Direct Stereoselective β-Arylation of Enol Ethers by a Decarboxylative Heck-Type Reaction

Article abstract of DOI:10.1002/ejoc.201901877

Despite remarkable advances to promote regio- and stereoselective decarboxylative arylation of inactivated olefins with benzoic acid derivatives, methodologies involving hetero-substituted alkenes are still lacking. Herein, Pd^II-catalyzed decarboxylative Heck coupling of α-alkoxyacrylates with (hetero)aryl carboxylic acids for the stereocontrolled production of (Z)-β-heteroarylated vinyl ethers is reported. This methodology offers a rational and step-economical route to the synthesis of attractive β-arylated α-alkoxy α,β-unsaturated carboxylates family which emerged as a relevant class of building blocks with different applications. Mechanistically, whereas electron rich benzoic acids undergo a Pd^II-catalyzed decarboxylation, electron-deficient substrates proceed through silver(I)-mediated decarboxylation, explaining thus the formation of stereoisomers (E) and (Z) of β-arylated vinyl ethers in presence of these latter.

Full text of DOI:10.1002/ejoc.201901877

A Journal of
Accepted Article
Title: Direct Stereoselective β-Arylation of Enol Ethers by
Decarboxylative Heck-type Reaction
Authors: Mahmoud Hachem, Cédric Schneider, and Christophe
Hoarau
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
Direct Stereoselective
β-Arylation
of Enol Ethers by
Decarboxylative Heck-type Reaction
Mahmoud Hachem,[a] Cédric Schneider,[a]* Christophe Hoarau*[a]
[a]
M. Hachem, Dr. C. Schneider,* Pr. C. Hoarau*
Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA (UMR 6014)
1 rue Tesnière 76 821 Mont-Saint-Aignan Cedex, France
E-mail: cedric.schneider@univ -rouen.fr ; christophe.hoarau@insa-rouen.fr
http://www.lab-cobra.fr
Abstract: Despite remarkable advances to promote regio- and
stereoselective decarboxylative arylation of unactivated olefins with
benzoic acid derivatives, methodologies involving hetero-substituted
alkenes are still lacking. Herein, Pd(II)-catalyzed decarboxylative Heck
coupling of -alkoxyacrylates with (hetero)arylcarboxylic acids for the
stereocontrolled production of (Z)-β-heteroarylated vinyl ethers is
reported. This methodology offers a rational and step-economical
route to the synthesis of attractive β-arylated α-alkoxy α,β-
unsaturated carboxylates family w hich emerged as a relevant class of
building blocks w ith different applications. Mechanistically, w hereas
electron rich benzoic acids undergo a Pd(II)-catalyzed decarboxylation,
electron-deficient substrates proceed through silver(I)-mediated
decarboxylation, explaining thus the formation of stereoisomers (E)
and (Z) of β-arylated vinylethers in presence of these latter.
alkenes.[9-10] To date, Heck coupling of non-prefunctionalized vinyl
ethers w ith halides is the most step-economical developed
strategy (Eq 1, Figure 1),[11-12] but fraught w ith difficulties due to
selectivity issues (/ and Z/E).[12] In consequence, traditional
cross-coupling reactions are preferred for a full control of the
regio- and the stereochemistry w hen pre-metalated vinyl ethers
are available (Eq 2).[10, 13]
Introduction
Palladium-catalyzed Heck reaction of aryl halides w ith olefins has
been regarded as one of the most pow erful method for the
formation of C-C bonds in organic synthesis.[1, 2] Its fundamental
importance in synthetic organic chemistry has given a great
impetus to the development of new versions of the Heck coupling,
in w hich the electrophilic aryl halide is replaced by distinct
substrates. Inexpensive, stable, easy to handle and to store, and
readily available, carboxylic acids are now identified as reliable
masked organometallic building blocks in the development of
innovative transition-metal catalyzed decarboxylative cross-
[3]
coupling reactions for the construction of various C(sp2)-C and
C(sp2)-heteroatom bonds.[4-6] In 2002, Myers and co-w orkers
have reported the first Pd(II)-catalyzed decarboxylative Heck
reaction of ortho-substituted arylcarboxylic acids w ith α,β-
unsaturated carbonyls and styrenes.[7] While remarkable
advances have been made to promote regio- and stereoselective
decarboxylative arylation of unactivated olefins w ith aryl
carboxylic acids,[8] few examples have been reported using
hetero-substituted alkenes.[9]
Figure 1: Pd-catalyzed arylation of enol ethers. [TM] = transition metal.
Among classes of hetero-substituted alkenes, vinyl ethers
represent one of the most reactive and valuable building blocks
for the synthesis of complex organic molecules. These electron-
rich alkenes are found in many natural products and biologically
active molecules. Employed as masked-ketones and activated
alkenes, vinyl ethers are involved in number of chemical
transformations such as hydrolysis, reduction, cycloaddition
reactions, Heck and related cross-coupling reactions to produce
In this context, -alkoxyacrylate derivatives have been selected
as coupling partners of choice to address important challenges in
the (hetero)arylation of enol ethers: (1) to control the selectivity in
the Heck coupling (Eq 3),[14] and (2) to give access to several
synthetically-challenging building blocks. Indeed, our group has
recently reported the first regio- and stereocontrolled formation of
α-heteroarylated enol ethers I by Pd-catalyzed decarboxylative C-
H coupling of -alkoxyacrylic acid derivatives, as w ell as the
poly-functionalized
ketones,
alcohols,
heterocycles
and
1
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
and 8d]
synthesis of (Z)--arylated enol ethers II by copper mediated
Myers and Liu observations,[8b
highlighting the key role of
protodecarboxylation
reactions.[15] Herein,
Pd(II)-catalyzed
Pd(TFA)2 in the decarboxylative step (Entries 5-7). A further
investigation of various oxidants revealed that Ag2CO3 remains
the best for this transformation.[20] We also noticed that
decarboxylative Heck coupling of -alkoxyacrylates w ith
(hetero)aryl carboxylic acids for the stereocontrolled production of
(Z)-β-heteroarylated vinyl ethers is reported (Figure 1, Eq 4). This
methodology offers a rational and step-economical route to
attractive β-arylated α-alkoxy α,β-unsaturated carboxylates.
These latter are important precursors of α–keto esters III[16] and
optically active α-oxo-functionalized carboxylic acids IV w hich are
know n to be valuable buildings blocks in pharmaceutical and
agrochemical industries, as w ellas in total synthesis (Figure 1).[17]
3
equivalents of Ag2CO3 as w ellas sub-stoichiometric amounts (1.5
equivalents) of ethyl 2-methoxyacrylate 1A are required to get an
efficient Pd(II)-catalyzed decarboxylative Heck reaction.[20] To get
complete conversion of 2-methoxybenzoic acid 2a, several
parameters have been screened such as the temperature, the
concentration and the reaction time (Entries 8-11). Although the
increase of temperature and concentration of the media are
deleterious (Entries 8-9), the decrease of this latter from 0.2 M to
0.08 M led to
a better production of ethyl -arylated 2-
methoxyacrylate 3Aa from 49% to 61% (Entry 9). Finally ,
extension of the reaction time from 12 h to 24 h allow ed to reach
a complete conversion of coupling partner 2a w ith an excellent
isolated yield of 82% in 3Aa (Entry 11). Importantly, only the
stereoisomer (Z) w as observed and its configuration was
confirmed by comparison w ith literature data.[17d].
Results and Discussion
Table 1. Optimization of the palladium-catalyzed decarboxylative Heck reaction
with ethyl 2-methoxyacrylate 1A.
Entry
1
[Pd]
Solvent
DMF
C (mol.L-1)
0.2
Yield (%)[b]
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
PdCl2
23
10
21
49
42
35
21
27
40
61
82
2
DMAc
0.2
3
DMSO
0.2
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
0.2
5
0.2
6
Pd(OAc)2
Pd(acac)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
0.2
7
0.2
8[c]
9
0.2
0.4
10
11[d]
0.08
0.08
Scheme 1. Substrate scope with electron-rich carboxylic acids.
[a] Conditions: 2a (1.0 equiv), 1A(1.5 equiv), [Pd] (20 mol%), Ag2CO3 (3 equiv),
Solvent, 130 °C, 12 h, C (mol.L-1). [b] Yield of the isolated product. [c] Reaction
carried out at 140 °C. [d] Reaction performed for 24 h.
With these optimized conditions in hands, the scope of the
decarboxylative Heck coupling w as undertaken on ethyl 2-
methoxyacrylate 1A w ith a panel of electron-rich benzoic acids.
As show n in Scheme 1, a variety of substituted 2-alkoxybenzoic
acids 2a, 2d and 2f displayed a good reactivity providing β-
arylated 2-methoxyacrylates 3Ab, 3Ad and 3Af as pure (Z)-
isomers in medium to good yields. Interestingly, β-arylated o,o’-
dialkoxy-products 3Ac, 3Ae and 3Ag w ere produced w ith slightly
low er yields than the corresponding ortho-monosubstituted
products. These results show ed that the high steric hindrance
associated w ith the high palladium-oxygen coordination reduce
the effectiveness of the decarboxylative Heck coupling. In the
same manner, the 2,4,6-trimethylbenzoic acid 2h turned out to be
a more effective substrate than the 2,4,6-trimethoxybenzoic acid,
leading to the ethyl -arylated 2-methoxyacrylate 3Ah in 80%
yield. To our delight, this methodology w as also suitable w hen
Our investigation about the β-arylation of ethyl 2-
methoxyacrylate 1A[18] by Pd-catalyzed decarboxylative Heck-
type coupling w as initiated w ith 2-methoxybenzoic acid 2a.
Choice of the coupling partner 2a w as driven by the steric
hindrance and the electronic nature of the ortho-methoxy
substituent, tw o factors w hich are know n to facilitate the
decarboxylative step.[19] Under the Myers’s experimental
conditions, the -arylated 2-methoxyacrylate
3Aa was
immediately isolated in 23% yield in presence of Pd(TFA)2 as
catalyst and Ag2CO3 as additive in DMF (Table 1, Entry 1).[8a] In
contrast to 1,4-dioxane/DMSO (95:5) system, the use of more
polar solvents, such as DMF/DMSO, DMAc/DMSO or pure DMSO
affected the efficiency of this coupling (Entries 2-4).[20] Other
palladium sources such as PdCl2, Pd(OAc)2 and Pd(acac)2 have
been tested and gave low er yields, in accordance w ith previous
2
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
using 3-methyl benzofuran-2-carboxylic acid 2i as coupling
partner, giving the desired Heck coupling product 3Ai in 70% yield.
construction of mono- or polyfluoroarylated vinyl ethers remains
unstudied to date.
Scheme 3. Substrate scope with fluorinated benzoic acid derivatives.
In this context, the decarboxylative Heck-coupling of ethyl
2-methoxyacrylate 1A w ith fluorinated benzoic acids 2o-q was
performed under the optimized reaction conditions (Scheme 3).
6-Bromo-2-fluorobenzoic acid 2o w as first employed and only
isomer Z-3Ao w as formed in 41% or 42% depending on the
nature of the solvent mixture, 1,4-dioxane/DMSO or DMF/DMSO
respectively. Unlike the result obtained w ith 2o, DMSO as additive
affected dramatically the coupling efficiency in presence of the
more electron-deficient 2,4,6-trifluorobenzoic acid 2p. Indeed, we
observed that the reaction performed in pure 1,4-dioxane or DMF
as solvent gave the isomer Z-3Ap in moderate 40% to good 80%
Scheme 2. Substrate scope with electron-poor carboxylic acids.
Next, w e turned our attention to the evaluation of electron-poor
nitrated and chlorinated benzoic acids 2j-n as coupling partners
under our optimized reaction conditions (Scheme 2). Globally, we
first noticed significant low er yields (40-28%) compared w ith
electron-rich benzoic acids, w hatever the solvent mixture is (1,4-
dioxane/DMSO, DMF/DMSO or in the absence of DMSO). This
loss of efficiency results from the production of tw o side products
4 and 5 generated by silver mediated protodecarboxylation
reaction and homocoupling reaction (Scheme 2). It is notew orthy
that the use of 1,4-dioxane alone affected the performance of this
process, thus pointing out the key role of highly polar solvent or
co-solvent as DMF or DMSO for this transformation. [21] Moreover,
all β-arylated 2-methoxyacrylates 3Aj-m are obtained as pure (Z)-
yields
respectively.
The
most
electron-deficient
pentafluorobenzoic acid 2q w as then engaged in the
decarboxylative Heck-type coupling w ith 1A. We w ere pleased to
find that the ethyl pentafluoroarylated 2-methoxyacrylate 3Aq was
produced in 51% yield as a mixture of isomers Z-3Aq and E-3Aq
w ith the (E)-isomer as the major one (ratio Z/E 1:2). It is
notew orthy that the (Z)-3Aq isomer can be mainly produced in
1,4-dioxane as solvent (ratio Z/E 5.7:1) but w ith a dramatic fall of
yield (20%). Finally, reactions performed in all others solvents
proved to be ineffective.
isomers,
excepted
for the coupling
betw een 2,3,4-
trichlorobenzoic acid 2n and 1A. Indeed, the ethyl β-arylated 2-
methoxyacrylate 3An is provided as a (Z/E)-isomers mixture (ratio
3:2) suggesting the involvement of a competitive mechanism.
While a better ratio in favor of (Z)-isomer (ratio Z/E 4.2:1) was
observed in DMSO/DMF mixture (5:95), the production of 3An as
pure (Z)-isomer w as achieved in pure DMF albeit in 20% poor
yield.
Fluorinated arenes are an important class of molecules that
are w idely used in pharmaceuticals, agrochemicals, functional
materials such as liquid crystals (LCs), organic light-emitting
diodes (OLED), and electron transport materials ow ing to the
unique property of the fluoride group.[22] Therefore, efficient and
selective methods for the facile introduction of fluorinated moiety
into organic backbone have become a fascinating field of
research in the last year,[8l] and transition metal catalysis has been
successfully employed for this purpose.[23] How ever, the selective
Scheme 4. Substrate scope with various α-alkoxyacrylates 1 and carboxylic
acids 2a and 2r. aDMF/DMSO (95/5) was used.
3
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
Scheme 5. Control experiments with ethyl 2-methoxybenzoic acid and various electron-deficient benzoic acids.
To further examine the versatility of the methodology, the
decarboxylative Heck-coupling of various α-alkoxy α,β-
to confirm or invalidate this mechanism pathw ay for the β-
arylation of ethyl 2-methoxyacrylate (1a) w ith electron-rich
benzoic acids, control experiment w ith a stoichiometric amount of
palladium in absence of Ag2CO3 has been performed (Scheme 5,
eq 1). We noticed that stoichiometric amounts of Pd(TFA) 2
enabled the reaction of ethyl 2-methoxyacrylate 1a w ith 2-
methoxybenzoic acid 2a in 1,4-dioxane/DMSO (95:5) mixture at
130 °C to generate the desired product 3Aa in 54% yield.
Additionally, a reaction w as carried out w ith 2-methoxybenzoic
acid 1a using an excess of Ag2CO3 and in absence of Pd(TFA)2
(Scheme 5, Eq 2). 1H NMR analysis of the crude product show ed
a 7:3 ratio betw een the protonated product 4a and the acid 1a.
Therefore, these results prove that the mechanistic hypothesis
involving a palladium monocatalysis described by Myers[8b] is
most likely happening in the presence of electron-rich benzoic
acids (Scheme 6, path A).
unsaturated carboxylates 1B-E and ortho-substituted benzoic
acids 2 w as next achieved (Scheme 4). We w ere pleased to
observe the stereocontrolled formation of desired (Z)-β-arylated
products 3Ba and 3Br in moderate yields from 1,3-dioxolan-4-one
1B w ith electron-rich and electron–deficient benzoic acids 2a and
2r. The benzyl -methoxyacrylate 1C as w ell as ethyl -phenoxy-
and -benzyloxyacrylates 1D-E have proved to be efficient
coupling partners leading to a library of various (Z)--arylated
acrylates 3Ca, 3Cn, 3Da, 3Ea and 3En in fair to good yields by
using either electron-rich 2a or electron-poor benzoic acid 2r.
How ever, based on w orks of Su[24] and Jana,[8l]
a
competitive process involving a Pd/Ag, bimetallic system can be
envisaged w ith electron-deficient substrates for the formation of
stereoisomers (Z), w here the decarboxylation step is now
mediated by silver(I) carbonate generating
species after transmetallation w ith Pd(OAc)2 as depicted in path
B, Scheme 6. Additional experimental controls using
a arylpalladium
Scheme 6. Plausible mechanisms for the decarboxylative Heck-coupling of -
methoxyacrylates with electron-rich (path A) and electron-poor (path B) benzoic
acids leading to (Z)--arylated -alkoxyacrylates.
stoichiometric amount of Pd(OAc)2 and silver(I)-mediated
protodecarboxylation reactions w ere thus carried out from several
electron-deficient benzoic acids (Scheme 5). The poor reactivity
in absence of silver (I) salt as additive for decarboxylative Heck
couplings (Eq 3 and 4), as w ell as the quantitative production of
protonated arenes 4 from Ag(I)-mediated protodecarboxylation
reactions, w hatever the selected solvent is (Eq 5),[25] highlighted
the predominant role of Ag2CO3 in the decarboxylation-metalat ion
step. Therefore, all the above results converge to the mechanistic
path B for w hich the Pd(TFA)2-catalyzed decarboxylative step is
To date, the respective role of Pd(TFA)2 and Ag2CO3 in the Heck
decarboxylative process w ith electron-rich benzoic acids has
been experimentally and theoretically w ell investigated by Myers
and 8d]
and Liu.[8b
Notably, it has been w ell established that the
decarboxylation step occurs in the presence of palladium salt
w hereas Ag2CO3 acts as an oxidant for catalytic turnover. In order
4
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
energetically higher than the Ag2CO3 mediated one due to the
poor stabilization of the resulting positive charge produced during
the ipso-decarboxylative transition state.
decarboxylation. From this hypothesis, three mechanistic
pathw ays have been speculated explaining the formation of
stereoisomers (E) and (Z) in presence of electron-deficient
benzoic acids (Schemes 6 and 7, Path B-D).
Experimental Section
General information: Solvents and reagents: All commercially available
reagents were used as received, except otherwise specified. Palladium
catalyst and phosphineligandswere stored in desiccators. Extra dry DMAc,
1,4-dioxane, DMF and DMSO were obtained from Accros Organic® in
sealed bottles over 3Å or 4Å molecular sieves and stored under N2.
Purification: Chromatography columns were performed using silica gel
(mesh size 60-80 mesh). TLC were performed using Merck® TLC silica
gel 60 F254 and product revealed by UV irradiation (λ = 254 nm). Analysis:
1H and 13C NMR spectra were recorded at room temperature ona Brucker
Advance spectrometer operating at 300 MHz and 75 MHz respectively.
Chemical shifts(δ) are given asppm relative to the residual solventpeak
(7.26 for 1H and 77.16 for 13C in CDCl3). Splitting patterns are indicating
as fellow: br: broad; s: singulet; d: doublet; t: triplet; q: quartet; qt:
quintuplet; sp: septuplet; dd: doublet of doublet; dt: doublet of triplet; tt:
triplet of triplet; qt: quintuplet; m: multiplet. IR spectra recorded on Perkin
Elmer Spectrum 100 FT IR spectrometers. Melting Point were measured
on a Fisher Scientific hot stage melting point apparatus and are
uncorrected. GC/MS analysis (EI, 70 Ev) were performed on the Agilent
GC: 6850, MS: 5975 using HP-5MS column (30 m x 0.25 mm x 0.25 µm)
with the following method: 50 °C (2 min) to 250 °C (15 min) with an
increase of 25 °C.min-1. Mass analysis (ESI) were performed on a LCQ
Scheme 7. Plausible mechanisms for the decarboxylative Heck-coupling of -
methoxyacrylates with electron-poor benzoic acids leading to (E)--arylated -
alkoxyacrylates.
By contrast, the production of -arylated -methoxyacrylates as
(E)-isomer and enol ether homocoupling product 5 might be
explained by a competitive mechanism to the Ag2CO3-mediated
decarboxylative step. This competitive mechanism might involve
an ortho-directed electrophilic palladation[26] of the enol ether in
the presence of electron-poor benzoic acids. Tw o mechanistic
pathw ays C and D can be considered for the formation of the
intermediate (E)-III w hich provides the β-arylated (E)-isomer by
reductive elimination (Scheme 7). Thus, the (E)-methoxyacrylate-
palladium intermediate (I)[27] issued from the heteroatom-guided
electrophilic palladation pathw ay[26] can undergo either (1) a
transmetallation step w ith -arylsilver(I) species (II) arising from
Ag2CO3-mediated decarboxylative-metalation step (Scheme 7,
path C), or (2) a decarboxylation step to provide the intermediate
(E)-III (Scheme 7, path D). This latter pathw ay can be envisaged
because the stereoisomer (E)-3Aq is obtained during the
Advantage. Ethyl 2-methoxyacrylate 1A[18]
, 2-(1,1-dimethylethyl)-5-
methylene-1,3-dioxolan-4-one 1B[28] are synthetized according to the
literature.
Synthesis of Cesium 2-methoxyacrylate 6, and 2-alkoxyacrylate
derivatives1C, 1D and 1E:
Cesium 2-methoxyacrylate 6: To a solution of cesium hydroxide
monohydrate (16.8 mmol, 2.8 g,) in 11 mL of propan-2-ol and 15 mL of
water was added in portion(very exothermic) ethyl 2-methoxyacrylate1A
(15.3 mml, 2g). The mixture washeated at reflux overnight andthesolvent
was evaporated to dryness under reduced pressure. The crude product
was then triturated in cold propan-2-ol and filteredto give the cesium salt
6. The solid wasthenwashed withmethanol and Et2O toafford the product
6 (3.16 g, 13.5 mmol) in 80% yield as a white solid. mp = 155-157 °C
(pentane). IR: 3445, 2972, 1728, 1156, 1094,857cm-1.1H NMR (300 MHz,
decarboxylation/olefination
coupling
betw een
the
pentafluorobenzoic acid 2q and the 2-methoxyacrylate 1A in
absence of Ag2CO3 but w ith stoichiometric amount of palladium.
(Scheme 5, Eq 4).
D2O) δ 5.05 (d, J = 2.0 Hz, 1H), 4.53 (d, J = 1.9 Hz, 1H), 3.57 (s, 3H). 13
C
Conclusion
NMR (75 MHz, D2O) δ 170.77 (C), 156.07 (C), 90.31 (CH), 55.05 (CH3).
MS (ESI-TOF) m/z 101.02 [M-H+].
In summary, w e have developed the regio- and stereocontrolled
synthesis of (Z)-β-(hetero)arylated vinyl ether via stereoselective
decarboxylative Heck-type coupling of various 2-alkoxyacrylates
under palladium catalysis using a variety of arene carboxylic acids
as electrophiles. This methodology offers a rational and step-
economical route to the synthesis of attractive β-arylated α-alkoxy
α,β-unsaturated carboxylates family w hich emerged as a relevant
class of building blocks w ith different applications. A noticeable
difference has been observed betw een electron-rich and electron-
deficient acids in terms of efficiency and stereochemistry. This
substrate dependence is due to mechanistic divergences during
the decarboxylation step. Whereas the mechanism pathw ay
described by Myers is most likely happening w ith electron-rich
benzoic acids (Scheme 7, Path A), the non-stabilization of the
positive charge produced during the palladium-catalyzed ipso-
decarboxylation transition state in presence of electron-deficient
acids favors a competitive process involving an Ag2CO3-media ted
Benzyl 2-methoxyacrylate 1C: To the solution of cesium salt 6(1 eq, 4.29
mmol, 1 g) in 10 mL of anhydrous1,4-dioxane wasadded HBTU (1.5 eq,
6.375 mmol, 2.4 g) and N,N-diisopropylethylamine (1.5 eq, 6.375 mmol,
1ml). The solution was then stirred for 5 min at r.t. To this mixture was
added benzyl alcohol (1.1 eq, 4.675 mmol, 0.5 ml) and 4-
dimethylaminopyridine (0.1 eq,0.425mmol, 52 mg), and thesolution was
then stirred at r.t. overnight. Solvents were removed under reduced
pressure. The crude product was purified by flash chromatography
(PE/Et2O 8:2) to afford 1C (500 mg, 2.635 mmol) in 62% as a yellow oil.
IR: 3063, 2954, 2850, 1680, 1550, 1489, 1165, 750, 682 cm-1. 1H NMR
(300 MHz, CDCl3) δ 7.37 (m, 5H), 5.39 (s, 1H), 5.26 (s, 2H), 4.65 (s, 1H),
3.66 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.6 (C), 145.5 (C), 136.1 (C),
128.7 (2xCH), 128.3 (2xCH), 118.0 (CH), 103,5 (2xCH), 66.8 (CH2), 59.4
(CH3). MS (ESI-TOF) m/z 193.07 [M+H+]. HMRS (EI-TOF): calc. for
C11H12O3; 192.0786found 192.0795.
Ethyl 2-phenoxyacrylate 1D: A suspension of ethyl 2-phenoxy-2-
diethylphosphonoacetate[29](200 mg, 0.632mmol) and DBU (120 µL, 1.58
5
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10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
mmol) in anhydrous THF (6 mL) was stirred for 10 minutes at rt. To this
mixture wasadded paraformaldehyde (28.46mg, 0.95mmol) and heated
at reflux overnight. The solvent wasthen removed under reduced pressure,
and the crude residue was dissolved in EtOAc. The organic layer was
washed with saturated aqueousNH4Cl solution, brine, driedover MgSO4
and filtered. and washed with saturated aqueousNH4Cl solution and brine.
Solventswere removed under reduced pressure to give 1D in quantitative
yield asa colorless oil. IR: 2983, 1730, 1623, 1592, 1490, 1094 692cm-1.
1H NMR (300 MHz, CDCl3) δ 7.35 (t, J = 7.9 Hz, 2H), 7.14 (t, J = 7.4 Hz,
1H), 7.04 (d, J = 7.8 Hz, 2H), 5.70 (d, J = 1.8 Hz, 1H), 4.90 (d, J = 1.8 Hz,
1H), 4.29 (q, J = 7.1 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 162.6 (C), 155.3 (C) 150.6 (C), 129.6 (2xCH), 124.0 (CH), 119.0
(2xCH), 104.0 (2xCH), 61.7 (CH2), 14.1 (CH3). MS (ESI-TOF) m/z 193.15
[M+H+]. HMRS (EI-TOF): calc. for C11H12O3; 192.0786:found192.0792.
(Z)-ethyl 3-(2,6-dimethoxyphenyl)-2-methoxyacrylate 3Ac: Compound
3Ac wasprepared from ethyl 2-methoxyacrylate 1A (39mg,0.3mmol) and
2,6-dimethoxybenzoic acid 2c (36 mg, 0.2mmol) according to thegeneral
procedure A. The crude prodcut was purified by flash chromatography
(PE/AcOEt 85:15) to afford 3Ac (24 mg, 0.09 mmol) in 45% yield as a
yellow oil. IR: 2989,2941, 2834, 1714,1582, 1471, 860 cm-1.1H NMR (300
MHz, CDCl3) δ 7.23 (t, J = 7.1 Hz, 1H), 6.89 (s, 1H), 6.55 (d, J = 8.4 Hz,
2H), 4.29 (q, J = 7.1 Hz, 2H), 3.82 (s, 6H), 3.59 (s, 3H), 1.35 (t, J = 7.1 Hz,
3H).13C NMR (75 MHz, CDCl3) δ 164.3 (C), 158.0 (2xC), 146.8 (C), 129.6
(CH), 112.9 (CH), 111.5 (C), 103.4 (2xCH), 61.2 (CH2), 58.9 (CH3), 55.8
(2xCH3), 14.4 (CH3). MS (ESI-TOF) m/z 267.1 [M+H+]. HMRS (EI+): calc.
for C14H18O5; 266.1154:found266.1147.
(Z)-ethyl
2-methoxy-3-(2,4,5-trimethoxyphenyl)acrylate
3Ad:
Compound 3Ad was prepared from ethyl 2-methoxyacrylate 1A (39 mg,
0.3 mmol) and 2,4,5-trimethoxybenzoic acid 2d (43 mg, 0.2 mmol)
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 75:25) to afford 3Ad (46 mg, 0.15 mmol)
in 78% yield a yellow oil. IR: 2954, 2845, 1720, 1607, 1550, 1450, 1211,
850 cm-1. 1H NMR (300 MHz, CDCl3) 7.83 (s, 1H), 7.44 (s, 1H), 6.49 (s,
1H), 4.30 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 3.85 (s, 6H), 3.74 (s, 3H), 1.36
(t, J = 7.1 Hz, 3H).13C NMR (75 MHz, CDCl3) δ 165.9 (C), 153.0 (C), 149.4
(C), 143.9 (C), 143.4 (C), 117.7 (CH), 114.0 (C), 113.2 (CH), 96.5 (CH),
61.1 (CH2), 59.3 (CH3), 56.6 (CH3), 56.3 (CH3), 56.0 (CH3), 14.5 (CH3). MS
(ESI-TOF) m/z 296.22 [M+H+]. HMRS (ESI-TOF): calc. for C15H21O6;
297.3190: found297.3195.
Ethyl 2-(benzyloxy)acrylate 1E: A suspension of ethyl 2-benzyloxy-2-
diethylphosphonoacetate[29-30] (200 mg, 0.6 mmol) and DBU (0.2 mL, 1.5
mmol) in THF (6 mL) was stirred for 10 minutesat rt. To this mixture was
added paraformaldehyde (27mg,0.9 mmol) and heatedat reflux overnight.
The solvent was then removed under reduced pressure, and the crude
residue was dissolved in EtOAc. The organic layer was washed with
saturated aqueous NH4Cl solution, brine, dried over MgSO4 and filtered.
Solventswere removed under reduced pressure to give 1E in quantitative
yield asa colorlessoil. 1H NMR (300 MHz, CDCl3)δ 7.4 (m, 5H), 5.35 (d,
J = 2.0 Hz, 1H), 4.85 (s, 2H), 4.62 (d, J = 2 Hz, 1H), 4.23 (q, J = 7.1 Hz
2H), 1.32 (t, J = 7.1 Hz, 3H). Exhibited spectra data identical to previous
reports.[31]
(Z)-ethyl
2-methoxy-3-(2,4,6-trimethoxyphenyl)acrylate
3Ae:
General procedure A for the decarboxylative Heck coupling: To an
oven-dried sealed tube containing a magnetic stir bar were added α-
alkoxyacrylates 1A–H (1.5 eq), benzoic acid derivatives 2a–g (1 eq),
PdTFA2 (20 mol%), and Ag2CO3 (3 eq). After purging the reaction vessel
with nitrogen, anhydrous 1,4-dioxane (2.3 mL) and DMSO (0.1 mL) was
added to the reactionmixture andthe vessel wassealed with a screw cap.
The reaction mixturewasheated at 130 °C for 24 hours. After completion
(as detected by TLC), the reactionmixture waspoured into water (10 mL)
and extracted with EtOAc (3x20 mL). The organic layer was dried over
MgSO4 andfilteredover celite. Solventswere thenremovedunder reduced
pressure. The crude product was then purified by flash column
chromatography.
Compound 3Ae was prepared from ethyl 2-methoxyacrylate 1A (39 mg,
0.3 mmol) and 2,4,6-trimethoxybenzoic acid 2e (43 mg, 0.2 mmol)
according to the general procedure A. The crude prodcut waspurified by
flash chromatography (PE/EtOAc 8:2) to afford 3Ae (32 mg, 0.108mmol)
in 54% yield a yellow oil. IR: 2941, 2841, 1711, 1603, 1582, 1454, 1202,
809 cm-1.1H NMR (300 MHz, CDCl3) 6.86 (s, 1H), 6.12 (s, 2H), 4.27 (q, J
= 7.1 Hz, 2H), 3.82 (s, 3H), 3.81 (s, 3H), 3.59 (s, 3H), 1.34 (t, J = 7.1 Hz,
3H).13C NMR (75 MHz, CDCl3) δ 164.6 (C), 161.7 (C), 158.9 (2xC), 146.1
(C), 113.1 (CH), 104.4 (C), 90.3 (2xCH), 61.1 (CH2), 58.9 (CH3), 55.8
(2xCH3), 55.4 (CH3), 14.4 (CH3). MS (ESI-TOF) m/z 296.22 [M+H+]. HMRS
(ESI-TOF): calc. for C15H21O6; 297.3190:found297.3195.
(Z)-ethyl 3-(2-ethoxyphenyl)-2-methoxyacrylate 3Af: Compound 3Af
was prepared from ethyl 2-methoxyacrylate 1A (39 mg,0.3 mmol) and 2,6-
diethoxybenzoic acid 2f (33 mg, 30μL, 0.2mmol) accordingto thegeneral
procedure A. The crude product was purified by flash chromatography
(PE/EtOAc 95:5) to afford 3Af (23 mg, 0.092 mmol) in 46% yield as a
yellow oil. IR: 2998, 2941, 2842, 1706, 1604, 1574, 1500, 832, 770 cm-
1.1H NMR (300 MHz, CDCl3) δ 8.13 (dd, J = 1.3 and 7.8 Hz, 1H), 7.49 (s,
1H), 7.29 – 7.24 (m, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H),
4.32 (q, J = 7.1 Hz, 2H), 4.11 (q, J = 7.0 Hz, 2H), 3.74 (s, 3H), 1.45 (t, J =
7.0 Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H).13C NMR (75 MHz, CDCl3) δ 164.8(C),
156.9 (C), 145.6 (C), 130.6 (CH), 130.3(CH), 122.5 (C), 120.6 (CH), 117.6
(CH), 111.7 (CH), 64.1 (CH2), 61.2 (CH2), 59.3 (CH3), 14.9 (CH3), 14.4
(CH3) MS (ESI-TOF) m/z 251.13 [M+H+].HMRS (ESI-TOF): calc. for
C14H19O4; 251.2940: found 251.2950.
(Z)-ethyl 2-methoxy-3-(2-methoxyphenyl)acrylate 3Aa: Compound
3Aa wasprepared from ethyl 2-methoxyacrylate 1A (39mg,0.3mmol) and
2-methoxy benzoic acid 2a (30 mg, 0.2 mmol) according to the general
procedure A. The crude product waspurifiedby flash chromatography (PE/
EtOAc 9/1) to afford 3Aa (39 mg, 0.165 mmol) in 83% yield asa coloress
oil. IR: 2990, 2841, 1715, 1620,1580,11474, 1113,840, 752 cm-1.1H NMR
(300 MHz, CDCl3) δ 8.10 (d, J = 7.7 Hz, 1H), 7.44 (s, 1H), 7.30 (t, J = 7.9
Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 8.3 Hz, 1H), 4.32 (q, J = 7.1
Hz, 2H), 3.87 (s, 3H), 3.74 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 164.7 (C), 157.4 (C), 145.7 (C), 130.6 (CH), 130.3 (CH),
122.3 (C), 120.7 (CH), 117.3 (CH), 110.5 (CH), 61.2 (CH2), 59.3 (CH3),
55.6 (CH3), 14.4 (CH3). MS (ESI-TOF) m/z 237.12 [M+H+]. HMRS (ESI-
TOF): calc. for C13H17O4; 237.1346: found279.1345.
(Z)-ethyl 3-(2,4-dimethoxyphenyl)-2-methoxyacrylate 3Ab: Compound
3Ab was prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol)
and 2,4-dimethoxybenzoic acid 2b (37 mg, 0.2 mmol) according to the
general procedure A. The crude product was purified by flash
chromatography (PE/AcOEt 95:5) to afford 3Ab (43 mg, 0.158 mmol) in
79% yield asa yellow oil. IR: 2983,2938, 1713, 1622, 1575, 1475, 862cm-
1. 1H NMR (300 MHz, CDCl3) δ 8.12 (d, J = 8.8 Hz, 1H), 7.41 (s, 1H), 6.52
(dd, J = 2.4 and 8.8 Hz, 1H), 6.43 (d, J = 2.4 Hz, 1H), 4.30 (q, J = 7.1 Hz,
2H), 3.84 (s, 3H), 3.83 (s, 3H), 3.72 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3) δ 165.0 (C), 161.6 (C), 158.9 (C), 144.1 (C), 131.7
(CH), 117.5 (CH), 115.3 (C), 105.0 (CH), 98.0 (CH), 61.0 (CH2), 59.1(CH3),
55.6 (CH3), 55.4 (CH3), 14.5 (CH3). MS (ESI-TOF) m/z 267.1 [M+H+].
HMRS (EI+): calc. for C14H18O5; 266.1154:found266.1166.
(Z)-ethyl 3-(2,6-diethoxyphenyl)-2-methoxyacrylate 3Ag: Compound
3Ag was prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol)
and 2,6-diethoxybenzoic acid 2g (42 mg, 0.2 mmol) according to the
general procedure A. The crude product was purified by flash
chromatography (PE/EtOAc 9:1) to afford 3Ag (27 mg, 0.1 mmol) in 51%
yield ascoloress oil. IR: 2982, 2936, 1715, 1581, 1453, 842, 711 cm-1. 1H
NMR (300 MHz, CDCl3) δ 7.19 (t, J = 8.3 Hz, 1H), 6.89 (s, 1H), 6.52 (d, J
= 8.3 Hz, 2H), 4.31 (q, J = 7.1 Hz, 2H), 4.06 (q, J = 7.0 Hz, 4H), 3.59 (s,
3H), 1.43 – 1.33 (m, 9H).13C NMR (75 MHz, CDCl3) δ 164.6 (C), 157.5
(2xC), 146.6 (C), 129.3 (CH), 112.8 (CH), 112.3 (C), 104.4 (2xCH), 64.1
(2xCH2), 61.1 (CH2), 58.9 (CH3), 14.9 (2x CH3), 14.4 (CH3). MS (ESI-TOF)
m/z 295.15 [M+H+].HMRS (ESI-TOF): calc. for C16H23O5;295.3470:found
295.3480.
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
(Z)-ethyl 3-mesityl-2-methoxyacrylate 3Ah: Compound 3Ah was
prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol) and 2,4,6-
trimethylbenzoic acid 2h (38 mg, 0.2 mmol) according to the general
procedure A. The crude product was purified by flash chromatography
(PE/EtOAc 95:5) to afford 3Ah (40 mg, 0.16 mmol) in 80% yield as a
colorlessoil. IR: 2985, 2939, 2851, 1718, 1611, 1567,1479, 852,771 cm-
1. 1H NMR (300 MHz, CDCl3) δ 6.99 (s, 1H), 6.87 (s, 2H), 4.33 (q, J = 7.1
Hz, 2H), 3.41 (s, 3H), 2.28 (s, 3H), 2.23 (s, 6H), 1.38 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 164.2 (C) , 146.2 (C), 137.3 (C), 136.4 (2xC),
129.7 (C), 128.0 (2xCH), 119.8 (CH), 61.4 (CH2), 59.4 (CH3), 21.1 (CH3),
20.54 (2xCH3), 14.38 (CH3). MS (ESI-TOF) m/z 249.20 [M+H+]. HMRS
(ESI-TOF): calc. for C15H21O3; 249.3220:found249.3235.
(Z)-ethyl 3-(2,6-dichlorophenyl)-2-methoxyacrylate 3Am: Compound
3Am was prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol),
and 2,6-dichlorobenzoic acid 2m (38 mg, 0.2 mmol) according to the
general procedure A. The crude product was purified by flash
chromatography (PE/EtOAc 9:1) to afford 3Am (15 mg, 0.054 mmol) in
27% yield asa yellow oil. IR: 2983, 1723, 1644, 1580, 1428, 839,777 cm-
1. 1H NMR (300 MHz, CDCl3) δ 7.34 – 7.32 (m, 2H), 7.21 – 7.15 (m, 1H),
6.82 (s, 1H), 4.34 (q, J = 7.1 Hz, 2H), 3.62 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ 163.4 (C), 148.0 (C), 135.0 (2xC), 132.3 (C),
129.4 (CH), 127.8 (2xCH), 114.5 (CH), 61.8 (CH2), 59.4 (CH3), 14.3 (CH3).
MS (ESI-TOF) m/z 276.11 [M+H+]. HMRS (ESI-TOF): calc. for
C12H13Cl2O3; 276.1130: found 276.1210.
(Z)-ethyl
2-methoxy-3-(3-methylbenzofuran-2-yl)acrylate
3Ai:
(Z)- and (E)-ethyl 2-methoxy-3-(2,4,6-trichlorophenyl)acrylate (Z)-3An
and (E)-3An: Compound (Z)-3An and (E)-3An were prepared from ethyl
2-methoxyacrylate 1A (39 mg, 0.3 mmol), and2,4,6-trichlorolbenzoic acid
2n (45 mg, 0.2 mmol) according to the general procedure A. The crude
product was purified by flash chromatography (PE/EtOAc 95:5) to afford
(Z)-3An (24 mg, 0.048 mmol) in 24% yieldasa colorlessoil, and (E)-3An
(10 mg, 0.032 mmol) in 16% yield ascolorlessoil. (Z)-ethyl 2-methoxy-3-
(2,4,6-trichlorophenyl)acrylate (Z)-3An: IR: 2983, 2942, 1724, 1646,
1578, 1439, 848 cm-1. 1H NMR (300 MHz, CDCl3) δ 7.36 (s, 2H), 6.73 (s,
1H), 4.34 (q, J = 7.1 Hz, 2H), 3.63 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3) δ 163.2 (C), 148.4 (C), 135.5 (2xC), 134.3 (C),
130.9 (C), 127.9 (2xCH), 113.7 (CH), 61.9 (CH2), 59.4 (CH3), 14.3 (CH3).
MS (ESI-TOF) m/z 308.97 [M+H+]. HMRS (ESI-TOF): calc. for
C12H12Cl3O3; 308.9874: found 308.9889. (E)-ethyl 2-methoxy-3-(2,4,6-
trichlorophenyl)acrylate (E)-3An: IR: 2983, 2942, 1724, 1646, 1578,
1439, 848 cm-1. 1H NMR (300 MHz, CDCl3) δ 7.34 (s, 2H), 5.80 (s, 1H),
4.12 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 1.09 (t, J = 7.1 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 162.3 (C), 149.4 (C), 135.5 (2xC), 133.3 (C), 132.8 (C),
127.7 (2xCH), 104.2 (CH), 61.6 (CH2), 56.3 (CH3), 13.8 (CH3).
Compound 3Ai wasprepared from ethyl 2-methoxyacrylate1A (39 mg, 0.3
mmol) and 3-methylbenzofuran-2-carboxylic acid 2i (35 mg, 0.2 mmol)
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 95:5) to afford 3Ai (37 mg, 0.142 mmol)
in 71% yieldasa yellow oil. IR: 2986, 2938, 2845,1711, 1613, 1570, 1016,
821 cm-1. 1H NMR (300 MHz, CDCl3) δ 7.54 – 7.47 (m, 2H), 7.36 – 7.31
(m, 1H), 7.28 – 7.21 (m, 1H), 7.10 (s, 1H), 4.33 (q, J = 7.1 Hz, 2H), 3.89
(s, 3H), 2.35 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
164.6 (C), 155.2 (C), 147.2 (C), 144.7 (C), 129.4 (C), 125.9 (CH), 122.7
(CH), 119.8 (CH), 119.5 (C), 111.5 (CH), 111.1 (CH), 61.5 (CH2), 61.2
(CH3), 14.5 (CH3), 8.8 (CH3). MS (ESI-TOF) m/z 261.11 [M+H+]. HMRS
(ESI-TOF): calc. for C15H17O4; 261.2890:found261.2901.
(Z)-ethyl 3-(2,4-dinitrophenyl)-2-methoxyacrylate 3Aj: Compound 3Aj
was prepared from ethyl 2-methoxyacrylate1A (39 mg, 0.300 mmol) and
2,4-dinitrobenzoic acid 2j (42.4 mg, 0.2 mmol) according to the general
procedure A. The crude product was purified by flash chromatography
(PE/EtOAc 9:1) to afford 3Aj (20 mg, 0.068mmol) in 34% yield asa yellow
oil. IR: 2938, 2845, 1710, 1520, 1322, 1163, 1096, 886, 821 cm-1. 1H NMR
(300 MHz, CDCl3) δ 9.09 (s, 1H), 8.58 (dd, J = 2.0 and 8.2 Hz 1H), 7.82 (t,
J = 8.2 Hz, 1H), 7.02 (s, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 1.35 (t,
J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 165.0 (C), 161.7 (C), 158.9
(C), 144.1 (C), 131.7 (C), 117.5 (CH), 115.3 (CH), 105.1 (CH), 98.1 (CH),
61.1 (CH2), 59.2 (CH3), 14.5 (CH3). MS (ESI-TOF) m/z 297.12 [M+H+].
HMRS (ESI-TOF): calc. for C12H13N2O7; 297.2350: found297.2420.
(Z)-ethyl
3-(2-bromo-6-fluorophenyl)-2-methoxyacrylate
3Ao:
Compound 3Ao was prepared from ethyl 2-methoxyacrylate 1A (39 mg,
0.300 mmol), and 6-bromo-2-fluorobenzoic acid 2o (44 mg, 0.2 mmol)
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 9:1) to afford 3Ao (25 mg, 0.082mmol)
in 41% yield as a colorless oil. IR: 2938, 2845, 1706, 1650, 1601, 1450,
1096, 896, 830, 680 cm-1. 19F NMR (282 MHz, CDCl3) δ -113.0 (d, J = 5.9
Hz, 1F). 1H NMR (300 MHz, CDCl3) δ 7.40 (d, J = 7.8 Hz, 1H), 7.20 – 7.13
(m, 1H), 7.09 – 7.03 (m, 1H), 6.76 (s, 1H), 4.34 (q, J = 7.2 Hz, 2H), 3.70
(s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 163.4 (C),
160.2 (d, JC-F = 251.3 Hz, C), 148.3 (C), 130.1(d, JC-F = 5.8 Hz, CH), 128.2
(d, JC-F = 3.8 Hz, CH), 124.6 (d, JC-F = 4.0 Hz, C), 123.3 (d, JC-F = 18.8 Hz,
C), 114, 8 (d, JC-F = 22.1 Hz, CH), 114.2 (CH), 61.7 (CH2), 59.5 (CH3), 14.3
(CH3). MS (EI-TOF) m/z 303.10 [M+H+]. HMRS (CI+): calc. for
C12H13BrFO3; 303.0032: found 303.0042.
(Z)-ethyl
2-methoxy-3-(4-methoxy-2-nitrophenyl)acrylate
3Ak:
Compound (Z)-3Ak was prepared for ethyl 2-methoxyacrylate 1A (39 mg,
0.3 mmol), and 4-methoxy-2-nitro-benzoic acid 2k (39.4 mg, 0.2 mmol)
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 9:1) to afford 3Ak(23 mg, 0.08 mmol) in
40% yield asa yellow oil. IR: 2938, 2845, 1690, 1520, 1330, 1163, 1096,
886, 821 cm-1.1H NMR (300 MHz, CDCl3) δ 7.99 (d, J = 8.9 Hz, 1H), 7.53
(d, J = 2.7 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.29 (s, 1H), 4.38 (q, J = 7.2
Hz, 2H), 3.96 (s, 3H), 3.78 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 165.0 (C), 161.6 (C), 158.9 (C), 144.1 (C), 131.7 (CH),
117.5 (CH), 115.3 (C), 105.0 (CH), 98.0 (CH), 61.0 (CH2), 55.6 (CH3), 55.5
(CH3), 14.5 (CH3). MS (ESI-TOF) m/z 282.12 [M+H+].HMRS (ESI-TOF):
calc. for C13H16NO6; 282.2640: found 282.2648.
(Z)-ethyl 2-methoxy-3-(2,4,6-trifluorophenyl)acrylate 3Ap: Compound
3Ap was prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol),
and 2,4,6-trifluorobenzoic acid 2p (43 mg, 0.2 mmol) in DMF instead of
1,4-dioxane/DMSO according to the general procedure A. The crude
product was purified by flash chromatography (PE/EtOAc 95:5) to afford
3Ap (42 mg, 0.16 mmol) in 80% yield asa yellow oil. IR: 2942,2845, 1705,
1690, 1595, 1322, 1163, 1096, 893, 810, 680 cm-1. 19F NMR (282 MHz,
CDCl3) δ -105.33 (m, 2F), -107.80 (m, 1F). 1H NMR (300 MHz, CDCl3) δ
6.72 – 6.66 (m, 3H), 4.33 (q, J = 7.1 Hz, 2H), 3.76 (s, 3H), 1.38 (t, J = 7.1
Hz, 6H). 13C NMR (75 MHz, CDCl3) δ 162.6 (dt, JC-F = 15.0 and 249 Hz,
C), 163.4 (C), 163.1 (C), 160.7 (ddd, JC-F = 10.1, 14.7 and 250 Hz, 2xC),
148.8 (C), 107.9 (CH), 100.5 (dd, JC-F = 3.1 and 25.5 Hz, CH), 100.1 (dd,
JC-F = 2.1 and 24.6 Hz, CH), 61.6 (CH2), 59.3 (CH3), 14.2 (CH3). MS (ESI-
TOF) m/z 261.12 [M+H+]. HMRS (ESI-TOF): calc. for C12H12F3O3;
261.2122: found261.2210.
(Z)-ethyl 3-(2-chlorophenyl)-2-methoxyacrylate 3Al: Compound 3Al
was prepared from ethyl 2-methoxyacrylate 1A (39 mg, 0.3 mmol), and2-
chlorobenzoic acid 2l (31 mg, 0.2 mmol) in DMF instead of 1.4-
dioxane/DMSO accordingto the general procedure A. The crude product
was purified by flash chromatography (PE/EtOAc 9:1) to afford 3Al (23mg,
0.096 mmol) in 32% yield asa yellow oil. IR: 2950, 2845, 1701, 1658, 1550,
1322, 1016, 753 cm-1. 1H NMR (300 MHz, CDCl3) δ 8.10 (dd, J = 2.0 and
5.7 Hz, 1H), 7.41 – 7.38 (m, 1H), 7.34 (s, 1H), 7.30 – 7.23 (m, 3H), 4.34
(q, J = 7.1 Hz, 2H), 3.76 (d, J = 6.5 Hz, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3) δ 164.2 (C), 147.1 (C), 134.3 (C), 131.6 (C), 131.1
(CH), 129.7 (CH), 129.6 (CH), 126.9 (CH), 118.6 (CH), 61.5 (CH2), 59.6
(CH3), 14.43 (CH3). MS (ESI-TOF) m/z 241.12 [M+H+]. HMRS (ESI-TOF):
calc. for C12H14ClO3; 241.6830: found 241.6920.
(Z)- and (E)-ethyl 2-methoxy-3-(pentafluorophenyl)acrylates (Z)-3Aq
and (E)-3Aq: Compounds(Z)-3Aq and (E)-3Aq were prepared from ethyl
2-methoxyacrylate 1A (39 mg, 0.3mmol), and pentafluorobenzoic acid 2q
7
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European Journal of Organic Chemistry
FULL PAPER
(43 mg, 0.2 mmol) according to the general procedure A. The crude
product was purified by flash chromatography (PE/EtOAc 95:5) to afford
(Z)-3Aq (10 mg, 0.034 mmol) in 17% yield asa yellow oil, and(E)-3Aq (20
mg, 0.068 mmol) in 34% yield as a yellow oil. (Z)-ethyl 2-methoxy-3-
(pentafluorophenyl)acrylate (Z)-3Aq: IR: 2880, 1705, 1672, 1598, 1322,
1163, 835 cm-1. 19F NMR (282 MHz, CDCl3) δ -136.9 – 136.6 (m, 2F), -
154.4 − -154.5 (t, J = 19.7 Hz, F), -162.4 − -162.5 (m, 2F). 1H NMR (300
MHz, CDCl3) δ 6.60 (bs, 1H), 4.34 (q, J = 7.1 Hz, 2H), 3.81 (s, 3H), 1.39
(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 162.6 (C), 150.2 (C), 146.3
– 146.0 (m, C), 143.0 – 142.6 (m, C), 139, 6 – 139,0 (m, C), 136.3– 135.9
(m, C), 108.9 (td, JC-F = 4.1 and 18.1 Hz, C), 105.4 (d, JC-F = 4.0 Hz, CH),
62.1 (CH2), 59.5 (CH3), 14.3 (CH3). MS (ESI-TOF) m/z 297.15 [M+H+].
HMRS (ESI-TOF): calc. for C12H10F5O3; 297.1930: found 297.1945. (E)-
ethyl 2-methoxy-3-(pentafluorophenyl)acrylate (E)-3Aq: IR: 2880,
1705, 1672, 1598, 1322, 1163, 835 cm-1. 19F NMR (282 MHz, CDCl3) δ -
139.9 (dd, J = 9.5 and 22.5 Hz, 2F),. -156.5 (t, J = 22.5 Hz, F), -163.3 (dd,
J = 14.1 and 19.7 Hz, 2F). 1H NMR (300 MHz, CDCl3) 5.59 (s, 1H), 4.22
(q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 162.2 (C), 152.8 (C), 146.3 −146.0 (m, C), 143.0 − 142.6(m, C),
139.7 – 139.1 (m, C), 136.3 − 135.9 (m, C), 139.2 − 138.8 (m, C), 135.9 −
135.8 (m, C), 108.9 (td, JC-F = 4.1 and 18.2 Hz), 105.3 (d, JC-F = 2,1 Hz,
CH), 61.9 (CH2), 59.6 (CH3), 14.3 (CH3). HMRS (ESI-TOF): calc. for
C12H10F5O3; 297.1930: found297.1945.
(Z)-benzyl 2-methoxy-3-(2-methoxyphenyl)acrylate 3Ca: Compound
3Ca was prepared from 1C (57 mg,0.3 mmol), and2-methoxybenzoic acid
1a (30 mg, 0.2 mmol) according to the general procedure A. The crude
product was purified by flash chromatography (PE/EtOAc 9:1) to afford
3Ca (30 mg, 0.1 mmol) in 50% yield asa yellow oil.IR: 2992, 2850,1720,
1625, 1580, 11474, 1111, 830, 752 cm-1. 1H NMR (300 MHz, CDCl3) δ
8.10 (dd, J = 1.7 and 7.8 Hz, 1H), 7.51 (s, 1H), 7.47 – 7.27 (m, 5H), 7.01
– 6.94 (m, 1H), 6.88 (dd, J = 1.2and8.3 Hz, 1H), 5.31 (s, 2H), 3.85 (s, 3H),
3.74 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.6 (C), 157.5 (C), 145.5 (C),
136.1 (C), 130.7 (CH), 130.4 (CH), 128.7(2xCH), 128.3(2xCH), 122.3(C),
120.7 (CH), 118.0 (CH), 110.5 (CH), 66.8 (CH2), 59.4 (CH3), 55.7 (CH3).
MS (ESI-TOF) m/z 299.15 [M+H+]. HMRS (ESI-TOF): calc. for C18H19O4;
299.3410: found299.3425.
(Z)-ethyl 3-(2-methoxyphenyl)-2-phenoxyacrylate 3Da: Compound
3Da was prepared from 1D (58 mg, 0.300 mmol), and 2-methoxybenzoic
acid 2a (31 mg, 0.2 mmol) according to the general procedure A. The
crude product was purified by flash chromatography (PE/EtOAc 9:1) to
afford 3Da (36 mg, 0.12 mmol) in60%yieldasa yellow oil.IR: 2938, 2845,
1705, 1680, 1450, 1096, 1016,821, 750cm-1. 1H NMR (300 MHz, CDCl3)
δ 7.90 (d, J = 7.7 Hz, 1H), 7.78 (s, 1H), 7.25 – 7.11 (m, 3H), 6.99 − 6.93
(m, 3H), 6.85 – 6.79 (m, 2H), 4.15 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 1.14 (t,
J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 164.0 (C), 157.7 (C), 156.9
(C), 140.0 (C), 130.9 (CH), 130.6 (CH), 129.7 (2xCH), 122.5 (CH), 121.6
(C), 120.9 (CH), 120.7 (CH), 115.7 (2xCH), 110.6 (CH), 61.4 (CH2), 55.7
(CH3), 14.2 (CH3). MS (ESI-TOF) m/z 299.15 [M+H+]. HMRS (ESI-TOF):
calc. for C18H19O4; 299.3380: found299.3395.
(Z)-2-(1,1-dimethylethyl)-5-(2-methoxybenzylidene)-1,3-dioxolan-4-
one 3Ba: Compound 3Ba wasprepared from 1B (47 mg, 0.3 mmol), and
2-methoxybenzoic acid 1a (35 mg, 0.2 mmol) according to the general
procedure A. The crude product was purified by flash chromatography
(PE/EtOAc 9:1)to afford 3Ba (21 mg, 0.08 mmol) in 40% yieldasa yellow
oil. IR: 2964, 1788, 1235, 753 cm-1. 1H NMR (300 MHz, CDCl3) δ 7.88(dd,
J = 1.6 and 7.8 Hz, 1H), 7.24 – 7.17 (m, 1H), 6.94 – 6.86 (m, 2H), 6.82 (d,
J = 8.3 Hz, 1H), 5.51 (s, 1H), 3.78 (s, 3H), 0.96 (s, 9H). 13C NMR (75 MHz,
CDCl3) δ 164.2 (C), 157.4 (C), 136.6 (C), 130.1 (CH), 129.9 (CH), 121.9
(C), 120.7 (CH), 110.6 (CH), 109.2 (CH), 101.7 (CH), 55.6 (CH3), 36.1 (C),
23.0 (3xCH3). MS (ESI-TOF) m/z 263.14 [M+H+]. HMRS (ESI-TOF): calc.
for C15H19O4; 263.3050:found263.3122.
(Z)-ethyl 2-benzyloxy-3-(2-methoxyphenyl)acrylate 3Ea: Compound
3Ea wasprepared from 1E (62 mg, 0.3mmol), and 2-methoxybenzoic acid
1a (31 mg, 0.2 mmol) according to the general procedure A.The crude
product was purified by flash chromatography (PE/EtOAc 9:1) to afford
3Ea (54 mg, 0.172 mmol) in 86% yield as a yellow oil. IR: 2940, 2845,
1710, 1670, 1550, 1100, 1016,821, 750cm-1. 1H NMR (300 MHz, CDCl3)
δ 8.16 (dd, J = 1.9 and 7.8 Hz, 1H), 7.53 (s, 1H), 7.45 – 7.36 (m, 2H), 7.34
– 7.27 (m, 4H), 6.96 – 6.88 (m, 2H), 4.93 (s, 2H), 4.34 (q, J = 7.1 Hz, 2H),
3.87 (s, 3H), 1.13 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 164.8
(C), 157.4 (C), 144.4 (C), 137.0 (C), 130.9 (CH), 130.3 (CH), 128.6 (CH),
128.5 (2xCH), 128.4 (CH), 128.1 (CH), 122.3 (C), 120.6 (CH), 118.3 (CH),
110.5 (CH), 73.6 (CH2), 61.2 (CH2), 55.6 (CH3), 14.4 (CH3). MS (ESI-TOF)
m/z 313.15 [M+H+]. HMRS (EI+): calc. for C19H20O4; 312.1361: found
312.1353.
(Z)-2-(1,1-dimethylethyl)-5-(2,6-difluorobenzylidene)-1,3-dioxolan-4-
one 3Br: Compound 3Br was prepared from 1B (47 mg, 0.3 mmol), and
2,6-difluorobenzoic acid 2r (37 mg, 0.2 mmol) in DMF/DMSO instead of
1,4-dioxane/DMSO according to the general procedure A. The crude
product waspurified by flash chromatography (PE/EtOAc 9:1) to afford 3Br
(16 mg, 0.06 mmol) in 30% yield as a yellow oil. IR: 2964, 2850, 1788,
1680, 1235, 852, 753,630 cm-1. 19F NMR (282 MHz, CDCl3) δ -107.3 (t, J
= 7.13 Hz, 2F). 1H NMR (300 MHz, CDCl3) δ 7.31 – 7.23 (m, 1H), 6.92 (t,
J = 8.2 Hz, 2H), 6.40 (s, 1H), 5.55 (s, 1H), 1.02 (s, 9H). 13C NMR (75 MHz,
CDCl3) δ 163.09 (C), 160.7 (dd, JC-F = 7.4 and 251 Hz, 2xC), 139.6 (C),
130.23 (t, JC-F = 10.3 Hz, CH), 111.6 (d, JC-F = 23.4 Hz, CH), 111.5 (d, JC-
F = 23.4 Hz, CH), 111.6 − 111.3 (m, C), 110.5 (CH), 93.7 (t, JC-F = 2.3 Hz,
CH), 36.3 (C), 23.0 (CH3), 22.9 (2xCH3). MS (ESI-TOF) m/z 269.12 [M+H+].
HMRS (ESI-TOF): calc. for C14H15F2O3; 269.2598:found269.2630.
(Z)-benzyl 2-benzyloxy-3-(2,6-difluorophenyl)acrylate 3Er: Compound
3Er was prepared for 1E (62 mg, 0.3 mmol), and2,6-difluorobenzoic acid
2r (37 mg, 0.2 mmol) in DFM/DMSO instead of 1,4-dioxane/DMSO
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 9:1) to afford 3Er (25 mg, 0.08mmol) in
40% yield as a yellow oil. IR: 2850, 1720, 1625, 1590, 1501, 1016, 890,
821, 705 cm-1. 19F NMR (282 MHz, CDCl3) δ -108.2 (t, J = 7.13 Hz, 2F).
1H NMR (300 MHz, CDCl3) δ 7.28 – 7.21 (m, 6H), 6.91 – 6.83 (m, 3H),
4.97 (s, 2H), 4.36 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.1 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 163.4 (C), 160.5 (dd, JC-F = 7.3 and 249.9 Hz, 2C), 147.5
(C), 136.7 (C), 129.8 (t, J = 10.4 Hz, CH), 128.3 (2xCH), 128.2 (2xCH),
128.0 (CH), 111.6-111.3 (m, C), 111.3 (d, JC-F = 23.8 Hz, CH), 111.2 (d,
JC-F = 23.8 Hz, CH), 110.9 (CH), 73.5 (CH2), 61.7 (CH2), 14.3 (CH3). MS
(ESI-TOF) m/z 319.12 [M+H+]. HMRS (ESI-TOF): calc. for C18H17F2O3;
319.3198: found319.3205.
(Z)-benzyl 2-methoxy-3-(2,6-difluorophenyl)acrylate 3Cr: Compound
3Cr was prepared from 1C (57 mg, 0.3 mmol), and 2,6-difluorobenzoic
acid 2r (37 mg, 0.2 mmol) in DMF/DMSO instead of 1,4-dioxane/DMSO
according to the general procedure A. The crude product waspurified by
flash chromatography (PE/EtOAc 95:5) to afford 3Cr (27 mg, 0.09 mmol)
in 46% yield asa yellow oil. IR: 2992, 2850, 1720, 1625, 1590, 1501, 1016,
890, 821, 710cm-1. 19F NMR (282 MHz, CDCl3) δ -108.3 (t, J = 7.1 Hz, 2F).
1H NMR (300 MHz, CDCl3) δ 7.47 – 7.34 (m, 5H), 7.29 – 7.20 (m, 1H),
6.90 (t, J = 8.1 Hz, 2H), 6.84 (s, 1H), 5.31 (s, 2H), 3.77 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ 163.2 (C), 160.6 (dd, JC-F = 7.3 and 249.9 Hz, 2xCH),
148.5 (C), 135.5 (C), 129.9 (t, JC-F = 10.4 Hz, CH), 128.7 (2xCH), 128.5
(CH), 128.4 (2xCH), 111.4 (d, JC-F = 23.7 Hz, CH), 111.3(d, JC-F = 23.8 Hz,
CH), 111.4 – 110.9 (m, C), 109.4 (CH), 67.3 (CH2), 59.5 (CH3) . MS (ESI-
TOF) m/z 305.13 [M+H+]. HMRS (ESI-TOF): calc. for C17H15F2O3;
305.2928: found305.2935.
Diethyl 2,5-dimethoxyhexa-2,4-dienedioate 5: Compound 5 was
obtained as a side product during the Myers coupling in presence of
electron-deficient benzoic acids. Colorless oil. IR: 3453.5, 2986.1, 1718,
1248.4, 1093.6, 857.3cm-1. 1H NMR (300 MHz, CDCl3) δ 7.02 (s, 1H), 4.29
(q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 163.3 (2xC), 148.4 (2xC), 116.7 (2xCH), 61.4 (2xCH2), 60.7
(2xCH3), 14.4 (2xCH3). MS (ESI-TOF) m/z 259.15 [M+H+]. HMRS (ESI-
TOF): calc. for C12H19O6; 259.2701: found259.2720.
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901877
European Journal of Organic Chemistry
FULL PAPER
m) X. Qin, C. Chen, L. Zhang, J. Xu, Y. Pan, H. Zhao, J. Han, H. Li, L.
Xu, Tetrahedron 2017, 73, 2242-2249.
Acknowledgements
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This w ork has been partially supported by INSA Rouen, Rouen
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Entry for the Table of Contents
Arylation Enol Ethers.
Pd(II)-catalyzed decarboxylative Heck coupling of -alkoxyacrylates w ith (hetero)aryl carboxylic acids for the stereocontrolled
production of (Z)-β-heteroarylated vinyl ethers is reported. This methodology offers a rational and step-economical route to the
synthesis of attractive β-arylated α-alkoxy α,β-unsaturated carboxylates family w hich emerged as a relevant class of building blocks
w ith different applications.
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