Arylation of perfluoroalkyl vinyl sulfoxides via the Heck reaction

Article abstract of DOI:10.1016/j.tetlet.2015.01.136

Heck reactions of perfluoroalkyl vinyl sulfoxides with aryl iodides are studied and palladium(II) acetate is shown to be the most convenient catalyst for this process. New E-1-aryl-2-perfluoroalkylsulfinylethylenes are synthesized. In all cases, by-products without a perfluoroalkylsulfinyl group are formed.

Full text of DOI:10.1016/j.tetlet.2015.01.136

Tetrahedron Letters 56 (2015) 1259–1262
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Tetrahedron Letters
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Arylation of perfluoroalkyl vinyl sulfoxides via the Heck reaction
a
a
b
Liubov V. Sokolenko a, , Yurii L. Yagupolskii , Yurii G. Vlasenko , Liudmila N. Babichenko ,
⇑
Volodimir O. Lipetskij c, Elsa Anselmi d,e, Emmanuel Magnier d
a Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmans’ka Str. 5, Kyiv 02094, Ukraine
b ChemBioCenter, Kyiv National Taras Shevchenko University, Chervonotkatska Street 61, Kyiv 02094, Ukraine
c Enamine Ltd, Matrosova Street 23, Kyiv 01103, Ukraine
d Bâtiment Lavoisier, Université de Versailles-Saint-Quentin, 45 avenue des Etats-Unis, 78035 Versailles, France
e Université de Tours (UFR Sciences & Techniques), INRA Nouzilly—UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Heck reactions of perfluoroalkyl vinyl sulfoxides with aryl iodides are studied and palladium(II) acetate is
shown to be the most convenient catalyst for this process. New E-1-aryl-2-perfluoroalkylsulfinylethyl-
enes are synthesized. In all cases, by-products without a perfluoroalkylsulfinyl group are formed.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 8 December 2014
Revised 30 December 2014
Accepted 20 January 2015
Available online 24 January 2015
Keywords:
Heck reaction
Vinylation
Cross-coupling
Palladium
Vinyl sulfoxides
Heck vinylation of aryl halides provides a very convenient route
to form carbon–carbon bonds at unsubstituted vinylic positions.
Despite the significant interest in this reaction, very important
challenges and new aspects of this transformation are still the con-
cern of many research groups. It should be mentioned that the
least investigated substrates are the sulfur-containing olefins
(e.g., vinyl sulfides, sulfoxides) since they are known to be palla-
dium-catalyst poisons as a result of the formation of stable
metal–sulfur complexes.1 To the best of our knowledge, only a
handful of successful Heck cross-coupling reactions based on sulf-
oxides are known, whereas these moieties have potential for many
synthetic applications.2 Among this class of molecules, perfluoroal-
kyl vinyl sulfoxides possess a strongly polarized double bond [e.g.,
rp (CF3SO) = 0.69],3 which is the reason behind the high reactivity
of these compounds and makes them interesting for investigation.
We have previously described convenient syntheses of perfluoroal-
kyl vinyl sulfoxides leading to the good availability of such
substrates.4
It was shown earlier that aryl iodides are a little more reactive
than aryl bromides in the Heck reaction.5 Therefore we chose aryl
iodides as the reagents. The reactions were performed in DMF
under argon at 110–115 °C with a 1:0.8 molar ratio of perfluoroal-
kyl vinyl sulfoxide/aryl iodide. Palladium(II) acetate is the most
commonly used catalyst for the Heck reaction with aryl iodides.
Nevertheless, we began our investigations by testing various other
palladium catalysts on our model system (Table 1).
Triethylamine and sodium hydrogen carbonate were tested as
bases. Reactions were carried out until no further change in the
1H NMR spectrum was observed. The reaction time was clearly
dependent on the palladium catalyst used. It is noteworthy to
mention that, in all cases, a by-product without a trifluoromethyl-
sulfonyl group, namely styrene, was formed. This product was
identified from its characteristic signals due to the protons of the
C@C double bond in the 1H NMR spectrum.
It is evident from Table 1 that the most suitable catalysts are
palladium(II) acetate (entry 3), and Pd(dppf)Cl2 (entry 10). The best
results with Pd(OAc)2 were achieved when the latter was added to
the reaction mixture in two equal portions: 10 mol % of catalyst at
first and a further 10 mol % when no changes were observed in the
1H NMR spectrum. Further addition of palladium(II) acetate did not
lead to any more changes while the starting material was still
present in the reaction mixture, probably as a result of catalyst poi-
soning by the sulfinyl moiety. In the case of palladium(II) acetate,
In this Letter we describe the Heck reaction of trifluoromethyl-
and tridecafluorohexyl vinyl sulfoxides with aryl iodides using
palladium(II) acetate as the catalyst.
⇑
Corresponding author. Tel.: +38 044 559 0349; fax: +38 044 573 2643.
E-mail address: sokolenko.liubov@gmail.com (L.V. Sokolenko).
http://dx.doi.org/10.1016/j.tetlet.2015.01.136
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

1260
L. V. Sokolenko et al. / Tetrahedron Letters 56 (2015) 1259–1262
Table 1
the ratio of 2a/styrene was 1:0.4 while a 1:1 ratio of products was
Optimization of the catalyst system
obtained when Pd(dppf)Cl2was used. A final attempt in dimethyl-
acetamide proved unsuccessful. We therefore chose palladium(II)
acetate as the catalyst (10%+10%), triethylamine as the base and
DMF as the solvent in our further investigations.
O
S
O
base, catalyst
DMF, 110-115 oC
S
PhI
+
CF3
Ph
CF3
1
2a
Vinylation reactions of
a variety of aryl iodides using
trifluoromethyl vinyl sulfoxides were performed following these
optimization studies (Table 2, entries 1–10).6 It was shown that
electron-deficient aryl iodides reacted readily and gave higher
yields. The Heck reaction of tridecafluorohexyl vinyl sulfoxide was
also realized with 4-iodonitrobenzene and methyl 4-iodobenzoate
with acceptable yields (Table 2, entries 11 and 12).6 Careful
examination of the 1H NMR spectra indicated that the formation
of 1-aryl-2-perfluoroalkylsulfinylethylenes was E-stereoselective
(3JH–H for the protons of the C@C double bond were about 15–16 Hz).
The alkene geometry was confirmed by an X-ray analysis of
compound 2h. The general crystal structure of the molecule of
2h is shown in Figure 1 (CCDC 1034847).
Entry
Catalyst
(mol %)
Base
Time
(h)
Conversiona
(%)
1
2
3
4
5
6
7
8
9
Pd(OAc)2 (2)
Et3N
Et3N
Et3N
Et3N
16
6
50
7
32
32
28
9
51
95
25
47
70
40
40
17
25
—
Pd(OAc)2 (10)
Pd(OAc)2 (10+10)b
Pd(PPh3)4 (2)
5% Pd(C) (10)
5% Pd(C) (10)
10% Pd(C) (10)
PdCl2 (10)
Et3N
NaHCO3
NaHCO3
NaHCO3
Et3N
Pd(dppf)Cl2 (10)
64
80
10
Pd(dppf)Cl2 (10+10)b
Et3N
Conversion was determined as the % of reacted aryl iodide according to 1H NMR
a
Products 2a–g,k,l were readily purified by column chromatog-
raphy on silica gel. Compounds 4a–g could not be isolated in the
same manner, perhaps as a result of decomposition on silica.
However, in the cases of products formed in ca. 1:1 ratios (Table 2,
spectroscopy; the isolated yield was not determined in these cases.
b
The catalyst was added to the reaction mixture in two equal portions: 10 mol %
at first and another 10 mol % when no changes were observed in the 1H NMR
spectrum.
Table 2
Heck reaction of perfluoroalkyl vinyl sulfoxides with aryl iodides
O
O
Et3N, Pd(OAc)2 (20 mol%)
S
+
RF
Ar
ArI
S
+
Ar
DMF, 110-115 o
C
RF
4a-j
2a-l
1,3
RF = CF3 (1,2a-j), C6F13 (3,2k,l)
Entry
1
Aryl iodide
Time (h)
Product 2
Product 4
Molar ratio 2:4
Yield of 2a (%)
O
S
4a
I
50
46
1:0.4
44
2a
CF3
O
4b
CH3O
H3C
Cl
I
S
CF3
2
3
4
1:0.4
1:0.2
1:1
30
23
2b
CH3O
H3C
Cl
CH3O
H3C
Cl
O
I
4c
S
CF3
75
27
2c
O
I
S
4d
b
CF3
Traces
Cl
2d
Cl
Cl
O
I
S
4e
CF3
5
15
1:0.13
48c
2e
HOOC
O2N
COOH
O2N
COOH
O
I
S
CF3
6
7
15
43
1:0.3
1:0.6
60
40
4f
2f
O2N
O
S
4g
F3C
I
2
g
CF3
CF3
F3C

L. V. Sokolenko et al. / Tetrahedron Letters 56 (2015) 1259–1262
1261
Table 2 (continued)
Entry
Aryl iodide
Time (h)
36
Product 2
Product 4
COOMe
MeOOC
AcHN
Molar ratio 2:4
Yield of 2a (%)
O
S
I
CF3
d
8
1:0.8
26
MeOOC
MeOOC
4h
2h
COOMe
MeOOC
AcHN
O
S
I
23e
4i
CF3
9
40
42
1:1
2i
O
S
AcHN
I
CF3
10
2j
1:1.3
37f
CF3
CF3
4j
4f
CF3
O
O2N
I
S
C6F13
11
12
15
64
1:0.8
1:0.4
68
30
O2N
2k
O2N
O
S
MeOOC
I
C6F13
MeOOC
4i
MeOOC
2l
a
b
c
d
e
f
Isolated yield of product.
This compound was not obtained in pure form. Its formation was observed in the 1H NMR spectrum and in the GC–MS analysis of the reaction mixture.
GC–MS yield. Compound 2e was obtained as a mixture with unreacted 3-iodobenzoic acid (64% of 2e).
Styrene 4h was isolated by HPLC as a mixture with the starting aryl iodide (50% of 4h). The GC–MS yield was 27%.
The isolated yield of styrene 4i was 27%.
The GC–MS yield of styrene 4j was 33%. It was obtained by HPLC as a mixture with the starting aryl iodide (50% of 4j).
O
S
H
O
S
-[Pd]
-H
Ar
R
F
Ar
R
F
2
[Pd]
O
S
O
S
R
-[Pd]
-H
F
R
F
O
[Ar-Pd]
Ar
H
S
R
[Pd]
F
-[Pd]
-[SORF]
Ar
Ar
4
Scheme 1.
Figure 1. ORTEP view of the molecule 2h (50% probability).
(Scheme 1). In the case of the terminal addition, b-elimination
of the palladium species and hydride takes place resulting in
compounds 2. If the addition of the aryl group occurs at the inter-
nal site of the double bond, b-elimination of the palladium species
and perfluoroalkylsulfinyl group (instead of hydride) leads to the
styrenes 4 being formed. The formation of stable Pd–S bonds can
facilitate this process.
In conclusion, we have studied the Heck reaction of trifluoro-
methyl and tridecafluorohexyl vinyl sulfoxides with aryl iodides.
It was found that palladium(II) acetate was the most suitable
catalyst for this reaction. A series of new E-1-aryl-2-perflu-
oroalkylsulfinylethylenes has been synthesized by a straightfor-
ward method. The products might show significant potential for
synthetic purposes, especially in the field of Michael additions.4a,8
Further studies on these new compounds are currently being
pursued.
entries 8–10), styrenes 4h–j could be isolated by HPLC. It should be
mentioned that compound 4i was obtained in pure form while
compounds 4h and 4j were separated as mixtures with unreacted
aryl iodides. Attempts to isolate pure styrenes 4h and 4j from these
mixtures failed. Nevertheless, the structures of these compounds
were confirmed by 1H and 13C NMR spectroscopy.
In Heck reactions of monosubstituted alkenes the regiochemist-
ry is determined by the balance between the addition of the aryl
group at the terminal and internal position of the alkenes. The
reaction is completed by b-elimination of the palladium species
and hydride.7 Although the addition of an aryl group to the internal
carbon atom is not typical for olefins bearing electron-withdraw-
ing substituents, we assumed that perfluoroalkyl vinyl sulfoxides
undergo both terminal and internal additions of the aryl group

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L. V. Sokolenko et al. / Tetrahedron Letters 56 (2015) 1259–1262
Carretero, J. C. J. Am. Chem. Soc. 1998, 120, 7129; (g) Wada, A.; Ohki, K.; Nagai, S.;
Acknowledgment
Kanatomo, Sh. J. Heterocycl. Chem. 1991, 28, 509; (h) Somei, M.; Yamada, F.;
Ohnishi, H.; Makita, Y.; Kuriki, M. Heterocycles 1987, 26, 2823.
We warmly acknowledge Loïc Pantaine for help with language
improvements.
3. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
4. (a) Sokolenko, L. V.; Maletina, I. I.; Yagupolskii, L. M.; Yagupolskii, Yu. L. Synlett
2010, 2075; (b) Magnier, E.; Tordeux, M.; Goumont, R.; Magder, K.; Wakselman,
C. J. Fluorine Chem. 2003, 124, 55–59.
5. Heck, R. F. In Organic Reactions; Dauben, W. G., Ed.; John Wiley & Sons Inc: New
York, 1982; vol. 27, pp 345–390.
Supplementary data
6. General experimental procedure for the Heck reaction: To an oven-dried, two-
necked, round-bottom flask equipped with a septum and a condenser were
added the perfluoroalkyl vinyl sulfoxide, aryl iodide, palladium(II) acetate, and
triethylamine in the mol ratio 1:0.8:0.08:1 followed by DMF under argon. The
flask was placed into an oil bath and was heated at 110–115 °C. The reaction
was followed by NMR. As soon as the conversion had stopped a second portion
of palladium(II) acetate (10 mol %) was added to the mixture. Heating at the
same temperature was continued until no changes in the 1H NMR spectra were
observed. The solution was cooled to room temperature and poured into dilute
HCl. The product was extracted with methyl t-butyl ether (6 Â 30 mL) and the
organic layer was washed with H2O (3 Â 25 mL) and dried over MgSO4. The
Supplementary data (experimental details, characterization
data, X-ray data and 1H, 19F and 13C NMR spectra of products 2a–
l and 4h–j) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2015.01.136.
References and notes
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