Copper-free oxime-palladacycle-catalyzed sonogashira alkynylation of deactivated aryl bromides and chlorides in water under microwave irradiation

Article abstract of DOI:10.1002/ejoc.201300785

Palladium-catalyzed Heck alkynylation cross-coupling reactions between terminal alkynes and deactivated aryl chlorides and aryl bromides can be performed in the absence of copper cocatalyst with water as solvent at 130 °C under microwave irradiation. An oxime-derived chloro-bridged palladacycle is an efficient precatalyst for this transformation with 2- dicyclohexylphosphanyl-2',4',6'-triisopropylbiphenyl (XPhos as ancillary ligand, pyrrolidine as base, and SBDS as surfactant. All of the reactions can be performed under air and with reagent-grade chemicals under low loading conditions (0.1-1 mol-% Pd). Deactivated and hindered aryl bromides and chlorides are cross-coupled with terminal alkynes by using low catalyst loadings of an oxime palladacycle, pyrrolidine as base, sodium dodecylbenzenesulfonate (SBDS as surfactant, water as solvent, and microwave irradiation (40 W at 130 °C. Under these reaction conditions a wide array of tolane derivatives are prepared in moderate-to-good yields. Copyright

Full text of DOI:10.1002/ejoc.201300785

FULL PAPER
DOI: 10.1002/ejoc.201300785
Copper-Free Oxime–Palladacycle-Catalyzed Sonogashira Alkynylation of
Deactivated Aryl Bromides and Chlorides in Water under Microwave
Irradiation
Eduardo Buxaderas,[a] Diego A. Alonso,*[a] and Carmen Nájera*[a]
Keywords: Cross-coupling / Microwave chemistry / Palladium / Aryl halides / Alkynes
Palladium-catalyzed Heck alkynylation cross-coupling reac-
tions between terminal alkynes and deactivated aryl chlor-
ides and aryl bromides can be performed in the absence of
copper cocatalyst with water as solvent at 130 °C under mi-
crowave irradiation. An oxime-derived chloro-bridged palla-
dacycle is an efficient precatalyst for this transformation
with 2-dicyclohexylphosphanyl-2Ј,4Ј,6Ј-triisopropylbiphenyl
(XPhos) as ancillary ligand, pyrrolidine as base, and SBDS as
surfactant. All of the reactions can be performed under air
and with reagent-grade chemicals under low loading condi-
tions (0.1–1 mol-% Pd).
ladacycles[11] (1, Figure 1) in a wide variety of cross-cou-
pling reactions with organic and aqueous solvents.[12] Par-
ticularly interesting results are those couplings performed
with neat water as solvent and deactivated electrophiles,
such as aryl chlorides (Suzuki reaction)[13] and aryl imid-
azolylsulfonates (Suzuki[14] and Sonogashira reactions),[6] in
the presence of surfactants.[7h,7l] In continuation of our ex-
ploration on the application of oxime palladacycles under
green conditions, we herein describe the Sonogashira cou-
pling reaction of deactivated aryl bromides and chlorides in
water under microwave (MW) irradiation.
Introduction
Palladium-catalyzed reactions for carbon–carbon and
carbon–heteroatom bond formations have gained a pre-
dominant place in the arsenal of synthetic chemists.[1] In
organic synthesis, among the leading “named” Pd-catalyzed
reactions, the Sonogashira–Hagihara coupling[2] is one of
the most important and widely used methods for the prepa-
ration of aryl- and alkylacetylenes as well as conjugated en-
ynes, which are precursors for natural products, pharma-
ceuticals, and optical and electronic materials.[2,3] Given the
relevance of the Sonogashira reaction, the design of sustain-
able protocols for green aqueous couplings[4] is nowadays
considered of high practical value, especially when deacti-
vated electrophiles such as aryl chlorides[5] and hydroxy-
arene derivatives[6] are involved in the process. The use of
water as a solvent in Pd-catalyzed reactions has gained in-
creasing attention during recent years[7] owing to the envi-
ronmental and economic benefits of replacing organic sol-
vents by water as well as its interesting chemical properties,
including high polarity and strong hydrogen-bonding abil-
ity, among others. However, with water as solvent, mostly
aryl iodides[8] and bromides[9] have been used as coupling
partners and only a few reports can be found on the suc-
cessful coupling of activated aryl chlorides.[5,10] In recent
years, we have demonstrated the high activity of oxime pal-
Figure 1. Oxime palladacycle catalysts.
Results and Discussion
Deactivated aryl chlorides are good indicators of optimal
catalyst performance. Thus, we initially investigated the mi-
crowave-promoted Sonogashira coupling of phenylacetyl-
ene (2a, 1.2 equiv.) with 4-chlorotoluene (3a, 1 equiv.) in
water in the presence of hexadecyltrimethylammonium
bromide (CTAB, 0.4 equiv.) as additive and triethylamine
(TEA, 2 equiv.) as base (Table 1). With an initial microwave
irradiation of 40 W, the reaction temperature was main-
tained at 130 °C for 30 min. As catalyst, oxime palladacycle
1b (1 mol-% Pd) in the presence of 2-dicyclohexylphos-
phanyl-2Ј,6Ј-dimethoxybiphenyl (SPhos, 2 mol-%) was se-
[a] Departamento de Química Orgánica & Instituto de Síntesis
Orgánica, Universidad de Alicante,
Carretera de San Vicente del Raspeig s/n, 03690 San Vicente
del Raspeig, Alicante, Spain
E-mail: diego.alonso@ua.es
cnajera@ua.es
Homepage: https://sites.google.com/site/diegoalonsolab/
http://iso.ua.es/es/personal/investigadores/
carmen-najera-domingo.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300785.
5864
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5864–5870

Sonogashira Alkynylation in Water under Microwave Irradiation
lected owing to the high activity of this catalytic system for phenylacetylene.[16] Indeed, the formation of linear enynes
the alkynylation of aryl imidazolylsulfonates in water.[6,15] from terminal alkynes, that is, head-to-head coupled prod-
Unfortunately, under these conditions (Table 1, Entry 1), ucts, has been previously achieved by employing a range of
the reaction afforded 1-methyl-4-(phenylethynyl)benzene metal catalysts.[17] An optimization of the reaction condi-
(4a) in only 14% isolated yield together with the enyne (E)- tions was then performed to improve the yield and espe-
but-1-en-3-yne-1,4-diyldibenzene (5a) in 7% yield. The for- cially the selectivity of the process (Table 1). When the reac-
mation of 5a has been previously detected in Heck alk- tion was performed under the same reaction conditions, but
ynylations of deactivated aryl chlorides and it is postulated with oxime catalyst 1a (1 mol-% Pd), negligible amounts of
to occur by a Pd-catalyzed head-to-head dimerization of 5a were observed in the crude reaction mixture, but a low
reaction conversion to 4a (21%) was still detected (Table 1,
Entry 2). A conversion of 77%was obtained when pyrrol-
idine was used as base regardless of the amount of surfac-
tant used (Table 1, Entries 3 and 4).
Table 1. Sonogashira alkynylation of 4-chlorotoluene with phenyl-
acetylene. Optimization of reaction conditions.
Then, a ligand study was performed with the most
chemoselective catalyst and base, namely, 1a and pyrrol-
idine, (see Supporting Information), which showed that 2-
dicyclohexylphosphanyl-2Ј,4Ј,6Ј-triisopropylbiphenyl
(XPhos) was the most effective ligand; compound 4a was
obtained in a 60% isolated yield when 1 equiv. of CTAB
was used (Table 1, Entry 6). Lisphutz has shown that
XPhos is the most effective ligand for the palladium-cata-
lyzed Sonogashira coupling of aryl bromides in water at
room temperature with polyoxyethanyl-α-tocopheryl seba-
cate (PTS) as surfactant.[9c] The effect of the surfactant on
the activity of the catalytic system was then studied
(Table 1, Entries 7–11). Nonionic surfactants, such as the
polyethers polyoxyethylene lauryl ether (Brij35) and poly-
ethylene glycol hexadecyl ether (BrijC10) as well as the an-
ionic sodium dodecyl benzene sulfonate (SDBS), afforded
good yields of 4a; the latter afforded the highest yield (76%,
Table 1, Entry 10).
Entry Pd cat. Ligand[a]
Surfactant
(equiv.)[b]
Base
Yield [%][c]
Significant sensitivity to base was also noted (Table 1,
Entries 12–16). Thus, good isolated yields were obtained
with other organic (dicyclohexylamine and piperidine) and
inorganic bases (K2CO3), though these experiments did not
improve the ability of pyrrolidine in this process.[18]
Regarding the catalyst, a 24% yield of 4a was obtained
under the optimized reaction conditions when oxime-de-
rived palladacycle 1b (1 mol-% Pd) was employed as cata-
lyst (Table 1, Entry 17). Other Pd sources such as Pd2-
(dba)3 (dba = dibenzylideneacetone) and Pd(OAc)2 were
also less effective than 1a and afforded lower yields of 4a
(Table 1, Entries 18 and 19).
1
2
3
4
5
6
7
8
1b
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
SPhos
SPhos
SPhos
SPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
CTAB (0.4)
CTAB (0.4)
CTAB (0.4)
CTAB (1)
CTAB (0.4)
CTAB (1)
PTS (1)
Brij 35 (1)
Brij C10 (1)
SDBS (1)
TBAB (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
SDBS (1)
TEA
TEA
pyrrolidine 77
50 (14)[d]
21
pyrrolidine 77
pyrrolidine 84 (54)
pyrrolidine 90 (60)
pyrrolidine 95 (40)
pyrrolidine Ͼ 95 (73)
pyrrolidine Ͼ 95 (73)
pyrrolidine Ͼ 95 (76)
pyrrolidine 65
TEA
ipr2EtN
Cy2NH
piperidine 89 (63)
K2CO3 90 (63)
pyrrolidine Ͼ 95 (24)
pyrrolidine 80 (40)
pyrrolidine 90 (68)
pyrrolidine (24)[g]
9
10
11
12
13
14
15
16
17
18
19
20
54
50
87 (54)
Finally, the efficiency of the microwave irradiation was
demonstrated as only a 24% reaction yield was obtained
when the reaction was performed under conventional ther-
mal conditions (130 °C, 24 h; Table 1, Entry 20).
1b
[e]
[f]
1a
To test the effectiveness of the optimized catalytic system
[a] XPhos: 2-dicyclohexylphosphanyl-2Ј,4Ј,6Ј-triisopropylbiphenyl; in the Pd-catalyzed Sonogashira coupling in water, a range
SPhos: 2-dicyclohexylphosphanyl-2Ј,6Ј-dimethoxybiphenyl. [b]
of aryl- and alkyl-substituted terminal alkynes were exam-
CTAB: hexadecyltrimethylammonium bromide; PTS: polyoxy-
ined in the reaction with different aryl chlorides (Table 2).
ethanyl-α-tocopheryl sebacate; Brij 35: polyoxyethylene lauryl
As previously described for 4-chlorotoluene, deactivated 4-
ether, Brij C10: polyethylene glycol hexadecyl ether; SDBS: sodium
chloroanisole was coupled with phenylacetylene to afford
4-methoxytolane in 80% yield (Table 2, Entry 2). The cou-
pling of these two deactivated aryl chlorides with electron-
rich terminal alkynes, such as (4-methoxyphenyl)acetylene,
(4-methyphenyl)acetylene, and (2-aminophenyl)acetylene,
led to the corresponding 1,2-diarylalkynes 4c and 4d in
dodecyl benzene sulfonate; TBAB: tetrabutylammonium bromide.
[c] Conversion determined by GC analysis. In parenthesis, isolated
yield after preparative thin layer chromatography. [d] A 7% yield
of (E)-but-1-en-3-yne-1,4-diyldibenzene (5a) was also obtained. [e]
Pd2(dba)3 (1 mol-% Pd) was used as catalyst. [f] Pd(OAc)2 (1 mol-
% Pd) was used as catalyst. [g] Isolated yield when the reaction was
performed under conventional thermal conditions (130 °C, 24 h).
Eur. J. Org. Chem. 2013, 5864–5870
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5865

E. Buxaderas, D. A. Alonso, C. Nájera
FULL PAPER
moderate-to-good yields (47–63%; Table 1, Entries 3–5). A underwent coupling with phenylacetylene to produce the
40% yield of the donor–acceptor tolane derivative 4e with desired alkyne 4i in a 63% isolated yield (Table 2, Entry 10).
potential optoelectronic properties[19] was obtained when 4- The coupling of heterocyclic 2-chloropyridine and 2-chloro-
chlorotoluene was coupled with the electron-poor 4-(tri- thiophene with phenylacetylene afforded the Sonogashira
fluoromethyl)phenylacetylene, a result that is in accordance derivatives 4j and 4k in 87 and 53% yield, respectively
with the low reactivity of alkynes bearing electron-with- (Table 2, Entries 11 and 12). Finally, the reactions of acti-
drawing groups (Table 2, Entry 6) in Sonogashira reactions. vated 4-acetylchlorobenzene and 4-(trifluoromethyl)benz-
The scope of this coupling was extended to other alkynes ene with phenylacetylene afforded 4l and 4m in a 84 and
such as N,N-dimethyl-2-propynylamine, cyclohexylacetyl- 80% isolated yield, respectively (Table 2, Entries 13 and 14).
ene, and 1-dodecyne, which after coupling with 4-chloroan-
Under the optimized reaction conditions for the Sonoga-
isole and 4-chlorotoluene afforded disubstituted alkynes 4f, shira coupling of aryl chlorides, we also evaluated the alk-
4g, and 4h in 50, 20, and 20% yield, respectively (Table 2, ynylation of aryl bromides in water (Table 3). After a cata-
Entries 7–9).
Hindered
2-chloro-1,3-dimethylbenzene lyst, temperature, and catalyst loading study (see Support-
Table 2. Sonogashira alkynylation of aryl chlorides.
[a] Isolated yield after preparative thin layer chromatography.
5866
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5864–5870

Sonogashira Alkynylation in Water under Microwave Irradiation
ing Information), we demonstrated that oxime palladacycle alkyne with an alkene functionality, such as 1-ethynylcy-
1a was the most active palladium source for these more clohexene, underwent Sonogashira coupling with 4-bromo-
active electrophiles and that the palladium loading could be anisole to afford the conjugated enyne 4n in 49% yield
reduced to 0.1 mol-%. As expected, 4-bromotoluene and 4- (Table 3, Entry 7). In a similar fashion, we next examined
bromoanisole afforded the desired products in high isolated aliphatic alkynes as coupling partners with 4-bromotoluene
yields after reaction with phenylacetylene and electron-rich and 4-bromoanisole. Again, we observed that, in general,
alkynes such as (4-methoxyphenyl)acetylene and 4-tolyl- aliphatic alkynes showed lower reactivities than arylalkynes.
acetylene respectively (Table 3, Entries 1–2 and 4–5). Lower The coupling reaction of 4-bromotoluene and 4-bromoan-
yields were observed for electron-poor nucleophiles, as isole with cyclohexylacetylene afforded disubstituted alk-
found in the reaction between 4-chloroanisole and (4-tri- ynes 4g and 4o in 40 and 37% yield, respectively (Table 3,
fluoromethylphenyl)acetylene, which led to the tolane deriv- Entries 3 and 9). A 61% yield of the semicarbazide-sensitive
ative 4e in 51% isolated yield (Table 3, Entry 6). A terminal amine oxidase (SSAO) inhibitor[20] 4f was obtained when 4-
Table 3. Sonogashira alkynylation of aryl bromides.
[a] Isolated yield after preparative thin-layer chromatography.
Eur. J. Org. Chem. 2013, 5864–5870
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5867

E. Buxaderas, D. A. Alonso, C. Nájera
FULL PAPER
Scheme 1. Sonogashira coupling with 1-phenyl-2-(trimethylsilyl)acetylene.
bromoanisole reacted with N,N-dimethyl-2-propynylamine
On the other hand, the reaction of 4-chloro- and 4-
under the optimized conditions (Table 3, Entry 8). A low bromoanisole with 2-methylbut-3-yn-2-ol afforded a mix-
30% yield of alkyne 4h was obtained by reaction of 4- ture of 4q and 6, as a consequence of the mono- or double
bromoanisole with 1-dodecyne (Table 3, Entry 10). The alk- alkynylation reaction with the acetylenic nucleophile
ynylation of the sterically hindered 2-bromo-1,3-dimeth- (Scheme 2).
ylbenzene with phenylacetylene and 4-tolylacetylene af-
Finally, we also studied the reactivity of deactivated aryl
forded 4i and 4p in 69 and 61% yield, respectively (Table 3, iodides in the Sonogashira reaction in water under the opti-
Entries 11 and 12). Good isolated yields were also obtained mized reaction conditions. With the catalyst loading em-
for the coupling of 2-bromopyridine and 2-bromothiophene ployed for aryl bromides, good isolated yields were ob-
with phenylacetylene, which led to the Sonogashira cou- tained for the coupling of 4-iodotoluene and 4-iodoanisole
pling products 4j and 4k in 91 and 63% yield, respectively with phenylacetylene, as depicted in Scheme 3.
(Table 3, Entries 13 and 14). Finally, the reaction between
activated 4-acetylbromobenzene and phenylacetylene af-
forded 4l in 87% isolated yield (Table 3, Entry 15).
We then decided to investigate the catalytic activity of
1a in the cross-coupling reaction between deactivated aryl
bromides and chlorides and other alkynes. Firstly, we
studied the coupling with silylated alkynes. As depicted in
Scheme 1, the reactions of 4-chloro- and 4-bromoanisole
with 1-phenyl-2-(trimethylsilyl)acetylene afforded 4-meth-
oxytolane (4b) in 51 and 70% yield, respectively, under the
Scheme 3. Sonogashira coupling of deactivated aryl iodides in
optimized reaction conditions through a desilylation/cross-
water.
coupling sequence.[21]
Conclusions
We have disclosed a copper-free oxime palladacycle-cata-
lyzed Sonogashira cross-coupling reaction of deactivated
aryl chlorides and aryl bromides with aryl- and alkyl-substi-
tuted terminal alkynes with water as solvent under micro-
wave irradiation. This reaction is performed in the presence
of XPhos as ligand (0.2–2 mol-%), SDBS as surfactant, and
the bench-stable oxime palladacycle 1a as precatalyst under
low loading conditions (0.1–1 mol-% Pd).
Experimental Section
Typical Procedure for the Sonogashira Coupling Under MW Irradia-
tion Conditions: A 10 mL MW vessel was charged with 4-chlorotol-
uene (0.038 g, 0.3 mmol, 1 equiv.), phenylacetylene (0.040 mL,
0.36 mmol, 1.2 equiv.), pyrrolidine (0.050 mL, 0.6 mmol, 2 equiv.),
sodium dodecylbenzenesulfonate (0.1045 g, 0.3 mmol, 100 mol-%),
Scheme 2. Sonogashira coupling with 2-methylbut-3-yn-2-ol.
5868
catalyst 1a (0.0012 g, 1 mol-% Pd), XPhos (0.0029 g, 2 mol-%), and
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5864–5870

Sonogashira Alkynylation in Water under Microwave Irradiation
thesis (Ed.: E. Negishi), Wiley, Hoboken, 2002, vol, 2, p. 2957;
d) Aqueous-Phase Organometallic Catalysis: Concepts and Ap-
plications, 2nd ed. (Eds.: B. Cornils, W. Herrmann), Wiley-
VCH, Weinheim, Germany, 2004; e) K. H. Shaughnessy, R. B.
DeVasher, Curr. Org. Chem. 2005, 9, 585; f) S. Liu, J. Xiao, J.
Mol. Catal. A 2007, 270, 1; g) R. A. Sheldon, in: Organic Reac-
tions in Water: Principles, Strategies and Applications (Ed.:
U. M. Lindström), Blackwell Publishing Ltd, Oxford, 2007; h)
B. H. Lipshutz, S. Ghorai, Aldrichim. Acta 2008, 41, 59; i) J.-
P. Genêt, S. Darses, V. Michelet, Pure Appl. Chem. 2008, 80,
831; j) M. Carril, R. SanMartín, E. Domínguez, Chem. Soc.
Rev. 2008, 37, 639; k) K. H. Shaughnessy, Chem. Rev. 2009,
H2O (1.5 mL). The vessel was sealed with a pressure lock, and the
mixture was heated at 130 °C for 30 min with the aid of an initial
40 W MW irradiation in a CEM Discover MW reactor. After this
time, the reaction mixture was extracted with EtOAc (3ϫ 10 mL),
and the organic layers were washed with H2O (3ϫ 10 mL), dried
with MgSO4, filtered through Celite, and concentrated under re-
duced pressure. The crude residue was purified by preparative thin
layer chromatography (hexane) to obtain the corresponding pure
coupling compound (0.044 g, 76% yield).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures for the cross-coupling reactions as
well as spectroscopic data for all synthesized products.
ˇ
109, 643; l) B. H. Lipshutz, A. R. Abela, Z. V. Bosˇkovic´, T.
Nishikata, C. Duplais, A. Krasovskiy, Top. Catal. 2010, 53,
985; m) A. R. Abela, S. Huang, R. Moser, B. H. Lipshutz,
Chim. Oggi 2010, 28, 50; n) M. Lamblin, L. Nassar-Hardy, J.-
C. Hierso, E. Fouquet, F.-X. Felpin, Adv. Synth. Catal. 2010,
352, 33.
[8]
[9]
For representative Sonogashira couplings of aryl iodides in
water, see: a) S. Bhattacharya, S. Sengupta, Tetrahedron Lett.
2004, 45, 8733–8736; b) B. Liang, M. D. Dai, J. Chen, Z. Yang,
J. Org. Chem. 2005, 70, 391–393; c) M. Bakherad, A. Keivan-
loo, B. Bahramian, M. Hashemi, Tetrahedron Lett. 2009, 50,
1557–1559; d) D. Saha, R. Dey, B. C. Ranu, Eur. J. Org. Chem.
2010, 6067–6071.
For representative Sonogashira couplings of aryl bromides in
water, see: a) C. Nájera, J. Gil-Moltó, S. Karlström, L. R. Fal-
vello, Org. Lett. 2003, 5, 1451–1454; b) J. Gil-Moltó, C. Nájera,
Adv. Synth. Catal. 2006, 348, 1874–1882; c) B. H. Lipshutz,
D. W. Chung, B. Rich, Org. Lett. 2008, 10, 3793–3796; d) K.
Park, J.-M. You, S. Jeon, S. Lee, Eur. J. Org. Chem. 2013, 1973–
1978.
a) C. Wolf, R. Lerebours, Org. Biomol. Chem. 2004, 2, 2161;
b) E. A. Reddy, D. K. Barange, A. Islam, K. Mukkanti, M.
Pal, Tetrahedron 2008, 64, 7143.
Palladacycles: Synthesis Characterization and Applications
(Eds.: J. Dupont, M. Pfeffer), Wiley-VCH, Weinheim, Ger-
many, 2008.
For reviews on the use of oxime palladacycles as precatalysts
in cross-coupling reactions, see: a) D. A. Alonso, L. Botella, C.
Nájera, M. C. Pacheco, Synthesis 2004, 1713; b) E. Alacid,
D. A. Alonso, L. Botella, C. Nájera, M. C. Pacheco, Chem.
Rec. 2006, 6, 117; c) D. A. Alonso, C. Nájera, Chem. Soc. Rev.
2010, 39, 2891.
L. Botella, C. Nájera, Angew. Chem. 2002, 114, 187; Angew.
Chem. Int. Ed. 2002, 41, 179–181.
J. F. Cívicos, D. A. Alonso, C. Nájera, Adv. Synth. Catal. 2012,
354, 2771–2776.
Previous studies in our group have shown that palladacycle 1b
is the most effective for the Sonogashira coupling of aryl brom-
ides and iodides in organic solvents: D. A. Alonso, C. Nájera,
M. C. Pacheco, Adv. Synth. Catal. 2003, 345, 1146–1158.
X. Pu, H. Li, T. J. Colacot, J. Org. Chem. 2013, 78, 658 and
references cited therein.
For a palladium-catalyzed head-to-head dimerization of ter-
minal alkynes, see: a) M. Rubina, V. Gevorgyan, J. Am. Chem.
Soc. 2001, 123, 11107–11108; For an iron-catalyzed head-to-
head dimerization of terminal alkynes, see: b) G. C. Midya, S.
Paladhi, K. Dhara, J. Dash, Chem. Commun. 2011, 47, 6698–
6700; for iridium-catalyzed head-to-head dimerization of ter-
minal alkynes, see: c) T. Ohmura, S. Yorozuya, Y. Yamamoto,
N. Miyaura, Organometallics 2000, 19, 365–367; d) C. D. For-
syth, W. J. Kerr, L. C. Peterson, Synlett 2013, 587–590. For a
nickel-catalyzed head-to-head dimerization of terminal al-
kynes, see: e) S. Ogoshi, M. Ueta, M. Oka, H. Kurosawa,
Chem. Commun. 2004, 2732–2733; For a rhodium-catalyzed
head-to-head dimerization of terminal alkynes, see: T. Katagiri,
H. Tsurugi, T. Satoh, M. Miura, Chem. Commun. 2008, 3405–
3407.
Acknowledgments
Financial support from the Ministerio de Economía y Competitivi-
dad (MINECO) (project CTQ2010-20387), Consolider INGENIO
(project 2010 CSD2007-00006), Fondos Europeos para el Desar-
rollo Regional (FEDER), the Generalitat Valenciana (project PRO-
METEO/2009/038), and the University of Alicante is acknowl-
edged.
[1] a) Metal-Catalyzed Cross-Coupling Reactions, (Eds.: F. Dieder-
ich, P. J. Stang), Wiley-VCH, Weinheim, Germany, 1998; b)
Handbook of Organopalladium Chemistry for Organic Synthesis
(Ed.: E. Negishi), Wiley-Interscience, New York, 2002; c)
Cross-Coupling Reactions. A Practical Guide (Ed.: N. Miyaura),
Springer, Berlin, 2002; d) J. Tsuji, Palladium Reagents and Cata-
lysts. Innovations in Organic Synthesis Wiley, Chichester, UK,
2004; e) V. Farina, N. Miyaura, S. L. Buchwald, Adv. Synth.
Catal. 2004, 346, 1505; f) Metal-Catalyzed Cross-Coupling Re-
actions, 2nd ed. (Eds.: F. Diederich, A. de Meijere), Wiley-
VCH, Weinheim, Germany, 2004; g) E. Negishi, Bull. Chem.
Soc. Jpn. 2007, 80, 233; h) Transition Metals for Organic Syn-
thesis Building Blocks and Fine Chemicals (Eds.: M. Beller, C.
Bolm), Wiley-VCH, Weinheim, Germany, 1998; i) Transition
Metals for Organic Synthesis Building Blocks and Fine Chemi-
cals, 2nd ed. (Eds.: M. Beller, C. Bolm), Wiley-VCH,
Weinheim, Germany, 2004.
[2] For reviews, see: a) K. Sonogashira, J. Organomet. Chem. 2002,
653, 46; b) E.-i. Negishi, L. Anastasia, Chem. Rev. 2003, 103,
1979; c) R. Chinchilla, C. Nájera, Chem. Rev. 2007, 107, 874;
d) H. Doucet, J.-C. Hierso, Angew. Chem. 2007, 119, 850; An-
gew. Chem. Int. Ed. 2007, 46, 834; e) H. Plenio, Angew. Chem.
2008, 120, 7060; Angew. Chem. Int. Ed. 2008, 47, 6954; f) R.
Chinchilla, C. Nájera, Chem. Soc. Rev. 2011, 40, 5084; g) N. M.
Jenny, M. Mayor, T. R. Eaton, Eur. J. Org. Chem. 2011, 4965.
[3] a) N. Weibel, S. Grunder, M. Mayor, Org. Biomol. Chem. 2007,
5, 2343; b) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew.
Chem. 2005, 117, 4516; Angew. Chem. Int. Ed. 2005, 44, 4442;
c) M. Kivala, F. Diederich, Pure Appl. Chem. 2008, 80, 411.
[4] Green Chemistry and Catalysis (Eds.: R. A. Sheldon, I. Arends,
U. Hanefeld), Wiley-VCH, Weinheim, Germany, 2007.
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[5] D. A. Alonso, C. Nájera, in: Science of Synthesis Water in Or-
ganic Synthesis (Ed.: S. Kobayashi), Thieme, Stuttgart, Ger-
many, 2012, vol. 2011/7, p. 535.
[6] J. F. Cívicos, D. A. Alonso, C. Nájera, Adv. Synth. Catal. 2013,
355, 203–208, and references cited therein.
[7] a) Aqueous-Phase Organometallic Catalysis (Eds.: B. Cornils,
W. Herrmann), Wiley-VCH, Weinheim, Germany 1998; b) F.
Joó, Aqueous Organometallic Catalysis, Kluwer Academic Pub-
lishers, Dordrecht, 2001; c) I. P. Beletskaya, A. V. Cheprakov,
in: Handbook of Organopalladium Chemistry for Organic Syn-
Eur. J. Org. Chem. 2013, 5864–5870
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5869

E. Buxaderas, D. A. Alonso, C. Nájera
FULL PAPER
[18]
[20] C. Conn, R. Shimmon, F. Cordaro, T.-L. Hargraves, P. Ib-
rahim, Bioorg. Med. Chem. Lett. 2001, 11, 2565–2568.
[21] Under the optimized reaction conditions but in the absence of
electrophile, 1-phenyl-2-(trimethylsilyl)acetylene was fully con-
verted to phenylacetylene.
At this point, and considering that the ligand study had been
performed with CTAB as additive (see Supporting Infor-
mation), we performed a new study with SDBS as surfactant,
which did not lead to any improvement of the reaction yield
of the reaction (see Supporting Information).
Received: May 27, 2013
Published Online: July 25, 2013
[19] C. R. Moylan, C. A. Walsh, Nonlinear Opt. 1993, 6, 113–121.
5870
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5864–5870