Benign Arylations of Dimethyl Itaconate via Heck–Matsuda Reaction Utilizing in-Situ Generated Palladium on Aluminum Oxide

Article abstract of DOI:10.1002/ejoc.201901708

In situ generated palladium on aluminum oxide provides an active and efficient catalytic system for the preparation of arylmethylidene succinates using the Heck–Matsuda reaction. Beside the monoarylation the first examples of the biarylation of these mono

Full text of DOI:10.1002/ejoc.201901708

A Journal of
Accepted Article
Title: Benign Arylations of Dimethyl Itaconate via Heck-Matsuda
Reaction Utilizing in-situ Generated Palladium on Aluminum
Oxide
Authors: Lauryna Mateliene (née Dauksaite), Jan Knaup, Frank von
Horsten, Xiaoting Gu, and Heiko Brunner
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901708
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901708
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10.1002/ejoc.201901708
European Journal of Organic Chemistry
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Benign Arylations of Dimethyl Itaconate via Heck-Matsuda
Reaction Utilizing in-situ Generated Palladium on Aluminum
Oxide
Lauryna Matelienė (née Dauksaîtė),[a] Jan Knaup,[a] Frank von Horsten,[a] Xiaoting Gu,[b] and Heiko
Brunner*[a]
butylphosphine mediated condensation reaction or aromatic and
heteroraromatic aldehydes with diethyl fumarate or diethyl
maleate.[11] Jiang et al. described a modification of this reaction
type by using tris(4-anisyl)phosphine.[12] A disadvantage of
classical condensation reactions due to possible aldol reactions
is the inability to synthesize arylmethylidene succinates bearing
carbonyl functionalities such as a keto group.
Abstract: In-situ generated palladium on aluminum oxide provides an
active and efficient catalytic system for the preparation of
arylmethylidene succinates using the Heck-Matsuda reaction. Beside
the monoarylation the first examples of the biarylation of these
monomers will be described.
Introduction
Wang et al. synthesized various dimethyl 2-arylidine succinates
in moderate to reasonable yields via an unexpected reaction of
dimethyl acetylenedicarboxylate with in situ generated
arylketenes catalyzed by 1-methylimidazole.[13]
Arylmethylidene succinates represent interesting building blocks
for the preparation of synthetic targets and natural products. Thus,
this class of substances were used as synthons for the
preparation
of
γ-butyrolactones,[1]
1,4-diphenylbutadiene
Next to the classical condensation reactions employing aromatic
and heteroaromatic aldehydes the Mizoroki-Heck reaction using
aromatic iodides and triflates was also successfully utilized for the
preparation of arylmethylidene succinates.[6, 14] However, these
reactions often had a long reaction time and had to be carried out
at elevated reaction temperatures for obtaining the desired
reaction products in moderate to good yields. Furthermore, the
use of amines as bases and DMF as an ecologically problematic
solvent was necessary. For exhibiting the efficiency of the
synthesis of arylmethylidene succinates via Mizoroki-Heck
reaction, Iyer et al. described very recently a ligand free catalytic
system consisting of Pd(OAc)2 and stoichiometric quantities of
silver salts as sequestration agents for halides.[15] Despite the
good results, the use of phosphines, bases and/or silver salts is
indispensable for the synthetic protocols mentioned above. An
additional disadvantage in the Heck reaction is the need for
expensive iodides or triflates as electrophiles. Furthermore,
halogenated arylidene succinates are not accessible via a
classical Mizoroki-Heck reaction.
derivatives2 and 2,3-butandioles.[3] Furthermore, they are
excellent precursors of chiral benzyl succinates via asymmetric
hydrogenation.[4]
Charlton et al. utilized the arylmethylidene succinates as key-
building blocks for the synthesis of lignans such as Magnostinin
and Cyclogalgravin.[5] Rama Devi and Rajaram used
arylmethylidene succinates as intermediates for the synthesis of
anthraquinone carboxylic acid- and coumarine acetic acid
derivatives that are useful agents for the treatment of rheumatoid
arthritis, osteoporosis and cancer.[6] Recently Shi and Pierce
described the total synthesis of (+)-Plagiogyrin A using E-4-
(allyloxy)-2-(4-allyloxy)benzylidene-4-oxobutanoic acid as key
building block.[7]
The synthetic access to this important class of substances is
frequently given by a classical Stobbe-condensation,[8] Wittig
reaction[9] or Horner-Emmons reaction[10] Beside these reaction
pathways McCombie and co-workers described
a
tri-n-
[a]
Lauryna Matelienė (née Dauksaîtė), MSc, ,Dr. Jan Knaup, Dr. Frank
The Heck-Matsuda reaction, which has provided valuable
services in organic synthesis over the past decades, opens up a
way out of the limitations of the previous presentation methods
described above.[16 – 25]
von Horsten, Dr. Heiko Brunner*
R&D Organic Chemistry
Atotech Deutschland GmbH
Erasmusstrasse 20, D-10553 Berlin
E-mail: heiko.brunner@atotech.com
Homepage: www.atotech.com
[b]
Dr. Xiaoting Gu
R&D Material Science
Atotech Inc. USA, c/o Case Western Reserve University
2111 Martin Luther King Jr. Dr., Cleveland, OH 44106, USA
Due to the high reactivity of the aryldiazonium salts compared to
the corresponding aryl halides, the above limitations can often be
circumvented. The production of arylmethylidene succinates has
hardly been described to date. Correia and Pastre have published
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201901708
European Journal of Organic Chemistry
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only the preparation of two derivatives.[26] However, it is
noteworthy that the reactions were carried out with a quite high
palladium concentration of 10 mol-% and comparatively high
reaction temperatures of 65°C in methanol. In this regard the
development of a more efficient synthetic protocol is a rewarding
target.[26]
Results and Discussion
The conversion of 4-methoxybenzenediazonium tetrafluoroborate
1a with dimethyl itaconate 2 was chosen as the starting point for
our studies and reaction optimization. Based on our previous
positive results with acrylates, the in-situ generated catalytic
system was to be prepared by a pre-reduction of Pd(OAc)2 in the
presence of olefin and aluminum oxide 90 in methanol (1.9 wt.-%
Pd(OAc)2 on Al2O3).[28]
Schmidt and colleagues recently described the successful
arylation of itaconimides using the Heck-Matsuda reaction. With
a catalyst concentration of 5 mol-% the synthesis of 3-
arylmethylidene pyrrolidine-2,5-diones in good to very good yields
was achieved.[27]
The objective of the optimization was to find and produce a
suitable catalyst which would enable the conversion to the desired
aryl-methylidene succinates in high yields with a low catalyst
quantity at 25°C. In addition to the influence of the catalyst
concentration and the ratio of reactants, the agitation speed
should also be investigated. For this purpose, the corresponding
optimization experiments are carried out at two different stirring
speeds (200 and 350 rpm).
Thus, stimulated by these findings and based on our precedent
results concerning the development and utilization of an in-situ
generated palladium on aluminum oxide in gram-scale Matsuda-
Heck reactions we wanted to apply this new catalytic system for
the preparation of functionalized arylmethylidene succinates.[28]
Herein, we would like to report a synthetic protocol using the
Heck-Matsuda reaction for a facile and benign synthesis of
functionalized arylmethylidene succinates in the presence of an
in-situ generated palladium on aluminum oxide as catalytic
system.
In addition to determining the yield, the reaction rate and the
catalytic activity of the reaction system were investigated by
measuring the gas quantity of the nitrogen released during the
reaction (Table 1).
Table 1. Optimization of reaction conditions.
(x mol-%)
COOMe
COOMe
N2BF4
COOMe
COOMe
Pd(OAc)2
+
Al
2O
3, MeOH
25°C
MeO
MeO
2
3a
1a
Entry[a]
Ratio 1a vs 2
Catalyst
[mol %]
Agitation speed [rpm]
Pre-reduction
Conv- Rate
[mmol mL-a h-1]
TOF
[h-1]
Yield [%]
Reference
1
2
3
4
5
7
1:1.5
1:1.5
1:1
1
1
200
200
200
200
350
n.a.
60 min
30 min
30 min
30 min
30 min
no
0.247
0.362
0.310
0.856
0.255
n.a.
74
109
93
60
86
89
89
97
86
This work
This work
This work
This work
This work
Ref: [26]
1
1:1
2
257
76
1:1
1
1:1
10
n.a.
[a] Reaction scale: 10 mmol diazonium salt in 30 mL MeOH
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As can be seen from Table 1, higher yields were obtained with a
pre-reduction time of 30 minutes compared to 60 minutes (Entry
2 vs. Entry 1). This is also ultimately reflected in the course of the
heat flow (Figure 1).
The effect of the agitation is noticeable. As can be seen from
Table 1, increasing the stirring speed from 200 rpm to 350 rpm
increased the yield to an excellent 97% on the one hand, but on
the other hand a significant reduction in reaction speed and
catalytic activity could be observed (Entry 5 vs. Entry 3, Table 1).
The almost quantitative yield is bought with a longer reaction time
(93 minutes at 350 rpm vs. 76 minutes at 200 rpm) and induction
time (718 seconds at 350 rpm vs. 403 seconds at 200 rpm) of the
reaction. This contrasts strikingly with the results of A. Schmidt et
al. which, in the case of
a Mizoroki-Heck reaction of
bromobenzene with styrene using various palladium(II)-pre-
catalysts and palladium on charcoal as well, showed that an
increase in agitation speed is accompanied by an increase in the
reaction rate and a shortening of the reaction time.[29]
For rationalizing these experimental findings we investigated on
the one hand the particle size distribution using scanning
transmission electron microscopy (STEM) in SEM (Figure 2) and
on the other hand the immobilized palladium content by means of
ICP-MS.
Figure 1. Impact of the pre-reduction time on the heat flow of the reaction.
Thus, the shorter pre-reduction time results in an earlier start of
the reaction on the one hand (induction time 492 seconds after 30
minutes pre-reduction vs. 690 seconds after 60 minutes pre-
reduction), and a higher exothermia, a higher reaction rate and
thus a higher catalytic activity on the other hand (Figure 1; Entries
1 and 2, Table 1). Similar results concerning the impact of
different pre-reduction times could be observed in the case of
cinnamic ester derivatives.[28]
Another interesting effect is the ratio of diazonium salts to
dimethyl itaconate. The investigations showed that, despite a
lower reaction rate, somewhat better results were achieved in a
ratio of 1:1, which is advantageous for a better atomic economy
(Entry 2 vs. Entry 3, Table 1). Thus, the reaction products
resulting from the reaction could be obtained in clean form without
further column purification after filtration of the immobilized
catalyst, quenching in water and extraction. In analogy to the
results for cinnamic ester derivatives, only traces of palladium (<
10ppm) could be detected using ICP-MS after the isolation
described above.(28)
Figure 2. Particle size distribution of in situ generated palladium on aluminum
oxide in dependence of the agitation speed.
As depicted in Figure 2, a slightly larger particle size distribution
is obtained at higher agitation speed than at lower agitation speed.
Another interesting aspect is the influence of the stirring speed on
the content of immobilized palladium on the carrier material. In
addition to the formation of smaller catalyst particles (Figure 2), a
higher degree of immobilized palladium is obtained at a lower
stirring speed (0.740% at 200 rpm vs. 0.680% at 350 rpm). Both
the smaller particle size distribution and the larger supported
palladium content explain to a certain extent the significantly
An increase of the catalyst quantity to 2 mol-% led to a significant
reaction acceleration and shortening of reaction time (34 minutes
instead of 76 minutes in the case of 1 mol %) but no considerable
improvement of yield (Table 1, Entry 4).
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higher reaction rates obtained at the lower agitation speed despite
the poorer mass transport. However, in contrast to previously
used olefins such as methyl acrylate,[28] a higher yield is obtained
despite the lower catalytic activity at the higher agitating speed,
in-situ generated palladium on aluminum oxide distinguishes itself
by a higher yield and more benign reaction conditions.
Having these optimized conditions for the Heck-Matsuda reaction
in our hands, we explored the scope of the synthetic protocol with
which to some extent might be explained by better mass transport. various diazonium salts (Table 2). As depicted in Table 2, with
However, compared to the corresponding reaction of methyl
acrylate, the dimethyl itaconate reacts much more slowly (0.255
mmol mL-1 h-1 vs 1.467 mmol mL-1 h-1) under comparable reaction
conditions despite a smaller particle size distribution (mean
particle size 18.1 nm vs. 52.3 nm).[28] This might be explained by
a stabilization of the Pd by the ester group in the Pd-complex,
which occurs after the insertion step in the catalytic cycle. DFT
calculations showed that complexation via carbonyl oxygen is
34.8 kJ/mol more stable than possible stabilization via the
methoxy group of the ester functionality. (Figure 3)
exception of the 4-nitrobenzenediazonium salt (Entry 13) and the
4-iodobenzenediazonium salt (Entry 7), all products are obtained
in good to excellent yields.
In the case of the 4-nitro derivative, the moderate yield may be
due to the poor solubility of the corresponding diazonium salt.
However, doubling the amount of solvent did not improve the yield.
Strikingly, in the case of the iodine derivative 3g (Entry 7) only a
moderate yield could be obtained in comparison to other
halogenated representatives. Whereas double arylvinylation was
also observed in the case of methyl acrylate in the 4-
iodobenzenediazonium salt, this did not occur when dimethyl
itaconate was used.[28] An extension of the reaction time from 720
minutes to 66 hours brought only a slight improvement of the yield.
Instead, unreacted dimethyl itaconate could be recovered.
On the positive side, it should be noted that both halogenated aryl-
methylidene succinates and arylmethylidene succinates with
carbonyl functionalities could be obtained in excellent yields with
the present synthesis protocol, which are not easily accessible by
classical Heck reaction or Stobbe condensation.
MeO
IIO
Pd
O
MeOOC
Figure 3. PdII-stabilization after syn insertion.
The stabilization might hamper the consecutive isomerization and
therefor, the β-H-elimination. Similar complexations have recently
been confirmed by Braga and colleagues in Heck-Matsuda
reactions with allyl esters.[30]
Also the presence of a cyano group, which turned out to be
problematic in the case of the production of the 4-
cyanobenzalacetone by Heck-Matsuda reaction, was tolerated
without any problems, so that the corresponding product 3l could
be obtained in excellent yields.[31] With the exception of some
representatives, most reactions are completed within one hour.
Compared to the prior results published by Correia and Pastre
(Entry 6, Table 1)[25] the presented synthetic protocol utilizing an
Table 2. Optimization of reaction conditions.
(1 mol-%)
COOMe
COOMe
N2BF4
COOMe
COOMe
Pd(OAc)2
+
Al
2O
3, MeOH
25°C
FG
FG
2
3
1
Entry[a]
FG
Product
3a
Reaction time
93 minutes
30 minutes
35 minutes
50 minutes
40 minutes
Yield [%]
1
2
3
4
5
4-OMe
3-OMe
97
75
89
93
84
3b
3,4,5-(OMe)3
4-Cl
3c
3d
3-Cl
3e
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6
4-F
4-I
3f
3g
3h
3i
35 minutes
720 minutes
30 minutes
105 minutes
50 minutes
40 minutes
160 minutes
60 minutes
30 minutes
90
7
53 (65)[b], [d]
8
4-Br
89
80
9
2-COOMe
4-COOMe
4-COMe
4-CN
10
11
12
13
14
3j
84
3k
3l
80
96
4-NO2
H
3m
3n
45 (47)[c]
90
[a] Reaction scale: 10 mmol diazonium salt in 30 mL MeOH; 350 rpm. [b] 66 hours reaction time, [c] reaction in 60 mL MeOH, [d] 15% dimethyl
itaconate recovered.
To demonstrate the further synthetic potential of our method, we
investigated the monoarylation using heterocyclic diazonium salts. diazonium tetrafluoroborate were reacted with dimethyl itaconate
For this purpose 2-oxo-2H-chromene-6-diazonium (Scheme 1).
tetrafluoroborate
and
2-(methoxycarbonyl)-thiophene-3-
O
O
N2BF4
O
N2BF4
O
COOMe
2
S
O
O
COOMe
(1 mol %)
MeOH, 25°C
Pd(OAc)2
COOMe
COOMe
Al
2O3,
COOMe
Me
CO2
S
O
O
5
4
38 % at 25 °C
32 % at 40 °C
89 %
Scheme 1. Heterocyclic Diazonium salts in the monoarylation of dimethyl itaconate
While in the case of the coumarine derivative an excellent yield
could be obtained, the conversion of the 2-(methoxycarbonyl)-
thiophene-3-diazonium tetrafluoroborate is more challenging.
Neither at 25°C nor at 40°C high yields of the product 5 were
obtained. In both cases, unreacted dimethyl itaconate (60% and
64%, respectively) could be recovered after completion of the
reaction. The reason for this could be found in an intermolecular
or intramolecular stabilization of the palladium after the oxidative
addition or in a catalyst poisoning by the thiophene sulphur. Since
in the literature the above mentioned diazonium salt was
successfully converted by Raduán et al. with ethyl acrylate and by
Brunner et al. with butanone in the Heck-Matsuda reaction,
catalyst poisoning seems unlikely.[31, 32]
Due to the very good yield obtained with the benzene analogues
2-carboxymethylbenzenediazonium tetrafluoroborate 1i (Table 2,
Entry 9), a purely intramolecular stabilization of the cationic
palladium species after oxidative addition can be substantially
excluded.
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However, DFT calculations indicate a more intermolecular
stabilization of palladium after olefin insertion, which makes
subsequent β-H-elimination significantly more difficult. (Figure 4)
According to the DFT calculations, in addition to the stabilization
of palladium by ester functionality described in Figure 3, further
interaction with the carboxymethyl-thiophene moiety is likely and
thus explains the moderate yields.
However, it should be pointed out, that in all cases the E-isomer
was exclusively formed, confirmed by 2D NOESY or ROESY
NMR.
Stimulated by the work of Correia and co-workers concerning the
biarylation of acrylates and maleic anhydride[33-35], the iterative
Heck-Matsuda couplings with itaconimides by B. Schmidt et al.[27]
and encouraged by our studies regarding the β,β-diarylation of
acrylates and vinylphosphonates[36] we decided to embark on the
biarylation of dimethyl iatconate. In accordance with our previous
reaction conditions regarding the β,β-diarylation of acrylates with
palladium on aluminum phosphate as catalyst, we converted
several diazonium salts (2.2 eq.) with dimethyl itaconate at 40°C
and 2 mol-% catalyst.[36] In the context of this study both electron-
rich and electron-poor aryldiazonium salts were investigated
(Table 3).
Figure 4. Proposed intermolecular interaction between Pd and thiophene
moiety.
Table 3. Diarylation of Dimethyl itaconate with various Aryldiazonium salts
FG
FG
O
O
O
N2BF4
O
2
OMe
+
+
OMe
OMe
OMe
OMe
2 mol-% Pd(OAc)2
OMe
FG
MeOH
FG
Al
2O3,
FG
FG
O
40 °C
O
1
7 a-e
6 a-e
3 c, j, e
Entry[a]
FG
Product 6 & 7[b]
Product 3[c]
Yield [%] 6 & 7[c]
(Ratio 6 : 7)
Yield [%] 3[c]
1
2
3
4-OMe
2-OMe
6a & 7a
6b & 7b
6c & 7c
-
-
93 (36:38)
90 (73:27)
-
-
3,4,5-(OMe)3
4-COOMe
4-Cl
3c
64 (13:87)
84 (17:83)[b]
31
8[b]
4
5
6d & 7d
6e & 7e
3j
37 (24:76)
33 (23:77)[b]
41
84[b]
3e
84 (25:75)
10
[a] Reaction conditions: 2 mol-% Pd(OAc)2; 40°C, 68mL MeOH, [b] Utilization of 5 mol-% catalyst, [c] Yields based on dimethyl itaconate used
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As can be seen from Table 3, with exception of electron-poor 4-
carboxymethyl-benzenediazonium tetrafluoroborate 1d (Entry 4),
biarylated products were obtained in good to excellent yields by
using 2 mol-% catalyst. In the case of the electron-rich 4-
methoxybenzenediazonium tetrafluoroborate (Entry 1) and the 2-
methoxybenzenediazonium tetrafluoroborate (Entry 2), the
diarylated products 6 and 7 have been produced in excellent
yields, the formation of the regiosiomer 6 being preferred over the
regioisomer 7. In both cases, no monoarylated products could be
isolated and detected. The 3,4,5-trimethoxy-benzenediazonium
tetrafluoroborate, which exhibited inverse regioselectivity in
comparison to the two methoxy derivatives mentioned above, was
a special case and exception (Entry 3). Furthermore, a significant
amount of monoarylated product 3c could be isolated in this case
with 31% (Entry 3). By increasing the catalyst quantity from 2
mol-% to 5 mol-%, a significant yield increase of the biarylated
products 6 and 7 up to 84% could be achieved in the case of the
3,4,5-trimethoxybenzenediazonium salt.
arenediazonium salts, the nucleophilicity of the olefinic moiety of
the monoarylated product is lower, which is detrimental to
nucleophilic attack on the cationic palladium-aryl complex and
thus to the formation of biarylated products.
Based on the available results, two different mechanistic paths
are taken with the regard to β-H-elimination (see supporting
information, p. 19). This type of double bond isomerization is a
frequently observed phenomenon in 1,1-disubstituted alkenes.
Thus, Correia and co-workers already observed a similar kind of
isomerization in the Heck-Matsuda reaction of methyl
methacrylate and 4-methoxybenzenediazonium salt, which gave
a 1:1 ratio of constitutional isomers.[33] Furthermore, B. Schmidt
and colleagues observed corresponding isomerizations during
the iterative Heck-Matsuda coupling of itaconimide and discussed
various migration mechanisms in this context.[27] In principle, the
occurrence of the respective regioisomers should be explained by
a respective kinetic or thermodynamic control. First orienting DFT
calculations indicate that for both the electron-rich and the
deactivated diazonium salts the products 6 are in all cases the
thermodynamically favored products (see supporting information,
page 6).
However, in the case of the deactivated arenediazonium salts, it
turned out that, as a rule, the formation of product 7 was strongly
preferred compared to product 6 (Entries 4 and 5). Furthermore,
significant quantities of monoarylated products were found for
both 4-carboxymethylbenzenediazonium tetrafluoroborate and 4-
chlorbenzenediazonium tetrafluoroborate (Entries 4 and 5) by
using 2 mol-% catalyst. Whereas in the case of the chlorinated
derivative with 84% a still very good yield of biarylated products
could be obtained (Entry 5), this was only possible to a limited
extent (37% yield) with the 4-carboxymethylbenzenediazonium
salt (entry 4). Monoarylation clearly predominated with 41%.
Furthermore, 9% methyl 4-methoxybenzoates could be isolated,
which indicates an additional decomposition reaction of the
diazonium salt by the solvent methanol. While in the case of the
In the case of 2-methoxybenzenediazonium and 4-
methoxybenzenediazonium salt, the energy differences of the
optimized geometries of products 6 and 7 in favor of products 6
are greatest and are in good agreement with the experimental
findings. In both cases, β-H-elimination is predominantly
thermodynamically controlled. However,
a different picture
emerges strikingly with the deactivated diazonium salts and the
3,4,5-trimethoxybenzenediazonium salt. Although the products 6
should also be thermodynamically favored, in these cases the
products 7 are predominantly retained, so that in these cases the
β-H-elimination takes place in a kinetically controlled manner.
3,4,5-trimethoxybenzenediazonium tetrafluoroborate
increase could be achieved by using larger catalyst amounts, this
was not successful in the case of the 4-
a
yield
Conclusions
carboxymethylbenzenediazonium salt. By using 5 mol-% only the
yield of monoarylated product 3e could be increased (Entry 4).
Thus, with an increasing deactivation the formation of diarylated
products is less favored. This effect could be rationalized by the
reduced electron density of the intermediately formed
arylmethylidene succinates, which have a decisive influence on
the π-complex formation in the second arylation step (see
supporting information). Given that we obtained significant
amounts of monoarylated products from electron-poor
In summary, the monoarylation and biarylation of dimethyl
itaconate via Heck-Matsuda reaction to obtain functionalized
arylmethylidene succinates, biarylated succinates and maleates
have been described. Depending on the stereoelectronic effects
of the utilized diazonium salts the biarylation proceeded with
different regioselectivities. The presented approach utilizing in-
situ generated palladium on aluminum oxide distinguished itself
by benign reaction conditions combined with low palladium
loadings and paved the way to these important building blocks in
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Computational Methods. Molecular structures and energies were
calculated using density functional theory (DFT)[38, 39] employing the B3-
good to excellent yields. The elaboration of the optimized reaction
conditions were supported by kinetic studies. The experimental
results and outcome were explained and verified by DFT
calculations.
LYP exchange correlation functional[40] with D3 dispersion corrections41
,
as implemented in the Turbomole Code Version 6.6.[42] The valence
electrons ware described using linear combination of atomic orbitals
(LCAO) in a triple-zeta basis set (def2-TZVP basis from the Turbomole
library). The self-consistent solution of the Kohn-Sham equations was
cycled until the change in energy between two cycles fell below 10E-6
Hartree. Cartesian atomic coordinates were optimized until the maximum
force coordinate was less than 10E-4 Hartree/Bohr. Representations of 3D
molecular structures were prepared using VMD.[43]
Experimental Section
General methods. All reactions, unless otherwise specified, were
performed in EasyMax 102 Advanced Synthesis Workstation from Mettler
Toledo where 100 mL one-piece glass reactors were used. All solvents
and reagents were purchased from commercial sources without further
purification. NMR spectra were recorded on a Bruker AscendTM 400
spectrometer. Chemical shifts were reported in parts per million (ppm)
upfield to trimethylsilane as an internal standard. Multiplicity is presented
as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
and coupling constant J in Hz. The assignment of the signals was carried
out, where possible, employing 2D NMR techniques (1H-1H ROESY).
Product distribution, were specified, was determined by advanced NMR
plugin ‘Simple Mixture Analysis’ (SMA) from Mestrelab Research.
Purification of organic compounds was carried out by flash
chromatography with PuriFlash® 450 Interchim equipment using 30 µm
silica gel. Eluents for the column were mixtures of ethyl
acetate/cyclohexane.
General procedure for preparation of immobilized Pd-NPs on
alumina:
To a solution of aluminium oxide (1.389 g; 13.62 mmol) and palladium(II)
acetate (45 mg; 0.2 mmol) in methanol (68 mL); olefin (10.0 mmol) was
added and reaction mixture was stirred at 25 °C for 30 min. Afterwards, it
was filtrated through fritted glass funnel and collected powder was washed
with diethyl ether (2x25 mL) and dried without heating under reduced
pressure for 30 min.
General procedure for the Matsuda-Heck monoarylation of dimethyl
itaconate (3a-p):
To a solution of aluminium oxide (561 mg; 5.5 mmol) and palladium(II)
acetate (22 mg; 0.1 mmol) in methanol (30 mL), dimethyl itaconate (1.582
g; 10.0 mmol, 1 eq.) was added and reaction mixture was stirred at 25 °C.
After 30 min of preconditioning, diazonium salt (10.0 mmol, 1 eq.) was
added and reaction development was monitored by heat flow control and
gas evolution. Afterwards, reaction mixture was filtrated through celite,
poured into ice-water and the water phase was extracted with diethyl ether
(3x50 mL). The combined organic phases were dried over anhydrous
Na2SO4 and then concentrated under reduced pressure to obtain desired
products.
IR spectra were recorded on a Perkin Elmer Spectrum One FT-IR
spectrometer with ATR (germanium crystal).
The STEM analysis was performed by an FEI Helios NanoLab 650 Dual
Beam System FIB with the state-of-the-art Elstar® electron column.
Samples were prepared by dispersing the powder samples in hexane and
three suspensions were dipped on Au-coated-holey-carbon Cu TEM grids.
SEM analysis and imaging was operated by Field emission scanning
microscopy (FESEM) and energy dispersive X-ray analysis (EDX).
Nitrogen gas evolution measurements for the studies of kinetic aspects of
the Matsuda-Heck reaction were performed with Drum-Type Gas Meter
TG05/7 from Dr.-Ing. Ritter Apparatebau GmbH & Co. KG. HPLC analysis
of product composition was carried out on the system Smart Line Knauer
Eurospher 100-5 via a C-18, 4 x 250 mm column with water/acetonitrile
gradient. For the detection UV detector 2600 at 354 nm was used.
HPLC-MS conditions for high resolution mass spectrometry: Bruker Micro
TOF II equipment with Agilent 1260 pump, poroshell 120; C18, 2.7 µm
column and ESI-TOF MS detector. Used eluent was mixtures of
water/acetonitrile.
Dimethyl (E)-2-(4-methoxybenzylidene) succinate 3a.[15] Pale yellow oil
(2.51 g, 95 %); 1H NMR (400 MHz, CDCl3): δ = 7.85 (s, 1H), 7.33
(d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H), 3.82 (s, 3H), 3.74
(s, 3H), 3.58 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 171.7, 168.0, 160.2,
141.8, 130.9, 127.3, 123.7, 114.1, 55.3, 52.2, 52.1, 33.5; HRMS
(ESI TOF): calcd for C14H17O5 [M+H]+ 265.1078, found 265.1074.
Dimethyl (E)-2-(3-methoxybenzylidene) succinate 3b.[44] Yellow oil
(1.976 g, 75 %); 1H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1H), 7.31 (td, J =
7.5, 1.3 Hz, 1H), 6.95-6.88 (m, 3H), 3.83 (s, 3H), 3.81 (s, 3H), 3.73 (s, 3H),
3.55 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 171.6, 167.8, 159.6, 142.1,
136.2, 129.7, 126.1, 121.4, 114.8, 114.2, 55.3, 52.3, 52.2, 33.6; HRMS
(ESI-TOF): calcd for C14H17O5 [M+H]+ 265.1078, found 265.1085.
Palladium content on inorganic support and its traces in the final products
was determined by inductively coupled plasma-optical emission
spectrometer (ICP-OES) Varian 720-ES with custom-designed CCD
detector.
Diazonium salts used in this study were all known and prepared as
described in the literature, see Ref. 37. Solvents and chemicals were
purchased from VWR or Aldrich and used as received.
Dimethyl (E)-2-(3,4,5-trimethoxybenzylidene) succinate 3c.[2] Yellow
1
oil (2.90 g, 89 %); H NMR (400 MHz, CDCl3): δ = 7.85 (s, 1H), 6.63 (s,
2H), 3.88 (s, 3H), 3.85 (s, 6H), 3.84 (s, 3H), 3.74 (s, 3H), 3.59 (s, 2H); 13
C
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10.1002/ejoc.201901708
European Journal of Organic Chemistry
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NMR (101 MHz, CDCl3): δ = 171.7, 167.7, 153.2, 142.3, 138.7, 130.3,
125.1, 106.3, 60.9, 56.1, 52.2, 33.7; HRMS (ESI-TOF): calcd for C16H21O7
[M+H]+ 325.1289, found 325.1297.
52.2, 33.4; HRMS (ESI-TOF): calcd for C15H17O6 [M+H]+ 293.1027, found
293.0992.
Dimethyl (E)-2-(4-acetylbenzylidene) succinate 3k. Yellow oil (2.22 g,
13]-
1
Dimethyl (E)-2-(4-chlorobenzylidene) succinate 3d.[12,
Yellow oil
80 %); H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.4 Hz, 2H), 7.91 (s,
(2.49 g, 93 %); 1H NMR (400 MHz, CDCl3): δ = 7.84 (s, 1H), 7.37 (d, J =
8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 3.83 (s, 3H), 3.74 (s, 3H), 3.51 (s,
2H); 13C NMR (101 MHz, CDCl3): δ = 171.4, 167.5, 140.9, 135.0, 133.3,
130.3, 128.9, 126.5, 52.4, 52.3, 33.4; HRMS (ESI-TOF): calcd for
1H), 7.44 (d, J = 8.2 Hz, 2H), 3.85 (s, 3H), 3.74 (s, 3H), 3.52 (s, 2H), 2.62
(s, 3H); 13C NMR (101 MHz, CDCl3): δ = 197.3, 171.2, 167.3, 140.8, 139.5,
137.0, 129.1, 128.6, 127.7, 52.4, 52.3, 33.4, 26.6; IR (Neat): νmax = 3003,
2954, 1737, 1714, 1684, 1604, 1436, 1264, 1205, 1173, 1095, 774 cm-1;
HRMS (ESI-TOF): calcd for C15H17O5 [M+H]+ 277.1078, found 277.1054.
C
13H14ClO4 [M+H]+ 269.0582, found 269.0569.
Dimethyl (E)-2-(3-chlorobenzylidene) succinate 3e.[12, 13] Pale yellow oil
(2.26 g, 84 %); 1H NMR (400 MHz, CDCl3): δ = 7.83 (s, 1H), 7.33 (d,
J = 4.7 Hz, 3H), 7.22 (ddt, J = 4.8, 3.0, 0.8 Hz, 1H), 3.83 (s, 3H), 3.74 (s,
3H), 3.51 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 171.2, 167.4, 140.5,
136.6, 134.6, 128.9, 128.9, 127.2, 126.9, 52.4, 52.2, 33.4; HRMS (ESI-
TOF): calcd for C13H14ClO4 [M+H]+ 269.0582, found 269.0543
Dimethyl (E)-2-(4-cyanobenzylidene) succinate 3l. Yellow oil (2.49 g,
1
96 %); H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1H), 7.70 (d, J = 8.3 Hz,
2H), 7.46 (d, J = 8.3 Hz, 2H), 3.85 (s, 3H), 3.75 (s, 3H), 3.48 (s, 2H); 13
C
NMR (101 MHz, CDCl3): δ = 171.0, 167.0, 139.9, 139.5, 132.4, 129.4,
128.5, 118.3, 112.4, 52.5, 52.4, 33.4; IR (Neat): νmax = 2924, 2229, 1737,
1716, 1436, 1269, 1207, 1174, 1095, 848, 775 cm-1; HRMS (ESI-TOF):
calcd for C14H14NO4 [M+H]+ 260.0925, found 260.0921.
Dimethyl (E)-2-(4-fluorobenzylidene) succinate 3f.[12, 13] Yellow oil (2.28
g, 90 %); 1H NMR (400 MHz, CDCl3): δ = 7.86 (s, 1H), 7.38 – 7.31 (m, 2H),
7.09 (t, J = 8.6 Hz, 2H), 3.83 (s, 3H), 3.74 (s, 3H), 3.52 (s, 2H); 13C NMR
(101 MHz, CDCl3): δ = 171.5, 167.7, 164.2, 161.7, 141.1, 131.0, 130.9,
125.8, 115.9, 115.7, 52.3, 52.3, 33.4; HRMS (ESI-TOF): calcd for
Dimethyl (E)-2-(4-nitrobenzylidene) succinate 3m.[13] Yellow solid (1.25
g, 45 %); mp: 110 °C (Lit.: 111-112 °C) 13 1H NMR (400 MHz, CDCl3): δ
;
= 8.26 (d, J = 8.7 Hz, 2H), 7.92 (s, 1H), 7.52 (d, J = 8.7 Hz, 2H), 3.86 (s,
3H), 3.76 (s, 3H), 3.49 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 170.9,
166.9, 147.7, 141.4, 139.5, 129.7, 129.0, 123.9, 52.6, 52.4, 33.4; HRMS
(ESI-TOF): calcd for C13H14NO6 [M+H]+ 280.0823, found 280.0801
C
13H14FO4 [M+H]+ 253.0878, found 253.0848.
Dimethyl (E)-2-(4-iodobenzylidene) succinate 3g.[12] Yellow oil (2.35 g,
1
65 %); H NMR (400 MHz, CDCl3): δ = 7.80 (s, 1H), 7.73 (d, J = 8.2 Hz,
Dimethyl (E)-2-benzylidene succinate 3n.[13] Yellow oil (2.11 g, 90 %);
1H NMR (400 MHz, CDCl3): δ = 7.91 (s, 1H), 7.44 – 7.31 (m, 5H), 3.83 (s,
3H), 3.73 (s, 3H), 3.55 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 171.6,
167.8, 142.2, 134.9, 129.0, 128.9, 128.7, 125.9, 52.3, 52.2, 33.5; HRMS
(ESI-TOF): calcd for C13H15O4 [M+H]+ 235.0972, found 235.0981.
2H), 7.08 (d, J = 8.2 Hz, 2H), 3.83 (s, 3H), 3.73 (s, 3H), 3.50 (s, 2H); 13
C
NMR (101 MHz, CDCl3): δ = 171.3, 167.5, 141.0, 137.8, 134.3, 130.6,
126.6, 95.1, 52.4, 52.2, 33.4; HRMS (ESI-TOF): calcd for C13H14IO4
[M+H]+ 360.9939, found 360.9933.
Dimethyl (E)-2-(4-bromobenzylidene) succinate 3h.[12] Reddish oil
(2.78 g, 89 %); 1H NMR (400 MHz, CDCl3): δ = 7.82 (s, 1H), 7.53 (d, J =
8.5 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 3.83 (s, 3H), 3.73 (s, 3H), 3.50 (s,
2H); 13C NMR (101 MHz, CDCl3): δ = 171.3, 167.5, 140.8, 133.7, 131.9,
130.5, 126.5, 123.2, 52.3, 52.2, 33.4; HRMS (ESI-TOF): calcd for
Dimethyl (E)-2-(2-oxo-2H-chromen-6-yl)methylene) succinate 4.
White solid (2.71 g, 89 %); mp: 100-101 °C; 1H NMR (400 MHz, MeOD):
δ = 7.96 (dd, J = 9.6, 0.7 Hz, 1H), 7.90 (s, 1H), 7.67 (d, J = 2.1 Hz, 1H),
7.61 (dd, J = 8.5, 2.1 Hz, 1H), 7.39 (d, J = 8.5 Hz, 1H), 6.47 (d, J = 9.6
Hz, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 3.56 (d, J = 0.7 Hz, 2H); 13C NMR
(101 MHz, MeOD): δ = 171.8, 167.6, 160.8, 154.0, 143.8, 139.9, 132.3,
131.4, 128.7, 126.8, 119.1, 116.7, 116.5, 51.5, 51.3, 32.8 (C-4); IR
(Neat): νmax = 2947, 1720, 1701, 1623, 1434, 1201, 1181, 1173, 1134,
1091, 906, 830 cm-1; HRMS (ESI-TOF): calcd for C16H15O6 [M+H]+
303.0870, found 303.0850.
C
13H14BrO4 [M+H]+ 313.0077, found 313.0069.
Dimethyl (E)-2-(2-methoxycarbonylbenzylidene) succinate 3i. Yellow
oil (2.35 g, 80 %); 1H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 0.9 Hz, 1H),
8.06 (dd, J = 7.9, 1.4 Hz, 1H), 7.55 (td, J = 7.6, 1.4 Hz, 1H), 7.47 – 7.41
(m, 1H), 7.35 (ddt, J = 7.7, 1.4, 0.6 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.71
(s, 3H), 3.30 (s, 2H); 13C NMR (101 MHz, CDCl3): δ = 171.8, 167.5, 166.7,
143.2, 137.0, 132.5, 130.9, 129.6, 128.9, 128.6, 125.2, 52.3, 52.3, 52.1,
33.5; HRMS (ESI-TOF): calcd for C15H17O6 [M+H]+ 293.1027, found
293.1016.
Dimethyl
(E)-2-((2-methoxycarbonyl)
thiophen-3-yl)methylene)
succinate 5. The precipitate formed in ice-water was filtrated and dried by
lyophilization to obtain beige solid (1.13 g, 38 %); mp: 82-83 °C; 1H NMR
(400 MHz, CDCl3): δ = 8.27 (s, 1H), 7.52 (d, J = 5.0 Hz, 1H), 7.15 (d,
J = 5.0 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.72 (s, 3H), 3.45 (s, 2H); 13
C
Dimethyl (E)-2-(4-methoxycarbonylbenzylidene) succinate 3j.[2]
Greenish solid (2.45 g, 84 %); mp: 64-65 °C; 1H NMR (400 MHz, CDCl3):
δ = 8.06 (d, J = 8.3 Hz, 2H), 7.91 (s, 1H), 7.41 (d, J = 8.2 Hz, 2H), 3.93 (s,
3H), 3.84 (s, 3H), 3.74 (s, 3H), 3.51 (s, 2H); 13C NMR (101 MHz, CDCl3):
δ = 171.2, 167.3, 166.4, 140.9, 139.3, 130.3, 129.8, 128.8, 127.5, 52.4,
NMR (101 MHz, CDCl3): δ = 171.3, 167.4, 162.1, 141.5, 135.8, 131.0,
130.5, 129.3, 126.9, 52.4, 52.3, 52.2, 33.9; IR (Neat): νmax = 3104, 2962,
1706, 1437, 1284, 1237, 1207, 1104, 787 cm-1; HRMS (ESI-TOF): calcd
for C13H15O6S [M+H]+ 299.0591, found 299.0593.
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10.1002/ejoc.201901708
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General procedure for the Matsuda-Heck biarylation of
dimethyl itaconate (6a-e and 7a-e):
Hz, 1H), 5.49 (d, J = 1.7 Hz, 1H), 3.76 (s, 6H), 3.69 (s, 3H), 3.66 (s, 3H);
13C NMR (101 MHz, CDCl3): δ = 168.6, 166.1, 157.1, 151.2, 129.9,
128.3, 127.7, 122.5, 120.2, 110.8, 55.7, 52.3, 51.8, 41.5; IR (Neat): νmax
= 2950, 2837, 1739, 1711, 1596, 1490, 1434, 1258, 1160, 1025, 753 cm-
1; HRMS (ESI-TOF): calcd for C21H23O6 [M+H]+ 371.1496, found
371.1490.
To
a solution of aluminium oxide (1.39 g; 13.62 mmol) and
palladium(II)acetate (45 mg; 0.2 mmol) in methanol (68 mL), dimethyl
itaconate (1.582 g; 10.0 mmol, 1 eq.) was added and reaction mixture was
stirred at 25 °C. After 30 min of pre-conditioning, temperature was
increased to 40 °C and diazonium salt (21.5 mmol, 2.15 eq.) was added.
The reaction development was monitored by heat flow control and gas
evolution. Afterwards, reaction mixture was filtrated through celite, poured
into ice-water and the water phase was extracted with dichloromethane
(3x50 mL). The combined organic phases were dried over anhydrous
Na2SO4 and then concentrated under reduced pressure. All crude
products were purified by column chromatography. In cases where
mixtures of constitutional isomers were isolated, percentage ratio was
determined by SMA analysis from 1H NMR.
Dimethyl 2-(bis(3,4,5-trimethoxyphenyl)methylene) succinate 6c and
Dimethyl 2-(bis(3,4,5-trimethoxyphenyl)methyl) maleate 7c.
Synthesis according the general procedure but utilization of 5 mol-%
catalyst. Purification by column chromatography (EtOAc/CycHex 25:75)
gave yellow solid (4.13 g, 84 %) as a mixture of constitutional isomers with
a percentage ratio of 13:87 (6c:7c); IR (Neat): νmax = 2950, 2839, 1736,
1588, 1505, 1242, 1120, 1007 cm-1; HRMS (ESI-TOF): calcd for C25H31O10
[M+H]+ 491.1919, found 491.1921.
Dimethyl 2-(bis(3,4,5-trimethoxyphenyl)methylene) succinate 6c
1H NMR (400 MHz, CDCl3): δ = 6.36 (s, 4H, H-9), 3.89 (s, 3H), 3.87 (s,
3H), 3.78 (s, 12H), 3.72 (s, 3H), 3.53 (s, 3H), 3.50 (s, 2H); 13C NMR (101
MHz, CDCl3): δ = 171.7, 170.5, 153.0, 152.8, 150.9, 137.2, 134.5, 124.5,
106.6, 106.2, 60.9, 56.2, 52.1, 52.0, 38.5.
Dimethyl 2-(bis(4-methoxyphenyl)methylene) succinate 6a.
Purification by column chromatography (EtOAc/CycHex 15:85) gave
yellow oil (2.136 g, 58%); 1H NMR (400 MHz, CDCl3): δ = 7.06 (d, J = 8.7
Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7
Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.71 (s, 3H), 3.51 (s, 3H), 3.49 (s,
2H); 13C NMR (101 MHz, CDCl3): δ = 172.0, 170.5, 159.7, 159.5, 151.5,
134.7, 133.2, 130.9, 130.4, 122.8, 113.7, 113.3, 55.3, 55.2, 52.1, 51.7,
38.5; IR (Neat): νmax = 2952, 2839, 1737, 1703, 1605, 1509, 1247, 1172,
1031, 834 cm-1; HRMS (ESI-TOF): calcd for C21H23O6 [M+H]+ 371.1496,
found 371.1492.
Dimethyl 2-(bis(3,4,5-trimethoxyphenyl)methyl) maleate 7c.
1H NMR (400 MHz, CDCl3): δ = 6.40 (s, 4H, H-9), 5.60 (d, J = 1.8 Hz, 1H,
H-4), 5.15 (d, J = 2.0 Hz, 1H, H-7), 3.84 (s, 6H, H-12), 3.80 (s, 12H, H-13),
3.74 (s, 3H, H-6), 3.70 (s, 3H, H-1); 13C NMR (101 MHz, CDCl3): δ = 168.5,
165.8, 153.3, 150.9, 137.2, 134.5, 124.4, 106.4, 60.9, 56.2, 55.2, 52.6,
52.1.
Dimethyl 2-(bis(4-methoxyphenyl)methyl) maleate 7a. Purification by
column chromatography (EtOAc/CycHex 15:85) gave yellow oil (1.309,
35%); 1H NMR (400 MHz, CDCl3): δ = 7.09 (d, J = 8.6 Hz, 4H), 6.84 (d, J
= 8.7 Hz, 4H), 5.53 (d, J = 1.8 Hz), 5.16 (d, J = 2.0 Hz, 1H), 3.78 (s, 6H),
3.70 (s, 3H), 3.65 (s, 3H); 13C NMR (101 MHz, CDCl3): δ = 168.7, 165.9,
158.7, 152.1, 131.4, 130.2, 123.6, 114.0, 55.2, 53.4, 52.4, 51.9; IR
(Neat): νmax = 2952, 2838, 1726, 1609, 1510, 1248, 1172, 1032, 832 cm-
1; HRMS (ESI-TOF): calcd for C21H23O6 [M+H]+ 371.1496, found
371.1506.
Dimethyl 2-(bis(4-(methoxycarbonyl)phenyl)methylene) succinate 6d
and Dimethyl 2-(bis(4-(methoxycarbonyl)phenyl)methyl) maleate 7d.
Purification by column chromatography (EtOAc/CycHex 15:85) gave pale
yellow oil (1.56 g, 37 %) as a mixture of constitutional isomers with a
percentage ratio of 24:76 (6d:7d); IR (Neat): νmax = 3001, 2953, 1721, 1608,
1435, 1278, 1194, 1172, 1106, 1020, 712 cm-1; HRMS (ESI-TOF): calcd
for C23H23O8 [M+H]+ 427.1395, found 427.1393.
Dimethyl 2-(bis(4-(methoxycarbonyl)phenyl)methylene) succinate
6d:
Dimethyl 2-(bis(2-methoxyphenyl)methylene) succinate 6b.
Purification by column chromatography (EtOAc/CycHex 15:85) gave
yellow oil (2.434 g, 66%); 1H NMR (400 MHz, CDCl3): δ = 7.31 – 7.16 (m,
2H, Ar-H), 7.03 (d, J = 7.4 Hz, 2H, Ar-H), 6.92 – 6.79 (m, 4H, Ar-H), 3.73
– 3.68 (s, 6H), 3.67 (s, 3H), 3.49 (s, 3H), 3.43 – 3.26 (m, 2H); 13C NMR
(101 MHz, CDCl3): δ = 171.7, 169.0, 156.2, 156.0, 143.6, 131.2, 130.3,
129.9, 129.6, 129.3, 128.7, 127.0, 120.4, 120.2, 110.9, 110.8, 55.6, 55.3,
51.8, 51.4, 37.4; IR (Neat): νmax = 3008, 2952, 2843, 1736, 1723, 1644,
1491, 1258, 1246, 1024, 758, 753 cm-1; HRMS (ESI-TOF): calcd for
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.5 Hz, 2H), 7.97 (d, J = 8.5
Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.19 (d, J = 8.5 Hz, 2H), 3.92 (s, 6H),
3.72 (s, 3H), 3.49 (s, 3H), 3.44 (s, 2H); 13C NMR (101 MHz, CDCl3): δ =
171.1, 168.9, 166.4, 149.9, 145.8, 144.3, 129.9, 129.6, 129.4, 129.0,
128.5, 126.7, 52.3, 52.1, 52.0, 37.8.
Dimethyl 2-(bis(4-(methoxycarbonyl)phenyl)methyl) maleate 7d
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 4H), 7.26 (d, J = 8.2
Hz, 4H), 5.54 (d, J = 1.7 Hz, 1H), 5.37 (d, J = 1.7 Hz, 1H), 3.91 (s, 6H),
3.72 (s, 3H), 3.65 (s, 3H); 13C NMR (101 MHz, CDCl3): δ = 167.8, 166.6,
165.4, 149.0, 143.6, 130.1, 129.6, 129.3, 125.4, 54.5, 52.6, 52.2, 52.1.
C
21H23O6 [M+H]+ 371.1496, found 371.1494.
Dimethyl 2-(bis(2-methoxyphenyl)methyl) maleate 7b. Purification by
column chromatography (EtOAc/CycHex 15:85) gave colourless oil
(0.900 g, 24%); 1H NMR (400 MHz, CDCl3): δ = 7.23 (td, J = 7.9, 1.8 Hz,
2H), 7.02 (dd, J = 7.5, 1.7 Hz, 2H), 6.91 – 6.84 (m, 4H), 5.97 (d, J = 1.7
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10.1002/ejoc.201901708
European Journal of Organic Chemistry
FULL PAPER
Dimethyl 2-(bis(4-chlorophenyl)methylene) succinate 6e and
Dimethyl 2-(bis(4-chlorophenyl)methyl) maleate 7e.
[10] S. Linke, J. Kurz, D. Lipinski, W. Gau, Annalen 1980, 542-556.
[11] S.W. McCombie, C.A. Luchaco, Tetrahedron Lett. 1997, 38, 5775-5776.
[12] H. Jiang, W. Wang, W. Liu, C. Quiao, Chin. J. Chem. 2010, 28, 263-268.
[13] H. Ding, C. Ma, Y. Yang, Y. Wang, Org. Lett. 2005, 7, 2125-2127.
[14] M.A. Schmidt, J.J. Talley, M.G. Scaros, P.K. Yonan in Chemical
Industries, Catalysis of Organic Reactions, Dekker, New York, 1995, 62,
105-114.
Purification by column chromatography (EtOAc/CycHex 10:90) gave
colourless oil (3.18 g, 84 %) as a mixture of constitutional isomers with a
percentage ratio of 25:75 (6e:7e); IR (Neat): νmax = 3001, 2952, 1728,
1649, 1490, 1435, 1264, 1199, 1170, 1090, 1015, 829 cm-1; HRMS (ESI-
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Keywords: arylation • arylmethylidene succinates • Dimethyl
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10.1002/ejoc.201901708
European Journal of Organic Chemistry
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Arylmethylidene succinates*
Lauryna Matelienė (née Dauksaîtė), Jan
Knaup, Frank von Horsten, Xiaoting Gu,
and Heiko Brunner*
N
2BF4
FG
FG
FG
Pd/Al2O3
+
COOMe
COOMe
COOMe
COOMe
COOMe
FG
FG
FG
COOMe
CN, COOMe, OCH CH
3,
FG: Ac, Hal, NO2,
3
21 examples
Page No. – Page No.
In-situ generated palladium on aluminium oxide provides an active and efficient
catalytic system for the preparation of arylmethylidene succinates using the Heck-
Matsuda reaction. Beside the monoarylation the first examples of the biarylation of
this monomer will be described.
Benign Arylations of Dimethyl
Itaconate via Heck-Matsuda Reaction
Utilizing in-situ Generated Palladium
on Aluminum Oxide
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