A novel and convenient synthetic method for producing α-(trifluoromethyl)styrenes (3)

Article abstract of DOI:10.1016/S0022-1139(99)00021-4

The Suzuki-type coupling reaction of arylboronic acids (1) with 2-bromo-3,3,3-trifluoropropene (2) in the presence of a catalytic amount of dichlorobis(triphenylphosphine)palladium {PdCl₂(PPh₃)₂} and a base can easily give α-(trifluoromethyl)styrenes (3) in good yields. It was also found that 1,2-dibromo-3,3,3-trifluoropropane (4) underwent dehydrobromination in the presence of KOH, and subsequently, palladium-catalyzed cross-coupling with 1 to directly afford 3 in a one pot manner in excellent yields.

Full text of DOI:10.1016/S0022-1139(99)00021-4

Journal of Fluorine Chemistry 95 (1999) 167±170
A novel and convenient synthetic method for producing
a-(tri¯uoromethyl)styrenes (3)
Rui-qi Pana, Xing-xin Liua, Min-zhi Dengb,*
aChemistry Department of Northwest University, Xi'an 710069, China
bLaboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Academia Sinica, 354 Fenglin Lu, Shanghai 200032, China
Received 27 November 1998; received in revised form 18 January 1999; accepted 15 February 1999
Abstract
The Suzuki-type coupling reaction of arylboronic acids (1) with 2-bromo-3,3,3-tri¯uoropropene (2) in the presence of a catalytic amount
of dichlorobis(triphenylphosphine)palladium {PdCl2(PPh3)2} and a base can easily give a-(tri¯uoromethyl)styrenes (3) in good yields. It
was also found that 1,2-dibromo-3,3,3-tri¯uoropropane (4) underwent dehydrobromination in the presence of KOH, and subsequently,
palladium-catalyzed cross-coupling with 1 to directly afford 3 in a one pot manner in excellent yields. # 1999 Elsevier Science S.A. All
rights reserved.
Keywords: a-(tri¯uoromethyl)styrenes; Suzuki-type coupling; Arylboronic acid; 2-bromo-tri¯uoropropene; 1,2-dibromo-3,3,3-tri¯uoropropane
1. Introduction
number of synthetic methods for the preparation of 3 have
been reported in the past years [31±33]. Although these
methods have their own excellent qualities, they still have
many limitations. For instance, the ¯uoro materials cannot
be easily obtained [31,32,34] or the operation is inconve-
nient because of sensitivity to water and air [31±33].
The palladium-catalyzed coupling reaction of organo-
boron compounds with electrophiles in the presence of a
base (the `Suzuki reaction' [35,36]) has many attractive
features: high yields, milder condition, many functional
groups surviving under reaction conditions, and the ability
to remain unaffected in the presence of water. Additionally,
2-bromo-3,3,3-tri¯uoropropene (2) could be obtained easily
by dehydrobromination of 1,2-dibromo-3,3,3-tri¯uoropro-
pane (4), one of the readily available and economically
feasible ¯uoro materials, with a base in high yield [37].
Thus, ®rstly, we have studied the coupling reaction of
arylboronic acids (1) with 2 to give 3, and herein, we wish
to report the experimental results.
As we know, tri¯uoromethylated compounds have
become increasingly important for a large number of indus-
trial applications, such as pharmaceuticals, agrochemicals,
polymers, and so on [1]. Just because of their unique
physical and biological properties, there is an increasing
interest in the convenient synthetic method for speci®cally
tri¯uoromethylated organic molecules [2±6]. There are two
ways of introducing the tri¯uoromethylated group in gen-
eral: (i) direct substitution, such as ¯uorination, the halogen
exchanging reaction etc. in a late stage of the synthesis [7±
12]; and (ii) using tri¯uoromethyl-substituted building
blocks derived from readily available starting materials
[13±25]. However, the former route is not so satisfactory
because of low reactivity and low selectivity. The latter one
is now becoming an important strategy for the preparation of
tri¯uoromethylated molecules because it allows us to obtain
these CF3-substituted compounds under milder conditions
and with tolerant functionalities.
There have been many reported methods using a-(tri-
¯uoromethyl)styrenes (3) to synthesize gem-di¯uoroalkene
[26±28] in recent years because di¯uoroalkene can be used
as a versatile building block to synthesize many compounds
with biological activity [29,30]. Thus, it is meaningful to
look for a novel convenient synthetic method for 3. A
2. Results and discussion
Initially, a-naphthylboronic acid and 2 were used as the
starting materials for optimizing the coupling conditions
((1); summarized in Table 1).
As PdCl2(PPh3)2 can be stored and handled in the pre-
sence of air without any special precaution, we selected it
*Corresponding aurhor. E-mail: dengmz@pub.sioc.ac.cn
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 0 2 1 - 4

168
R.-q. Pan et al. / Journal of Fluorine Chemistry 95 (1999) 167±170
Table 1
The coupling of a-naphthylboronic acid with 2-bromo-3,3,3-trifluoropropene
Entrya
Solvents
Catalysts
Temperature (8C)/time (h)
Base (aq, 2M)
Yields (%)b
1
2
3
4
5
6
7
THF
Pd(PPh3)4
20/10
20/12
70/10
80/11
85/12
75/12
70/11
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
KOH
0
10
50
0
DME
PdCl2(PPh3)2
Pd(PPh3)4
Pd(PPh3)4
THF
Benzene
DME
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
65
70
94
DME
DME±THF (1 : 1, v/v)
KOH
a All reactions were carried out in nitrogen atmosphere using a catalyst (3 mmol%), a-naphthylboronic acid (1 mmol), 2 (1.5 mmol), a base (2 ml), AsPh3
(15 mmol%) in a solvent (3 ml).
b Isolated yields based on a-naphthylboronic acid.
Table 2
Palladium-catalyzed cross-coupling of arylboronic acids with 2-bromo-
rather than Pd(PPh3)4 as the catalyst. Table 1 demonstrates
that in the presence of KOH and when using PdCl2(PPh3)2
3,3,3-trifluoropropene
as the catalyst and a mixture of DME±THF (1 : 1, v/v) as a
solvent, the Suzuki-type coupling of a-naphthylboronic
acid with 2 could undergo easily (entry 7).
As given in Table 1, we selected the best condition (entry
7) to proceed with the coupling of 1 with 2 (2), and the
results are summarized in Table 2.
It can be seen in Table 2 that various 3 could be obtained
readily by the Suzuki-type coupling of 2 with the corre-
sponding 1 in good yields under milder conditions. The
reaction procedure might be a novel method for preparing 3,
one of the useful CF3-substituted compounds.
As 2 can be prepared easily from 4 using KOH as a base in
high yield [37], and the Suzuki-type reaction was generally
proceeded with under similar conditions, it was possible to
®nish the coupling directly using 4 in place of 2 as the
starting material (3). The results of the experiment are
summarized in Table 3. The results shown in Table 3 indi-
cate that 3 could be obtained directly by the reaction of 1 and
4 using THF±DME±H2O (1 : 1 : 1, v/v/v) as a solvent in the
presence of PdCl2(PPh3)2, KOH and AsPh3 in a one pot
manner in high yields. This might be a more convenient
method for preparing 3.
a The coupling reaction of arylboronic acids (1.0 mmol) with 2 (1.5 mmol)
In summary, we have provided a novel and convenient
synthetic method of producing 3 by the coupling of 1 with 2
proceeded with using THF-DME (1 : 1, v/v, 3 ml) as a solvent in the presence of
PdCl2(PPh3)2 (3 mmol%), KOH (aq, 2M, 2 ml) and AsPh3 (15 mmol%).
b All the products were fully characterized by IR 1H NMR, 19F NMR, MS, and C,
(or directly with 4). The method has many attractive
H elemental analyses or HRMS.
c Isolated yields based on arylboronic acids.
advantages: high yields, milder conditions, the ability to
remain unaffected in the presence of water, the usage of
economical and available ¯uoro materials, and convenience
(especially, 3 could be obtained from 4 in a one pot manner).
dard. 19F NMR spectra were obtained on a Varian EM-360L
spectrometer with tri¯uoroacetic acid as an internal stan-
dard, and down®eld shifts were designated as negative.
Mass spectra were done on a Finnigan 4021 GC/MS/DC
instrument.
3. Experimental
Infrared spectra were obtained on a Shimadzu IR-440
spectrometer using ®lms. 1H NMR spectra were recorded on
a Varian EM-360A spectra with TMS as an internal stan-
The general procedure for the coupling of 1 with 2: To a
solution of 2 (1.5 mmol) in THF±DME (1 : 1; v/v; 3 ml) and
KOH (aq, 2M, 2 ml),
1 (1.0 mmol), PdCl2(PPh3)2

R.-q. Pan et al. / Journal of Fluorine Chemistry 95 (1999) 167±170
169
Table 3
1-(a-(tri¯uoromethyl)ethenyl)naphthalene (3b): pale yel-
low oil; 94% yield. IR (®lm) (cm 1): 1600; 1400; 1350;
1230. 1H NMR (CDCl3) ꢀ: 5.80 (s, 1H); 6.46 (s, 1H); 7.60
(m, 7H) ppm. 19F NMR (CDCl3) d: 10.8 (s, 3F) ppm. MS
m/z (relative intensity): 222 (M, 72); 153 (100); 126 (3).
Anal. Calc. for C13H9F3: C, 70.27; H, 4.08%. Found: C,
70.05; H, 4.20%.
The Synthesis of a-(trifluoromethyl)styrenes from arylboronic acids and
1,2-dibromo-3,3,3-trifluoropropane
2-methyl-a-(tri¯uoromethyl)styrene (3c): pale yellow
1
oil; b.p. 52±538C 18 mm
Hg, 84% yield. IR (®lm)
(cm 1): 1600; 1500; 1350; 1240. 1H NMR (CDCl3) ꢀ:
2.57 (s, 3H); 5.84 (s, 1H); 6.03 (s, 1H); 7.35 (s, 4H)
ppm. 19F NMR (CDCl3) ꢀ: 13.1 (s, 3F) ppm. MS m/z
(relative intensity): 186 (M, 100); 117 (48); 91 (11). HRMS
Calc. for C10H9F3: 186.0656. Found: 186.0679.
3-methyl-a-(tri¯uoromethyl)styrene (3d): pale yellow
1
oil; b.p. 51±538C 18 mm
Hg, 83% yield. IR (®lm)
(cm 1): 1600; 1580; 1350; 1210. 1H NMR (CDCl3) ꢀ:
2.58 (s, 3H); 5.92 (s, 1H); 6.12 (s, 1H); 7.43 (m, 4H)
ppm. 19F NMR (CDCl3) ꢀ: 13.0 (s, 3F) ppm. MS m/z
(relative intensity): 186 (M, 100); 117 (75); 91 (24). HRMS
Calc. for C10H9F3: 186.0656. Found: 186.0651.
4-methyl-a-(tri¯uoromethyl)styrene (3e): pale yellow
1
oil; b.p. 52±548C 18 mm
Hg, 84% yield. IR (®lm)
(cm 1): 1600; 1580; 1350; 1170. 1H NMR (CDCl3) ꢀ:
2.52 (s, 3H); 5.85 (s, 1H); 6.02 (s, 1H); 7.35 (m, 4H)
ppm. 19F NMR (CDCl3) ꢀ: 13.2 (s, 3F) ppm. MS m/z
(relative intensity): 186 (M, 84); 117 (100); 91 (37). HRMS
Calc. for C10H9F3: 186.0656. Found: 186.0671.
a The mixture of 1 (1.0 mmol), 4 (1.5 mmol), KOH (6 mmol), AsPh3 (15 mmol%),
PdCl2(PPh3)2 (4 mmol%) in THF±DME±H2O (1 : 1 : 1, v/v/v) in
a
nitrogen
atmosphere was stirred at 0±58C for
temperature for the given time.
b Isolated yields based on 1.
5 min, and then reacted at the given
2-methoxyl-a-(tri¯uoromethyl)styrene (3f): pale yellow
oil; 71% yield. IR (®lm) (cm 1): 1600; 1500; 1350; 1170.
1H NMR (CDCl3) ꢀ: 4.00 (s, 3H); 5.79 (s, 1H); 6.22 (s, 1H);
7.40 (m, 4H) ppm. 19F NMR (CDCl3) ꢀ: 12.3 (s, 3F) ppm.
MS m/z (relative intensity): 202 (M, 100); 187 (32); 133
(46); 105 (54). Anal. Calc. for C10H9F3O: C, 59.41%; H,
4.48%. Found: C, 58.80; H, 4.32%.
3-chloro-a-(tri¯uoromethyl)styrene (3g): pale yellow oil;
70% yield. IR (®lm) (cm 1): 1600; 1580; 1400; 1350; 1180;
800. 1H NMR (CDCl3) ꢀ: 5.75 (s, 1H); 5.96 (s, 1H); 7.30 (m,
4H) ppm. 19F NMR (CDCl3) ꢀ: 12.8 (s, 3F) ppm. MS m/z
(relative intensity): 206 (M, 100); 137 (50); 102 (32). Anal.
Calc. for C9H6ClF3: C, 52.32; H, 2.93%. Found: C, 52.43;
H, 2.99%.
(3 mmol%) and AsPh3 (15 mmol%) were added in a nitro-
gen atmosphere. The reaction mixture was stirred at 70±
748C for 11±12 h (see Table 2). After being cooled to room
temperature, water (10 ml) was added, then the mixture was
extracted with ether (2 Â 10 ml). The combined organic
layer was washed with brine (3 Â 10 ml) and dried over
MgSO4. After removing the solvent in vacuo, the residue
was puri®ed by short-path distillation under reduced pres-
sure (for compounds 3a, 3c, 3d, 3e) or by silica gel
chromatography, eluting with petroleum ether±ethyl acetate
(100 : 1, v/v) (for 3b, 3f, 3g).
The procedure for preparing 3 from 4 in a one pot manner:
To a solution of 4 (1.5 mmol) in THF±DME±H2O (1 : 1 : 1;
v/v/v; 3 ml), 1 (1.0 mmol), PdCl2(PPh3)2 (4 mmol%),
AsPh3 (15 mmol%) and KOH (6.0 mmol) were added in
a nitrogen atmosphere. The reaction mixture was stirred at
0±58C for 5 min, and subsequently, the reaction was pro-
ceeded with at the given temperature for the given time (see
Table 3). Then the work-up was carried out by the above-
mentioned procedures.
Acknowledgements
We thank the National Natural Science Foundation of
China for its ®nancial support.
a-(tri¯uoromethyl)styrene (3a): colorless oil; b.p. 48±
1
508C 18 mm Hg, 82% yield. IR (®lm) (cm 1): 1580;
References
1500; 1400; 1350; 1160. 1H NMR (CDCl3) ꢀ: 5.84 (s,
1H); 6.03 (s, 1H); 7.50 (m, 5H) ppm. 19F NMR (CDCl3)
ꢀ: 13.0 (s, 3F) ppm. MS m/z (relative intensity): 172 (M,
52); 103 (100); 78 (35). HRMS Calc. for C9H7F3: 172.0050.
Found: 172.0513.
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