Fe(OTf)2-Catalyzed Thia-Michael Addition Reaction: A Green Synthetic Approach to β-Thioethers

Article abstract of DOI:10.1002/ejoc.201800780

A convenient Fe(OTf)₂-catalyzed Michael addition reaction of thiols to α,β-unsaturated carbonyl compounds was developed. The use of a simple procedure (EtOH, room temperature, air atmosphere) allowed to set up effective green catalytic conditions for C–S bond formation. The scope of the reaction was demonstrated using various substituted thiols and original Michael acceptors. The corresponding β-thioethers were obtained in good to excellent yields (up to 99 %). Also, the derivatization into the one-pot thia-Michael addition/oxidation reaction of 3-[3-(phenylthio)butanoyl]oxazolidin-2-one using H₂O₂ has proven to be efficient.

Full text of DOI:10.1002/ejoc.201800780

A Journal of
Accepted Article
Title: Fe(OTf)2-Catalyzed Thia-Michael Addition Reaction: A Green
Synthetic Approach to beta-Thioethers
Authors: Samuel Lauzon, Mao Li, Hoda Keipour, and Thierry Ollevier
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800780
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800780
Supported by

10.1002/ejoc.201800780
European Journal of Organic Chemistry
COMMUNICATION
Fe(OTf)2-Catalyzed Thia-Michael Addition Reaction: A Green
Synthetic Approach to β-Thioethers
Samuel Lauzon,[a][‡] Mao Li,[a][‡] Hoda Keipour,[a] and Thierry Ollevier[a]*
Abstract: A convenient Fe(OTf)2-catalyzed Michael addition reaction
of thiols to α,β-unsaturated carbonyl compounds was developed. The
use of a simple procedure (EtOH, room temperature, air atmosphere)
allowed to set up effective green catalytic conditions for the C–S bond
formation. The scope of the reaction was demonstrated using various
substituted thiols and original Michael acceptors. The corresponding
β-thioethers were obtained in good to excellent yields (up to 99%).
and disposal.[20] Ionic liquids have severe drawbacks, e.g., very
energy consuming syntheses.[21] Water, even though highly
attractive in organic synthesis,[22] is associated with solubility
problems. Consequently, it is clearly essential to broaden the
scope of green organic solvents applicable for this transformation.
Scheme 1. Lewis acid-catalyzed thia-Michael addition reaction–Background
a) Lewis acid catalysis: Michael acceptor types
Also,
the
derivatization
into
the
one-pot
thia-Michael
addition/oxidation reaction of 3-(3-(phenylthio)butanoyl)oxazolidin-2-
one using H2O2 has proven to be efficient.
Mostly explored
Rarely explored
O
O
O
O
R2
O
N
R1
X
Introduction
R1
X = OR2, esters
X = H, aldehydes
cyclic/acyclic ketones
oxazolidin-2-ones
Synthetic strategies towards C-S bond formation is gaining
widespread interest, owing to the biological activity of sulfur
containing molecules.[1] Among them, the nucleophilic addition
reaction of thiols to α,β-unsaturated carbonyl compounds remains
an important and widely documented transformation.[2] The
incorporation of a sulfur group has been demonstrated using
heterogeneous catalysis,[3] odorless and cheap sulfur salts,[4] and
miscellaneous catalysts, i.e., I2, simple amines, or
trichlorotriazine.[5] Previous work in homogeneous catalysis has
been disclosed using various Lewis acids, derived from VIV,[6]
InIII,[7] YbIII,[8] ReV,[9] LaIII,[10] NiII,[11], CuII,[12] ZnII,[13] BiIII,[14] and FeIII
salts,[15] as effective catalysts for the thia-Michael addition
reaction. However, most of these methods are suitable for α,β-
unsaturated ketones, esters and aldehydes, while α,β-
unsaturated oxazolidin-2-ones are reported in very few examples
(Scheme 1a). With the progress made in metal-catalyzed thia-
Michael addition reaction, there is still room for the development
of greener synthetic approaches. The adoption of green chemistry
within drug manufacturing has direct benefits on economical,
technological, and environmental issues.[16] The interest behind
using FeII/FeIII salts to replace noble transition metals in
homogeneous catalysis has recently emerged to provide efficient
alternatives with high availability, low toxicity, low cost, and
environmental-friendliness.[17] In order to avoid the use of
chlorinated solvents, a few conjugate 1,4-addition reactions of
thiols have been developed in recyclable ionic liquids,[18] and in
water.[19] Besides low impacts on health and environment, a
solvent should fulfil low energy issues related to its manufacture
Only 9 examples
Substituted thiophenols
Over 100 examples
Various thiols
b) This work: green synthetic approach
O
O
SR
O
O
O
O
Fe(OTf)2 (5 mol-%)
EtOH, air, 25 °C
+
RSH
R1
N
R1
N
O
O
O
R2
R2
O
• original Michael acceptors
• various thiols
• one-pot synthesis
Ph
∗ S
H2O2
∗
N
• practical reaction conditions
Previously, iron catalysts have been studied in our laboratory for
various synthetic transformations, i.e., the asymmetric thia-
Michael addition and other reactions.[23] Hence, a green and
simple Michael addition reaction of thiols to α,β-unsaturated
systems using Fe(OTf)2 as an environmentally benign catalyst is
disclosed herein (Scheme 1b). Importantly, the scope of the
reaction was broadened to α,β-unsaturated ketones and amides,
including the choice of original substrates. In addition, the one-pot
two-step oxidation of the β-thioethers is demonstrated.
Results and Discussion
The Michael addition reaction of thiophenol 2a to (E)-3-
crotonoyloxazolidin-2-one 1a, catalyzed by Fe(ClO4)3·6H2O, was
firstly selected as the model reaction for the screening of green
solvents (Table 1). Only traces of the desired product were
obtained when EtOAc and H2O were used as solvents (entries 1
and 2). CO2-derived solvents, such as propylene carbonate (PC)
and dimethyl carbonate (DMC), are highly biodegradable, low in
toxicity, and synthesized through green industrial processes.[24]
Unfortunately, they afforded 3a with low to moderate conversions
[a]
[‡]
Département de chimie, Université Laval
1045 avenue de la Médecine, Québec, QC, G1V 0A6, Canada
E-mail: thierry.ollevier@chm.ulaval.ca
https://www.chm.ulaval.ca/tollevier/
These authors equally contributed to this manuscript.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201800780
European Journal of Organic Chemistry
COMMUNICATION
Table 1. FeIII-catalyzed thia-Michael addition reaction: green solvent
optimization[a]
Table 2. Metal-catalyzed thia-Michael addition reaction: Lewis acid
optimization[a]
O
O
SPh
O
O
Fe(ClO4)3·6H2O
(5 mol-%)
MXn (5 mol-%)
O
O
SPh
O
O
+
PhSH
+
PhSH
N
O
N
O
EtOH, air
25 °C, 3 h
O
O
N
N
solvent, air
25 °C, 3 h
1.1 equiv.
1.1 equiv.
1a
2a
3a
1a
2a
3a
Entry
MXn
Conversion[b] (%)
Entry
Solvent
Conversion[b] (%)
1
FeCl3
10
1
2
3
4
5
6
7
8
9
EtOAc
H2O
4
2
Fe(OTf)3
26
8
3
FeCl2
88
PC
5
4
Fe(BF4)2·6H2O
Fe(ClO4)2·6H2O
Fe(OTf)2
90
DMC
Et2O
41
10
14
32
61
72
5
92
6
100 (94)[c]
CPME
THF
7
Ca(OTf)2
94
58
17
39
5
8
Ga(OTf)3
Al(OTf)3
2-Me-THF
EtOH
9
10
11
Bi(OTf)3·4H2O
None
[a] Conditions: Fe(ClO4)3·6H2O (5 mol-%), 1a (0.250 mmol), 2a (0.275
mmol), solvent (0.25 mL). [b] Calculated by 1H NMR.
(entries 3 and 4). Coordinating ether solvents, such as Et2O and
CPME, led to low conversions (entries 5 and 6). 2-Me-THF,
known as a biomass-originated solvent,[25] afforded 3a with an
increased conversion, as compared with THF (entry 8 vs. 7).
EtOH afforded an optimum 72% conversion (entry 9), and,
thereby, this cheap and environmentally benign solvent was
chosen for further studies.
The optimization process was further extended to various FeIII
(Table 2, entries 1 and 2) and FeII salts (entries 3-6). Other FeIII
salts were studied, i.e., FeCl3 and Fe(OTf)3, but led to lower
conversions than their ClO4- counterion analogue (entries 1 and 2
vs. Table 1, entry 9). FeCl2 afforded 3a with a high conversion
(entry 3). Then, cationic FeII salts, such as Fe(BF4)2·6H2O and
Fe(ClO4)2·6H2O, allowed conversions up to 92% (entries 4 and 5).
The formation of β-thioether 3a was complete in only 3 hours
when Fe(OTf)2 was used and a 94% yield was afforded (entry 6).
Furthermore, various green Lewis acids were tested to compare
[a] Conditions: MXn (5 mol-%), 1a (0.250 mmol), 2a (0.275 mmol), EtOH
(0.25 mL). [b] Calculated by 1H NMR. [c] Isolated yield of 3a.
challenging when the electron-properties of R1 were changed (3b
and 3c vs. 3a). However, the electron-donating group at the α-
position (R2 = Me) also led to poor solubility and reactivity of the
substrate (3d). Although β-thioethers 3e and 3f were obtained in
high yields, an extended reaction time was required for 3f (60 h
vs. 15 h). The absence of a dicarbonyl chelating system with FeII
decreased the reactivity of α,β-unsaturated amide 1g, and due to
incomplete conversion, a modest 51% yield of β-thioether 3g was
afforded. α,β-Unsaturated ketone derivatives, such as pyridyl,
pyridyl N-oxide, and phenyl as R3 substituents, allowed a
comparison of the differences in the chelation with FeII. Shorter
reaction times and higher yields in the corresponding β-thioethers
were obtained (3h 3k vs. 3b). It is noteworthy to mention that no
-
reaction occurred when ester 1l was used in the optimized
conditions (0% of 3l, recovered starting material).
their catalytic activity (entries 7-10). Ca(OTf)2 showed
a
Since the activation of the dicarbonyl core of (E)-3-
crotonoyloxazolidin-2-one 1a by Fe(OTf)2 would provide a more
reactive Michael acceptor, the nucleophilic character of the thiol
was examined; hence, aromatic, heterocyclic, and aliphatic thiols
were used (Scheme 3). Various thiophenols, such as para- and
ortho-substituted ones, afforded the desired products in high
yields, independently of the electronic nature of the substituent
promising reactivity with a high conversion in the desired product
(entry 7). Catalysts derived from other main metal salts allowed
low to moderate conversions of 3a (entries 8 and 9). BiIII-catalyzed
1,4-conjugate addition reaction have been scarcely described;[14,
26]
in this case, only 39% conversion was obtained (entry 10).
Virtually no conversion was observed when the Michael addition
reaction of thiophenol 2a was run in the absence of a catalyst
(entry 11). This green catalytic system using Fe(OTf)2/EtOH was
efficient, and, consequently, was chosen as the optimized
conditions.
(4b
electron-withdrawing substituents, afforded the corresponding β-
thioethers from moderate to high yields (4g 4k). The difference
4f). Benzylthiols 2g k, comprising electron-donating and
- -
-
in reaction times provided a clear evidence that a thiol linked to
the aromatic ring led to better nucleophilic ability and reactivity of
the S-atom. The developed catalytic method tolerated
heterocyclic thiols, and high yields were obtained for both the 2-
mercaptopyridyl and furfuryl thiols (4l and 4m). Extended reaction
The scope of the reaction was next investigated using various α,β-
unsaturated Michael acceptors (Scheme 2). In terms of reactivity,
the electronic properties of the R1 substituent were compared to
the model substrate (1a). Besides solubility issues related to
substrates 1b and 1c, the addition of thiol 2a remained more
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10.1002/ejoc.201800780
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COMMUNICATION
Scheme 2. Fe(OTf)2-catalyzed conjugate addition reaction of thiophenol to α,β-
unsaturated carbonyl compounds[a]
Scheme 3. Fe(OTf)2-catalyzed conjugate addition reaction of thiols to (E)-3-
crotonoyloxazolidin-2-one[a]
O
O
SR
O
O
Fe(OTf)2 (5 mol-%)
O
SPh O
+
RSH
Fe(OTf)2 (5 mol-%)
O
O
N
N
EtOH, air
25 °C, 3−120 h
PhSH
+
R1
R3
R1
R3
1.1 equiv.
2a−o
EtOH, air
25 °C, 3−96 h
1a
3a, 4b−o
R2
1.1 equiv.
R2
3a−l
1a−l
2a
MeO
S
S
O
O
S
O
O
S
S
O
N
O
O
S
O
O
O
S
O
O
O
S
O
O
O
O
O
O
N
N
O
O
O
N
N
N
H
H
N
N
3a
94%
4b
95%
4c
98%
Br
Cl
3a
94%
3b
63%
3c
69%
O
O
S
O
O
O
N
O
S
S
O
S
S
O
S
S
O
O
O
O
O
N
O
N
N
4d
88%
4e
97%
4f
99%
O
N
N
3d
60%
3e
98%
3f
96%
S
S
SR
O
O
4h R = 4-tBuBn
99%
4i R = 4-MeOBn 84%
O
N
N
O
O
O
4j R = 4-ClBn
90%
4g[b]
59%
4h−j[b]
N
N
Cl
3g[b]
51%
3h
92%
3i
94%
MeO
S
O
O
O
O
O
N
S
O
O
O
O
N
O
N
S
O
O
N
S
O
S
O
4l[c]
87%
4m[b]
94%
4k[b]
99%
OEt
S
O
O
S
O
O
3j
89%
3k[c]
90%
3l
14
No conversion
O
O
N
N
4n[b]
85%
4o[b]
55%
[a] Conditions: Fe(OTf)2 (5 mol-%), 1a l (0.250 mmol), 2a (0.275 mmol), EtOH
-
(0.25 mL). [b] 2 equiv. of thiol 2a were used. [c] 2 equiv. of thiol 2a and 0.5 mL
of EtOH were used.
[a] Conditions: Fe(OTf)2 (5 mol-%), 1a (0.250 mmol), 2a o (0.275 mmol), EtOH
-
(0.25 mL). [b] 5 equiv. of thiol were used. [c] 2 equiv. of thiol were used.
times were needed to complete the 1,4-addition reaction of
aliphatic thiols, but moderate to good yields were afforded (4n and
4o). A stoichiometric amount of thiol was no longer suitable when
triflic acid, possibly released by the hydrolysis of Fe(OTf)2, could
act as a Brønsted acid was disclaimed when 2,6-di-tert-butyl
pyridine was used in the optimized conditions (Scheme 4b).[27]
The formation of 3a with an excellent yield, thus, suggests an
exclusive Lewis acid activation.
less reactive thiols 2g
-
o were used, and up to 5 equivalents of
o in
thiol were required in order to form β-thioethers 4g
-
reasonable reaction times. Nevertheless, the excess of thiol was
easily separated in the purification process.
Comparison with literature precedent, together with a control
experiment, was performed to gain insights into the reaction
mechanism (Scheme 4). As explained from previous studies on
the thia-Michael addition reaction,[23b] DFT calculations supported
the idea of a hepta-coordinated FeII chelated by the two carbonyls
of the α,β-unsaturated oxazolidin-2-one. In this work, the
hypothesized model of a transition state, in which 1a chelated
Fe(OTf)2 to form a stable 6-membered cycle complex (A), was
postulated in agreement with these precedents (Scheme 4a). In
this model, the thiol would attack the β-carbon of the Michael
acceptor, electronically-impoverished by the Lewis acid activation,
to give an FeII-enolate intermediate. Finally, a protonation step
would occur and generate the expected β-thioether. As
highlighted with 1g, 1k, and 1l, the mono activation of the
substrates by FeII was considered. As expected, higher
electrophilicity of the ketone 1k vs. amide 1g increased the
reactivity of the substrate toward the nucleophilic addition, but,
surprisingly, no reaction occurred with the ester analogue 1l in the
conditions. Moreover, the hypothesis that a catalytic quantity of
Scheme 4. Insights into the reaction mechanism
a) Postulated model of a transition state
(OTf)2
RSH
Fe
SR
O
O
O
O
O
O
O
N
O
N
O
N
1a
A
b) Control experiment
(10 mol-%)
tBu
N
tBu
O
O
SPh
O
O
Fe(OTf)2 (5 mol-%)
+
PhSH
O
O
N
N
EtOH, air
25 °C, 3 h
1.1 equiv.
1a
2a
3a
96%
In order to illustrate the utility of the developed greener conditions
and their preparative value, the conjugate addition reaction of
thiophenol 2a to (E)-3-crotonoyloxazolidin-2-one 1a was
performed on a multigram scale (Scheme 5). Treatment of 1a on
a 4 gram scale (25 mmol) allowed the preparation of β-thioether
3a with an excellent yield of 93%. The viability of a gram-scale
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10.1002/ejoc.201800780
European Journal of Organic Chemistry
COMMUNICATION
Scheme 5. Thia-Michael addition: gram-scale reaction
Scheme 6. One-pot reaction in green synthetic conditions
O
O
SPh
O
O
Ph
O
1) PhSH (2a, 1.1 equiv.), 3 h
2) H2O2 (30%) (4 equiv.), 5 h
Fe(OTf)2 (5 mol-%)
O
O
∗ S
O
O
+
PhSH
O
O
N
N
∗
EtOH, air
25 °C, 3 h
1.1 equiv.
N
O
N
O
Fe(OTf)2 (5 mol-%)
EtOH, air, 25 °C
1a
2a
3a
93%
(25 mmol)
1a
5a
71%
synthesis using an air-stable FeII catalyst and undried EtOH was
therefore demonstrated.
Overall, a one-pot thia-Michael addition/oxidation reaction using
completely green conditions was developed (Scheme 6). Indeed,
sulfoxide 5a was obtained as the major product (1H NMR: 5% of
1a, 7% of 3a, 82% of 5a, and 6% of 6a) and an overall 71% yield
was obtained. Hence, the first example of a thia-Michael
addition/oxidation reaction of an α,β-unsaturated oxazolidin-2-
one compound in a one-pot fashion was demonstrated.
Further derivatization of the β-thioether obtained by the thia-
Michael addition reaction was undertaken. In the recent years,
iron salts have been conjointly used with PhI(OAc)2,[28] O2,[29] or
urea–hydrogen peroxide (UHP),[30] for the highly selective sulfide
oxidation reaction. Iron-catalyzed asymmetric versions have
disclosed high enantioselectivities of aromatic sulfoxides obtained
by catalytic methods using H2O2 as a green oxidant.[23c, 31] Also,
m-CPBA[32] and Na2WO4/H2O2[33] have been reported as efficient
systems for the oxidation, in a separate step, of enantioenriched
β-thioethers to the respective sulfones without racemization. In
this study, the oxidation step of β-thioether 3a using the green
FeII/H2O2 catalytic system was considered (Table 3). While
increasing the amount of H2O2 (30%) from 1.1 to 4 equivalents,
the formation of sulfoxide 5a was thus accelerated and a complete
selectivity in the first oxidation product was observed (entries 1-3).
A large excess in the oxidizing agent only showed the appearance
of sulfone 6a, in addition to sulfoxide 5a, before complete
consumption of sulfide 3a (entry 4). Uncomplete conversions
were observed with reaction times inferior to 5 hours (entries 5
and 6). However, sulfoxide 5a was slowly oxidized in a prolonged
reaction time (entry 7). A low 16% conversion was obtained when
H2O2 was used in the absence of the FeII salt (entry 8). The highly
selective Fe(OTf)2/H2O2 catalytic system afforded an optimal 88%
Conclusions
In summary, an FeII-catalyzed Michael addition reaction of various
thiols to α,β-unsaturated carbonyl compounds was developed.
Green synthetic conditions using Fe(OTf)2 and EtOH afforded β-
thioethers in high yields (up to 99%). Aromatic, heterocyclic and
aliphatic thiols, and less reactive α,β-unsaturated amides were
substrates of choice. In addition, a highly efficient one-pot sulfide
oxidation using H2O2 as a green oxidant was also presented in
this study. The simplicity of the described method lies in the use
of room temperature and air atmosphere, highlighting practical
and easy conditions for the catalyzed reaction. Further
development will be reported in due course.
yield of sulfoxide 5a (entry 3).
Experimental Section
Table 3. Fe(OTf)2-catalyzed oxidation of β-thioether 3a[a]
O
General Procedure A: FeII-Catalyzed Thia-Michael Addition Reaction
to α,β-Unsaturated Carbonyl Compounds: In a glass test tube, Fe(OTf)2
(4.4 mg, 0.0125 mmol, 0.050 equiv.) was added to EtOH (0.10 mL).
Ph
O
Ph
Fe(OTf)2 (5 mol-%)
H2O2 (30%) (x equiv.)
∗ S
∗
O
O
S
O O
O
+
3a
O
O
N
N
EtOH, air, 25 °C
Michael acceptor 1a
EtOH (0.15 mL) was added. After magnetic stirring at 25 ºC under air
atmosphere for 5 min, thiol 2a o (0.275 mmol, 1.1 equiv.) was added
-
l (0.250 mmol, 1.0 equiv.) was introduced before
5a
6a
Entry
x (equiv.)
time (h)
3a:5a:6a[b]
70:30:0
-
dropwise. The mixture was stirred at 25 ºC, and the progress of the
reaction was monitored by TLC. After completion of the reaction, the
mixture was diluted with H2O (10 mL), and the residue was extracted with
Et2O (3 x 10 mL). The combined organic layers were washed with
saturated aqueous NaHCO3 (10 mL), brine (10 mL), and dried over
anhydrous MgSO4. After filtration and evaporation of the solvent in vacuo,
the crude product was purified using a normal phase chromatography
(Biotage®SNAP Ultra 25 g/Biotage®HP-Sphere™ 25 µm) with a gradient
1
1.1
2
5
2
5
35:65:0
3
4
5
0:93:7 (88)[c]
5:78:17
4
10
4
5
elution of hexane/EtOAc = 90:10-40:60 (3a
-
f, and 4b
-
o), hexane/EtOAc
5
0.5
2
64:36:0
= 80:20-10:90 (3g), hexane/EtOAc = 95:5-70:30 (3h
80:20-20:80 (3j), and hexane/EtOAc = 99:1-95:5 (3k) to give the
-
i), hexane/EtOAc =
6
4
27:73:0
corresponding β-thioethers.
7
4
16
5
0:73:27
General Procedure B: FeII-Catalyzed Oxidation Reaction of β-
Thioether 3a to β-Sulfoxide 5a: In a glass test tube, Fe(OTf)2 (4.4 mg,
0.0125 mmol, 0.050 equiv.) was added to EtOH (0.10 mL). β-Thioether 3a
(66.6 mg, 0.250 mmol, 1.0 equiv.) was introduced before EtOH (0.15 mL)
was added. After magnetic stirring at 25 ºC under air atmosphere for 5 min,
H2O2 (30 wt.-% in H2O; 102 µL, 1.00 mmol, 4.0 equiv.) was added and the
mixture was stirred for 5 hours. H2O (10 mL) was added to quench the
reaction mixture and the residue was extracted with EtOAc (3 x 10 mL).
The combined organic layers were washed with saturated aqueous
NaHCO3 (10 mL), brine (10 mL), and dried over anhydrous MgSO4. After
8[d]
4
84:16:0
[a] Conditions: Fe(OTf)2 (5 mol-%), 3a (0.250 mmol), H2O2 (30 wt.-% in H2O;
0.275-2.50 mmol), EtOH (0.25 mL). [b] Ratio 3a:5a:6a calculated by 1H
NMR. β-Sulfoxide 5a was obtained as a 53:47 mixture of diastereoisomers.
[c] Isolated yield of 5a (%). [d] No Fe(OTf)2 was used.
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10.1002/ejoc.201800780
European Journal of Organic Chemistry
COMMUNICATION
filtration and evaporation of the solvent in vacuo, the crude product was
purified using a normal phase chromatography (Biotage®SNAP Ultra 25
g/Biotage®HP-Sphere™ 25 µm) with a gradient elution of hexane/EtOAc =
40:60-5:95 to give sulfoxide diastereoisomers 5a and 5a’ as a white solid.
[12] a) S. K. Garg, R. Kumar, A. K. Chakraborti, Tetrahedron Lett. 2005, 46,
1721-1724; b) R. K. Saunthwal, M. Patel, S. Kumar, A. K. Verma,
Tetrahedron Lett. 2015, 56, 677-681.
[13] S. K. Garg, R. Kumar, A. K. Chakraborti, Synlett 2005, 1370-1374.
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Acknowledgements
We gratefully acknowledge the Natural Sciences and Engineering
Research Council of Canada (NSERC), and the Centre in Green
Chemistry and Catalysis (CGCC) for financial support of our
program. S.L. thanks NSERC and FRQ-NT for scholarships. M.L.
thanks Chinese Scholarship Council (CSC) for a scholarship.
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800780
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
SR
O
O
Iron Catalysis
RSH
up to 99% yield
27 examples
R1
R2
O
O
Fe(OTf)2
Samuel Lauzon, Mao Li, Hoda Keipour,
Thierry Ollevier*
R1
R2
EtOH, air
25 °C
Ph
∗ S
O
1) PhSH
2) H2O2
71% yield
One-pot reaction
∗
N
O
Page No. – Page No.
Title
A convenient Fe(OTf)2-catalyzed Michael addition reaction of thiols to α,β-
unsaturated carbonyl compounds was developed. The use of a simple procedure
(EtOH, room temperature, air atmosphere) allowed to set up effective green
catalytic conditions for the C–S bond formation.
This article is protected by copyright. All rights reserved.