Pd-catalyzed aerobic direct olefination of polyfluoroarenes

Article abstract of DOI:10.1016/j.tetlet.2014.03.096

The first example of Pd-catalyzed aerobic direct olefination of polyfluoroarenes has been developed. The reaction makes use of molecular O ₂ as terminal oxidant, and provides a cost-efficient and environmentally benign access to polyfluoroarene-alkene structures that are of interest in life and material sciences.

Full text of DOI:10.1016/j.tetlet.2014.03.096

Tetrahedron Letters 55 (2014) 2962–2964
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Pd-catalyzed aerobic direct olefination of polyfluoroarenes
Chun-Yang He a, Feng-Ling Qing a,b, Xingang Zhang b,
⇑
a College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first example of Pd-catalyzed aerobic direct olefination of polyfluoroarenes has been developed. The
reaction makes use of molecular O2 as terminal oxidant, and provides a cost-efficient and environmen-
tally benign access to polyfluoroarene–alkene structures that are of interest in life and material sciences.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 30 January 2014
Revised 8 March 2014
Accepted 20 March 2014
Available online 27 March 2014
Keywords:
CAH functionalization
Olefination
Oxygen
Palladium
Polyfluoroarenes
Previous work
Due to the important role of polyfluoroarene derivatives in life
and material sciences,1 in particular in advanced functional mate-
rials, such as liquid crystals, organic light-emitting diodes (OLEDs),
and field-effect transistors (FETs),2 it is of great interest to develop
new and efficient methods to access such a class of fluorinated
compounds.3 Over the past few years, although considerable pro-
gresses have been achieved in transition-metal-catalyzed direct
CAH bond functionalization4,5 of polyfluoroarenes,6,7 efficient
methods for the construction of polyfluorarylated olefins remain
few. Very recently, we reported the first example of palladium-cat-
alyzed direct olefination of polyfluoroarenes via CAH bond activa-
tion,7a which represents one of the rare examples of catalytic direct
olefination of electron-deficient arenes.8 However, one drawback
of this method is the requirement of excessive silver salt (Ag2CO3),
which decreases its atom economy. To address this issue, the use of
molecular O2 as oxidant is appealing, because only water is pro-
duced as a byproduct. Inspired by our recent work on palladium-
catalyzed oxidative cross-coupling of polyfluoroarenes with thio-
phenes by using O2 as the terminal oxidant,7i herein, we report
the first example of palladium-catalyzed aerobic direct olefination
of polyfluoroarenes, which provides a cost-efficient and environ-
mentally benign access to polyfluoroarene–alkene structures
(Scheme 1). Furthermore, the use of thioether (PhSCH3) as a ligand
enables the reaction conducting with 1:1 ratio of polyfluoroarene
and alkene in high efficiency, thus highlighting the advantages of
this protocol.
cat. Pd
Ag2CO3 (2.0 equiv)
Fn
H
H
+
+
R
DMSO (5%)
Fn
R
R
1.0 equiv
2.0-3.0 equiv
This work
cat. Pd
Ag2CO3 (0.1 equiv)
Fn
H
H
R
O2 (1 atm)
Fn
1.0 equiv
PhSCH3 (2.0 equiv)
1.0 equiv
Scheme 1. Pd-catalyzed direct olefination of polyfluoroarenes.
We began this study by treatment of pentafluorobenzene 1a
(1.0 equiv) with tert-butyl acrylate 2a (2.0 equiv) in the presence
of Pd(OAc)2 (10 mol %) and PhSCH3 (2.8 equiv) in DMF under
1 atm O2 at 120 °C (Table 1, entry 1), in which PhSCH3 has been
previously demonstrated to be a good ligand to activate the palla-
dium species and benefit the catalytic cycle.9 However, only a trace
amount of the desired product 3a was detected. The addition of
K2CO3 or K3PO4 to the reaction led to negative results as well
(Table 1, entries 2 and 3). Considering that silver salts could facil-
itate the deprotonation of polyfluoroarene and benefit formation
of Pd(polyfluoroaryl) complex,7i a catalytic amount of Ag2CO3
(0.1 equiv) was employed. To our delight, the yield was dramati-
cally improved to 60% yield (determined by 19F NMR) (Table 1,
entry 4). These findings demonstrated that silver plays an essential
role in the catalytic cycle. Encouraged by this result, different sol-
vent and thioether were investigated (Table 1, entries 5–13). It was
⇑
Corresponding author. Tel.: +86 21 54925333.
E-mail address: xgzhang@mail.sioc.ac.cn (X. Zhang).
http://dx.doi.org/10.1016/j.tetlet.2014.03.096
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

C.-Y. He et al. / Tetrahedron Letters 55 (2014) 2962–2964
2963
Table 1
yields with high E/Z selectivities were obtained through this new
catalytic system. Compared to electron-rich alkenes, higher yields
were provided when electron-deficient alkenes were employed
as coupling partners (3a–e). The moderate yields obtained from
electron-rich alkenes are because of the formation of some alde-
hydes that were resulted from the oxidation of aromatic alkenes
under O2 atmosphere (3f–g). However, further optimization of
the reaction conditions by using 2.0 equiv of alkenes led to poor
yields (20–25% determined by 19F NMR). The substrate scope of
fluoroarene is not restricted to pentafluorobenzene, variations of
fluoroarenes containing 3–4 fluorines were also competent part-
ners. Moderate to good yields were obtained when 2.0 equiv of al-
kenes were used for 3-substituted tetrafluorobenzenes (3h–i).
Fluorinated pyridine also furnished its corresponding product in
synthetically useful yield (3j). For fluoroarenes containing more
than one reaction site, moderate yields of monoolefinated products
were still observed with using 3.0 equiv of fluoroarenes (3k–l).
In conclusion, a palladium-catalyzed aerobic direct olefination
of polyfluoroarenes has been developed. The reaction makes use
of molecular O2 as terminal oxidant, thus providing a cost-efficient
and environmentally benign access to polyfluoroarene–alkene
structures. The silver and thioether play important roles in the
reaction efficiency, further investigation of the reaction mecha-
nism is now in progress in our group.
Optimization of Pd-catalyzed aerobic direct olefination of pentafluorobenzene 1a
with tert-butyl acrylate 2aa
F
F
O
F
Pd(OAc)2 (10 mol %)
[Ag], additive
F
F
F
F
F
Ot-Bu
Ot-Bu
+
O2 (1 atm)
F
O
Solvent, 120 o
C
F
1a
2a
3a
Entry 2a (equiv) [Ag] (equiv) Solvent
Additive (equiv) Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22c
23d
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
—
DMF
DMF
DMF
PhSCH3(2.8)
PhSCH3(2.8)
PhSCH3(2.8)
PhSCH3(2.8)
PhSCH3(2.8)
Trace
10
K2CO3(0.1)
K3PO4(0.1)
nr
60
44
5
Ag2CO3(0.1) DMF
Ag2CO3(0.1) DMSO
Ag2CO3(0.1) Dioxane PhSCH3(2.8)
Ag2CO3(0.1) Toluene
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
PhSCH3(2.8)
PhSCH3(2.8)
PhSPh(2.8)
Trace
69
8
(t-Bu)2S(2.8)
t-BuSCH3(2.8)
CH3SCH3(2.8)
DMSO(2.8)
Trace
40
41
58
79
76
PhSCH3(2.8)
PhSCH3(1.5)
PhSCH3(2.0)
PhSCH3(2.5)
PhSCH3(3.0)
PhSCH3(4.0)
PhSCH3(2.0)
PhSCH3(2.0)
PhSCH3(2.0)
PhSCH3(2.0)
83(73)
81(72)
78
63
65
75
9
AgOAc(0.2)
Ag2O(0.1)
DMA
DMA
Table 2
Ag2CO3(0.1) DMA
Ag2CO3(0.1) DMA
Pd-catalyzed aerobic direct olefination of fluoroarenes 4 with various alkenes 2a
nr
Pd(OAc)2 (10 mol %)
Ag2CO3 (0.1 equiv)
a
H
Reaction conditions (unless otherwise specified): 1a (0.3 mmol, 1 equiv), 2a
R
Fn
+
R
Fn
(1.0–2.0 equiv), solvent (1 mL) at 120 °C for 8 h.
b
NMR yield determined by 19F NMR using fluorobenzene as an internal standard
PhSCH3 (2.0 equiv)
3
2
O2 (1 atm), DMA, 120 o
C
1
(isolated yield in parentheses).
c
The reaction was carried out in the absence of O2.
The reaction was carried out in the absence of Pd(OAc)2.
d
F
O
F
F
O
F
F
O
F
F
F
F
F
F
found that polar solvent DMA was the best reaction medium, pro-
viding 3a in 69% yield (Table 1, entry 8), but non-polar solvent tol-
uene failed to afford the desired product (Table 1, entry 7). It was
also revealed that the steric effect of the thioethers significantly
influenced the reaction efficiency (Table 1, entries 9–12). Thio-
ethers bearing two bulky groups, such as PhSPh and tBuStBu al-
most inhibited the reaction (Table 1, entries 9–10). While
synthetically useful yields were obtained by employing tBuSCH3
or CH3SCH3 as an additive (Table 1, entries 11–12). We reasoned
that the different reactivities of the tested thioethers might be as-
cribed to the different coordination abilities of thioethers to palla-
dium. Compared to PhSCH3, the strong or poor coordination of
thioether to palladium all led to some palladium intermediates
with low catalytic activities. This is in accordance to our previous
report.7 Additionally, DMSO10 could also be used as an additive
and provided 3a in moderate yields (Table 1, entries 13). Further-
more, we found that the ratio between 1a and 2a also influenced
the reaction efficiency. Even a higher yield (79%, determined by
19F NMR) of 3a was obtained, when the reaction was carried out
with 1:1 ratio of 1a and 2a, thus highlighting the advantage of
the present catalytic system (Table 1, entry 14). Other silver salts,
such as AgOAc and Ag2O, were also effective, but provided lower
yields than Ag2CO3 did (Table 1, entries 20–21). Finally, the optimal
reaction conditions were identified by using 2.0 equiv of PhSCH3,
with 73% isolated yield of 3a obtained (Table 1, entry 16). The ab-
sence of O2 or Pd(OAc)2 led to poor yields or no product, thus dem-
onstrating that a palladium redox catalytic cycle is involved in the
reaction (Table 1, entries 22–23).
OEt
On-Bu
Ot-Bu
F
F
F
F
3a, 73% (35:1)
3b, 62% (30:1)
3c, 60% (38:1)
F
F
O
F
F
O
P
F
F
N
F
F
F
OEt
OEt
F
F
F
F
F
F
F
3d, 72%
3e, 57% (20:1)
3f, 43%
F
O
F
F
O
F
F
F
F
Ot-Bu
F
F
Ot-Bu
F3C
F
MeO
F
F
F
3h, 71%b
3i, 61%b
3g, 42%
F
O
F
F
O
F
O
F
F
Ot-Bu
Ot-Bu
Ot-Bu
N
F
F
F
F
F
3k, 41% (9%)c
3l, 40% (6%)c
3j, 42%
a
Reaction conditions (unless otherwise specified): 1 (0.3 mmol, 1.0 equiv), 2
(1.0 equiv), DMA (1 mL) for 8 h. Number in parentheses is the ratio of E/Z.
b
1 (0.3 mmol, 1.0 equiv) and 2 (2.0 equiv) were used.
c
1 (3.0 equiv) and 2 (0.3 mmol) were used. Number in parentheses is dialkeny-
With the optimal reaction conditions in hand, a variety of al-
kenes were investigated (Table 2). Generally, moderate to good
lated product.

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C.-Y. He et al. / Tetrahedron Letters 55 (2014) 2962–2964
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The National Natural Science Foundation of China (NSFC) (nos.
21172242 and 20832008), and SIOC are greatly acknowledged for
funding this work.
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Supplementary data
Supplementary data (detailed experimental procedures, and
characterization data for new compounds) associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.tetlet.2014.03.096
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