMR spectra were
recorded in CDCl3 on a Varian Gemini 200, Varian Mercury 400 or Bruker Avance
1
III 600 spectrometer operating at 200, 400 and 600 MHz (for H), and 50, 100 and
13
150 MHz (for C). NMR signals were referenced to residual non-deuterated solvent
signals (7.26 ppm for 1H, 77.0 ppm for 13C). The abbreviations used are: s (singlet), d
(doublet), dd (doublet of doublet), m (multiplet), b (broad). Mass spectra were
determined by ESI using a LCQ Fleet™ Thermo Scientific spectrometer, HRMS
(ESI) on a Bruker maxis spectrometer. Elemental analysis was carried out with a
Perkin–Elmer 2400 series II elemental analyser.
Reaction of 2-mercaptoaniline (6b) and pyrimidine-2-thione (10a) with diethyl
dicyanofumarate (1b) – general procedure
Diethyl dicyanofumarate (1b, 0.222g, 1 mmol) was added to a solution of 2-
mercaptoaniline (6b, 0.250 g, 2 mmol) or pyrimidine-2-thione (10a, 0.224 g, 2 mmol)
in CH2Cl2 (4 mL). The mixture was stirred at r.t. for 20 min (for 6b) or 6 d (for 10a).
Next, the solvent was evaporated and the crude products were purified by PLC using
in both experiments a 1:1 mixture of petroleum ether and ethyl acetate. Analytically
pure samples were obtained after crystallization from methanol.
2,2’-Diaminodiphenyldisulfide (9a): Yellow crystals (220 mg, 99%); m.p. 88–90 °C
1
(ref.[16a], m.p. 94−96 °C). H NMR (600 MHz, CDCl3): δ = 4.33 (bs, 4H; 2 NH2),
6.57–6.62 (m, 2H; 2 CH), 6.71 (dd, J = 7.8, 1.2 Hz, 2H; 2 CH), 7.14–7.19 (m, 4H; 4
CH) ppm; 13C NMR (150 MHz, CDCl3): δ = 115.2, 118.2, 131.5, 136.8 (8 CH),
118.8, 148.6 (2 C–N, 2 C–S) ppm; IR (KBr): 458 (m), 472 (m), 673 (m), 699 (m), 746
(vs), 754 (vs), 1157 (m), 11247 (m), 1302 (m), 1311 (m), 1446 (s), 1473 (vs), 1584
(m), 1614 (s), 1625 (s), 3301 (s), 3380 (s) cm–1.
14
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2,2’-Dipyrimidyldisulfide (9b): Colorless crystals (after crystallization: 140 mg, 63%);
1
m.p. 139−141 °C (ref.[16b], m.p. 134−137 °C). H NMR (600 MHz, CDCl3): δ = 7.06
(pt, J = 4.8 Hz, 2CHarom), 8.56 (d, J = 4.8 Hz, 4CHarom).
Reaction of 1-butyl-2-mercapto-4,5-dimethylimidazole (10b) with dimethyl
dicyanofumarate (1a)
To a magnetically stirred solution of 10b (0.092 g, 0.5 mmol) in 2 mL of CH2Cl2,
crystalline 1a (0.097 g, 0.5 mmol) was added and the blue colored reaction solution
was stirred overnight at r.t. Then, the blue colored solution was evaporated and a
colorless solid residue was obtained after removal of the solvent. The obtained solid
was triturated with a portion of Et2O and filtered off. The crystalline material (m.p.
1
115–117 °C) obtained thereafter was analysed by running the H NMR spectrum,
which evidenced its identity with the starting 10b (ref.[16b], m.p. 134 °C).
Reactions of cysteamine (11a) with dialkyl dicyanofumarates 1a–c – general
procedure
To a solution of cysteamine (0.077g, 1 mmol) in CH2Cl2 (2 mL), the corresponding
dialkyl dicyanofumarate 1 (1 mmol) was added. The mixture was stirred at r.t. for 20
min. After this time, the solvent was evaporated and the crude product was purified
by chromatography (silica gel, petroleum ether/ethyl acetate 7:3).
N,N’-(Dithiodiethylene)bis((Z)-2-amino-3-cyano-2-butenedioic acid dimethyl ester)
(12a): Viscous colorless oil (77 mg, 32%); 1H NMR (600 MHz, CDCl3): δ = 2.85 (t, J
= 6.6 Hz, 4H; 2 CH2), 3.58–3.63 (m, 4H; 2 CH2), 3.79 (s, 6H; 2 CH3O), 3.99 (s, 6H; 2
13
CH3O), 9.65 (t, J = 5.4 Hz, 2H; 2 NH) ppm; C NMR (150 MHz, CDCl3): δ = 37.3,
44.7 (4 CH2), 52.2, 53.9 (4 CH3O), 72.0, 168.1 (2 C=C), 116.1 (2 C–N), 161.0, 161.2
(4 C=O) ppm; IR (KBr): 783 (m), 881 (w), 1062 (m), 1154 (m), 1271 (vs), 1434 (s),
1594 (vs), 1682 (s, C=O), 1746 (s, C=O), 2211 (s, CN), 2961 (m), 3243 (m) cm–1;
(+)-HRMS (ESI) (m/z): calcd. for C18H22N4NaS2O8 509.07713; found 509.07682.
N,N’-(Dithiodiethylene)bis((Z)-2-amino-3-cyano-2-butenedioic acid diethyl ester)
(12b): Viscous colorless oil (100 mg, 45%); 1H NMR (600 MHz, CDCl3): δ = 1.31 (t,
15
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J = 7.2 Hz, 6H; 2 CH3), 1.42 (t, J = 7.2 Hz, 6H; 2 CH3), 2.85 (t, J = 6.6 Hz, 4H; 2
CH2), 3.61 (q, J = 6.6 Hz, 4H; 2 CH2), 4.24 (q, J = 7.2 Hz, 4H; 2 CH2O), 4.45 (q, J =
13
7.2 Hz, 4H; 2 CH2O), 9.66 (t, J = 6.0 Hz, 2H; 2 NH) ppm; C NMR (150 MHz,
CDCl3): δ = 13.7, 14.2 (4 CH3), 37.4, 44.6 (4 CH2), 61.3, 63.9 (4 CH2O), 72.2, 167.9
(2 C=C), 116.0 (2 C–N), 160.9, 161.1 (4 C=O) ppm; IR (KBr): 783 (m), 857 (w),
1058 (m), 1174 (m), 1238 (s), 1270 (vs), 1369 (m), 1457 (m), 1592 (vs), 1675 (s,
C=O), 1744 (s, C=O), 2213 (s, CN), 2983 (m), 3237 (m), 3442 (m) cm–1. (+)-HRMS
(ESI) (m/z): calcd. for C22H30N4NaS2O8 565.13973; found 565.13926.
N,N’-(Dithiodiethylene)bis((Z)-2-amino-3-cyano-2-butenedioic acid diisopropyl
1
ester) (12c): Viscous colorless oil (100 mg, 33%); H NMR (600 MHz, CDCl3): δ =
1.29 (d, J = 6.6 Hz, 12H; 4 CH3), 1.42 (d, J = 6.6 Hz, 12H; 4 CH3), 2.86 (t, J = 6.6
Hz, 4H; 2 CH2), 3.60 (q, J = 6.6 Hz, 4H; 2 CH2), 5.04–5.10 (m, 2H; 2 CHO), 5.27–
13
5.32 (m, 2H; 2 CHO), 9.68 (t, J = 6.0 Hz, 2H; 2 NH) ppm; C NMR (150 MHz,
CDCl3): δ = 21.5, 21.8 (8 CH3), 37.4, 44.6 (4 CH2), 69.1, 72.7 (4 CHO), 72.3, 167.6
(2 C=C), 116.1 (2 C–N), 160.5, 161.2 (4 C=O) ppm; IR (KBr): 783 (m), 1100 (s),
1274 (vs), 1591 (vs, C=C−N), 1670 (vs, C=O), 1739 (vs, C=O), 2214 (s, C≡N), 2984
(s), 3234 (m), 3332 (m), 3443 (m) cm–1. (–)-HRMS (ESI) (m/z): calcd. for
C26H37N4S2O8 597.20583; found 597.20646.
Reaction of L-cysteine methyl ester (11b) with dimethyl dicyanofumarate (1a)
A magnetically stirred solution of commercial L-cysteine methyl ester hydrochloride
(0.189 g, 1.1 mmol) in MeOH (5 mL) was neutralized with a portion of potassium
carbonate (0.455 g, 3.3 mmol). After 15 min the solid material was filtered off and the
methanolic solution of free 11b was evaporated to dryness. The oily residue was
dissolved in 2 mL of CH2Cl2. Then, crystalline 1a (0.194 g, 1.0 mmol) was added in
small portions. The solution was stirred magnetically at r.t. for 15 min and
subsequently a portion of CH2Cl2 was added. The precipitate was filtered off and the
clear filtrate was evaporated yielding 198 mg of a viscous material, which was
1
analyzed by H NMR spectroscopy, showing the absence of isomeric dimethyl
dicyanosuccinates. Subsequent chromatographic separation on preparative plates
(SiO2, 7:3 mixture of petroleum ether and ethyl acetate) led to an oily fraction (100
mg) with Rf = 0.5 as the only product. The isolated product did not solidify while
storing in a refrigerator over several days.
16
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N,N’-(Dithiodi[(R)-(1-methoxycarbonyl)ethylene])bis((Z)-2-amino-3-cyano-2-
1
butenedioic acid dimethyl ester) (12d): Viscous colorless oil (100 mg, 30 %); H
NMR (600 MHz, CDCl3): δ = 3.12 (m, 4H; 2 CH2), 3.79, 3.80 (2s, 12H; 4 CH3O),
3.96 (s, 6H; 2 CH3O), 4.49 (m, 2H; 2 CH), 10.03 (d, 3J = 8.4 Hz, NH) ppm; 13C NMR
(150 MHz, CDCl3): δ = 33.4 (2 CH2), 36.5 (2 CH), 52.4, 53.3, 53.9 (6 CH3O), 57.3,
169.1 (2 C=C), 115.7 (2 C≡N), 159.0, 161.1, 167.9 (6 C=O) ppm; IR (KBr): 723 (m),
777 (m), 1008 (m), 1090 (m), 1280 (broad, vs), 1436 (s), 1587 (vs, C=N), 1679 (s,
C=O), 1746 (vs, C=O), 2217 (s, CN), 2958 (m), 3240 (m, NH) cm–1; Elemental
analysis: calcd for C22H26N4O12S2 (602.59): C 43.85%, H 4.35%, N 9.30, S 10.64;
found: C 43.86%, H 4.56%, N 9.07, S 10.52.
Reaction of L-methionine methyl ester (11c) with dimethyl dicyanofumarate (1a)
A magnetically stirred solution of commercial L-methionine methyl ester
hydrochloride (0.204 g, 1.1 mmol) in MeOH (5 mL) was neutralized with a portion of
potassium carbonate (0.455 g, 3.3 mmol). After 15 min, the solid material was filtered
off and the methanolic solution of free 11c was evaporated to dryness. The oily
residue was dissolved in 2 mL of CH2Cl2, and crystalline 1a (0.194 g, 1.0 mmol) was
added in small portions. The solution was stirred magnetically at r.t. for 15 min and
subsequently the solvent was evaporated in vacuum. The crude product was analyzed
by 1H NMR spectroscopy, showing the absence of isomeric dimethyl
dicyanosuccinates 8a. Chromatographic separation on preparative plates (SiO2, 7:3
mixture of petroleum ether and ethyl acetate) led to an oily fraction (100 mg) with Rf
= 0.4 as the only product. The isolated material did not solidify while storing in a
refrigerator over several days.
Dimethyl
(Z)-N-((1’-methoxycarbonyl-3’-methylsulfanyl)propan-1’-yl]-2-amino-3-
cyano-2-butenedioate (7e): Viscous colorless oil (100 mg, 32%); 1H NMR (600 MHz,
CDCl3): δ = 2.05−2.12 (m, 1H, CH), 2.10 (s, 3H, CH3S), 2.15−2.22 (m, 1H, CH),
2.49−2.54, 2.55−2.61 (2m, 2H, CH2), 3.80, 3.83, 3.98 (3s, 9H, 3 CH3O), 4.37−4.43
13
(m,1H, CH), 9.84 (d, J = 8.2 Hz, NH) ppm; C NMR (150 MHz, CDCl3): δ = 15.1
(SCH3), 29.4, 32.3 (2 CH2), 52.2, 52.9, 53.8 36.5 (3 CH3O), 56.8 (CH), 73.3, 160.9
(C=C), 115.7 (C≡N), 159.8, 167.9, 170.1 (3 C=O) ppm; IR (KBr): 732 (m), 786 (m),
913 (w), 1024 (m), 1100 (m), 1239 (broad, vs), 1439 (s), 1594 (vs, C=C-N), 1679 (s,
C=O), 1746 (vs, C=O), 2214 (s, C≡N), 2920 (w), 2958 (m), 3144 (m, NH), 3229 cm–
17
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1; Elemental analysis: calcd for C13H18N2O6S (330.36): C 47.26%, H 5.49%, N 8.48, S
9.71; found: C 47.36%, H 5.51%, N 8.45%, S 9.60% [α]D25 = –31.1 (c 0.25, CHCl3).
Reactions of dimethyl dicyanofumarate (1a) with chalcogenols – general
procedure
To a solution of a thiol or selenol (0.4 mmol (2 equiv.) or 0.2 mmol (1 equiv.) in the
case of dithiols and β-mercaptoselenols) in 1 mL of CH2Cl2 or MeOH (for Cys (13i),
GSH (13j) and 13l), 1a (39 mg, 0.2 mmol, 1 equiv.) was added at 0 °C. The mixture
was stirred for 12 h at r.t., the solvent was evaporated under vacuum, and the crude
material was purified by flash chromatography (petroleum ether/ethyl acetate 3:1).
Conversion of 1a and thiols or selenols into the corresponding dicyanosuccinate 8a
and disulfides 14 or diselenides 16 was almost quantitative (>96%, Tables 1 and 2). In
experiments performed with tritylthiol and tert-butylthiol intense odor detected even
1
after 24h and the registered H NMR spectra of crude mixtures revealed the presence
of unconverted substrates; characteristic singlet for two MeO groups of DCFM was
found at δ (CDCl3) = 4.05 ppm. Yields of known disulfides 14a−c,k,n and were
1
determined based on the H NMR analysis of the crude reaction mixtures with
weighted portion of xylene added as a concentration standard.
Diphenyldisulfide (1,2-diphenyldisulfane)[18] (14a, Table 1, entry 1): Colorless oil
(98%).
1,2-Dioctadecyldisulfane[18] (14b, Table 1, entry 2): Glossy white solid (96%).
2,2’-Disulfandiyldiethanol[18] (14c, Table 1, entry 3): Colorless oil (96%).
1,1’-Disulfanediylbis(propan-2-ol)[19] (14d, Table 1, entry 4): Colorless oil (97%).
3,3'-Disulfanediylbis[1-(benzyloxy)propan-2-ol] (14e, Table 1, entry 5): Following
the general procedure, 1-(benzyloxy)-3-mercaptopropan-2-ol (13e, 0.4 mmol, 80 mg)
and 1a (39 mg, 0.2 mmol) gave after purification the corresponding disulfide 14e (75
1
mg, 95%) as a 1:1 mixture of diastereoisomers. Yellowish oil. H NMR (400 MHz,
CDCl3): δ = 7.28–7.38 (m, 20H), 4.05–4.11 (m, 4H, CHOH), 3.60 (bdd, J = 3.9, 9.6
18
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European Journal of Organic Chemistry
Hz, part of an ABX system, 4H, CH2O), 3.59 (bdd, J = 3.9, 9.5 Hz, part of an ABX
system, 4H, CH2O), 3.52 (bdd, J = 6.1, 9.5 Hz, part of an ABX system, 4H, CH2O),
3.51 (bdd, J = 6.5, 9.6 Hz, part of an ABX system, 4H, CH2O), 2.89–2.94 (m, 4H,
CH2S), 2.83 (dd, J = 7.4, 12.8 Hz, 4H, CH2S), 2.69 (bs, 4H, OH) ppm; 13C NMR (100
MHz, CDCl3): δ = 138.4, 129.1, 128.5, 128.4 (Ph), 74.1 (OCH2Ph), 73.2 (CHCH2O),
69.9 (CHOH), 69.8 (CHOH), 43.1 (CH2S) ppm; MS (ESI positive) (m/z): 417
[M+Na]+, (100). Elemental analysis: calcd for C20H26O4S2 (394.55): C 60.88%, H
6.64%; found: C 60.82%, H 6.67%.
3,3'-Disulfanediylbis[1-(allyloxy)propan-2-ol] (14f, Table 1, entry 6): Following the
general procedure, 1-(allyloxy)-3-mercaptopropan-2-ol (13f, 0.4 mmol, 59 mg) and
1a (39 mg, 0.2 mmol) gave after purification the corresponding disulfide 14f (55 mg,
1
94%) as a 1:1 mixture of diastereoisomers. Colorless oil. H NMR (400 MHz,
CDCl3): δ = 5.80–5.99 (m, 4H), 5.15–5.32 (m, 8H), 3.99–4.05 (m, 8H), 3.87–3.96 (m,
4H, CHOH), 3.40–3.55 (m, 8H), 2.87 (bs, 4H, OH), 2.78 (dd, J = 4.9, 13.9 Hz, part of
an ABX system, 4H, CHaHbS), 2.65 (dd, J = 7.3, 13.9 Hz, part of an ABX system,
13
4H, CHaHbS) ppm; C NMR (100 MHz, CDCl3): δ = 134.3 (=CH), 117.4 (=CH2),
72.5, 72.4, 72.3 (CH2O), 69.2, 69.1 (CHOH), 42.5, 42.4 (CH2S) ppm; MS (ESI
positive) (m/z): 317 [M+Na]+, (100). Elemental analysis: calcd for C12H22O4S2
(294.43): C 48.95%, H 7.53%. Found: C 49.01%, H 7.51%.
Di(tert-butyl)
[(2S,2’S)-disulfanediylbis(3-methylbutane-2,1-diyl)]dicarbamate[20]
(14g, Table 1, entry 7): White solid (92%).
N,N’-[(2S,2’S)-Disulfanediylbis(3-methylbutane-2,1-diyl)]bis(4-methylbenzenesulfon-
amide)[21] (14h, Table 1, entry 8): White solid (94%).
(2S,2’S)-3,3’-Disulfanediylbis(2-aminopropanoic acid) (cystine)[22] (14i, Table 1,
entry 9): White solid (98%).
Glutathione disulfide (GSSG)[22] (14j, Table 1, entry 10): White solid (98%).
1,2-Dithiolane[23] (14k, Table 1, entry 11): Yellowish oil (89%).
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1,2-Dithiane-4,5-diol[24] (14l, Table 1, entry 12): White solid (98%).
3,7-Bis[(benzyloxy)methyl]1,2,5-dithiadelenepane[25] (14m, Table 1, entry 13):
Yellowish oil (96%).
1,2,5,6-Tetrathiocane[26] (14n, Table 1, entry 14): Yellowish oil (82%).
Dipenyldiselenide (1,2-diphenyldiselene)[27] (16a, Table 2, entry 1): Yellow solid
(98%).
3,3’-Diselanediylbis[1-(benzyloxy)propan-2-ol[28] (16b, Table 2, entry 1): Yellowish
oil (95%).
3,3’-Diselanediylbis[1-(allyloxy)propan-2-ol[28] (16c, Table 2, entry 1): Yellowish oil
(96%).
N,N’-[(2S,2’S)-Diselanylbis(4-methylpentane-2,1-diyl)]bis{4-methylbenzenesulfon-
amide)[28] (16d, Table 2, entry 4): Yellow solid (97%).
References
[1] a) R.J. Cremlyn, An Introduction to Organosulfur Chemistry, John Wiley &
Sons, Chichester, 1996; b) I.V. Koval’, Russ. Chem. Rev. 1994, 63, 735–750.
[2] a) C.S. Sevier, C.A. Kaiser, Nature Rev. Mol. Cell Biol.2002, 3, 836–847; b)
H.F. Gilbert, Adv. Enzymol. 1990, 63, 69–172; c) N.J. Bulleid, L. Ellgaard,
Trends Biochem. Sci. 2011, 36, 485–492.
[3] M. Gόngora-Benítez, J. Tulla-Puche, F. Albericio, Chem. Rev. 2014, 114, 901–
926.
[4] a) D. Witt, Synthesis 2008, 2491–2509; b) M. Musiejuk, D. Witt, Org. Prep.
Proc. Int. 2015, 47, 95–131.
[5] G. Ribeiro Morais, R.A. Falconer, Tetrahedron Lett. 2007, 48, 7637–7641.
[6] A. Christoforou, G. Nicolaou, Y. Elemes, Tetrahedron Lett. 2006, 47, 9211–
9213.
20
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10.1002/ejoc.201701066
European Journal of Organic Chemistry
[7] A.A. Hassan, N.K. Mohamed, B.A. Ali, A.-F.E. Mourad, Tetrahedron 1994, 50,
9997–10010.
[8] O.E. Nasakin, E.G. Nikolaev, P.B. Terent’ev, A.K. Bulai, B.A. Khaskin, Russ.
J. Gen. Chem. 1986, 56, 510–516.
[9] G. Mlostoń, M. Celeda, A. Linden, H. Heimgartner, Helv. Chim. Acta 2009, 92,
1520–1537.
[10] G. Mlostoń, A. Pieczonka, K.A. Ali, A. Linden, H. Heimgartner, Arkivoc 2012,
(iii) 181–192.
[11] G. Mlostoń, A. Pieczonka, A. Wróblewska, A. Linden, H. Heimgartner,
Heterocycles 2012, 86, 343–356.
[12] C. Yin, F. Huo, J. Zhang, R. Martínez-Máñez, Y. Yang, H. Lv, S. Li, Chem.
Soc. Rev. 2013, 42, 6032–6059.
[13] D.P. Nair, M. Podgórski, S. Chatani, T. Gong, W. Xi, C.R. Fenoli, C.N.
Bowman, Chem. Mater.2014, 26, 724–744.
[14] a) J.S. Stamler, A. Slivka, Nutr. Rev.1996, 54, 1–30; b) C. Bayle, E. Caussé, F.
Couderc, Electrophoresis 2004, 25, 1457–1472; c) In Comprehensive Organic
Functional Group Transformations II, Vol. 1, A.R. Katritzky, R.J.K. Taylor,
Eds., Elsevier, Pergamon (2005).
[15] G. Mlostoń, M. Celeda, H. Heimgartner, Phosphorous Sulfur Silicon Relat.
Elem. 2016, 191, 207–210.
[16] a) A.A. Dar, M. Shadab, S. Khan, N. Ali, A.T. Khan, J. Org. Chem. 2016, 81,
3149−3160; b) L. Fatimi, Ch. Duroux, R. Buxeraud, Chem. Pharm. Bull. 1994,
42, 698−701; c) J.P. Danehy, V.J. Ella, Ch.J. Lavelle, J. Org. Chem. 1971, 36,
1003−1006; d) K. Palanisamy, A. Sivanesan, J.S. Abraham, J. Phys. Chem. A
2007, 111, 12086–12092.
[17] a) W.S. Tyree, C. Slebodnick, M.C. Spencer, G. Wang, J.S. Merola, G.T. Yee,
Polyhedron 2005, 24, 2133–2140; b) G. Wang, C. Slebodnick, R.J. Butcher,
M.C.Tam, J. Am. Chem. Soc. 2004, 126, 16890–16895; c) L. Cerisoli, M.
Lombardo, C. Trombini, A. Quintavalla, Chem. Eur. J. 2016, 22, 3865–3872; d)
C. Avonto, O. Taglialatela-Scafati, F. Pollastro, A. Minassi, V. Di Marzo, L. De
Petrocellis, G. Appendino, Angew. Chem. Int. Ed. 2011, 50, 467–471; e) J.-J.
Yan, D. Wang, D.-Ch. Wu, Y.-Z. You, Chem. Commun., 2013, 49, 6057−6059.
[18] T. Chatterjee, B.C. Ranu, RSC Advances 2013, 3, 10680–10686.
21
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701066
European Journal of Organic Chemistry
[19] N. Saleh, S. Zrig, T. Roisnel, L. Guy, R. Bast, T. Saue, B. Darquié, J. Crassous,
Phys. Chem. Chem. Phys. 2013, 15, 10952–10959.
[20] A.L. Braga, F.Z. Galleto, O.E.D. Rodrigues, C.C. Silveira, M.W. Paixão,
Chirality 2008, 20, 839–845.
[21] D. Sureshkumar, T. Gunasundari, V. Ganesh, S. Chandrasekaran, J. Org. Chem.
2007, 72, 2106–2117.
[22] T. Nakayama, T. Isobe, K. Nakamiya, J.S. Edmonds, Y. Shibata, M. Morita,
Magn. Reson. Chem. 2005, 43, 543–550.
[23] S.S. Shah, S. Karthik, N.D.P. Singh, RSC Advances 2015, 5, 45416–45419.
[24] N.A. Calandra, Y.L. Cheng, K.A. Kocak, J.S. Miller, Org. Lett. 2009, 11, 1971–
1974.
[25] A. Capperucci, D. Tanini, C. Borgogni, A. Degl’Innocenti, Heteroatom Chem.
2014, 25, 678–683.
[26] A. Berkovich-Berger, N.G. Lemcoff, S. Abramson, M. Grabarnik, S. Weinman,
B. Fuchs, Chem. Eur. J. 2010, 16, 6365–6373.
[27] D. Singh, A.M. Deobald, L.R.S. Camargo, G. Tabarelli, O.E.D. Rodrigues, A.L.
Braga, Org. Lett. 2010, 12, 3288–3291.
[28] D. Tanini, A. Capperucci, A. Degl’Innocenti, Eur. J. Org. Chem. 2015, 357–
369.
[29] a) A.A. Ashraf, S. Bräse, J. Sulfur Chem. 2017, 38, 291–302; b) A.
Degl’Innocenti, S. Pollicino, A. Capperucci, Chem. Commun. 2006, 4881–4893.
[30] a) C. Oppenheimer, K. G. Stern, In Biological Oxidation, Springer-Science +
Business Media, B. V., 1939, p. 53; b) C. A. R. Engel, A. J. J. Straathof, T. W.
Zijlmans, W. M. van Gulik, L. A. M. van der Wielen, Appl. Microbiol.
Biotechnol. 2008, 78, 379–389.
[31] a) D. Tanini, G. Barchielli, F. Benelli, A. Degl’Innocenti, A. Capperucci,
Phosphorus Sulfur Silicon Relat. Elem. 2015, 190, 1265–1270; b) A.
Capperucci, D. Tanini, A. Degl’Innocenti, Phosphorus Sulfur Silicon Relat.
Elem. 2013, 188, 437–440.
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Table of Contents
Dialkyl dicyanofumarates act as efficient hydrogen acceptors towards diverse thiols
and selenols yielding the desired disulfides and diselenides, respectively; aliphatic
dithiols form cyclic disulfides. In most cases yields are high to excellent. The only side
products are isomeric dicyanosuccinates formed in a 1:1 ratio. A SET mechanism offers
a likely explanation of the reaction course.
Graphical abstract:
23
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