PdCl2-catalyzed cross-coupling reaction of arylacetylene iodides with arylboronic acids to diarylacetylenes

Article abstract of DOI:10.1016/j.tetlet.2010.05.011

A new Suzuki-type cross-coupling reaction between 1-iodo-2-arylalkynes and arylboronic acids to afford a wide variety of functionalized diarylacetylenes in a mild reaction condition was developed. The reaction was catalyzed by a small amount of a structurally simple, commercially available, and stable PdCl ₂. This unique sp-sp² carbon-carbon bond formation provides a new protocol for the synthesis of diarylacetylenes, which is a new addition to the Suzuki cross-coupling reaction.

Full text of DOI:10.1016/j.tetlet.2010.05.011

Tetrahedron Letters 51 (2010) 3626–3628
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
PdCl2-catalyzed cross-coupling reaction of arylacetylene iodides
with arylboronic acids to diarylacetylenes
c
a,d,
Yu Shi a, Xiaoyu Li b, Jianhui Liu a, , Wenfeng Jiang , Licheng Sun
*
*
a State Key Laboratory of Fine Chemicals, DUT-KTH Joint Education and Research Center on Molecular Devices, Dalian University of Technology (DUT), Dalian 116012, PR China
b Dalian Hissen Bio-Pharm. Co., Ltd, No.17 Tieshan West Rd. Dalian Economic and Technological Development Zone, Dalian 116600, PR China
c Department of Chemistry, Dalian University of Technology (DUT), Dalian 110024, PR China
d Department of Chemistry, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden
a r t i c l e i n f o
a b s t r a c t
Article history:
A new Suzuki-type cross-coupling reaction between 1-iodo-2-arylalkynes and arylboronic acids to afford
a wide variety of functionalized diarylacetylenes in a mild reaction condition was developed. The reaction
was catalyzed by a small amount of a structurally simple, commercially available, and stable PdCl2. This
unique sp–sp2 carbon–carbon bond formation provides a new protocol for the synthesis of diarylacetyl-
enes, which is a new addition to the Suzuki cross-coupling reaction.
Received 11 March 2010
Revised 14 April 2010
Accepted 7 May 2010
Available online 12 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Dedicated to Professor Henry N. C. Wong on
the occasion of his 60th birthday
Keywords:
Suzuki cross-coupling
Diarylacetylene
Palladium chloride
Alkynylation
The Suzuki coupling is one of the most versatile and widely
used reactions for the selective construction of a carbon–carbon
bond between organoboron and organic halides or triflates.1 The
original version included the Pd-catalyzed coupling of the vinyl
boronate with an aromatic halide (Br or I) to form the sp2–sp2
C–C bond. Later, it became the most powerful tool for aryl–aryl
cross-coupling. Recently its scope has gradually extended, and
the ability to couple with the sp3-hybridized alkyl halides to form
sp2–sp3 and sp3–sp3 C–C bonds has been extensively explored.2 In
general, aryl, alkenyl, and even alkyl halides were employed in the
organoboron involved reactions, which all use sp2 or sp3 C–X
(X = halogen) substrates to couple with organoboron derivatives.
In contrast, it is quite rare to report the sp2–sp C–C bond formation
by the use of sp C–X bonds and arylboronic acids to afford the
diarylacetylenes due mainly to cross-homo scrambling, although
the sp2–sp alkenyl–alkynyl coupling has been occasionally re-
ported3 (Scheme 1). In this Letter, we disclose a new type of Suzuki
cross-coupling (sp2–sp) from iodoalkynes and arylboronic acids to
form the diarylacetylenes.
TMS groups and coupling with p-methoxyphenylboronic acid
(Scheme 2). The structure of compound 3 was established by
X-ray crystallography (CCDC 768902), although the original struc-
ture was incorrectly defined by routine spectra.4 Obviously it was
formed by iodination of the alkynyltrimethylsilane and then trans-
formed through Suzuki cross-coupling. Selective iodination and the
arylboronic acid coupling with the iodide on the sp carbon atom
were two significant features for such a transformation. As we know
this is the first case of 1-iodo-2-arylalkyne to couple with arylbo-
ronic acid to form diarylacetylene under Suzuki-type condition.
Based on this unexpected result, we were very interested to see if
more reaction examples could be involved under this condition.
To find the optimal reaction conditions, the 4-iodoethynyl ben-
zoic acid methyl ester (4) was used as the electrophile and p-meth-
ylphenyl boronic acid (5) as the nucleophile to perform the Suzuki
reaction under a variety of conditions (Table 1). The reaction was
first tried under the typical Suzuki conditions (entry 1), which have
been used to proceed from pyrrole 2 to pyrrole 3, but the yield was
no more than 50%, and the homo-coupling product 7 was obtained
in a yield of 20%. When the reaction was carried out in MeOH
In our previous studies for the synthesis of 2,3,4-trisubstituted
pyrroles, pyrrole 3 was obtained by iodination of one of the two
R2BR2
1
2
1
R
R
R
X
Pd
* Corresponding authors. Tel.: +86 411 88993886; fax: +86 411 83702185 (J.L.).
E-mail addresses: liujh@dlut.edu.cn (J. Liu), lichengs@kth.se (L. Sun).
Scheme 1. The Pd-catalyzed alkynylation by Suzuki cross-coupling.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.011

Y. Shi et al. / Tetrahedron Letters 51 (2010) 3626–3628
3627
MeO
I
Me Si
3
p-MeOC6H5B(OH)2
Pd(PPh3)4
SiMe
3
SiMe
3
I2, CF3CO2Ag
THF, -78 oC, 1 h
2M Na2CO3
MeOH-PhMe
110 oC, 2 h
SiMe
3
CO Me
CO Me
N
N
2
2
SO NMe
SO NMe
2
2
2
2
CO Me
N
2
1
2
SO NMe
2
2
3
Scheme 2. The transformation of pyrrole 1 to pyrrole 3.
Table 1
The coupling of 4-iodoethynyl benzoic acid methyl ester and p-methylphenylboronic acid as the optimization of reaction conditions
cat. (1-5 mol %)
K2CO3, solvent
MeO2C
+
B(OH)2
I
reflux, 8 h
4
5
+
+
MeO2C
MeO2C
CO2Me
8
6
7
Entry
Catalyst
Temp (°C)
Base
Solvent
Isolated yield (%)
6
7
8
a
a
a
a
a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
80
70
60
60
60
80
80
80
25
80
80
80
80
80
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Toluene/MeOH/H2Od
MeOH
49
17
Trace
39
45
16
12
88
15
—
20
Trace
Trace
25
15
69
75
8
58
—
10
7
—
33
71
—
—
—
—
0
0
—
0
0
0
THF
THF/H2Oe
THF/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
Toluene/MeOH/H2Od
a
Pd(PPh3)2Cl2
a
Pd(OAc)2
b
PdCl2
c
PdCl2
c
NiCl2
b
PdCl2
CH3ONa
NaOH
Et3N
85
88
85
80
b
PdCl2
b
PdCl2
8
10
b
PdCl2
K3PO4
0
a
b
c
The catalyst amount was 2.5 mol %.
The catalyst amount was 1 mol %.
The catalyst amount was 5 mol %.
The ratio of the solvents was 3:3:1.
The ratio of the solvent was 4:1.
d
e
(entry 2), another homo-coupling product 8 was discovered in a
yield of 33%, with the desired product 6 in poor yield. In the case
of THF, the situation was even worse, with trace desired molecule
and a substantial amount of homo-coupling product 8 (entry 3).
When more polar solvent (THF/H2O) was used, a better result
was observed with an increased yield of 6 and less 7 (entry 4).
We can see that H2O plays an important role to facilitate the
cross-coupling reaction and restrain the homo-coupling of aryl-
acetylene iodides. The effective solvent system (THF/MeOH/H2O)
was observed to afford more desired 6 and less by-product 7 (entry
5), but this was still inferior to Toluene/MeOH/H2O (entry 1).
Therefore the original solvent system was utilized, in which the
catalyst screening in the solvent mixture was conducted. When
the reaction was carried out with catalysts PdCl2(PPh3)2 (entry 6)
or Pd(OAc)2 (entry 7), the major product was 7 with yields of
69% and 75%, respectively. When the simple and stable PdCl2 was
employed as the catalyst with the increased amount of p-meth-
ylphenylboronic acid (1.5 equiv), surprisingly, the yield of cross-
coupled product 6 was raised to 88% (entry 8). Different amounts
of PdCl2 (1, 2, 5, 10 mol %) afforded almost the same yield of prod-
uct 6 (88%, 85%, 88%, 86%), respectively. Thus, the subsequent cou-
pling reaction was undertaken with 1–5 mol % of PdCl2. A higher
reaction temperature improved the coupling significantly, whereas
the reaction could not be finished in 24 h, and the major product
was 7 at room temperature (entry 9). Other bases such as CH3ONa,
NaOH, Et3N, and K3PO4 were also employed in parallel reactions,
and the results indicated that the differences of the base hold little
influence over the reaction (entries 11–14). It should be pointed
out that NiCl2 has no catalytic activity (entry 10).
Having optimized the reaction conditions, the experimental
scope was extended to include more Suzuki coupling substrates,
resulting in the successful reactions of various substituted aryl-
acetylene iodides and arylboronic acids (Table 2). The phenyl
subunit on arylethynyl iodide can tolerate different types of sub-
stituents: not only the electron-deficient substrates with –CO2Me,
–CHO, –COMe, and –CN (entries 1–4), but also the electron-rich
substrates with Me and –OMe (entries 6 and 7) reacted smoothly
with arylboronic acid. This method is also suitable for many substi-
tuted arylboronic acids such as naphthyl, 4-methoxyphenyl,
2-hydroxyphenyl, phenyl, and 4-fluorophenylboronic acids
(entries 8–13). It should be noted that in the case of arylboronic
acid with an electron-withdrawing group (F), the reaction pro-
ceeded as well in good yield (entry 13). This catalytic system seems
to allow diverse electron density around the aromatic rings. The

3628
Y. Shi et al. / Tetrahedron Letters 51 (2010) 3626–3628
Table 2
acids, which extends the scope of the Suzuki-coupling reaction.
The coupling of arylacetylene iodides and arylboronic acids
This reaction takes place efficiently with the –CHO group-contain-
ing substrate compared to ordinary Sonogashira coupling reaction.
Although it is two steps longer than the Sonogashira reaction, this
method provides an alternative synthetic pathway for
diarylacetylenes.
PdCl2 (1mol %), K2CO3
Ar1
I
Ar2 B(OH)2
Ar1
Ar2
MeOH-PhMe-H2O,
reflux, 8 h
Entry
Ar1
Ar2
Isolated yield (%)
Acknowledgments
1
2
3
4
5
6
7
MeOOC
OHC
CH3
CH3
CH3
CH3
CH3
88
84a
92
We are grateful to the Ministry of Science and Technology of
China and the Chinese National Natural Science Foundation (Grant
No. 20633020, 20672017), the National Basic Research Program of
China (2009CB220009), the Program for Changjiang Scholars and
Innovative Research Team in University (IRT0711), the K & A Wal-
lenberg Foundation for financial support of this work and the
Swedish Energy Agency and the Swedish Research Council for sup-
port. We also thank Dr. Bradley Stocks at University of Western
Ontario for his careful revision and language improvement to this
Letter.
MeOC
NC
85a
74b,c
82d
OMe
CH3
H3C
79d
69
MeO
Supplementary data
MeOOC
8
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.05.011.
9
MeOOC
MeOC
MeOC
82
84
OMe
OMe
References and notes
10
1. (a) Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979, 866; (b) Miura, M.
Angew. Chem., Int. Ed. 2004, 43, 2201; (c) Molander, G. A.; Biolatto, B. Org. Lett.
2002, 4, 1867; (d) Alonso, F.; Beletskaya, I. P.; Yus, M. Tetrahedron 2008, 64,
3047; (e) Rudolph, A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 2656; (f) Zhou,
J.-R.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340; (g) Kudo, N.; Perseghini, M.; Fu,
G. C. Angew. Chem., Int. Ed. 2006, 45, 1282.
2. (a) Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 9602; (b) Saito, B.; Fu, G. C. J.
Am. Chem. Soc. 2008, 130, 6694; (c) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed.
2005, 44, 674; (d) Netherton, M. R.; Fu, G. C. In Topics in Organometallic
Chemistry: Palladium in Organic Synthesis; Tsuji, J., Ed.; Springer: New York, 2005;
(e) Netherton, M. R.; Fu, G. C. Adv. Synth. Catal. 2004, 346, 1525; (f) Ishiyama, T.;
Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992, 691; (g) Devasagayaraj, A.;
Stüdemann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1995, 34, 2723; (h) Martin,
R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (i) Netherton, M. R.; Dai, C.;
Neuschütz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099.
11
73
HO
MeOC
MeOC
12
13
78
84
F
a
b
c
The solvent is THF/MeOH/H2O.
Yield determined by 1H NMR.
The catalyst amount was 2.5 mol %.
The catalyst amount was 5 mol %.
d
3. (a) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem. Soc. 1985, 107,
972; (b) Brown, H. C.; Molander, G. A. J. Org. Chem. 1981, 46, 645; (c) Miyaura, N.;
Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 3437; (d) Molander, G. A.; Katona,
B. W.; Machrouhi, F. J. Org. Chem. 2002, 67, 8416; (e) Yu, C.-M.; Kweon, J.-H.; Ho,
P.-S.; Kang, S.-C.; Lee, G. Y. Synlett 2005, 2631; (f) Liu, P.-H.; Li, L.; Webb, J. A.;
Zhang, Y.; Goroff, N. S. Org. Lett. 2004, 6, 2081.
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3587; (b) Liu, J.-H.; Yang, Q.-C.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 2009,
74, 6906.
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Lee, D.-H.; Jun, B.-H.; Lee, Y.-S. Tetrahedron Lett. 2007, 48, 7079; (c) Olivier, J.-H.;
Camerel, F.; Ziessel, R.; Retailleau, P.; Amadou, J.; Pham-Huu, C. New J. Chem.
2008, 32, 920; (d) Nishihara, Y.; Inoue, E.; Ogawa, D.; Okada, Y.; Noyori, S.;
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yields for most of the products are comparable to those by Sono-
gashira reaction.5 However for the preparation of 4-[2-(4-methyl-
phenyl)ethynyl] benzaldehyde (entry 2), much improved yield
(84%) was achieved compared to that of the literature method
(31%) by ordinary Sonogashira coupling.6 Although high conver-
sion of this product was recently reported, an abnormal N-hetero-
cyclic carbenes precatalyst was required, which has complicated
structure and need multi-step synthesis.7 All the compounds
synthesized were characterized by 1H, 13C NMR, and mass
spectrometry.
6. Baker, G. A.; Bright, F. V.; Detty, M. R.; Pandey, S.; Stilts, C. E.; Yao, H. J. Porphyrins
Phthalocyanines 2000, 4, 669.
7. John, A.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2009, 47, 10581.
In summary, we have developed a novel coupling reaction for
the Pd-catalyzed alkynylation from iodoalkynes and arylboronic