Direct Transformation of Tetrafluoroethylene to Trifluorovinylzinc via sp2C-F Bond Activation

Article abstract of DOI:10.1021/acs.orglett.0c03189

Trifluorovinylzinc is a common synthetic intermediate for trifluorovinyl derivatives, including α,β,β-trifluorostyrenes and hexafluorobutadiene. Here, we report a novel synthetic approach for the formation of trifluorovinylzinc chloride via a C-F bond activation of tetrafluoroethylene (TFE), which is an industrially cost-effective bulk feedstock with a negligible GWP. The present system provides a practical synthetic route to various trifluorovinyl derivatives with very low energy consumption.

Full text of DOI:10.1021/acs.orglett.0c03189

pubs.acs.org/OrgLett
Letter
Direct Transformation of Tetrafluoroethylene to Trifluorovinylzinc
via sp2 C−F Bond Activation
Kotaro Kikushima, Yuusuke Etou, Ryohei Kamura, Ippei Takeda, Hideki Ito, Masato Ohashi,
and Sensuke Ogoshi*
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ABSTRACT: Trifluorovinylzinc is a common synthetic intermediate for
trifluorovinyl derivatives, including α,β,β-trifluorostyrenes and hexafluorobutadiene.
Here, we report a novel synthetic approach for the formation of trifluorovinylzinc
chloride via a C−F bond activation of tetrafluoroethylene (TFE), which is an
industrially cost-effective bulk feedstock with a negligible GWP. The present system
provides a practical synthetic route to various trifluorovinyl derivatives with very
low energy consumption.
rifluorovinyl compounds have attracted great attention, as
they represent promising potential monomers for the
Tetrafluoroethylene (TFE) is an industrially cost-effective
bulk feedstock for the production of fluorine-containing
polymers that exhibits a negligible GWP.4,15,16 TFE thus
represents an ideal starting material for fluoroethylene-based
compounds.,16c17 We have demonstrated the direct trans-
formation of TFE into α,β,β-trifluorostyrene derivatives via
palladium-catalyzed cross-coupling reactions of TFE with
arylzinc, arylboronate, and arylsilane reagents, involving C−F
bond activation by a transition-metal catalyst.17a−c,18 Our next
target was the direct transformation of TFE into stable
trifluorovinylzinc halides, which are common intermediates for
trifluorovinyl compounds.17d We envisioned that the cleavage
of a C−F bond could be achieved by treating TFE with a
mixture of a zinc halide and an appropriate reductant to
generate the corresponding trifluorovinylzinc halide. Crabtree
and co-workers have reported that magnesium anthracene
reacts with perfluoroarenes to generate the corresponding
organomagnesium reagents, which are unstable and are
subsequently converted to fluorinated benzoic acid.19 Un-
eyama and Amii have demonstrated that a combination of
magnesium and chlorotrimethylsilane can be used for cleavage
of the C−F bond in trifluoromethyl ketones to produce the
corresponding difluoro enol silyl ethers.20 These reports
prompted us to employ magnesium metal as a reductant for
the C−F bond activation in TFE. Herein, we disclose a simple
and cost-effective synthesis of trifluorovinylzinc chloride
T
synthesis of functionalized polymers with fluorinated main
chains,1 including α,β,β-trifluorostyrenes.2,3 In addition,
hexafluorobutadiene is the best-performing dry-etching gas
with a low global warming potential (GWP),4 which enables
the fabrication of complicated networks of narrow and deep
microchannels on silicon substrates for large-scale integration
(LSI) chips.5 Furthermore, the trifluorovinyl group has
attracted attention as a potentially interesting fluorinated
functional group for the design of drug candidates.6
α,β,β-Trifluorostyrene derivatives have been synthesized
through the palladium-catalyzed cross-coupling of aryl halides
with trifluorovinylmetal intermediates (metal = Zn,7−9 Sn,10 or
B11). These intermediates have been prepared from chlorotri-
fluoroethylene (CTFE)7 and 1,1,1,2-tetrafluoroethane (HFC-
134a)8,10,11 via halogen exchange or deprotonation with
butyllithium generating unstable trifluorovinyllithium. How-
ever, 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113, the start-
ing material for CTFE) and HFC-134a have high GWP100
values of 5000 and 1430, respectively. Both bromo- and
iodotrifluoroethylene can be converted into the corresponding
trifluorovinylzinc halides by treatment with zinc powder,9 but
these halotrifluoroethylenes are very expensive. Trifluorovi-
nylzinc halides are also key intermediates for the synthesis of
hexafluorobutadiene. The groups of Burton and Ramachan-
dran have independently reported the synthesis of hexafluor-
obutadiene via the homocoupling of trifluorovinylzinc
halides12 as an alternative to the conventional multistep
syntheses.13,14 Therefore, the development of new strategies
for the preparation of trifluorovinylzinc halides from environ-
mentally benign and economical starting materials would
provide a practical approach to the synthesis of the above-
mentioned trifluorovinyl derivatives.
Received: September 23, 2020
https://dx.doi.org/10.1021/acs.orglett.0c03189
© XXXX American Chemical Society
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A

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(TFVZ) from TFE in the presence of zinc chloride and
magnesium turnings; all reagents involved are abundant and
inexpensive. The resulting TFVZ was effectively converted into
various trifluorovinyl derivatives, such as α,β,β-trifluorostyr-
enes, α,β,β-trifluoroacrylic acid derivatives, and trifluorovinyl-
silane. Furthermore, hexafluorobutadiene was synthesized
quantitatively from the prepared TFVZ.
Exposure of a 1,3-dimethyl-2-imidazolidinone (DMI)
suspension of ZnCl2 and Mg turnings to a TFE atmosphere
at room temperature for 6 h afforded TFVZ (1) in 5% yield
(Table 1, run 1). In this reaction, the insertion of TFE into a
C−H bond of DMI also occurred to generate 2 in 2% yield.
When a mixture of ZnCl2 and Mg turnings was stirred in DMI
without TFE, the Mg surface and the entire suspension
gradually turned black, which suggests the generation of highly
activated Mg and/or Zn metal. Employing 2.0 equiv of ZnCl2
improved the yield to 50% (run 2). The Knochel group has
reported the convenient preparation of organozinc reagents
from organohalides using a combination Mg, ZnCl2, and
LiCl;21 however, in the present study, the addition of LiCl
resulted in decreased yield (run 3). Conducting the reaction at
60 °C for 6 h improved the reaction yield to 74% (run 4),
whereas increasing the reaction time (24 h) led to a decreased
yield (run 5). In these cases, the formation of bis-
(trifluorovinyl)zinc (1′) was also observed (2%; runs 2,4,
and 5) as the result of the Schlenk equilibrium. The yields
listed in Table 1 represent the combined yields of TFVZ based
on the trifluorovinyl moiety. Then we surveyed the effect of
varying the solvent on the yield of TFVZ. The use of N-
methylpyrrolodone (NMP) gave 1 in 11% yield, although
neither N,N-dimethylacetamide (DMA) nor N,N-dimethylfor-
mamide (DMF) afforded the desired product (runs 6−8).
Conversely, employing THF did not produce 1; instead, the
insertion of TFE into a C−H bond of THF proceeded to give
3 and 4 in 10% and 3% yield, respectively (run 9).
Based on these results, we chose DMI as the optimum
solvent for the direct transformation of TFE into TFVZ.22 The
reaction yield was further improved by employing a two-step
procedure and maintaining a high concentration of TFE
(Scheme 1a). Specifically, a mixture of Mg and ZnCl2 was
stirred in DMI at room temperature for 2 h, and the reactor
was then pressurized with TFE. The reaction mixture was
stirred at 60 °C for 6 h before the reactor was pressurized again
with TFE in order to maintain a high TFE concentration. The
mixture was then stirred for a further 16 h at 60 °C to afford
TFVZ in 89% yield. Subsequently, we next surveyed methods
to purify TFVZ in the reaction mixture, which contained
Table 1. Optimization of Reaction Conditions for
a
Transformation of TFE into TFVZ
run ZnCl2 (equiv) solvent temp (°C) time (h) yield of 1 + 1′ (%)
b
1
2
3
4
5
6
7
8
9
1.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
DMI
DMI
DMI
DMI
DMI
NMP
DMA
DMF
THF
rt
rt
rt
60
60
60
60
60
60
6
24
24
6
24
24
24
24
24
5
50
27
74
62
11
c
d
e
trace
0
f
0
a
b
Conducted in a glass autoclave reactor (55 mL). NMR yield. With
c
d
e
2 (2%). In the presence of 0.5 equiv of LiCl. With 2 (4%). With 2
(6%). With 3 (10%) and 4 (3%).
f
Scheme 1. Preparation and Purification of TFVZ
B
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a
Scheme 2. Coupling Reactions of TFVZ to Produce Various Trifluorovinyl Monomers
a
b
c
See the SI for experimental details. NMR yield. Isolated yield.
unreacted metal (Zn and/or Mg) as well as a substantial
amount of metal halides. Filtration of the freshly prepared
crude TFVZ through a Celite plug removed metal powder to
furnish a black solution (Scheme 1a, method A). A 19F NMR
analysis of this filtrate showed that the overall TFVZ yield was
83%. A clear solution was obtained by adding diethyl ether to
the crude mixture rather than filtering it directly over Celite;
stirring the resulting solution for several hours at room
temperature afforded a yellow solution with a gray precipitate.
The insoluble material was removed by filtration through a
glass filter. After concentration of the filtrate, a transparent
yellow DMI solution containing 79% TFVZ was obtained
(Scheme 1a, method B). This TFVZ reagent (as yellow DMI
solution) could be stored without decomposition for at least
three years at 25 °C under an N2 atmosphere.
Based on these results, we attempted to further improve the
reaction yield (Scheme 1b). After Mg and ZnCl2 were mixed in
DMI at room temperature for 2 h, the reactor was pressurized
with TFE and the mixture was stirred at 60 °C. To maintain a
high concentration of TFE throughout the reaction, the reactor
was completely pressurized (to 5 atm) every 3 h. A 19F NMR
analysis of the crude mixture revealed that TFVZ was
generated in 97% yield, and purification of the crude mixture
via method B afforded a clear yellow DMI solution; the overall
TFVZ yield after filtration was 93%. The transformation of
CTFE to TFVZ was also investigated at the bench scale using
the optimized conditions for TFE.23 The reaction proceeded
to produce TFVZ quantitatively; after a subsequent
purification using method B a yellow solution with an overall
TFVZ yield of 95% was obtained (Scheme 1b*). The
transformation of TFE into TFVZ was then scaled up using
1.6 g of Mg and 18 g of ZnCl2 under 850 kPa (= 8.39 atm) of
TFE in a SUS 316 autoclave reactor (total volume: 500 mL)
(Scheme 1c).24 The reactor was repeatedly pressurized to 850
kPa with TFE untilno internal pressure decrease was observed.
A
19F NMR analysis of the resulting mixture revealed that
TFVZ was generated in 93% yield (61.4 mmol, ∼11 g).
We next examined the Pd(0)-catalyzed cross-coupling
reaction of the prepared TFVZ with 2-bromonaphthalene
(5a) (Scheme 2a). Heating a suspension of freshly prepared,
unpurified TFVZ (1.1 equiv) in DMI and 5a in the presence of
10 mol % of Pd(PPh3)4 at 80 °C for 24 h resulted in the
formation of the corresponding product (6a) in 36% yield
(Scheme 2a, run 1). The use of the black TFVZ solution
obtained from purification method A improved the reaction
yield drastically to 97% within 0.5 h (run 2). The catalyst
loading could be decreased to 1 mol % to obtain 6a in 94%
yield (run 3), although further decreasing the catalyst loading
to 0.1 mol % reduced the reaction yield (run 4). Furthermore,
the yellow TFVZ solution purified by method B showed higher
reactivity (run 5). Using only 0.1 mol % of Pd(PPh3)4, the
catalytic reaction proceeded to afford 6a in 93% yield (run 6).
With the optimized reaction conditions in hand, Pd(0)-
catalyzed cross-coupling reactions of various aryl bromides
with the TFVZ solution purified by method B were
investigated (Scheme 2b). A bromoarene with an electron-
deficient group, such as ester (5b, 5c and 5d) or
trifluoromethyl (5e) group, produced the corresponding
product (6b−e). α,β,β-Trifluorostyrene derivatives bearing
an electron-donating group, such as a methoxy group (6f), was
obtained in excellent yield. Although sterically hindered aryl
bromides, such as 1-bromonaphthalene (5g) and 9-bromoan-
C
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thracene (5h), required higher reaction temperatures, the
corresponding products (6g and 6h) were obtained in high
yield. When the TFVZ solution purified by method A was
used, the yields decreased due to the decomposition of TFVZ
at high temperature. These coupling reactions could also be
successfully applied to the synthesis of trifluorovinyl
heteroaromatics (6i and 6j).
such as functional fluorinated polymers, LSI chips, and new
drugs.
ASSOCIATED CONTENT
* Supporting Information
■
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c03189.
Subsequently, we investigated the synthesis of trifluorovinyl
carbonyl compounds employing the TFVZ solution obtained
from purification method B (Scheme 2c). α,β,β-Trifluoroacry-
lates have been prepared via the palladium-catalyzed coupling
reactions of trifluorovinylstannane with chloroformate or the
reduction of 2-bromo-2,3,3,3-tetrafuoropropanoate by zinc.25
Conversely, organozinc intermediates have not yet been
employed as a trifluorovinyl source. The coupling reaction
between TFVZ and methyl chloroformate (7a) in the presence
of the catalyst Pd(PPh3)4 generated the desired product 8a,
albeit together with unidentified byproducts. When the
reaction was conducted at 60 °C using CuCl and bipyridine
instead of Pd(PPh3)4, 8a was afforded as the sole product in
quantitative yield. Employing chloroformates and carbamoyl
chlorides produced the respective α,β,β-trifluoroacrylates (8b
and 8c) and α,β,β-trifluoroacrylamides (8d and 8e). When
benzoyl chloride was used as a coupling partner, trifluorovinyl
phenyl ketone (8f) was obtained smoothly in quantitative
yield. Furthermore, the reaction with trimethylsilyl chloride
afforded trifluorovinylsilane 10, which could be converted to
other trifluorovinyl derivatives (Scheme 2d).26
Experimental procedures, characterization data, and
NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Sensuke Ogoshi − Department of Applied Chemistry, Faculty of
Engineering, Osaka University, Suita, Osaka 565-0871, Japan;
orcid.org/0000-0003-4188-8555; Email: ogoshi@
chem.eng.osaka-u.ac.jp
Authors
Kotaro Kikushima − College of Pharmaceutical Sciences,
Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
Yuusuke Etou − Product R&D Department Chemicals Division,
Daikin Industries, Ltd., Settu, Osaka 566-8585, Japan
Ryohei Kamura − Department of Applied Chemistry, Faculty of
Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Ippei Takeda − Department of Applied Chemistry, Faculty of
Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Hideki Ito − Department of Applied Chemistry, Faculty of
Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Masato Ohashi − Department of Applied Chemistry, Faculty of
Engineering, Osaka University, Suita, Osaka 565-0871, Japan;
orcid.org/0000-0001-8718-2799
The treatment of the TFVZ solution obtained from
purification method B with a stoichiometric amount of
CuCl2 generated hexafluorobutadiene smoothly as the sole
product in quantitative yield (Scheme 3). The previously
Scheme 3. Efficient Synthesis of Hexafluorobutadiene
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c03189
Notes
The authors declare the following competing financial
interest(s): A patent application (P2016-128415A, Japan)
dealing with the preparation of TFVZ and its derivatization,
has been filed; K.K., Y.E., M.O., and S.O. may benefit from
royalty payments.
reported methods12 provide hexafluorobutadiene in low yield
and/or together with side products such as bromo- and
chlorotrifluoroethylene probably due to contamination of
unpurified trifluorovinylzinc halides with metal salts generated
during the preparation. In contrast, the yellow TFVZ solution
prepared using our method does not contain metal salt
impurities. Accordingly, side reactions were suppressed, and
the desired reaction proceeded to quantitatively afford
hexafluorobutadiene. The use of the black TFVZ solution
(without ether treatment; Scheme 1, method A) furnished
hexafluorobutadiene together with chlorotrifluoroethylene.27
In conclusion, we have achieved the direct transformation of
TFE into TFVZ in the presence of Mg and ZnCl2 via C−F
bond activation. The resulting salt impurities, including
magnesium halides, were successfully removed by treatment
with ether followed by filtration and concentration to afford a
clear yellow solution of TFVZ in DMI. The resulting TFVZ
was employed as a key intermediate to efficiently produce
various trifluorovinyl derivatives including α,β,β-trifluorostyr-
enes and hexafluorobutadiene. The present findings can be
expected to provide access to useful fluorine-containing
chemicals from cost-effective and environmentally benign
feedstocks and thus aid the development of industrial products,
ACKNOWLEDGMENTS
■
This research was partially supported by the JSPS in the form
of Grants-in-Aid for Scientific Research (A) (16H02276 to
S.O.) and (B) (16KT0057 to M.O. and 18H02014 to K.K.), a
Grant-in-Aid for Young Scientists (A) (25708018 to M.O.)
and (B) (16K17899 to K.K.), and a Grant-in-Aid for Scientific
Research on Innovative Areas “Precisely Designed Catalysts
with Customized Scaffolding” (15H05803 to S.O.).
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fluorine-containing polymers, it is commercially not available to lab
(20) Amii, H.; Kobayashi, T.; Hatamoto, Y.; Uneyama, K. Mg0-
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the electron transfer in these reactions and stabilizes the reduced
E
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intermediate, although the details of the critical role of DMI have not
been clarified yet. For selected examples, see: (a) Utsumi, S.; Katagiri,
T.; Uneyama, K. Defluorination−silylation of alkyl trifluoroacetates to
2,2-difluoro-2-(trimethylsilyl)acetates by copper-deposited magnesi-
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bis(trimethylsilyl)benzene derivatives from 1,2-dichlorobenzenes
using a hybrid metal Mg/CuCl in the presence of LiCl in 1,3-
dimethyl-2-imidazolidinone. J. Org. Chem. 2013, 78, 3421−3424.
(23) CTFE is commercially available, although its GWP value is
much higher than that of TFE.
(24) Highly pressurized TFE can potentially explode. The scaled-up
reaction was performed using the facilities at Daikin Industries, Ltd.
(25) Yamada, S.; Noma, M.; Hondo, K.; Konno, T.; Ishihara, T.
Preparation and addition-elimination reactions of benzyl α,α,β-
trifluoroacrylate. A new stereoselective approach to (Z)-α-substituted
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(26) Zhang, Y.; Wu, D.; Weng, Z. Synthesis of 1,2,2-trifluorovinyl
sulphides and selenides from trifluorovinylation of organic thiocya-
nates and selenocyanates. Org. Chem. Front. 2017, 4, 2226−2229.
(27) See the Supporting Information.
F
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