Flow-based, cerium oxide enhanced, low-level palladium sonogashira and heck coupling reactions by perovskite catalysts

Article abstract of DOI:10.1002/ijch.201300049

A flow chemistry procedure for Sonogashira and Heck cross-coupling reactions using a low-level palladium perovskite catalyst (LaFe _0.95Pd_0.05O₃) deposited on cerium oxide is reported. The catalyst was generated in situ at

Full text of DOI:10.1002/ijch.201300049

Full Paper
DOI: 10.1002/ijch.201300049
Flow-Based, Cerium Oxide Enhanced, Low-Level
Palladium Sonogashira and Heck Coupling Reactions by
Perovskite Catalysts
Claudio Battilocchio,[a] Benjamin N. Bhawal,[a] Rajeev Chorghade,[a] Benjamin J. Deadman,[a]
Joel M. Hawkins,[b] and Steven V. Ley*[a]
Abstract: A flow chemistry procedure for Sonogashira and
Heck cross-coupling reactions using a low-level palladium
perovskite catalyst (LaFe0.95Pd0.05O3) deposited on cerium
oxide is reported. The catalyst was generated in situ at high
temperature using a flow platform. The system could be ap-
plied to a wide range of functionalised substrates, allowing
clean and fast delivery of the products within a few minutes
(10–30 min), after scavenging with thiourea polymer (QP-
TU) and sulfonic acid resin (QP-SA). The use of an in-line
evaporator/solvent switching device allowed us to recover
the solvent and transport the material into the following
stage. The catalyst could be continuously used for at least
24 h, without any noticeable decrease in the catalytic effi-
ciency. In one example the system was scaled to deliver
10 mmol of product.
Keywords: cerium oxide · cross-coupling · flow chemistry · heterogeneous catalysis · perovskite phases
Introduction
Cleaner and environmentally benign protocols are in
great demand for all chemical processes.[1] In particular,
metal-catalysed cross-coupling reactions are important in
many synthesis programs.[2]
In our own work,[3] we have been focusing efforts on
developing improved tools for organic synthesis.[4] Re-
cently, we have demonstrated that the use of monolithic
reactors, solid-phase reagents and inorganic metal oxides
can provide efficient heterogeneous systems for flow-
based applications.[5] These combinations facilitate recy-
cling and promote minimum downstream processing.
Perovskite-type catalysts are mixed-metal oxides that
present a typical formulation structure of ABO3, where
the elements A and B are represented mainly by rare
earth, alkaline earth, alkali and other large atomic metal
cations.[6] Doping of these systems can be used to modify
the oxygen mobility within the lattice of the perovskite
structure, altering the valance state of the heterogeneous
matrix and creating oxygen vacancies, which represent
important catalytic sites.[7] This is usually achieved by in-
corporating noble metals into the perovskite lattice to ex-
change the B sites and create mixed-valance states.[7,8]
In the past, we reported studies on several ABO3 per-
ovskites and found that perovskites with B sites doped by
palladium were particularly effective in catalytic cross-
coupling processes.[7–11]
Figure 1. General matrix structure of ABO3 perovskites.
[a] C. Battilocchio, B. N. Bhawal, R. Chorghade, B. J. Deadman,
S. V. Ley
Innovative Technology Centre
Department of Chemistry
University of Cambridge
Lensfield Road, Cambridge CB21EW (UK)
Fax: (+)44(0)1223336442
e-mail: svl1000@cam.ac.uk
[b] J. M. Hawkins
Pfizer Worldwide Research & Development
Eastern Point Road
Groton, CT 06340 (USA)
The most attractive features of these catalysts are the
low levels of palladium and their potential to be reused
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without loss of catalytic turnover.[9] We have also demon-
strated that partial desorption of palladium catalyst from
the “heterogeneous” lattice can occur. This results in
a conventional homogeneous-phase catalytic cycle, fol-
lowed by redeposition of palladium on the modified solid
phase after the reaction is complete.[10] However, partial
desorption of palladium catalyst from the “heterogene-
ous” matrix can be considered a potential issue, since it
implies leaching of palladium.[9] This, therefore, reduces
Results and Discussion
We began by investigating the use of different perovskite/
metal oxide binary systems under microwave conditions
to establish the best catalyst for the Sonogashira cross-
coupling reaction. Notably, only palladium-containing
perovskites were active and the addition of CeO2
(10 mol%) increased the catalytic turnover of the system
(Table 1).
the advantage of utilising
a heterogeneous system,
namely, that the catalyst should be easily recovered by fil-
tration.
Table 1. Screening of different catalysts for the Sonogashira cross-
coupling reaction in the presence or absence of CeO2.
Ceria or cerium oxide (CeO2) has found widespread
use in several industrial applications due to its unique
properties, ranging from optical to mechanical, thermal
and chemical stability.[12] Depending on temperature and
oxygen pressure, different final stoichiometries can arise,
for example intermediate oxides whose composition is in
the range between Ce2O3 and CeO2. The property of
these oxides, acting as oxygen reservoirs, is controlled by
the valence change of its cations from 4+ to 3+. It is well
known, however, that reduction of the cerium ions is a re-
versible process, leading to easy oxidation of Ce3+ spe-
cies.[13]
Recently, the role of ceria in the water gas shift (WGS)
reaction, in which hydrogen and carbon dioxide are ob-
tained from water and carbon monoxide, has been ex-
plored.[14] Indeed, CeO2 nanoparticles on gold (normally
not active in this reaction) have been observed to facili-
tate the metalꢀs oxidation of CO.[14,15] Fornasiero et al.
demonstrated that the CeO2-coated palladium unit was
endowed with an enhanced rate of methane oxidation at
lower temperatures (below 700 K) than those previously
reported and displayed outstanding thermal stability.[16]
CeO2-supported metal nanoparticles (NPs) present higher
turnover and better stability, which can be attributed to
the CeO2 support. Attractive features of these systems
are the fine dispersion of the supported particles and the
prevention of agglomeration of the catalytic species due
to the interaction between the CeO2 surface and metal
atoms.[17]
Given these previously mentioned features of palladi-
um-containing perovskite-type oxides and of CeO2, we
have studied their synergetic properties for the Sonoga-
shira[18] and Heck[19] cross-coupling reactions. In particu-
lar, we aimed to generate an in situ deposition of the cat-
alytic metal onto the surface of CeO2 and use their posi-
tive interactions in the heterogeneous flow cross-coupling
of various substrates. In our case, we have used flow
chemistry methods not only to contain the heterogeneous
catalyst, but also for the deposition of the catalyst itself
on the surface of the support within our flow device. The
method does not require any multistep procedures or par-
ticular handling of materials and simplifies greatly the
mixing procedure, hence, representing an advantage over
other procedures.
Entry
Catalyst[a]
Conversion[b]
No additive [%]
CeO2[c] [%]
1
2
3
4
5
6
7
8
La1.02Fe0.58Cu0.37Pd0.05O3
La0.96Fe0.96Au0.04 Pd0.04O3
La2CuO4
LaSrFeNbO6
LaFe0.95Pd0.05O3
La2CoNbO6
La3CoRuO9
LaFe0.54Co0.36Pd0.1O3
YBaCu3O7
LaFe0.56Co0.38Pd0.05O3
Pd/C
Pd(AcO)2
4
2
0
0
5
0
0
5
0
2
5
0
10
5
0
0
13
0
0
15
0
10
13
0
9
10
11
12
[a] 5 mol% of catalyst was used in the reaction between 2,5-dime-
thylphenylacetylene (1.1 mmol), 4-iodoacetophenone (1 mmol) and
tetramethylguanidine (TMG, 2 mmol) for 20 min. [b] Conversion of
compounds was based on the H NMR spectrum of the crude ma-
terial. [c] 50 mol%.
1
Running the reaction for 140 min (Figure 2) with La-
Fe0.95Pd0.05O3 (5 mol%) in the presence of CeO2
(10 mol%) and TMG (2 equiv) gave a 70% conversion.
Completion was reached after 200 min without any by-
products being detected.
In the absence of CeO2, the reaction took approximate-
ly 6 h to reach completion. Additionally, the use of alumi-
nium oxide, zirconium oxide or silica gel did not give
comparable reaction rates compared to CeO2 as an addi-
tive. To assess the catalytic activity of CeO2, we measured
the conversion in the presence of different amounts of
the metal oxide at a given time and in the presence of
a standard reaction mixture. We were pleased to find that
increasing the amount of CeO2 enhanced the catalytic
turnover of the system, resulting in higher conversions
(Figure 3).
Additionally, we investigated the importance of using
wet DMF (5% H2O in DMF) for the reaction and we
found that in the absence of water the reaction was de-
fined by a slower turnover and reduced yield. Ethyl ace-
tate or toluene gave a slower coupling turnover, whereas
there was no cooperation between CeO2 and perovskites
when ethanol was employed as a solvent. Interestingly,
we observed the formation of ethyl acetate when using
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Enhanced Coupling Reactions by Perovskite Catalysts
Figure 4. Generation of the catalyst through deposition onto the
surface of ceria.
Figure 2. Catalytic activity of LaFe0.95Pd0.05O3 in the presence of
CeO2 (10 mol%) at different intervals.
Figure 5. XRD spectra of perovskite LaFe0.95Pd0.05O3 (red spectrum)
and LaFe0.95Pd0.05O3 on CeO2 (blue spectrum).
valent Pd species are transformed into the catalytically
active species Pd0 and these are deposited as clusters or
aggregates onto the surface of cerium oxide. Although we
believe the catalytic activity of the Pd species produced
by deposition on the surface of ceria is key to the effi-
ciency of the system, we cannot exclude any proper role
of the ceria surface in the catalytic cycle and these specu-
lations are still under scrutiny in our research group.
Having developed this interesting heterogeneous cata-
lyst, we established the flow parameters for the Sonoga-
shira elaboration of a range of commercially available
substituted aryl iodides and phenylacetylenes. Under the
optimised conditions, a solution of acetylene (1 mmol),
aryl iodide (1 mmol) and TMG (2 mmol) in wet DMF
(5% H2O in DMF, 4 mL) was passed through an Omnif-
itꢁ glass column (6.6 mm i.d.ꢂ100.0 mm length) packed
with the catalyst (0.4 g) and heated at 1308C. The solu-
tion was then flowed through an Omnifitꢁ glass column
(6.6 mm i.d.ꢂ100.0 mm length) packed with polymer-sup-
ported base and metal-scavenging resins,[22] namely,
QuadrapureÀsulfonic acidꢁ (QP-SA) and QuadrapureÀ
thioureaꢁ (QP-TU), respectively (Scheme 1).
Figure 3. Catalytic activity of different amounts of CeO2 in the
presence of LaFe0.95Pd0.05O3 (5 mol%; microwave 1308C, 20 min).
ethanol, which was thought to arise from partial oxidation
of ethanol with the CeO2 surface in the presence of per-
ovskite catalysts.[20]
The heterogeneous catalyst for the flow experiments
was prepared simply by mixing CeO2 and LaFe0.95Pd0.05O3
within a shaker, before packing it into an Omnifitꢁ glass
column.[21] The catalyst was then activated by passing
DMF through the column at 1308C (Figure 4).
The X-ray diffraction analysis pattern of the catalyst
(Figure 5) confirmed that there was a difference between
CeO2, LaFe0.95Pd0.05O3 and the catalyst formed “in situ”
through deposition on the ceria surface. We speculate this
to be the result of interactions of ceria with the lattice of
the perovskite material, inducing a transformation within
the oxygen mobility, hence, a change in the structure of
the catalyst itself. In particular, we believe that the poly-
One of the main advantages of this system was the fast
delivery of the products with residence times ranging
from 15 to 30 min. Under these conditions, we were able
to process a useful number of substrates with both elec-
tron-withdrawing and -donating substituents (Table 2).
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Scheme 1. General flow scheme for the Sonogashira cross-cou-
pling reaction.
We were also pleased to observe that the low level of
palladium present (just 1.6 mg wt in total, corresponding
to 15 mmol of palladium) in the column was able to con-
tinuously process 10 mmol of substrate (entry 6, Table 2)
without noticeable alteration of the catalytic efficiency.
When we changed the solvent to ethyl acetate, we found
that the same conversion could be obtained over longer
times (25–45 min). However, the presence of by-products
discouraged us from using this solvent.
Using a recently designed solvent evaporator system,
we have demonstrated an in-line solvent switch from
high-boiling solvent to low-boiling solvents and vice
versa.[23] We then opted to apply this technology for the
purpose of reducing the environmental impact of using
harmful solvents such as DMF by allowing their simple
removal and recycling.
Under the optimised conditions, the reaction mixture
(entry 3, Table 2) was passed through the catalyst at
1308C. After exiting the column, the mixture was scav-
enged by passage through QP-SA, QP-TU and MgSO4
packed in an Omnifitꢁ glass column. Feeding the bespoke
evaporating system with this solution, we were able to
concentrate the output and switch from DMF to a more
acceptable solvent (isopropanol (IPA)), with 92% of the
product recovered (Scheme 2). Additionally, we were
able to recover and recycle part of the DMF used for the
reaction (around 60%).
Scheme 2. Solvent switching from DMF to IPA using our bespoke
system.
combination with CeO2. The heterogeneous catalyst
system was “assembled” using the same conditions as
those for the Sonogashira reaction and applied to the
processing of different aryl iodides with tert-butyl acrylate
by Heck cross-coupling (Table 4). Under the optimised
conditions, a solution of tert-butyl acrylate (1 mmol), aryl
iodide (1 mmol) and TEA (1 mmol) in DMF (4 mL) was
passed through an Omnifitꢁ glass column (6.6 mm i.d.ꢂ
100.0 mm length) containing the catalyst (0.4 g), and
heated at 1308C. The solution was then flowed through
an Omnifitꢁ glass column (6.6 mm i.d.ꢂ100.0 mm length)
packed with polymer-supported acid and metal-scaveng-
ing resin, namely QP-SA (2 g) and QP-TU (1 g), respec-
tively (Scheme 3).
While we had prior knowledge of perovskite catalysis
for the Sonogashira cross-coupling reaction, the same was
not true for Heck cross-couplings. We therefore investi-
gated the opportunity to elaborate Heck reactions with
these new catalytic systems using microwave irradiation.
The results are reported in Table 3. Again it was observed
that palladium inclusion in the perovskites was critical for
the reaction. Gratifyingly, excellent conversions could be
obtained after just 20 min reaction time.
We were pleased to observe that the low level of palla-
dium present (just 1.6 mg wt in total, corresponding to
15 mmol of palladium) in the column was able to continu-
ously process different substrates without any apparent
decrease of the catalytic activity (over 24 h).
A similar cooperation between CeO2 and the catalyst
was observed for the Heck reaction as that found for the
Sonogashira process. However, this cooperation was
found to be dependent on the solvent because we did not
observe any cooperation when exchanging DMF for any
other solvent. We believe that, at high temperature, DMF
can play an active role in the reduction of Pd species
within the heterogeneous lattice; hence, enhancing the
cooperation between Pd and CeO2.
Scheme 3. General flow scheme for the Heck cross-coupling reac-
tion.
Conclusion
We have developed an efficient and facile system for the
rapid delivery of Sonogashira and Heck cross-coupling
products with an extremely low level of palladium cata-
We selected LaFe0.95Pd0.05O3 as the catalyst of choice,
since it proved to have the best catalytic properties in
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Enhanced Coupling Reactions by Perovskite Catalysts
Table 2. Sonogashira cross-coupling in flow using La1.02Fe0.57Pd0.05O3 deposited on CeO2.
Entry[a]
Alkyne
Iodide
Product
(yield [%])[b]
1
95
2
3
93[d]
93[d]
4
86
98
5
6
7
98[d]
87(83)[c]
8
9
98
95
10
11
98[d]
49[d]
12
13
52[d]
78[e]
[a] A solution of acetylene (1 mmol), aromatic iodide (1 mmol) and TMG (2 mmol) in wet DMF (5% H2O in DMF, 4 mL) was pumped (flow
rate 30–100 mLmin-1) through an Omnifitꢁ glass column (6.6 mm i.d.ꢂ100.0 mm length) containing the catalyst (0.4 g) and heated at
1308C. The solution was then passed through an Omnifitꢁ glass column (6.6 mm i.d.ꢂ100.0 mm length) packed with polymer supported
base and metal scavenging resin, namely, QP-SA (2 g) and QP-TU (1 g), respectively. [b] Yield was calculated after extraction and concentra-
tion in vacuo. [c] 10 mmol scale. [d] The QP-SA scavenging process was avoided. [e] After column chromatography.
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Table 3. Screening of different catalysts for the Heck cross-coupling
Table 4. Heck cross-coupling in flow using La1.02Fe0.57Pd0.05O3 depos-
reaction in the presence or absence of CeO2.
ited on CeO2.
Entry
Catalyst[a]
Conversion[b]
No additive [%]
Entry[a]
Iodide
Product
CeO2[c] [%]
(yield [%])[b]
1
2
3
4
5
6
7
La0.96FeAu0.04O3
La0.96Fe0.96Au0.04 Pd0.04O3
LaFe0.95Pd0.05O3
La2CuO4
YBa2Cu3O7
La4PdO7
0
14
83
0
0
39
13
–
–
92[d]
–
14
–
>98
56[d]
63[d]
La1.02Fe0.58Cu0.37Pd0.05O3
15
[a] 5 mol% of catalyst was used in the reaction between tert-butyl
acrylate (1.0 mmol), 4-iodoacetophenone (1 mmol) and triethyla-
mine (TEA, 1 mmol) in DMF (4 mL) for 20 min at 1308C. [b] Con-
versions of compounds are based on the H-NMR spectrum of the
crude material. [c] 50 mol%. [d] Heated at 1308C for 10 min.
>98
16
17
>98[c]
>98
lyst. In particular, we were able to contain a catalyst gen-
erated in situ by favourable interactions between palladi-
um-containing perovskites and cerium oxide. This system
was uniquely achieved using a flow-chemistry platform.
Under the optimised conditions, we were able to scale
one of the reactions to deliver 10 mmol of product. The
use of our bespoke solvent evaporator allowed us to re-
cover the solvent (60%) and recycle it for further use,
hence, reducing the environmental impact of these chem-
istries. We strongly believe that the application of this
system can be useful for a wide range of functionalities.
However, we noticed that the elaboration of Sonogashira
and Heck couplings using aryl bromide derivatives was
characterised by a very slow reaction time profile and for-
mation of by-products. We are still working on these
transformations to access catalysts whose application
would be universal to all aryl halides.
18
45[d]
[a] A solution of tert-butyl acrylate (1 mmol), aromatic iodide
(1 mmol) and TEA (1 mmol) in DMF (4 mL) was pumped (flow rate
50–100 mL/min) through an Omnifitꢁ glass column (6.6 mm i.d.ꢂ
100.0 mm length) containing the catalyst (0.4 g) and heated at
1308C. The solution was then passed through an Omnifitꢁ glass
column (6.6 mm i.d.ꢂ100.0 mm length) packed with polymer-sup-
ported base and metal-scavenging resin, namely, QP-SA (2 g) and
QP-TU (1 g), respectively. [b] Yield was calculated after extraction
and concentration in vacuo. [c] The QP-SA scavenging process was
avoided. [d] After column chromatography.
Experimental Section
a PerkinElmer Spectrum One FTIR spectrometer using
Universal ATR sampling accessories. Unless stated other-
wise, reagents were obtained from commercial sources
and used without purification. Laboratory reagent grade
EtOAc, petroleum ether 40–60, and DCM were obtained
from Fischer Scientific and distilled before use. Unless
stated otherwise, heating was conducted using standard
laboratory apparatus. The removal of solvent under re-
duced pressure was carried out on a standard rotary evap-
orator. Melting points were performed on either a Stan-
ford Research Systems MPA100 (OptiMelt) automated
melting point system and are uncorrected. High-resolu-
tion mass spectrometry (HRMS) was performed using
a Waters Micromass LCT Premierꢃ spectrometer using
time of flight with positive ESI, or conducted by Paul
Skelton on a Bruker BioApex 47e FTICR spectrometer
using positive ESI or EI at 70 eV to within a tolerance of
5 ppm of the theoretically calculated value. LC-MS analy-
sis was performed on an Agilent HP 1100 series chroma-
1
General: H NMR spectra were recorded on a Bruker
Avance DPX-400 spectrometer with the residual solvent
signal as the internal reference (CDCl3 =7.26 ppm,
[D6]DMSO=2.50 ppm). 1H resonances are reported to
the nearest 0.01 ppm. 13C NMR spectra were recorded on
the same spectrometers with the central resonance of the
solvent signal as the internal reference (CDCl3 =
77.16 ppm, [D6]DMSO=39.52 ppm). All 13C resonances
are reported to the nearest 0.1 ppm. DEPT 135, COSY,
HMQC and HMBC experiments were used to aid struc-
tural determination and spectral assignment. The multi-
1
plicity of H signals are indicated as follows: s=singlet,
d=doublet, t=triplet, sext=sextet, m=multiplet, br=
broad, or combinations of thereof. Coupling constants (J)
are quoted in Hz and reported to the nearest 0.1 Hz.
Where appropriate, averages of the signals from signals
displaying multiplicity were used to calculate the value of
the coupling constant. IR spectra were recorded neat on
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Enhanced Coupling Reactions by Perovskite Catalysts
tography (Mercury Luna 3u C18 (2) column) attached to
a Waters ZQ2000 mass spectrometer with ESCi ionisation
source in ESI mode. Elution was carried out at a flow
rate of 0.6 mLminÀ1 using a reverse-phase gradient of
acetonitrile and water containing 0.1% formic acid. Re-
tention time is given in min to the nearest 0.1 min and
the m/z value is reported to the nearest mass unit (m.u.).
Elemental analyses within a tolerance of Æ0.3% of the
theoretical values were determined by Alan Dickerson
and Patricia Irele in the microanalytical laboratories at
the Department of Chemistry, University of Cambridge.
X-ray powder diffraction analyses were performed using
a Panalytical Empyrean High throughput, high resolution
X-ray powder diffractometer. Unless otherwise specified,
all flow reactions were performed with a Vapourtec R2/
R4+ flow platform.[24]
General flow procedure for the Sonogashira cross-cou-
pling: A solution of acetylene (1 mmol), aromatic iodide
(1 mmol) and TMG (2 mmol) in wet DMF (5% H2O in
DMF, 4 mL) was pumped (flow rate 30–100 mL/min)
through an Omnifitꢁ glass column (6.6 mm i.d.ꢂ100.0 mm
length) containing the catalyst and heated at 1308C. The
solution was then passed through an Omnifitꢁ glass
column (6.6 mm i.d.ꢂ100.0 mm length) packed with poly-
mer-supported base and metal-scavenging resin, namely,
QP-SA (2 g) and QP-TU (1 g), respectively. Ethyl acetate
(10 mL) was added to the organic solution containing the
product. The organic fraction was washed with water (4ꢂ
10 mL), brine (20 mL) and dried over Na2SO4. Filtration
and concentration in vacuo of the organic solution gave
the desired product. Unless otherwise stated, no chroma-
tographic purification was carried out.
Solvent-switching procedure: The solution output was
collected and directed (0.15 mLminÀ1) to a T-piece,
where it was combined with a flowing stream of IPA
(0.75 mLminÀ1). The resulting mixture was directed into
the device and the flow rate of the nitrogen desolvation
gas was maintained at 10 LminÀ1. The evaporation cham-
ber[23] (an Omnifitꢁ column) was heated at 608C using
a Vapourtec R2/R4+ column heater. The output of unva-
pourised solvent was controlled by a WPI Peristar-Pro
peristaltic pump (0.2 mLminÀ1).
General flow procedure for the Heck cross-coupling re-
action: A solution of tert-butyl acrylate (1 mmol), aromat-
ic iodide (1 mmol) and TEA (1 mmol) in DMF (4 mL)
was pumped (flow rate 50-À100 mLminÀ1) through an
Omnifitꢁ glass column (6.6 mm i.d.ꢂ100.0 mm length)
containing the catalyst and heated at 1308C. The solution
was then passed through an Omnifitꢁ glass column
(6.6 mm i.d.ꢂ100.0 mm length) packed with polymer-sup-
ported base and metal-scavenging resin, namely, QP-SA
(2 g) and QP-TU (1 g), respectively. Ethyl acetate
(10 mL) was added to the organic solution containing the
product. The organic fraction was washed with water (4ꢂ
10 mL), brine (20 mL) and dried over Na2SO4. Filtration
and concentration in vacuo of the organic solution gave
the desired product. Unless otherwise stated, no chroma-
tography purification was carried out.
1-Chloro-2-(phenylethynyl)benzene (1): Yellow oil; H
NMR (400 MHz, CDCl3, 258C): d=7.70 (s, 1H), 7.60 (d,
1H, J=8.6 Hz), 7.37–7.26 (m, 5H), 7.01 ppm (t, 2H); 13C
NMR (100 MHz, CDCl3, 258C): d=137.13 (CH), 135.67
(CH), 135.07 (CH), 131.68 (CH), 131.44 (C), 130.96
(CH), 128.48 (CH), 128.40 (CH), 125.02 (C), 122.76 ppm
1
~
(C); FTIR (neat): n=3000, 2990, 1601, 1581, 1470, 1414,
1358, 1282, 1149, 1107, 781, 759, 735 cmÀ1; LC-MS: reten-
tion time 4.39 min, m/z: 213.13 [M+H]; HRMS (ESI): m/
z calcd for C14H10Cl+: 213.0944; found: 213.0946; elemen-
tal analysis calcd (%) for C14H9Cl: C 79.07, H 4.27, Cl
16.67; found: C 79.00, H 4.18, Cl 16.55.
2-(Phenylethynyl)pyrazine (2): Yellow oil; 1H NMR
(400 MHz, CDCl3, 258C): d=8.73 (s, 1H), 8.57 (d, 1H,
J=7.5 Hz), 8.50 (d, 1H, J=7.5 Hz), 7.61 (d, 2H, J=
8.6 Hz), 7.41–7.30 ppm (m, 3H); 13C NMR (100 MHz,
CDCl3, 258C): d=147.74 (CH), 144.43 (CH), 142.77
(CH), 140.40 (C), 132.15 (CH), 129.57 (CH), 128.51
(CH), 121.49 (C), 93.30 (C), 85.78 ppm (C); FTIR (neat):
~
n=3060, 1598, 1515, 1490, 1461, 1394, 1140, 1052, 1010,
846, 752, 688 cmÀ1; LC-MS: retention time 4.48 min, m/z:
+
181.13 [M+H]; HRMS (ESI): m/z calcd for C12H9N2
:
181.0766; found: 181.0773; elemental analysis calcd (%)
for C12H8N2: C 79.98, H 4.47, N 15.55; found: C 79.82, H
4.33, N 15.19.
1-[4-(Phenylethynyl)phenyl]ethan-1-one (3): Yellowish
1
solid; m.p. 94–968C; H NMR (400 MHz, CDCl3, 258C):
d=7.92 (d, 2H, J=8.6 Hz), 7.61 (d, 2H, J=8.6 Hz), 7.55
(m, 2H), 7.32 (m, 3H), 2.61 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3, 258C): d=197.29 (C), 135.45 (C),
131.73 (CH), 131.69 (CH), 128.80 (CH), 128.43 (CH),
128.26 (CH), 122.65 (C), 92.70 (C), 87.54 (C), 26.60 ppm
~
(CH3); FTIR (neat): n=2950, 2920, 2853, 1692, 1592,
1400, 1343, 1243, 1156, 983, 831 cmÀ1; LC-MS: retention
time 5.09 min, m/z: 221.19 [M+H]; HRMS (ESI): m/z
calcd for C16H13O+: 221.0961; found: 221.0958.
1-[2-(Phenylethynyl)phenyl]ethan-1-one (4): Orange
1
oil; H NMR (400 MHz, CDCl3, 258C): d=7.76 (d, 1H,
J=8.0 Hz), 7.64 (d, 1H, J=8.0 Hz), 7.57–7.55 (m, 2H),
7.48 (t, 1H, J=8 Hz), 7.42–7.36 (m, 4H), 2.80 ppm (s,
3H); 13C NMR (100 MHz, CDCl3, 258C): d=200.35 (C),
140.77 (C), 133.88 (CH), 131.52 (CH), 131.30 (CH),
128.77 (CH), 128.70 (CH), 128.47 (CH), 128.28 (CH),
122.89 (C), 121.70 (C), 95.03 (C), 88.49 (C), 30.00 ppm
~
(CH3); FTIR (neat): n=3061, 1680, 1591, 1561, 1492,
1473, 1442, 1356, 1276, 1245, 1233, 1163, 1109, 1069, 1025,
954, 915, 849 cmÀ1; HRMS (ESI): m/z calcd for C14H10Cl+
: 220.0888; found: 220.0895.
1-{4-[(4-Butylphenyl)ethynyl]phenyl}ethan-1-one (5):
Yellowish solid; m.p. 66–688C; 1H NMR (400 MHz,
CDCl3, 258C): d=7.93 (d, 2H, J=8.6 Hz), 7.61 (d, 2H,
J=8.6 Hz), 7.43 (d, 2H, J=8.6 Hz), 7.18 (d, 2H, J=
8.6 Hz), 2.62 (m, 5H), 1.62 (sext, 2H, J=7.5 Hz), 1.37
(sext, 2H, J=7.5 Hz), 0.92 ppm (t, 3H, J=7.5 Hz); 13C
Isr. J. Chem. 2013, 53, 1 – 10
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
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Full Paper
S. V. Ley et al.
~
NMR (100 MHz, CDCl3, 258C): d=197.31 (C), 144.07
(C), 136.02 (C), 132.02 (C), 131.65 (CH), 131.60 CH),
128.56 (CH), 128.48 (CH), 119.75 (C), 93.07 (C), 87.54
(C), 35.62 (CH2), 33.34 (CH2), 26.59 (CH2), 22.29 (CH3),
FTIR (neat): n=2926, 1726, 1670, 1602, 1310, 1264, 829,
798 cmÀ1; LC-MS: retention time 5.18 min, m/z: 249.13
[M+H]; HRMS (ESI): m/z calcd for C18H17O+: 249.5767;
found: 249.5757.
~
13.91 ppm (CH3); FTIR (neat): n=2956, 2925, 2858, 1681,
2-[(4-Phenoxyphenyl)ethynyl]pyridine (10): Yellow oil;
1H NMR (400 MHz, CDCl3, 258C): d=8.62 (d, 1H, J=
3.6 Hz), 7.67 (td, 1H, J=1.8, Hz, J=7.7 Hz), 7.56 (d, 2H,
J=8.8 Hz), 7.51 (d, 1H, J=8.1 Hz), 7.38 (m, 2H), 7.23 (m,
1H), 7.16 (m, 1H), 7.05 (d, 2H, J=8.1 Hz), 6.97 ppm (d,
2H, J=8.8 Hz); 13C NMR (100 MHz, CDCl3, 258C): d=
156.12 (C), 150.03 (C), 146.13 (C), 136.08 (CH), 133.69
(CH), 129.92 (CH), 129.89 (CH), 126.98 (CH), 124.03
(CH), 122.56 (CH), 119.66 (CH), 118.13 (CH), 117.23
1596, 1403, 1355, 1261, 1175, 956, 820 cmÀ1; LC-MS: re-
tention time 5.70 min, m/z: 277.16 [M+H]; HRMS (ESI):
m/z calcd for C20H21O+: 277.1587; found: 277.1580.
2-[(4-Butylphenyl)ethynyl]pyridine (6): Yellowish oil;
1H NMR (400 MHz, CDCl3, 258C): d=8.61 (d, 1H, J=
4.3 Hz), 7.66–7.60 (m, 1H), 7.60–7.41 (m, 3H), 7.25–7.07
(m, 3H), 2.62 (t, 2H, J=7.5 Hz), 1.60 (q, 2H, J=7.5 Hz),
1.37 (sext, 2H, J=7.5 Hz), 0.92 ppm (t, 3H, J=7.5 Hz);
13C NMR (100 MHz, CDCl3, 258C): d=149.98 (CH),
144.20 (C), 143.66 (C), 136.08 (CH), 131.95 (CH), 128.49
(CH), 127.04 (CH), 119.34 (CH), 115.46 (C), 89.60 (C),
88.06 (C), 35.63 (CH2), 33.30 (CH2), 22.29 (CH3),
~
(C), 89.95 (C), 88.09 ppm (C); FTIR (neat): n=3040,
2988, 2926, 1706, 1655, 1600, 1509, 1300, 1288, 1264, 829,
798 cmÀ1; LC-MS: retention time 5.07 min, m/z: 272.05
[M+H]; HRMS (ESI): m/z calcd for C19H15NO+:
272.2234; found: 272.2237.
~
13.90 ppm (CH3); FTIR (neat): n=3004, 2955, 2929, 2858,
1718, 1580, 1560, 1506, 1460, 1426, 1365, 1229, 1154, 829,
775 cmÀ1; LC-MS: retention time 5.28 min, m/z: 236.22
[M+H]; HRMS (ESI): m/z calcd for C17H18N+: 236.1434;
found: 236.1430.
1-Butyl-4-(phenylethynyl)benzene (7): Yellowish oil;
1H NMR (400 MHz, CDCl3, 258C): d=7.62 (m, 2H),
7.51–7.32 (m, 5H), 7.20 (d, 2H, J=8.4 Hz), 2.63 (t, 2H,
J=7.5 Hz), 1.61 (q, 2H, J=7.5 Hz), 1.38 (sext, 2H, J=
7.5 Hz), 0.92 ppm (t, 3H, J=7.5 Hz); 13C NMR
(100 MHz, CDCl3, 258C): d=143.66 (C), 136.20 (CH),
131.95 (CH), 128.55 (CH), 128.13 (CH), 127.19 (CH),
120.14 (CH), 119.30 (C), 89.22 (C), 88.06 (C), 35.62
(CH2), 33.31 (CH2), 22.28 (CH3), 13.90 ppm (CH3); FTIR
5-(6-Fluoropyridin-3-yl)pent-4-yn-1-ol (11): Yellow oil;
1H NMR (400 MHz, CDCl3, 258C): d=8.21 (s, 1H), 7.83
(m, 1H), 6.89 (m, 1H) 3.82 (t, 2H, J=7.2 Hz), 2.57 (q, 2H,
J=7.2 Hz), 1.87 (q, 2H, J=7.2 Hz), 1.76 ppm (br s, 1H);
13C NMR (100 MHz, CDCl3, 258C): d=164.22 (C), 147.89
(CH), 139.08 (CH), 118.17 (CH), 114.99 (C), 89.05 (C),
65.20 (CH), 32.33 (CH2), 30.50 ppm (CH2); FTIR (neat):
~
n=3359, 2928, 1634, 1593, 1567, 1490, 1455, 1406, 1374,
1342, 1258, 1063, 1037, 836, 687 cmÀ1; LC-MS: retention
time 4.04 min, m/z: 180.15 [M+H]; HRMS (ESI): m/z
calcd for C10H11NFO+: 180.0825; found: 180.0831.
1-(6-Fluoropyridin-3-yl)pent-1-yn-3-ol (12): Yellow oil;
1H NMR (400 MHz, CDCl3, 258C): d=8.30 (m, 1H), 7.83
(m, 1H), 6.90 (m, 1H) 4.56 (t, 2H, J=7.2 Hz), 3.10 (s,
3H), 2.57 (q, 2H, J=7.2 Hz), 1.93 ppm (t, 3H, J=7.2 Hz);
13C NMR (100 MHz, CDCl3, 258C): d=164.22 (C), 147.89
(CH), 139.08 (CH), 118.17 (CH), 114.99 (C), 89.05 (C),
65.20 (CH), 32.33 (CH2), 30.50 ppm (CH3); FTIR (neat):
~
(neat): n=3010, 2955, 2929, 2858, 1520, 1511, 1432, 1200,
1154, 829, 733 cmÀ1; LC-MS: retention time 6.24 min, m/
+
z: 235.17 [M+H]; HRMS (ESI): m/z calcd for C18H19
:
236.1808; found: 236.1809.
1-{4-[(3-Fluorophenyl)ethynyl]phenyl}ethan-1-one (8):
Yellowish solid; m.p. 90–938C; 1H NMR (400 MHz,
CDCl3, 258C): d=7.91 (d, 2H, J=8.4 Hz), 7.60 (d, 2H,
J=8.4 Hz), 7.32 (m, 2H), 7.25 (m, 1H), 7.08 (m, 1H),
2.63 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, 258C): d=
197.24 (C), 163.61 (C), 136.48 (C), 131.78 (CH), 130.08
(CH), 129.99 (CH), 127.63 (CH), 118.60 (CH), 116.04
(CH), 89.45 (C), 88.22 (C), 26.61 ppm (CH3); FTIR
~
n=3353, 2964, 2933, 1653, 1603, 1515, 1482, 1392, 1255,
1121, 1008, 962, 833, 668 cmÀ1; LC-MS: retention time
4.00 min, m/z: 180.14 [M+H]; HRMS (ESI): m/z calcd
for C10H11NFO+: 180.0825; found: 180.0833.
1-Fluoro-3-[(3-methoxyphenyl)ethynyl]benzene
(13):
1
Yellow oil; H NMR (400 MHz, CDCl3, 258C): d=7.66
(s, 1H), 7.40–7.20 (m, 5H), 7.11 (m, 1H), 6.93 (m, 1H),
3.84 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, 258C): d=
163.61 (C), 136.48 (C), 131.78 (CH), 130.08 (CH), 129.99
(CH), 128.75 (CH), 128. 55 (CH), 128.15 (CH), 128.01
(CH), 127.63 (CH), 118.60 (C), 116.04 (C), 89.45 (C),
~
(neat): n=2922, 1725, 1676, 1600, 1310, 1264, 829,
782 cmÀ1; LC-MS: retention time 5.14 min, m/z: 239.12
[M+H]; HRMS (ESI): m/z calcd for C16H12FO+:
239.1400; found: 239.1403.
~
1-{4-[(2,5-Dimethylphenyl)ethynyl]phenyl}ethan-1-one
(9): Yellowish solid; m.p. 89–928C; H NMR (400 MHz,
88.22 (C), 26.61 ppm (CH3); FTIR (neat): n=3072, 3005,
1
2938, 1607, 1577, 1491, 1433, 1323, 1282, 1238, 1194, 1175,
1155, 1040, 961, 870, 778, 746, 680 cmÀ1; LC-MS: reten-
tion time 6.08 min, m/z: 227.17 [M+H]; HRMS (ESI): m/
z calcd for C15H12FO+: 227.0867; found: 227.0860.
tert-Butyl (E)-3-(4-acetylphenyl)acrylate (14): Yellow
solid; m.p. 98–1008C; H NMR (400 MHz, CDCl3, 258C):
CDCl3, 258C): d=7.96 (d, 2H, J=8.4 Hz), 7.66 (d, 2H,
J=8.4 Hz), 7.35 (m, 1H), 7.13 (m, 1H), 7.09 (m, 1H), 2.64
(s, 3H), 2.45 (s, 3H), 2.30 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3, 258C): d=197.4 (C), 137.4 (C), 132.5
(C), 131.6 (CH), 130.10 (CH), 129.8 (C), 128.6 (CH),
127.3 (CH), 122.2 (CH), 118.9 (CH), 117.8 (CH), 89.7
(C), 88.1 (C), 26.7 (CH3),20.8 (CH3), 20.2 ppm (CH3);
1
d=7.84 (d, 2H, J=8.0 Hz), 7.47 (m, 3H), 6.34 (d, 1H, J=
16.0 Hz), 2.49 (s, 3H), 1.43 ppm (s, 9H); 13C NMR
&
8
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www.ijc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2013, 53, 1 – 10
ÝÝ
These are not the final page numbers!

Enhanced Coupling Reactions by Perovskite Catalysts
(100 MHz, CDCl3, 258C): d=197.11 (C), 165.56 (C),
141.82 (CH), 138.89 (C), 137.65 (C), 128.68 (CH), 127.89
(CH), 122.63 (CH), 80.71 (C), 28.03 (CH3), 26.53 ppm
(CH3) LC-MS: retention time 4.98 min, m/z: 191.16 [M-t-
Butyl]; HRMS (ESI): m/z calcd for C15H19O3+: 247.1334;
found: 247.1330.
191.12 [M-t-Butyl]; HRMS (ESI): m/z calcd for
C15H19O3+: 247.1334; found: 247.1330.
Acknowledgements
tert-Butyl (E)-3-(1H-indol-5-yl)acrylate (15): Yellow
oil; 1H NMR (400 MHz, CDCl3, 258C): d=8.68 (br s,
1H), 7.78–7.75 (m, 2H), 7.38 (m, 2H), 7.19 (m, 1H), 6.57
(m, 1H), 6.37 (d, 1H, J=16.1 Hz), 1.59 ppm (s, 9H); 13C
NMR (100 MHz, CDCl3, 258C): d=167.23 (C), 145.54
(CH), 136.95 (C), 128.12 (CH), 126.58 (C), 125.34 (CH),
122.14 (CH), 121.42 (CH), 116.90 (CH), 111.59 (CH),
103.24 (CH), 80.17 (C), 28.07 ppm (CH3); FTIR (neat):
We gratefully acknowledge funding from Pfizer World-
wide Research & Development (C. B. and J. M. H.),
EPSRC (B. N. B.), the Commonwealth Scholarship Com-
mission (B. J. D.) the BP 1702 endowment (S. V. L.) and
Carnegie Mellon University (R. C.) for study leave. We
are also grateful to Daihatsu Motor Co. Ltd and Hokko
Chemical Ltd for their kind gift of perovskite catalysts.
~
n=3415, 3101, 2972, 1724, 1681, 1609, 1442, 1408, 1366,
1337, 1311, 1282, 1219, 1145, 1128, 1089, 1064, 981, 856,
797, 731 cmÀ1; LC-MS: retention time 5.00 min, m/z:
170.18 [M-O-C(CH3)3]+; HRMS (ESI): m/z calcd for
C14H16NO2+: 230.2936; found: 230.2939.
References
[1] a) S. V. Ley, Chem. Rec. 2012, 12, 378–390; b) J. Wegner, S.
Ceylan, A. Kirschning, Chem. Commun. 2011, 47, 4583–
4592.
tert-Butyl (E)-3-(6-fluoropyridin-3-yl)acrylate (16): Yel-
[2] a) G. A. Molander, I. Shin, Org. Lett. 2013, 15, 2534–2537;
b) G. Feng, F. Liu, C. Lin, W. Li, S. Wang, C. Qi, Catal.
Commun. 2013, 37, 27–31; c) M. S. Szulmanowicz, A. Gnie-
wek, W. Gil, A. M. Trzeciak, ChemCatChem, 2013, 5, 1211;
d) M. Semler, J. Cejka, P. Stepnicka, Appl. Organomet.
Chem. 2013,27(6), 353-360; e) K. B. Sahu, A. Maity, S.
Mondal, R. Paira, P. Saha, S. Naskar, A. Hazra, S. Banerjee,
N. B. Mondal, J. Heterocycl. Chem. 2013, 50, E166–E173;
f) T. S. Khaibulova, I. A. Boyarskaya, V. P. Boyarskii, Russ.
J. Org. Chem. 2013, 49, 360–365; g) J. A. Corral, M. I.
Lopez, D. Esquivel, M. Mora, C. Jimenez-Sanchidrian, F. J.
Romero-Salguero, Materials 2013, 6, 1554–1565; h) T.
Suzuka, M. Adachi, Z. S. Yang, K. Ogihara, M. Higa, Trans.
Mater. Res. Soc. Jpn. 2013, 38, 119–122; i) M. Al-Amin, M.
Akimoto, T. Tameno, Y. Ohki, N. Takahashi, N. Hoshiya, S.
Shuto, M. Arisawa, Green Chem. 2013, 15, 1142–1145;
j) D. R. Stuart, K. Fagnou, Top. Organomet. Chem. 2013, 44,
91–120; k) C. K. Haley, C. D. Gilmore, B. M. Stoltz, Tetra-
hedron 2013,69, 5732-5736; l) X. Han, Z. Yue, X. Zhang, Q.
He, C. Yang, J. Org. Chem. 2013, 78(10), 4850-4856 -; m) Y.
Wu, J. Wang, F. Y. Kwong, Science of Synthesis, Cross Cou-
pling and Heck-Type Reactions, Vol. 2, Thieme, Stuttgart,
2013, p. 621; n) R. Shang, Q. Xu, Y. Jiang, Y. Wang, L. Liu,
Org. Lett. 2010, 12, 1000–1003; o) F. Manarin, J. A. Roehrs,
R. Brandao, C. W. Nogueira, G. Zeni, Synthesis 2009, 23,
4001–4009; p) K. C. Majumdar, S. Chakravorty, T. Ghosh,
B. Sridhar, Synlett 2009, 19, 3127–3130.
[3] a) C. F. Carter, H. Lange, S. V. Ley, I. R. Baxendale, B. Witt-
kamp, J. G. Goode, N. L. Gaunt, Org. Process Res. Dev.
2010, 14, 393–404; b) H. Lange, C. F. Carter, M. D. Hopkin,
A. Burke, J. G. Goode, I. R. Baxendale, S. V. Ley, Chem.
Sci. 2011, 2, 765; c) S. A. M. W. van den Broek, J. R. Leli-
veld, R. Becker, M. M. E. Delville, P. J. Nieuwland, K.
Koch, F. P. J. T Rutjes, Org. Process Res. Dev. 2012, 16, 934–
938; d) X. Liu, B. ꢄnal, K. F. Jensen, Catal. Sci. Technol.
2012, 2, 2134–2138; e) D. L. Browne, S. Wright, B. J. Dead-
man, S. Dunnage, I. R. Baxendale, R. M. Turner, S. V. Ley,
Rapid Commun. Mass Spectrom. 2012, 26, 1999–2010; f) M.
OꢀBrien, P. Koos, D. L. Browne, S. V. Ley, Org. Biomol.
Chem. 2012, 10, 7031–7036; g) D. X. Hu, M. OꢀBrien, S.V.
Ley, Org. Lett. 2012, 14, 4246–4249; h) T. P. Peterson, A.
Polyzos, M. OꢀBrien, T. Ulven, I. R. Baxendale, S. V. Ley,
1
lowish solid; m.p. 89–918C; H NMR (400 MHz, CDCl3,
258C): d=8.33 (d, 2H, J=2.2 Hz), 7.93 (m, 1H), 7.54 (d,
1H, J=16.1 Hz), 6.95 (dd, 1H, J=8.4 Hz, J=2.9 Hz), 6.38
(d, 1H, J=16.1 Hz), 1.55 ppm (s, 9H); 13C NMR
(100 MHz, CDCl3, 258C): d=165.38 (C), 164.30 (C),
147.89 (CH), 139.08 (CH), 138.17 (CH), 128.67 (C),
122.20 (CH), 110.16 (CH), 81.06 (C), 28.12 ppm (CH3);
~
FTIR (neat): n=2999, 2975, 2932, 1737, 1697, 1644, 1594,
1487, 1391, 1366, 1300, 1243, 1216, 1148, 993, 883,
832 cmÀ1; LC-MS: retention time 4.80 min, m/z: 168.12
[M-C(CH3)3]+; HRMS (ESI): m/z calcd for C12H15FNO2
:
+
224.1081; found: 224.1076. elemental analysis calcd (%)
for C12H14FNO2: C 64.56, H 6.32, N 6.27; found: C 64.50,
H 6.22, N 6.10.
tert-Butyl
(E)-3-(4-methoxyphenyl)acrylate
(17):
1
Yellow oil; H NMR (400 MHz, CDCl3, 258C): d=7.55
(d, 1H, J=16.1 Hz), 7.42 (d, 2H, J=8.5 Hz), 6.88 (d, 2H,
J=8.5 Hz), 6.24 (d, 1H, J=16.1 Hz), 3.81 (s, 3H),
1.53 ppm (s, 9H); 13C NMR (100 MHz, CDCl3, 258C): d=
166.64 (C), 161.11 (C), 143.17 (CH), 129.52 (CH), 127.37
(C), 117.83 (CH), 114.23 (CH), 80.17 (C), 55.29 (CH3),
~
28.21 ppm (CH3); FTIR (neat): n=2971, 2933, 2893, 1738,
1701, 1633, 1603, 1575, 1511, 1391, 1366, 1248, 1140, 1030,
979, 874, 825 cmÀ1; LC-MS: retention time 5.11 min, m/z:
161.11 [M-C(CH3)3]+; HRMS (ESI): m/z calcd for
C14H17O3Na+: 257.1148; found: 257.1144.
tert-Butyl (E)-3-(2-acetylphenyl)acrylate (18): Brown-
1
ish oil; H NMR (400 MHz, CDCl3, 258C): d=8.02 (d,
1H, J=8.0 Hz), 7.69 (d, 1H, J=7.5 Hz), 7.46 (d, 1H, J=
7.5 Hz), 7.40 (d, 1H, J=7.5 Hz), 6.19 (d, 1H, J=8.0 Hz),
2.57 (s, 3H), 1.50 ppm (s, 9H); 13C NMR (100 MHz,
CDCl3, 258C): d=200.89 (C), 165.76 (C), 142.67 (CH),
138.26 (C), 134.82 (C), 131.81 (CH), 129.17 (CH), 129.09
(CH), 128.26 (CH), 122.85 (CH), 80.49 (C), 29.35 (CH3),
28.15 ppm (CH3); LC-MS: retention time 4.96 min, m/z:
Isr. J. Chem. 2013, 53, 1 – 10
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
&9
&
ÞÞ
These are not the final page numbers!

Full Paper
S. V. Ley et al.
ChemSusChem 2012, 5, 274–277; i) P. Koos, U. Gross, A.
Polyzos, M. OꢀBrien, I. R. Baxendale, S. V. Ley, Org.
Biomol. Chem. 2011, 9, 6903–6908; l) M. OꢀBrien, N.
Taylor, A. Polyzos, I. R. Baxendale, S. V. Ley, Chem. Sci.
2011, 2, 1250–1257; m) S. Kasinathan, S. L. Bourne, P. Tol-
stoy, P. Koos, M. OꢀBrien, R. W. Bates, I. R. Baxendale,
S. V. Ley, Synlett, 2011, 2648–2651; n) L. Guetzoyan, N.
Nikbin, I. R. Baxendale, S. V. Ley, Chem. Sci. 2013, 4, 764–
769.
[8] D. J. Liu, M. Krumpelt Int. J. Appl. Ceram. Technol. 2005, 2,
301–307.
[9] S. Lohmann, S. P. Andrews, B. J. Burke, M. D. Smith, J. P.
Attfield, H. Tanaka, K. Kaneko, S.V. Ley, Synlett 2005,
1291–1295.
[10] S. P. Andrews, A. F. Stepan, H. Tanaka, S. V. Ley, M. D.
Smith, Adv. Synth. Catal. 2005, 347, 647–654.
[11] M. D. Smith, A. F. Stepan, C. Ramarao, P. E. Brennan, S. V.
Ley, Chem. Commun. 2003, 2652–2653.
[4] a) M. Rasheed, T. Wirth, Angew. Chem. Int. Ed. 2011, 50,
357–358; b) S. A. M. W. van den Broek, J. R. Leliveld, R.
Becker, M. M. E. Delville, P. J. Nieuwland, K. Koch, F. P. J.
T Rutjes, Org. Process Res. Dev. 2012, 16, 934–938; c) X.
Liu, B. ꢄnal, K. F. Jensen, Catal. Sci. Technol. 2012, 2,
2134–2138; d) J. P. Knowles, L. D. Elliott, K. I. Booker-Mil-
burn, Beilstein J. Org. Chem. 2012, 8, 2025–2052; e) J. G.
Stevens, R. A. Bourne, M. Poliakoff, Green Chem. 2009, 11,
409–416; f) F. Lꢅvesque, P. H. Seeberger, Angew. Chem. Int.
Ed. 2012, 51, 1706–1709; g) M. Damm, B. Gutmann, C. O.
Kappe, ChemSusChem, 2013, 6, 978–982; h) B. Pieber,
C. O. Kappe, Green Chem. 2013, 15, 320–324; i) J. C.
Brandt, S. C. Elmore, R. I. Robinson, T. Wirth, Synlett,
2010, 20, 3099–3103; j) E. Borrꢅ, M. Rouen, I. Laurent, M.
Magrez, F. Caijo, C. Crꢅvisy, W. Solodenko, L. Toupet, R.
Frankfurter, C. Vogt, A. Kirschning, M. Mauduit, Chem.
Eur. J. 2012, 18, 16369–16382; k) L. Kupracz, A. Kirschning,
J. Flow Chem. 2013, 3, 11–16; l) S. M. Opalka, J. K. Park,
A. R. Longstreet, D. T. McQuade, Org. Lett. 2013, 15, 996–
999; m) A. R. Bogdan, S. L. Poe, D. C. Kubis, S. J. Broadwa-
ter, D. T. McQuade, Angew. Chem. Int. Ed. 2009, 48, 8547–
8550; n) M. D. Roydhouse, A. Ghaini, A. Constantinou, A.
Cantu-Perez, W. B. Motherwell, A. Gavriilidis, Org. Process
Res. Dev. 2011, 15, 989–996.
[5] a) S. V. Ley, I. R. Baxendale, R. Ingham, E. Riva, N. Nikbin,
Org. Lett. 2012, 14, 3920–3923; b) S. V. Ley, I. R. Baxen-
dale, M. Baumann, N. Nikbin, C. D. Smith, Org. Biomol.
Chem. 2008, 6, 1587–1593; c) S. V. Ley, I. R. Baxendale,
C. J. Smith, C. D. Smith, N. Nikbin, Org. Biomol. Chem.
2011, 9, 1927–1937l; d) S. V. Ley, I. R. Baxendale, H.
Lange, M. Capener, A. Jones, C. J. Smith, N. Nikbin, Synlett
2011, 869–873; f) S. V. Ley, N. Nikbin, M. Ladlow, Org. Pro-
cess Res. Dev. 2007, 11, 458–462; g) S. V. Ley, I. R. Baxen-
dale, K. Roper, H. Lange, A. Polyzos, M. B. Berry, Beilstein
J. Org. Chem. 2011, 7, 1648–1655; h) S. V. Ley, I. R. Baxen-
dale, L. Guetzoyan, N. Nikbin, Chem. Sci. 2013, 4, 764–769;
i) S. V. Ley, I. R. Baxendale, C. Battilocchio, B. J. Deadman,
N. Nikbin, M. O. Kitching, Chem. Eur. J. 2013, 19, 7917–
7930; m) S. V. Ley, I. R. Baxendale, A. L. Lee, J. Chem. Soc.
Perkin Trans. 1 2002, 16, 1850–1857; n) S. V. Ley, J. Haber-
mann, R. Smits, J. Chem. Soc. Perkin Trans. 1 1999, 2421–
2423; o) S. V. Ley, I. R. Baxendale, M. Nesi, C. Piutti, Tetra-
hedron 2002, 58, 6285–6304; p) S. V. Ley, I. R. Baxendale,
M. Baumann, N. Nikbin, C. D. Smith, J. P. Tieney, Org.
Biomol. Chem. 2008, 6, 1577–1586; q) S. V. Ley, I. R. Bax-
endale, M. Baumann, N. Nikbin, C. D. Smith, Org. Biomol.
Chem. 2008, 6, 1587–1593; r) C. Battilocchio, J. M. Haw-
kins, S. V. Ley, Org. Lett. 2013, 15, 2278–2281.
[12] A. Trovarelli, C. de Leitenburg, M. Boaro, G, Dolcetti,
Catal. Today 1999, 50, 353–367.
[13] a) L. R. Morss, Handbook on the Physics and Chemistry of
Rare Earths, Elsevier, New York, 1994; b) S. Fabris, S. De
Gironcoli, S. Baroni, G. Vicario, G. Balducci, Phys. Rev. B
2005, 71, 41–102; c) C. J. Summers, S. Van Houtte, D.
Psaras, Appl. Catal. B 1996, 10, 139–156.
[14] a) J. A. Rodriguez, S. Ma, P. Liu, J. Hrbek, J. Evans, M.
Perez, Science 2007, 318, 1757–1760; b) Q. Fu, H. Saltsburg,
M. Flytzani-Stephanopoulus, Science 2003, 301, 935–938.
[15] V. Aguilar-Guerrero, B. C. Gates, Chem. Commun. 2007,
3210–3212.
[16] M. Cargnello, J. J. Delgado Jaꢅn, J. C. Hernꢆndez Garrido,
K. Bakhmutsky, T. Montini, J. J. Calvino Gꢆmez, R. J.
Gorte, P. Fornasiero, Science 2012, 337, 713–717.
[17] a) J. C. Summers, S. A. Ausen, J. Catal. 1979, 58, 131–143;
b) L. F. Liotta, G. Deganello, D. Sannino, M. C. Gaudino, P.
Ciambelli, S. Gialanella, Appl. Catal. A 2002, 229, 217–227;
c) A. Wongkaew, Chiang Mai J. Sci. 2008; 35, 156–162;
d) A. Abad, P. Concepcion, A. Corma, H. Garcia, Angew.
Chem. Int. Ed. 2005, 44, 4066–4069; e) K. H. Park, Y. W.
Lee, Y. Kim, S. W. Kang, S. W. Han, Chem. Eur. J. 2013,
19(25), 8053-8057.
[18] a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
1975, 16, 4467–4470; b) Y. Liang, Y. X. Xie, J. H. Li. J. Org.
Chem. 2006, 71, 379–381; c) R. A. Batey, M. Shen, A. J.
Lough. Org. Lett. 2002, 4, 1411–1414; d) H. Nakatsuji, K.
Ueno, T. Misaki, Y. Tanabe, Org. Lett. 2008, 10, 2131–2134;
e) W. Shi, Y. Luo, X. Luo, L. Chao, H. Zhang, J. Wang, A.
Lei, J. Am. Chem. Soc. 2008, 130, 14713–14720; f) A. J.
Sandy, D. G. I. Petra, J. N. H. Reek, P. C. J. Kramer,
P. W. N. M. van Leewen. Chem. Eur. J. 2001, 7, 1202–1208;
g) K. Mennecke, W. Solodenko, A. Kirschining. Synthesis
2008, 10, 1589–1599; h) I. R. Baxendale, S. C. Schou, J. Se-
delmeier, S. V. Ley. Chem. Eur. J. 2010, 16, 89–94.
[19] a) S. E. Gibson, R. J. Middleton, Contemp. Org. Synth. 1996,
3, 447–471; b) M. M. Abelman, T. Oh, L. E. Overman, J.
Org. Chem. 1987, 52, 4133–4135; c) A. F. Littke, G. C. Fu, J.
Org. Chem. 1999, 64, 10–11; d) M. L. Kantam, P. Srinivas, J.
Yadav, P. R. Likhar, S. Bhargava , J. Org. Chem. 2009, 74,
4882–4885; e) L. R. Moore, K. H. Shaughnessy, Org. Lett.
2004, 6, 225–228; f) E. W. Werner, M. S. Sigman , J. Am.
Chem. Soc. 2011, 133, 9692–9695.
[20] B. S. Jiang, R. Chang, Y. C. Lin, Ind. Eng. Chem. Res. 2013,
52, 37–42.
[21] http://www.omnifit.com/
[22] http://www.biotage.com/DynPage.aspx?id=120778
[23] B. J. Deadman, C. Battilocchio, E. Sliwinski and S. V. Ley,
Green Chem. 2013, 15, 2050-2055.
[6] a) T. Screen, Platinum Met. Rev. 2007, 51, 87–92; b) A. S.
Bhalla, R. Guo, R. Roy, Mater. Res. Innovations 2000, 4, 3–
26; c) S. Kato, M. Ogasawara, M. Sugai, S. Nakata, Catal.
Surv. Asia 2004, 8, 27–34; d) M. Misono, Catal. Today 2005,
100, 95–100.
[7] S. V. Ley, M. D. Smith, C. Ramarao, A. F. Stepan, H.
Tanaka, US Patent, US 2005215804, 2005.
[24] http://www.vapourtec.co.uk/
Received: May 27, 2013
Accepted: July 18, 2013
Published online: && &&, 0000
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