Solvent-Free Ruthenium(II)-Catalyzed C-H Activation: Synthesis of Alkenylarylpyrazole Derivatives

Article abstract of DOI:10.1002/ejoc.201500634

The Ru^II carboxylate complex Ru(MesCO₂)₂(p-cymene) (Mes = mesityl) was found to be an efficient catalyst for the direct dehydrogenative alkenylation of N-arylpyrazoles by using styrenes and acrylates in the presence of Cu(

Full text of DOI:10.1002/ejoc.201500634

FULL PAPER
DOI: 10.1002/ejoc.201500634
Solvent-Free Ruthenium(II)-Catalyzed C–H Activation: Synthesis of
Alkenylarylpyrazole Derivatives
[a]
[a]
Sanchari Shome and Surya Prakash Singh*
Dedicated to Dr. A. V. Rama Rao on the occasion of his 80th birthday
Keywords: C–H activation / Ruthenium / Alkenylation / Nitrogen heterocycles
II
The Ru carboxylate complex Ru(MesCO
mesityl) was found to be an efficient catalyst for the direct
dehydrogenative alkenylation of N-arylpyrazoles by using
styrenes and acrylates in the presence of Cu(OAc) ·H O in
2
)
2
(p-cymene) (Mes
ditions or by using a user-friendly solvent system in which
water was present as the major component. With less-reac-
tive styrenes, monoalkenylation took place, whereas with
alkyl acrylates ortho-dialkenylation occurred. This approach
may provide new insight into the design of an environmen-
tally benign method for the oxidative heterocoupling of N-
=
2
2
open air. The highly step-economical C–H bond functionali-
zation process is characterized by a wide substrate scope and
significant chemoselectivity, which allowed direct alkenyl- phenylpyrazole.
ation to be performed either under solvent-free reaction con-
Introduction
esters[27] by using [Ru(p-cymene)Cl ] dimer as the catalyst.
2
The transition-metal-catalyzed Heck coupling reaction is
[28]
Moreover, Ackermann et al. also reported alkylation and
arguably the most versatile tool for the synthesis of unsatu-
[29]
arylation
reactions by using some well-defined ruth-
rated molecules and conjugated materials,[
1–5]
and it is a key
enium carboxylate catalysts along with Cu(OAc) as the ox-
2
[
6,7]
structural probe in materials and medicinal chemistry.
II
idant. The use of AgSbF as an additive to Ru was intro-
6
[30]
Notably, this particular synthetic technique depends on the
use of an inexpensive stable catalyst having solvent compat-
ibility and also allowing the use of different directing
groups. However, the oxidative alkenylation of heteroarenes
is named the Moritani–Fujiwara reaction.
different palladium
duced by Jeganmohan. The use of costly additives such
as AgSbF makes the reaction environmentally hostile and
6
also increases the number of byproducts, which thereby de-
creases the yield.
Owing to their different biological importance and appli-
cations in materials chemistry, substituted 1H-pyrazoles
[8,9]
In this regard,
[
10–13]
[14–16]
and rhodium catalysts
have
already been used to promote the oxidative alkenylation of
heteroarenes with a variety of directing groups, namely,
and related molecules have been intensively researched over
[31–34]
the recent years.
As a consequence, functionalization
[
17,18]
[19]
[20,21]
imines,
amines,
and carboxylates.
Ruthenium-
of the C–H bonds of these heteroarenes by using inacti-
catalyst-directed arylation of unactivated C–H bonds with
2
2
vated styrenes (sp –sp coupling) has always been a chal-
lenging route for the synthesis of desired organic molecules.
Although significant advancements have been made in this
particular area, more extensive studies are still warranted.
As a part of our investigation, we found that a bulky
acid group in the catalyst enhanced its site selectivity and
phenols was reported by Ackermann.[
22]
Milstein et al.
pioneered the activation of benzene by using alkyl acry-
[
23]
lates.
Principally, carboxylic acid and ester groups have
some directing nature, which favors the site-selective alken-
ylation of the acrylates. In particular, deprotonation of C–H
bonds assisted by carboxylates and a RuII center proceeds
through an autocatalytic process, in which the formed
triggered attack of the coupling partner specifically to the
[35–38]
ortho position of the aryl group.
N-Arylpyrazoles are
[24,25]
RCO H acid plays a crucial role.
In contrast, both
2
an important class of heterocycles and can easily be func-
tionalized by a variety of alkenes at the ortho position by
using acetic acid to form the Ru(MeCO ) (p-cymene) cata-
Miura and Ackermann recently reported the alkenylation
of thiophene-2-carboxylic acid[ and simple benzoic acid
26]
2
2
[
39]
lyst. The use of a bulky acid group, for example, mesitoic
acid, in the catalyst for the synthesis of alkenyl derivatives
of arylpyrazoles or oxazolines has not been reported.
Herein, we report the first dehydrogenative alkenylation of
[
a] Inorganic and Physical Chemistry Division, CSIR – Indian
Institute of Chemical Technology,
Uppal Road, Tarnaka, Hyderabad 500607, Telangana, India
E-mail: spsingh@iict.res.in
http://www.iictindia.org/
arylpyrazoles by using Ru(MesCO )(p-cymene) (Mes =
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500634.
2
mesityl) and a stoichiometric amount of Cu(OAc) as the
2
Eur. J. Org. Chem. 2015, 6025–6032
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6025

S. Shome, S. P. Singh
FULL PAPER
Figure 1. Oxidative alkenylation of heteroarenes.
oxidant in air under neat conditions without the use of any may suppress the release of acetic acid in the catalytic cycle.
additive or an excess amount of acid as a co-catalyst (Fig- To investigate the dependence of reaction feasibility on
ure 1). The use of a solvent-free reaction system makes this the oxidant, a series of experiments were performed with
synthesis an efficient and environment friendly one.
three different oxidants along with various loadings of the
oxidant. Systematic studies showed that the highest yield
was obtained by using a catalytic amount of Cu(OAc) ·H O
(20 mol-%), and the results were superior to those obtained
by using the same amount of CuI and benzophenone under
neat conditions for 5–6 h at 80 °C (Table 2). The ratio of
the yield of the formation of 1-(2-styrylphenyl)-1H-pyrazole
2
2
Results and Discussion
Initially, the reaction of phenylpyrazole with styrene was
performed with Ru(MesCO ) (p-cymene) by using
2
2
Cu(OAc)2 as the oxidant in different solvent systems
Table 1) yielding 1-(2-styrylphenyl)-1H-pyrazole (3a) at
0 °C for 5–6 h.
(3a) to that of the formation of 2,2Ј-di(1H-pyrazol-1-yl)-
(
8
1,1Ј-biphenyl (4a) is shown in Table 2.
Table 2. Optimization of the alkenylation of phenylpyrazole with
styrene by using different amounts of the oxidant.[
Table 1. Solvent screening of the reaction of phenylpyrazole (1a)
a]
[
a]
with styrene (2a).
Loading [mol-%] Yield [%][b] of 3a/4a
Yield[b] [%] of 3a
Entry Oxidant
Entry
Solvent
AcOH
(
neat conditions)
1
2
3
4
5
6
7
8
9
0
1
2
3
55
24
1
2
3
4
5
6
7
none
–
5
10
20
25
20
20
10:62
22:40
53:24
81:10
72:30
23:68
9:71
H
2
O
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
CuI
2
2
2
2
THF
MeCN
DME
no reaction
69
7.8
1,4-dioxane
15
MeCN/H
MeCN/H
MeCN/H
DMF
acetone/H
acetone
neat
2
2
2
O (1:1)
O (0.5:1)
O (0.2:1)
62.56
70.3
78.6
23
46
38.26
81
benzophenone
[a] Reagents and conditions: 1a (0.5 mmol), 2a (1.25 mmol), cata-
lyst (10 mol-%), 5–6 h at 80 °C. [b] Yield of isolated product.
1
1
1
1
2
O
The role of the Ru(MesCO ) (p-cymene) catalyst was in-
2
2
vestigated by varying the amount used, and the results are
shown in Table 3. In the absence of a catalyst, no alkenyl-
[
a] Reagents and conditions: 1a (0.5 mmol), 2a (1.25 mmol), addi-
tive (20 mol-%), 5–6 h at 80 °C. [b] Yield of isolated product.
[
41]
ation or homocoupling reaction took place. The yield in-
creased with an increase in the amount of catalyst used and
reached a maximum with a yield of 81%, but it then fol-
Polar aprotic solvents such as DMF, acetonitrile, and
acetone alone did not produce good yields, though a rela-
tively moderate yield was obtained in acetonitrile, which
was selected to optimize the reaction under mixed-solvent
lowed a decreasing trend. Notably, without Cu(OAc) ·H O,
2
2
only 62% conversion of the homocoupled product and 10%
of the heterocoupled product took place, and the absence
of air and a lower temperature also disfavored the reaction.
conditions. Notably, an increase in the volume of water (po-
lar protic solvent) increased the yield.[40–44] A maximum
yield of ca. 79% was obtained in 0.2:1 acetonitrile/water.
On the other hand, the yield decreased dramatically (24%)
if the reaction was performed in pure water. Thus, from the
solvent screening it was understood that the addition of a
polar protic solvent to the reaction mixture increased the
yield of the product. If the reaction was performed under
neat conditions, the yield was higher than that obtained in
the mixed-solvent system. This is plausibly due to acetic
Table 3. Optimization of the alkenylation reaction by using dif-
ferent amounts of catalyst.
[a]
Entry
Catalyst loading [mol-%]
Yield [%][b] of 3a
(
neat conditions)
1
2
3
4
5
0
5
10
15
20
no reaction
64
81
76
72
acid that is in situ generated from Cu(OAc) , as affirmed
2
by HRMS analysis of 6j (see the Supporting Information)
[
45]
A similar phenomena was found in an earlier report. On
[
a] Reagents and conditions: 1a (0.5 mmol), 2a (1.25 mmol),
the other hand, the presence of any other aprotic solvent Cu(OAc)
2
·H O (20 mol-%). [b] Yield of isolated product.
2
6026
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6025–6032

Synthesis of Alkenylarylpyrazole Derivatives
The reaction of the styrenes was also screened with dif- drawing group in the para position enhances the yield rela-
ferent substituted phenylpyrazoles. The presence of elec- tive to that obtained with a weak electron-withdrawing
tron-withdrawing groups in the meta and para positions of group. The reaction goes well with a keto group, however,
phenylpyrazole (i.e., substrates 1c–f) did not yield the de- and 1-(4-cyanophenyl)-1H-pyrazole (1f) undergoes metal-
[
47]
sired product, even after 24 h of reaction, whereas the 4- mediated hydrolysis of cyanide under the reaction condi-
methoxyphenyl-substituted pyrazole gave a promising yield tions, which thereby yields 6l in 76% yield. The reaction of
after only 5–6 h. The use of oxazolines with styrene under an amide was also attempted with the acrylate under similar
the optimized reaction conditions resulted in a number of conditions, but the desired product was not obtained. The
spots on the TLC plate, but none of them were identified as presence of a fluorine atom in the meta position slowed the
the product. Therefore, to solve this problem, under similar reaction down further to give a yield as low as 38%. How-
experimental conditions, ethanol (2 mL) was added, and ever, under these conditions, the corresponding homocou-
the reaction was performed open to air.[ This resulted in pling product was never observed. Upon increasing the
the formation of a dialkenylated product. Even upon amount of butyl acrylate up to 1.5–2 equivalents, a signifi-
decreasing the reaction time, the amount of styrene, and the cant amount of dialkenylated pyrazoles (i.e., 6d–e and 6k–
temperature, coupling on both sides of the phenyloxazoline l) was obtained (Scheme 2).
46]
could not be controlled, and this may be due to the rela-
tively high reactivity of the chosen catalyst under the speci- ation and dialkenylation simply by monitoring the number
fied reaction conditions. of equivalents of the coupling partner along with the reac-
The reaction can be controlled in terms of monoalkenyl-
A large number of functional groups on the phenylpyr- tion time and temperature. An excess amount of styrene
azole is tolerated in reactions with butyl acrylate and must always be used (2.5 equiv.) to get the maximum yield,
Cu(OAc) ·H O (1 equiv.); (E)-monoalkenylated derivatives as styrenes are low-boiling liquids, and therefore, they can
2
2
(i.e., 6a–d) and (E)-dialkenylated derivatives (i.e., 6e, 6f, 6k, mostly evaporate during the course of the reaction
and 6l) are afforded in yields of 70 to 90%. The reaction (Scheme 1). By using the same number of equivalents of the
with 1-(4-methoxyphenyl)-1H-pyrazole was slower than acrylate as the number of equivalents of the styrene, the
[
48]
that with parent compound 1a, which shows that the elec- dialkenylation product is exclusively formed. This can be
tron-donating para-methoxy group slows down the alkenyl- explained by the fact that acrylates are more reactive than
[
49,50]
ation. The presence of a moderate to strong electron-with- styrenes,
and only the dialkenylated products are
Scheme 1. Alkenylation of heteroarenes with styrenes. Reagents and conditions: 1a,b (0.5 mmol), 2a–c (1.25 mmol), Ru(MesCO
2
)
2
(p-
1
cymene) (0.015 mmol) Cu(OAc) ·H O (20 mol-%), neat reaction, 100 °C, 10–12 h. For 3e,f, 2 mL of ethanol was added. If R = meta-F
2 2
(
1d) or para-F (1c), no reaction occurred, even after increasing the temperature, and the starting material was converted into the homocou-
pling product. If 4-fluorostyrene, 3-nitrostyrene, vinylpyridine, or vinylpyrazine was used, no reaction occurred up to 48 h, and starting
material 1a was converted into the homocoupling product.
Eur. J. Org. Chem. 2015, 6025–6032
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6027

S. Shome, S. P. Singh
FULL PAPER
Scheme 2. Alkenylation of heteroarenes with butyl acrylate. Reagents and conditions: 1a–f (0.5 mmol), 5a (0.65 mmol), Ru(MesCO
2
)
2
(p-
cymene) (0.015 mmol) Cu(OAc)
ethanol (2 mL) was added.
2 2
·H O (20 mol-%), neat reaction, 100 °C, 5–6 h. For 6e–g and 6k–l, 5a (1.25 mmol) was used. For 6h,i,
formed. Therefore, the reaction was controlled by using
.5 equivalents of the acrylate and a shorter reaction time was attempted under optimal conditions with a variety of
Scheme 2), and this resulted in the exclusive formation of functional alkenes at 100 °C by varying the reaction time
the monoalkenylated product. and the ratio of Cu(OAc) ·H O (20 mol-% or 1 equiv.) For
For the preparation of 3 (Table 4), the alkenylation of 1a
1
(
2
2
The formation of the products (i.e., 6a,b and 6i–h) was less-reactive styrenes 2b and 2c, complete conversion could
faster if acrylates were employed instead of simple styrene. not be reached after 30 h with 20 mol-% of Cu(OAc) ·H O,
2
2
This is likely due to faster insertion of the polarized and which led to the formation of 4 in high yield.
II
electron-deficient C–C bond of acrylate into the C–Ru
In contrast, the heterocyclic styrenes 2-vinylpyridine and
bond of cyclometalated intermediate B. The observed re- 2-vinylpyrazole were inactive, and the reactions led to
gioselectivity of insertion is consistent with the polar C–Ru homocoupled products, most likely due to the presence of a
bond of the cyclometalated intermediate.[
29]
heteroatom, which reduces the electrophilicity of the double
As a parallel observation, it was shown that the Ru(Me- bond. Alkyl-substituted styrenes were less reactive than
sCO ) (p-cymene) catalyst with Cu(OAc) ·H O (20 mol-%) simple styrene, whereas styrenes having an electron-donat-
2
2
2
2
as the oxidant also promotes homocoupling of functional ing group in the para position gave 3 as the much-favored
[
41]
arenes.
Notably, the alkenylation of 1a with styrene is product over 4. On the other hand, electron-withdrawing
faster than homocoupling of 1a, as under almost similar groups in the para position of the styrene promoted the
experimental conditions, the presence of 2.5 equivalents of formation of only the homocoupled product.
II
styrene inhibited the formation of 4a over the formation of
a.
A possible mechanism for the Ru -catalyzed C–H acti-
vation and functionalization of heteroarenes is conceptually
3
6028
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6025–6032

Synthesis of Alkenylarylpyrazole Derivatives
Table 4. Alkenylation of phenylpyrazoles under solvent free condi- mediate C. The C–H activation process is possibly assisted
[
a]
tions.
–
[51]
by the carbonyl oxygen atom of the MesCOO group,
Yield[b] [%]
Mono Di
as represented in B. Notably, possible dissociation of the
Entry
Substrate Styrene/
acrylate
–
Homo
MesCOO group from C, followed by oxidative addition
IV
with the arylalkenyl derivative gives cationic Ru interme-
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1c
1d
1e
1f
2a
2b
2c
2a
2a
2a
2a
2a
2a
2a
5a
5a
5a
5a
5a
5a
12 (after 10 h) 3a 81
18 (after 10 h) 3b 51
31 (after 20 h) 3d 43
22 (after 10 h) 3c 73
–
–
–
–
diate D. Subsequently, reductive elimination of D take
place, which affords the 2-functionalized phenylpyrazole
adducts and regenerates catalyst A.
–
–
–
–
–
–
–
–
–
–
–
–
–
–
We surmise that the presence of this pyrazole moiety is
–
–
–
–
an indispensable component of the modern medicinal
[
52]
–
–
chemistry repertoire. These moieties are hardly found in
nature and serves as an important core for many pharma-
ceutical leads with a wide range of biological activities (e.g.,
anticholesterol, anti-inflammatory, antidepressant, and an-
tipsychotic).
[
c]
9
1
1g
1h
1a
1b
1c
1d
1e
1f
trace
3f 68
6a 78
6b 92
6c 77
6d 68
–
3e 78
–
–
6g 81
6e 73
6f 38
6k 83
after in situ
hydrolysis: 6l
0[
c]
[d]
1
1
[e]
1
2
[e]
1
3
[e]
1
4
[f]
15
[f,g]
16
–
Conclusions
7
–
–
6
In conclusion, we successfully employed a ruthenium(II)
mesitoate catalyst for the highly efficient and direct oxidat-
ive alkenylation of N-phenylpyrazoles through C–H bond
activation in air with conventional heating. Acceptable
yields of the alkenylarylpyrazoles were obtained for some
1 [
18
7
h]
1g
1h
5a
5a
–
–
6h 59
6i 53
[h]
[
a] Reagents and conditions: 1a (0.5 mmol), 2a (1.25 mmol), cata-
lyst (10 mol-%), Cu(OAc) ·H O (20 mol-%), 100 °C, 10–12 h.
b] Yield of isolated product; homo = homocoupled product, mono
2
2
[
=
monoalkenylated product, di = dialkenylated product. [c] 1a substrates without using of solvent or by using a greener
(
0.5 mmol), 2a (1.25 mmol), ethanol (2 mL), catalyst (10 mol-%),
Cu(OAc) ·H O (20 mol-%), 100 °C, 10–12 h. [d] 1a (0.5 mmol), 5a
0.65 mmol), catalyst (10 mol-%), Cu(OAc) ·H (20 mol-%),
00 °C, 10–12 h. [e] 5a (0.65 mmol) gave monoalkenylated product,
solvent medium consisting of water as the major compo-
nent. The reactions with acrylates were faster than those
with styrenes. C–H bond cleavage followed by addition of
2
2
(
1
2
2
O
and 5a (1.25 mmol) gave dialkenylated product. [f] 5a (1.5 mmol), the alkene derivative probably follows an autocatalytic pro-
only dialkenylation was observed. [g] Hydrolysis took place during
cess, wherein a cyclometalated ruthenium intermediate was
proposed to be involved in the catalytic cycle. Further ex-
the course of the reaction. [h] 5a (0.65 mmol), ethanol (2 mL).
ploration and utility of ruthenium carboxylate catalysts for
depicted in Scheme 3. Coordination of the N atom of the the direct activation of arenes in the absence of any direct-
pyrazole unit with the catalyst gives A, and this is followed ing group is still under investigation.
by concerted metalation–deprotonation C–H activation
processes at the 2-position of the phenyl group to give inter-
Experimental Section
General Information: Thin-layer chromatography plates were visu-
1
13
alized by exposure to UV light/iodine. H NMR and C NMR
spectra were obtained with a 300 MHz spectrometer with tet-
1
ramethylsilane and [D ]chloroform, respectively, as the internal
standards. Chemical shifts (δ) are reported in ppm relative to the
1
residual solvent signal (δ = 7.26 ppm for H NMR and δ = 77.0 pm
1
3
for C NMR). Mass spectra were recorded with a Shimadzu model
LCMS-2010EV system that was equipped with an electrospray ion-
ization (ESI) probe.
Materials: The following chemicals were obtained from Sigma–Al-
drich and were used as received: iodobenzene and its derivatives,
1
H-pyrazole, styrene and its derivatives, butyl acrylate, Cu(OAc)
2
·
H
2
O, CuI, Cs CO , and Fe(acac) (acac = acetylacetonate). The
2
3
3
solvents used for the reactions were AR grade FINAR, and sol-
vents used for column chromatography were LR grade. Silica used
for column chromatography was either 60–120 or 100–200 as re-
quired.
General Procedure for the Synthesis of Arylpyrazoles: Arylpyrazoles
1
b–d were synthesized following the reported procedure by using
[
53]
3
Fe(acac) in dry DMF under sealed-tube reaction conditions.
Scheme 3. Probable mechanistic pathway for the carboxylate-as-
sisted alkenylation of heteroarenes.
General Procedure for the Synthesis of the Ruthenium Catalyst: The
reported procedure was followed.[ A suspension of [RuCl
54]
(p-cy-
2
Eur. J. Org. Chem. 2015, 6025–6032
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6029

S. Shome, S. P. Singh
FULL PAPER
mene)]
07 mg, 0.653 mmol), and K
15 mL) was stirred under an atmosphere of N
temperature. The solvent was removed under reduced pressure, and
the remaining residue was dissolved in dry CH Cl (20 mL). Then,
the resulting suspension was filtered under an atmosphere of N
2
(1; 100 mg, 0.163 mmol), 2,4,6-trimethylbenzoic acid (2; 1-(4-Methoxy-2-styrylphenyl)-1H-pyrazole (3c): The general pro-
1
(
2
CO (225 mg, 1.63 mmol) in toluene cedure was followed by using 1-(4-methoxyphenyl)pyrazole (1b;
3
2
for 2 h at ambient
87 mg, 0.5 mmol) and styrene (2a; 0.14 mL, 1.25 mmol). Purifica-
tion was done by column chromatography (hexane/EtOAc, 90:10)
1
2
2
to yield 3c (73%). Yellow liquid. H NMR (300 MHz, CDCl
3
): δ
2
= 7.75 (d, 1 H), 7.59 (d, 1 H), 7.387–7.301 (m, 4 H), 7.25–7.23 (m,
through a short pad of Celite. The solvent was removed under re-
duced pressure to yield 3 (183 mg, 99%) as an orange solid, m.p.
3 H), 7.01 (d, J = 16.174 Hz, 1 H), 6.82 (d, J = 16.174 Hz, 1 H),
6.45 (t, 1 H), 3.91 (s, 3 H) ppm. C NMR (75 MHz, CDCl ): δ =
3
1
3
126–128 °C (decomp.). The complex was recrystallized from n-hex-
156.0, 140.4, 131.9, 131.0, 126.8, 128.8, 128.6, 128.2, 127.9, 127.7,
ane/acetone (5:1) at –20 °C.
127.4, 126.6, 113.6, 110.7, 106.2, 55.5 ppm. MS (ESI): m/z = 277
+
[M + H]+ 277.13422;
[
M + H] . HRMS: calcd. for C18
H
17ON
2
General Procedure for the Catalytic Transformation: A clean and
found 277.13354.
dry round-bottomed flask was charged with Cu(OAc)
100 mg, 25 mol-%), 1-phenylpyrazole (72 mg, 0.5 mmol, 1 equiv.),
and alkene (1.25 mmol, 2.5 equiv.). Then, Ru(MesCO (p-cymene)
21 mg, 0.05 mmol, 10 mol-%) was added to the flask under aerobic
conditions. Thereafter, the mixture was heated at reflux at 100–
20 °C under sealed conditions. The progress of the reaction was
2 2
·H O
(
1-{2-[(E)-2-(4-Methylphenyl)ethenyl]phenyl}-1H-pyrazole (3d): The
2
)
2
general procedure was followed by using 1-phenylpyrazole (1a;
6 μL, 0.5 mmol) and 4-methylstyrene (2c; 0.16 mL, 1.25 mmol).
(
6
Purification by column chromatography (hexane/EtOAc, 70:30)
1
yielded 3d (43%). Yellow liquid. NMR spectroscopic data were
examined by continuous checking by TLC. After cooling the mix-
ture to room temperature, water (10 mL) and EtOAc (15 mL) were
added, and the organic layer was separated, washed with NaHCO
solution (10 mL) several times, and dried with anhydrous Na SO
The final crude product was obtained by evaporating the solvent
under reduced pressure. Finally, the product was purified by col-
umn chromatography (EtOAc/hexane).
[39] 1
consistent with reported data.
3
H NMR (300 MHz, CDCl ): δ
=
7.75 (d, 1 H), 7.59 (d, 1 H), 7.39–7.30 (m, 5 H), 7.25–7.23 (m, 3
3
H), 7.02 (d, J = 16.174 Hz, 1 H), 6.83 (d, J = 16.174 Hz, 1 H), 6.45
2
4
.
(
t, 1 H), 2.18 (s, 3 H) ppm. C NMR (75 MHz, CDCl
3
13
): δ = 140.6,
1
1
38.5, 137.9, 133.6, 133.3, 131.4, 130.7, 129.8, 128.3, 127.9, 126.7,
+
26.5, 121.6, 106.4, 21.2 ppm. MS (ESI): m/z = 261 [M + H] .
+
HRMS: calcd. for
18 17 2
C H N [M + H] 261.13754; found
261.13863.
General Procedure for the Catalytic Transformation by Using Oxaz-
olines: A clean and dry round-bottomed flask was charged with
4
,5-Dihydro-2-(2,6-distyrylphenyl)oxazole (3e): The general pro-
Cu(OAc)
.5 mmol, 1 equiv.), and alkene (1.25 mmol, 2.5 equiv.). Then, Ru-
MesCO (p-cymene) (0.015 mmol) was added under aerobic con-
2 2
·H O (100 mg, 20 mol-%), 1-phenylpyrazole (72 mg,
cedure was followed by using phenyloxazoline (1e; 66 μL,
.5 mmol), styrene (2a; 0.16 mL, 1.25 mmol), and ethanol (2 mL).
0
0
(
2 2
)
Purification by column chromatography (hexane/EtOAc, 70:30)
ditions, along with ethanol (2 mL). Thereafter, the mixture was
heated at reflux at 100–120 °C open to air. The progress of the
reaction was examined by continuous checking by TLC. After cool-
ing the mixture to room temperature, water (10 mL) and EtOAc
yielded 3d (78%). White solid. NMR spectroscopic data were con-
sistent with reported data.[
46]
1
H NMR (300 MHz, CDCl
3
): δ =
7.63 (d, 2 H), 7.52–7.40 (m, 6 H), 7.36 (t, 4 H), 7.07 (d, J = 16.0 Hz,
2
1
3
3
H), 4.51 (t, 2 H), 4.22 (t, 2 H) ppm. C NMR (75 MHz, CDCl ):
(
15 mL) were added, and the organic layer was separated, washed
with NaHCO solution (10 mL) several times, and dried with anhy-
drous Na SO . The final crude product was obtained by evaporat-
δ = 164.0, 137.2, 137.3, 131.2, 129.9, 128.6, 128.2, 127.8, 126.7,
1
HRMS: calcd. for C25
3
3
+
25.8, 124.5, 67.6, 55.2 ppm. MS (ESI): m/z = 352 [M + H] .
2
4
22ON [M + H]+ 352.16989; found
H
ing the solvent under reduced pressure. Finally, the product was
purified by column chromatography (EtOAc/hexane).
52.16959.
4
,5-Dihydro-4,4-dimethyl-2-(2-styrylphenyl)oxazole (3f): The gene-
1
-(2-Styrylphenyl)-1H-pyrazole (3a): The general procedure was fol-
lowed by using 1-phenylpyrazole (1a; 66 μL, 0.5 mmol) and styrene
2a; 0.14 mL, 1.25 mmol). Purification was done by column
ral procedure was followed by using 4,4-dimethyl-2-phenyl-2-oxaz-
oline (1f; 66 μL, 0.5 mmol), styrene (2a; 0.16 mL, 1.25 mmol), and
ethanol (2 mL). Purification by column chromatography (hexane/
(
chromatography (hexane/EtOAc, 90:10) to yield 3a (81%). Yellow
oil. NMR spectroscopic data were consistent with the reported
EtOAc, 80:20) yielded 3d (68%). NMR spectroscopic data were
consistent with reported data.[
46] 1
[
37] 1
3
H NMR (300 MHz, CDCl ): δ
data.
br. s, 1 H), 7.665 (d, J = 2.2 Hz, 1 H), 7.435–7.385 (m, 5 H), 7.345–
.296 (m, 3 H), 7.082 (d, J = 16 Hz, 1 H), 6.967 (d, J = 16 Hz, 1
H NMR (300 MHz, CDCl
3
): δ = 7.783 (br. d, 1 H), 7.763
=
=
7.72 (d, 1 H), 7.57–7.49 (m, 3 H), 7.30–7.25 (m, 2 H), 7.03 (d, J
(
7
1
3
16 Hz, 1 H), 4.16 (s, 2 H), 1.47 (s, 6 H) ppm. C NMR (75 MHz,
13
3
CDCl ): δ = 163.1, 137.5, 137.2, 133.4, 131.2, 129.4, 128.6, 128.5,
H), 6.481 (t, 1 H) ppm. C NMR (75 MHz, CDCl
1
1
3
): δ = 140.7,
127.6, 126.7, 126.1, 123.9, 79.1, 60.9, 28.2 ppm. MS (ESI): m/z =
38.8, 137.0, 133.0, 131.5, 131.2, 128.6, 128.4, 128.1, 127.9, 126.7,
+
+
+
278 [M + H] . HRMS: calcd. for C H ON [M + H] 278.15381;
found 278.15394.
26.6, 126.3, 123.9, 106.6 ppm. MS (ESI): m/z = = 247 [M + H] .
19 20
+
HRMS: calcd. for
17 15 2
C H N [M + H] 247.12292; found
2
47.12298.
Butyl (E)-3-[2-(1H-Pyrazol-1-yl)phenyl]acrylate (6a): The general
procedure was followed by using 1-phenylpyrazole (1a; 66 μL,
0.5 mmol) and butyl acrylate (3a; 0.049 mL, 0.55 mmol). Purifica-
1-[2-(4-Methoxystyryl)phenyl]-1H-pyrazole (3b): The general pro-
cedure was followed by using 1-phenylpyrazole (1a; 66 μL,
.5 mmol) and 4-methoxystyrene (2b; 0.166 mL, 1.25 mmol). Puri-
fication by column chromatography (hexane/EtOAc, 70:30) yielded
0
tion by column chromatography (hexane/EtOAc, 90:10) yielded 6a
1
(78%). H NMR (300 MHz, CDCl
3
): δ = 7.77 (d, 1 H), 7.71 (d, 1
1
3
b (51%). Yellow oil. H NMR (300 MHz, CDCl
3
): δ = 7.77 (d, 1 H), 7.63 (d, 1 H), 7.59 (d, J = 16.0 Hz, 1 H), 7.52–7.41 (m, 3 H),
H), 7.65 (d, 1 H), 7.44–7.31 (m, 5 H), 7.00 (d, J = 16.1 Hz, 1 H), 6.49 (t, 1 H), 6.37 (d, J = 16.0 Hz, 1 H); 4.16 (t, 2 H), 1.67–1.61
13
6
(
.86–6.82 (m, 3 H), 6.46 (t, 1 H), 3.79 (s, 3 H) ppm. 13C NMR
75 MHz, CDCl ): δ = 159.4, 140.6, 138.5, 133.3, 131.4, 130.7, (75 MHz, CDCl
29.8, 129.2, 127.9, 127.8, 127.6, 126.3, 121.6, 114.6, 106.4, 128.3, 128.2, 127.4, 136.0, 121.6, 120.5, 107.0, 64.2, 64.2, 30.4, 18.9,
(m, 2 H), 1.42–1.36 (m, 2 H), 0.94 (t, 3 H) ppm. C NMR
): δ = 164.3, 141.0, 139.3, 138.3, 131.2, 130.4,
3
3
1
5
+
+
5.25 ppm. MS (ESI): m/z = 277 [M + H] . HRMS: calcd. for
13.5 ppm. MS (ESI): m/z = 271 [M + H] . HRMS: calcd. for
C
18
H
17ON
2
[M + H]+ 277.13422; found 277.13354.
16 19 2 2
C H O N
[M + H]+ 271.14295; found 271.14410.
6030
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6025–6032

Synthesis of Alkenylarylpyrazole Derivatives
Butyl (E)-3-[5-Methoxy-2-(1H-pyrazol-1-yl)phenyl]acrylate (6b): 1-{2,6-Bis[(E)-2-(butoxycarbonyl)ethenyl]-4-methoxyphenyl}-1H-
The general procedure was followed by using 1-(4-methoxyphenyl)
pyrazole (1b; 87 mg, 0.5 mmol) and butyl acrylate (5a; 0.049 mL,
pyrazole (6g): The general procedure was followed by using 1-(4-
methoxyphenyl)pyrazole (1b; 87 mg, 0.5 mmol) and butyl acrylate
0
.55 mmol). Purification by column chromatography (hexane/
(5a; 0.147 mL, 1.5 mmol). Purification by column chromatography
1
1
EtOAc, 90:10) yielded 6b (92%). H NMR (300 MHz, CDCl
7.79 (d, 1 H), 7.56 (d, 1 H); 7.37 (d, 1 H), 7.17 (d, 1 H), 7.04 (d,
J = 16.0 Hz, 1 H), 7.00 (dd, 1 H), 6.52 (t, 1 H), 6.27 (d, J = 16.0 Hz,
3
): δ (petroleum ether/Et
2
O, 90:10) yielded 6g (81 %). H NMR
=
(300 MHz, CDCl
3
): δ = 7.8 (d 1 H), 7.47 (d, 1 H), 7.22 (s, 2 H),
7.04 (d, J = 16.02 Hz, 1 H), 6.52 (t, 1 H), 6.27 (d, J = 16.02 Hz, 2
1
2
1
6
H), 4.12 (t, 2 H), 3.91 (s,3 H), 1.63–1.58 (m, 2 H), 1.39–1.35 (m,
H), 4.12 (t, 4 H), 3.92 (s, 3 H), 1.65–1.59 (m, 4 H), 1.40–1.34 (m,
4 H), 0.93 (t, 6 H) ppm. C NMR (75 MHz, CDCl ): δ = 166.02,
3
159.66, 141.15, 138.50, 134.66, 133.00, 132.22, 121.80, 113.11,
H), 0.88 (t, 3 H) ppm. 13C NMR (75 MHz, CDCl
13
3
): δ = 166.1,
59.7, 141.2, 138.5, 129.5, 127.8, 120.9, 116.3, 113.2, 111.6, 107.1,
+
4.5, 55.6, 31.9, 19.1, 13.6 ppm. MS (ESI): m/z = 301 [M + H] .
107.02, 64.41, 55.65, 30.46, 18.99, 13.58 ppm. MS (ESI): m/z = 427
+
+
31 5 2
H O N
[M + H]+ 427.2204;
HRMS: calcd. for C17
01.15467.
H
21
O
3
N
2
[M + H] 301.15522; found
[M + H] . HRMS: calcd. for C24
found 427.22275.
3
Butyl (E)-3-[5-Fluoro-2-(1H-pyrazol-1-yl)phenyl]acrylate (6c): The Butyl (2E)-3-[2-(4,5-Dihydrooxazol-2-yl)phenyl]acrylate (6h): The
general procedure was followed by using 1-(4-fluorophenyl)pyr-
azole (1c; 87 mg, 0.5 mmol) and butyl acrylate (5a; 0.049 mL,
general procedure was followed by using 2-phenyloxazoline (1g;
66 μL, 0.5 mmol), butyl acrylate (5a; 0.07 mL, 0.55 mmol), and eth-
0
.55 mmol). Purification by column chromatography (hexane/
anol (2 mL). Purification by column chromatography (hexane/
1
1
EtOAc, 90:10) yielded 6g (77%). H NMR (300 MHz, CDCl
3
): δ EtOAc, 70:30) yielded 6h (59%). H NMR (300 MHz, CDCl
3
): δ
=
7.76 (d,1 H), 7.79 (d,1 H), 7.48 (d, J = 16.0 Hz, 1 H), 7.45–7.38 = 8.53 (d, J = 16.0 Hz, 1 H), 7.86 (dd, 1 H), 7.65 (dd, 1 H), 7.51–
m, 2 H), 7.20–7.15 (m, 1 H), 6.49 (t, 1 H), 6.36 (d, J = 16.0 Hz, 1 7.41 (m, 2 H), 6.36 (d, J = 16.0 Hz, 1 H), 4.45 (t, 2 H), 4.21 (t, 2
H), 4.16 (t, 2 H), 1.67–1.61 (m, 2 H), 1.44–1.35 (m, 2 H), 0.94 (t, H), 4.07 (t, 2 H), 1.73–1.65 (m, 2 H), 1.49–1.43 (m, 2 H), 0.97 (t,
(
13
3
1
1
H) ppm. 13C NMR (75 MHz, CDCl
07.4, 114.5, 114.8, 117.3, 121.9, 128.7, 133.0, 138.6, 141.6, 160.7,
3
): δ = 13.6, 19.0, 30.5, 64.6, 3 H) ppm. C NMR (75 MHz, CDCl
135.0, 131.8, 130.8, 130.0, 127.4, 127.2, 120.1, 67.4, 65.0, 55.3, 30.7,
3
): δ = 166.9, 164.0, 143.6,
+
+
64.0, 165.7 ppm. MS (ESI): m/z = 289 [M + H] . HRMS: calcd. 19.1, 13.7 ppm. MS (ESI): m/z = 274 [M + H] . HRMS: calcd. for
+
16 20 3
C H O
N [M + H]+ 274.14375; found 274.14377.
for C16
H
18FN
2
O
2
[M + H] 289.13468; found 289.13335.
Butyl (E)-3-[2-Fluoro-6-(1H-pyrazol-1-yl)phenyl]acrylate (6d): The Butyl (2E)-3-[2-(4,5-Dihydro-4,4-dimethyloxazol-2-yl)phenyl]acryl-
general procedure was followed by using 1-(3-fluorophenyl)pyr-
azole (1d; 87 mg, 0.5 mmol) and butyl acrylate (5a; 0.049 mL,
ate (6i): The general procedure was followed by using 4,4-dimethyl-
2-phenyl-2-oxazoline (1h; 66 μL, 0.5 mmol), butyl acrylate (5a;
0
.55 mmol). Purification by column chromatography (hexane/
0.07 mL, 0.55 mmol), and ethanol (2 mL). Purification by column
1
1
EtOAc, 90:10) yielded 6d (68%). H NMR (300 MHz, CDCl
3
): δ chromatography (hexane/EtOAc, 70:30) yielded 6h (53%). H NMR
=
1
=
2
7.79 (d, 1 H), 7.70 (m, 1 H), 7.64 (d, 1 H), 7.60 (d, J = 16.021 Hz,
H), 7.25 (dd, 1 H), 7.17–7.13 (m, 1 H), 6.51 (t, 1 H), 6.34 (d, J 7.65 (dd, 1 H), 7.48–7.38 (m, 2 H), 6.37 (d, J = 16 Hz, 1 H), 4.21
16.021 Hz, 1 H), 4.17 (t, 2 H), 1.68–1.61 (m, 2 H), 1.43–1.37 (m, (t, 2 H), 4.13 (s, 2 H), 1.72–1.65 (m,2 H), 1.50–1.45 (m, 2 H), 1.25
H), 0.95 (t, 3 H) ppm. 13C NMR (75 MHz, CDCl
): δ = 13.7,
3
(300 MHz, CDCl ): δ = 8.48 (d, J = 16.0 Hz, 1 H), 7.81 (dd, 1 H),
13
3
3
(s, 6 H), 0.97 (t, 3 H) ppm. C NMR (75 MHz, CDCl ): δ = 166.9,
1
1
9.1, 30.5, 64.6, 107.6, 113.2, 113.5, 115.5, 115.9, 116.2, 117.5,
161.4, 143.2, 134.7, 130.7, 130.0, 129.3, 128.1, 127.0, 120.0, 79.0,
25.7, 125.9, 132.5, 135.4, 137.7, 141.6, 160.1, 163.6, 166.4 ppm.
68.3, 64.3, 30.7, 28.3, 19.2, 13.7 ppm. MS (ESI): m/z = 302 [M +
+
+
24 3
H O
N [M + H]+ 302.17429; found
MS (ESI): m/z = 289 [M + H] . HRMS: calcd. for C16
H
18FN
2
O
2
H] . HRMS: calcd. for C18
302.17507.
[
M + H]+ 289.13335; found 289.13468.
1
-{2,6-Bis[(E)-2-(butoxycarbonyl)ethenyl]-4-fluorophenyl}-1H-pyr- 1-{2,6-Bis[(E)-2-(Butoxycarbonyl)ethenyl]-4-acetylphenyl}-1H-pyr-
azole (6e): The general procedure was followed by using 1-(4-
fluorophenyl)pyrazole (1c; 87 mg, 0.5 mmol) and butyl acrylate
azole (6k): The general procedure was followed by using 1-[4-(1H-
pyrazol-1-yl)phenyl]ethanone (1e; 93 mg, 0.5 mmol) and butyl ac-
rylate (5a; 0.147 mL, 1.5 mmol). Purification by column
(
(
5a; 0.147 mL, 1.5 mmol). Purification by column chromatography
hexane/EtOAc, 90:10) yielded 6e (73 %). H NMR (300 MHz,
1
1
chromatography (hexane/EtOAc, 70:30) yielded 6k (83 %). H
CDCl
3 3
): δ = 7.82 (d, 1 H); 7.49 (d, 1 H), 7.02 (d, J = 16.017 Hz, 2 NMR (300 MHz, CDCl ): δ = 8.28 (s, 2 H), 7.86 (d, 1 H), 7.53 (d,
H), 6.55 (t, 1 H), 6.30 (d, J = 16.017 Hz, 2 H); 4.13 (t, 4 H), 1.64– 1 H), 7.15 (d, J = 16 Hz, 2 H), 6.58 (t, 1 H), 6.42 (d, J = 16 Hz, 2
1
3
1
(
1
.58 (m, 4 H), 1.39–1.33 (m, 4 H), 0.93 (t, 6 H) ppm. C NMR
75 MHz, CDCl ): δ = 166.0, 164.0, 141.8, 137.7, 133.3, 131.8, 4 H), 0.94 (t,6 H) ppm. C NMR (75 MHz, CDCl
23.2, 114.7, 115.1, 107.7, 64.9, 30.8, 19.3, 13.9 ppm. MS (ESI): 165.8, 141.9, 138.0, 134.0, 132.7, 128.5, 127.8, 122.9, 107.7, 64.7,
H), 4.15 (t, 4 H), 2.71 (s, 3 H), 1.65–1.42 (m, 4 H), 1.41–1.37 (m,
1
3
3
3
): δ = 196.0,
+
[M + H]+
+
m/z = 415 [M + H] . HRMS: calcd. for C23
4
H
28FN
2
O
4
31.9, 30.5, 19.1, 13.6 ppm. MS (ESI): m/z = 439 [M + H] . HRMS:
15.20413; found 415.20276.
calcd. for C25
31 5 2
H O N
[M + H]+ 439.22262; found 439.22275.
1
-{2,6-Bis[(E)-2-(butoxycarbonyl)ethenyl]-3-fluorophenyl}-1H-pyr- 1-{2,6-Bis[(E)-2-(Butoxycarbonyl)ethenyl]benzamidophenyl}-1H-pyr-
azole (6f): The general procedure was followed by using 1-(3-fluoro-
phenyl)pyrazole (1d; 87 mg, 0.5 mmol) and butyl acrylate (5a;
azole (6l): The general procedure was followed by using 4-(1H-pyr-
azol-1-yl)benzonitrile (1g; 43 mg, 0.25 mmol) and butyl acrylate
(5a; 0.147 mL, 1.5 mmol). Purification by column chromatography
0
.147 mL, 1.5 mmol). Purification by column chromatography
1
1
(
hexane/EtOAc, 90:10) yielded 6f (38 %). H NMR (300 MHz,
CDCl ): δ = 7.84 (d, 1 H), 7.70 (dd, 1 H), 7.51 (d, 1 H), 7.33–7.27
m, 2 H), 6.98 (dd, 2 H), 6.56 (t, 1 H), 6.31 (dd, 2 H), 4.31 (t, 4
(hexane/EtOAc, 70:30) yielded 6l (76 %). H NMR (300 MHz,
3
CDCl
3
): δ = 8.16 (s, 2 H), 7.85 (d, 1 H), 7.52 (d, 1 H), 7.11 (d, J
(
= 16 Hz, 2 H), 6.58 (t, 1 H), 6.41 (d, J = 16 Hz, 2 H), 4.14 (t, 4
1
3
13
H), 1.64–1.57 (m, 4 H), 1.40–1.33 (m, 4 H), 0.93 (t, 6 H) ppm.
C
H), 1.66–1.58 (m, 4 H), 1.42–1.34 (m, 4 H), 0.93 (t, 6 H) ppm.
): δ = 167.4, 165.9, 141.8, 140.8, 137.8,
134.5, 133.9, 132.8, 127.1, 122.8, 107.7, 64.6, 30.5, 19.6,13.6 ppm.
C
NMR (75 MHz, CDCl ): δ = 166.4, 163.6, 160.1, 141.6, 137.7, NMR (75 MHz, CDCl
3
3
1
3
32.5, 128.5, 125.9, 121.5, 117.5, 116.2, 115.9, 115.5, 107.6, 64.6,
+
+
0.5, 19.1, 13.7 ppm. MS (ESI): m/z = 415 [M + H] . HRMS:
29 3 5
MS (ESI): m/z = 440 [M + H] . HRMS: calcd. for C24H N O
+
[M + H]+ 440.21738; found 440.21800.
calcd. for C23
H
28FN
2
O
4
[M + H] 415.20413; found 415.20276.
Eur. J. Org. Chem. 2015, 6025–6032
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6031

S. Shome, S. P. Singh
FULL PAPER
Supporting Information (see footnote on the first page of this arti-
[25] I. Fabre, N. von Wolff, G. Le Duc, E. Ferrer-Flegeau, C. Bru-
cle): Copies of the 1H NMR and 13C NMR spectra of all final
products.
neau, P. H. Dixneuf, A. Jutand, Chem. Eur. J. 2013, 19, 7595–
7
604.
[
26] T. Ueyama, S. Mochida, T. Fukutani, K. Hirano, T. Satoh, M.
Miura, Org. Lett. 2011, 13, 706–708.
[
27] L. Ackermann, J. Phosphech, Org. Lett. 2011, 13, 4153–4155.
Acknowledgments
[28] L. Ackermann, N. Hofmann, R. Vicente, Org. Lett. 2011, 13,
1
875–1877.
29] L. Ackermann, E. Diers, A. Manvar, Org. Lett. 2012, 14, 1154–
157.
[
The authors are grateful to the Department of Science & Technol-
ogy (DST), New Delhi (CS-83/2012, Fast Track Young Scientist
Project) for financial support.
1
[
[
30] K. Padala, M. Jeganmohan, Org. Lett. 2011, 13, 6144–6147.
31] M. Matsuo, K. Tsuji, N. Konishi, K. Nakamura, EP Patent,
4
18845, 1991 [Chem. Abstr. 1991, 115, 71593z].
[
32] M. Matsuo, K. Tsuji, T. Ogino, N. Konishi, EP Patent, 554829,
[
[
[
1] A. B. Dounay, L. E. Overman, Chem. Rev. 2003, 103, 2945–
964.
2] I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009–
066.
3] A. de Meijere, F. E. Meyer, Angew. Chem. Int. Ed. Engl. 1995,
1993 [Chem. Abstr. 1994, 120, 8589r].
2
[33] J. J. Tolley, T. D. Penning, P. W. Collins, D. J. Rogier Jr., J. W.
Malecha, J. M. Miyashiro, S. R. Bertenshaw, I. K. Khanna,
M. J. Granets, P. S. Rodge, D. S. Karter, S. J. Dokter, S. S. Iyu,
WO Patent, 9515316, 1993 [Chem. Abstr. 1995, 123, 340112h].
[34] B. G. Antipov, V. A. Kim, V. S. Lisitsa, Y. F. Nadysev, RU
Patent, 2132187, 1999 [Chem. Abstr. 2001, 133, 213139d].
[35] F. Pozgan, P. H. Dixneuf, Adv. Synth. Catal. 2009, 351, 1737–
1743.
3
3
3, 2379–2411; Angew. Chem. 1994, 106, 2473–2506.
[
[
[
4] R. F. Heck, Org. React. 2005, 43.
5] R. F. Heck, Acc. Chem. Res. 1979, 12, 146.
6] L. Ackermann, Modern Arylation Methods, Wiley-VCH,
Weinheim, Germany, 2009.
[36] P. Arockiam, V. Poirier, C. Fischmeister, C. Bruneau, P. H.
Dixneuf, Green Chem. 2009, 11, 1871–1875.
[37] P. B. Arockiam, C. Fischmeister, C. Bruneau, P. H. Dixneuf,
Angew. Chem. Int. Ed. 2010, 49, 6629–6632; Angew. Chem.
2010, 122, 6779–6782.
[38] I. D. Özdemir, S. B. Cetinkaya, C. Gourlaouen, F. Maseras, C.
Bruneau, P. H. Dixneuf, J. Am. Chem. Soc. 2008, 130, 1156–
1157.
[39] P. B. Arockiam, C. Fischmeister, C. Bruneau, P. H. Dixneuf,
Green Chem. 2011, 13, 3075–3078.
[40] C. J. Li, Handbook of Green Chemistry, vol. 5: Green Solvents,
Reactions in Water, Wiley-VCH, Weinheim, Germany, 2010.
[41] C. J. Li, Acc. Chem. Res. 2010, 43, 581–590.
[42] B. H. Lipshutz, A. R. Abela, Z. V. Boskovic, T. Nishikata, C.
Duplais, A. Krasovskiy, Top. Catal. 2010, 53, 985–990.
[43] R. N. Butler, A. G. Coyne, Chem. Rev. 2010, 110, 6302–6337.
[44] C. I. Herrerias, X. Yao, Z. Li, C. J. Li, Chem. Rev. 2007, 107,
2546–2562.
[7] A. de Mejijere, F. Diederich (Eds.), Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed., Wiley-VCH, Weinheim, Germany,
2004.
[
[
[
[
[
[
[
8] Y. Fujiwara, I. Moritani, M. Matsuda, S. Teranishi, Tetrahe-
dron 1968, 25, 4815–4818.
9] C. Jia, T. Kitamura, Y. Fujiwara, Acc. Chem. Res. 2001, 34,
633–639.
10] M. Yu, Z. Liang, Y. Wang, Y. Zhang, J. Org. Chem. 2011, 76,
987–4994.
11] K. J. Stowers, K. C. Fortner, M. S. Sanford, J. Am. Chem. Soc.
011, 133, 6541–6544.
12] D. H. Wang, K. M. Engle, B. F. Shi, J. Q. Yu, Science 2010,
27, 315–319.
13] A. Vasseur, J. Muzart, J. Le Bras, Chem. Eur. J. 2011, 17,
2556–12560.
4
2
3
1
14] M. P. Huestis, L. Chan, D. R. Stuart, K. Fagnou, Angew.
Chem. Int. Ed. 2011, 50, 1338–1341; Angew. Chem. 2011, 123,
1
374–1377.
15] A. S. Tsai, M. Brasse, R. G. Bergman, J. A. Ellman, Org. Lett.
011, 13, 540–542.
16] T. K. Hyster, T. Rovis, J. Am. Chem. Soc. 2010, 132, 10565–
0569.
17] N. Guimond, K. Fagnou, J. Am. Chem. Soc. 2009, 131, 12050–
2051.
18] T. Fukutani, N. Umeda, K. Hirano, T. Satoh, M. Miura,
Chem. Commun. 2009, 5141–5143.
19] M. Krishnamoorthy, H. Radhakrishnan, P. Sekar, C. C. Hong,
Adv. Synth. Catal. 2015, 357, 761–766.
20] M. Shimizu, K. Hirano, T. Satoh, M. Miura, J. Org. Chem.
009, 74, 3478–3483.
21] S. Mochida, K. Hirano, T. Satoh, M. Miura, Org. Lett. 2010,
2, 5776–5779.
22] L. Ackermann, J. Phosphech, H. K. Potukuchi, Org. Lett.
012, 14, 2146–2149.
23] H. Weissman, X. Song, D. Milstein, J. Am. Chem. Soc. 2001,
23, 337–338.
[45] K. Graczyk, W. Ma, L. Ackermann, Org. Lett. 2012, 14, 4110–
[
[
[
[
[
[
[
[
[
[
4113.
2
[46] B. Li, K. Devaraj, C. Darcel, P. H. Dixneuf, Green Chem. 2012,
14, 2706–2709.
1
[47] V. Yu. Kukushkin, A. J. L. Pombeiro, Inorg. Chim. Acta 2005,
358,1–21.
1
[48] T. Ueyama, S. Mochida, T. Fukutani, K. Hirano, T. Satoh, M.
Miura, Org. Lett. 2011, 13, 706–708.
[49] L. Q. Zhang, S. Yang, X. Huang, J. You, F. Song, Chem. Com-
mun. 2013, 49, 8830–8832.
[50] S. R. Borhade, S. B. Waghmode, Tetrahedron Lett. 2008, 49,
3423–3429.
2
[51] Y.-Q. He, Y.-W. Zhong, Chem. Commun. 2015, 51, 3411–3414.
[52] K. Malinowska, E. Gałecka, R. Modranka, M. Rutkowski, J.
Kedziora, Pol. Merk. Lek. 2008, 24, 151–157.
[53] T. Marc, X. Ning, O. Armelle, Angew. Chem. Int. Ed. 2007, 46,
934–936; Angew. Chem. 2007, 119, 952–954.
[54] L. Ackermann, R. Vicente, H. K. Potukuchi, V. Pirovano, Org.
Lett. 2010, 12, 5032–5035.
1
2
1
24] E. Ferrer-Flegeau, C. Bruneau, P. H. Dixneuf, A. Jutand, J.
Am. Chem. Soc. 2011, 133, 10161–10170.
Received: May 15, 2015
Published Online: August 6, 2015
6032
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6025–6032