Synthesis of α-trifluoromethylstyrene derivatives via Ni-catalyzed cross-coupling of 2-bromo-3,3,3-trifluoropropene and aryl Grignard reagents

Article abstract of DOI:10.1016/j.jfluchem.2009.03.002

The Ni-catalyzed cross-coupling of 2-bromo-3,3,3-trifluoropropene and aryl Grignard reagents was investigated. When NiCl₂(PPh₃)₂ was used as a catalyst, the highest yield of α-trifluoromethylstyrene (89%) from 2-bromo-3,3,

Full text of DOI:10.1016/j.jfluchem.2009.03.002

Journal of Fluorine Chemistry 130 (2009) 591–594
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Short communication
Synthesis of a-trifluoromethylstyrene derivatives via Ni-catalyzed cross-coupling
of 2-bromo-3,3,3-trifluoropropene and aryl Grignard reagents
1
*
Osamu Kobayashi, Daisuke Uraguchi , Tetsu Yamakawa
Sagami Chemical Research Center, Hayakawa 2743-1, Ayase, Kanagawa 252-1193, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
The Ni-catalyzed cross-coupling of 2-bromo-3,3,3-trifluoropropene and aryl Grignard reagents was
investigated. When NiCl2(PPh3)2 was used as a catalyst, the highest yield of -trifluoromethylstyrene
(89%) from 2-bromo-3,3,3-trifluoropropene and PhMgBr was obtained in 1,3-dimethyl-2-imidazolidi-
none at 50 8C for 30 min. Various -trifluoromethylstyrene derivatives could be produced in satisfactory
yields by NiCl2(PPh3)2-catalyzed coupling using aryl Grignard reagents.
ß 2009 Elsevier B.V. All rights reserved.
Received 14 January 2009
Received in revised form 4 March 2009
Accepted 5 March 2009
a
a
Available online 20 March 2009
Keywords:
a-Trifluoromethylstyrene
2-Bromo-3,3,3-trifluoropropene
Aryl Grignard reagents
Nickel catalyst
Cross-coupling
1. Introduction
to cleave frequently C–F bonds in alkyl fluorides [7]. Therefore, the
appropriate conditions for the suppression of C–F bond cleavage of
the desired products and/or BTP should be developed for realizing
requisite Ni-catalyzed coupling of BTP.
a
-Trifluoromethylstyrene derivatives have attracted consider-
able attention because they are industrially important compounds
in the fields of medicinal, agricultural and material sciences [1].
With regard to the metal-catalyzed coupling for their synthesis,
the Pd-catalyzed coupling of zinc or boronic acid reagents derived
from 2-bromo-3,3,3-trifluoropropene (BTP) with aryl halides [2]
and BTP with arylboronic acid [3] have been reported thus far.
Recently, we carried out the Pd-catalyzed coupling of BTP and
arylmagnesium bromides (ArMgBr) in order to demonstrate the
use of more environmentally benign reagent [4]. It is well known
that nickel compounds catalyze cross-coupling of vinyl halides and
In this study, we investigated the synthesis of
a-trifluoro-
methylstyrene derivatives by the use of the Ni-catalyzed coupling
of BTP and ArMgBr. We found that NiCl2(PPh3)2 efficiently
catalyzed the synthesis of
a-trifluoromethylstyrene derivatives
in satisfactory yields without any by-products formed through C–F
bond cleavage.
2. Results and discussion
ArMgBr [5]. Therefore, more economical process for
omethylstyrene derivatives synthesis using nickel catalysts will be
developed.
a-trifluor-
First, we used one of the conventional Ni(II)-phosphine
complexes, NiCl2(PPh3)2, as a catalyst in the coupling of BTP and
PhMgBr; PhMgBr is mainly responsible for the reduction of Ni(II) to
In the Pd-catalyzed coupling of BTP and ArMgBr, C–F bonds in
BTP were intact [4] as well as the other Pd-catalyzed coupling [2,3].
Ni(0). Table 1 shows the yields of a-trifluoromethylstyrene by the
use of various solvents under the condition that NiCl2(PPh3)2 is
1.0 mol% of BTP (0.01 mmol) and the addition rate of THF solution
In addition, by-products, which are formed by the reaction of
a-
trifluoromethylstyrene and phenylmagnesium bromide (PhMgBr)
[6], were not detected by GC and 19F NMR at all. On the other hand,
the combination of Ni catalysts and Grignard reagents are known
of PhMgBr is 50
by GC and 19F NMR in any solvents. It should be mentioned that by-
products formed by the cleavage of C–F bonds of -trifluoro-
mL/min. a-Trifluoromethylstyrene was detected
a
methylstyrene [6] were not detected [4]. Polar and basic solvents
(NMP, DMPU and DMI) gave the higher yields (entries 5–7) than
the other solvents commonly used in Grignard reactions (entries
1–3) and 1,4-dioxane (entry 4) in which the Pd-catalyzed coupling
occurred exclusively [4]. Particularly, the use of DMI resulted in
satisfactory yield (entry 7).
* Corresponding author. Tel.: +81 467769268; fax: +81 467774113.
E-mail address: t_yamakawa@sagami.or.jp (T. Yamakawa).
1
Present address: Nagoya University, Graduate School of Engineering, Depart-
ment of Applied Chemistry, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan.
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.03.002

592
O. Kobayashi et al. / Journal of Fluorine Chemistry 130 (2009) 591–594
Table 1
Table 3
NiCl2(PPh3)2-catalyzed coupling of BTP and PhMgBr in various solvents.a
The coupling of BTP and PhMgBr using various Ni(II) compounds and phosphines.a.
Entry
Ni(II) compound
Phosphineb
GC yield (%)
1
2
Ni(acac)2
PPh3
74
67
74
48
8
Ni(acac)2
P(p-tolyl)3
3
Ni(acac)2
P(4-fluorophenyl)3
.
4
Ni(acac)2
P(o-tolyl)3
5
Ni(acac)2
dppm
dppe
dppp
dppb
dppf
–
Entry
Solvent
GC yield (%)
6
Ni(acac)2
5
1
2
3
4
5
6
7
THF
21
21
12
18
43
44
85
7
Ni(acac)2
55
64
7
1,4-Dioxane
Diethylether
DMEb
DMPUc
NMPd
DMIe
8
Ni(acac)2
9
Ni(acac)2
10
11
12
13
14
NiCl2(dppm)
NiCl2(dppe)
NiCl2(dppp)
NiCl2(dppb)
NiCl2(dppf)
49
40
66
65
14
–
–
–
–
a
NiCl2(PPh3)2 0.01 mmol, BTP 1.0 mmol, THF solution of PhMgBr (ca. 1.1 mol/L)
a
1.3 mL, addition rate of THF solution of PhMgBr 50
atmosphere.
mL/min, solvent 1.0 mL, 50 8C, Ar
Ni(II) compound 0.01 mmol, [P]/[Ni] = 2, BTP 1.0 mmol, THF solution of PhMgBr
(ca. 1.1 mol/L) 1.3 mL, addition rate of THF solution of PhMgBr 50
mL/min, DMI
b
1,2-Dimethoxyethane.
1.0 mL, 50 8C, Ar atmosphere.
c
b
1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone.
N-Methyl-2-pyrrolidone.
dppm bis(diphenylphosphino)methane, dppe 1,2-bis(diphenylphosphi-
no)ethane, dppp 1,3-bis(diphenylphosphino)propane, dppb 1,4-bis(diphenylpho-
sphino)butane, dppf 1,10-bis(diphenylphosphino)ferrocene.
d
e
1,3-Dimethyl-2-imidazolidinone.
Next, we examined the dependence of the addition rate and the
loaded amount of NiCl2(PPh3)2 on yield. The results are shown in
Table 2. The yield gradually increased with the addition rate
with dppm is in contrast to the findings that dppm is exclusively
efficient in the Pd-catalyzed coupling of BTP and PhMgBr [4]. The
combination of Ni(acac)2 and dppp or dppb gave moderate yields
(entries 7 and 8) as well as NiCl2(dppp) and NiCl2(dppb) (entries 12
and 13). The other Ni(II) bidentate phosphine complexes were more
active than the combination of Ni(acac)2 and the corresponding
bidentate phosphines, though the yields were less than 50% (entries
10, 11 and 14).
(entries 1–3) and reached 85% at 50
120 L/min (entries 4–7), the yields were approximately constant.
Since it is generally accepted that slow addition of a metallic
reagent suppresses side reactions [8], we selected 50 L/min in the
reactions hereinafter. Actually, any by-products formed by
abstraction of fluorine from -trifluoromethylstyrene and BTP
mL/min. In the range of 50–
m
m
a
Table 4 lists the results of the coupling using NiCl2(PPh3)2 and
various ArMgBr. Considering the practical use, the reaction scale
was raised up to 10 times of that in Table 1. The optimized addition
were not detected at all and the formed amounts of biphenyl were
3–5% in all entries. The low yields in entries 1–3 are possibly due to
the small ratios of [PhMgBr]/[Ni]. The yields with various loaded
amount of NiCl2(PPh3)2 after the optimization of the addition rate
are listed in entries 8–10. 0.5 mol% and 0.25 mol% of NiCl2(PPh3)2
afforded remarkably low yields (entries 8 and 9). Since 5.0 mol% of
NiCl2(PPh3)2 provided 85% yield (entry 10), 1.0 mol% of the catalyst
is enough for the satisfactory yield.
Under the conditions thus optimized, various Ni(II) compounds
and phosphines were examined for the coupling of BTP and PhMgBr
in DMI (Table 3). The yield obtained using the combination of
Ni(acac)2 and PPh3 (entry 1) was somewhat lower than that using
NiCl2(PPh3)2 (85%, entry 6 in Table 1). The yield was independent of
the electronic nature of the substituents on the phenyl rings in
triarylphosphines (entries 2 and 3), while it decreased probably due
to the steric hindrance of the substituent at the ortho position (entry
4). With the exception of dppp and dppb, the bidentate phosphine
ligands were less effective than monodentate ligands inthe coupling
(entries 5, 6 and 9). Particularly, the remarkably low yield obtained
rate of the THF solution of PhMgBr was 200
mL/min, giving 89%
yield of -trifluoromethylstyrene. The moderate to satisfactory
a
yields were obtained for each substrates. The fluorine or the
chlorine substituent in 4-fluorophenylmagnesium bromide or 4-
chlorophenylmagnesium bromide remained unreacted. This result
indicates that not only C–F bond in BTP but also C–F or C–Cl bonds
on the phenyl ring of the aryl Grignard reagents are not cleaved by
this Ni catalyst under the given conditions [9]. This high selectivity
as well as that the yield was not affected by the electronic nature of
the substituents (entries 3–5) will represent a direct method for
the synthesis of functionally substituted
derivatives from BTP.
a-trifluoromethylstyrene
In summary, we demonstrated the Ni-catalyzed coupling of
BTP and ArMgBr. -Trifluoromethylstyrene was obtained by the
a
use of the versatile Ni(II) complex, NiCl2(PPh3)2, in a satisfactory
yield. This Ni(II) complex exhibited the high tolerance to the
substituent in the reactions with various ArMgBr. The present
method will provide more versatile and economical synthesis
of
a-trifluoromethylstyrene derivatives than the Pd-catalyzed
Table 2
NiCl2(PPh3)2-catalyzed coupling of BTP and PhMgBr with various loaded amount of
Ni and at various addition rate.a.
coupling reported previously [4].
3. Experimental
Entry
NiCl2(PPh3)2
Addition rate of PhMgBr
GC yield (%)
(mol% of BTP)
solution (mL/min)
3.1. General experimental procedures
1
2
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.25
5.0
15
25
64
72
81
85
89
85
6
1H and 19F NMR spectra were recorded in CDCl3 on Bruker DRX-
500 (1H 500 MHz) and DRX-250 (19F 235 MHz) spectrometers
using tetramethylsilane for 1H NMR as an internal reference and
fluorotrichloromethane for 19F NMR as an external reference.
3
40
4
50
5
80
7
120
40
8
9
40
Trace
85
Chemical shifts are expressed in ppm (
indicated by s (singlet), d (doublet), dd (doublet of doublet), q
(quartet), (multiplet) and brs (broad singlet). Developed
chromatograms were visualized by UV light. Flash chromatogra-
d). Multiplicities are
10
160
a
m
BTP 1.0 mmol, THF solution of PhMgBr (ca. 1.1 mol/L) 1.3 mL, solvent 1.0 mL,
50 8C, Ar atmosphere.

O. Kobayashi et al. / Journal of Fluorine Chemistry 130 (2009) 591–594
593
Table 4
NiCl2(PPh3)2-catalyzed coupling of BTP and various aryl Grignard reagents.a
.
Entry
Ar
Product
Isolated yield (%)
1
Phenyl
89
2
4-Fluorophenyl
77
3
4
5
4-Chlorophenyl
70
70
85
4-tert-Butylphenyl
4-Methoxyphenyl
6
7
3-Methoxyphenyl
2-Methoxyphenyl
75
55
8
6-Methoxynaphthyl
64
a
NiCl2(PPh3)2 0.1 mmol, BTP 10 mmol, THF solution of ArMgBr (ca. 1.1 mol/L) 13 mL, addition rate of THF solution of ArMgBr 200
m
L/min, DMI 10 mL, 50 8C, Ar
atmosphere.
phy was performed on silica gel (Kanto Chemical Co., N60). All
commercially available reagents were used without further
purification.
All reactions were carried out in flame-dried glassware under
an Ar atmosphere. To a solvent containing a nickel compound
(1.0 mol% of BTP), a phosphine ([P]/[Ni] = 2) and BTP, THF solution
of an ArMgBr (ca. 1.1 mol/L, [ArMgBr]/[BTP] = ca. 1.4) was added at
50 8C using a syringe pump. The reaction mixture was then stirred
for 30 min at the same temperature. After cooling to room
temperature, an aliquot of the reaction mixture was diluted with

594
O. Kobayashi et al. / Journal of Fluorine Chemistry 130 (2009) 591–594
pentane and the resulting solution was subjected to quantitative
analyses by GC and 19F NMR. Tridecane and 2,2,2-trifluoroethanol
were used as internal standards for GC and 19F NMR, respectively.
The reaction mixture was passed through a silica gel column, and
the eluted solution was concentrated in vacuo or distilled to isolate
the desired products. All yields were calculated on the basis of the
initial concentration of BTP.
5.71 (d, JHF = 1.7 Hz, 1H). 19F NMR (CDCl3)
z): 190 [M]+.
d
: ꢀ112.8, ꢀ65.4. MS (m/
3.2.7. 4-Chloro-1-(trifluoromethyl)vinylbenzene
1H NMR (CDCl3)
d: 7.41–7.34 (m, 4H), 5.97 (q, JHF = 1.3 Hz, 1H),
5.76 (q, JHF = 1.6 Hz, 1H). 19F NMR (CDCl3)
d
: ꢀ65.2. MS (m/z): 206
[M]+.
3.2. Characterization of products
3.2.8. 6-Methoxy-2-[1-(trifluoromethyl)vinyl]naphthalene
1H NMR (CDCl3)
: 7.86 (s, 1H), 7.76–7.71 (m, 2H), 7.54–7.50 (m,
d
All products are known compounds. The full characterization of
these compounds are shown in our previus report [4] and the
references therein.
1H), 7.19–7.15 (m, 1H), 7.14–7.11 (m, 1H), 5.99 (d, JHF = 1.2 Hz, 1H),
5.86 (d, JHF = 1.6 Hz, 1H), 3.92 (s, 3H). 19F NMR (CDCl3)
(m/z): 252 [M]+.
d
: ꢀ64.6. MS
3.2.1.
a
-Trifluoromethylstyrene
1H NMR (CDCl3)
d
: 7.47–7.43 (m, 2H), 7.40–7.35 (m, 3H), 5.95
Acknowledgement
(q, JHF = 1.4 Hz, 1H), 5.76 (q, JHF = 1.4 Hz, 1H). 19F NMR (CDCl3)
ꢀ65.1. MS (m/z): 172 [M]+.
d:
We are grateful to Tosoh F-Tech Co., Ltd. for providing BTP.
3.2.2. 4-Methoxy-1-(trifluoromethyl)vinylbenzene
1H NMR (CDCl3)
d: 7.39 (d, JHH = 8.7 Hz, 2H), 6.90 (d,
References
JHH = 8.7 Hz, 2H), 5.86 (q, JHF = 1.3 Hz, 1H), 5.69 (q, JHF = 1.7 Hz,
[1] A. Thompson, E.G. Corely, M.F. Huntington, E.J.J. Grabowski, J.F. Remenar, D.B.
Collum, J. Am. Chem. Soc. 120 (1998) 2028–2038;
1H), 3.83 (s, 3H). 19F NMR (CDCl3)
d
: ꢀ65.1. MS (m/z): 202 [M]+.
L. Tan, C.Y. Chen, R.D. Tillyer, E.J.J. Grabowski, P.J. Reider, Angew. Chem. Int. Ed. 38
(1999) 711–713;
S. Kishimura, M. Endo, M. Sasago, M. Shirai, M. Kadooka, Kokai Tokkyo Koho
JP2002-311588.;
3.2.3. 3-Methoxy-1-(trifluoromethyl)vinylbenzene
1H NMR (CDCl3)
: 7.32–7.27 (m, 1H), 7.05–7.02 (m, 1H), 6.98
d
(brs, 1H), 6.94–6.91 (m, 1H), 5.95 (q, JHF = 1.3 Hz, 1H), 5.77 (q,
R.D. Allen, P.J. Brock, H. Ito, G.N. Wallraff, US Patent 0 164 538 (2002).
[2] B. Jiang, Y. Xu, J. Org. Chem. 56 (1991) 7336–7340;
B. Jiang, Q. Wang, C. Yang, M. Xu, Tetrahedron Lett. 42 (2001) 4083–4085.
[3] R.Q. Pan, X.-X. Liu, M.Z. Deng, J. Fluorine Chem. 95 (1999) 167–170;
K. Matoba, T. Mizukoshi, Y. Moriyama, PCT Int. Appl. WO200709431.
[4] O. Kobayashi, D. Uraguchi, T. Yamakawa, J. Mol. Catal. A: Chem. 302 (2009)
7–10.
[5] K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. 94 (1972) 4374–4376;
R.J.P. Corriu, J.P. Masse, J. Chem. Soc., Chem. Commun. (1972) 144.
[6] H. Ito, A.F. Renaldo, M. Ueda, Macromolecules 22 (1989) 45–51.
[7] J. Terao, A. Ikumi, H. Kuniyasu, N. Kambe, J. Am. Chem. Soc. 125 (2003) 5646–
5647;
JHF = 1.6 Hz, 1H), 3.82 (s, 3H). 19F NMR (CDCl3)
d: ꢀ65.1. MS (m/z):
202 [M]+.
3.2.4. 2-Methoxy-1-(trifluoromethyl)vinylbenzene
1H NMR (CDCl3)
: 7.36–7.32 (m, 1H), 7.23–7.20 (m, 1H), 6.98–
d
6.92 (m, 2H), 6.07 (d, JHF = 1.4 Hz, 1H), 5.64 (d, JHF = 1.0 Hz, 1H),
3.82 (s, 3H). 19F NMR (CDCl3)
d
: ꢀ65.9. MS (m/z): 202 [M]+.
3.2.5. 4-Tert-butyl-1-(trifluoromethyl)vinylbenzene
J. Terao, H. Toda, H. Watanabe, A. Ikumi, N. Kambe, Angew. Chem. Int. Ed. 43 (2004)
6180–6182;
J. Terao, H. Watanabe, N. Kambe, J. Am. Chem. Soc. 127 (2005) 3656–3657.
[8] G. Cahiez, C. Duplais, A. Moyeux, Org. Lett. 9 (2007) 3253–3254;
M. Nakamura, K. Matsuo, S. Ito, E. Nakamura, J. Am. Chem. Soc. 126 (2004) 3686–
3687.
1H NMR (CDCl3)
d: 7.40 (brs, 4H), 5.91 (q, JHF = 1.3 Hz, 1H), 5.75
(q, JHF = 1.7 Hz, 1H), 1.33 (s, 9H). 19F NMR (CDCl3)
z): 228 [M]+.
d
: ꢀ65.1. MS (m/
[9] L. Ackermann, R. Born, J.H. Spatz, D. Meyer, Angew. Chem. Int. Ed. 44 (2005) 7216–
7219;
3.2.6. 4-Fluoro-1-(trifluoromethyl)vinylbenzene
1H NMR (CDCl3)
d
: 7.42 (dd, JHH = 8.7 Hz, JHF = 5.3 Hz, 2H),
A. Steffen, M.I. Sladek, T. Braun, B. Neumann, H.-G. Stammler, Organometallics 24
(2005) 4057–4064.
7.06 (dd, JHH = 8.7 Hz, JHF = 8.7 Hz, 2H), 5.94 (d, JHF = 1.3 Hz, 1H),