Copper/silver-mediated decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids with CF3SO2Na

Article abstract of DOI:10.1055/s-0033-1338578

A copper/silver-catalyzed decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids with CF₃SO₂Na was performed under relatively mild conditions. The reaction shows high E/Z selectivity and wide substrate tolerance. Ag₂CO₃ plays an important role in promoting the decarboxylation process. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1338578

PAPER
▌607
paper
Copper/Silver-Mediated Decarboxylative Trifluoromethylation of
α,β-Unsaturated Carboxylic Acids with CF3SO2Na
Trifluoromethylation of α,β-Unsaturated Carboxylic Acids
Jun Yin, Yaming Li,* Rong Zhang, Kun Jin, Chunying Duan*
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. of China
Fax +86(411)84986295; E-mail: ymli@dlut.edu.cn
Received: 18.08.2013; Accepted after revision: 29.11.2013
coupling processes can facilitate the construction of Csp2–
CF3 bonds under milder reaction conditions, rendering
them more amenable to late-stage modification of highly
functionalized molecules.6 Toward this end, a variety of
copper-2a,7 and palladium-8 mediated reactions have re-
cently been developed. These transition-metal-catalyzed
trifluoromethylations are, however, mainly limited to the
installation of Caryl–CF3 groups.
Abstract: A copper/silver-catalyzed decarboxylative trifluoro-
methylation of α,β-unsaturated carboxylic acids with CF3SO2Na
was performed under relatively mild conditions. The reaction shows
high E/Z selectivity and wide substrate tolerance. Ag2CO3 plays an
important role in promoting the decarboxylation process.
Key words: fluorine, transition metals, copper, catalysis, radicals
A few approaches to the construction of Cvinyl–CF3 bonds
have been reported (Scheme 1).9 The processes developed
by Liu9d and Hu9c depend heavily on the use of costly,
electrophilic trifluoromethyl reagents, whereas Buchwald’s9a,b
and Cho’s9f procedures require expensive Pd or Ru cata-
lysts. Herein, we report a new and efficient method for
copper-/silver-catalyzed decarboxylative trifluoromethyl-
ation of α,β-unsaturated carboxylic acids by using the
stable and inexpensive reagent sodium trifluoromethane-
sulfinate (CF3SO2Na, Langlois reagent).
The introduction of trifluoromethyl (CF3) groups into or-
ganic molecules can substantially improve their chemical
and metabolic stability, lipophilicity, and binding selec-
tivity as a result of the strong electron-withdrawing nature
and large hydrophobic domain of the trifluoromethyl
groups.1 On this basis, there has been a recent surge in the
number of reports describing the formation of carbon–tri-
fluoromethyl (C–CF3) bonds.2 A variety of processes for
the construction of Csp3–CF3 bonds have been reported us-
ing electrophilic,3 nucleophilic,4 and radical-based5 re-
agents. However, the construction of Csp2–CF3 bonds,
especially Cvinyl–CF3 bonds, is rarely reported. Cross-
Langlois reagent is an attractive CF3 source. It has been
known since 1989 that alkali metal trifluoromethanesul-
cat. Cu(I)
Ar
Ar
+
Liu 2011
B(OH)2
CF3
S
OTf
Umemoto reagent
F3C
F3C
I
O
R1
R1
cat. Cu(II)
cat. Pd(II)
+
Hu 2012
CF3
COOH
O
R2
R2
Togni reagent
TMSCF3
R
R
R
+
+
CF3
CF3
Buchwald 2011
X
Ruppert reagent
X = OTf, ONf
cat. Ru(II)
R
CF3I
Cho 2012
Liu 2013
R = H, cat. Cu(II)
Ar
Ar
CF3
R = H, cat. Fe(III)
CF3SO2Na
Langlois reagent
Maiti 2013
+
COOH
R
R
this work
R = H, Me, Ph
cat. Cu(I)/Ag2CO3
Scheme 1 Formation of Cvinyl–CF3 bonds
SYNTHESIS 2014, 46, 0607–0612
Advanced online publication: 17.12.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338578; Art ID: SS-2013-H0572-OP
© Georg Thieme Verlag Stuttgart · New York

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J. Yin et al.
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•
Table 1 Optimization of the Conditionsa
finates can transfer the CF3 group to CF3 species that, in
turn, can trifluoromethylate electron-rich double bonds
and arenes.10a Since the original publication, a consider-
able number of papers have appeared reporting the use of
CF3SO2Na and also zinc difluoromethanesulfinate
[(CF2HSO2)2Zn, DFMS].10 In the past several years, de-
carboxylative couplings of aryl carboxylic acids or their
salts have gained interest because they are readily avail-
able and inexpensive.11 An interesting process of Cu/Ag-
mediated decarboxylation of cinnamic acid and phenyl-
propiolic acid was reported by Yang.12 Our group has also
reported the Cu/Ag-mediated trifluoromethylation of aryl
iodides.13 More recently, Liu’s10i group reported Cu(II)-
catalyzed reaction of cinnamic acid with CF3SO2Na, and
Maiti10j reported a Fe(III)-catalyzed trifluoromethylation
of cinnamic acid. However neither Liu’s nor Maiti’s work
apply to halogenated compounds or α,β-unsaturated car-
boxylic acid compounds that are substituted at the β-posi-
tion with methyl or phenyl groups. Inspired by the process
mentioned above, we wondered whether the Cu/Ag cata-
lyst system could be active in the trifluoromethylation of
α,β-unsaturated carboxylic acids.
CF3
[Cu], Ag(I), TBHP
COOH
+
CF3SO2Na
solvent, T, 24 h
2c
1c
Entry
Catalyst (mol%)
Additives (equiv)
Yield (%)b
1
2
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuI (20)
Ag2CO3 (1.0)
AgOTf (2.0)
AgNO3 (2.0)
Ag2O (1.0)
89
48
36
62
63
31
89
67
46
45
79
82
88
77
83
22
81
32
40
3
4
5
AgOAc (2.0)
AgI (2.0)
6
7
Ag2CO3 (0.6)
Ag2CO3 (0.5)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
Ag2CO3 (0.6)
–
8
9
10
11
12
13
14
15
16c
17d
18
19
CuO (20)
Cu (20)
At the outset of this investigation, we screened the combi-
nations of transition-metal catalysts, additives, and sol-
vents that were essential for the trifluoromethylation of
cinnamic acid (Table 1; for details see the Supporting In-
formation). Initially, we speculated that Ag2CO3 should
be the best additive because of the release of CO2 during
the formation of silver cinnamate. Indeed, as expected, the
use of AgOTf, AgNO3, or Ag2O as additives in place of
Ag2CO3 did not improve the yield, affording 2c in only
31–63% yields (Table 1, entries 1–6). It was found that
the use of 0.6 equiv Ag2CO3 was sufficient to complete
the reaction, further reducing the amount of Ag2CO3 re-
sulted in a significant decrease in the yield (Table 1,
entries 7 and 8). CuCl2·H2O and CuCl turned out to be
equally effective, whereas other Cu salts such as CuI,
Cu2O (20)
CuCl2·H2O (20)
CuCl (10)
CuCl (40)
CuCl (20)
CuCl (20)
CuCl (20)
–
Ag2CO3 (0.6)
a Reaction conditions: 1c (0.1 mmol), CF3SO2Na (0.3 mmol), TBHP
CuO, Cu, or Cu2O were less effective than CuCl (Table 1, (70% aqueous, 0.5 mmol), DCE (2 mL), 70 °C, 24 h.
b Yields were determined by GC analysis.
entries 9–13). It was necessary to use 20 mol% CuCl for
complete conversion (Table 1, entries 14 and 15). The
yield decreased dramatically when the temperature was
c The reaction was conducted at 90 °C.
d The reaction was conducted at 50 °C.
increased to 90 °C, but only declined slightly when the re-
action was conducted at 50 °C (22 and 81%, respectively;
Table 1, entries 16 and 17). The use of 1,2-dichloroethane
(DCE) proved to be more efficient than other solvents
such as methanol, acetonitrile, or N-methyl-2-pyrrolidi-
none (NMP) (see the Supporting Information). The de-
sired product was obtained in 89% yield by using
5 equivalents tert-butyl hydroperoxide (TBHP). Howev-
er, addition of 3 or 7 equivalents TBHP led to generation
of the product in 47 and 90% yields, respectively (see the
Supporting Information). Finally, control experiments
showed that Cu catalyst and Ag additives were both nec-
essary for the reaction to proceed (Table 1, entries 18 and
19). Ag2CO3 promoted the reaction greatly, since it makes
the decarboxylation process much easier.
conditions, a series of α,β-unsaturated carboxylic acids
were treated with CF3SO2Na and TBHP, and the reaction
proceeded smoothly to produce the desired compounds
2a–m in 48–72% yield. Among the various cinnamic acid
derivatives, electron-rich cinnamic acids bearing a meth-
oxyl group were particularly favorable, generating the de-
sired products in yields of more than 65% (2a and 2b),
whereas others gave lower — yet still synthetically useful
— yields. Polysubstituted cinnamic acids are more reac-
tive than monosubstituted derivatives. The yield of the
isolated product 2c (52%) was lower than that determined
by GC because of the volatility of the product. It is worth
mentioning that halogenated acrylic acids also gave the
desired products in moderate yields (2e, 2f, 2i, and 2j),
which are useful for further chemical conversion in, for
example, Heck and Suzuki reactions. When methyl and
With the optimized conditions in hand, we next explored
the substrate scope (Scheme 2). By using the standard
Synthesis 2014, 46, 607–612
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Trifluoromethylation of α,β-Unsaturated Carboxylic Acids
609
R1
R1
CuCl (20 mol%)
CF3
Ag2CO3 (0.6 equiv)
COOH
R2
CF3SO2Na
+
R2
TBHP (5 equiv)
DCE, 70 °C, 24 h
R1 = H, Me, Ph
1
2
MeO
MeO
CF3
CF3
CF3
CF3
CF3
MeO
Cl
OMe
2a 65%
E/Z > 99:1
2b 72%
E/Z > 99:1
2c 52%
E/Z > 98:2
2d 54%
E/Z > 99:1
2e 58%
E/Z > 99:1
Ph
CF3
CF3
CF3
CF3
CF3
Cl
Br
Cl
2g 57 %
E/Z > 96:4
2j 62%
E/Z > 98:2
2f 48%
E/Z > 99:1
2h 60%
E/Z > 96:4
2i 64%
E/Z > 98:2
Ph
CF3
CF3
S
CF3
HO
2k 60%
E/Z > 99:1
2l 63%
E/Z > 99:1
2m 70%
E/Z > 98:2
Scheme 2 Copper-catalyzed decarboxylative trifluoromethylation of cinnamic acids with sodium trifluoromethanesufinate. Reagents and con-
ditions: 1 (0.2 mmol), CF3SO2Na (0.6 mmol), CuCl (0.04 mmol), Ag2CO3 (0.12 mmol), TBHP (1.0 mmol, 70% aqueous), DCE (2 mL), 70 °C,
24 h; isolated yields, except for 2m (GC/MS yield); E/Z ratios were determined by 19F NMR analysis.
phenyl groups were introduced into the β-position of the of 2c was formed and TEMPO-CF3 was formed in 60%
α,β-unsaturated carboxylic acid, the decarboxylative tri- yield (detected by GC/MS) when 3.0 equivalents of
fluoromethylation could be performed more efficiently TEMPO were added.
(2g–k). Notably, the trifluoromethylation reaction was
also found to be stereoselective, with the CF3-functional-
ized alkenes being formed with an E/Z ratio ranging from
94:6 to more than 99:1.
Based on above experimental results, we concluded that
the CF3 radical is involved in the transformation (Scheme
4). The reaction starts with the decarboxylation of cin-
namic acid under Ag2CO3, forming an alkenyl–silver spe-
A detailed mechanism remains to be elucidated. On the cies A. Compound A would then transfer the alkenyl
basis of the previous work on the trifluoromethylation of group to copper by transmetallation to give the organo-
aromatics10 and copper-catalyzed C–P coupling of cin- copper intermediate B. In parallel, the trifluoromethyl
namic acids,12 it is reasonable that the reaction proceeds radical will be generated by the reaction of tert-butyl hy-
through a route that involves radical species. To gain in- droperoxide with NaSO2CF3. Addition of the trifluoro-
sight into the mechanism of this reaction, a radical scav- methyl radical at the α-position of the double bond in
enger 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) cupric cinnamate would give complex C. Finally, the de-
was added under the standard reaction conditions sired product would be released, generating the Cu(I) spe-
(Scheme 3). The result indicated that only a trace amount cies. Oxidation of Cu(I) by tert-butyl hydroperoxide
would regenerate the Cu(II) species and resume the cata-
lytic cycle, which explains the initial experimental result
that CuCl2·H2O and were equally effective.
TEMPO (3 equiv)
CuCl (20 mol%)
Ag2CO3 (0.6 equiv)
N
O
CF3SO2Na
(3.0 equiv)
In conclusion, we have developed a protocol for the con-
struction of Cvinyl–CF3 bonds through a Cu/Ag-catalyzed
decarboxylative trifluoromethylation of α,β-unsaturated
carboxylic acid derivatives with CF3SO2Na. This reaction
proceeds well for a wide range of α,β-unsaturated carbox-
ylic acids (including alkyl- and aryl- substituted deriva-
1c
2c
TBHP (5 equiv)
DCE, 70 °C, 24 h
CF3
TEMPO-CF3
60%
trace
(yields determined by GC/MS)
Scheme 3 Capture of CF3 radical by TEMPO
© Georg Thieme Verlag Stuttgart · New York
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J. Yin et al.
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CF3SO2 + t-BuOOH
CF3SO2 + t-BuO + HO
SO2
CF3
COOH
Ag+
Ar
Cu
2
Ar
B
Cu
2
CO2
Ar
CF3
C
TBHP
Ag
Cu2+
Ar
A
CF3
Ar
Scheme 4 Proposed mechanism for vinylic trifluoromethylation
Decarboxylative Trifluoromethylation of α,β-Unsaturated
Acids (Scheme 2); General Procedure
tives) with excellent E/Z selectivity. The inclusion of
Ag2CO3 additives was crucial for promoting the decar-
boxylation of α,β-unsaturated carboxylic acids.
To a solution of substrate 1 (0.2 mmol, 1 equiv), CuCl (4 mg, 0.04
mmol, 1 equiv), Ag2CO3 (33 mg, 0.12 mmol, 0.6 equiv), and
NaSO2CF3 (93.6 mg, 0.6 mmol, 3.0 equiv) in DCE (2 mL) at 0 °C,
was slowly added TBHP (70% in water, 136 μL, 1.0 mmol, 5.0
equiv) with stirring. The reaction was allowed to warm to 70 °C and
then stirred for 24 h. The resulting mixture was extracted with
EtOAc (3 × 8 mL) and the combined organic layers were dried with
Na2SO4 and then concentrated under vacuum. After evaporation,
the residue was purified by column chromatography using silica gel
(300–400 mesh; PE–EtOAc, 100:1→20:1).
Unless otherwise noted, all reagents were obtained from commer-
cial sources and used without further purification. Thin-layer chro-
matography (TLC) was performed by using commercially prepared
60 mesh silica gel plates visualized with short-wavelength UV light
(254 nm). The products were isolated by column chromatography
on silica gel (300–400 mesh size) by using petroleum ether (PE; 60–
90 °C) and EtOAc as eluents. All compounds were characterized by
1H, 13C and 19F NMR spectroscopic analysis. 1H, 13C and 19F NMR
spectra were recorded with an INOVA 400 instrument with an op-
erating frequency of 400, 100 and 377 MHz, respectively. Chemical
shifts for 1H NMR spectra are reported in ppm relative to TMS. The
following abbreviations are used to indicate multiplicities:
s = singlet, d = doublet, t = triplet, dd = doublet of doublets,
dq = doublet of quartets, m = multiplet. Coupling constants (J) are
reported in hertz (Hz). Gas chromatography analyses were per-
formed with an FID detector. High-resolution mass spectrometry
(HRMS) data were performed with an Q-Tof MS instrument.
(E)-1-Methoxy-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (2a)10i
Yield: 26.3 mg (65%); white solid; mp 37–39 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 8.7 Hz, 2 H), 7.08 (dd,
J = 16.1, 1.9 Hz, 1 H), 6.90 (d, J = 8.7 Hz, 2 H), 6.06 (dq, J = 16.1,
6.5 Hz, 1 H), 3.83 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.19, 137.25 (q, J = 6.8 Hz),
129.19, 126.0, 123.9 (q, J = 266.3 Hz), 114.5, 113.5 (q,
J = 31.5 Hz), 55.53.
19F NMR (377 MHz, CDCl3): δ = –63.29 (dd, J = 6.5, 1.8 Hz).
MS (EI): m/z = 202.0 [M]+.
Preparation of α,β-Unsaturated Carboxylic Acids 1; Typical
Procedure14
A 100 mL two-necked, round-bottom flask equipped with a mag-
netic stir bar, thermometer, and condenser, was charged with trieth-
yl phosphonoacetate (1.344 g, 6 mmol) followed by THF (20 mL).
The flask was cooled to 5 °C and NaH (60% in mineral oil, 265 mg,
6.6 mmol) was added in portions over 10 min. The flask was
warmed to about 25 °C and to this clear solution was added 4-
methoxybenzaldehyde (816 mg, 6 mmol) by addition funnel. The
flask was heated to reflux for 8 h, then the reaction was cautiously
quenched by the slow addition of H2O (Caution: Vigorous gas evo-
lution!). The contents of the flask were then poured into H2O and
extracted with Et2O and washed with 0.1 N HCl and brine. The sol-
vent was removed to afford a crude oil. A 50 mL single-neck round-
bottom flask was charged with the obtained oil, THF (2 mL), and 2
M NaOH (2.4 mL, 4.8 mmol) and heated at reflux for 3 h. The con-
tents were diluted with Et2O and acidified with conc. HCl, extracted
twice with Et2O, washed with brine, dried over MgSO4, filtered, and
concentrated to obtain 1a (540 mg; 97% purity GC) as a white solid.
(E)-1,2,3-Trimethoxy-5-(3,3,3-trifluoroprop-1-en-1-yl)benzene
(2b)10j
Yield: 37.8 mg (72%); white solid; mp 61–63 °C.
1H NMR (400 MHz, CDCl3): δ = 7.05 (dd, J = 16.0, 2.0 Hz, 1 H),
6.65 (s, 2 H), 6.10 (dq, J = 16.0, 6.5 Hz, 1 H), 3.86 (br, 9 H).
13C NMR (100 MHz, CDCl3): δ = 153.64, 139.87, 137.79 (q,
J = 13.0, 6.2 Hz), 129.09, 123.8 (q, J = 269.7 Hz), 115.54 (q,
J = 33.4 Hz), 104.82, 61.13, 56.32.
19F NMR (377 MHz, CDCl3): δ = –63.53 (dd, J = 6.4, 1.8 Hz).
MS (EI): m/z = 262.1 [M]+.
(E)-(3,3,3-Trifluoroprop-1-en-1-yl)benzene (2c)15a
Yield: 17.9 mg (52%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 3.6 Hz, 2 H), 7.41–
7.37 (m, 3 H), 7.15 (dd, J = 16.0, 1.8 Hz, 1 H), 6.20 (dq, J = 16.0,
6.5 Hz, 1 H).
Synthesis 2014, 46, 607–612
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Trifluoromethylation of α,β-Unsaturated Carboxylic Acids
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13C NMR (100 MHz, CDCl3): δ = 137.83 (q, J = 6.4 Hz), 133.57,
130.18, 129.10, 127.69, 123.8 (q, J = 269 Hz), 116.01 (q,
J = 33.8 Hz).
19F NMR (377 MHz, CDCl3): δ = –63.78 (dd, J = 6.3, 1.5 Hz).
MS (EI): m/z = 172.1 [M]+.
(E)-1-Chloro-4-(4,4,4-trifluorobut-2-en-2-yl)benzene (2i)
Yield: 28.2 mg (64%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.35 (m, 4 H), 5.87 (q, J = 8.4 Hz,
1 H), 2.27 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.99 (q, J = 5.7 Hz), 139.31,
135.20, 128.95, 127.55, 123.66 (q, J = 271.8 Hz), 116.50 (q,
J = 34.3 Hz), 17.52.
19F NMR (377 MHz, CDCl3): δ = –57.59 (dd, J = 8.3, 1.8 Hz).
MS (EI): m/z = 220.6 [M]+.
(E)-1-Methyl-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (2d)10i
Yield: 20.1 mg (54%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.0 Hz, 2 H), 7.19 (d,
J = 8.0 Hz, 2 H), 7.11 (dd, J = 16.1, 1.9 Hz, 1 H), 6.14 (dq,
J = 16.1, 6.6 Hz, 1 H), 2.37 (s, 3 H).
HRMS (EI-TOF): m/z [M]+ calcd for C10H8ClF3: 220.0267; found:
220.0266.
13C NMR (100 MHz, CDCl3): δ = 140.42, 137.67 (q, J = 6.6 Hz),
130.78, 129.75, 127.60, 123.9 (q, J = 269 Hz), 114.89 (q,
J = 33.6 Hz), 29.88.
19F NMR (377 MHz, CDCl3): δ = –63.51 to –63.64 (m).
MS (EI): m/z = 186.2 [M]+.
(E)-1-Chloro-4-(3,3,3-trifluoro-1-phenylprop-1-en-1-yl)ben-
zene (2j)15d
Yield: 35.0 mg (62%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.28 (m, 5 H), 7.24–7.16 (m,
4 H), 6.12 (q, J = 8.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 152.04 (q, J = 5.7 Hz), 139.82,
137.85, 135.79, 134.85, 130.69, 129.317, 128.82, 128.22, 123.1 (q,
J = 270 Hz), 116.15 (q, J = 33.3 Hz).
(E)-1-Chloro-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (2e)9e
Yield: 24.0 mg (58%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.37 (m, 4 H), 7.10 (dd, J = 16.1,
2.0 Hz, 1 H), 6.18 (dq, J = 16.1, 6.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 136.55 (q, J = 6.7 Hz), 136.12,
132.02, 129.35, 128.88, 122.22 (q, J = 270 Hz), 116.59 (q,
J = 34.1 Hz).
19F NMR (377 MHz, CDCl3): δ = –63.80 to –64.08 (m).
MS (EI): m/z = 206.5 [M]+.
19F NMR (377 MHz, CDCl3): δ = –56.09 (dd, J = 46.5, 8.2 Hz).
MS (EI): m/z = 282.5 [M]+.
(3,3,3-Trifluoroprop-1-ene-1,1-diyl)dibenzene (2k)15d
Yield: 29.8 mg (60%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.29 (m, 6 H), 7.24 (m, 4 H),
6.12 (q, J = 8.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 152.63 (q, J = 5.6 Hz), 140.29,
137.43, 129.03, 128.17, 124.60 (q, J = 270 Hz), 115.77 (q,
J = 33.2 Hz).
19F NMR (377 MHz, CDCl3): δ = –56.04 (d, J = 8.3 Hz).
MS (EI): m/z = 248.1 [M]+.
(E)-1-Bromo-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (2f)15b
Yield: 24.1 mg (48%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 8.3 Hz, 2 H), 7.32 (d,
J = 8.3 Hz, 2 H), 7.09 (dd, J = 16.1, 2.0 Hz, 1 H), 6.21 (dq,
J = 16.1, 6.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 136.66 (q, J = 6.7 Hz), 132.48,
132.34, 129.13, 123.6 (q, J = 270 Hz), 124.42, 116.72 (q,
J = 33.8 Hz).
(E)-4-(3,3,3-Trifluoroprop-1-en-1-yl)phenol (2l)10i
Yield: 23.7 mg (63%); light-yellow solid; mp 71.2–72.5 °C.
19F NMR (377 MHz, CDCl3): δ = –63.93 (dd, J = 6.3, 1.7 Hz).
MS (EI): m/z = 251.0 [M]+.
1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.5 Hz, 2 H), 7.07 (dd,
J = 16.1, 2.0 Hz, 1 H), 6.84 (d, J = 8.5 Hz, 2 H), 6.05 (dq, J = 16.1,
6.6 Hz, 1 H), 5.36 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 157.33, 137.21 (q, J = 6.8 Hz),
129.44, 126.57, 124.07 (q, J = 268.5 Hz), 116.04, 113.80 (q,
J = 33.7 Hz).
19F NMR (376 MHz, CDCl3): δ = –62.89 (s).
MS (EI): m/z = 188.1 [M]+.
(E)-(4,4,4-Trifluorobut-2-en-2-yl)benzene (2g)15c
Yield: 21.2 mg (57%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 6.7 Hz, 2 H), 7.39–
7.34 (m, 3 H), 5.87 (q, J = 8.4 Hz, 1 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.21 (q, J = 5.2 Hz), 141.01,
129.182, 128.768, 126.23, 123.88 (q, J = 281.9 Hz), 116.10 (q,
J = 33.8 Hz), 17.57.
19F NMR (377 MHz, CDCl3): δ = –57.51 (dd, J = 8.4, 2.0 Hz).
MS (EI): m/z = 186.1 [M]+.
(E)-2-(4,4,4-Trifluorobut-2-en-2-yl)thiophene (2m)
Yield: 20.0 mg (52%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 5.0 Hz, 1 H), 7.23 (d,
J = 3.2 Hz, 1 H), 7.06–7.00 (m, 1 H), 6.01 (q, J = 8.4 Hz, 1 H), 2.31
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.86 (s), 141.74 (q, J = 5.7 Hz),
127.98 (s), 126.84 (s), 126.31 (s), 123.86 (q, J = 270.0 Hz), 113.40
(q, J = 33.7 Hz), 17.22 (s).
(E)-1-Methyl-4-(4,4,4-trifluorobut-2-en-2-yl)benzene (2h)
Yield: 24.0 mg (60%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 8.0 Hz, 2 H), 7.17 (d,
J = 8.0 Hz, 2 H), 5.85 (q, J = 8.4 Hz, 1 H), 2.36 (s, 3 H), 2.27 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 148.98 (q, J = 5.3 Hz), 139.27,
138.02, 129.43, 126.11, 124.01 (q, J = 271.7 Hz), 115.25 (q,
J = 33.3 Hz), 21.31, 17.47.
HRMS (EI-TOF): m/z [M]+ calcd for C8H7F3S: 192.0221; found:
192.0221.
Acknowledgment
19F NMR (377 MHz, CDCl3): δ = –57.27 (dd, J = 8.5, 1.9 Hz).
MS (EI): m/z = 200.2 [M]+.
HRMS (EI-TOF): m/z [M]+ calcd for C11H11F3: 200.0813; found:
This work was supported by the National Natural Science Founda-
tion of China (Project No. 21176039 and 20923006).
200.0814.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 607–612

612
J. Yin et al.
PAPER
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Zheng, X.; Gu, Y. C.; Xiao, J. C. Chem. Commun. 2011, 47,
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
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