Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones

Article abstract of DOI:10.1021/acs.joc.8b01910

A fast and effective one-pot tandem process that generates Heck coupled products from readily available anilines via stable aryl diazonium tosylate salts was developed. The mild and simple procedure involves rapid formation of aryl diazonium salts using a polymer-supported nitrite reagent and p-tosic acid, followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using 2-nitroanilines as substrates, the one-pot tandem process was extended for the direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4-dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion channel modulator.

Full text of DOI:10.1021/acs.joc.8b01910

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Article
Multibond Forming Tandem Reactions of Anilines via Stable Aryl
Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones
Reka J. Faggyas, Megan Grace, Lewis Williams, and Andrew Sutherland
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01910 • Publication Date (Web): 19 Sep 2018
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The Journal of Organic Chemistry
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Multibond Forming Tandem Reactions of Anilines via
Stable Aryl Diazonium Salts: OneꢀPot Synthesis of 3,4ꢀ
Dihydroquinolinꢀ2ꢀones
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Réka J. Faggyas, Megan Grace, Lewis Williams and Andrew Sutherland*
WestCHEM, School of Chemistry, The Joseph Black Building, University of Glasgow,
Glasgow G12 8QQ, United Kingdom.
Andrew.Sutherland@glasgow.ac.uk
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
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Table of Contents Graphic:
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Abstract: A fast and effective oneꢀpot tandem process that generates Heck coupled products from
readily available anilines via stable aryl diazonium tosylate salts has been developed. The mild and
simple procedure involves rapid formation of aryl diazonium salts using a polymerꢀsupported nitrite
reagent and pꢀtosic acid, followed by a baseꢀfree HeckꢀMatsuda coupling with acrylates and styrenes.
Using 2ꢀnitroanilines as substrates, the oneꢀpot tandem process was extended for the direct synthesis of
3,4ꢀdihydroquinolinꢀ2ꢀones. In this case, following diazotization and HeckꢀMatsuda coupling to give
methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the
nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4ꢀdihydroquinolinꢀ2ꢀ
ones. The synthetic utility of this oneꢀpot, fourꢀstage process was demonstrated with the fiveꢀpot
synthesis of a quinolinone based sodium ion channel modulator.
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The Journal of Organic Chemistry
INTRODUCTION
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The MizorokiꢀHeck coupling of aryl halides with olefins in the presence of a palladium catalyst and a
base has become a general method for carbonꢀcarbon bond formation.1 This powerful transformation
allows the stereoselective synthesis of highly substituted alkenes, key synthetic building blocks for
organic chemistry.2 Despite the many applications of the MizorokiꢀHeck reaction, the transformation
can be limited by the requirement of a base, elevated temperatures and olefin migration. A lessꢀutilized
variant of this crossꢀcoupling is the HeckꢀMatsuda reaction that uses aryl diazonium salts as more
reactive aryl halide surrogates (Scheme 1a).3 The increased electrophilic nature of aryl diazonium salts
allows the HeckꢀMatsuda reaction to proceed at lower temperatures and often without the need for
ligands or a base.4 Under these milder conditions, alkene migration is minimized, generating cleaner
products.
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Despite these advantages, the safety hazards associated with aryl diazonium salts has restricted the
widespread use of the HeckꢀMatsuda reaction. This has partly been countered by replacing aryl
diazonium chlorides and acetates that are unstable above 0 °C, with more stable tetrafluoroborate
crystalline salts.5 However, these compounds still require storage at low temperatures and in the dark.
To minimize the safety issues of handling and storing aryl diazonium salts, oneꢀpot methods in which
the aryl diazonium salts are formed in situ and directly subjected to a HeckꢀMatsuda reaction have been
developed.6 Examples include a procedure reported by Andrus and coꢀworkers that used an imidazolium
carbene as a palladium ligand for the baseꢀfree coupling of a focused series of substrates in 17–62%
yield (Scheme 1b).7 In recent years, the Felpin group have made a major contribution in understanding
and advancing the applications of the HeckꢀMatsuda reaction.8 This has included the development of a
oneꢀpot tandem synthesis of Heck adducts from anilines using catalytic amounts of diazonium salts via
a double catalytic cycle (Scheme 1c).8c This process was found to be general for the efficient coupling
of a wide range of substituted anilines with methyl acrylate, giving the Heck adducts in excellent yields
over a reaction time of 48–65 hours.
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Scheme 1. Synthesis of Heck Adducts from Anilines
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In 2008, the groups of Filimonov and Chi reported the synthesis and characterization of aryl
diazonium tosylate salts.9 These were prepared from anilines using a polymerꢀsupported nitrite reagent
under mild conditions and were found to have particularly high thermal and aging stability. Despite
these properties, aryl diazonium tosylate salts are still reactive and have been utilized in standard
substitution and crossꢀcoupling reactions.9,10 We recently demonstrated that aryl diazonium tosylate
salts could be generated in situ and subjected to an iodination reaction for the oneꢀpot tandem synthesis
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of aryl iodides from anilines.11 Because of the relatively stable nature of aryl diazonium tosylate salts
and this initial demonstration of their application in oneꢀpot tandem processes, we were interested in
further exploiting these compounds for additional multistep transformations. Herein, we now report a
rapid, mild and nonꢀhazardous oneꢀpot tandem diazotization and Heck reaction of anilines for the
general preparation of cinnamates and styrenes (Scheme 1d). The highly chemoselective nature of this
tandem process is demonstrated with halogenated anilines that following diazotization and Heck
reaction can undergo further functionalization via additional crossꢀcoupling reactions. We also describe
an extension of the tandem process with 2ꢀnitroanilines in which the Heck adducts can be directly
converted to 3,4ꢀdihydroquinolinꢀ2ꢀones by the addition of hydrogen and reutilization of the palladium
catalyst.
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RESULTS AND DISCUSSION
In several studies of the HeckꢀMatsuda reaction, nitroꢀsubstituted anilines have been found to be
problem substrates.5,6d,12 The high redox potential and a favorable homolytic dediazonization pathway
of nitroꢀsubstituted aryl diazonium salts have been used to explain the facile decomposition of these
compounds and the complex mixtures from attempted HeckꢀMatsuda reactions. Felpin and coꢀworkers
demonstrated that their oneꢀpot diazotization and HeckꢀMatsuda reaction process could overcome these
issues, allowing the efficient generation of coupled products (Scheme 1c).8c Because of the issues
associated with nitro analogues and to investigate whether our oneꢀpot tandem process could also
overcome these problems, our study began by investigating the oneꢀpot synthesis of aryl diazonium
tosylate salts and HeckꢀMatsuda coupling reaction using 4ꢀnitroaniline (1a) as a substrate. Initially, a
oneꢀpot tandem process in which all the reagents were added together was investigated. This included
the polymerꢀsupported nitrite reagent, which prevents the release of nitrogen oxides and is easily
prepared by the ion exchange of tetraalkylammonium functionalized resins, such as Amberlyst Aꢀ26
with aqueous solutions of sodium nitrite.9,11 Initially, the use of tetrafluoroboric acid as a proton source
was compared with pꢀtosic acid (Table 1, entries 1 and 2). A higher conversion and cleaner reaction
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were observed for pꢀtosic acid and so this was used for further optimization. An increase in temperature
to 60 ºC, resulted in a higher conversion and a much shorter reaction time (entry 4). Increasing both the
palladium acetate catalyst loading to 15 mol % and the reaction time to 1.5 hours allowed full
conversion (entry 5). Finally, lowering the catalyst loading to 5 mol %, under the optimized conditions
still gave full conversion and an isolated yield of 68% for cinnamate 2a. Throughout this optimization
study and in accordance with the Felpin oneꢀpot process,8c no issues of dediazonization and
decomposition of the aryl diazonium tosylate salt intermediate were observed. It should also be noted
that during the early stages of optimization of this process, a wide range of palladium catalysts (e.g.
PdCl2, Pd(PPh3)4, Pd(tfa)2, Pd(hfacac)2, Pd(acac)2, Pd2dba3, PdCl2(dppf) etc.) and associated ligands
(e.g. (nꢀBu)3P, (2ꢀfuryl)3P, SꢀPhos, DaveꢀPhos, XꢀPhos etc.) were trialed, however, the standard baseꢀ
free conditions using palladium acetate gave the best results.
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Table 1.
Optimization of the One-Pot Tandem Diazotization and Heck-Matsuda Reaction.
entry Pd(OAc)2 (mol %) temp (ºC) time (h) conv (%)a,b
1c
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aConversions were measured using 1,3,5ꢀtrimethoxybenzene as an internal standard. Isolated yields are
in parenthesis. cUsing HBF4 as the proton source.
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Following the optimization of a rapid and mild oneꢀpot tandem process for diazotization and Heck
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coupling, the scope of this transformation was explored using various anilines and methyl acrylate
(Scheme 2). Irrespective of the electronic nature or the substitution pattern of the aniline, all examples
investigated were fully converted under the standard conditions to the corresponding Heck adduct in
yields of 53–83%. Interestingly, the oneꢀpot diazotization and HeckꢀMatsuda coupling of halogenated
anilines was completely chemoselective, giving compounds 2d–2f, 2i and 2l as the sole products. These
results, particularly for 2e, 2f and 2i, exemplify the superior electrophilic nature of diazonium salts
compared to halides. The oneꢀpot process was also investigated for the synthesis of Eꢀstilbenes.
Reaction of 4ꢀnitroaniline (1a) with styrene or 4ꢀfluorostyrene gave Eꢀstilbenes 2n and 2o in 74% and
46% yields, respectively.
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Scheme 2. Scope of One-Pot Tandem Diazotization and Heck-Matsuda Processa
aIsolated yields are shown.
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As the oneꢀpot process with halogenated anilines gave only HeckꢀMatsuda adducts and none of the
MizorokiꢀHeck products, we wanted to exploit this chemoselectivity for the twoꢀpot synthesis of
orthogonally functionalized aryl compounds.13 The oneꢀpot diazotization and HeckꢀMatsuda coupling of
4ꢀbromoaniline (1e) was scaled up, allowing the multigram synthesis of methyl (E)ꢀ3ꢀ(4ꢀ
bromophenyl)acrylate (2e) (Scheme 3). Having used the amino group to implement the first crossꢀ
coupling process, 2e was then subjected to a MizorokiꢀHeck reaction with styrene.14 This gave Eꢀ
stilbene 3 in 72% yield. In a similar fashion, arylation or allylation by SuzukiꢀMiyaura reaction of 2e
completed the efficient twoꢀpot synthesis of acrylates 4a–4d. This study shows that a combination of the
oneꢀpot diazotization and HeckꢀMatsuda process with a further crossꢀcoupling reaction allows the
highly controlled and selective introduction of multiple unsaturated moieties onto a central arene core.
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Scheme 3. Orthogonal Chemoselective Functionalization of 4-Bromoaniline (1e)a
aIsolated yields are shown.
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A key objective of this project was to expand the scope of the oneꢀpot diazotization and Heckꢀ
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Matsuda process to include 2ꢀnitroanilines as substrates. It was proposed that the resulting 2ꢀnitrophenyl
acrylates could be converted to 3,4ꢀdihydroquinolinꢀ2ꢀones by extending the oneꢀpot process to include
reduction and cyclization steps. Before attempting the extended oneꢀpot process, a series of substituted
2ꢀnitroanilines were initially examined as substrates for the oneꢀpot twoꢀstep tandem process (Scheme
4). Using the previously developed standard conditions, a wide range of acrylates 6a–6n, bearing
various functional groups and substitution patterns were prepared in 56–87% yields. Again, complete
chemoselectivity was observed with brominated (5i) and iodinated (5j) anilines.
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Scheme 4. Scope of One-Pot Tandem Diazotization and Heck-Matsuda Process using 2-
Nitroanilinesa
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As 2ꢀnitroanilines were found to be excellent substrates for the oneꢀpot diazotization and Heckꢀ
Matsuda reaction, the use of these in an extended oneꢀpot multibond forming process for the preparation
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of 3,4ꢀdihydroquinolinꢀ2ꢀones was next investigated. 3,4ꢀDihydroquinolinꢀ2ꢀones are important
heterocyclic scaffolds for synthesis and are found in a wide range of pharmaceutically active agents.15
Because of this importance, numerous methods have been developed for their synthesis, including oneꢀ
pot processes. For example, Jiao and coꢀworkers used a combination of radical and ionic processes for
the reaction of 2ꢀiodoanilines with ethyl acrylate for the preparation of 3,4ꢀdihydroquinolinꢀ2ꢀones in
17–71% yields,16 while the Lautens groups developed a oneꢀpot Rh/Pd catalyzed conjugate addition and
amidation process of 2ꢀchlorophenyl boronic acids with acrylamide to generate a series of these
compounds in 53–96% yields.17 Felpin and coꢀworkers have also reported a oneꢀpot synthesis of 3,4ꢀ
dihydroquinolinꢀ2ꢀones from 2ꢀnitroaryl tetrafluoroborate diazonium salts using a HeckꢀMatsuda
reaction with acrylates followed by the addition of charcoal and a reduction and cyclization sequence.8b
In our study, we wanted to demonstrate that 3,4ꢀdihydroquinolinꢀ2ꢀones could be prepared directly from
2ꢀnitroanilines using the palladium catalyst to effect the HeckꢀMatsuda coupling and the
hydrogenation/reduction steps without the use of any additives. Using 2ꢀnitroaniline (5a), the oneꢀpot
tandem diazotization and HeckꢀMatsuda sequence was performed as before (Scheme 5). On complete
conversion to methyl acrylate 6a, the reaction mixture was placed under an atmosphere of hydrogen.
After 24 hours, this gave 3,4ꢀdihydroquinolinꢀ2ꢀone 7a in 73% overall yield. Having shown that a oneꢀ
pot diazotization/HeckꢀMatsuda/reduction/cyclization sequence could lead directly to 3,4ꢀ
dihydroquinolinꢀ2ꢀones, the scope and limitations of this process were investigated. Alkyl substituted 2ꢀ
nitroanilines and a substrate bearing a fluorine substituent were readily converted to the corresponding
3,4ꢀdihydroquinolinꢀ2ꢀones 7a–7d and 7g, in yields of 64–79%, under these conditions. Electronꢀrich
methoxy substituted 2ꢀnitroanilines 5e and 5f could also be converted to 3,4ꢀdihydroquinolinꢀ2ꢀones 7e
and 7f, however, the hydrogenation/reduction step at atmospheric pressure was slow, leading to
mixtures of the target 3,4ꢀdihydroquinolinꢀ2ꢀones and methyl 2ꢀnitrophenylpropionate intermediates
after 24 hours.18 To effect cleaner, more efficient syntheses of these compounds, the oneꢀpot process
was repeated by conducting the reduction stage under pressure, at 2.5 bar. This gave 3,4ꢀ
dihydroquinolinꢀ2ꢀones 7e and 7f as the sole products, in 74% and 57% yields, respectively. A
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limitation of this oneꢀpot process is that 2ꢀnitroanilines bearing labile carbonꢀhalogen bonds are subject
to dehalogenation at the reduction stage. For example, the attempted use of 5ꢀchloroꢀ2ꢀnitroaniline (5h)
as a substrate for this process gave 5ꢀchloroꢀ3,4ꢀdihydroquinolinꢀ2ꢀone in 28% yield but as a 1:1
inseparable mixture with the desꢀchlorinated product 7a. Our interest in preparing halogenated 3,4ꢀ
dihydroquinolinꢀ2ꢀones was for the potential structural diversification of these through crossꢀcoupling
reactions after the oneꢀpot process. To overcome this limitation, crossꢀcoupling reactions were
conducted prior to the oneꢀpot process for the efficient twoꢀpot synthesis of 7ꢀarylꢀ3,4ꢀdihydroquinolinꢀ
2ꢀones. SuzukiꢀMiyaura reaction of 4ꢀiodoꢀ2ꢀnitroaniline (5j) with various aryl boronic acids (see SI for
full details), was then followed by the oneꢀpot process, which gave 7h–7j in 57–73% yield. While the
standard diazotization and HeckꢀMatsuda steps for the 4ꢀarylꢀ2ꢀnitroanilines could be conducted under
standard conditions, again the use of 2.5 bar of pressure for the reduction stage allowed the most
efficient synthesis of these analogues.
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Scheme 5. One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones using 2-Nitroanilinesa
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aIsolated yields are shown. Reduction stage was conducted under a hydrogen atmosphere of 2.5 bar
and at room temperature.
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The synthetic potential of the 3,4ꢀdihydroquinolinꢀ2ꢀones prepared from the extended oneꢀpot process
was then demonstrated with the synthesis of a pharmaceutically active target. Nꢀacetic acid derived 3,4ꢀ
dihydroquinolinꢀ2ꢀones bearing 6ꢀ or 7ꢀaryl groups are late stage sodium channel blockers and have the
potential to be used in the treatment of cardiovascular diseases and diabetes.19 In this study, a sodium
channel modulator, 3,4ꢀdihydroquinolinꢀ2ꢀone 11 was prepared via a fiveꢀpot synthesis (Scheme 6). As
shown above, the extended oneꢀpot process was used to convert 5ꢀmethoxyꢀ2ꢀnitroaniline (5e) to the
corresponding 3,4ꢀdihydroquinolinꢀ2ꢀone 7e on a gram scale, in 57% yield. Quinolinꢀ2ꢀone 7e was
alkylated in quantitative yield using tꢀbutyl chloroacetate and sodium hydride. A highly regioselective
iron(III) triflimideꢀcatalyzed halogenation with Nꢀbromosuccinimide (NBS) was used to functionalize
the 6ꢀposition of the aryl ring.20 The combination of catalytic amounts of iron(III) chloride and the ionic
liquid, [BMIM]NTf2 forms iron(III) triflimide in situ, which acts as a powerful Lewis acid for the
activation of NBS. This reaction gave 6ꢀbromoꢀ3,4ꢀdihydroquinolinꢀ2ꢀone 9 as the sole product in 81%
yield. SuzukiꢀMiyaura coupling of 9 with 4ꢀchlorophenyl boronic acid under standard conditions gave
6ꢀarylꢀ3,4ꢀdihydroquinolinꢀ2ꢀone 10 in 75% yield. Finally, TFA mediated deprotection of the tꢀbutyl
ester completed the synthesis of sodium ion channel modulator 11 in 32% overall yield from 2ꢀ
nitroaniline 5e.
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Scheme 6. Five-Pot Synthesis of Quinolinone Based Sodium Ion Channel Modulator 11a
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aIsolated yields are shown.
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CONCLUSIONS
In summary, a rapid oneꢀpot tandem process involving diazotization and baseꢀfree HeckꢀMatsuda
coupling of anilines with acrylates and styrenes has been developed. The use of a particularly mild
procedure to form stable aryl diazonium tosylate salts using a polymerꢀsupported nitrite reagent and pꢀ
tosic acid as the proton source allowed the synthesis of a wideꢀrange of Heck adducts. A particular
feature of this process was the chemoselective coupling of brominated and iodinated anilines, which
could then be further functionalized using additional crossꢀcoupling reactions, leading to orthogonally
substituted arenes. Using 2ꢀnitroanilines as substrates, the oneꢀpot process was extended for the direct
synthesis of 3,4ꢀdihydroquinolinꢀ2ꢀones. Following the diazotization and HeckꢀMatsuda steps,
reutilization of the palladium catalyst without the requirement of additional ligands or additives allowed
hydrogenation of the alkene, reduction of the nitro group and in situ cyclization to give a series of 3,4ꢀ
dihydroquinolinꢀ2ꢀones. The potential of these oneꢀpot multibond forming processes for application in
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total synthesis and medicinal chemistry was demonstrated with the fiveꢀpot preparation of a sodium ion
channel modulator. Investigation of further applications of stable aryl diazonium salts in oneꢀpot
multistep processes is currently underway.
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EXPERIMENTAL SECTION
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All reagents and starting materials were obtained from commercial sources and used as received
unless otherwise stated. Dry solvents were purified using a solvent purification system. Brine refers to a
saturated solution of sodium chloride. All reactions were performed in ovenꢀdried glassware under an
atmosphere of argon unless otherwise stated. Flash column chromatography was carried out using silica
gel (40–63 ꢁm) and neutral aluminium oxide (50–200 ꢁm). Aluminiumꢀbacked plates preꢀcoated with
silica gel 60 (UV254) were used for thin layer chromatography and were visualized under ultraviolet
light and by staining with KMnO4 or ninhydrin. 1H NMR spectra were recorded on a NMR spectrometer
at 400 MHz and data are reported as follows: chemical shift in ppm relative to tetramethylsilane or the
solvent as the internal standard (CDCl3, δ 7.26 ppm), multiplicity (s = singlet, d = doublet, t = triplet, q
13
= quartet, m = multiplet or overlap of nonequivalent resonances, integration). C NMR spectra were
recorded on a NMR spectrometer at 101 MHz and data are reported as follows: chemical shift in ppm
relative to tetramethylsilane or the solvent as internal standard (CDCl3, δ 77.0 ppm), multiplicity with
respect to hydrogen (deduced from DEPT experiments, C, CH, CH2 or CH3). IR spectra were recorded
on a FTIR spectrometer; wavenumbers are indicated in cm–1. Mass spectra were recorded using electron
impact or electrospray techniques. HRMS spectra were recorded using a dualꢀfocusing magnetic
analyzer mass spectrometer. Melting points are uncorrected.
General procedure for the preparation of the polymer-supported nitrite. To a stirred solution of
sodium nitrite (0.55 g, 8.00 mmol) in water (20 mL) was added Amberlyst A26 hydroxide form resin
(1.00 g, 4.00 mmol). The resulting mixture was stirred at room temperature for 0.5 h, and then polymerꢀ
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supported resin was filtered and washed with water until the pH of filtrate became neutral. The content
of prepared polymerꢀsupported nitrite was 3.5 mmol of NO2 per g of resin.9
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Methyl (E)-3-(4’-nitrophenyl)acrylate (2a).8c To a stirred solution of 4ꢀnitroaniline (1a) (0.028 g,
0.20 mmol), polymerꢀsupported nitrite (0.17 g, containing 0.60 mmol of NO2), pꢀtoluenesulfonic acid
monohydrate (0.10 g, 0.60 mmol) and palladium(II) acetate (0.0020 g, 0.010 mmol) in methanol (2 mL)
was added methyl acrylate (0.090 mL, 1.0 mmol). The reaction mixture was heated to 60 °C and stirred
for 1.5 h. The mixture was cooled to room temperature, filtered and the resin was washed with methanol
(2 mL). The combined organic layers were concentrated in vacuo. Purification by silica gel flash
column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀ
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nitrophenyl)acrylate (2a) (0.028 g, 68%) as a pale yellow solid. Mp 159‒161 °C (lit.8c 161 °C); H
NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.56 (d, J = 16.1 Hz, 1H), 7.67 (d, J = 8.7 Hz, 2H), 7.71 (d, J =
16.1 Hz, 1H), 8.24 (d, J = 8.7 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 52.1 (CH3), 122.1 (CH), 124.2 (2
× CH), 128.7 (2 × CH), 140.5 (C), 141.9 (CH), 148.6 (C), 166.5 (C); MS (EI) m/z 207 (M+, 66), 176
(100), 130 (24), 102 (26).
Methyl (E)-3-(4’-acetylphenyl)acrylate (2b).21 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀ
aminoacetophenone (1b) (0.050 g, 0.37 mmol), polymerꢀsupported nitrite (0.32 g, containing 1.1 mmol
of NO2), pꢀtoluenesulfonic acid monohydrate (0.19 g, 1.1 mmol), palladium(II) acetate (0.0040 g, 0.019
mmol) and methyl acrylate (0.17 mL, 1.9 mmol). Purification by silica gel flash column
chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀacetylphenyl)acrylate
(2b) (0.050 g, 64%) as an orange oil. Spectroscopic data were consistent with the literature.21 1H NMR
(400 MHz, CDCl3) δ 2.62 (s, 3H), 3.83 (s, 3H), 6.53 (d, J = 16.1 Hz, 1H), 7.61 (d, J = 8.3 Hz, 2H), 7.71
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(d, J = 16.1 Hz, 1H), 7.97 (d, J = 8.3 Hz, 2H); C NMR (101 MHz, CDCl3) δ 26.6 (CH3), 51.9 (CH3),
120.3 (CH), 128.1 (2 × CH), 128.8 (2 × CH), 138.1 (C), 138.7 (C), 143.3 (CH), 166.9 (C), 197.2 (C);
MS (ESI) m/z 205 (M+H+, 100).
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Methyl (E)-3-(4’-cyanophenyl)acrylate (2c).22 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀ
aminobenzonitrile (1c) (0.050 g, 0.42 mmol), polymerꢀsupported nitrite (0.36 g, containing 1.3 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.22 g, 1.3 mmol), palladium(II) acetate (0.005 g, 0.02
mmol) and methyl acrylate (0.19 mL, 2.1 mmol). Purification by neutral alumina and then silica gel
flash column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀ
cyanophenyl)acrylate (2c) (0.046 g, 59%) as a yellow solid. Mp 120‒122 °C (lit.22 121.7‒122.1 °C); 1H
NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.52 (d, J = 16.0 Hz, 1H), 7.61 (d, J = 8.3 Hz, 2H), 7.64‒7.71
(m, 3H); 13C NMR (101 MHz, CDCl3) δ 52.1 (CH3), 113.5 (C), 118.4 (C), 121.4 (CH), 128.4 (2 × CH),
132.7 (2 × CH), 138.7 (C), 142.4 (CH), 166.6 (C); MS (EI) m/z 187 (M+, 50), 156 (100), 128 (42), 84
(27).
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Methyl (E)-3-(4’-chlorophenyl)acrylate (2d).8d The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀchloroaniline
(1d) (0.050 g, 0.39 mmol), polymerꢀsupported nitrite (0.33 g, containing 1.2 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.20 g, 1.2 mmol), palladium(II) acetate (0.0040 g, 0.020 mmol) and
methyl acrylate (0.18 mL, 2.0 mmol). Purification by neutral alumina and then silica gel flash column
chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀchlorophenyl)acrylate
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(2d) (0.040 g, 53%) as a yellow solid. Mp 73‒75 °C (lit.8d 74‒75 °C); H NMR (400 MHz, CDCl3) δ
3.80 (s, 3H), 6.41 (d, J = 16.0 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 7.63 (d, J =
16.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 51.8 (CH3), 118.4 (CH), 129.2 (2 × CH), 129.2 (2 × CH),
132.9 (C), 136.2 (C), 143.4 (CH), 167.2 (C); MS (EI) m/z 196 (M+, 68), 165 (100), 137 (27), 101 (24),
78 (22), 63 (25).
Methyl (E)-3-(4’-bromophenyl)acrylate (2e).22 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀbromoaniline
(1e) (0.050 g, 0.29 mmol), polymerꢀsupported nitrite (0.25 g, containing 0.87 mmol of NO2), pꢀ
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toluenesulfonic acid monohydrate (0.15 g, 0.87 mmol), palladium(II) acetate (0.0030 g, 0.015 mmol)
and methyl acrylate (0.13 mL, 1.5 mmol). Purification by neutral alumina flash column
chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀbromophenyl)acrylate
(2e) (0.050 g, 72%) as a yellow solid. Mp 86‒88 °C (lit.22 87.9‒88.2 °C); 1H NMR (400 MHz, CDCl3) δ
3.81 (s, 3H), 6.43 (d, J = 16.0 Hz, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 7.62 (d, J =
16.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 51.8 (CH3), 118.5 (CH), 124.6 (C), 129.5 (2 × CH), 132.2
(2 × CH), 133.3 (C), 143.5 (CH), 167.2 (C); MS (EI) m/z 242 (M+, 95), 240 (96), 211 (99), 209 (100),
102 (87), 84 (55).
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Methyl (E)-3-(4’-iodophenyl)acrylate (2f).22 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀiodoaniline (1f)
(0.050 g, 0.23 mmol), polymerꢀsupported nitrite (0.20 g, containing 0.69 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.12 g, 0.69 mmol), palladium(II) acetate (0.0030 g, 0.012 mmol)
and methyl acrylate (0.10 mL, 1.2 mmol). Purification by alumina flash column chromatography,
eluting with 2% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀiodophenyl)acrylate (2f) (0.036 g, 55%)
as a white solid. Mp 117‒119 °C (lit.22 119‒123.9 °C); 1H NMR (400 MHz, CDCl3) δ 3.80 (s, 3H), 6.44
(d, J = 16.0 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 16.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H); 13C
NMR (101 MHz, CDCl3) δ 51.8 (CH3), 96.5 (C), 118.6 (CH), 129.5 (2 × CH), 133.9 (C), 138.1 (2 ×
CH), 143.7 (CH), 167.2 (C); MS (EI) m/z 288 (M+, 96), 257 (40), 130 (27), 102 (20), 84 (100).
Methyl (E)-3-(4’-methoxyphenyl)acrylate (2g).23 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀmethoxyaniline
(1g) (0.050 g, 0.41 mmol), polymerꢀsupported nitrite (0.35 g, containing 1.2 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.21 g, 1.2 mmol), palladium(II) acetate (0.0050 g, 0.021 mmol) and
methyl acrylate (0.18 mL, 2.1 mmol). Purification by neutral alumina flash column chromatography,
eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀmethoxyphenyl)acrylate (2g) (0.052 g,
66%) as a white solid. Mp 85‒87 °C (lit.23 86 °C); 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.84 (s,
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3H), 6.31 (d, J = 16.0 Hz, 1H), 6.90 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 16.0 Hz,
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1H); C NMR (101 MHz, CDCl3) δ 51.6 (CH3), 55.4 (CH3), 114.3 (2 × CH), 115.3 (CH), 127.2 (C),
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129.7 (2 × CH), 144.5 (CH), 161.4 (C), 167.8 (C); MS (ESI) m/z 193 (M+H+, 100).
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Methyl (E)-3-(3’-nitrophenyl)acrylate (2h).24 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 3ꢀnitroaniline (1h)
(0.050 g, 0.36 mmol), polymerꢀsupported nitrite (0.31 g, containing 1.1 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.19 g, 1.1 mmol), palladium(II) acetate (0.0040 g, 0.018 mmol) and
methyl acrylate (0.16 mL, 1.8 mmol). Purification by neutral alumina flash column chromatography,
eluting with 5% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(3’ꢀnitrophenyl)acrylate (2h) (0.040 g, 54%)
as a pale yellow solid. Mp 120‒122 °C (lit.24 122‒123 °C); 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H),
6.56 (d, J = 16.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.72 (d, J = 16.0 Hz, 1H), 7.82 (br d, J = 8.0 Hz, 1H),
8.22 (ddd, J = 8.0, 2.0, 0.8 Hz, 1H), 8.37 (t, J = 2.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 52.0 (CH3),
121.0 (CH), 122.5 (CH), 124.6 (CH), 130.0 (CH), 133.6 (CH), 136.1 (C), 142.0 (CH), 148.7 (C), 166.6
(C); MS (ESI) m/z 230 (M+Na+, 100).
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Methyl (E)-3-(2’-iodophenyl)acrylate (2i).25 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀiodoaniline (1i)
(0.050 g, 0.23 mmol), polymerꢀsupported nitrite (0.20 g, containing 0.69 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.12 g, 0.69 mmol), palladium(II) acetate (0.0030 g, 0.011 mmol)
and methyl acrylate (0.10 mL, 1.2 mmol). Purification by neutral alumina and then silica gel flash
column chromatography, eluting with 2% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’ꢀ
iodophenyl)acrylate (2i) (0.042 g, 63%) as a yellow oil. Spectroscopic data were consistent with the
literature.25 1H NMR (400 MHz, CDCl3) δ 3.82 (s, 3H), 6.31 (d, J = 15.8 Hz, 1H), 7.05 (td, J = 8.0, 1.6
Hz, 1H), 7.35 (td, J = 8.0, 1.2 Hz, 1H), 7.55 (dd, J = 8.0, 1.6 Hz, 1H), 7.89 (dd, J = 8.0, 1.2 Hz, 1H),
7.90 (d, J = 15.8 Hz, 1H); δC (101 MHz, CDCl3) δ 51.9 (CH3), 101.2 (C), 120.8 (CH), 127.4 (CH),
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128.6 (CH), 131.3 (CH), 137.8 (C), 140.0 (CH), 147.9 (CH), 166.7 (C); MS (ESI) m/z 311 (M+Na+,
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100).
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Methyl (E)-3-[2’-(trifluoromethyl)phenyl]acrylate (2j).26 The reaction was carried out according to
the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀ
trifluoromethylaniline (1j) (0.040 mL, 0.31 mmol), polymerꢀsupported nitrite (0.27 g, containing 0.93
mmol of NO2), pꢀtoluenesulfonic acid monohydrate (0.16 g, 0.93 mmol), palladium(II) acetate (0.0040
g, 0.016 mmol) and methyl acrylate (0.14 mL, 1.6 mmol). Purification by neutral alumina and then
silica gel flash column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ
[2’ꢀ(trifluoromethyl)phenyl]acrylate (2j) (0.059 g, 83%) as a yellow oil. Spectroscopic data were
consistent with the literature.26 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.41 (d, J = 16.0 Hz, 1H),
7.48 (t, J = 8.0 Hz, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.70 (br d, J = 8.0 Hz, 2H), 8.06 (dq, J = 16.0, 2.0 Hz,
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1H); C NMR (101 MHz, CDCl3) δ 51.9 (CH3), 122.2 (CH), 123.9 (q, JCꢀF = 274.0 Hz, C), 126.2 (q,
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3JCꢀF = 5.6 Hz, CH), 127.9 (CH), 128.9 (q, JCꢀF = 30.4 Hz, C), 129.6 (CH), 132.1 (q, JCꢀF = 1.0 Hz,
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CH), 133.4 (q, JCꢀF = 1.3 Hz, C), 140.3 (q, JCꢀF = 1.9 Hz, CH), 166.5 (C); MS (ESI) m/z 231 (M+H+,
100).
Methyl (E)-3-(2’-benzoylphenyl)acrylate (2k).27 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀ
aminobenzophenone (1k) (0.050 g, 0.25 mmol), polymerꢀsupported nitrite (0.21 g, 0.75 mmol), pꢀ
toluenesulfonic acid monohydrate (0.13 g, 0.75 mmol), palladium(II) acetate (0.0030, 0.013 mmol) and
methyl acrylate (0.11 mL, 1.3 mmol). Purification by neutral alumina flash column chromatography,
eluting with 5% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’ꢀbenzoylphenyl)acrylate (2k) as a yellow
oil (0.047 g, 71%). Spectroscopic data were consistent with the literature.27 1H NMR (400 MHz, CDCl3)
δ 3.72 (s, 3H), 6.38 (d, J = 16.0 Hz, 1H), 7.39‒7.49 (m, 4H), 7.53 (td, J = 7.6, 2.4 Hz, 1H), 7.60 (ddt, J
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= 7.6, 7.2, 1.2 Hz, 1H), 7.71‒7.82 (m, 4H); C NMR (101 MHz, CDCl3) δ 51.7 (CH3), 120.5 (CH),
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127.3 (CH), 128.6 (2 × CH), 129.2 (CH), 129.2 (CH), 130.4 (2 × CH), 130.8 (CH), 133.6 (CH), 133.9
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(C), 137.3 (C), 139.4 (C), 142.0 (CH), 166.8 (C), 197.2 (C); MS (ESI) m/z 289 (M+Na+, 100).
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Methyl (E)-3-(2’,4’,6’-trichlorophenyl)acrylate (2l). The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2,4,6ꢀ
trichloroaniline (1l) (0.050 g, 0.25 mmol), polymerꢀsupported nitrite (0.21 g, containing 0.75 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.13 g, 0.75 mmol), palladium(II) acetate (0.0030 g, 0.010
mmol) and methyl acrylate (0.11 mL, 1.3 mmol). Purification by silica gel flash column
chromatography, eluting with 2% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’,4’,6’ꢀ
trichlorophenyl)acrylate (2l) (0.045 g, 68%) as a pale yellow solid. Mp 64‒66 °C; IR (neat) 2926, 1726,
1651, 1314, 1292, 1202, 1173, 970 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.57 (d, J = 16.4
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Hz, 1H), 7.37 (s, 2H), 7.70 (d, J = 16.4 Hz, 1H); C NMR (101 MHz, CDCl3) δ 52.0 (CH3), 126.8
(CH), 128.8 (2 × CH), 130.6 (C), 134.9 (C), 135.5 (2 × C), 137.3 (CH), 166.4 (C); MS (ESI) m/z 229
([M–Cl]+, 100), 207 (13), 170 (17), 84 (39); HRMS (EI) calcd for C10H7 Cl2O2 ([M–Cl]+) 228.9823,
35
found 228.9821.
Methyl (E)-3-(2’-methoxy-5’-methylphenyl)acrylate (2m).28 The reaction was carried out
according to the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀ
methoxyꢀ5ꢀmethylaniline (1m) (0.050 g, 0.36 mmol), polymerꢀsupported nitrite (0.31 g, containing 1.1
mmol of NO2), pꢀtoluenesulfonic acid monohydrate (0.19 g, 1.1 mmol), palladium(II) acetate (0.0040 g,
0.018 mmol) and methyl acrylate (0.16 mL, 1.8 mmol). Purification by neutral alumina flash column
chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’ꢀmethoxyꢀ5’ꢀ
methylphenyl)acrylate (2m) (0.045 g, 60%) as a yellow oil. Spectroscopic data were consistent with the
literature.28 1H NMR (400 MHz, CDCl3) δ 2.29 (s, 3H), 3.80 (s, 3H), 3.85 (s, 3H), 6.52 (d, J = 16.0 Hz,
1H), 6.81 (d, J = 8.4 Hz, 1H), 7.14 (dd, J = 8.4, 2.0 Hz, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 16.0
13
Hz, 1H); C NMR (101 MHz, CDCl3) δ 20.4 (CH3), 51.6 (CH3), 55.6 (CH3), 111.1 (CH), 118.1 (CH),
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123.0 (C), 129.4 (CH), 129.9 (C), 132.0 (CH), 140.4 (CH), 156.4 (C), 168.0 (C); MS (ESI) m/z 229
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(M+Na+, 100).
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(E)-1-Nitro-4-styrylbenzene (2n).29 The reaction was carried out according to the previously
described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀnitroaniline (1a) (0.050 g,
0.36 mmol), polymerꢀsupported nitrite (0.31 g, containing 1.1 mmol of NO2), pꢀtoluenesulfonic acid
monohydrate (0.19 g, 1.1 mmol), palladium(II) acetate (0.0080 g, 0.036 mmol) and styrene (0.21 mL,
1.8 mmol). Purification by neutral alumina and then silica gel flash column chromatography, eluting
with 10% diethyl ether in hexane gave (E)ꢀ1ꢀnitroꢀ4ꢀstyrylbenzene (2n) (0.060 g, 74%) as a yellow
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solid. Mp 154‒156 °C (lit.29 155‒158 °C); H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 16.4 Hz, 1H),
7.27 (d, J = 16.4 Hz, 1H), 7.31‒7.44 (m, 3H), 7.53‒7.58 (m, 2H), 7.63 (d, J = 8.8 Hz, 2H), 8.22 (d, J =
13
8.8 Hz, 2H); C NMR (101 MHz, CDCl3) δ 124.2 (2 × CH), 126.3 (CH), 126.9 (2 × CH), 127.0 (2 ×
CH), 128.9 (CH), 128.9 (2 × CH), 133.3 (CH), 136.2 (C), 143.9 (C), 146.8 (C); MS (EI) m/z 225 (M+,
100), 178 (84), 152 (21), 84 (35).
(E)-4-Fluoro-1-(4”-nitrostyryl)benzene (2o).30 The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀnitroaniline (1a)
(0.050 g, 0.36 mmol), polymerꢀsupported nitrite (0.31 g, containing 1.1 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.17 g, 1.1 mmol), palladium(II) acetate (0.0040 g, 0.018 mmol) and
4ꢀfluorostyrene (0.22 mL, 1.8 mmol). Purification by neutral alumina and then silica gel flash column
chromatography, eluting with 10% diethyl ether in hexane gave (E)ꢀ4ꢀfluoroꢀ1ꢀ(4”ꢀnitrostyryl)benzene
(2o) (0.040 g, 46%) as a yellow solid. Spectroscopic data were consistent with the literature.30 Mp 110‒
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113 °C; H NMR (400 MHz, CDCl3) δ 7.03‒7.13 (m, 3H), 7.22 (d, J = 16.0 Hz, 1H), 7.49‒7.56 (m,
2H), 7.61 (d, J = 8.4 Hz, 2H), 8.21 (d, J = 8.4 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 116.0 (d, 2JCꢀF
=
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21.9 Hz, 2 × CH), 124.2 (2 × CH), 126.1 (d, JCꢀF = 2.4 Hz, CH), 126.8 (2 × CH), 128.7 (d, JCꢀF = 8.1
Hz, 2 × CH), 132.0 (d, 6JCꢀF = 0.8 Hz, CH), 132.4 (d, 4JCꢀF = 3.3 Hz, C), 143.7 (C), 146.8 (C), 163.0 (d,
1JCꢀF = 250.3 Hz, C); MS (EI) m/z 243 (M+, 72), 196 (62), 179 (32), 84 (100), 51 (42).
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Methyl (2E)-3-(4’-(1’’E)-styrylphenyl)acrylate (3).31 To a mixture of methyl (E)ꢀ3ꢀ(4’ꢀ
bromophenyl)acrylate (2e) (0.50 g, 0.21 mmol), potassium carbonate (0.058 g, 0.42 mmol) and
bis(triphenylphosphine)palladium(II) dichloride (0.0070 g, 0.011 mmol) in acetonitrile (2.5 mL) was
added styrene (0.036 mL, 0.31 mmol). The reaction mixture was then heated to 90 °C and stirred for 24
h. On cooling to room temperature, the mixture was filtered through Celite, washed with diethyl ether
(20 mL) and concentrated in vacuo. Purification by silica gel flash column chromatography, eluting with
5% diethyl ether in hexane gave methyl (2E)ꢀ3ꢀ(4’ꢀ(1’’E)ꢀstyrylphenyl)acrylate (3) (0.040 g, 72%) as a
white solid. Mp 179‒181 °C (lit.31 183‒184 °C); 1H NMR (400 MHz, CDCl3) δ 3.82 (s, 3H), 6.45 (d, J
= 16.0 Hz, 1H), 7.10 (d, J = 16.3 Hz, 1H), 7.18 (d, J = 16.3 Hz, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.38 (t, J =
7.4 Hz, 2H), 7.50‒7.58 (m, 6H), 7.69 (d, J = 16.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 51.7 (CH3),
117.4 (CH), 126.7 (2 × CH), 126.9 (2 × CH), 127.8 (CH), 128.0 (CH), 128.5 (2 × CH), 128.8 (2 × CH),
130.1 (CH), 133.6 (C), 137.0 (C), 139.4 (C), 144.4 (CH), 167.5 (C); MS (EI) m/z 264 (M+, 100), 233
(10), 203 (12), 189 (6), 178 (8), 83 (22).
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Methyl (E)-3-([1’,1’’-biphenyl]-4’-yl)acrylate (4a).32 To a mixture of methyl (E)ꢀ3ꢀ(4’ꢀ
bromophenyl)acrylate (2e) (0.50 g, 0.21 mmol), phenyl boronic acid (0.26 g, 0.21 mmol) and [1,1’ꢀ
bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.0090 g, 0.011 mmol) in dioxane (4 mL)
was added cesium fluoride (0.064 g, 0.42 mmol). The reaction mixture was degassed with argon under
sonication for 0.5 h and then heated to 80 °C for 24 h. On cooling to room temperature, the mixture was
filtered through Celite, washed with diethyl ether (20 mL) and concentrated in vacuo. Purification by
silica gel flash column chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ
([1’,1’’ꢀbiphenyl]ꢀ4’ꢀyl)acrylate (4a) (0.044 g, 88%) as a pale yellow solid. Mp 146‒148 °C (lit.32 147‒
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148 °C); H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.49 (d, J = 16.0 Hz, 1H), 7.35‒7.41 (m, 1H),
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7.43‒7.50 (m, 2H), 7.57‒7.66 (m, 6H), 7.75 (d, J = 16.0 Hz, 1H); C NMR (101 MHz, CDCl3) δ 51.7
(CH3), 117.7 (CH), 127.1 (2 × CH), 127.6 (2 × CH), 127.9 (CH), 128.6 (2 × CH), 128.9 (2 × CH), 133.4
(C), 140.2 (C), 143.1 (C), 144.4 (CH), 167.5 (C); MS (ESI) m/z 261 (M+Na+, 100).
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Methyl (E)-3-(2’’-methyl-[1’,1’’-biphenyl]-4’-yl)acrylate (4b). The reaction was carried out
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according to the previously described procedure for methyl (E)ꢀ3ꢀ([1’,1’’ꢀbiphenyl]ꢀ4’ꢀyl)acrylate (4a)
using methyl (E)ꢀ3ꢀ(4’ꢀbromophenyl)acrylate (2e) (0.50 g, 0.21 mmol), 2ꢀmethylphenyl boronic acid
(0.44 g, 0.21 mmol), [1,1’ꢀbis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.0090 g, 0.011
mmol) and cesium fluoride (0.064 g, 0.42 mmol). Purification by silica gel flash column
chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’’ꢀmethylꢀ[1’,1’’ꢀ
biphenyl]ꢀ4’ꢀyl)acrylate (4b) (0.044 g, 83%) as a white solid. Mp 51‒53 °C; IR (neat) 2949, 1708, 1632,
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1313, 1169, 998, 935, 765 cm−1; H NMR (400 MHz, CDCl3) δ 2.27 (s, 3H), 3.81 (s, 3H), 6.47 (d, J =
16.0 Hz, 1H), 7.19‒7.29 (m, 4H), 7.34 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.74 (d, J = 16.0
Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 20.4 (CH3), 51.7 (CH3), 117.6 (CH), 125.9 (CH), 127.7 (CH),
127.9 (2 × CH), 129.6 (CH), 129.8 (2 × CH), 130.5 (CH), 132.9 (C), 135.2 (C), 141.0 (C), 144.1 (C),
144.6 (CH), 167.5 (C); MS (EI) m/z 252 (M+, 100), 221 (28), 178 (21), 111 (6), 84 (14); HRMS (EI)
calcd for C17H16O2 (M+) 252.1150, found 252.1142.
Methyl (E)-3-(3’’-fluoro-4’’-methoxy-[1’,1’’-biphenyl]-4’-yl)acrylate (4c). The reaction was
carried out according to the previously described procedure for methyl (E)ꢀ3ꢀ([1’,1’’ꢀbiphenyl]ꢀ4’ꢀ
yl)acrylate (4a) using methyl (E)ꢀ3ꢀ(4’ꢀbromophenyl)acrylate (2e) (0.50 g, 0.21 mmol), 3ꢀfluoroꢀ4ꢀ
methoxyphenyl boronic acid (0.36 g, 0.21 mmol), [1,1’ꢀbis(diphenylphosphino)ferrocene]palladium(II)
dichloride (0.0090 g, 0.011 mmol) and cesium fluoride (0.064 g, 0.42 mmol). Purification by silica gel
flash column chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(3’’ꢀfluoroꢀ
4’’ꢀmethoxyꢀ[1’,1’’ꢀbiphenyl]ꢀ4’ꢀyl)acrylate (4c) (0.045 g, 75%) as a white solid. Mp 118‒121 °C; IR
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(neat) 2954, 1723, 1316, 1173, 1135, 806 cm−1; H NMR (400 MHz, CDCl3) δ 3.82 (s, 3H), 3.93 (s,
3H), 6.46 (d, J = 16.0 Hz, 1H), 7.03 (t, J = 8.8 Hz, 1H), 7.30‒7.38 (m, 2H), 7.54 (d, J = 8.8 Hz, 2H),
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7.58 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 16.0 Hz, 1H); C NMR (101 MHz, CDCl3) δ 51.7 (CH3), 56.4
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(CH3), 113.7 (d, JCꢀF = 2.2 Hz, CH), 114.7 (d, JCꢀF = 19.2 Hz, CH), 117.7 (CH), 122.7 (d, JCꢀF = 3.3
3
Hz, CH), 127.0 (2 × CH), 128.7 (2 × CH), 133.2 (C), 133.3 (C), 141.5 (d, JCꢀF = 1.9 Hz, C), 144.2
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(CH), 147.6 (d, JCꢀF = 10.2 Hz, C), 152.6 (d, JCꢀF = 246.9 Hz, C), 167.4 (C); MS (ESI) m/z 309
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(M+Na+, 100); HRMS (ESI) calcd for C17H15FNaO3 (M+Na+) 309.0897, found 309.0899.
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Methyl (E)-3-(4’-allylphenyl)acrylate (4d). The reaction was carried out according to the previously
described procedure for methyl (E)ꢀ3ꢀ([1’,1’’ꢀbiphenyl]ꢀ4’ꢀyl)acrylate (4a) using methyl (E)ꢀ3ꢀ(4’ꢀ
bromophenyl)acrylate (2e) (0.50 g, 0.21 mmol), allylboronic acid pinacol ester (0.060 mL, 0.32 mmol),
[1,1’ꢀbis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.0017 g, 0.021 mmol) and cesium
fluoride (0.064 g, 0.42 mmol). Purification by silica gel flash column chromatography, eluting with 20%
diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀallylphenyl)acrylate (4d) (0.027 g, 64%) as a yellow oil.
IR (neat) 2950, 1717, 1635, 1317, 1271, 1204, 1166, 983, 826 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.41
(d, J = 6.8 Hz, 2H), 3.80 (s, 3H), 5.06‒5.13 (m, 2H), 5.95 (ddt, J = 17.2, 9.6, 6.8 Hz, 1H), 6.41 (d, J =
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16.0 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 16.0 Hz, 1H); C NMR
(101 MHz, CDCl3) δ 40.1 (CH2), 51.7 (CH3), 116.4 (CH2), 117.1 (CH), 128.2 (2 × CH), 129.2 (2 × CH),
132.4 (C), 136.7 (CH), 142.8 (C), 144.7 (CH), 167.6 (C); MS (ESI) m/z 427 ([2M+Na]+, 100); HRMS
(ESI) calcd for C26H28NaO4 ([2M+Na]+) 427.1880, found 427.1886.
Methyl (E)-3-(2’-nitrophenyl)acrylate (6a).8d The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀnitroaniline (5a)
(0.055 g, 0.40 mmol), polymerꢀsupported nitrite (0.34 g, containing 1.2 mmol of NO2), pꢀ
toluenesulfonic acid monohydrate (0.21 g, 1.2 mmol), palladium(II) acetate (0.0040 g, 0.020 mmol) and
methyl acrylate (0.18 mL, 2.0 mmol). Purification by neutral alumina flash column chromatography,
eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(2’ꢀnitrophenyl)acrylate (6a) (0.070 g,
84%) as a yellow solid. Mp 68‒70 °C (lit.8d 71‒72 °C); 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.37
(d, J = 16.0 Hz, 1H), 7.51‒7.58 (m, 1H), 7.60‒7.69 (m, 2H), 8.04 (d, J = 8.7 Hz, 1H), 8.12 (d, J = 16.0
Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 52.0 (CH3), 122.9 (CH), 124.9 (CH), 129.1 (CH), 130.3 (CH),
130.6 (C), 133.5 (CH), 140.2 (CH), 148.4 (C), 166.2 (C); MS (EI) m/z 207 (M+, 28), 175 (78), 143
(100), 115 (59), 89 (53).
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Methyl (E)-3-(4’-methyl-2’-nitrophenyl)acrylate (6b).8d The reaction was carried out according to
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the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀmethylꢀ2ꢀ
nitroaniline (5b) (0.050 g, 0.33 mmol), polymerꢀsupported nitrite (0.28 g, containing 0.99 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.17 g, 0.99 mmol), palladium(II) acetate (0.0040 g, 0.016
mmol) and methyl acrylate (0.15 mL, 1.6 mmol). Purification by neutral alumina flash column
chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀmethylꢀ2’ꢀ
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nitrophenyl)acrylate (6b) (0.056 g, 77%) as a pale yellow solid. Mp 72‒74 °C (lit.8d 73‒75 °C); H
NMR (400 MHz, CDCl3) δ 2.45 (s, 3H), 3.81 (s, 3H), 6.33 (d, J = 15.6 Hz, 1H), 7.41‒7.46 (m, 1H),
13
7.52 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 0.4 Hz, 1H), 8.06 (d, J = 15.6 Hz, 1H); C NMR (101 MHz,
CDCl3) δ 21.1 (CH3), 52.0 (CH3), 122.0 (CH), 125.2 (CH), 127.6 (C), 128.8 (CH), 134.3 (CH), 140.0
(CH), 141.4 (C), 148.3 (C), 166.4 (C); MS (ESI) m/z 244 (M+Na+, 100).
Methyl (E)-3-(5’-methyl-2’-nitrophenyl)acrylate (6c). The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 5ꢀmethylꢀ2ꢀ
nitroaniline (5c) (0.050 g, 0.33 mmol), polymerꢀsupported nitrite (0.28 g, containing 0.99 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.17 g, 0.99 mmol), palladium(II) acetate (0.0060 g, 0.025
mmol) and methyl acrylate (0.15 mL, 1.7 mmol). Purification by neutral alumina and then silica gel
flash column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(5’ꢀmethylꢀ
2’ꢀnitrophenyl)acrylate (6c) (0.055 g, 75%) as a bright yellow solid. Mp 66‒70 °C; IR (neat) 2957,
1715, 1634, 1510, 1342, 1260, 976, 824 cm−1; 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 3.82 (s, 3H),
6.33 (d, J = 15.8 Hz, 1H), 7.32 (dd, J = 8.4, 1.2 Hz, 1H), 7.37–7.42 (m, 1H), 7.97 (d, J = 8.4 Hz, 1H),
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8.14 (d, J = 15.8 Hz, 1H); C NMR (101 MHz, CDCl3) δ 21.5 (CH3), 52.0 (CH3), 122.6 (CH), 125.1
(CH), 129.7 (CH), 130.8 (C), 130.8 (CH), 140.8 (CH), 144.9 (C), 146.1 (C), 166.3 (C); MS (ESI) m/z
244 (M+Na+, 100); HRMS (ESI) calcd for C11H11NNaO4 (M+Na+) 244.0580, found 244.0577.
Methyl (E)-3-(4’,5’-dimethyl-2’-nitrophenyl)acrylate (6d). The reaction was carried out according
to the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4,5ꢀdimethylꢀ
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2ꢀnitroaniline (5d) (0.050 g, 0.30 mmol), polymerꢀsupported nitrite (0.26 g, containing 0.90 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.16 g, 0.90 mmol), palladium(II) acetate (0.0030 g, 0.015
mmol) and methyl acrylate (0.14 mL, 1.5 mmol). Purification by neutral alumina flash column
chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’,5’ꢀdimethylꢀ2’ꢀ
nitrophenyl)acrylate (6d) (0.050 g, 71%) as an orange solid. Mp 85‒87 °C; IR (neat) 2922, 1729, 1514,
1335, 1165, 1024, 839 cm−1; 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.36 (s, 3H), 3.81 (s, 3H), 6.31
(d, J = 16.0 Hz, 1H), 7.36 (s, 1H), 7.84 (s, 1H), 8.11 (d, J = 16.0 Hz, 1H); 13C NMR (101 MHz, CDCl3)
δ 19.6 (CH3), 19.9 (CH3), 51.9 (CH3), 121.8 (CH), 125.8 (CH), 128.1 (C), 129.9 (CH), 139.8 (C), 140.6
(CH), 143.5 (C), 146.0 (C), 166.5 (C); MS (ESI) m/z 258 (M+Na+, 100); HRMS (ESI) calcd for
C12H13NNaO4 (M+Na+) 258.0737, found 258.0743.
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Methyl (E)-3-(4’-methoxy-2’-nitrophenyl)acrylate (6e).8d The reaction was carried out according to
the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀmethoxyꢀ2ꢀ
nitroaniline (5e) (0.050 g, 0.30 mmol), polymerꢀsupported nitrite (0.26 g, containing 0.90 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.16 g, 0.90 mmol), palladium(II) acetate (0.0030 g, 0.015
mmol) and methyl acrylate (0.13 mL, 1.5 mmol). Purification by neutral alumina flash column
chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀmethoxyꢀ2’ꢀ
nitrophenyl)acrylate (6e) (0.062 g, 87%) as a pale yellow solid. Mp 87‒89 °C (lit.8d 90‒91 °C); 1H NMR
(400 MHz, CDCl3) δ 3.80 (s, 3H), 3.90 (s, 3H), 6.30 (d, J = 15.8 Hz, 1H), 7.16 (dd, J = 8.7, 2.0 Hz, 1H),
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7.49 (d, J = 2.0 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 15.8 Hz, 1H); C NMR (101 MHz,
CDCl3) δ 51.9 (CH3), 56.1 (CH3), 109.5 (CH), 120.0 (CH), 121.0 (CH), 122.4 (C), 130.0 (CH), 139.5
(CH), 149.4 (C), 160.9 (C), 166.5 (C); MS (ESI) m/z 260 (M+Na+, 100).
Methyl (E)-3-(5’-methoxy-2’-nitrophenyl)acrylate (6f).33 The reaction was carried out according to
the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 5ꢀmethoxyꢀ2ꢀ
nitroaniline (5f) (0.050 g, 0.30 mmol), polymerꢀsupported nitrite (0.26 g, containing 0.90 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.16 g, 0.90 mmol), palladium(II) acetate (0.0030 g, 0.015
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mmol) and methyl acrylate (0.13 mL, 1.5 mmol). Purification by neutral alumina flash column
chromatography, eluting with 20% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(5’ꢀmethoxyꢀ2’ꢀ
nitrophenyl)acrylate (6f) (0.054 g, 77%) as an orange solid. Spectroscopic data were consistent with the
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literature.33 Mp 98‒100 °C; H NMR (400 MHz, CDCl3) δ 3.82 (s, 3H), 3.92 (s, 3H), 6.29 (d, J = 15.8
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Hz, 1H), 6.95‒7.00 (m, 2H), 8.10‒8.15 (m, 1H), 8.20 (d, J = 15.8 Hz, 1H); 13C NMR (101 MHz,
CDCl3) δ 52.0 (CH3), 56.1 (CH3), 114.2 (CH), 114.9 (CH), 122.7 (CH), 127.7 (CH), 133.8 (C), 141.1
(C), 141.5 (CH), 163.5 (C), 166.3 (C); MS (ESI) m/z 260 (M+Na+, 100).
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Methyl (E)-3-(4’-fluoro-2’-nitrophenyl)acrylate (6g).33 The reaction was carried out according to
the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀfluoroꢀ2ꢀ
nitroaniline (5g) (0.05 g, 0.32 mmol), polymerꢀsupported nitrite (0.27 g, containing 0.96 mmol of NO2),
pꢀtoluenesulfonic acid monohydrate (0.17 g, 0.96 mmol), palladium(II) acetate (0.0040 g, 0.016 mmol)
and methyl acrylate (0.14 mL, 1.6 mmol). Purification by neutral alumina and then silica gel flash
column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀfluoroꢀ2’ꢀ
nitrophenyl)acrylate (6g) (0.056 g, 78%) as a pale yellow solid. Spectroscopic data were consistent with
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the literature.33 Mp 87‒89 °C; H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.33 (d, J = 16.0 Hz, 1H),
7.39 (dddd, J = 8.8, 7.2, 2.6, 0.4 Hz, 1H), 7.64 (dd, J = 8.8, 5.9 Hz, 1H), 7.78 (dd, J = 8.0, 2.6 Hz, 1H),
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8.06 (dd, J = 16.0, 0.4 Hz, 1H); C NMR (101 MHz, CDCl3) δ 52.1 (CH3), 112.7 (d, JCꢀF = 26.8 Hz,
CH), 121.1 (d, 2JCꢀF = 21.5 Hz, CH), 123.1 (d, 5JCꢀF = 0.5 Hz, CH), 126.9 (d, 3JCꢀF = 4.0 Hz, C), 130.9 (d,
3JCꢀF = 8.2 Hz, CH), 139.1 (CH), 148.8 (C), 162.6 (d, 1JCꢀF = 255.1 Hz, C), 166.1 (C); MS (ESI) m/z 248
(M+Na+, 100).
Methyl (E)-3-(5’-chloro-2’-nitrophenyl)acrylate (6h). The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 5ꢀchloroꢀ2ꢀ
nitroaniline (5h) (0.070 g, 0.40 mmol), polymerꢀsupported nitrite (0.34 g, containing 1.2 mmol of NO2),
pꢀtoluenesulfonic acid monohydrate (0.21 g, 1.2 mmol), palladium(II) acetate (0.0040 g, 0.020 mmol)
and methyl acrylate (0.18 mL, 2.0 mmol). Purification by neutral alumina and then silica gel flash
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column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(5’ꢀchloroꢀ2’ꢀ
nitrophenyl)acrylate (6h) (0.066 g, 68%) as a yellow solid. Mp 110‒113 °C; IR (neat) 2961, 1715, 1516,
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1343, 1279, 1250, 1034, 976, 829 cm−1; H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.35 (d, J = 15.8
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Hz, 1H), 7.50 (dd, J = 8.8, 2.5 Hz, 1H), 7.59 (d, J = 2.5 Hz, 1H), 8.03 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
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15.8 Hz, 1H); C NMR (101 MHz, CDCl3) δ 52.2 (CH3), 124.0 (CH), 126.5 (CH), 129.2 (CH), 130.2
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(CH), 132.5 (C), 139.1 (CH), 140.1 (C), 146.4 (C), 165.8 (C); MS (ESI) m/z 264 (M+Na+, 100); HRMS
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(ESI) calcd for C10H8 ClNNaO4 (M+Na+) 264.0034, found 264.0036.
Methyl (E)-3-(4’-bromo-2’-nitrophenyl)acrylate (6i).8d The reaction was carried out according to
the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀbromoꢀ2ꢀ
nitroaniline (5i) (0.050 g, 0.23 mmol), polymerꢀsupported nitrite (0.20 g, containing 0.69 mmol of NO2),
pꢀtoluenesulfonic acid monohydrate (0.12 g, 0.69 mmol), palladium(II) acetate (0.0030 g, 0.012 mmol)
and methyl acrylate (0.10 mL, 1.2 mmol). Purification by neutral alumina and then silica gel flash
column chromatography, eluting with 10% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀbromoꢀ2’ꢀ
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nitrophenyl)acrylate (6h) (0.050 g, 76%) as a yellow solid. Mp 84‒86 °C (lit.8d 84‒85 °C); H NMR
(400 MHz, CDCl3) δ 3.83 (s, 3H), 6.37 (d, J = 16.0 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 8.5,
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2.0 Hz, 1H), 8.03 (d, J = 16.0 Hz, 1H), 8.18 (d, J = 2.0 Hz, 1H); C NMR (101 MHz, CDCl3) δ 52.1
(CH3), 123.4 (CH), 123.8 (C), 128.0 (CH), 129.4 (C), 130.3 (CH), 136.6 (CH), 139.0 (CH), 148.5 (C),
166.0 (C); MS (ESI) m/z 309 (M+Na+, 98), 307 (100).
Methyl (E)-3-(4’-iodo-2’-nitrophenyl)acrylate (6j). The reaction was carried out according to the
previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 4ꢀiodoꢀ2ꢀ
nitroaniline (5j) (0.050 g, 0.19 mmol), polymerꢀsupported nitrite (0.16 g, containing 0.57 mmol of
NO2), pꢀtoluenesulfonic acid monohydrate (0.098 g, 0.57 mmol), palladium(II) acetate (0.0030 g, 0.014
mmol) and methyl acrylate (0.085 mL, 0.95 mmol). Purification by neutral alumina flash column
chromatography, eluting with 5% diethyl ether in hexane gave methyl (E)ꢀ3ꢀ(4’ꢀiodoꢀ2’ꢀ
nitrophenyl)acrylate (6j) (0.046 g, 73%) as a yellow solid. Mp 83‒85 °C; IR (neat) 2951, 1699, 1524,
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1356, 1271, 1034, 824 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 6.37 (d, J = 16.0 Hz, 1H), 7.35
(d, J = 8.2, Hz, 1H), 7.97 (dd, J = 8.2, 0.8 Hz, 1H), 8.01 (d, J = 16.0 Hz, 1H), 8.35 (d, J = 0.8 Hz, 1H);
13C NMR (101 MHz, CDCl3) δ 52.1 (CH3), 94.5 (C), 123.4 (CH), 129.9 (C), 130.2 (CH), 133.6 (CH),
139.1 (CH), 142.5 (CH), 148.4 (C), 166.0 (C); MS (ESI) m/z 356 (M+Na+, 100); HRMS (ESI) calcd for
C10H8INNaO4 (M+Na+) 355.9390, found 355.9391.
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Methyl (E)-3-[2’-nitro-4’-(trifluoromethyl)phenyl]acrylate (6k).34 The reaction was carried out
according to the previously described procedure for methyl (E)ꢀ3ꢀ(4’ꢀnitrophenyl)acrylate (2a) using 2ꢀ
nitroꢀ4ꢀ(trifluoromethyl)aniline (5k) (0.050 g, 0.24 mmol), polymerꢀsupported nitrite (0.21 g, containing
0.72 mmol of NO2), pꢀtoluenesulfonic acid monohydrate (0.12 g, 0.72 mmol), palladium(II) acetate
(0.0040 g, 0.018 mmol) and methyl acrylate (0.11 mL, 1.2 mmol). Purification by neutral alumina and
then silica gel flash column chromatography, eluting with 15% diethyl ether in hexane gave methyl (E)ꢀ
3ꢀ[2’ꢀnitroꢀ4’ꢀ(trifluoromethyl)phenyl]acrylate (6k) (0.037 g, 56%) as a bright yellow solid. Mp 74‒76
°C (lit.34 77.6‒79.3 °C); 1H NMR (400 MHz, CDCl3) δ 3.84 (s, 3H), 6.42 (d, J = 15.9 Hz, 1H), 7.78 (d, J
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= 8.2 Hz, 1H), 7.90 (dd, J = 8.2, 1.0 Hz, 1H), 8.11 (d, J = 15.9 Hz, 1H), 8.31 (d, J = 1.0 Hz, 1H); C
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NMR (101 MHz, CDCl3) δ 52.2 (CH3), 122.4 (q, JCꢀF = 3.9 Hz, CH), 122.5 (q, JCꢀF = 273.4 Hz, C),
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124.9 (CH) 130.0 (q, JCꢀF = 3.4 Hz, CH), 130.2 (CH), 132.6 (q, JCꢀF = 35.0 Hz, C), 134.1 (C), 138.7
(CH), 148.1 (C), 165.7 (C); MS (ESI) m/z 298 (M+Na+, 100).
4-Phenyl-2-nitroaniline (5l).35 To a mixture of 4ꢀiodoꢀ2ꢀnitroaniline (5j) (0.20 g, 0.75 mmol), phenyl
boronic acid (0.10 g, 0.83 mmol) and palladium(II) chloride (0.0030 g, 0.019 mmol) in methanol (3 mL)
was added a solution of sodium hydroxide (0.12 g, 3.0 mmol) in water (1.5 mL) at room temperature.
The reaction mixture was degassed with argon under sonication for 0.5 h, stirred for 24 h and then
heated under reflux for a further 2 h. After cooling to room temperature, the solvent was evaporated and
the residue was washed with a 5% aqueous solution of hydrochloric acid (5 mL) until the pH of the
solution became neutral. The mixture was extracted with ethyl acetate (3 × 15 mL) and the combined
organic layers were washed with brine (2 × 15 mL). The organic layer was dried (MgSO4), filtered and
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