Preparation of trifluorovinyl compounds by lithium salt-promoted monoalkylation of tetrafluoroethene

Article abstract of DOI:10.1246/cl.130294

Treatment of tetrafluoroethene (TFE) with diethylzinc in the presence of lithium iodide gave 1,1,2-trifluoro-1-butene in moderate yield. In the absence of lithium iodide, however, the nucleophilic addition of diethylzinc to TFE proceeded very slowly to afford ethyl 1,1,2,2-tetrafluorobutylzinc. The addition of lithium iodide to a solution of ethyl-1,1,2,2-tetrafluorobutylzinc resulted in a smooth transformation into 1,1,2-trifluoro-1-butene. In the presence of lithium chloride, the reaction of TFE with benzyl or allyl Grignard reagents afforded the corresponding monosubstituted products in good to excellent yields.

Full text of DOI:10.1246/cl.130294

doi:10.1246/cl.130294
Published on the web May 31, 2013
933
Preparation of Trifluorovinyl Compounds by Lithium Salt-promoted Monoalkylation
of Tetrafluoroethene
Masato Ohashi,*1 Ryohei Kamura,1 Ryohei Doi,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
(Received April 4, 2013; CL-130294; E-mail: ogoshi@chem.eng.osaka-u.ac.jp)
Table 1. Pd(0)-catalyzed coupling reaction of TFE with ZnEt2
in the presence of lithium iodidea
Treatment of tetrafluoroethene (TFE) with diethylzinc in
the presence of lithium iodide gave 1,1,2-trifluoro-1-butene in
moderate yield. In the absence of lithium iodide, however, the
nucleophilic addition of diethylzinc to TFE proceeded very
slowly to afford ethyl 1,1,2,2-tetrafluorobutylzinc. The addition
of lithium iodide to a solution of ethyl-1,1,2,2-tetrafluorobutyl-
zinc resulted in a smooth transformation into 1,1,2-trifluoro-1-
butene. In the presence of lithium chloride, the reaction of TFE
with benzyl or allyl Grignard reagents afforded the correspond-
ing monosubstituted products in good to excellent yields.
Yield/%b
Run
Ligand
1
2
3
1
2
3
4
none
PCy3
Pn-Bu3
Pt-Bu3
N. D.
N. D.
N. D.
21
N. D.
65
68
20
9
4
Trifluorovinyl compounds, in particular trifluorostyrene and
its derivatives, have increasingly attracted attention, since they
are regarded as a potential monomer for the preparation of
polymers with a perfluorinated main chain.1 However, conven-
tional methods for their preparation thus far have not been fully
established. For example, most initial preparation routes of
trifluorostyrenes have required multistep reactions.2,3 The Pd(0)-
catalyzed cross-coupling reaction of trifluorovinylzinc or tin
reagents emerged in the 1980s as a more direct synthetic
method.2e,4,5 Alternative routes to synthesize ¡,¢,¢-trifluoro-
styrenes via the cross-coupling of chlorotrifluoroethene with
arylboronic acids have recently been reported.6 The usefulness
of tetrafluoroethene (TFE) as an ideal starting material for the
preparation of organofluorine products developed from its utility
as economical bulk organofluorine feedstock. Therefore, we
demonstrated a Pd-catalyzed coupling reaction of TFE with aryl
zinc compounds to yield ¡,¢,¢-trifluorostyrene derivatives.7
Furthermore, we recently developed a Pd(0)/PR3-catalyzed
cross-coupling reaction of fluoroalkenes with arylboronates.8
Our next concern was the development of a synthetic
method for monoalkylated trifluorovinyl species. However, an
initial attempt to apply the use of ZnEt2 to our reaction
conditions failed to give the desired 1,1,2-trifluoro-1-butene (1).
Instead, trifluorovinylzinc iodide (3) was obtained in 20% yield
with the concomitant generation of ethane and ethene (Table 1,
Run 1).9 As anticipated, the use of tertiary phosphines such as
PCy3 and Pn-Bu3 as the ligand afforded trifluoroethene (2) in
moderate yield (Runs 2 and 3). These results clearly showed that
¢-hydride elimination took place in preference to reductive
elimination from a (PR3)2Pd(Et)(CF=CF2) intermediate to give
1. Employing Pt-Bu3 with a strong ·-donation ability and
substantial bulkiness promoted reductive elimination to give the
desired product 1, but the yield (21%) was low, and 3 was
obtained concomitantly as the major product in this reaction
(Run 4). These results prompted a review of the reaction of TFE
with organometallic reagents. Although some groups have
already reported such a reaction,2c,3,10 the selective monoalky-
N. D.
31
aGeneral conditions: TFE (3.5 atm, >0.30 mmol), ZnEt2
(0.10 mmol), LiI (0.24 mmol), THF/THF-d8 (0.6 mL, v/v¤ =
b
2/1), PhCF3 (0.10 mmol, as a standard for 19F NMR). Yields
were determined by 19F NMR.
lation of TFE still remains unexploited. We herein report a series
of reactions using TFE with either ZnEt2 or alkylmagnesium
reagents. The use of appropriate additives enabled the selective
monoalkylation of TFE in moderate to excellent yields.
In the presence of lithium iodide, the treatment of TFE11
with diethylzinc in CD3CN at 60 °C for 24 h resulted in the
formation of 1 in 40% yield (eq 1). In this reaction, the
formation of disubstituted isomers, EtCF=CFEt (4), was
observed as a minor product. By contrast, NMR observation
revealed that the same reaction conducted in the absence of
lithium iodide gave a carbozincation product, EtCF2CF2ZnEt
(5), in 15% yield. The reaction of the adduct 5 generated in situ
with lithium iodide in CD3CN at room temperature smoothly
underwent the elimination of ethylzinc halide to give 1 in a
quantitative yield (eq 2).
ð1Þ
ð2Þ
These results indicated that lithium iodide promoted the
elimination reaction via a putative 6-membered transition state,12
Chem. Lett. 2013, 42, 933-935
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

934
Table 2. LiCl-promoted monosubstitution reaction of TFE
with RMgCl 6a
leading to the conversion of the initial carbozincation product 5
into 1. Another role of lithium iodide might be rationalized by
enhancing the nucleophilicity of diethylzinc as a result of
generating an active zincate species such as Li[Et2ZnI].13,14
The yield of 1 was improved to 51% under the same
reaction conditions with the exception of the employment of
t-BuCN in the place of MeCN as the reaction solvent (eq 3),
because an undesired side reaction involving diethylzinc with
MeCN in the presence of lithium iodide, generating ethane as a
result of deprotonation of the ¡-carbon, was suppressed.15
However, the resultant ethylzinc iodide showed less reactivity
toward TFE under the same reaction conditions (eq 4), and
therefore, the yield of 1 was improved to approximately 50%.
Yield/%b
Conv. of
Run
1
RMgCl (6b–6j)
6/%
7b–7j or 1
8b–8j or 4
93 (7b)
(6b)
(6c)
100
4 (8b)
MgCl
[55]
51 (7c)
2
100
4 (8c)
[18]
ð3Þ
MgCl
MgCl
>99 (7d)
3
4
(6d)
(6e)
100
100
<1 (8d)
<1 (8e)
[96]
ð4Þ
>99 (7e)
MgCl
[94]
5c
6d
7e
8
EtMgCl
t-BuMgCl
MgCl
(6f)
(6g)
(6h)
(6i)
(6j)
100
100
100
100
100
0 (4)
0 (8g)
21 (8h)
39 (8i)
0 (8j)
13 (1)
We next investigated the reaction of alkylmagnesium
reagents with TFE. The reaction of benzylmagnesium chloride
(6a) with TFE in THF/THF-d8 at room temperature for 0.5 h led
to the formation of (2,3,3-trifluoroallyl)benzene (7a) in a
moderate yield (eq 5). As reported by Jiang et al.,2c formation
of the corresponding disubstituted product 8a was observed.
Monitoring of the reaction by means of 19F NMR spectroscopy
detected no generation of the carbomagnesiation product. We
found that the addition of lithium chloride improved the rate and
selectivity of the reaction to give 7a in a quantitative yield.
Lithium chloride might enhance the reactivity of benzylmagne-
sium chloride as a result of the formation of ate species.16
22 (7g)
74 (7h)
31 (7i)
17 (7j)
MgCl
9f
MgCl
aGeneral conditions: TFE (3.5 atm, >0.30 mmol), 6 (0.10
mmol), LiCl (0.12 mmol), THF/THF-d8 (0.6 mL, v/v¤ = 2/1),
PhCF3 (0.10 mmol, as a standard for 19F NMR). Yields were
b
determined by 19F NMR. The values in brackets were of
ð5Þ
c
d
e
f
isolated yields. For 18 h. For 48 h. For 27 h. For 22 h.
as a major product (Run 7). However, a considerable amount of
a mixture of difluorostilbenes 8h was formed, which was
consistent with a previous report by Jiang.2c A similar tendency
to form a substantial quantity of disubstituted product was
observed when vinylmagnesium chloride (6i) was employed as
the substrate, and the yield of 1,1,2-trifluoro-1,3-butadiene (7i)
was 31% (Run 8). The reaction of ethynylmagnesium chloride
(6j) for 22 h gave 1,1,2-trifluoro-1-buten-3-yne (7j) in 17% yield
(Run 9).
The reaction of crotylmagnesium chloride (6k) with TFE in
the presence of lithium chloride resulted in the quantitative
formation of a mixture of monoalkylated products (eq 6). In this
major product 9k, a C-C bond was formed at the £-position of
crotylmagnesium chloride. In addition, the use of £-methylcrotyl
Grignard reagent 6l also gave the £-substituted product 9l as a
major product. However, when cinnamylmagnesium chloride
(6m) was used, a C-C bond formation occurred predominantly
between the ¡-position of the cinnamyl group and the
trifluorovinyl group to give the corresponding ¡-substituted
product 10m as a major product, while this reaction was
somewhat retarded.
Table 2 shows the scope and limitation of the LiCl-
promoted monosubstitution reaction of TFE with respect to
various Grignard reagents. The reaction of (4-vinylbenzyl)mag-
nesium chloride (6b) with TFE gave the desired product 7b in an
excellent yield (Run 1). The use of (1-naphthylmethyl)magne-
sium chloride (6c) afforded 1,1,2-trifluorovinyl compound 7c
in a moderate yield (Run 2). Both allylmagnesium chloride (6d)
and 2-methylallylmagnesium chloride (6e) allowed a clean
formation of 1,1,2-trifluoropentane-1,4-diene derivatives 7d and
7e (Runs 3 and 4). Simple alkylmagnesium reagents such as
ethylmagnesium chloride (6f) retarded the reaction, and 6f was
completely consumed after 18 h to give a complicated mixture
that contained 1 in 13% yield (Run 5). In addition, the use of
t-butylmagnesium chloride (6g) afforded the corresponding
monosubstituted product 7g in 22% yield, along with the
concomitant formation of a complicated mixture of fluorine-
containing molecules (Run 6). Further substrate scope using
aryl, vinyl, and alkynyl Grignard reagents was examined.
Treatment with phenylmagnesium chloride (6h) with TFE in
the presence of lithium chloride gave ¡,¢,¢-trifluorostyrene (7h)
Chem. Lett. 2013, 42, 933-935
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

935
J.-P. Gillet, R. Sauvetre, J.-F. Normant, Tetrahedron Lett.
1985, 26, 3999. c) P. L. Heinze, D. J. Burton, J. Fluorine
Chem. 1986, 31, 115. d) F. Tellier, R. Sauvêtre, J. F.
Normant, Y. Dromzee, Y. Jeannin, J. Organomet. Chem.
1987, 331, 281. e) P. L. Heinze, D. J. Burton, J. Org. Chem.
1988, 53, 2714. f) R. Anilkumar, D. J. Burton, Tetrahedron
Lett. 2002, 43, 2731. g) A. Raghavanpillai, D. J. Burton,
J. Org. Chem. 2004, 69, 7083. h) T. Lechel, J. Dash, P.
Hommes, D. Lentz, H.-U. Reissig, J. Org. Chem. 2010, 75,
726. i) M. Roemer, D. Lentz, Chem. Commun. 2011, 47,
7239. j) M. Roemer, P. Schmiel, D. Lentz, Organometallics
2011, 30, 2063.
A synthetic route of a more stable trifluorovinyl borate has
recently been developed to replace the zinc or tin reagent. a)
S. Duric, B. M. Schmidt, N. M. Ninnemann, D. Lentz, C. C.
Tzschucke, Chem.®Eur. J. 2012, 18, 437. See also: b) H.-J.
Frohn, N. Y. Adonin, V. V. Bardin, V. F. Starichenko,
Tetrahedron Lett. 2002, 43, 8111.
a) T. Yamamoto, T. Yamakawa, Org. Lett. 2012, 14, 3454. b)
C. Xu, S. Chen, L. Lu, Q. Shen, J. Org. Chem. 2012, 77,
10314.
M. Ohashi, T. Kambara, T. Hatanaka, H. Saijo, R. Doi, S.
Ogoshi, J. Am. Chem. Soc. 2011, 133, 3256.
M. Ohashi, H. Saijo, M. Shibata, S. Ogoshi, Eur. J. Org.
Chem. 2013, 443.
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
ð6Þ
In conclusion, we have demonstrated the selective mono-
substitution reaction of TFE with either diethylzinc or alkyl-
magnesium chloride. The use of suitable lithium salts enhanced
both the yield and selectivity of the desired monoalkylated
products in both reactions. A lithium iodide-promoted mono-
ethylation reaction employing diethylzinc would involve an
addition-elimination mechanism. In addition, the combination
of benzyl- and allylmagnesium reagents and lithium chloride
gave the corresponding monoalkylated products in excellent
yields.
5
6
This work was supported by Grant-in-Aid for Scientific
Research (A) (No. 21245028), Grant-in-Aid for Young Scien-
tists (A) (No. 25708018), and Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” (No. 23105546) from
MEXT. M.O. also acknowledges The Noguchi Institute.
7
8
9
References and Notes
1
a) R. Souzy, B. Ameduri, B. Boutevin, Prog. Polym. Sci.
2004, 29, 75. b) R. Souzy, B. Ameduri, Prog. Polym. Sci.
2005, 30, 644. c) Fluoropolymers 1: Synthesis in Topics in
Applied Chemistry, ed. by G. Hougham, P. E. Cassidy, K.
Johns, T. Davidson, Kluwer academic/Plenum Publisher,
New York, 2002. doi:10.1007/b114559.
10 P. Tarrant, J. Heyes, J. Org. Chem. 1965, 30, 1485.
11 Tetrafluoroethene is suspected to be carcinogens. The
reaction mixture must be handled in a well-ventilated fume
hood.
2
a) S. G. Cohen, H. T. Wolosinski, P. J. Scheuer, J. Am. Chem.
Soc. 1949, 71, 3439. b) M. Prober, J. Am. Chem. Soc. 1953,
75, 968. c) X.-K. Jiang, C.-J. Wu, Z.-Z. Wu, Acta Chim. Sin.
(Engl. Ed.) 1983, 1, 42. d) K. V. Dvornikova, V. E. Platonov,
G. G. Yakobson, J. Fluorine Chem. 1985, 28, 99. e) R.
Anilkumar, D. J. Burton, Tetrahedron Lett. 2003, 44, 6661.
f) R. Anilkumar, D. J. Burton, J. Fluorine Chem. 2005, 126,
1174. g) S. Mizuta, N. Shibata, Y. Goto, T. Furukawa, S.
Nakamura, T. Toru, J. Am. Chem. Soc. 2007, 129, 6394.
Dixon reported the reaction of n-BuLi with TFE in Et2O at
¹80 °C to give n-BuFC=CF2 in 80% yield. S. Dixon,
J. Org. Chem. 1956, 21, 400.
12 S. Yamada, M. Noma, K. Hondo, T. Konno, T. Ishihara,
J. Org. Chem. 2008, 73, 522.
13 The effect of additives on the reaction of TFE with ZnEt2 are
summarized in the Supporting Information.
14 G. T. Achonduh, N. Hadei, C. Valente, S. Avola, C. J.
O’Brien, M. G. Organ, Chem. Commun. 2010, 46, 4109.
15 In the absence of lithium iodide, diethylzinc hardly reacts
with MeCN at 60 °C to generate ethane.
16 a) N. H. Buttrus, C. Eaborn, M. N. A. El-Kheli, P. B.
Hitchcock, J. D. Smith, A. C. Sullivan, K. Tavakkoli,
J. Chem. Soc., Dalton Trans. 1988, 381. b) A. Krasovskiy, P.
Knochel, Angew. Chem., Int. Ed. 2004, 43, 3333.
3
4
a) I. P. Beletskaya, J. Organomet. Chem. 1983, 250, 551. b)
Chem. Lett. 2013, 42, 933-935
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/