Synthesis of α-Fluorinated Acrylates by a Palladium-Catalyzed Decarboxylative Olefination Reaction

Article abstract of DOI:10.1002/ejoc.201701709

Ligand-free palladium-catalyzed subsequent decarboxylation/olefination reaction between 2-fluorinated acrylates and benzoic acids is reported. Valuable trisubstituted 2-fluoroacrylates and 2-trifluoromethylacrylates were produced in low to excellent yield

Full text of DOI:10.1002/ejoc.201701709

A Journal of
Accepted Article
Title: Synthesis of alpha-fluorinated acrylates by Palladium-catalyzed
Decarboxylative Olefination Reaction
Authors: Ouafa Bouazzaoui, kévin rousée, Joseph Kajima Mulengi,
xavier pannecoucke, jean-philippe bouillon, and Samuel
Couve-Bonnaire
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701709
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
Synthesis of α-Fluorinated Acrylates by Palladium-Catalyzed
Decarboxylative Olefination Reaction
Ouafa Bouazzaoui,[a,b] Kevin Rousée,[a] Joseph Kajima Mulengi,[b] Xavier Pannecoucke,[a] Jean-Philippe
Bouillon,[a]* and Samuel Couve-Bonnaire[a]*
Abstract:
Ligand-free
palladium-catalyzed
subsequent
pioneering report of Myers,[8]
a decade ago, about the
decarboxylation/olefination reaction between 2-fluorinated acrylates
and benzoic acids is reported. Valuables trisubstituted 2-
fluoroacrylates and 2-trifluoromethylacrylates were produced in low to
excellent yields, constituting a new interesting greener synthetic
alternative to these fluorinated molecules.
decarboxylation/olefination reaction between aryl carboxylic acids
and alkenes using simple catalytic system seemed interesting for
the formation of fluorinated acrylates. We report herein, the
ligand-free
palladium-catalyzed
decarboxylation/olefination
reaction between 2-fluoroacrylates or 2-trifluoromethylacrylates
and arylcarboxylic acids for the production of polysubstituted
relevant fluorinated acrylates
Introduction
Results and Discussion
Organofluorine chemistry has dramatically blossomed over the
past decade and is now one of the most active research areas in
organic synthesis. One of the main reasons of this impressive rise
most certainly lies in the strong implications of fluorinated
molecules in many areas of research and science (medicinal
chemistry, medical imaging, agrochemistry, materials...).[1]
Among the organofluorinated compounds, the fluoroacrylates
family emerged as a relevant class of compounds with many
different applications.[2] The fluoroacrylates are commonly
synthesized by olefination reaction[3] and we recently reported the
efficient Mizoroki-Heck reaction[4] between iodoarenes and α-
fluoroacrylates as an effective synthetic alternative to these
valuable compounds. In our program devoted to develop new
routes to fluoroacrylates, we turned out our attention to the
decarboxylative/olefination process which appeared as a new
interesting greener way to obtain the targeted fluoroacrylates.
Indeed, decarboxylative cross-coupling[5] usually involved
carboxylic acids, which are common and available reagents, as
coupling partners allowing to avoid a) the use of halogenated or
“pseudo-halogenated” substrates or b) the use of expensive
organometallic reagents or the preformation of sensitive
organometallic partner. Moreover, the release of CO2 as a by-
product compared to possible toxic by-products generated by
classical cross-coupling reactions makes the decarboxylative
reaction a more “green” process. These last years carboxylic
acids have been extensively used in various catalytic reactions
such as arylation,[5,6] olefination[5,7]…In that context, the
Taking into account that at least one ortho-substituent was
required for decarboxylation reaction to proceed,[5,7,8] we began to
study the decarboxylative/olefination reaction with 2-
methoxybenzoic acid as a model substrate.[9] We started the
screening of experimental conditions using the Myers’s conditions
leading to poor 23% yield (Table 1, entry 1). The replacement of
DMF by DMA allowed a slight increase of the reaction yield (Table
1, entry 2). The use of 1,4-dioxane in combination with DMSO
enabled us to get a high 80% yield of 3a (Table 1, entry 3). The
use of 1,4-dioxane alone led to 55% yield whereas DMSO alone
did not furnish the desired product (Table 1, entries 4-5).
Table 1. Optimization of the palladium-catalyzed decarboxylation/olefination
reaction with methyl 2-fluoroacrylate 2.
Entry
Solvent (95/5)
[Pd]
Time (h)
Yield[a]
1
2
3
4
5
6
DMF/DMSO
DMA/DMSO
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
4
4
23
31
1,4-Dioxane/DMSO
DMSO
4
80
4
0
55
[a]
[b]
Normandie Université, COBRA, UMR 6014 et FR 3038, Université
de Rouen, INSA Rouen, CNRS
1 rue Tesnière, 76821 Mont Saint-Aignan Cedex, France
E-mail: samuel.couve-bonnaire@insa-rouen.fr, jean-
philippe.bouillon@univ-rouen.fr
Laboratoire de Chimie Organique Substances Naturelles et
Analyses (COSNA), Université de Tlemcen, 13000 Tlemcen,
Algérie.
1,4-Dioxane
4
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
12
12
12
12
100 (92)
68 (63)
26
7[b
]
8[c
]
9[d
7
]
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
implied the non-reoxidation of palladium at the end of the catalytic
cycle furnishing only 11% yield of 3a (Scheme 1, Eq. 5). Although
this side-reaction was not the heart of this manuscript, it seemed
important to communicate about it.
10
11[e
12
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
1,4-Dioxane/DMSO
12
12
12
12
12
12
12
12
12
0
0
]
Pd(TFA)2
Pd(OAc)2
PdCl2
72 (66)
50
13
14
PdBr2
50
15
Pd(acac)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
20
16[f]
78 (71)
30
17[g
]
18[h
52 (48)
]
[a]19F NMR yields, isolated yields in bracket. [b]1,4-Dioxane/DMSO (90:10). [c]
2
equiv of Ag2CO3. [d]10 mol% of Pd(TFA)2. [e]With K2CO3 as base. [f]Reaction
carried out at 130°C. [g]Reaction carried out at 100°C. [h]Ratio 1a/2 = 1.5/1.
Extended reaction time to 12h allowed us to get a complete
conversion with an excellent isolated yield of 92% in 3a (Table 1,
entry 6). The modification of 1,4-dioxane/DMSO ratio to 90:10 or
the use of only 2 equivalents of base as well as the use of 10
mol% catalyst only led to lower yields (Table 1, entries 7-9). The
presence of palladium catalyst as well as silver carbonate was
crucial for the reaction to succeed (Table 1, entries 10-11). The
change of palladium source (Table 1, entries 12-15) did not
improve yields, giving evidence that palladium triflate was more
adapted for this kind of reaction, as already demonstrated in Fu
and Liu’s report.[10] Finally, the modification of the reaction
temperature (Table 1, entries 16-17) or the change of 1a/2 ratio
(Table 1, entry 18) did not allow increasing the reaction yield.
Then, we tried to add some common ligands in order to modify
the catalytic sphere of the palladium to improve the former results.
Nevertheless, the use of ligand proved to be detrimental to the
reaction. The use of nitrogen-based ligand (phenanthroline) or
trialkylphosphine (PCy3, 1,2-bis(dicyclohexylphosphino)ethane
(dcpe), P(t-Bu)3) only led to non-reaction or poor NMR yield
(<40%). The use of more common triphenylphosphine as a ligand
led to an intriguish mixture of products, i.e. 3a along with methyl
3-phenyl-2-fluoroacrylate A (Scheme 1, Eq. 1) whereas the use
of tris(o-methoxyphenyl)phosphine as a ligand led to a NMR yield
superior to 100% of 3a (Scheme 1, Eq. 2). Regarding the literature
precedent, it appears that our experimental conditions were
closed to those used in palladium-catalyzed oxidative olefination
reaction of triarylphosphines with alkenes via C-P bond cleavage.
Indeed, this kind of reaction was already reported by several
authors as early as the sixties[11] and more recently
triarylphosphine was used in various catalytic reactions as a
source of aryl moiety.[12] So, our side-product would come from
the C-H activation of the aryl moiety of the phosphine ligand
followed by phosphorous-carbon bond cleavage to give an aryl-
palladium reactive intermediate. To confirm this hypothesis, we
Scheme 1. Effect of the addition of triarylphosphines on the
decarboxylation/olefination reaction (NMR yields indicated).
Nevertheless, to prevent any undesired side reaction, we decided
to use the ligand-free optimal experimental conditions (Table 1,
entry 6) to study the scope of the reaction. It is worth noting that
it was not necessary to carry out the reaction under inert
atmosphere or using dry vials strongly simplifying the
experimental procedure.
Pd(TFA)2 (20 mol%)
Ag2CO3 (3 equiv)
COOH
CO2Me
CO2Me
F
F
1,4-dioxane/DMSO (95/5)
120 °C, 12h
R
R
1
2 (1.5 equiv)
3 (Z/E: > 95/5)
OMe
OMe
OMe
CO2Me
CO2Me
CO2Me
F
F
OMe
MeO
F
3b
, 98% (100%)
95% (100%)[a]
3c, 86% (90%)
3a, 92% (100%)
Me
OBn
OEt
CO2Me
CO2Me
CO2Me
F
F
F
Me
Me
3f, 89% (90%)
3e
, 65% (67%)
3d
, 76% (87%)
unreactive
OH
OMe
CO2Me
MeO
CO2Me
F
F
(0%)
(6%)
Scheme 2. Scope of decarboxylation/olefination reaction with electron rich
carboxylic acids (isolated yields indicated, NMR yields under brackets). [a]On 1.2
mmol of acid 1b.
engaged
only
tris(o-methoxyphenyl)phosphine
with
2-
fluoroacrylate 2, without any use of carboxylic acid 1a. Under our
experimental conditions we were able to obtain the corresponding
product 3a in good yield. (Scheme 1, Eq. 3). As expected, the
absence of palladium did not allow the C-H activation step
(Scheme 1, Eq. 4) whereas the absence of silver carbonate
First, we studied electron-rich benzoic acids (Scheme 2). Good
results were obtained with 2-methoxy (1a), 2,6-dimethoxy (1b)
and 2,4-dimethoxybenzoic acids (1c). The use of 2-ethoxy (1d)
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
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as well as the valuable 2-benzyloxybenzoic acids (1e) proved to
be compatible yielding products 3d and 3e in 76% and 65%,
respectively. 2,4,6-Trimethylbenzoic acid (1f) proved also to be
highly reactive furnishing product 3f in 89% yield. Nevertheless,
some enriched substrates revealed to be unreactive such as 2-
hydroxy- or more surprisingly 2,3-dimethoxybenzoic acids.
Next, we turned our attention to halogenated benzoic acids
(Scheme 3). 2,6-Difluorobenzoic acid 1g furnished the product 3g
in good 82% yield. To get fair yield with valuable 2-bromo-6-
fluorobenzoic acid 1h, it was necessary to decrease the reaction
time to 6h at 140°C allowing us to get product 3h in 45% yield. It
has to be noted that no side-reaction occurred at the bromo
position.
and 54% of 3o respectively, without any side reactions at the
halogenated position. Introducing an electron-donating methoxy
group did not really increase the reaction yield producing the 2-
fluoroacrylate 3p in 55% yield at 140°C for 6h. Moving the
methoxy group in position 5 gave the product 3q in 35% yield.
Taking into account, all these results, it was rather difficult to
rationalize them in terms of steric or electronic effect.
Scheme 4. Scope of decarboxylation/olefination reaction with electron-poor
carboxylic acids (isolated yields indicated, NMR yields under brackets).
[a](Z)/(E): 81:19. [b]On 0.8 mmol of acid 1m, (Z)/(E): 90/10. [c]At 140°C for 6h.
While numerous catalytic systems were described to do such
decarboxylation/olefination
reaction,[4,7]
with
our
(Pd(TFA)2/Ag2CO3) system we assume that the mechanism
should occur, as previously reported by Myers[8] and later
supported by Fu and Liu’s report[10], in four steps: a first
decarboxylation step and concomitant formation of arylpalladium
species, followed by olefin insertion, β-H elimination and
regeneration of Pd(II) active catalyst by the oxidant (Ag2CO3). The
latter being supported by the presence of metallic silver (Ag(0)-
silver mirror) at the end of the reaction. The recent work published
in 2016 by Jana[7g] pointed out two possible mechanistic pathways
depending on the electronic nature of benzoic acids while these
observations were only based on highly activated substrates, i.e.
2,6-dialkyloxy or 2,4,6-trimethoxybenzoic acids for electron rich
substrates and pentafluorobenzoic acids for electron-poor
substrates. Their study suggested that DMSO was not required
with electron poor benzoic acids but this hypothesis was only
demonstrated with pentafluorobenzoic acids; DMSO at high
temperature (120°C) was required when using other
Scheme 3. Scope of decarboxylation/olefination reaction with halogenated
carboxylic acids (isolated yields indicated, NMR yields under brackets). [a]At
140°C for 6h. [b]1h.
2,6-Dichlorobenzoic acid 1i proved to be less reactive that the
fluorinated acid 1g giving 62% yield of 3g at 140°C in 6h.
Surprisingly, 2,4,6-trichlorobenzoic acid led to 3j in only 40% yield
and no improvement was observed modifying either the reaction
time or the temperature. 2-Chloro-5-nitrobenzoic acid 1k was less
reactive furnishing 27% yield of 3k. 2-Fluoro, 2-chloro and 2,4-
difluorobenzoic acids proved to be almost unreactive in our
experimental conditions. With 2-fluoro and 2,4-difluorobenzoic
acids, we could monitor the reaction by 19F NMR analysis. These
experiments showed only poor conversion with the acid remaining
almost unaffected by the decarboxylation step, ie. absence of
fluorobenzene or 1,3-difluorobenzene at the end of the reaction.
Pentafluorobenzoic acid gave only 16% NMR yield after 1h of
reaction, whereas longer reaction times led to decreased yields.
Finally, some benzoic acids with electron-withdrawing groups
were checked for the reaction (Scheme 4). Globally, all substrates
gave poor to fair yields of reaction. As a matter of fact, compound
nitro 1l gave 28% yield of 3l. Introduction of an additional nitro
group in para-position of acid moiety (1m) decreased the yield of
the reaction to 15%. Introducing a halogenated moiety (4-chloro
1n, or 4-bromo 1o) allowed us to get better yields with 60% of 3n
perfluorobenzoic
acids
(2,4,5,6-tetrafluoro-
and
2,6-
difluorobenzoic acids). Moreover their reaction conditions were
inefficient with activated alkenes such as methyl acrylate
suggesting that their mechanistic proposition was inappropriate
with our methyl 2-fluoroacrylate 2.
Concerning the stereoselectivity, in all reactions presented above,
the Z-stereoisomer was always the major one (>95%) and was
easily detected by 19F NMR with a characteristic coupling constant
value ranging from 31 to 40 Hz. The Z-selectivity arised from the
β-hydride elimination step where the Pd−Cα and Cβ−H bonds
needed to be aligned in a syn coplanar arrangement.[13] The
formation of the Z-isomer was favoured by the steric hindrance of
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
the ester group with the aryl moiety implying a trans relationship
between these two entities (see Scheme 7, Eq. 1).[4]
Table 2. Optimization of the palladium-catalyzed decarboxylation/olefination
reaction with methyl 2-trifluoromethylacrylate 8.
Then, to showcase the usefulness of our fluoroacrylates, we
demonstrated the possible post-functionnalization into various
relevant molecules (Scheme 5).
Ratio
1a/8
[Pd] (X
mol%)
Base (Y
equiv)
Entry
1
Solvent (95/5)
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane
Yield[a]
75
Pd(TFA)2
(20)
Ag2CO3
(3)
1/2
Pd(TFA)2
(20)
Ag2CO3
(3)
2
1/1.5
1/1
75 (74)
67
Pd(TFA)2
(20)
Ag2CO3
(3)
3
Pd(TFA)2
(20)
Ag2CO3
(3)
4
1.5/1
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
63
Pd(TFA)2
(20)
Ag2CO3
(3)
5
7
Pd(TFA)2
(20)
Ag2CO3
(3)
6
DMSO
-
Pd(OAc)2
(20)
Ag2CO3
(3)
7
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
1,4-dioxane/DMSO
28
Pd(TFA)2
(10)
Ag2CO3
(3)
8
73 (70)
17
Pd(TFA)2
Ag2CO3
(3)
Scheme 5. Chemical transformations of various 2-fluoroacrylates (isolated
yields indicated).
9
(5)
Pd(TFA)2
(10)
Ag2CO3
(2)
10
11
12
13
73 (69)
73 (72)
65 (60)
44 (40)
26
First, hydrolysis of 2-fluoroacrylates 3a and 3g with KOH in
MeOH/H2O afforded 2-fluoroacrylic acids 4a and 4g in 90% and
80% yields, respectively. These carboxylic acids could serve as
Pd(TFA)2
(10)
Ag2CO3
(1.5)
starting
materials
for
further
decarboxylative/C-H
Pd(TFA)2
(10)
Ag2CO3
(1)
fluoroalkenylation of heteroarenes.[14] Then, we submitted
compound 3o to a Suzuki cross-coupling[15] giving the coupling-
product 5o in 42% yield along with the corresponding acid 6o in
17% yield, the latter arising from the in situ hydrolysis of 5o during
the course of the reaction. Finally, the reduction of the nitro
group[16] of 3p led to the corresponding free amine 7p in 70% yield.
Pd(TFA)2
(10)
Ag2CO3
(0.5)
Pd(TFA)2
(10)
Ag2CO3
(2)
]
14[b
Pd(TFA)2
(10)
Cs2CO3
(2)
15
-
To expand the scope of decarboxylative/olefination process we
decided to use the valuable 2-trifluoromethylacrylate 8 in order to
get the corresponding relevant 3-aryl-2-trifluoromethyl-acrylates 9.
Very few methods are described in the literature to synthesize
[a]19F NMR yields, isolated yields in bracket. [b] Reaction carried out at 100°C.
these
compounds,[17]
essentially
by
copper-mediated
The optimal ratio between carboxylic acid and 2-
trifluoromethylacrylate was found to be 1 equiv of 1a for 1.5 equiv
of 4 (Table 2, entries 1-4). Once again, the use of 1,4-dioxane
along with DMSO proved to be crucial for the reaction to occur,
the use of pure 1,4-dioxane or pure DMSO as a solvent giving
poor yield or no reaction, respectively (Table 2, entries 5-6).
Palladium acetate was not efficient giving only a poor 28% yield
of product 9a (Table 2, entry 7). We were pleased to see that the
reaction could be as efficient with 10 mol% of Pd(TFA)2 catalyst
as with 20 mol% catalyst (Table 2, entry 8), this latter amount
being required with 2-fluoroacrylate 2 (see Table 1). Decreasing
the catalyst loading to 5 mol% led to poor yield of reaction (Table
trifluoromethylation of halogenated alkenes; therefore, this
decarboxylative/olefination reaction could be considered as a new
interesting way to access to such compounds. Starting from our
optimal procedure used with methyl 2-fluoroacrylate 2, we tested
different experimental conditions with the model substrate 1a to
find the best catalytic system in order to afford 3-aryl-2-
trifluoromethylacrylates 9 in high yields (Table 2).
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
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2, entry 9). Interestingly, we could decrease the number of
equivalent of silver carbonate to 1.5 equivalent without loss of
efficiency (Table 2, entries 10-11). The reaction with 1 or 0.5
equivalent of base proved to be less efficient (Table 2, entries 12-
13). The decrease of temperature or the use of other base such
as caesium carbonate was not suitable for the reaction to occur
(Table 2, entries 14-15). Therefore, we decided to use 10 mol%
of Pd(TFA)2 and 1.5 equiv of Ag2CO3 in 1,4-dioxane/DMSO (95/5)
In the case of methyl 2-trifluoromethylacrylate 8, the reaction was
not as stereoselective as with methyl 2-fluoroacrylate 2,[4] and the
ratios of diastereoisomer (E)/(Z) were ranged from 60/40 to 12/88.
This loss of stereoselectivity was probably due to lack of steric
control between CF3 and ester moieties implying a poor
differenciation between both possible intermediates III and IV for
the β-hydride elimination step (Scheme 7, Eq. 2).
as
optimal
conditions
for
the
synthesis
of
2-
trifluoromethylacrylates 9 (Scheme 6).
The decarboxylation/olefination with 2-trifluoromethyl reagent 8,
gave only good yield with electron-rich carboxylic acids. Whereas
product 9a was isolated in 72% yield, more enriched carboxylic
acid 1b and 1c allowed to increase the yield of 9b and 9c to 99%
and 84%, respectively. From 9b, it was possible to isolate each
stereoisomer separately allowing us to assign without any doubt
the configuration of the double bond, by HOESY experiments (see
SI). 2-Ethoxy (1d) and 2-benzyloxy (1e) benzoic acids gave good
(74%) to fair (54%) yields of 9d and 9e, respectively. The yield
was also very good for 9f (80%) starting from the 2,4,6-
trimethylbenzoic acid 1f. Switching to electron-poor carboxylic
acid 1n and 1p bearing a nitro group in ortho position of the acid
moiety led only to low 24% yield of products 9n and 9p.
Interestingly, the diastereoselectivity was reversed in these cases
probably because of electronic and steric repulsions between the
nitro and the trifluoromethyl groups. Finally, as with methyl 2-
fluoroacrylate 2, the 2,3-dimethoxybenzoic acid did not react with
fluorinated reagent 8 whereas dihalogenated benzoic acids were
only poorly reactive giving less than 27% of NMR yield.
Scheme 7. Intermediates (I-IV) for the β-hydride elimination reaction with both
acrylates 2 and 8.
Conclusions
We developed a decarboxylation/olefination reaction between
carboxylic acids and methyl 2-fluoroacrylate 2 affording the
desired trisubstituted fluoroalkenes in various yields depending
on the electronic demand of the carboxylic acids. The use of
phosphine ligand was inappropriate and led to undesired side-
reaction. To prevent the latter, we used a ligand-free palladium-
catalyzed decarboxylative olefination process enabling us to
obtain excellent to good yields with electron-rich carboxylic acids
and fair to low yields with electron-poor carboxylic acids. We then
functionnalized some polysubstituted 2-fluoroacrylates by
hydrolysis, reduction of nitro group or also cross-coupling
reactions. Finally, we extended the reaction to the synthesis of
highly valuable trisubstituted 2-trifluoromethylacrylates. Taking
into account few reactions reported in the literature to get these
compounds, the decarboxylative olefination reaction appeared as
an interesting alternative. Excellent to moderate yields were only
obtained with electron-rich carboxylic acids. The development of
new effective catalytic reactions towards trifluoromethylalkenes
are currently under study and will be reported in due course.
Pd(TFA)2 (10 mol%)
Ag2CO3 (1.5 equiv)
R
R
CO2Me
CF3
CO2H
CO2Me
CF3
1,4-dioxane/DMSO (95/5)
120 °C, 12h
1
8 (1.5 equiv)
9
OMe
OMe
OMe
CO2Me
CO2Me
CF3
CO2Me
CF3
CF3
OMe
MeO
9a, 72% (73%)
(E)/(Z) : 60/40
9b, 99% (100%)
9c, 84% (98%)
(E)/(Z) : 60/40
(E)/(Z) : 56/44
pure 9b(E): 56%
OEt
OBn
Z)
pure 9b( : 43%
CO2Me
CF3
CO2Me
CF3
9d, 74% (80%)
(E)/(Z) : 60/40
9e, 54% (56%)
(E)/(Z) : 60/40
Me
NO2
NO2
CO2Me
CF3
CO2Me
CO2Me
CF3
CF3
Me
Me
Cl
MeO
9f, 80% (87%)
(E)/(Z) : 43/57
9n, 24% (40%)
(E)/(Z) : 12/88
9p, 24% (37%)[a]
(E)/(Z) : 37/63
poorly reactive
F
Cl
OMe
MeO
CO2Me
CF3
CO2Me
CF3
CO2Me
Experimental Section
CF3
(0%)
F
Cl
(27%)
(20%)
General information: methyl 2-fluoroacrylate (2), methyl 2-trifluoro-
methylacrylate (8), anhydrous solvents and other compounds were
purchased from Sigma-Aldrich. Coupling reactions were carried out under
air atmosphere, into a sealed tube. Flash chromatography was carried out
using Silicaflash P60 silica gel (40-60 µm); solvents used: PE = petroleum
ether, EA = ethyl acetate. Melting points (Mp) were determined on a Fisher
Scientific hot stage melting point apparatus and are uncorrected. 1H, 13C
Scheme 6. Scope of decarboxylation/olefination reaction with carboxylic acids
and methyl 2-trifluoromethylacrylate 8 (isolated yields indicated, NMR yields
under brackets). [a]24h.
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
and 19F NMR spectra were recorded using
a
Bruker Avance-300
= 0.7 Hz, CH), 111.7 (d, J = 3.0 Hz, CH), 120.0 (d, J = 4.5 Hz, Cq), 120.6
(s, CH), 130.9 (s, CH), 131.1 (d, J = 2.3 Hz, CH), 146.7 (d, J = 264.0 Hz,
Cq), 156.8 (d, J = 1.5 Hz, Cq), 162.1 (d, J = 34.3 Hz, Cq). HRMS (EI-TOF):
calcd for C12H13FO3 m/z 224.0850 [M+], found 224.0856. (E)-Isomer: 19F
NMR (282 MHz, CDCl3): δ -118.3 (d, J = 22.6 Hz).
spectrometer operating at 300 MHz (1H), 75 MHz (13C) and 282 MHz (19F),
using CDCl3, CD3OD, or DMSO-d6 as NMR solvent. The chemical shifts
(δ) were calibrated on residual proton and carbon resonances of CDCl3
(1H, δ = 7.26 ppm and 13C, δ = 77.0 ppm) or relative to external CFCl3 (19F,
δ = 0.0 ppm). In the 13C NMR spectra, signals corresponding to CH, CH2,
or CH3 groups were assigned from DEPT-135. The multiplicity signals
were indicated with the common abbreviations: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), and 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 in
electrospray ionization (ESI), chemical ionization (CI) or electron ionization
(EI) mode.
(Z)-Methyl 2-fluoro-3-(2-benzyloxyphenyl)acrylate (3e): Yellow liquid.
IR: 2953, 1727, 1598, 1486, 1436, 1291, 1239, 1114, 1092, 973, 748
cm-1. 19F NMR (282 MHz, CDCl3): δ -127.0 (d, J = 36.7 Hz). 1H NMR (300
MHz, CDCl3): 3.90 (s, 3H), 5.20 (s, 2H), 6.95 (d, J = 6.0 Hz, 1H), 7.01 (t, J
= 6.0 Hz, 1H), 7.35 (m, 6H), 7.51 (d, J = 36.0 Hz, 1H), 7.91 (dd, J = 9.0,
1.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 52.5 (s, CH3), 69.4 (s, CH2),
110.5 (d, J = 3.0 Hz, CH), 111.3 (s, CH), 119.4 (d, J = 5.3 Hz, Cq), 120.1
(s, CH), 126.1 (s, 2*CH), 127 (s, CH), 127.6 (s, 2*CH), 130.0 (d, J = 2.3
Hz, CH), 130.1 (d, J = 14.3 Hz, CH), 135.6 (s, Cq), 145.8 (d, J = 264.0 Hz,
Cq), 155.5 (d, J = 2.3 Hz, Cq), 161.0 (d, J = 34.5 Hz, Cq). HRMS (EI-TOF):
calcd for C17H15FO3 m/z 286.1005 [M+], found 286.0994. (E)-Isomer: 19F
NMR (282 MHz, CDCl3): -117.9 (d, J = 22.5 Hz).
Typical procedure for the synthesis of compounds 3: Methyl 2-
fluoroacrylate (2) (31 mg, 0.30 mmol), 2-methoxybenzoic acid (1a) (30 mg,
0.20 mmol), Pd(TFA)2 (14 mg, 0.04 mmol), Ag2CO3 (162 mg, 0.60 mmol)
in a mixture DMSO (0.05 mL) and 1,4-dioxane (0.95 mL) were heated at
120°C for 12h (for compounds 3h, 3i, 3p: at 140°C for 6h). The crude was
filtrated over celite, washed with ethyl acetate (50 mL), then solvents were
evaporated under reduced pressure. The crude product was purified by
silica gel column chromatography (PE/EA, 9/1) affording the desired
compound 3a in 92% yield (34 mg) as a white solid. The same procedure
was applied for the synthesis of trifluoromethyl analogues 9, except that
Pd(TFA)2 (10 mol %) and Ag2CO3 (1.5 equiv) were used.
(Z)-Methyl 2-fluoro-3-(2,4,6-trimethylphenyl)acrylate (3f):[4] Yellow
liquid. IR: 2954, 1733, 1668, 1437, 1334, 1268, 1205, 1098, 974, 849
cm-1. 19F NMR (282 MHz, CDCl3): δ -121.8 (d, J = 36.7 Hz). 1H NMR (300
MHz, CDCl3): δ 2.23 (s, 6H), 2.28 (s, 3H), 3.92 (s, 3H), 6.90 (s, 2H), 7.06
(d, J = 36.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 20.5 (d, J = 3.0 Hz,
2*CH3), 21.1 (s, CH3), 52.8 (s, CH3), 117.1 (d, J = 10.5 Hz, CH), 126.4 (s,
Cq), 128.5 (s, 2*CH), 136.7 (d, J = 0.8 Hz, 2*Cq), 138.5 (s, Cq), 146.5 (d,
J = 261.8 Hz, Cq), 162.6 (d, J = 35.3 Hz, Cq). HRMS (CI-TOF): calcd for
(Z)-Methyl 2-fluoro-3-(2-methoxyphenyl)acrylate (3a):[4] Yellow solid.
19F NMR (282 MHz, CDCl3): δ -127.2 (d, J = 36.7Hz). 1H NMR (300 MHz,
CDCl3): δ 3.88 (s, 3H), 3.89 (s, 3H), 6.91 (d, J = 6.0 Hz, 1H), 7.00 (dd, J =
7.7, 7.7 Hz, 1H), 7.33 (d, J = 9.0 Hz, 1H), 7.43 (d, J = 36.7 Hz, 1H), 7.89
(dd, J = 7.7, 7.7 Hz, 1H).
C
13H16FO2 m/z 223.1134 [M+H]+, found 223.1135.
(Z)-Methyl 2-fluoro-3-(2,6-difluorophenyl)acrylate (3g): Yellow liquid.
IR: 2959, 1737, 1673, 1587, 1465, 1439, 1350, 1274, 1110, 975 cm-1. 19
F
NMR (282 MHz, CDCl3): δ -107.7 (dt, J = 31.0, 8.5 Hz, 2F), -114.7 (dt, J =
33.8, 28.2 Hz, 1F). 1H NMR (300 MHz, CDCl3): δ 3.92 (s, 3H), 6.9 - 7.0 (m,
2H), 6.96 (d, J = 33.0 Hz, 1H), 7.34 (m, 1H). 13C NMR (75 MHz, CDCl3): δ
52.9 (s, CH3), 105.3 (dt, J = 9.0, 1.5 Hz, CH), 108.5 (m, Cq), 111.5 (m,
2*CH), 131.1 (t, J = 9.8 Hz, CH), 148.3 (d, J = 271.5 Hz, Cq), 160.4 (ddd,
J = 252.0, 6.7, 1.5 Hz, 2*Cq), 160.9 (d, J = 35.3 Hz, Cq). HRMS (ESI-TOF):
calcd for C10H7F3O2Na m/z 239.0296 [M+Na]+, found 239.0303. (E)-
Isomer: 19F NMR (282 MHz, CDCl3): -110.0 (m, 2F), -112.3 (dt, J = 16.9,
5.6 Hz, 1F).
(Z)-Methyl 2-fluoro-3-(2,6-dimethoxyphenyl)acrylate (3b): Yellow solid.
Mp: 81-83 °C. IR: 2947, 1723, 1586, 1463, 1253, 1094, 969, 866, 779, 759
cm-1. 19F NMR (282 MHz, CDCl3): δ -116.7 (d, J = 36.7 Hz).1H NMR (300
MHz, CDCl3): δ 3.85 (s, 6H), 3.88 (s, 3H), 6.57 (d, J = 9.0 Hz, 2H), 7.05 (d,
J = 36.0 Hz, 1H), 7.30 (t, J = 9.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ
52.5 (d, J = 0.8 Hz, CH3), 55.8 (s, 2*CH3), 103.6 (s, 2*CH), 108.5 (d, J =
2.3 Hz, Cq), 110.5 (d, J = 9.8 Hz, CH), 130.7 (s, CH), 146.6 (d, J = 264.0
Hz, Cq), 158.3 (d, J = 0.7 Hz, 2*Cq), 161.9 (d, J = 35.3 Hz, Cq). HRMS
(CI-TOF): calcd for C12H14FO4 m/z 241.0876 [M+H]+, found 241.0869. (E)-
Isomer: 19F NMR (282 MHz, CDCl3): δ -117.3 (d, J = 19.7 Hz).
(Z)-Methyl 2-fluoro-3-(2-bromo, 6-fluorophenyl)acrylate (3h): Yellow
liquid. IR: 2956, 1737, 1673, 1565, 1459, 1438, 1345, 1287, 1100, 973,
884 cm-1. 19F NMR (282 MHz, CDCl3): δ -104.7 (ddd, J = 39.5, 11.3, 5.6
Hz, 1F), -116.2 (dd, J = 39.5, 33.8 Hz, 1F). 1H NMR (300 MHz, CDCl3): δ
3.93 (s, 3H), 6.95 (d, J = 33.0 Hz, 1H), 7.11 (t, J = 9.0 Hz, 1H), 7.24 (m,
1H), 7.43 (d, J = 9.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 51.9 (s, CH3),
110.1 (dd, J = 9.0, 1.5 Hz, CH), 114.1 (d, J = 22.5 Hz, CH), 119.1 (dd, J =
18.7, 1.5 Hz, Cq), 123.3 (dd, J = 3.7, 1.5 Hz, Cq), 127.3 (d, J = 3.8 Hz,
CH), 130.2 (d, J = 9.0 Hz, CH), 147.0 (dd, J = 270.7, 2.3 Hz, Cq), 159.2
(dd, J = 254.3, 1.5 Hz, Cq), 160.3 (d, J = 35.3 Hz, Cq). HRMS (EI-TOF):
calcd for C10H781BrF2O2 m/z 277.9577 [M+], found 277.9572. (E)-Isomer:
19F NMR (282 MHz, CDCl3): -107.5 (m, 1F), -114.5 (dd, J = 16.9, 2.8 Hz,
1F).
(Z)-Methyl 2-fluoro-3-(2,4-dimethoxyphenyl)acrylate (3c): Yellow solid.
Mp: 109-111 °C. IR: 2954, 1720, 1604, 1505, 1436, 1273, 1211, 1114,
1027, 979, 837 cm-1. 19F NMR (282 MHz, CDCl3): δ -130.0 (d, J = 36.7
Hz). 1H NMR (300 MHz, CDCl3): δ 3.848 (s, 3H), 3.852 (s, 3H), 3.87 (s,
3H), 6.44 (d, J = 2.8 Hz, 1H), 6.53 (d, J = 8.5 Hz, 1H), 7.36 (d, J = 36.7 Hz,
1H), 7.86 (d, J = 8.5 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 52.4 (s, CH3),
55.4 (s, CH3), 55.6 (s, CH3), 98.1 (s, CH), 105.2 (s, CH), 111.4 (d, J = 3.0
Hz, CH), 113.0 (d, J = 5.3 Hz, Cq), 132.1 (d, J = 15.0 Hz, CH), 145.5 (d, J
= 260.3 Hz, Cq), 158.9 (d, J = 2.3 Hz, Cq), 162.3 (d, J = 3.0 Hz, Cq), 162.3
(d, J = 34.5 Hz, Cq). HRMS (EI-TOF): calcd for C12H13FO4 m/z 240.0798
[M+], found 240.0800. (E)-Isomer: 19F NMR (282 MHz, CDCl3): δ -120.0 (d,
J = 22.6 Hz).
(Z)-Methyl 2-fluoro-3-(2,6-dichlorophenyl)acrylate (3i): Yellow solid.
Mp: 44-46 °C. IR: 2962, 1732, 1679, 1557, 1428, 1343, 1284, 1258, 1092,
1
(Z)-Methyl 2-fluoro-3-(2-ethoxyphenyl)acrylate (3d): Yellow solid. Mp:
73-75 °C. IR: 2955, 1715, 1651, 1593, 1436, 1289, 1245, 1119, 1042, 975,
761 cm-1. 19F NMR (282 MHz, CDCl3): δ -127.5 (d, J = 36.7 Hz). 1H NMR
(300 MHz, CDCl3): δ 1.46 (t, J = 6.0 Hz, 3H), 3.90 (s, 3H), 4.09 (q, J = 6.0
Hz, 2H), 6.89 (d, J = 9.0 Hz, 1H), 6.98 (dd, J = 9.0, 6.0 Hz, 1H), 7.32 (t, J
= 6.0 Hz, 1H), 7.45 (d, J = 36.0 Hz, 1H), 7.89 (d, J = 6.0 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 14.7 (s, CH3), 52.6 (s, CH3), 64.1 (s, CH2), 111.6 (d, J
972, 866 cm-1. 19F NMR (282 MHz, CDCl3): δ -115.3 (d, J = 33.8 Hz). H
NMR (300 MHz, CDCl3): δ 3.93 (s, 3H), 7.02 (d, J = 33.0 Hz, 1H), 7.35 (m,
2H), 7.38 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 51.9 (s, CH3), 111.8 (d, J
= 9.8 Hz, CH), 127.0 (s, 2*CH), 127.8 (s, Cq), 129.2 (s, CH), 133.9 (d, J =
1.5 Hz, 2*Cq), 147.0 (d, J = 268.5 Hz, Cq), 159.8 (d, J = 34.5 Hz, Cq).
HRMS (CI-TOF): calcd for C10H8Cl2FO2 m/z 248.9885 [M+H]+, found
248.9892.
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10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
(Z)-Methyl 2-fluoro-3-(2,4,6-trichlorophenyl)acrylate (3j): Yellow solid.
Mp: 99-101 °C. IR: 2963, 1736, 1683, 1577, 1437, 1349, 1286, 1099, 971,
857, 803, 787 cm-1. 19F NMR (282 MHz, CDCl3): δ -114.2 (d, J = 31.0 Hz).
1H NMR (300 MHz, CDCl3): δ 3.93 (s, 3H), 6.95 (d, J = 31.0 Hz, 1H), 7.39
(s, 2H). 13C NMR (75 MHz, CDCl3): δ 51.9 (s, CH3), 110.9 (d, J = 9.0 Hz,
CH), 126.5 (d, J = 0.8 Hz, Cq), 127.1 (s, 2*CH), 134.40 (d, J = 0.8 Hz,
2*Cq), 134.42 (s, Cq), 147.3 (d, J = 270.0 Hz, Cq), 159.5 (d, J = 34.5 Hz,
Cq). HRMS (CI-TOF): calcd for C10H735Cl3FO2 m/z 282.9496 [M+H]+, found
282.9502.
(Z)-Methyl 2-fluoro-3-(4-bromo, 2-nitrophenyl)acrylate (3o): Yellow
solid. Mp: 91-93 °C. IR: 2957, 1738, 1667, 1528, 1438, 1344, 1242, 1210,
1093, 968, 878, 762 cm-1. 19F NMR (282 MHz, CDCl3): δ -122.7 (d, J =
33.8 Hz). 1H NMR (300 MHz, CDCl3): δ 3.92 (s, 3H), 7.33 (d, J = 33.0 Hz,
1H), 7.71 (d, J = 9.0 Hz, 1H), 7.80 (dd, J = 9.0, 3.0 Hz, 1H), 8.20 (d, J =
3.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 53.1 (s, CH3), 111.7 (d, J = 4.5
Hz, CH), 123.5 (d, J = 1.5 Hz, Cq), 124.5 (d, J = 1.5 Hz, Cq), 128.1 (s, CH),
133.0 (d, J = 9.8 Hz, CH), 136.5 (s, CH), 148.3 (s, Cq), 148.3 (d, J = 270.0
Hz, Cq), 160.7 (d, J = 35.3 Hz, Cq). HRMS (EI-TOF): calcd for
C10H779BrFNO4 m/z 302.9542 [M+], found 302.9540. (E)-Isomer: 19F NMR
(282 MHz, CDCl3): δ -116.8 (d, J = 16.9 Hz). Selected 1H NMR (300 MHz,
CDCl3): δ 3.71 (s, 3H), 7.16 (d, J = 9.0 Hz, 1H), 8.37 (d, J = 3.0 Hz, 1H).
Selected 13C NMR (75 MHz, CDCl3): δ 52.6 (s, CH3), 117.8 (d, J = 29.3
Hz, CH), 127.7 (s, CH), 132.0 (s, CH), 136.6 (s, CH).
(Z)-Methyl 2-fluoro-3-(2-chloro, 5-nitrophenyl)acrylate (3k): Yellow
solid. Mp: 79-81 °C. IR: 2968, 1740, 1605, 1519, 1438, 1339, 1263, 1199,
1097, 971, 821, 738 cm-1. 19F NMR (282 MHz, CDCl3): δ -120.3 (d, J =
31.0 Hz). 1H NMR (300 MHz, CDCl3): δ 3.95 (s, 3H), 7.35 (d, J = 30.0 Hz,
1H), 7.63 (d, J = 9.0 Hz, 1H), 8.17 (dd, J = 9.0, 3.0 Hz, 1H), 8.76 (br s, 1H).
13C NMR (75 MHz, CDCl3): δ 53.2 (s, CH3), 111.3 (d, J = 3.0 Hz, CH),
124.9 (d, J = 1.5 Hz, CH), 126.0 (d, J = 14.3 Hz, CH), 130.5 (d, J = 3.8 Hz,
Cq), 130.8 (s, CH), 140.6 (d, J = 2.3 Hz, Cq), 146.7 (s, Cq), 149.1 (d, J =
273.8 Hz, Cq), 160.7 (d, J = 34.5 Hz, Cq). HRMS (ESI-TOF): calcd for
C10H7ClFNO4Na m/z 281.9945 [M+Na]+, found 281.9951. (E)-Isomer: 19F
NMR (282 MHz, CDCl3): δ -113.3 (d, J = 16.9 Hz).
(Z)-Methyl 2-fluoro-3-(4-methoxy, 2-nitrophenyl)acrylate (3p): Yellow
solid. Mp: 111-113 °C. IR: 2957, 1722, 1613, 1523, 1494, 1318, 1249,
1241, 1067, 1030, 963, 873 cm-1. 19F NMR (282 MHz, CDCl3): δ -125.9 (d,
J = 31.0 Hz). 1H NMR (300 MHz, CDCl3): δ 3.91 (s, 6H), 7.19 (dd, J = 9.0,
3.0 Hz, 1H), 7.34 (d, J = 33.0 Hz, 1H), 7.54 (d, J = 2.8 Hz, 1H), 7.82 (d, J
= 9.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 52.9 (s, CH3), 56.0 (s, CH3),
109.9 (s, CH), 112.3 (d, J = 3.7 Hz, CH), 117.6 (d, J = 3.7 Hz, Cq), 119.0
(s, CH), 132.9 (d, J = 10.5 Hz, CH), 147.3 (d, J = 265.5 Hz, Cq), 149.2 (s,
Cq), 160.4 (d, J = 2.3 Hz, Cq), 161.2 (d, J = 34.5 Hz, Cq). HRMS (EI-TOF):
calcd for C11H10FNO5 m/z 255.0543 [M+], found 255.0528.
(Z)-Methyl 2-fluoro-3-(2-nitrophenyl)acrylate (3l): Yellow solid. Mp: 91-
93 °C. IR: 2919, 1731, 1669, 1518, 1433, 1342, 1282, 1096, 969, 867, 760
cm-1. 19F NMR (282 MHz, CDCl3): δ -124.4 (d, J = 31.0 Hz). 1H NMR (300
MHz, CDCl3): δ 3.93 (s, 3H), 7.42 (d, J = 30.0 Hz, 1H), 7.54 (t, J = 9.0 Hz,
1H), 7.68 (t, J = 9.0 Hz, 1H), 7.84 (d, J = 6.0 Hz, 1H), 8.08 (d, J = 9.0 Hz,
1H). 13C NMR (75 MHz, CDCl3): δ 53.0 (s, CH3), 112.8 (d, J = 3.8 Hz, CH),
125.0 (s, CH), 125.6 (d, J = 2.3 Hz, Cq), 130.0 (s, CH), 131.8 (d, J = 9.0
Hz, CH), 133.4 (s, CH), 148.0 (d, J = 267.7 Hz, Cq), 148.1 (s, Cq), 161.0
(d, J = 35.3 Hz, Cq). HRMS (CI-TOF): calcd for C10H9FNO4 m/z 226.0515
[M+H]+, found 226.0510.
(Z)-Methyl 2-fluoro-3-(5-methoxy, 2-nitrophenyl)acrylate (3q): Beige
solid. Mp: 107-109 °C. IR: 2968, 1730, 1671, 1575, 1512, 1435, 1326,
1230, 1088, 1032, 962, 893 cm-1. 19F NMR (282 MHz, CDCl3): δ -125.2 (d,
J = 31.0 Hz). 1H NMR (300 MHz, CDCl3): δ 3.91 (s, 3H), 3.93 (s, 3H), 7.00
(dd, J = 9.0, 3.0 Hz, 1H), 7.21 (d, J = 3.0 Hz, 1H), 7.53 (d, J = 30.0 Hz,
1H), 8.17 (d, J = 9.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 53.0 (s, CH3),
56.0 (s, CH3), 113.9 (d, J = 3.7 Hz, CH), 114.9 (s, CH), 116.5 (d, J = 9.0
Hz, CH), 127.7 (s, CH), 128.3 (d, J = 2.3 Hz, Cq), 140.9 (s, Cq), 147.7 (d,
J = 266.3 Hz, Cq), 161.0 (d, J = 35.3 Hz, Cq), 163.2 (s, Cq). HRMS (ESI-
TOF): calcd for C11H10FNO5Na m/z 278.0441 [M+Na]+, found 278.0443.
(E)-Isomer: 19F NMR (282 MHz, CDCl3): δ -119.0 (d, J = 16.9 Hz).
(Z)-Methyl 2-fluoro-3-(2,4-dinitrophenyl)acrylate (3m): Yellow solid.
Mixture Z/E 81/19. IR: 2955, 1733, 1664, 1598, 1524, 1439, 1342, 1241,
1111, 1065, 1030, 972, 834 cm-1. 19F NMR (282 MHz, CDCl3): δ -119.3 (d,
J = 31.0 Hz). 1H NMR (300 MHz, CDCl3): δ 3.96 (s, 3H), 7.45 (d, J = 30.0
Hz, 1H), 8.05 (d, J = 9.0, 1H), 8.51 (dd, J = 9.0, 2.4 Hz, 1H), 8.92 (d, J =
2.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 53.4 (s, CH3), 110.7 (d, J = 3.7
Hz, CH), 117.0 (s, Cq), 120.5 (s, CH), 127.4 (s, CH), 131.6 (d, J = 3.0 Hz,
Cq), 133.2 (d, J = 9.7 Hz, CH), 147.7 (s, Cq), 149.6 (d, J = 274.5 Hz, Cq),
160.2 (d, J = 33.3 Hz, Cq). HRMS (EI-TOF): calcd for C10H7FN2O6 m/z
270.0288 [M+], found 270.0286. (E)-Isomer: 19F NMR (282 MHz, CDCl3):
δ -114.7 (d, J = 22.6 Hz). Selected 1H NMR (300 MHz, CDCl3): δ 3.71 (s,
3H), 7.21 (d, J = 18.0 Hz, 1H), 7.64 (d, J = 9.0 Hz, 1H), 9.01 (d, J = 3.0 Hz,
1H). Selected 13C NMR (75 MHz, CDCl3): δ 52.8 (s, CH3), 120.2 (s, CH),
127.1 (s, CH), 133.5 (d, J = 3.0 Hz, CH), 147.7 (d, J = 267.0 Hz, Cq), 148.1
(s, Cq).
Typical procedure for the saponification reaction: To a solution of
methyl acrylate 3g (47 mg, 0.21 mmol) in MeOH (1.5 mL) were added KOH
(18 mg, 0.32 mmol) and H2O (0.3 mL). The reaction was refluxed for 18
hours. After cooling at room temperature, the mixture was acidified to pH
= 1 with 3 N HCl solution (~1.0 mL) and concentrated under vacuum. After
extraction with ethyl acetate (3 x 5 mL), the organic layers were dried over
MgSO4, filtered and concentrated under reduced pressure. The resulting
solid was purified over a pad of silica gel (5-6 cm, eluent: EtOAc) to afford
the desired product 4g in 80% yield (34 mg) as a white solid.
(Z)-2-Fluoro-3-(2-methoxyphenyl)acrylic acid (4a):[13] Colorless
solid.19F NMR (282 MHz, DMSO-d6): δ -125.4 (d, J = 37.2 Hz). 1H NMR
(300 MHz, DMSO-d6): δ 3.86 (s, 3H), 7.03 (t, J = 7.8 Hz, 1H), 7.11 (d, J =
8.3 Hz, 1H), 7.26 (d, J = 37.2 Hz, 1H), 7.42 (td, J = 8.3, 1.6 Hz, 1H), 7.76
(dd, J = 7.8, 1.6 Hz, 1H), 13.62 (s, 1H).
(Z)-Methyl 2-fluoro-3-(4-chloro, 2-nitrophenyl)acrylate (3n): Yellow
solid. Mp: 81-83 °C. IR: 2961, 1740, 1675, 1522, 1437, 1346, 1259, 1208,
1103, 968, 877, 763 cm-1. 19F NMR (282 MHz, CDCl3): δ -123.0 (d, J =
31.0 Hz). 1H NMR (300 MHz, CDCl3): δ 3.93 (s, 3H), 7.36 (d, J = 30.0 Hz,
1H), 7.65 (dd, J = 9.0, 3.0 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 8.07 (d, J =
3.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 52.1 (s, CH3), 110.6 (d, J = 4.5
Hz, CH), 123.0 (d, J = 3.0 Hz, Cq), 124.2 (s, CH), 131.8 (d, J = 9.8 Hz,
CH), 132.5 (s, CH), 134.9 (d, J = 1.5 Hz, Cq), 147.3 (s, Cq), 147.3 (d, J =
269.3 Hz, Cq), 159.7 (d, J = 35.3 Hz, Cq). HRMS (CI-TOF): calcd for
C10H835ClFNO4 m/z 260.0126 [M+H]+, found 260.0124. (E)-Isomer: 19F
NMR (282 MHz, CDCl3): δ -116.9 (d, J = 16.9 Hz). Selected 1H NMR (300
MHz, CDCl3): δ 3.71 (s, 3H). Selected 13C NMR (75 MHz, CDCl3): δ 51.6
(s, CH3), 123.9 (s, CH), 130.9 (s, CH), 132.2 (s, CH), 132.7 (s, CH).
(Z)-2-Fluoro-3-(2,6-difluorophenyl) acrylic acid (4g): White solid. Mp:
113-115 °C. IR: 2923, 2510, 1710, 1666, 1624, 1586, 1466, 1338, 1278,
1119, 1000, 779 cm-1. 19F NMR (282 MHz, CD3OD): δ -110.5 (m, 2F),
-115.3 (m, 1F). 1H NMR (300 MHz, CD3OD): δ 6.94 (d, J = 33.0 Hz, 1H),
7.05 (dd, J = 9.0, 6.0 Hz, 2H), 7.46 (m, 1H). 13C NMR (75 MHz, CD3OD):
δ 105.3 (d, J = 9.8 Hz, CH), 109.7 (t, J = 19.5 Hz, Cq), 112.6 (m, 2*CH),
132.6 (t, J = 10.5 Hz, CH), 150.6 (d, J = 271.5 Hz, Cq), 161.7 (dd, J =
251.3, 6.7 Hz, 2*Cq), 163.0 (m, Cq). HRMS (ESI-TOF): calcd for C9H4F3O2
m/z 201.0163 [M-H]-, found 201.0159.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
Typical procedure for the Suzuki cross-coupling reaction of acrylate
3o with p-methoxyphenyl boronic acid: A mixture of methyl 2-fluoro-3-
(m, E). 1H NMR (300 MHz, CDCl3): δ 3.71 (s, 3H, E), 3.83 (s, 3H, E), 3.84
(s, 3H, Z), 3.87 (s, 3H, Z), 6.9 – 7.0 (m, 2H, E + Z), 7.1 – 7.3 (m, 1H, E +
Z), 7.3 – 7.4 (m, 1H, E + Z), 7.63 (s, 1H, E), 8.23 (s, 1H, Z).
(4-bromo, 2-nitrophenyl)acrylate (3o) (40.0 mg, 0.13 mmol)
, p-
methoxyphenyl boronic acid (98.8 mg, 0.65 mmol), tetrakis(triphenyl-
phosphine)palladium (14.5 mg, 0.013 mmol), cesium carbonate (42.4 mg,
0.13 mmol), aqueous solution of potassium carbonate (2M, 0.13 mmol),
and ethanol (1 mL) in degassed toluene (15 mL) was refluxed under argon
atmosphere for 30 hours. Then, the reaction mixture was cooled, diluted
with a (1:1) mixture of water and ethyl acetate (20 mL) and the organic
layer was separated. The aqueous phase was extracted with ethyl acetate
(2 x 30 mL). The combined organic extracts were then dried over
magnesium sulfate and evaporated under reduced pressure. The crude
product was purified by silica gel column chromatography (EtOAc)
affording the desired compound 5o in 42% yield (18 mg) as a brown solid
and the corresponding acrylic acid 6o in 17% yield (7 mg) as a brown solid.
Methyl 3-(2,6-dimethoxyphenyl)-2-trifluoromethylacrylate (9b): The
two stereomers were fully separated by silica gel column chromatography.
(E)-Isomer: Yellow solid. Mp: 125-127 °C. IR: 2962, 1735, 1650, 1593,
1476, 1436, 1258, 1110, 1018, 773, 734 cm-1. 19F NMR (282 MHz, CDCl3):
δ -63.63 (d, J = 1.7 Hz). 1H NMR (300 MHz, CDCl3): δ 3.68 (s, 3H), 3.81
(s, 6H), 6.54 (d, J = 9.0 Hz, 2H), 7.30 (t, J = 9.0 Hz, 1H), 8.01 (m, 1H). 13
C
NMR (75 MHz, CDCl3): δ 50.7 (s, CH3), 54.6 (s, 2*CH3), 102.5 (s, 2*CH),
110.0 (s, Cq), 121.6 (q, J = 271.5 Hz, Cq), 122.9 (q, J = 30.0 Hz, Cq), 130.7
(s, CH), 132.4 (q, J = 6.0 Hz, CH), 157.0 (s, 2*Cq), 163.7 (m, Cq). HRMS
(ESI-TOF): calcd for C13H13F3O4Na m/z 313.0669 [M+Na]+, found
313.0654. (Z)-Isomer: Yellow solid. Mp: 113-115 °C. IR: 2962, 1727,
1633, 1593, 1477, 1436, 1385, 1260, 1110, 1033, 963, 938, 765 cm-1. 19
F
(Z)-Methyl 2-fluoro-3-(4-(p-methoxyphenyl), 2-nitrophenyl) acrylate
(5o): Brown solid. Mp: 78-80 °C. IR: 2961, 2840, 1735, 1605, 1515, 1438,
1345, 1299, 1247, 1179, 1102, 1023, 801 cm-1. 19F NMR (282 MHz,
NMR (282 MHz, CDCl3): δ -63.67 (s). 1H NMR (300 MHz, CDCl3): δ 3.82
(s, 6H), 3.88 (s, 3H), 6.54 (d, J = 9.0 Hz, 2H), 7.30 (m, 1H), 8.01 (s, 1H).
13C NMR (75 MHz, CDCl3): δ 52.5 (s, CH3), 55.6 (s, 2*CH3), 103.3 (s,
2*CH), 111.0 (s, Cq), 122.2 (q, J = 272.3 Hz, Cq), 123.6 (q, J = 31.5 Hz,
Cq), 131.5 (s, CH), 140.7 (q, J = 3.0 Hz, CH), 157.7 (m, 2*Cq), 163.7 (q, J
= 1.5 Hz, Cq). HRMS (ESI-TOF): calcd for C13H13F3O4Na m/z 313.0664
[M+Na]+, found 313.0654.
1
CDCl3): δ -124.1 (d, J = 33.8 Hz). H NMR (300 MHz, CDCl3): δ 3.88 (s,
3H), 3.93 (s, 3H), 7.02 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 33.0 Hz, 1H), 7.58
(d, J = 9.0 Hz, 2H), 7.84 (dd, J = 9.0, 3.0 Hz, 1H), 7.91 (d, J = 6.0 Hz, 1H),
8.23 (d, J = 3.0 Hz, 1H). 13C NMR (75 MHz, CD3OD): δ 53.0 (s, CH3), 55.5
(s, CH3), 112.4 (d, J = 3.8 Hz, CH), 114.7 (s, 2*CH), 122.6 (s, CH), 123.2
(d, J = 3.0 Hz, Cq), 128.2 (s, 2*CH), 130.1 (s, Cq), 130.8 (s, CH), 132.2 (d,
J = 10.5 Hz, CH), 143.0 (s, Cq), 148.0 (d, J = 267.8 Hz, Cq), 148.7 (s, Cq),
160.5 (s, Cq), 161.1 (d, J = 34.5 Hz, Cq). HRMS (ESI-TOF): calcd for
Methyl 3-(2,4-dimethoxyphenyl)-2-trifluoromethylacrylate (9c): Yellow
oil. Mixture E/Z 60/40. IR: 2955, 1725, 1605, 1504, 1438, 1320, 1289,
1265, 1209, 1112, 1028, 825 cm-1. 19F NMR (282 MHz, CDCl3): δ
-58.6 (d, J = 2.8 Hz, Z), -63.2 (d, J = 1.7 Hz, E). 1H NMR (300 MHz, CDCl3):
δ 3.76 (s, 3H), 3.82 (s, 3H), 3.83 (s, 3H), 3.84 (s, 3H), 3.85 (s, 3H), 3.87
(s, 3H), 6.4-6.5 (m, 2H, E + Z), 7.2 – 7.3 (m, 1H, E + Z), 7.60 (m, 1H, E),
8.22 (s, 1H, Z). 13C NMR (75 MHz, CDCl3): δ 52.2 (s, CH3, E), 52.4 (s, CH3,
Z), 55.41 (s, CH3), 55.43 (s, CH3), 55.5 (s, CH3), 55.6 (s, CH3), 97.8 (s,
CH, Z), 98.1 (s, CH, E), 104.8 (s, CH, Z), 104.9 (s, CH, E), 114.2 (s, Cq,
E), 114.3 (s, Cq, Z), 119.3 (q, J = 31.5 Hz, Cq, Z), 120.2 (q, J = 30.8 Hz,
Cq, E), 122.5 (q, J = 272.3 Hz, Cq, Z), 122.7 (q, J = 270.8 Hz, Cq, E), 132.1
(q, J = 3.8 Hz, CH, Z), 136.8 (q, J = 6.0 Hz, CH, E), 144.3 (q, J = 3.0 Hz,
CH, Z), 159.3 (s, Cq, E), 159.5 (s, Cq, Z), 163.2 (s, Cq, E), 163.5 (s, Cq,
Z), 164.3 (q, J = 1.5 Hz, Cq, E), 164.4 (m, Cq, Z). HRMS (ESI-TOF): calcd
for C13H13F3O4Na m/z 313.0664 [M+Na]+, found 313.0668.
C
17H14FNO5Na m/z 354.0754 [M+Na]+, found 354.0760.
(Z)-2-Fluoro-3-(4-(p-methoxyphenyl), 2-nitrophenyl) acrylic acid (6o):
Brown solid. Mp: 174-176 °C. IR: 3208, 2918, 2850, 1726, 1668, 1605,
1516, 1342, 1293, 1253, 1180, 1063, 982 cm-1. 19F NMR (282 MHz,
1
CDCl3): δ -123.9 (d, J = 33.8 Hz). H NMR (300 MHz, CDCl3): δ 3.88 (s,
3H), 7.02 (d, J = 9.0 Hz, 2H), 7.41 (d, J = 33.0 Hz, 1H), 7.58 (d, J = 9.0 Hz,
2H), 7.84 (dd, J = 9.0, 3.0 Hz, 1H), 7.91 (d, J = 6.0 Hz, 1H), 8.23 (d, J =
3.0 Hz, 1H).
Typical procedure for the reduction of nitroarene 3p: To a suspension
of nitroarene 3p (30 mg, 0.12 mmol) in a mixture of EtOH (1 mL) and H2O
(0.1 mL), iron powder (20 mg, 0.36 mmol), and CaCl2 (16 mg, 0.14 mmol)
were added. The resulting suspension was stirred at 60 °C for 6 hours (the
progress of the reaction was monitored by TLC). After completion, the
reaction mixture was filtered over celite to remove the iron residue, and the
resulting pad was washed two times with EtOAc (2 x 10 mL). The
combined organic extracts were washed with H2O (3 × 10 mL), brine (2 ×
10 mL), and dried over Na2SO4. After evaporation under reduced pressure,
the crude product was purified by silica gel column chromatography
(PE/EA, 70/30) affording the desired compound 7p in 70% yield (19 mg)
as a yellow solid.
Methyl 3-(2-ethoxyphenyl)-2-trifluoromethylacrylate (9d): Yellow oil.
Mixture E/Z 60/40. IR: 2987, 1729, 1643, 1599, 1455, 1438, 1251, 1219,
1158, 1119, 1036, 926, 750 cm-1. 19F NMR (282 MHz, CDCl3): δ -58.7 (d,
J = 1.4 Hz, Z), -63.8 (d, J = 1.7 Hz, E). 1H NMR (300 MHz, CDCl3): δ 1.40
– 1.46 (m, 3H, E + Z), 3.73 (s, 3H, E), 3.89 (s, 3H, E + Z), 4.04 - 4.13 (m,
2H, E + Z), 6.88 – 6.97 (m, 2H, E + Z), 7.26 – 7.39 (m, 2H, E + Z), 7.68 (s,
1H, E), 8.26 (s, 1H, Z). 13C NMR (75 MHz, CDCl3): δ 14.59 (s, CH3),14.62
(s, CH3), 52.2 (s, OCH3, E), 52.6 (s, OCH3, Z), 64.0 (s, OCH2, Z), 64.2 (s,
OCH2, E), 111.3 (s, CH, Z), 111.8 (s, CH, E), 120.0 (s, CH, Z), 120.2 (s,
CH, E), 121.7 (s, Cq, E), 121.9 (s, Cq, Z), 122.2 (q, J = 271.5 Hz, Cq, Z),
122.4 (q, J = 272.3 Hz, Cq, E), 122.9 (q, J = 30.0 Hz, Cq, Z), 123.6 (q, J =
31.5 Hz, Cq, E), 129.8 (s, CH, E), 130.4 (q, J = 3.8 Hz, CH, Z), 131.84 (s,
CH, Z), 131.88 (s, CH, E), 137.6 (q, J = 6.0 Hz, CH, E), 145.3 (q, J = 3.0
Hz, CH, Z), 156.9 (s, Cq, Z), 157.0 (s, Cq, E), 163.95 (q, J = 3.8 Hz, Cq,
E), 163.98 (m, Cq, Z). HRMS (ESI-TOF): calcd for C13H13F3O3Na m/z
297.0714 [M+Na]+, found 297.0710.
(Z)-Methyl 2-fluoro-3-(2-amino, 4-methoxyphenyl) acrylate (7p):
Yellow solid. Mp: 209-211 °C. IR: 3050, 2914, 2843, 1722, 1672, 1626,
1574, 1414, 1276, 1237, 1117, 1023, 906, 873 cm-1. 19F NMR (282 MHz,
1
CDCl3): δ -130.2 (d, J = 33.8 Hz). H NMR (300 MHz, CDCl3): δ 3.80 (s,
3H), 3.88 (s, 3H), 3.92 (br s, 2H), 6.24 (d, J = 3.0 Hz, 1H), 6.40 (dd, J =
9.0, 3.0 Hz, 1H), 6.93 (d, J = 36.0 Hz, 1H), 7.62 (d, J = 9.0 Hz, 1H). 13C
NMR (75 MHz, CDCl3): δ 52.5 (s, CH3), 55.2 (s, CH3), 101.2 (s, CH), 105.7
(s, CH), 109.4 (d, J = 4.5 Hz, Cq), 112.4 (d, J = 5.3 Hz, CH), 132.4 (d, J =
12.0 Hz, CH), 145.6 (d, J = 263.5 Hz, Cq), 146.9 (d, J = 1.5 Hz, Cq), 162.0
(d, J = 1.5 Hz, Cq), 162.2 (d, J = 33.8 Hz, Cq). HRMS (ESI-TOF): calcd for
C11H13FNO3 m/z 226.0879 [M+H]+, found 226.0876.
Methyl 3-(2-benzyloxyphenyl)-2-trifluoromethylacrylate (9e): Yellow
oil. Mixture E/Z 60/40. IR: 2955, 1728, 1642, 1600, 1487, 1437, 1257,
1217, 1159, 1113, 1042, 915, 750 cm-1. 19F NMR (282 MHz, CDCl3): δ
-58.4 (d, J = 1.1 Hz, Z). -63.7 (d, J = 1.7 Hz, E). 1H NMR (300 MHz, CDCl3):
δ 3.70 (s, 3H), 3.89 (s, 3H), 5.14 (s, 2H), 5.17 (s, 2H), 6.97 (m, 2H), 7.2 –
7.4 (m, 7H), 7.75 (m, 1H, E), 8.34 (s, 1H, Z). 13C NMR (75 MHz, CDCl3): δ
52.3 (s, CH2), 52.7 (s, CH2), 70.40 (s, CH3), 70.49 (s, CH3), 112.2 (s, CH),
Methyl 3-(2-methoxyphenyl)-2-trifluoromethylacrylate (9a):[16b] Yellow
oil. Mixture E/Z 60/40. 19F NMR (282 MHz, CDCl3): δ -58.8 (m, Z), -63.7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701709
European Journal of Organic Chemistry
FULL PAPER
112.6 (s, CH), 120.6 (s, CH), 120.8 (s, CH), 122.10 (s, Cq), 122.12 (q, J =
272.3 Hz, Cq), 122.29 (s, Cq,), 122.30 (q, J = 33.0 Hz, Cq), 122.32 (q, J =
271.5 Hz, Cq), 123.0 (q, J = 31.5 Hz, Cq), 126.99 (s, 2*CH), 127.03 (s,
2*CH), 128.04 (s, CH), 128.08 (s, CH), 128.66 (s, 2*CH), 128.67 (s, 2*CH),
129.8 (s, CH), 130.5 (q, J = 3.8 Hz, CH), 131.85 (s, CH), 131.89 (s, CH),
136.4 (s, Cq), 136.5 (s, Cq), 137.6 (q, J = 6.0 Hz, CH), 145.2 (q, J = 3.0
Hz, CH), 156.6 (s, Cq), 156.7 (s, Cq), 163.8 (m, Cq), 163.9 (m, Cq). HRMS
(ESI-TOF): calcd for C18H15F3O3Na m/z 359.0871 [M+Na]+, found
359.0876.
Program for a fellowship (Ref. N° BT16DM3627). The authors
also thank Dr. D. Harakat (Reims University) for HMRS analyses.
Keywords: fluoroalkene • fluoroacrylate • decarboxylative
olefination • catalysis • palladium
[1]
[2]
a) T. Hiyama in Organofluorine Compounds: Chemistry and Applications
(ed: H. Yamamoto), Springer-Verlag, Berlin, 2000; b) K. Uneyama, in
Organofluorine Chemistry, Blackwell, Oxford, 2006; c) I. Ojima, in
Fluorine in Medicinal Chemistry and Chemical Biology, Wiley-Blackwell,
Chichester, 2009; d) for a recent issue on fluorine chemistry, see: Chem.
Rev. 2015, 115, 563.
Methyl 3-(2,4,6-trimethylphenyl)-2-trifluoromethylacrylate (9f): Yellow
oil. Mixture E/Z 43/57. IR: 2957, 1733, 1648, 1438, 1379, 1271, 1229,
1167, 1132, 1044, 851 cm-1. 19F NMR (282 MHz, CDCl3):
δ
-61.7 (s, Z), -64.0 (d, J = 2.8 Hz, E). 1H NMR (300 MHz, CDCl3): δ 2.15 (d,
J = 3.0 Hz, 6H, E + Z), 2.28 (s, 3H, E + Z), 3.63 (s, 3H, E), 3.92 (s, 3H, Z),
6.87 (s, 2H, E + Z), 7.64 (s, 1H, E), 8.14 (s, 1H, Z). 13C NMR (75 MHz,
CDCl3): δ 18.8 (s, 2*CH3), 19.0 (s, 2*CH3), 19.9 (s, CH3), 20.0 (s, CH3),
51.2 (s, OCH3, E), 51.7 (s, OCH3, Z), 120.8 (q, J = 273.0 Hz, Cq, Z), 121.0
(q, J = 271.5 Hz, Cq, E), 124.1 (q, J = 30.8 Hz, Cq, Z), 125.1 (q, J = 30.0
Hz, Cq, E), 127.0 (s, 2*CH), 127.2 (s, 2*CH), 128.6 (s, Cq, E), 128.8 (s,
Cq, Z), 132.8 (m, Cq, Z), 133.4 (s, Cq, E), 136.9 (s, Cq, Z), 137.0 (s, Cq,
E), 143.8 (q, J = 5.3 Hz, CH, E), 148.3 (q, J = 3.0 Hz, CH, Z), 161.4 (s, Cq,
E), 162.0 (m, Cq, Z). HRMS (ESI-TOF): calcd for C14H15F3O2Na 295.0922
m/z [M+Na]+, found 295.0914
See for some applications of fluoroacrylates in materials and medicinal
chemistry: a) H. Honda, S. Sato, K. Isomae, J. Ookawa, T. Kuwamura,
(SS Pharmaceutical Co.) DE3407806, 1984; b) E. P. Jaeger, P. C. Jurs,
T. R. E. Stouch, Eur. J. Med. Chem. 1993, 28, 275; c) S. Hibi, K. Kikuchi,
H. Yoshimura, M. Nagai, K. Tagami, S. Abe, I. Hishinuma, J. Nagakawa,
N. Miyamoto, (Eisai Co., Ltd.), WO9613478, 1996; d) T. Kaneko, R. Clark,
N. Ohi, F. Ozaki, T. Kawahara, A. Kamada, K. Okano, H. Yokohama, K.
Muramoto, T. Arai, M. Ohkuro, O. Takenaka, J. Sonoda, (Eisai Co., Ltd.)
WO9806720, 1998; e) P. E. Wiedeman, S. W. Djuric, M. Pilushchev, R.
J. Sciotti, D. J. Madar, H. Kopecka, US20020115669(A1), 2002; f) J.-M.
Cracowski, V. Montembault, D. Bosc, B. Ameduri, F. Odobel, L. Fontaine,
J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 1403; g) J. Sun, Y. Yang,
Y. Huang, (Chengdu Inst. Biology), CN103254053(A), 2013; h)
Handbook of Fluoropolymer Science and Technology (eds: D. W. Smith,
S. T. Iacono, S. S. Iyer), John Wiley & Sons, Inc., Hoboken, NJ, 2014.
See for examples: a) D. K. Barma, A. Kundu, H. Zhang, C. Mioskowski,
J. R. Falck, J. Am. Chem. Soc. 2003, 125, 3218; b) M. Yoshimatsu, Y.
Murase, A. Itoh, G. Tanabe, O. Muraoka, Chem. Lett. 2005, 34, 998; c)
L. Zoute, G. Dutheuil, J.-C Quirion, P. Jubault, X. Pannecoucke,
Synthesis 2006, 3409; d) S. Sano, Y. Kuroda, K. Saito, Y. Ose, Y. Nagao,
Tetrahedron 2006, 62, 11881; e) G. Lemonnier, L. Zoute, G. Dupas, J.-
C. Quirion, P. Jubault, J. Org. Chem. 2009, 74, 4124; f) J. K. Augustine,
A. Bombrun, S. Venkatachaliah, A. Jothi, Org. Biomol. Chem. 2013, 11,
8065; g) F. Larnaud, E. Pfund, B. Linclau, T. Lequeux, Tetrahedron 2014,
70, 5632 and references cited therein.
Methyl 3-(4-chloro, 2-nitrophenyl)-2-trifluoromethylacrylate (9n):
Yellow oil. Mixture E/Z 12/88. IR: 2959, 1732, 1655, 1561, 1531, 1438,
1384, 1344, 1289, 1267, 1134, 1043, 891 cm-1. 19F NMR (282 MHz,
CDCl3): δ -58.1 (s, Z), -64.3 (d, J = 1.7 Hz, E). 1H NMR (300 MHz, CDCl3):
δ 3.66 (s, 3H, E), 3.94 (s, 3H, Z), 7.30 (d, J = 9.0 Hz, 1H, Z), 7.69 (dd, J =
9.0, 3.0 Hz, 1H, Z), 7.96 (s, 1H, E), 8.26 (d, J = 3.0 Hz, 1H, E), 8.28 (d, J =
3.0 Hz, 1H, Z), 8.36 (s, 1H, Z). 13C NMR (75 MHz, CDCl3): δ 52.6 (s, CH3,
E), 53.1 (s, CH3, Z), 121.5 (q, J = 273.0 Hz, Cq, Z), 123.6 (q, J = 31.5 Hz,
Cq, Z), 125.1 (s, CH, E), 125.2 (s, CH, Z), 128.1 (s, Cq, Z), 128.5 (s, Cq,
E), 131.0 (m, CH, E), 131.1 (q, J = 3.0 Hz, CH, Z), 133.9 (s, CH, E), 134.0
(s, CH, Z), 136.2 (s, Cq, E), 136.4 (s, Cq, Z), 141.9 (m, Cq, E), 144.7 (q, J
= 3.0 Hz, CH, Z), 146.3 (s, Cq, Z), 162.4 (m, Cq, Z). HRMS (ESI-TOF):
calcd for C11H7ClF3NO4Na m/z 331.9913 [M+Na]+, found 331.9906.
[3]
[4]
[5]
K. Rousée, J.-P. Bouillon, S. Couve-Bonnaire, X. Pannecoucke, Org.
Lett. 2016, 18, 540.
Methyl 3-(4-methoxy, 2-nitrophenyl)-2-trifluoromethylacrylate (9p):
Yellow oil. Mixture E/Z 37/63. IR: 2959, 1731, 1620, 1529, 1499, 1439,
1345, 1276, 1251, 1130, 1032, 843, 804 cm-1. 19F NMR (282 MHz, CDCl3):
δ -58.0 (s, Z), -64.1 (d, J = 1.7 Hz, E). 1H NMR (300 MHz, CDCl3): δ 3.66
(s, 3H, E), 3.92 (s, 6H, Z), 3.93 (s, 3H, E), 7.1- 7.3 (m, 2H, E + Z), 7.75
(dd, J = 9.0, 3.0 Hz, 1H, Z), 7.95 (m, 1H, E), 8.38 (s, 1H, Z). 13C NMR (75
MHz, CDCl3): δ 52.5 (s, CH3, E), 52.9 (s, CH3, Z), 56.0 (s, CH3, E), 56.1
(s, CH3, Z), 109.47 (s, CH, E), 109.52 (s, CH, Z), 120.2 (s, CH, E), 120.3
(s, CH, Z), 121.5 (s, Cq, Z), 121.7 (q, J = 273.0 Hz, Cq, Z), 121.78 (s, Cq,
E), 121.79 (q, J = 271.5 Hz, Cq, E), 122.4 (q, J = 30.8 Hz, Cq, Z), 123.5
(q, J = 31.5 Hz, Cq, E), 131.2 (s, CH), 131.4 (q, J = 3.0 Hz, CH), 142.2 (q,
J = 6.8 Hz, CH, E), 146.1 (q, J = 3.0 Hz, CH, Z), 147.0 (s, Cq, Z), 147.5 (s,
Cq, E), 160.8 (s, Cq, E), 160.9 (s, Cq, Z), 162.4 (s, Cq, E), 162.9 (q, J =
1.5 Hz, Cq, Z). HRMS (ESI-TOF): calcd for C12H10F3NO5Na m/z 328.0409
[M+Na]+, found 328.0403.
For reviews about decarboxylative cross-coupling reactions, see: a) N.
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Acknowledgements
As expected, the reaction performed with benzoic acid without ortho-
substituent, i.e. benzoic acid or meta- or para-methoxybenzoic acids as
substrates, led only to traces of product.
This work was supported by INSA Rouen, Rouen University,
CNRS, EFRD, Labex SynOrg (ANR-11-LABX-0029) and Région
Normandie (Crunch Network). O.B. thanks the Erasmus Battuta
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European Journal of Organic Chemistry
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Decarboxylation/fluoroalkenylation*
Ouafa Bouazzaoui, Kevin Rousée,
Joseph Kajima Mulengi, Xavier
Pannecoucke, Jean-Philippe Bouillon,*
Samuel Couve-Bonnaire*
Page No. – Page No.
A ligand-free palladium-catalyzed decarboxylative olefination process is reported
between carboxylic acids and valuables methyl 2-fluoroacrylate or methyl 2-
trifluoromethylacrylate. The reaction affords the desired trisubstituted fluorinated
alkenes in low to fair yields with electron-poor carboxylic acids and good to excellent
yields with electron-rich carboxylic acids.
Synthesis of α-Fluorinated Acrylates
by Palladium-Catalyzed
Decarboxylative Olefination Reaction
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