Copper-mediated one-pot synthesis of trifluorostyrene derivatives from tetrafluoroethylene and arylboronate

Article abstract of DOI:10.1246/cl.150322

We developed the copper-mediated synthesis of trifluorostyrene derivatives. β-Fluorine elimination of a 2-aryl-1,1,2,2- tetrafluoroethylcopper complex, generated in situ from arylboronate, copper tert-butoxide, and 1,10-phenanthroline with tetrafluoroethylene (TFE) via carbocupration, was promoted by the addition of a Lewis acid. The present reaction system was applied to the one-pot synthesis of various trifluorostyrene derivatives, through the transmetalationcarbocuprationβ-fluorine elimination sequence.

Full text of DOI:10.1246/cl.150322

Received: April 7, 2015 | Accepted: April 23, 2015 | Web Released: May 1, 2015
CL-150322
Copper-mediated One-pot Synthesis of Trifluorostyrene Derivatives
from Tetrafluoroethylene and Arylboronate
Kotaro Kikushima,1 Hironobu Sakaguchi,1 Hiroki Saijo,1 Masato Ohashi,*1 and Sensuke Ogoshi*1,2
1Faculty of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871
2Advanced Catalytic Transformation Program for Carbon Utilization (ACT-C), JST, 2-1 Yamada-oka, Suita, Osaka 565-0871
(E-mail: ogoshi@chem.eng.osaka-u.ac.jp)
[CuOtBu]
ligand
We developed the copper-mediated synthesis of trifluoros-
tyrene derivatives. β-Fluorine elimination of a 2-aryl-1,1,2,2-
tetrafluoroethylcopper complex, generated in situ from aryl-
boronate, copper tert-butoxide, and 1,10-phenanthroline with
tetrafluoroethylene (TFE) via carbocupration, was promoted by
the addition of a Lewis acid. The present reaction system was
applied to the one-pot synthesis of various trifluorostyrene
derivatives, through the transmetalation-carbocupration-β-fluo-
rine elimination sequence.
O
B
F
F
Lewis Acid
F
F
+
O
F
Ar
Ar
F
F
one-pot procedure
[CuOtBu]
F
F
F
F F
CuL
Lewis Acid
CuL
F
Ar
Ar
F F
β
-fluorine
elimination
carbocupration
Trifluorovinyl compounds, including trifluorostyrene and its
derivatives, could be the favored candidates for a potential
monomer for fluorine-containing polymers.1 To access the tri-
fluorostyrene derivatives, several methods have been reported.2-8
For example, the reaction of tetrafluoroethylene (TFE) and
strong nucleophilic reagents, such as organolithium3 or organo-
magnesium compounds,4 yields the trifluorostyrene derivatives
through the addition of the nucleophile to TFE and β-fluorine
elimination. The palladium-catalyzed cross-coupling reactions of
trifluorovinylzinc, stannane, and boronate compounds with aryl
halides have been demonstrated as more direct approaches.2d,5
Alternatively, a catalytic coupling reaction of aryl nucleophiles
with trifluorovinyl halides is also an attractive approach for
obtaining trifluorostyrene derivatives.6,7 The cross-coupling
reaction of chloro- or bromotrifluoroethylene with arylboronic
acids was reported for obtaining trifluorostyrene derivatives.6
On the other hand, our group has focused on the catalytic
coupling reaction using TFE as a starting material via C-F bond
activation.7 We developed the first palladium-catalyzed arylation
of TFE with diarylzinc compounds,7a,8 arylboronates,7b or
organosilicon reagents7c to give trifluorostyrene derivatives.
Additionally, selective monosubstitutions of TFE with dieth-
ylzinc or organomagnesium compounds in the presence of a
lithium salt have been reported.8 TFE is one of the most
important materials for the production of fluorine-containing
polymers such as PTFE and is an economical and environ-
mentally benign feed stock with near-zero global warming
potential (GWP) for the fluorine industry.9 Therefore, the
development of transformations of TFE into other valuable
organofluorine compounds could increase the potential of TFE
as a useful starting material. Very recently, our group demon-
strated the synthesis of 2-aryl-1,1,2,2-tetrafluoroethylcopper
complexes through the carbocupration10 of TFE with an
arylcopper, prepared from arylboronate, copper tert-butoxide,
and 1,10-phenanthroline (phen) as a key step.11 In this literature,
we also described that the reaction of phenylmagnesium
bromide instead of phenylboronate produced trifluorostyrene.
Magnesium salts generated in situ might serve as a Lewis acid
and promote the β-fluorine elimination of 2-aryl-1,1,2,2-tetra-
Figure 1. One-pot copper-mediated synthesis of trifluorostyrene
derivatives through the transmetalation-carbocupration-β-fluorine
elimination process.
fluoroethylcopper. To access the trifluorostyrene derivatives
bearing various functional groups, however, the use of strong
nucleophiles such as organomagnesium compounds should be
avoided. In the course of our study, we found that the isolated
2-phenyl-1,1,2,2-tetrafluoroethylcopper complex was converted
into trifluorostyrene in the presence of MgBr2.11 We herein
describe the development of the one-pot copper-mediated
synthesis of trifluorostyrene derivatives through carbocupration
and β-fluorine elimination process using the less expensive
copper salt (Figure 1). The present reaction system could be an
alternative route toward trifluorostyrene derivatives without
palladium catalyst.
The present study was commenced with the examination of
the one-pot synthesis of trifluorostyrene from arylboronate and
TFE with a copper salt.12 The mixture of 2-naphthylboronate
(1a), copper tert-butoxide, and phen in THF and THF-d8 was
exposed to TFE (3.5 atm) and stored at 40 °C for 24 h, followed
by the addition of LiI. After the mixture was stored at room
temperature for 1 h, 2-trifluorovinylnaphthalene (2a) was ob-
served on 19F NMR in 57% yield based on the amount of copper
salt (Figure 2). Although the desired product was obtained in
moderate yield compared with the reaction using isolated
2-phenyl-1,1,2,2-tetrafluoroethylcopper complex and MgBr2
(75%),11 the one-pot procedure was confirmed to undergo the
transmetalation-carbocupration-β-fluorine elimination process
to give the corresponding trifluorostyrene derivative. When the
reaction was carried out with bathophenanthroline (bathophen)
instead of phen, the yield was slightly increased to 67%. The use
of 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) or 2,2¤-
bipyridine (bpy) as ligands was ineffective and gave no desired
product or dropped the yield to 16%, respectively. Although
various ligands including phosphine or NHC ligands and other
solvents were screened, the yield was not improved (Supporting
Information, Tables S1 and S2).
Chem. Lett. 2015, 44, 1019–1021 | doi:10.1246/cl.150322
© 2015 The Chemical Society of Japan | 1019

Table 2. Substrate scopea
F
O
B
F
[CuOtBu]
F
F
O
+
F
F
O
B
phen (1.0 equiv)
NaI (2.0 equiv)
rt, 1 h
F
F
F
+
3.5 atm
(excess)
O
Ar
Ar
F
THF/THF-d8
1a (1.1 equiv)
F
F
3.5 atm
(excess)
40 °C, 24 h
[CuOtBu]
ligand (1.0 equiv)
1 (1.1 equiv)
F
2
F
LiI (2.0 equiv)
rt, 1 h
F
F
F
F
THF/THF-d8
40 °C, 24 h
F
F
2a
F
F
F
F
MeO
2b, 70%
2c, 78%
2d, 55%
(70%)b
N
N
N
N
N
N
N
N
F
F
F
phen
57%
Me4-phen
0%
bathophen
67%
bpy
16%
F
F
F
F
F
MeOOC
OHC
NC
Figure 2. Screening of ligands. General conditions: [CuOtBu]
(0.02 mmol), ligand (0.02 mmol), 1a (0.022 mmol), PhCF3 (0.02
mmol, as a standard for 19F NMR) in THF/THF-d8 (0.5 mL,
v/v¤ = 4/1), TFE (3.5 atm, excess) at 40 °C for 24 h, and then
stored at rt for 1 h with LiI (0.04 mmol). Each yield was
determined by 19F NMR analysis.
2e, 50%c
2f, 68%c
2g, 54%c,d
(71%)b,e
F
F
F
F
F
F
O2N
F
F
F
F3C
Br
Table 1. Screening of Lewis acidsa
2h, 60%c,e
2i, 66%f
2j, 0%c
[CuOtBu]
phen (1.0 equiv)
F
Lewis acid
(2.0 equiv)
aGeneral conditions: [CuOtBu] (0.02 mmol), phen (0.02
mmol), 1 (0.022 mmol), PhCF3 (0.02 mmol, as a standard
for 19F NMR) in THF/THF-d8 (0.5 mL, v/v¤ = 4/1), TFE
(3.5 atm, excess) at 40 °C for 24 h, and then stored at rt for 1 h
with NaI (0.04 mmol). Each yield was determined by 19F NMR
analysis. bBathophen was used as a ligand instead of phen.
O
B
F
+
F
O
F
THF/THF-d8
40 °C, 24 h
rt, 1 h
3.5 atm
(excess)
1a (1.1 equiv)
F
F
F
F F
F F
cStored for 48 h before addition of NaI. Heated at 40 °C for
d
+
10 h after addition of NaI. eHeated at 40 °C for 1 h after
addition of NaI. fIsolated yield. Reaction conditions: see,
Supporting Information.
F
F
2a
3a
Yield/%
Run
Lewis acid
2a
3a
fluorine elimination would also occur and the resulting carbene
species reacts with 2-trifluoronaphthalene to give 3a, although
the reason is not clear at this time. On the other hand, LiF was
ineffective and produced neither 2a nor 3a (Run 6). When
BF3¢OEt2 was used as the Lewis acid, 2a was not produced, but
only 3a was obtained in 17% yield (Run 7). Exploration of other
Lewis acids did not provide any better results and did not afford
any products (Supporting Information, Table S3).
1
2
3
4
5
6
7
MgBr2
NaI
LiI
LiBr
LiCl
LiF
61
70
57
46
25
0
0
0
0
5
4
0
17
BF3¢OEt
0
With the optimized reaction conditions in hand, we next
surveyed the substrate scope for the copper-mediated one-pot
synthesis of trifluorostyrene derivatives using various arylboro-
nates (Table 2). A mixture of arylboronates 1, copper tert-
butoxide, and phen in THF and THF-d8 was exposed to TFE
(3.5 atm) and stored at 40 °C for 24 h, followed by the addition of
NaI. After the mixture was stored at room temperature for 1 h, the
resulting mixture was analyzed by 19F NMR. Starting from 5,5-
dimethyl-2-phenyl-1,3,2-dioxaborinane (1b) as a boronate, tri-
fluorostyrene (2b) was observed on 19F NMR in 70% yield. The
present reaction system tolerated electronically and sterically
diverse substituents. The reaction using 1-naphthylboronate 1c
proceeded well to yield the corresponding compound 2c in
high yield. Although 4-methoxyphenylboronate 1d produced
2d moderately under the standard conditions, the yield was
aGeneral conditions: [CuOtBu] (0.02 mmol), phen (0.02
mmol), 1a (0.022 mmol), PhCF3 (0.02 mmol, as a standard
for 19F NMR) in THF/THF-d8 (0.5 mL, v/v¤ = 4/1), TFE
(3.5 atm, excess) at 40 °C for 24 h, and then stored at rt for 1 h
with Lewis acid (0.04 mmol). Each yield was determined by
19F NMR analysis.
We next examined the varieties of Lewis acid (Table 1).
On using MgBr2, the desired reaction occurred and afforded
the desired product 2a in 61% yield (Run 1). The yield was
improved to 70% when NaI was used as the Lewis acid (Run 2).
Although LiI caused only β-fluorine elimination and gave 2a
selectively (Run 3), addition of LiBr or LiCl gave a mixture of
2a contaminated with 3a (Runs 4 and 5). In these cases, α-
1020 | Chem. Lett. 2015, 44, 1019–1021 | doi:10.1246/cl.150322
© 2015 The Chemical Society of Japan

improved to 70% by using bathophen in place of phen. The
reaction of arylboronates bearing ester (1e) or aldehyde groups
(1f) also proceeded to give the corresponding compounds 2e and
f without any problems. When 4-cyanophenylboronate 1g was
employed, heating at 40 °C and a longer reaction time were
required to promote β-fluorine elimination. In this case, changing
the ligand to bathophen was effective in giving the desired
product 2g in 71% yield. Additionally, 4-trifluoromethyltrifluo-
rostyrene (2h) was generated in 60% yield under the modified
reaction conditions. It is notable that the present reaction system
exhibits compatibility for bromide 1i and 4-bromotrifluoro-
styrene (2i) was isolated in 66% yield. In our previous reaction
system catalyzed by palladium,7 bromide was not suitable as a
substrate and could not survive. On the other hand, 3-nitro-
phenylboronate (1j) did not yield the desired product even with
the present system.
In conclusion, we have developed the copper-mediated
synthesis of trifluorostyrene derivatives from arylboronate and
TFE through the transmetalation-carbocupration-β-fluorine
elimination process under a one-pot procedure. In this system,
the carbocupration of TFE was achieved by using in situ
generated aryl copper and the β-fluorine elimination of the
resulting 2-aryl-1,1,2,2-tetrafluoroethylcopper complex was pro-
moted by the addition of a Lewis acid. The present reaction
system does not require strong nucleophiles like organomagne-
sium compounds or expensive palladium, and provides rela-
tively mild conditions. The application to other reaction systems,
including synthesis of trifluorovinylalkane, alkene, or alkyne,
and the development of catalytic variants with copper are under
investigation in our group.
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This work was partially supported by a Grant-in-Aid for
Young Scientist (A) (No. 25708018) and a Grant-in-Aid for
Scientific Research on Innovative Areas “Molecular Activation
Directed toward Straightforward Synthesis” (No. 23105546)
from MEXT and by the ACT-C and A-STEP programs from the
JST. M.O. also acknowledges The Noguchi Institute.
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Supporting Information is available electronically on J-STAGE.
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Chem. Lett. 2015, 44, 1019–1021 | doi:10.1246/cl.150322
© 2015 The Chemical Society of Japan | 1021