Thioether-promoted direct olefination of polyfluoroarenes catalyzed by palladium

Article abstract of DOI:10.1021/ol402492s

A methyl(phenyl)sulfane-promoted direct olefination of polyfluoroarenes catalyzed by palladium has been reported. With use of this new thioether ligand, a high reaction efficiency and excellent E/Z ratio of desired olefinated polyfluoroarenes were obtained. This represents a first example of thioether promoted oxidative Heck reaction.

Full text of DOI:10.1021/ol402492s

ORGANIC
LETTERS
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Vol. XX, No. XX
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Thioether-Promoted Direct Olefination of
Polyfluoroarenes Catalyzed by Palladium
Cai-Zhi Wu,‡ Chun-Yang He,‡ Yangen Huang,‡ and Xingang Zhang*,†
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University,
2999 North Renmin Lu, Shanghai 201620, China, and Key Laboratory of Organofluorine
Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, China
xgzhang@mail.sioc.ac.cn
Received August 30, 2013
ABSTRACT
A methyl(phenyl)sulfane-promoted direct olefination of polyfluoroarenes catalyzed by palladium has been reported. With use of this new thioether
ligand, a high reaction efficiency and excellent E/Z ratio of desired olefinated polyfluoroarenes were obtained. This represents a first example of
thioether promoted oxidative Heck reaction.
Polyfluoroaryl groups are an important structural motif
found in a wide range of bioactive compounds and func-
tional materials.1 In particular, such fluorinated compounds
constitute a distinct class of active materials in liquid
crystals and electronic devices.2 Over the past few years,
many efforts have been made to access polyfluoroaryl-
substituted compounds, and some impressive methods of
transition-metal-catalyzed direct functionalization of
polyfluoroarenes have been developed.3,4 Since the use
of simple and readily available polyfluoroarenes as starting
material without requirement of a “prefunctionalization”
‡ Donghua University.
† Shanghai Institute of Organic Chemistry.
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(5) For selected recent reviews related to CÀH bond activation, see:
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Rev. 2009, 38, 3242. (b) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc.
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10.1021/ol402492s
XXXX American Chemical Society

process, this direct CÀH bond functionalization strategy
represents an attractive and ideal alternative to the tradi-
tional techniques.5,6 Very recently, we reported a first
example of Pd-catalyzed direct olefination of polyfluoro-
arenes,4a which represents one of the rare examples of
catalytic direct olefination of electron-deficient arenes.7
During the studies, it was found that DMSO plays an
important role for the reaction efficiency and may func-
tionalize as a ligand to active the palladium catalyst.8 This
finding inspired us to question that whether other DMSO
derivatives or sulfur containing compounds, such as
thioethers, could also benefit the reaction efficiency,
and improve the yields of some “inert” substrates, such
as 3-substituted tetrafluorobenzene, previously affording
low yields. Herein, we report a methyl(phenyl)sulfane-
promoted direct olefination of polyfluoroarenes cata-
lyzed by palladium. With use of this new thioether
ligand, high yields of desired olefinated polyfluoroar-
enes were obtained. In particular, for 3-substituted
tetrafluorobenezenes, much higher yields than our
previous results were afforded. This represents the
first example of thioether promoted oxidative Heck
reaction.
confirming that PhSMe itself has a beneficial effect on
the reaction. This is opposite to our common knowledge,
as thioethers usually poison the palladium catalyst and
inhibit the reaction.10 We reasoned that the highest activity
of PhSMe might be ascribed to the proper coordination
ability of PhSMe to palladium,11 leading to an active
palladium intermediate. However, the detailed mechanism
remains a point of discussion.
Table 1. Ligand Effect of Pd-Catalyzed Direct Olefination of
Pentafluorobenzene 1 with tert-Butyl Acrylate 2aa
Initially, different sulfoxides were tested by treatment of
pentafluorobenzene 1 (1.0 equiv) with tert-butyl acrylate
(2.0 equiv) and Ag2CO3 (2.0 equiv) in the presence of
Pd(OAc)2 (10 mol %) and sulfoxide (2.8 equiv) in DMF at
120 °C (Table 1). It turned out that diethyl sulfoxide is
better than DMSO, providing 3a in a slightly higher yield
(Table 1, entry 2), while diphenyl sulfoxide and methyl
(phenyl) sulfoxide showed little or no effect (Table 1,
entries 3 and 4). On the basis of these results, a series of
sulfanes corresponding to the above sulfoxides were
further examined to compare the activities between these
two types of similar ligands (Table 1, entries 5À8). In sharp
contrast to sulfoxides, a reverse activity was observed for
sulfanes. Dimethylsulfane and diethylsulfane almost in-
hibited the reaction (Table 1, entries 5 and 6), but with
increasing the size of substituents on the sulfanes, higher
yields of 3a were obtained (Table 1, entries 7À8), in which
methyl(phenyl)sulfane is superior to diphenylsulfane, pro-
viding the highest yield (80%) (Table 1, entry 8). However,
only 30% yield of 3a was provided when methyl (phenyl)
sulfoxide was employed (Table 1, entry 4). These results
demonstrated that PhSMe may functionalize as a ligand to
activate palladium species and benefit the reaction effi-
ciency.9 Additionally, a GCÀMS analysis of the reaction
showed only PhSMe was observed, and no formation of
methyl (phenyl) sulfoxide generated from the oxidation of
PhSMe was detected during the reaction, thus further
a Reaction conditions (unless otherwise specified): 1a (0.6 mmol), 2a
(2.0 equiv), Pd(OAc)2 (10 mol %), L (2.8 equiv, L/Pd(OAc)2 = 28:1,
mol/mol), and DMF (2.4 mL) at 120 °C for 12 h. b Isolated yield and the
number in parentheses is the E/Z ratio of 3a determined by 19F NMR.
c NMR yield determined by 19F NMR using fluorobenzene as internal
standard.
With the identification of the optimal ligand PhSMe, the
substrate scope with respect to direct olefination of penta-
fluorobenzene was illustrated in Scheme 1. Both electron-
deficient and electron-rich alkenes provided alkenylated
pentafluorobenzenes in good yields. Importantly, higher
yields and stereoselectivities (E/Z) than our previous re-
sults were obtained for electron-deficient alkenes (3aÀd).
For aromatic alkenes (3eÀg), a substrate bearing an
electron-donating group was more reactive than that of
electron-withdrawing one, providing an excellent yield
(94%). However, in the cases of 3d and 3e, slightly
lower yields were obtained. Notably, protected allyla-
mine also underwent reaction smoothly, with 3h ob-
tained as the major product, thus providing a good
opportunity for further transformation. The X-ray
crystallographic analysis of 3h further confirmed its
structure (see the Supporting Information). In addi-
tion, more electron-rich alkene, such as enamide, also
furnished its corresponding product in good yield with
high stereoselectivity (3i). However, the enol ether
(8) For the role of DMSO in Pd(OAc)2-catalyzed reactions, see:
Steinhoff, B. A.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348 and
references cited therein.
(10) (a) Feuerriegel, U.; Klose, W. Chem. Eng. Technol. 1998, 21, 562.
(b) Munakata, N.; Reinhard, M. Appl. Catal. B: Environ. 2007, 75, 1.
(11) For studies related to interaction between thioether and palla-
dium, see: (a) Singh, A.; Ramanan, A.; Bandyopadhyay, D. Cryst.
Growth Des. 2011, 11, 2743. (b) Wong, H. L, S.; Allan, D. R.; Champness,
N. R.; McMster, J.; Schroder, M.; Blake, A. J. Angew. Chem., Int. Ed. 2013,
52, 5093.
(9) (a) Kuriyama, M.; Shimazawa, R.; Shirai, R. Tetrahedron 2007,
63, 9393. (b) Amadio, E.; Scrivanti, A.; Bortuluzzi, M.; Bertoldini, M.;
Beghetto, V.; Matteoli, U.; Chessa, G. Inorg. Chim. Acta 2013, 405, 188.
(c) Henderson, W. H.; Check, C. T.; Proust, N.; Stambuil, J. P. Org. Lett.
2010, 12, 824. (d) Li, H.; Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Org. Lett. 2011,
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C. T.; Stambuli, J. P. Chem.;Eur. J. 2013, 19, 11153.
B
Org. Lett., Vol. XX, No. XX, XXXX

1-(vinyloxy)butane provided a mixture of olefinated
products in 42% yield (determined by 19F NMR).
Cyclohexene was a unsuitable substrate, leading to a
poor yield (10% determined by 19F NMR).
Scheme 2. Pd-Catalyzed Direct Olefination of Fluoroarenes 4
with Various Alkenes 2a
Scheme 1. Pd-Catalyzed Direct Olefination of
Pentafluorobenzene 1 with Various Alkenes 2a
a Reaction conditions (unless otherwise specified): 4 (0.6 mmol), 2
(1.0 equiv), DMF (2.4 mL) for 9 h. Number in parentheses is the ratio of
E/Z. b 2.0 equiv of 2 was used. c 3.0 equiv of 1 was used, and 10% of
dialkenylated product was obtained. d Previous method (ref 4a): 1 (0.6
mmol), 2 (2.0 equiv), Pd(OAc)2 (10 mol %), DMSO (2.8 equiv), DMF
(2.4 mL), 120 °C, 9 h.
a Reaction conditions (unless otherwise specified): 1 (0.6 mmol), 2
(2.0 equiv), Pd(OAc)2 (10 mol %), PhSCH3 (2.8 equiv), DMF (2.4 mL),
120 °C, 9 h. Number in parentheses is the ratio of E/Z. b 1.0 equiv of 1
was used. c Previous method (ref 4a): 1 (0.6 mmol), 2 (2.0 equiv),
Pd(OAc)2 (10 mol %), DMSO (2.8 equiv), DMF (2.4 mL), 120 °C, 9 h.
A competitive reaction between electron-deficient
and electron-rich alkenes with pentafluorobenzene
was also conducted (Scheme 3), providing their corre-
sponding products 3a and 3e in an almost 1:1 ratio
(determined by 19F NMR), thus demonstrating that
the direct olefination of polyfluoroarenes has no bias
on the nature of alkenes under the present reaction
conditions.
In addition to the demonstrated broad range of poly-
fluoroarenes, various fluoroarenes 4 containing three or
four fluorines were also competent partners (Scheme 2). It
is noteworthy that the “inert” substrates, such as 3-sub-
stituted tetrafluorobenzenes that previously furnished
their corresponding products in low yields, afforded alke-
nylated products in high yields and excellent stereoselec-
tivities with using only 1.0 equiv of alkenes (5aÀh), thus
featuring the power of the thioether ligand PhSMe.
For example, a much higher yield of 5a than previously
was obtained when PhSMe was used as a ligand (5a).
Similar significant results were also observed when 1,2,4,5-
tetrafluoro-3-methylbenzene and 1,2,4,5-tetrafluoro-3-tri-
fluoromethylbenzene were used as substrates (5cÀd). Ad-
ditionally, other substituents on the tetrafluorobenzene at
the para position to the hydride, such as alkenyl, benzyl
and aryl groups, also proceeded smoothly (5eÀf), thus
allowing the facile synthesis of highly functionalized
polyfluoroarene derivatives. For the substrate bearing
more than one reaction site, moderate yields of mono-
alkyenylated products still could be obtained (5iÀj). A
pyridyl group was also compatible with the coupl-
ing reaction, providing a lower yield than previous
result (5k).
Scheme 3. Competitive Reaction
In summary, a thioether-promoted direct olefination of
polyfluoroarenes catalyzed by palladium has been devel-
oped. The power of the new ligand PhSMe has been
demonstrated by the reaction of those previous ‘inert’
Org. Lett., Vol. XX, No. XX, XXXX
C

substrates to provide high yields, thus offering us a
new choice to discover more efficient catalytic systems.
Further investigation of the reaction mechanism and using
thioether as a ligand for other reactions are now in
progress.
NSFC (No 21172242), and SIOC are greatly acknowl-
edged for funding this work.
Supporting Information Available. Detailed experimen-
tal procedures and characterization data for new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org
Acknowledgment. The National Basic Research Pro-
gram of China (973 Program) (No. 2012CB821600), the
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX