Synthesis of α-Trifluoromethylacrylates by Ligand-Free Palladium-Catalyzed Mizoroki-Heck Reaction

Article abstract of DOI:10.1021/acs.joc.8b03085

Efficient ligand-free palladium catalyzed Mizoroki-Heck reaction allowed the formation of trisubstituted α-trifluoromethylacrylates. The reaction showed good chemical tolerance and furnished moderate to excellent yields of reaction. Silver salt additive proved to be essential for the reaction. The reaction has been then applied to the formation of 3-trifluoromethyl coumarins and analogues of therapeutic agents.

Full text of DOI:10.1021/acs.joc.8b03085

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Article
Synthesis of #-Trifluoromethylacrylates by Ligand-
Free Palladium-Catalyzed Mirozoki-Heck Reaction
Pan Xiao, Claire Schlinquer, Xavier Pannecoucke, Jean-Philippe Bouillon, and Samuel Couve-Bonnaire
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03085 • Publication Date (Web): 11 Jan 2019
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Synthesis of α-Trifluoromethylacrylates by Ligand-Free Palladium-Cat-
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alyzed Mirozoki-Heck Reaction
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Pan Xiao, Claire Schlinquer, Xavier Pannecoucke, Jean-Philippe Bouillon* and Samuel Couve-Bon-
naire*
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Normandie Université, COBRA, UMR 6014 et FR 3038, Université de Rouen, INSA Rouen, CNRS, 1 rue Tesnière, 76821
Mont Saint-Aignan Cedex, France
Supporting Information
ABSTRACT: Efficient ligand-free palladium catalyzed Mizoroki-Heck reaction allowed the formation of trisubstituted α-trifluoro-
methylacrylates. The reaction showed good chemical tolerance and furnished good to excellent yields of reaction. Silver salt additive
proved to be essential for the reaction. The reaction has been then applied to the formation of 3-trifluoromethyl coumarins and ana-
logues of therapeutic agents.
Introduction
Scheme 1. State of the art about the synthesis of α-trifluoro-
methylacrylates
Organofluorine chemistry is a tremendous research area with
plenty of different applications in materials, pharmaceuticals or
agrochemical sciences.1 Among the highly diversified groups
containing one or more fluorine atoms, the trifluoromethyl moi-
ety have received a lot of attention these last years.2 Indeed, its
impact on physical properties of molecules, ie. acidity, hydro-
phobicity, steric hindrance…, is spectacular. The trifluorometh-
ylalkenes-containing molecules can be found, for instance, as
therapeutic agents or agrochemicals.3,4 Moreover, the trifluoro-
methylalkene group is known as an efficient peptide bond sur-
rogate.5,6 Among the various trifluoromethylalkene derivatives,
α-trifluoromethyl-acrylate moiety is a valuable building block
which can be found in various relevant molecules (materials,
medicinal) or can serve as intermediate towards fine chemicals
such as trifluoromethyl nucleosides or peptidomimetics for ex-
amples.6 Despite obvious interest in such kind of scaffolds,
there is very few general access to the α-trifluoromethylacry-
lates. Indeed, most of reported reactions gave only few exam-
ples of α-trifluoromethylacrylate synthesis (Scheme 1). In the
early 2000s, Schlosser used the Wittig reaction with methyl
3,3,3-trifluoropyruvate to synthesize one specific α-trifluoro-
methylacrylate in 51% yield and low E/Z selectivity (60/40).7
Later, Paleta et al. used the same reaction to get four α-trifluo-
romethylacrylates in good yields (68 to 78%) with selectivities
depending of the substrate (E/Z from 43/57 to 92/8) (Scheme 1,
Eq. a).8 During the same time, Qing reported the synthesis of α-
trifluoromethylacrylate via the in-situ formation of trifluorome-
thyl-copper species. The cross-coupling reaction between these
latter and seven vinyl halides gave the corresponding products
in fair to good yields (42-93%) and selectivities (E/Z from 61/39
to 89/11) starting from vinyl bromides.5d,9
Yields and selectivities were improved using vinyl iodides as
substrates (Scheme 1, Eq. b).10 Nevertheless, these reactions re-
quired the multi-step pre-synthesis of the corresponding halo-
phosphonoacetate and then the obtention of halogenoalkenes as
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key intermediates for the reaction. Other authors used the same
dropped down to 17% and 19% in 4 and 24 h reaction, respec-
strategy later without improvement of yield or selectivity.4c,11
Another strategy developed in 2006 by Jiang and Zhu involved
the use of potentially explosive diazo compound (methyl 3,3,3-
trifluoro-2-diazopropionate) in combination with aldehyde un-
der transition metal-catalysis (Rh or Cu) to get the desired α-
trifluoromethylacrylate in low to good yields and moderate se-
lectivity (eight examples, 36-81% yield, E/Z from 24/76 to
84/16) (Scheme 1, Eq. c).12 More recently, the radical trifluoro-
methylation (from Langlois’s reagent, trifluoromethyl iodide or
Togni’s reagent) of acrylates through a radical addition-elimi-
nation process was developed but only few examples were ded-
icated to α-trifluoromethylacrylate and only fair to good yields
(63-80%) were obtained in these cases (Scheme 1, Eq. d).13
Even more recently, photoredox-catalyzed transformation of al-
kynes into α-(trifluoromethyl)alkenes were developed by Akita
and then Han, respectively.14 These reactions were only applied
once to ethyl phenylpropiolate to furnish one example of α-tri-
fluoromethylacrylate in good stereoselectivity, albeit in moder-
ate yields (4414b and 57%,14a respectively) (Scheme 1, Eq. e). In
2018, we described the synthesis of trisubstituted α-trifluoro-
methylacrylates by a palladium-catalyzed decarboxylative ole-
fination reaction in low to excellent yields (24-99%) with vari-
ous selectivities (E/Z from 60/40 to 12/88) but this access al-
lows only the formation of aromatic ortho-substituted α-trifluo-
romethylacrylates (Scheme 1, Eq. f).15 Moreover good yields
were only obtained starting from electron-rich benzoic acids.
To resume, for the above-mentioned methods, most of them
showed narrow substrate scope furnishing only moderate to
good yields of α-trifluoromethylacrylate; moreover, some of
them required pre-synthesis of substrates, used expensive fluor-
inated reagents or unstable starting materials. Herein, we pro-
pose an efficient and general straightforward access, in one step,
to a large variety of α-trifluoromethylacrylates via a ligand-free
palladium-catalyzed Mizoroki-Heck reaction. This methodol-
ogy has then been applied to the synthesis of trifluororomethyl-
ated analogues of fine chemicals.
tively (Table 1, entry 7). So, we then tested a plethora of other
bases18 and clearly, silver cation proved to be essential for the
reaction (table 1, entries 8-11). At this stage, we decided to test
other silver additives (Table 1, entries 12-16) and pleasingly,
among them, silver triflate furnished the highest yield of 3a
(93%) using 2 (Table 1, entry 13) or even 1.5 equiv in 2 hours
reaction time (Table 1, entry 17).
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Table 1. Optimization of the trifluoromethylalkenylation
reactiona
Base or Yield of E/Z ra-
Entry
Solvent
Catalyst
additive
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
-
3a (%)b
86
tio
1
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(OAc)2
PdBr2
77/23
66/34
60/40
74/26
60/40
-
1,4-Dioxane
Toluene
2
93
3
16
DMF
4
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
Toluene
22
5
4
6
3
Pd(PPh3)4
Pd(TFA)2
Pd(PPh3)4
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(OAc)2
PdBr2
7
17 [19]c
80/20
75/25
67/33
67/33
67/33
74/26
77/23
77/23
70/30
76/24
76/24
77/23
64/36
76/24
74/26
75/25
8
13
NEt3
9
NEt3
15
10
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12
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16
17d
18d
19d
20d
21d
22d
23d
24d
25d
26d,f
27d,g
17
K2CO3
CuOAc
AgOAc
AgOTf
AgTFA
Ag3PO4
AgNO3
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
5
74
93
86
63
34
93 (86)e
Results and discussion
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98
We started the optimization of the reaction studying the Mi-
zoroki-Heck reaction between p-methoxyphenyl iodide 1a as
model substrate and commercially available methyl α-trifluoro-
methylacrylate 2 (Table 1). To our knowledge, among the vari-
ous fluorinated alkenes used in Mizoroki-Heck reaction, it was
the first time that reagent 2 was used in such reaction.16 We used
our previous optimized experimental conditions reported for the
synthesis of α-fluoroacrylates17 (Table1, entry 1). These condi-
tions furnished encouraging results and led to 86% yield of
compound 3a using 10 mol% of electrophilic catalyst,
Pd(TFA)2. We then tested several solvents and among them tol-
uene allowed to slightly improve the yield of the reaction along
with, nevertheless, a decrease of selectivity (Table 1, entry 2).
Highly polar solvent such as DMF gave lower yield of com-
pound 3a (Table 1, entry 3). Other tested solvents did not give
any improved results compared to those obtained with 1,4-di-
oxane.18 Changing the nature of the catalyst proved to be detri-
mental for the reaction giving a poor 22% yield of 3a with
Pd(OAc)2 and almost no reaction with PdBr2 or Pd(PPh3)4, a
Pd(0) catalyst. (Table 1, entries 4-6). In order to gain in selec-
tivity, we used different common ligands such as monodentate
or bidentate phosphines but the results were lower in terms of
yield and selectivity.18 The use of silver carbonate proved to be
important for the reaction as without this base the yields
DMF
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
91 (84)e
90 (83)e
59
Pd(PPh3)4
Pd(dba)2
Pd2(dba)3
-
traces
traces
0
Pd(TFA)2
92 (86)e
90 (84)e
76/24
76/24
Pd(TFA)2
aReaction conditions: 1a (0.2 mmol, 1.0 equiv), 2 (0.3 mmol,
1.5 equiv), [Pd] catalyst (10 mol%), base or additive (0.4 mmol,
2.0 equiv), solvent (1.0 mL), 4 h, 90 °C. b19F NMR yields were
obtained by using PhCOCF3 as an internal standard. c24 h. dAg-
e
f
OTf (1.5 equiv), 2 h. Isolated yield. Pd(TFA)2 (1.5 mol%).
gPd(TFA)2 (0.5 mol%).
Taking into account that this silver triflate cannot be consid-
ered as a base but more as a halide abstracter allowing the for-
mation of cationic palladium species,19 we speculated that a
highly polar solvent should stabilize it and favored the reaction.
Indeed, with silver triflate, toluene gave only poor 29% yield
(Table 1, entry 18) whereas DMF allowed us to reach 98%
yield, albeit with lower selectivity (Table 1, entry 19). These
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results clearly showed that the mechanism of the reaction is dif-
AgOTf (0.3 mmol, 1.5 equiv), 1,4-dioxane (1.0 mL) in 2 h, at
90°C.
Various aryl iodides 1 were suitable for the reaction which
ferent when silver carbonate or silver triflate is employed (table
1, comparison entries 1-3 with entries 17-19). Another proof of
this hypothesis is the possibility with silver triflate to use other
palladium catalysts than the electrophilic Pd(TFA)2 leading to
good yield of 3a (Table 1, entries 20-21). The yield was lower
using Pd(0) catalyst in presence of phosphine ligand (entry 22)
whereas without ligand stabilization, Pd(0) catalyst did afford
only traces of product (entries 23-24). The absence of palladium
in the reaction media proved to be detrimental as no reaction
occured (Table 1, entry 25). Finally, it was possible to decrease
the catalyst loading to 1.5 mol% or even 0.5 mol% still with
good isolated yields (Table 1, entries 26 and 27). Nevertheless,
it was not a general trend as some substrates required at least 5
or 10 mol% catalyst to go to completion.
proved to be highly tolerant in regards of substituents beared by
the aryl moiety (Scheme 3). Interestingly, para-iodophenol did
not need to be protected and furnished 76% yield of 3b. The
reaction was scaled up with iodobenzene 1c, 3.5 mmol instead
of usual 0.2 mmol, and the corresponding product 3c was ob-
tained with excellent 92% of isolated yield (740 mg). Other hal-
ogens (chlorine or bromine) did not interfer during the reaction
which was regioselective at the iodine position leading to post-
functionnalizable products 3e and 3f in very good 85% and 89%
yield, respectively. Valuable withdrawing functional groups for
further post-functionalizations such as cyano 1g, nitro 1h, ester
1i or methylketone 1j, displayed very good reactivities leading
to high yields, (84 to 92%), albeit the yield was lower starting
from 1j (71%). Pleasingly, the carboxylic acid 1k could also be
used directly in the reaction giving high 88% yield of the corre-
sponding 3k. Finally, we succeeded using highly relevant 4-
iodophenylboronic acid pinacol ester as substrate, albeit the
yield was lower (59%) in this case. Replacing the para-iodoan-
isole by para-bromoanisole as substrate only led to 34% of 3a.
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Based on experimental findings, hereafter, we proposed the
following mechanism for this trifluoromethylalkenylation reac-
tion (Scheme 2). After an oxidative addition, the Pd(II) is trans-
formed in Pd(IV), complex A. Silver triflate acted as an halide
abstracter furnishing the cationic palladium B. This latter is sta-
bilized in polar solvent as well as in the presence of electro-
enriched substituent in the aryl moiety. Then a coordination of
α-trifluoromethylacrylate 2 to complex B occurred to obtain in-
termediate C. This coordination is favored because the energy
gap between the HOMO of the electron-deficient alkene 2 and
the LUMO of palladium B is decreased by the electrophilic na-
ture of B. Then an insertion of aryl into the double bond gave
complex D. Deprotonation by the closed triflate counteranion
or concerted deprotonation by TFA ligand regenerates PdX2
and led to desired product 3 as well as the formation of triflic or
trifluoroacetic acid. Indeed, at the end of the reaction, the pH in
the reaction media appeared to be highly acidic (pH ≈1 with the
presence of triflic acid and trifluoroacetic acid in 19F NMR of
the crude).
Scheme 3. Scope of the reactiona
Scheme 2. Proposed mechanism.
A lot of other experimental conditions were tested18 and wor-
thy of note that depending on aryl iodides used, the reaction
time can be reduced down to 5 min for some electron-rich sub-
strates, which is consistant with stabilization of the cationic pal-
ladium. The reaction’s temperature can also be decreased to
60°C in some cases. Nevertheless, in order to propose a general
method, all the following scope has been obtained using the fol-
lowing experimental procedure: aryl iodide 1 (0.2 mmol, 1.0
equiv), 2 (0.3 mmol, 1.5 equiv), [Pd] catalyst (10 or 1.5 mol%),
aGeneral conditions: Ar-I 1 (0.2 mmol, 1.0 equiv), methyl 2-
trifluoromethylacrylate 2 (0.3 mmol, 1.5 equiv), Pd(TFA)2 (10
mol%), AgOTf (0.3 mmol, 1.5 equiv), 1,4-dioxane (1.0 mL), 2
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h, 90 °C. bYield based on isolated product after flash chroma-
same selectivity and yield of 3 than obtained with 10 mol% cat-
alyst (Scheme 3, results in blue).
c
d
tography. Reaction proceeded in 5 min. with para-bromoan-
e
isole, 19F NMR yield. The reaction was scaled up: 1c (3.5
Then we decided to apply our methodology to the production
of fine fluorinated chemicals (Scheme 5). Using our strategy, it
was possible, in one step to obtain a fluorinated analogue 3y,
albeit in E/Z mixture, of methyl 3, 4, 5-trimethoxycinnamate,
an anti-inflammatory agent in high 89% yield.20 The reaction
was then applied to the production of a fluorinated analogue 3z
(E/Z mixture) of the methyl caffeate, an antitumoral and anti-
microbial agent,21 in moderate 45% yield.22
mmol, 1.0 equiv), and 740 mg of 3c was obtained. f1.2 equiv of
2.
The stereoselectivity of the reaction was undoubtedly as-
signed by NMR spectroscopy (19F NMR and HOESY experi-
ments)18 and X-ray diffraction analysis (Scheme 4). The less
constrained E-product was always the major isomer obtained.
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Scheme 4. X-ray of product (Z)-3g.
Taking into account that we are in acid media at the end of
the reaction, we wondered if it could be possible to use ortho-
iodophenol and performed an in-situ cyclization between hy-
droxyl and ester function in order to get a direct access to 3-
trifluoromethyl coumarin. So we submitted the ortho-iodophe-
nol to the reaction conditions and we were pleased to obtain, as
the sole product, the 3-trifluoromethyl coumarin 4a in good
72% yield. We applied this methodology to the synthesis of
three other relevant substituted 3-trifluoromethyl coumarins
(4b-d) in moderate to very good yields. Usual synthesis of 3-
trifluoromethyl coumarins involved the radical trifluoromethyl-
ation of coumarin scaffolds or specific designed substrates
providing the desired coumarin in moderate yields.23 So, this
direct synthesis of 3-trifluoromethyl coumarins in one step by
Mizoroki-Heck reaction represents a nice synthetic alternative
obtaining this valuable scaffold with many application in fluo-
rescence or medicine.24
Then we submitted different meta- and ortho-substituted aryl
iodides to our reaction conditions (Scheme 3). We always ob-
tained good yields excepted with ortho-methoxy substituent
leading to a fair 54% yield of 3q.
The selectivity of the reaction was rather independent of the
substituent whether it was electron-donating or electron-with-
drawing group, ie E/Z ratio between 79/21 to 72/28, excepted
for some substrates. Indeed, surprisingly, para-cyano 3g, para-
nitro 3h and meta-nitro 3n were obtained with a lower E/Z ratio
of 63/37, 55/45 and 62/38 respectively whereas ortho-substi-
tuted 3r (o-Me) and 3s (o-NO2) were obtained in the same range
of E/Z ratio, 65/35 and 64/36 respectively, probably due for the
latters of steric interaction close to the reaction center.
Conclusion
To resume we described a general and efficient method to
obtain valuables α-trifluoromethylacrylates. The reaction
proved to be highly tolerant with respect to substituents beared
by the aryl moiety. Indeed, substrates with non protected hy-
droxyl as well as carboxylic acid function displayed high reac-
tivities. We then applied successfully our reaction to the syn-
thesis of fluorinated therapeutic agents. Worthy of note that we
also proposed, via this Mizoroki-Heck reaction, an efficient al-
ternative to the production of highly relevant 3-trifluoromethyl
coumarins.
Polysubstituted aryl iodides could also be coupled efficiently
with good yields. Among them, the valuable methyl 2-amino-
5-iodobenzoate 1x provided the corresponding product 3x in
high 81% yield without protection of the amine function.
Nevertheless, it has to be noted that whereas a lot of aryl io-
dides can be used in this reaction the use of heteroaryl iodides
(azines, thiophen, furan) displayed only very low or no reactiv-
ity.18
We selected some substrates 1 and demonstrated that we can
used only 1.5 mol% of catalyst affording, most of the time, the
Scheme 5. Applications to the synthesis of fine fluorinated chemicals.a
aYields are based on isolated product after flash chromatography. bwith Pd(TFA)2 (0.5 mol%).
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Experimental section
Methyl
(E)-3-(4-hydroxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3b) and Methyl (Z)-3-(4-hydroxyphenyl)-2-
(trifluoromethyl)acrylate (Z-3b). 4-Iodophenol (0.2 mmol,
44.0 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
10/1 to 5/1, v/v), affording compound 3b in 76% yield [mixture
General Information: Commercially available reagents and
anhydrous solvents were purchased from standard chemical
suppliers (Fisher, Sigma-Aldrich, Fluorochem, Alfa Aesar) and
used as received without further purification. Among them, me-
thyl 2-(trifluoromethyl)acrylate (97% purity) was purchased
from Sigma-Aldrich or Fluorochem. Thin layer chromatog-
raphy (TLC) analyses were done using aluminium sheets coated
with silica gel 60 F254; Flash column chromatography was car-
ried out using Silicaflash P60 silica gel (40-60 µm). Melting
points (Mp) were determined on a Fisher Scientific hot stage
melting point apparatus and are uncorrected. NMR spectra were
recorded using a Bruker Avance-300 spectrometer operating at
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1
of E/Z isomers (78/22), 37.3 mg] as a pale yellow solid. H
NMR (300 MHz, CDCl3): δ 8.00 (s, 1H, Z), 7.42 – 7.27 (m, 2H,
Z + 3H, E), 6.91 – 6.73 (m, 2H, Z + 2H, E), 6.06 (s, 1H, E), 5.95
(s, 1H, Z), 3.89 (s, 3H, Z), 3.85 (s, 3H, E). 19F NMR (282 MHz,
CDCl3): δ -58.5 (s, Z), -63.8 (d, J = 1.7 Hz, E). 13C{1H} NMR
(75 MHz, CDCl3): δ 165.1 – 165.0 (m), 165.0 (q, J = 2.0 Hz),
158.22, 158.19, 148.7 (q, J = 2.7 Hz), 141.0 (q, J = 5.7 Hz),
132.7 (q, J = 2.7 Hz), 131.8, 124.7, 124.5, 122.5 (q, J = 271.1
Hz), 122.3 (q, J = 272.2 Hz), 120.2 (q, J = 31.1 Hz), 119.5 (q,
J = 32.3 Hz), 115.9, 115.6, 53.0, 52.9. IR: 3292, 1699, 1608,
1515, 1438, 1383, 1279, 1250, 1210, 1157, 1126, 1109, 1019,
843, 493 cm-1. HRMS (EI-TOF): Calcd for C11H9F3O3 (m/z):
246.0504 [M]+, found: 246.0496.
300 MHz (1H), 282 MHz (19F), and 75 MHz (13C). 1H and 13
C
NMR chemical shifts (δ) were calibrated on residual proton and
carbon resonances of CDCl3 (1H, δ = 7.26 ppm and 13C, δ =
77.16 ppm) or CD3OD (1H, δ = 3.31 ppm and 13C, δ = 49.00
ppm) or (CD3)2SO (1H, δ = 2.50 ppm and 13C, δ = 39.52 ppm);
19F NMR chemical shifts (δ) were determined relative to CFCl3
as an internal standard (19F, δ = 0.0 ppm). The multiplicity sig-
nals were indicated with the common abbreviations: s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), br (broad) and
the combinations thereof. IR spectra were recorded on Perkin
Elmer Spectrum 100 FT IR spectrometer. High Resolution
Mass Spectra (HRMS) were recorded on a JEOL AccuTof 4G
spectrometer coupled to a GC HP Agilent 7890. Crystallo-
graphic data were collected using a Bruker SMART APEX dif-
fractometer with a CCD area detector.
Methyl (E)-3-phenyl-2-(trifluoromethyl)acrylate (E-3c)
and Methyl (Z)-3-phenyl-2-(trifluoromethyl)acrylate (Z-3c).
Iodobenzene (0.2 mmol, 40.8 mg), AgOTf (0.3 mmol, 77.1
mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluoro-
methyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL)
were reacted for 2 hours according to the general procedure.
The crude was purified by silica gel column chromatography
(petroleum ether/EtOAc, from 60/1 to 30/1, v/v), affording
compound 3c in 85% yield [mixture of E/Z isomers (72/28),
39.3 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.12
(s, 1H, Z), 7.53 – 7.34 (m, 5H, Z + 6H, E), 3.90 (s, 3H, Z), 3.79
(s, 3H, E). 19F NMR (282 MHz, CDCl3): δ -58.5 (s, Z), -64.4 (d,
J = 1.4 Hz, E). 13C{1H} NMR (75 MHz, CDCl3): δ 163.9, 148.6
(q, J = 2.9 Hz), 140.6 (q, J = 5.7 Hz), 132.6, 132.3, 130.5, 130.3,
129.4 (q, J = 2.3 Hz), 129.2, 128.8, 128.4, 123.3 (q, J = 31.3
Hz), 122.5 (q, J = 31.9 Hz), 122.2 (q, J = 271.4 Hz), 122.0 (q,
J = 272.6 Hz), 52.9, 52.7. IR: 2961, 1730, 1645, 1438, 1386,
1278, 1231, 1158, 1125, 1033, 1020, 755, 693 cm-1. HRMS (EI-
TOF): Calcd for C11H9F3O2 (m/z): 230.0555 [M]+, found:
230.0544.
General Procedure for Heck Reaction: To a vial (2 mL)
were added iodoarene (0.2 mmol, 1.0 equiv), AgOTf (0.3
mmol, 1.5 equiv), Pd(TFA)2 (0.02 mmol, 10 mol%), methyl 2-
(trifluoromethyl)acrylate (0.3 mmol, 1.5 equiv), and 1,4-diox-
ane (1.0 mL, 5 mL/mmol of iodoarene). The vial was then
sealed. The reaction mixture was stirred at 90 °C for 2 hours
and was then cooled to room temperature. The reaction mixture
was transferred to a 50 mL flask (with the vial washed with 20
mL EtOAc) and was mixed with celite. After evaporation of
solvents, the crude was purified by silica gel column chroma-
tography (eluent: petroleum ether/EtOAc or CH3Cl/MeOH).
Characterization data for products 3:
Methyl
(E)-3-(4-methoxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3a) and Methyl (Z)-3-(4-methoxyphenyl)-2-
(trifluoromethyl)acrylate (Z-3a). 4-Iodoanisole (0.2 mmol,
46.8 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 5 minutes
according to the general procedure. The crude was purified by
silica gel column chromatography (petroleum ether/EtOAc,
from 30/1 to 15/1, v/v), affording compound 3a in 86% yield
Methyl
(E)-3-([1,1'-biphenyl]-4-yl)-2-(trifluorome-
thyl)acrylate (E-3d) and Methyl (Z)-3-([1,1'-biphenyl]-4-yl)-
2-(trifluoromethyl)acrylate (Z-3d). 4-Iodobiphenyl (0.2
mmol, 56.0 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2
(0.02 mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3
mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2
hours according to the general procedure. The crude was puri-
fied by silica gel column chromatography (petroleum
ether/EtOAc, from 60/1 to 30/1, v/v), affording compound 3d
in 81% yield [mixture of E/Z isomers (79/21), 49.4 mg. E/Z iso-
mers were completely separated by column: compound E-3d
39.1 mg, yellow oil; impure Z-isomer was subsequently washed
with petroleum ether (0.5 mL × 3) to obtain pure compound Z-
3d 10.3 mg, white solid].
1
[mixture of E/Z isomers (75/25), 44.5 mg] as a yellow oil. H
NMR (300 MHz, CDCl3): δ 8.01 (s, 1H, Z), 7.51 – 7.29 (m, 2H,
Z + 3H, E), 6.99 – 6.84 (m, 2H, Z + 2H, E), 3.88 (s, 3H, Z), 3.86
– 3.83 (m, 3H, Z + 3H, E), 3.82 (s, 3H, E). 19F NMR (282 MHz,
CDCl3): δ -58.5 (s, Z), -63.8 (d, J = 1.7 Hz, E). 13C{1H} NMR
(75 MHz, CDCl3): δ 164.5 – 164.3 (m), 161.70, 161.66, 148.3
(q, J = 3.0 Hz), 140.4 (q, J = 5.7 Hz), 132.4 (q, J = 2.7 Hz),
131.7, 124.7, 124.5, 122.6 (q, J = 271.0 Hz), 122.3 (q, J = 272.0
Hz), 120.4 (q, J = 31.0 Hz), 119.6 (q, J = 32.0 Hz), 114.2, 114.0,
55.4, 52.7, 52.6. IR: 2960, 2847, 1726, 1604, 1513, 1439, 1322,
1281, 1260, 1155, 1116, 1028, 832, 523 cm-1. HRMS (EI-TOF):
Calcd for C12H11F3O3 (m/z): 260.0660 [M]+, found: 260.0659.
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[E-isomer (major)] H NMR (300 MHz, CDCl3): δ 7.68 –
7.60 (m, 4H), 7.54 – 7.44 (m, 5H), 7.44 – 7.36 (m, 1H), 3.84 (s,
3H). 19F NMR (282 MHz, CDCl3): δ -64.2 (d, J = 1.7 Hz).
13C{1H} NMR (75 MHz, CDCl3): δ 164.0, 143.4, 140.2 (q, J =
5.7 Hz), 140.0, 131.1, 130.0, 129.1, 128.2, 127.3, 127.2, 122.9
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(q, J = 31.2 Hz), 122.3 (q, J = 271.4 Hz), 52.8. IR: 3034, 2954,
= 32.0 Hz), 122.1 (q, J = 271.6 Hz), 121.8 (q, J = 272.7 Hz),
1730, 1645, 1492, 1439, 1384, 1322, 1293, 1280, 1230, 1158,
1124, 1018, 763, 696 cm-1. HRMS (EI-TOF): Calcd for
C17H13F3O2 (m/z): 306.0868 [M]+, found: 306.0868.
53.0, 52.8. IR: 2961, 1731, 1645, 1589, 1489, 1439, 1385, 1312,
1288, 1274, 1230, 1161, 1128, 1073, 1021, 1011, 839, 814, 498
cm-1. HRMS (ES-TOF): Calcd for C11H879BrF3O2Na (m/z):
330.9557 [M+Na]+, found: 330.9554.
o
[Z-isomer (minor)] Mp 84-85 C. 1H NMR (300 MHz,
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CDCl3) δ 8.13 (s, 1H), 7.68 – 7.59 (m, 4H), 7.54 – 7.43 (m, 4H),
7.43 – 7.34 (m, 1H), 3.92 (s, 3H). 19F NMR (282 MHz, CDCl3)
δ -58.5 (s). 13C{1H} NMR (75 MHz, CDCl3) δ 164.1 (q, J = 2.0
Hz), 148.2 (q, J = 2.9 Hz), 143.2, 140.1, 131.4, 130.4 (q, J = 2.6
Hz), 129.1, 128.2, 127.3, 127.1, 122.2 (q, J = 32.0 Hz), 122.1
(q, J = 272.5 Hz), 53.0. IR: 3040, 2961, 2921, 2855, 1731, 1714,
1631, 1438, 1379, 1278, 1206, 1126, 1038, 845, 753, 701 cm-1.
HRMS (EI-TOF): Calcd for C17H13F3O2 (m/z): 306.0868 [M]+,
found: 306.0855.
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Methyl (E)-3-(4-cyanophenyl)-2-(trifluoromethyl)acry-
late (E-3g) and Methyl (Z)-3-(4-cyanophenyl)-2-(trifluoro-
methyl)acrylate (Z-3g). 4-Iodobenzonitrile (0.2 mmol, 45.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol,
6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.24 mmol, 37.0
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 20/1 to
5/1, v/v), affording compound 3g in 84% yield [mixture of E/Z
isomers (63/37), 42.7 mg. E/Z isomers were completely sepa-
rated by column: compound E-3g 27.1 mg, white solid; impure
Z-isomer was subsequently washed with petroleum ether (0.5
mL × 5) to obtain pure compound Z-3g 15.6 mg, white solid].
[E-isomer (major)] Mp <44 oC. 1H NMR (300 MHz,
CDCl3): δ 7.69 (d, J = 8.1 Hz, 2H), 7.52 – 7.42 (m, 3H), 3.78
(s, 3H). 19F NMR (282 MHz, CDCl3): δ -64.7 (d, J = 1.4 Hz).
13C{1H} NMR (75 MHz, CDCl3): δ 162.9 – 162.7 (m), 139.2
(q, J = 5.8 Hz), 136.9, 132.4, 129.5, 126.2 (q, J = 31.7 Hz),
121.7 (q, J = 271.9 Hz), 118.2, 113.8, 53.0. IR: 2959, 2231,
1732, 1653, 1440, 1381, 1292, 1275, 1235, 1160, 1129, 1020,
554 cm-1. HRMS (EI-TOF): Calcd for C12H8F3NO2 (m/z):
255.0507 [M]+, found: 255.0512.
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Methyl (E)-3-(4-chlorophenyl)-2-(trifluoromethyl)acry-
late (E-3e) and Methyl (Z)-3-(4-chlorophenyl)-2-(trifluoro-
methyl)acrylate (Z-3e). 1-Chloro-4-iodobenzene (0.2 mmol,
47.7 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
60/1 to 50/1, v/v), affording compound 3e in 85% yield [mix-
ture of E/Z isomers (74/26), 45.2 mg. E/Z isomers were com-
pletely separated by column: E-3e 33.5 mg, yellow oil; Z-3e
11.7 mg, yellow oil].
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[E-isomer (major)] H NMR (300 MHz, CDCl3): δ 7.43 –
7.28 (m, 5H), 3.80 (s, 3H). 19F NMR (282 MHz, CDCl3): δ -
64.4 (d, J = 1.7 Hz). 13C{1H} NMR (75 MHz, CDCl3): δ 163.6
– 163.5 (m), 139.6 (q, J = 5.8 Hz), 136.7, 130.7, 130.6, 129.1,
123.8 (q, J = 31.4 Hz), 122.1 (q, J = 271.5 Hz), 52.9. IR: 2961,
1732, 1650, 1492, 1312, 1290, 1273, 1232, 1160, 1128, 1095,
1015, 842, 816, 502, 434 cm-1. HRMS (EI-TOF): Calcd for
C11H835ClF3O2 (m/z): 264.0165 [M]+, found: 264.0156.
[Z-isomer (minor)] Mp 120-121 C. H NMR (300 MHz,
CDCl3): δ 8.09 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.1
Hz, 2H), 3.92 (s, 3H). 19F NMR (282 MHz, CDCl3): δ -58.5 (s).
13C{1H} NMR (75 MHz, CDCl3): δ 163.1 (q, J = 1.8 Hz), 146.0
(q, J = 3.0 Hz), 137.3, 132.1, 129.4 (q, J = 2.3 Hz), 125.2 (q, J
= 32.0 Hz), 121.5 (q, J = 273.0 Hz), 118.2, 113.6, 53.2. IR:
2230, 1716, 1639, 1440, 1386, 1289, 1225, 1149, 1127, 1041,
837, 657, 555 cm-1. HRMS (EI-TOF): Calcd for C12H8F3NO2
(m/z): 255.0507 [M]+, found: 255.0511.
o
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[Z-isomer (minor)] 1H NMR (300 MHz, CDCl3): δ 8.03 (s,
1H), 7.43 – 7.30 (m, 4H), 3.90 (s, 3H). 19F NMR (282 MHz,
CDCl3): δ -58.6 (s). 13C{1H} NMR (75 MHz, CDCl3): δ 163.7
(q, J = 2.0 Hz), 147.2 (q, J = 2.9 Hz), 136.6, 131.0, 130.8 (q, J
= 2.5 Hz), 128.8, 123.0 (q, J = 32.0 Hz), 121.8 (q, J = 272.7
Hz), 53.1. IR: 2961, 2921, 2855, 1731, 1640, 1491, 1438, 1392,
1279, 1257, 1131, 1091, 1041, 828, 788, 755 cm-1. HRMS (EI-
TOF): Calcd for C11H835ClF3O2 (m/z): 264.0165 [M]+, found:
264.0152.
Methyl (E)-3-(4-nitrophenyl)-2-(trifluoromethyl)acrylate
(E-3h) and Methyl (Z)-3-(4-nitrophenyl)-2-(trifluorome-
thyl)acrylate (Z-3h). 1-Iodo-4-nitrobenzene (0.2 mmol, 49.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol,
6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 15/1 to
7/1, v/v), affording compound 3h in 86% yield [mixture of E/Z
isomers (55/45), 47.6 mg; among which, partly pure compound
Methyl (E)-3-(4-bromophenyl)-2-(trifluoromethyl)acry-
late (E-3f) and Methyl (Z)-3-(4-bromophenyl)-2-(trifluoro-
methyl)acrylate (Z-3f). 1-Bromo-4-iodobenzene (0.2 mmol,
56.6 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
60/1 to 50/1, v/v), affording compound 3f in 89% yield [mixture
of E/Z isomers (73/27), 55.0 mg] as a yellow oil. 1H NMR (300
MHz, CDCl3): δ 7.92 (s, 1H, Z), 7.50 – 7.40 (m, 2H, Z + 2H,
E), 7.27 (s, 1H, E), 7.17 (d, J = 8.4 Hz, 2H, Z + 2H, E), 3.81 (s,
3H, Z), 3.71 (s, 3H, E). 19F NMR (282 MHz, CDCl3): δ -58.5
(s, Z), -64.5 (d, J = 1.7 Hz, E). 13C{1H} NMR (75 MHz, CDCl3):
δ 163.7 (q, J = 1.9 Hz), 163.6 – 163.5 (m), 147.2 (q, J = 2.9 Hz),
139.6 (q, J = 5.8 Hz), 132.0, 131.7, 131.4, 131.2, 130.9 (q, J =
2.4 Hz), 130.8, 125.0, 124.9, 123.9 (q, J = 31.4 Hz), 123.1 (q, J
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Z-3h was obtained] as a yellow oil. H NMR (300 MHz,
CDCl3): δ 8.25 (m, 2H, Z + 2H, E), 8.12 (s, 1H, Z), 7.63 – 7.43
(m, 2H, Z + 3H, E), 3.92 (s, 3H, Z), 3.78 (s, 3H, E). 19F NMR
(282 MHz, CDCl3): δ -58.5 (s, Z), -64.8 (d, J = 1.1 Hz, E).
13C{1H} NMR (75 MHz, CDCl3): δ 163.0 (q, J = 1.8 Hz), 162.8
– 162.6 (m), 148.6, 148.4, 145.6 (q, J = 3.0 Hz), 139.2, 139.0
(q, J = 5.9 Hz), 138.9, 129.8, 129.6 (q, J = 2.3 Hz), 126.7 (q, J
= 31.7 Hz), 125.7 (q, J = 32.0 Hz), 123.8, 123.6, 121.6 (q, J =
272.1 Hz), 121.4 (q, J = 272.9 Hz), 53.3, 53.0. IR: 2963, 1732,
1600, 1522, 1439, 1347, 1277, 1132, 1042, 855, 691 cm-1.
HRMS (ES-TOF): Calcd for C11H8F3NO4Na (m/z): 298.0303
[M+Na]+, found: 298.0312.
o
[Z-isomer (minor)] White solid. Mp 78-79 C. 1H NMR
(300 MHz, CDCl3) δ 8.27 (d, J = 8.7 Hz, 2H), 8.13 (s, 1H), 7.52
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(d, J = 8.4 Hz, 2H), 3.93 (s, 3H). 19F NMR (282 MHz, CDCl3)
compound 3k in 88% yield [mixture of E/Z isomers (76/24),
48.1 mg] as a white solid. 1H NMR (300 MHz, CD3OD): δ 8.20
(s, 1H, Z), 8.04 (d, J = 7.8 Hz, 2H, Z + 2H, E), 7.64 (s, 1H, E),
7.48 (d, J = 7.8 Hz, 2H, Z + 2H, E), 3.88 (s, 3H, Z), 3.75 (s, 3H,
E). 19F NMR (282 MHz, CD3OD): δ -59.2 (s, Z), -65.5 (d, J =
0.8 Hz, E). 13C{1H} NMR (75 MHz, CD3OD): δ 169.0, 168.9,
164.8 – 164.7 (m), 164.5 (q, J = 1.9 Hz), 148.7 (q, J = 3.0 Hz),
141.0 (q, J = 5.8 Hz), 138.5, 138.1, 133.3, 133.0, 130.9, 130.5,
130.0, 129.9 (q, J = 2.3 Hz), 125.9 (q, J = 31.4 Hz), 124.9 (q, J
= 31.5 Hz), 123.3 (q, J = 270.8 Hz), 123.1 (q, J = 272.1 Hz),
53.4, 533. IR: 2961, 2815, 2670, 2550, 1734, 1683, 1610, 1571,
1425, 1277, 1239, 1211, 1135, 1020, 929, 768, 696, 548 cm-1.
HRMS (ES-TOF): Calcd for C12H9F3O4Na (m/z): 297.0351
[M+Na]+, found: 297.0345.
δ -58.5 (s). 13C{1H} NMR (75 MHz, CDCl3) δ 163.0 (q, J = 1.8
Hz), 148.4, 145.7 (q, J = 3.0 Hz), 139.2, 129.7 (q, J = 2.3 Hz),
125.8 (q, J = 32.0 Hz), 121.4 (q, J = 273.0 Hz), 53.3. IR: 3107,
2968, 1722, 1638, 1598, 1518, 1429, 1348, 1276, 1206, 1143,
1126, 1041, 856, 693 cm-1. HRMS (EI-TOF): Calcd for
C11H8F3NO4 (m/z): 275.0405 [M]+, found: 275.0396.
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Methyl (E)-4-(3,3,3-trifluoro-2-(methoxycarbonyl)prop-
1-en-1-yl)benzoate (E-3i) and Methyl (Z)-4-(3,3,3-trifluoro-
2-(methoxycarbonyl)prop-1-en-1-yl)benzoate (Z-3i). Methyl
4-iodobenzoate (0.2 mmol, 52.4 mg), AgOTf (0.3 mmol, 77.1
mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluoro-
methyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL)
were reacted for 2 hours according to the general procedure.
The crude was purified by silica gel column chromatography
(petroleum ether/EtOAc, from 20/1 to 10/1, v/v), affording
compound 3i in 92% yield [mixture of E/Z isomers (74/26),
52.9 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.11
(s, 1H, Z), 8.09 – 7.99 (m, 2H, Z + 2H, E), 7.46 (s, 1H, E), 7.41
(d, J = 8.1 Hz, 2H, Z + 2H, E), 3.92 (s, 3H, Z + 3H, E), 3.90 (s,
3H, Z), 3.75 (s, 3H, Z). 19F NMR (282 MHz, CDCl3): δ -58.5 (s,
Z), -64.6 (d, J = 1.4 Hz, E). 13C{1H} NMR (75 MHz, CDCl3): δ
166.34, 166.29, 163.4 (q, J = 1.9 Hz), 163.3 – 163.2 (m), 142.2
(q, J = 3.0 Hz), 139.7 (q, J = 5.7 Hz), 137.1, 136.7, 131.5, 131.3,
129.8, 129.5 128.9, 125.1 (q, J = 30.2 Hz), 124.2 (q, J = 32.0
Hz), 121.9 (q, J = 271.7 Hz), 121.6 (q, J = 272.9 Hz), 53.0, 52.8,
52.4. IR: 2961, 1721, 1650, 1437, 1384, 1272, 1234, 1131,
1108, 1020, 766, 698 cm-1. HRMS (EI-TOF): Calcd for
C13H11F3O4 (m/z): 288.0609 [M]+, found: 288.0599.
Methyl (E)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)phenyl)-2-(trifluoromethyl)acrylate (E-3l) and Methyl
(Z)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phe-
nyl)-2-(trifluoromethyl)acrylate
(Z-3l).
4-Iodoben-
zeneboronic acid pinacol ester (0.2 mmol, 66.0 mg), AgOTf
(0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), me-
thyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-di-
oxane (1.0 mL) were reacted for 2 hours according to the gen-
eral procedure. The reaction mixture was directly purified by
flash silica gel column chromatography (petroleum
ether/EtOAc, from 40/1 to 20/1, v/v), affording compound 3l in
59% yield [mixture of E/Z isomers (68/32), 41.9 mg] as a yel-
low oil. 1H NMR (300 MHz, CDCl3): δ 8.11 (s, 1H, Z), 7.90 –
7.77 (m, 2H, Z + 2H, E), 7.44 (s, 1H, E), 7.42 – 7.28 (m, 2H, Z
+ 2H, E), 3.89 (s, 3H, Z), 3.76 (s, 3H, E), 1.35 (s, 12H, Z + 12H,
E). 19F NMR (282 MHz, CDCl3): δ -58.5 (s, Z), -64.5 (d, J = 1.1
Hz, E). 13C{1H} NMR (75 MHz, CDCl3): δ 163.9 – 163.7 (m),
148.5 (q, J = 2.9 Hz), 140.4 (q, J = 5.7 Hz), 135.2, 135.0, 134.9,
134.7, 128.4 (q, J = 2.3 Hz), 128.2, 124.0 (q, J = 31.2 Hz), 123.0
(q, J = 32.3 Hz), 122.1 (q, J = 271.4 Hz), 121.9 (q, J = 272.7
Hz), 84.24, 84.23, 52.9, 52.7, 25.0. IR: 2980, 1733, 1610, 1439,
1398, 1359, 1276, 1227, 1163, 1134, 1089, 1021, 858, 656 cm-
1. HRMS (AP-TOF): Calcd for C17H2011BF3O4 (m/z): 356.1407
[M]−, found: 356.1401.
Methyl (E)-3-(4-acetylphenyl)-2-(trifluoromethyl)acry-
late (E-3j) and Methyl (Z)-3-(4-acetylphenyl)-2-(trifluoro-
methyl)acrylate (Z-3j). 1-(4-Iodophenyl)ethan-1-one (0.2
mmol, 49.2 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2
(0.02 mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3
mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2
hours according to the general procedure. The crude was puri-
fied by silica gel column chromatography (petroleum
ether/EtOAc, from 15/1 to 8/1, v/v), affording compound 3j in
71% yield [mixture of E/Z isomers (78/22), 38.9 mg] as a yel-
low oil. 1H NMR (300 MHz, CDCl3): δ 8.10 (s, 1H, Z), 8.01 –
7.91 (m, 2H, Z + 2H, E), 7.57 – 7.38 (m, 2H, Z + 3H, E), 3.89
(s, 3H, Z), 3.76 (s, 3H, E), 2.60 (s, 3H, Z + 3H, E). 19F NMR
(282 MHz, CDCl3): δ -58.5 (s, Z), -64.6 (d, J = 1.7 Hz, E).
13C{1H} NMR (75 MHz, CDCl3): δ 197.4, 197.3, 163.4 (q, J =
1.8 Hz), 163.3 – 163.2 (m), 147.1 (q, J = 2.8 Hz), 139.7 (q, J =
5.7 Hz), 138.0, 137.8, 137.2, 136.8, 129.5 – 128.9 (m), 128.5,
128.2, 125.2 (q, J = 31.5 Hz), 124.3 (q, J = 31.9 Hz), 121.9 (q,
J = 271.7 Hz), 121.6 (q, J = 272.9 Hz), 53.1, 52.9, 26.8. IR:
2961, 1731, 1685, 1649, 1606, 1439, 1361, 1262, 1234, 1161,
1128, 1021, 835, 693, 598 cm-1. HRMS (ES-TOF): Calcd for
C13H11F3O3Na (m/z): 295.0558 [M+Na]+, found: 295.0562.
Methyl
(E)-3-(3-methoxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3m) and Methyl (Z)-3-(3-methoxyphenyl)-
2-(trifluoromethyl)acrylate (Z-3m). 3-Iodoanisole (0.2 mmol,
46.8 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
30/1 to 15/1, v/v), affording compound 3m in 82% yield [mix-
ture of E/Z isomers (73/27), 42.7 mg] as a yellow oil. 1H NMR
(300 MHz, CDCl3): δ 7.99 (s, 1H, Z), 7.30 (d, J = 0.9 Hz, 1H,
E), 7.26 – 7.17 (m, 1H, Z + 1H, E), 6.94 – 6.79 (m, 3H, Z + 3H,
E), 3.81 (s, 3H, Z), 3.78 – 3.67 (m, 3H, Z + 6H, E). 19F NMR
(282 MHz, CDCl3): δ -58.4 (s, Z), -64.4 (d, J = 1.7 Hz, E).
13C{1H} NMR (75 MHz, CDCl3): δ 164.0 – 163.8 (m), 159.8,
159.4, 148.5 (q, J = 3.0 Hz), 140.1 (q, J = 5.7 Hz), 133.9, 133.6,
129.8, 129.5, 123.6 (q, J = 31.4 Hz), 122.8 (q, J = 31.8 Hz),
122.2 (q, J = 271.4 Hz), 121.9 (q, J = 272.7 Hz), 121.8 (q, J =
2.4 Hz), 121.6, 116.4, 116.0, 114.5 (q, J = 2.4 Hz), 114.3, 55.4,
52.9, 52.8. IR: 2958, 2845, 1731, 1581, 1436, 1302, 1254, 1227,
1125, 1203, 784, 690 cm-1. HRMS (EI-TOF): Calcd for
C12H11F3O3 (m/z): 260.0660 [M]+, found: 260.0650.
(E)-4-(3,3,3-trifluoro-2-(methoxycarbonyl)prop-1-en-1-
yl)benzoic acid (E-3k) and (Z)-4-(3,3,3-trifluoro-2-(methox-
ycarbonyl)prop-1-en-1-yl)benzoic acid (Z-3k). 4-Iodoben-
zoic acid (0.2 mmol, 49.6 mg), AgOTf (0.3 mmol, 77.1 mg),
and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluorome-
thyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were
reacted for 2 hours according to the general procedure. The
crude was purified by silica gel column chromatography (petro-
leum ether/EtOAc, 5/1, with 1% CH3COOH, v/v), affording
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7/1, v/v), affording compound 3p in 85% yield [mixture of E/Z
Methyl (E)-3-(3-nitrophenyl)-2-(trifluoromethyl)acrylate
(E-3n) and Methyl (Z)-3-(3-nitrophenyl)-2-(trifluorome-
thyl)acrylate (Z-3n). 1-Iodo-3-nitrobenzene (0.2 mmol, 49.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.003 mmol,
1.0 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 15/1 to
8/1, v/v), affording compound 3n in 84% yield [mixture of E/Z
isomers (62/38), 42.0 mg; among which, partly pure compound
isomers (70/30), 43.6 mg. E/Z isomers were completely sepa-
rated by column: compound E-3p 30.4 mg, colorless oil; im-
pure Z-isomer was subsequently washed with petroleum ether
(0.3 mL × 3) to obtain pure compound Z-3p 13.2 mg, white
solid].
[E-isomer (major)] 1H NMR (300 MHz, CDCl3): δ 7.69 (d,
J = 8.1 Hz, 2H), 7.64 – 7.48 (m, 2H), 7.44 (s, 1H), 3.79 (s, 3H).
19F NMR (282 MHz, CDCl3): δ -64.7 (d, J = 1.7 Hz). 13C{1H}
NMR (75 MHz, CDCl3): δ 162.8, 139.0 (q, J = 5.8 Hz), 133.8,
133.5, 133.1, 132.4, 129.6, 125.8 (q, J = 31.7 Hz), 121.7 (q, J =
271.9 Hz), 118.0, 113.2, 53.0. IR: 2958, 2234, 1731, 1654,
1440, 1379, 1296, 1282, 1229, 1129, 1024, 799, 686 cm-1.
HRMS (ES-TOF): Calcd for C12H8F3NO2Na (m/z): 278.0405
[M+Na]+, found: 278.0414.
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E-3n was obtained] as a yellow oil. H NMR (300 MHz,
CDCl3): δ 8.39 – 8.20 (m, 2H, Z + 2H, E), 8.11 (s, 1H, Z), 7.69
(t, J = 6.6 Hz, 1H, Z + 1H, E), 7.65 – 7.55 (m, 1H, Z + 1H, E),
7.50 (s, 1H, E), 3.92 (2s, 3H, Z), 3.81 (2s, 3H, E). 19F NMR (282
MHz, CDCl3): δ -58.5 (s, Z), -64.7 (d, J = 1.4 Hz, E). 13C{1H}
NMR (75 MHz, CDCl3): δ 163.0 (q, J = 1.8 Hz), 162.8, 148.3,
148.2, 145.4 (q, J = 3.0 Hz), 138.7 (q, J = 5.8 Hz), 134.9, 134.6
(q, J = 2.5 Hz), 134.3, 134.0, 129.8, 129.6, 126.1 (q, J = 31.7
Hz), 125.3 (q, J = 32.0 Hz), 124.8, 124.7, 123.9, 123.8 (q, J =
2.3 Hz), 121.7 (q, J = 272.0 Hz), 121.5 (q, J = 273.0 Hz), 53.2,
53.0. IR: 2958, 1731, 1531, 1439, 1352, 1274, 1236, 1163,
1130, 1025, 731, 678 cm-1. HRMS (AP-TOF): Calcd for
C11H8F3NO4 (m/z): 275.0405 [M]−, found: 275.0411.
[E-isomer (minor)] Yellow oil. 1H NMR (300 MHz, CDCl3)
δ 8.39 – 8.20 (m, 2H), 7.70 (d, J = 7.8 Hz, 1H), 7.65 – 7.57 (m,
1H), 7.50 (s, 1H), 3.81 (s, 3H). 19F NMR (282 MHz, CDCl3) δ
-64.7 (d, J = 1.7 Hz). 13C{1H} NMR (75 MHz, CDCl3) δ 162.8,
148.4, 135.0 (q, J = 5.8 Hz), 134.9, 134.0, 129.8, 126.1 (q, J =
31.7 Hz), 124.9, 123.9, 121.7 (q, J = 272.0 Hz), 53.0. IR: 3093,
2960, 1731, 1531, 1439, 1353, 1302, 1274, 1236, 1163, 1130,
1023, 822, 736, 676 cm-1. HRMS (AP-TOF): Calcd for
C11H8F3NO4 (m/z): 275.0405 [M]−, found: 275.0411.
o
1
[Z-isomer (minor)] Mp 45-46 C. H NMR (300 MHz,
CDCl3): δ 8.05 (s, 1H), 7.70 (d, J = 7.5 Hz, 1H), 7.64 (s, 1H),
7.62 – 7.48 (m, 2H), 3.92 (s, 3H). 19F NMR (282 MHz, CDCl3):
δ -58.5 (s). 13C{1H} NMR (75 MHz, CDCl3): δ 163.1 (q, J = 1.9
Hz), 145.5 (q, J = 3.0 Hz), 134.0, 133.3, 133.0 (q, J = 2.3 Hz),
132.2 (q, J = 2.3 Hz), 129.4, 125.1 (q, J = 32.0 Hz), 121.5 (q, J
= 272.9 Hz), 118.0, 113.1, 53.3. IR: 2958, 2237, 1731, 1648,
1439, 1391, 1282, 1125, 1131, 1042, 804, 688 cm-1. HRMS
(ES-TOF): Calcd for C12H8F3NO2Na (m/z): 278.0405 [M+Na]+,
found: 278.0402.
Methyl
(E)-3-(2-methoxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3q) and Methyl (Z)-3-(2-methoxyphenyl)-2-
(trifluoromethyl)acrylate (Z-3q). 2-Iodoanisole (0.2 mmol,
46.8 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
40/1 to 20/1, v/v), affording compound 3q in 54% yield [mix-
ture of E/Z isomers (73/27), 28.2 mg; E/Z isomers were partly
Methyl (E)-3-(m-tolyl)-2-(trifluoromethyl)acrylate (E-3o)
and Methyl (Z)-3-(m-tolyl)-2-(trifluoromethyl)acrylate (Z-
3o). 3-Iodotoluene (0.2 mmol, 43.6 mg), AgOTf (0.3 mmol,
77.1 mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(tri-
fluoromethyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0
mL) were reacted for 2 hours according to the general proce-
dure. The crude was purified by silica gel column chromatog-
raphy (petroleum ether/EtOAc, from 50/1 to 40/1, v/v), afford-
ing compound 3o in 91% yield [mixture of E/Z isomers (72/28),
44.3 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.00
(s, 1H, Z), 7.30 (s, 1H, E), 7.25 – 7.05 (m, 4H, Z + 4H, E), 3.81
1
separated by column] as a yellow oil. H NMR (300 MHz,
CDCl3): δ 8.17 (s, 1H, Z), 7.57 (s, 1H, E), 7.37 – 7.26 (m, 1H,
Z + 1H, E), 7.24 – 7.15 (m, 1H, Z + 1H, E), 6.93 – 6.79 (m, 2H,
Z + 2H, E), 3.81 (s, 3H, Z), 3.80 – 3.73 (m, 3H, Z + 3H, E), 3.65
(s, 3H, E). 19F NMR (282 MHz, CDCl3): δ -59.3 (d, J = 0.6 Hz,
Z), -64.2 (d, J = 1.7 Hz, E). 13C{1H} NMR (75 MHz, CDCl3): δ
164.1 – 164.0 (m), 163.9 (q, J = 2.1 Hz), 157.61, 157.57, 145.2
(q, J = 3.0 Hz), 137.5 (q, J = 5.9 Hz), 132.1, 132.0, 130.5 (q, J
= 3.6 Hz), 130.0, 123.0 (q, J = 30.9 Hz), 122.4 (q, J = 271.2
Hz), 122.2 (q, J = 272.4 Hz), 122.1 (q, J = 31.5 Hz), 121.9,
121.7, 110.9, 110.5, 55.64, 55.58, 52.8, 52.4. IR: 2961, 2842,
1729, 1646, 1600, 1490, 1466, 1437, 1276, 1252, 1224, 1158,
1123, 1114, 1021, 752 cm-1. HRMS (EI-TOF): Calcd for
C12H11F3O3 (m/z): 260.0660 [M]+, found: 260.0661.
(s, 3H, Z), 3.70 (s, 3H, E), 2.39 – 2.21 (s, 3H, Z + 3H, E). 19
F
NMR (282 MHz, CDCl3): δ -58.5 (s, Z), -64.3 (d, J = 1.4 Hz,
E). 13C{1H} NMR (75 MHz, CDCl3): δ 164.2 – 163.9 (m), 148.9
(q, J = 2.9 Hz), 140.6 (q, J = 5.7 Hz), 138.5, 138.1, 132.6, 132.3,
131.3, 131.1, 130.2 – 129.9 (m), 128.7, 128.3, 126.6 (q, J = 2.6
Hz), 126.2, 123.1 (q, J = 31.2 Hz), 122.29 (q, J = 31.7 Hz),
122.26 (q, J = 271.3 Hz), 122.0 (q, J = 272.7 Hz), 52.9, 52.7,
21.4. IR: 2958, 1731, 1647, 1438, 1383, 1284, 1224, 1152,
1126, 1032, 784, 694 cm-1. HRMS (EI-TOF): Calcd for
C12H11F3O2 (m/z): 244.0711 [M]+, found: 244.0714.
1
[E-isomer (major)] H NMR (300 MHz, CDCl3) δ 7.65 (s,
1H), 7.43 – 7.35 (m, 1H), 7.27 (d, J = 8.4 Hz, 1H), 6.98 – 6.88
(m, 2H), 3.85 (s, 3H), 3.74 (s, 3H). 19F NMR (282 MHz, CDCl3)
δ -64.2 (d, J = 1.7 Hz).
1
[Z-isomer (minor)] H NMR (300 MHz, CDCl3) δ 8.24 (s,
Methyl (E)-3-(3-cyanophenyl)-2-(trifluoromethyl)acry-
late (E-3p) and Methyl (Z)-3-(3-cyanophenyl)-2-(trifluoro-
methyl)acrylate (Z-3p). 3-Iodobenzonitrile (0.2 mmol, 45.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.003 mmol,
1.0 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 20/1 to
1H), 7.44 – 7.36 (m, 1H), 7.29 (d, J = 7.5 Hz, 1H), 6.97 (t, J =
7.5 Hz, 1H), 6.91 (d, J = 8.1 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H).
19F NMR (282 MHz, CDCl3) δ -59.3 (d, J = 1.1 Hz).
Methyl (E)-3-(o-tolyl)-2-(trifluoromethyl)acrylate (E-3r)
and Methyl (Z)-3-(o-tolyl)-2-(trifluoromethyl)acrylate (Z-
3r). 2-Iodotoluene (0.2 mmol, 43.6 mg), AgOTf (0.3 mmol,
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77.1 mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(tri-
The crude was purified by silica gel column chromatography
(petroleum ether/EtOAc, from 20/1 to 10/1, v/v), affording
compound 3t in 80% yield [mixture of E/Z isomers (78/22),
46.0 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.51
(s, 1H, Z), δ 8.07 (s, 1H, E), δ 8.02 (d, J = 7.8 Hz, 1H, Z + 1H,
E), 7.53 – 7.35 (m, 2H, Z + 2H, E), 7.16 (d, J = 7.5 Hz, 1H, Z +
1H, E), 3.83 (s, 6H, Z + 3H, E), 3.51 (s, 3H, E). 19F NMR (282
MHz, CDCl3): δ -58.2 (s, Z), -64.5 (d, J = 1.4 Hz, E). 13C{1H}
NMR (75 MHz, CDCl3): δ 166.5, 166.4, 163.4 (q, J = 1.7 Hz),
163.0, 150.2 (q, J = 3.2 Hz), 145.5 (q, J = 6.0 Hz), 135.9, 135.7,
132.5, 132.4, 130.8, 130.6, 129.34, 129.29, 129.1 – 128.9 (m),
128.2, 127.7, 122.7 (q, J = 31.0 Hz), 122.2 (q, J = 271.3 Hz),
122.1 (q, J = 272.8 Hz), 121.4 (q, J = 30.6 Hz), 52.9, 52.5, 52.4,
52.3. IR: 2961, 1717, 1649, 1437, 1376, 1264, 1127, 1082,
1023, 755, 700 cm-1. HRMS (EI-TOF): Calcd for C13H11F3O4
(m/z): 288.0609 [M]+, found: 288.0614.
fluoromethyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0
mL) were reacted for 2 hours according to the general proce-
dure. The crude was purified by silica gel column chromatog-
raphy (petroleum ether/EtOAc, from 50/1 to 30/1, v/v), afford-
ing compound 3r in 79% yield [mixture of E/Z isomers (65/35),
38.6 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.13
(s, 1H, Z), 7.56 (s, 1H, E), 7.26 – 7.05 (m, 4H, Z + 4H, E), 3.82
(s, 3H, Z), 3.59 (s, 3H, E), 2.24 (s, 3H, E), 2.22 (s, 3H, Z). 19
F
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NMR (282 MHz, CDCl3): δ -58.9 (s, Z), -64.5 (d, J = 1.4 Hz,
E). 13C{1H} NMR (75 MHz, CDCl3): δ 163.6 (q, J = 1.7 Hz),
163.6 – 163.4 (m), 148.5 (q, J = 3.0 Hz), 141.3 (q, J = 5.7 Hz),
136.7, 136.0, 132.6, 132.3, 130.3, 130.01, 129.95, 129.8, 128.3
(q, J = 3.1 Hz), 128.0, 125.9, 125.7, 124.6 (q, J = 30.9 Hz),
123.6 (q, J = 31.2 Hz), 122.1 (q, J = 271.4 Hz), 122.0 (q, J =
272.9 Hz), 52.9, 52.5, 20.0, 19.8. IR: 2961, 1732, 1647, 1438,
1379, 1294, 1276, 1238, 1216, 1160, 1129, 1032, 1021, 751 cm-
1. HRMS (ES-TOF): Calcd for C12H11F3O2Na (m/z): 267.0609
[M+Na]+, found: 267.0613.
Methyl
(E)-3-(3,5-dichlorophenyl)-2-(trifluorome-
thyl)acrylate (E-3u) and Methyl (Z)-3-(3,5-dichlorophenyl)-
2-(trifluoromethyl)acrylate (Z-3u). 3,5-Dichloroiodobenzene
(0.2 mmol, 54.6 mg), AgOTf (0.3 mmol, 77.1 mg), and
Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluorome-
thyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were
reacted for 2 hours according to the general procedure. The
crude was purified by silica gel column chromatography (petro-
leum ether/EtOAc, from 60/1 to 50/1, v/v), affording compound
3u in 90% yield [mixture of E/Z isomers (74/26), 54.1 mg] as a
yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.88 (s, 1H, Z), 7.35
– 7.29 (m, 1H, Z + 1H, E), 7.25 (s, 1H, E), 7.21 – 7.12 (m, 2H,
Z + 2H, E), 3.83 (s, 3H, Z), 3.73 (s, 3H, E). 19F NMR (282 MHz,
CDCl3): δ -58.6 (s, Z), -64.7 (d, J = 1.7 Hz, E). 13C{1H} NMR
(75 MHz, CDCl3): δ 163.1 (q, J = 1.7 Hz), 162.9 – 162.8 (m),
145.2 (q, J = 3.0 Hz), 138.1 (q, J = 5.8 Hz), 135.5, 135.4, 135.2,
130.1, 129.9, 127.3, 127.1 (q, J = 2.4 Hz), 126.0 (q, J = 31.7
Hz), 125.1 (q, J = 32.1 Hz), 121.7 (q, J = 271.9 Hz), 121.4 (q,
J = 273.0 Hz), 53.2, 53.0. IR: 3087, 2954, 1734, 1653, 1587,
1562, 1439, 1377, 1285, 1216, 1167, 1134, 1025, 861, 802, 678
cm-1. HRMS (ES-TOF): Calcd for C11H735Cl2F3O2Na (m/z):
320.9673 [M+Na]+, found: 320.9666.
Methyl (E)-3-(2-nitrophenyl)-2-(trifluoromethyl)acrylate
(E-3s) and Methyl (Z)-3-(2-nitrophenyl)-2-(trifluorome-
thyl)acrylate (Z-3s). 1-Iodo-2-nitrobenzene (0.2 mmol, 49.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol,
6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 15/1 to
8/1, v/v), affording compound 3s in 86% yield [mixture of E/Z
isomers (64/36), 47.3 mg; among which, partly pure compound
1
Z-3s was obtained] as a yellow oil. H NMR (300 MHz,
CDCl3): δ 8.46 (s, 1H, Z), 8.32 – 8.22 (m, 1H, Z + 1H, E), 8.04
(s, 1H, E), 7.75 – 7.55 (m, 2H, Z + 2H, E), 7.33 (t, J = 7.8 Hz,
1H, Z + 1H, E), 3.92 (s, 3H, Z), 3.61 (s, 3H, E). 19F NMR (282
MHz, CDCl3): δ -58.6 (s, Z), -64.8 (d, J = 1.7 Hz, E). 13C{1H}
NMR (75 MHz, CDCl3): δ 162.7 (q, J = 1.5 Hz), 162.1, 146.5,
146.2 (q, J = 3.2 Hz), 145.9, 142.9 (q, J = 6.3 Hz), 134.1, 133.9,
130.4 130.3, 130.2, 130.1 (q, J = 2.7 Hz), 129.9 – 129.8 (m),
124.98, 124.95, 124.0 (q, J = 31.4 Hz), 123.0 (q, J = 31.0 Hz),
121.73 (q, J = 271.5 Hz), 121.70 (q, J = 272.9 Hz), 53.1, 52.5.
IR: 2961, 1731, 1524, 1439, 1343, 1277, 1236, 1131, 1045,
1024, 865, 789, 793 cm-1. HRMS (CI-TOF): Calcd for
C11H9F3NO4 (m/z): 276.0484 [M+H]+, found: 276.0480.
Methyl (E)-3-(naphthalen-2-yl)-2-(trifluoromethyl)acry-
late (E-3v) and methyl (Z)-3-(naphthalen-2-yl)-2-(trifluoro-
methyl)acrylate (Z-3v). 2-Iodonaphthalene (0.2 mmol, 50.8
mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol,
6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2
mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours according
to the general procedure. The crude was purified by silica gel
column chromatography (petroleum ether/EtOAc, from 60/1 to
50/1, v/v), affording compound 3v in 80% yield [mixture of E/Z
isomers (74/26), 44.7 mg; among which, partly pure compound
o
[Z-isomer (minor)] Pale yellow solid. Mp 77-78 C. 1H
NMR (300 MHz, CDCl3) δ 8.46 (s, 1H), 8.28 (dd, J = 8.3, 1.4
Hz, 1H), 7.71 (td, J = 7.5, 1.5 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H),
7.35 (d, J = 7.8 Hz, 1H), 3.93 (s, 3H). 19F NMR (282 MHz,
CDCl3) δ -58.6 (s). 13C{1H} NMR (75 MHz, CDCl3) δ 162.7 (q,
J = 1.5 Hz), 146.2 (q, J = 3.2 Hz), 146.0, 134.0, 130.4, 130.1
(q, J = 2.7 Hz), 130.0, 125.0, 123.1 (q, J = 31.0 Hz), 121.7 (q,
J = 272.9 Hz), 53.1. IR: 2974, 2921, 2855, 1731, 1611, 1525,
1440, 1386, 1338, 1284, 1265, 1154, 1126, 1052, 728 cm-1.
HRMS (CI-TOF): Calcd for C11H9F3NO4 (m/z): 276.0484
[M+H]+, found: 276.0481.
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E-3v was obtained] as a yellow solid. H NMR (300 MHz,
CDCl3): δ 8.27 (s, 1H, Z), 7.93 – 7.79 (m, 4H, Z + 4H, E), 7.62
– 7.41 (m, 3H, Z + 4H, E), 3.94 (s, 3H, Z), 3.81 (s, 3H, E). 19
F
NMR (282 MHz, CDCl3): δ -58.3 (s, Z), -64.2 (d, J = 1.4 Hz,
E). 13C{1H} NMR (75 MHz, CDCl3): δ 164.1 – 164.0 (m), 148.7
(q, J = 2.9 Hz), 140.7 (q, J = 5.7 Hz), 134.1, 133.9, 133.0, 132.7,
130.4, 130.3 (q, J = 2.1 Hz), 130.0, 129.8, 128.8, 128.7, 128.4,
128.1, 127.85, 127.83, 127.8, 126.94, 127.89, 126.1 (q, J = 2.7
Hz), 125.4, 123.2 (q, J = 31.2 Hz), 122.39 (q, J = 31.8 Hz),
122.35 (q, J = 271.5 Hz), 122.1 (q, J = 272.6 Hz), 52.9, 52.7.
IR: 2956, 2924, 1728, 1643, 1438, 1352, 1282, 1269, 1233,
1122, 1019, 815, 744, 475 cm-1. HRMS (EI-TOF): Calcd for
C15H11F3O2 (m/z): 280.0711 [M]+, found: 280.0707.
Methyl (E)-2-(3,3,3-trifluoro-2-(methoxycarbonyl)prop-
1-en-1-yl)benzoate (E-3t) and Methyl (Z)-2-(3,3,3-trifluoro-
2-(methoxycarbonyl)prop-1-en-1-yl)benzoate (Z-3t). Methyl
2-iodobenzoate (0.2 mmol, 52.4 mg), AgOTf (0.3 mmol, 77.1
mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluoro-
methyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL)
were reacted for 2 hours according to the general procedure.
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[E-isomer (major)] Mp <46 oC. 1H NMR (300 MHz,
crude was purified by silica gel column chromatography (petro-
CDCl3): δ 7.91 – 7.81 (m, 4H), 7.61 – 7.50 (m, 3H), 7.44 (dd, J
= 8.7, 1.5 Hz, 1H), 3.81 (s, 3H). 19F NMR (282 MHz, CDCl3):
δ -64.2 (d, J = 1.4 Hz).
leum ether/EtOAc, from 10/1 to 5/1, v/v), affording compound
3y in 89% yield [mixture of E/Z isomers (75/25), 57.0 mg] as a
yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.97 (s, 1H, Z), 7.28
(s, 1H, E), 6.80 – 6.54 (m, 2H, Z + 2H, E), 3.99 – 3.67 (m, 12H,
Z + 12H, E). 19F NMR (282 MHz, CDCl3): δ -58.2 (s, Z), -64.1
(d, J = 1.4 Hz, E). 13C{1H} NMR (75 MHz, CDCl3): δ 164.3 –
164.1 (m), 164.0 (q, J = 2.2 Hz), 153.2, 153.0, 148.4 (q, J = 2.9
Hz), 140.2, 140.1, 139.9 (q, J = 5.7 Hz), 127.5, 127.4, 122.4 (q,
J = 31.3 Hz), 122.2 (q, J = 271.4 Hz), 122.0 (q, J = 271.5 Hz),
121.5 (q, J = 32.1 Hz), 107.3 (q, J = 2.6 Hz), 106.8, 61.0, 60.98,
56.2, 56.18, 52.8, 52.77. IR: 2954, 2842, 1729, 1582, 1507,
1456, 1422, 1271, 1227, 1118, 1026, 1002 cm-1. HRMS (ES+):
Calcd for C14H15F3O5Na (m/z): 343.0769 [M+Na]+, found:
343.0766.
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Methyl
(E)-3-(3,4-dimethoxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3w) and Methyl (Z)-3-(3,4-dimethoxy-
phenyl)-2-(trifluoromethyl)acrylate (Z-3w). 4-Iodo-1,2-di-
methoxybenzene (1.0 mmol, 264.1 mg), AgOTf (1.5 mmol,
385.4 mg), and Pd(TFA)2 (0.015 mmol, 4.8 mg), methyl 2-(tri-
fluoromethyl)acrylate (1.5 mmol, 231.1 mg) in 1,4-dioxane (5.0
mL) were reacted for 2 hours according to the general proce-
dure. The crude was purified by silica gel column chromatog-
raphy (petroleum ether/EtOAc, from 10/1 to 5/1, v/v), affording
compound 3w in 83% yield [mixture of E/Z isomers (E/Z =
75/25), 242.2 mg] as a yellow oil. 1H NMR (300 MHz, CDCl3):
δ 7.98 (s, 1H, Z), 7.30 (s, 1H, E), 7.10 – 6.96 (m, 2H, Z + 2H,
E), 6.93 – 6.80 (m, 1H, Z + 1H, E), 3.93 – 3.89 (m, 3H, Z + 3H,
E), 3.89 – 3.83 (m, 6H, Z + 3H, E), 3.81 (s, 3H, E). 19F NMR
(282 MHz, CDCl3): δ -58.3 (s, Z), -63.8 (d, J = 1.7 Hz, E).
13C{1H} NMR (75 MHz, CDCl3): δ 164.5 – 164.2 (m), 151.32,
151.29, 148.9, 148.6, 148.4 (q, J = 2.9 Hz), 140.4 (q, J = 5.7
Hz), 124.8, 124.8 – 124.6 (m), 124.1, 122.5 (q, J = 271.2 Hz),
122.3 (q, J = 272.2 Hz), 120.6 (q, J = 31.1 Hz), 119.8 (q, J =
32.0 Hz), 112.9 (q, J = 3.0 Hz), 112.1, 110.9, 110.7, 56.0, 56.9,
52.75, 52.66. IR: 2958, 2842, 1726, 1599, 1515, 1440, 1258,
1225, 1140, 1117, 1020, 808, 574 cm-1. HRMS (AP-TOF):
Calcd for C13H14F3O4 (m/z): 291.0844 [M+H]+, found:
291.0851.
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Methyl
(E)-3-(3,4-dihydroxyphenyl)-2-(trifluorome-
thyl)acrylate (E-3z) and Methyl (Z)-3-(3,4-dihydroxy-
phenyl)-2-(trifluoromethyl)acrylate (Z-3z). 1.0 mg Pd(TFA)2
was dissolved in 3.0 mL 1,4-dioxane by ultrasound. 4-Iodoben-
zene-1,2-diol (0.2 mmol, 47.2 mg), AgOTf (0.3 mmol, 77.1
mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2 mg),
and 1.0 mL the above prepared Pd(TFA)2/1,4-dioxane solution
[0.5 mol% Pd(TFA)2] were reacted for 30 min. After evapora-
tion of solvents, the crude was purified by silica gel column
chromatography (CHCl3/MeOH, from 100/1 to 60/1, v/v), af-
fording compound 3z in 45% yield [mixture of E/Z isomers
(E/Z = 71/29), 23.7 mg] as a pale yellow solid. 1H NMR (300
MHz, CD3OD): δ 7.94 (s, 1H, Z), 7.28 ((d, J = 1.2 Hz, 1H, E),
7.00 (s, 1H, Z), 6.98 – 6.71 (m, 2H, Z + 3H, E), 3.84 (s, 3H, Z),
3.82 (s, 3H, E). 19F NMR (282 MHz, CD3OD): δ -59.2 (s, Z), -
64.7 (d, J = 1.4 Hz, E). 13C{1H} NMR (75 MHz, CD3OD): δ
166.2 – 166.0 (m), 165.7 (q, J = 2.3 Hz), 150.2 (q, J = 2.9 Hz),
150.0, 149.8, 146.5, 146.3, 141.2 (q, J = 5.8 Hz), 125.4 (q, J =
2.4 Hz), 125.0, 124.5, 124.1 (q, J = 269.9 Hz), 123.8 (q, J =
270.5 Hz), 120.2 (q, J = 31.1 Hz), 119.1 (q, J = 32.1 Hz), 118.3
(q, J = 3.2 Hz), 117.0, 116.3, 116.1, 53.1, 53.0. IR: 3508, 3338,
1694, 1602, 1524, 1443, 1255, 1112, 1023, 933 cm-1. HRMS
(ES-TOF): Calcd for C11H8F3O4 (m/z): 261.0375 [M-H]−,
found: 261.0365.
Methyl
(E)-2-amino-5-(3,3,3-trifluoro-2-(methoxycar-
bonyl)prop-1-en-1-yl)benzoate (E-3x) and Methyl (Z)-2-
amino-5-(3,3,3-trifluoro-2-(methoxycarbonyl)prop-1-en-1-
yl)benzoate (Z-3x). Methyl 2-amino-5-iodobenzoate (0.2
mmol, 55.4 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2
(0.02 mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3
mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2
hours according to the general procedure. The crude was puri-
fied by silica gel column chromatography (petroleum
ether/EtOAc, from 10/1 to 5/1, v/v), affording compound 3x in
81% yield [mixture of E/Z isomers (63/37), 49.3 mg] as a yel-
low solid. 1H NMR (300 MHz, CDCl3): δ 8.19 – 7.95 (m, 1H,
Z + 1H, E), 7.89 (s, 1H, Z), 7.41 (t, J = 8.0 Hz, 1H, Z + 1H, E),
7.23 (s, 1H, E), 6.76 – 6.55 (m, 1H, Z + 1H, E), 6.18 (br, 2H, Z
+ 2H, E), 3.92 – 3.78 (m, 6H, Z + 6H, E). 19F NMR (282 MHz,
CDCl3): δ -58.4 (s, Z), -63.4 (d, J = 1.7 Hz, E). 13C{1H} NMR
(75 MHz, CDCl3): δ 168.0, 167.9, 164.6 (q, J = 2.3 Hz), 164.5,
152.4, 152.3, 148.1 (q, J = 2.7 Hz), 140.7 (q, J = 5.8 Hz), 136.3
(q, J = 2.2 Hz), 136.0 (q, J = 3.8 Hz), 135.3, 135.2, 122.8 (q, J
= 270.8 Hz), 122.6 (q, J = 271.8 Hz), 119.8, 119.7, 118.3 (q, J
= 30.9 Hz), 117.5 (q, J = 32.3 Hz), 116.7, 116.6, 110.2, 110.1,
52.6, 52.5, 51.92, 51.88. IR: 3477, 3364, 2961, 1722, 1694,
1610, 1499, 1440, 1278, 1256, 1202, 1152, 1116, 1024, 825,
546, 492 cm-1. HRMS (ES-TOF): Calcd for C13H12F3NO4Na
(m/z): 326.0616 [M+Na]+, found: 326.0622.
Synthesis of Iodoarenes 1w and 1z
Iodoarenes 1y and 1z were prepared according to a reported
method.25a Analytical data of 1w and 1z are in agreement with
those reported in the literature.
4-Iodo-1,2-dimethoxybenzene (1y).25a 1H NMR (300 MHz,
CDCl3): δ 7.22 (dd, J = 8.4, 1.5 Hz, 1H), 7.11 (d, J = 1.5 Hz,
1H), 6.61 (d, J = 8.4 Hz, 1H), 3.85 (s, 3H), 3.84 (s, 3H).
4-Iodobenzene-1,2-diol (1z).25b 1H NMR (300 MHz,
CDCl3): δ 7.19 (d, J = 1.8 Hz, 1H), 7.12 (dd, J = 8.4, 1.8 Hz,
1H), 6.63 (d, J = 8.4 Hz, 1H), 5.13 (s, 1H), 5.10 (s, 1H).
Characterization data for 3-CF3-coumarins 4:
3-(Trifluoromethyl)-2H-chromen-2-one (4a). 2-Iodophe-
nol (0.2 mmol, 44.0 mg), AgOTf (0.3 mmol, 77.1 mg), and
Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(trifluorome-
thyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were
reacted for 2 hours according to the general procedure. The
crude was purified by silica gel column chromatography (petro-
leum ether/EtOAc, from 20/1 to 10/1, v/v), affording compound
4 in 72% yield (30.8 mg) as a pale yellow solid. Mp 121-122
oC. 1H NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.75 – 7.57 (m,
Methyl
(E)-2-(trifluoromethyl)-3-(3,4,5-trimethoxy-
phenyl)acrylate (E-3y) and Methyl (Z)-2-(trifluoromethyl)-
3-(3,4,5-trimethoxyphenyl)acrylate (Z-3y). 5-Iodo-1,2,3-tri-
methoxybenzene (0.2 mmol, 58.8 mg), AgOTf (0.3 mmol, 77.1
mg), and Pd(TFA)2 (0.003 mmol, 1 mg), methyl 2-(trifluorome-
thyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0 mL) were
reacted for 2 hours according to the general procedure. The
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2H), 7.49 – 7.31 (m, 2H). 19F NMR (282 MHz, CDCl3): δ -66.7
Supporting Information
(s). 13C{1H} NMR (75 MHz, CDCl3): δ 156.1 – 155.9 (m),
154.7, 143.5 (q, J = 4.8 Hz), 134.6, 129.6, 125.4, 121.5 (q, J =
270.3 Hz), 118.0 (q, J = 33.1 Hz), 117.1, 116.9. IR: 3074, 2921,
1727, 1636, 1610, 1573, 1460, 1383, 1242, 1175, 1119, 975,
759, 733, 588, 464 cm-1. HRMS (ES-TOF): Calcd for
C10H5F3O2Na (m/z): 237.0139 [M+Na]+, found: 237.0132.
The Supporting Information is available free of charge on the ACS
Publications website.
Optimization tables, NMR spectra of new compounds, X-ray crys-
tallography data and CIF files (PDF).
AUTHOR INFORMATION
Corresponding Author
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8-Methoxy-2-oxo-3-(trifluoromethyl)-2H-chromene-6-
carbaldehyde (4b) 5-Iodovanillin (0.2 mmol, 55.6 mg), AgOTf
(0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), me-
thyl 2-(trifluoromethyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-di-
oxane (1.0 mL) were reacted for 2 hours according to the gen-
eral procedure. The crude was purified by silica gel column
chromatography (petroleum ether/EtOAc, from 5/1 to 3/1, v/v),
and was subsequently washed with MeOH (0.5 mL × 2), afford-
ing compound 4b in 35% yield (18.8 mg) as a white solid. Mp
*E-mails : jean-philippe.bouillon@univ-rouen.fr;
samuel.couve-bonnaire@insa-rouen.fr
ORCID
Jean-Philippe Bouillon : 0000-0002-6274-1125
Samuel Couve-Bonnaire : 0000-0003-2149-0849
Author Contributions
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manu-
script.
Notes
1
162-163 oC. H NMR [300 MHz, (CD3)2SO]: δ 10.01 (s, 1H),
8.87 (s, 1H), 8.05 (s, 1H), 7.83 (s, 1H), 4.02 (s, 3H). 19F NMR
[282 MHz, (CD3)2SO]: δ -64.9 (s). 13C{1H} NMR [75 MHz,
(CD3)2SO]: δ 191.3, 155.0 – 154.7 (m), 147.4, 147.1, 145.1 (q,
J = 4.8 Hz), 132.8, 124.3, 121.5 (q, J = 269.9 Hz), 117.8, 116.8
(q, J = 32.4 Hz), 114.4, 56.3. IR: 3067, 2868, 1738, 1698, 1636,
1593, 1464, 1384, 1278, 1134, 1112, 952, 684 cm-1. HRMS
(AP-TOF): Calcd for C12H7F3O4 (m/z): 272.0296 [M]−, found:
272.0301.
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was partially supported by INSA Rouen, Rouen Univer-
sity, CNRS, EFRD, Labex SynOrg (ANR-11-LABX-0029), and
Région Haute-Normandie (Crunch Network). P. X. thanks the CSC
(China Scholarship Council) for a doctoral fellowship.
6-Chloro-3-(trifluoromethyl)-2H-chromen-2-one (4c) 4-
Chloro-2-iodophenol (0.2 mmol, 50.9 mg), AgOTf (0.3 mmol,
77.1 mg), and Pd(TFA)2 (0.02 mmol, 6.5 mg), methyl 2-(tri-
fluoromethyl)acrylate (0.3 mmol, 46.2 mg) in 1,4-dioxane (1.0
mL) were reacted for 2 hours according to the general proce-
dure. The crude was purified by silica gel column chromatog-
raphy (petroleum ether/EtOAc, from 20/1 to 10/1, v/v), afford-
ing compound 4c in 74% yield (36.8 mg) as a white solid. Mp
167-168 oC. 1H NMR (300 MHz, CD3OD): δ 8.49 (s, 1H), 7.86
(d, J = 2.4 Hz, 1H), 7.72 (dd, J = 9.0, 2.4 Hz, 1H), 7.42 (d, J =
9.0 Hz, 1H). 19F NMR (282 MHz, CD3OD): δ -67.7 (s). 13C{1H}
NMR (75 MHz, CD3OD): δ 157.0 – 156.9 (m), 154.5, 144.7 (q,
J = 5.0 Hz), 135.3, 131.4, 130.3, 122.9 (q, J = 269.4 Hz), 119.7,
119.5, 119.2 (q, J = 33.0 Hz). IR: 3064, 1721, 1635, 1602, 1570,
1378, 1301, 1243, 1213, 1175, 1144, 1086, 980, 824, 679 cm-1.
HRMS (EI-TOF): Calcd for C10H435ClF3O2 (m/z): 247.9852
[M]+, found: 247.9853.
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in the Copper-Catalyzed Trifluoromethylation of Boronic Acids with
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(3) For review of the synthesis of CF3-alkenes see: (a) Egami, H.;
Sodeoka, M. Trifluoromethylation of Alkenes with Concomitant Intro-
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(4) For some applications of CF3-alkenes see: (a) Ma, J.; Yi, W.;
Lu, G.; Cai, C. Decarboxylative and Denitrative Trifluoromethylation
for the Synthesis of Cvinyl-CF3 Compounds with Togni (II) Reagent.
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Desroches, J.; Paquin, J.-F. Introduction of the 4,4,4-Trifluorobut-2-
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Hafner, A.; Brase, S. Efficient Trifluoromethylation of Activated and
Methyl 2-oxo-3-(trifluoromethyl)-2H-chromene-6-car-
boxylate (4d) Methyl 4-hydroxy-3-iodobenzoate (0.2 mmol,
55.6 mg), AgOTf (0.3 mmol, 77.1 mg), and Pd(TFA)2 (0.02
mmol, 6.5 mg), methyl 2-(trifluoromethyl)acrylate (0.3 mmol,
46.2 mg) in 1,4-dioxane (1.0 mL) were reacted for 2 hours ac-
cording to the general procedure. The crude was purified by sil-
ica gel column chromatography (petroleum ether/EtOAc, from
10/1 to 5/1, v/v), affording compound 4d in 82% yield (44.7
o
1
mg) as a white solid. Mp 177-178 C. H NMR [300 MHz,
(CD3)2SO]: δ 8.89 (s, 1H), 8.55 (d, J = 1.8 Hz, 1H), 8.24 (dd, J
= 8.7, 2.1 Hz, 1H), 7.59 (d, J = 8.7 Hz, 1H), 3.90 (s, 3H). 19F
NMR [282 MHz, (CD3)2SO]: δ -64.9 (s). 13C{1H} NMR [75
MHz, (CD3)2SO]: δ 164.8, 157.0, 155.4 – 155.2 (m), 144.9 (q,
J = 4.9 Hz), 134.7, 132.0, 126.3, 121.6 (q, J = 270.0 Hz), 117.2,
117.1, 116.6 (q, J = 32.3 Hz), 52.6. IR: 3073, 2965, 2924, 2852,
1750, 1710, 1639, 1615, 1443, 1378, 1306, 1243, 1216, 1172,
1140, 965, 768 cm-1. HRMS (EI-TOF): Calcd for C12H7F3O4
(m/z): 272.0296 [M]+, found: 272.0294.
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