Sonogashira/hydroarylation sequential reactions: Catalyzed by NHC-Pd complexes

Article abstract of DOI:10.1016/j.tet.2013.04.061

It was found that an air-stable NHC-palladium complex of Pd[(s)-3-C ₃H₅-4-(C₅H₅CH₂)-1-(2,6- ⁱPr₂C₆H₃)-C₃H ₃N₂](C₅H₅N)Br₂ derived from l-phenylalanine is an effective pre-catalyst for copper-free and phosphine-free Sonogashira reaction of alkynes under aerobic conditions in short reaction time. Moreover, the palladium compound would be reused to catalyze the hydroarylation of alkyne prepared from Sonogashira reaction, which makes firstly Sonogashira/Hydroarylation sequential reactions successful. The arylation of alkynes underwent with a high regio- and stereoselectivity and only trans-arylation of alkyne was observed. No Z/E isomerization of the olefin was observed in the system.

Full text of DOI:10.1016/j.tet.2013.04.061

Tetrahedron 69 (2013) 5178e5184
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sonogashira/hydroarylation sequential reactions: catalyzed by
NHCePd complexes
,
Longguang Yang a, Yunfei Li a, Qian Chen a, Yufeng Du a, Changsheng Cao a
,
*
,
b
,
c
Yanhui Shi a , Guangsheng Pang
*
a College of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials,
Jiangsu Normal University, Xuzhou 221116, PR China
b State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China
c State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun 130012, PR China
a r t i c l e i n f o
a b s t r a c t
It was found that an air-stable NHCepalladium complex of Pd[(s)-3-C3H5-4-(C5H5CH2)-1-(2,6-iPr2C6H3)-
Article history:
Received 26 January 2013
Received in revised form 2 April 2013
Accepted 15 April 2013
C3H3N2](C5H5N)Br2 derived from
L-phenylalanine is an effective pre-catalyst for copper-free and
phosphine-free Sonogashira reaction of alkynes under aerobic conditions in short reaction time. More-
over, the palladium compound would be reused to catalyze the hydroarylation of alkyne prepared from
Sonogashira reaction, which makes firstly Sonogashira/Hydroarylation sequential reactions successful.
The arylation of alkynes underwent with a high regio- and stereoselectivity and only trans-arylation of
alkyne was observed. No Z/E isomerization of the olefin was observed in the system.
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 18 April 2013
Keywords:
Sonogashira reaction
Hydroarylation
Carbenes
Palladium complexes
1. Introduction
so far,6 to the best of our knowledge, no Sonogashira/hydro-
arylation sequential reactions of alkynes have been studied. The
Palladium catalyzed copper-free Sonogashira coupling reaction1
and the hydroarylation of alkynes2 are extremely powerful tools for
constructing compounds with unsaturated carbonecarbon bonds,
which are often encountered in nature products, biologically im-
portant molecules, agrochemicals as well as fine chemicals.3 Al-
though the N-heterocyclic carbenes (NHCs) have been used widely
in organometallic chemistry and catalysis,4 comparison to reports
of phosphine based Pd catalyst for Sonogashira reaction, consid-
erably fewer studies have appeared using NHC based Pd catalyst.
However, unlike their phosphine analogs, inexpensive PdeNHC
complexes are very user friendly due to their significant air and
moisture stability, and less toxicity. Consequently, the development
of air-stable, robust, and well-defined NHCePd complexes for
a copper-free Sonogashira reaction is an important objective in this
effort.5 As alkyne is the starting material of the hydroarylation and
commercially available alkynes are limited, it is interesting and
necessary to develop a practical procedure of Sonogashira/hydro-
arylation sequential reactions, realizing the reuse of Pd catalyst.
Although various of hydroarylation of alkynes have been reported
possible reason for this is that these two reactions require very
different conditions. Excessive base should be used in Sonogashira
reaction, whereas, the hydroarylation of alkynes is promoted by
Lewis acid,6d,7 and even carried out in strong protonic acid some
times.2b Therefore, most catalysts would lose activity in these two
conflicting conditions.
On the extension of our work in exploring efficient catalysts for
copper-free phosphine-free Sonogashira coupling reaction under
aerobic conditions, a new efficient NHCepalladium catalyst was
reported herein. Furthermore, we would like to report for the first
time palladium catalyzed Sonogashira/hydroarylation sequential
reactions.
2. Results and discussion
In our previous study, palladiumeNHC complexes derived from
L
-phenylanaline have been successfully applied to copper-free
phosphine-free Sonogashira reaction.8 Benzyl Pd complex (1)
(Fig.1) showed the best catalytic activity in all catalysts studied, and
we suggest the possible reason is the weak
benzene, which stabilizes the highly reactive low-valent catalytic
intermediate. Because the allyl group is a good or donor, it is
p donation properties of
* Corresponding authors. Tel./fax: þ86 516 8350 0349; e-mail address: yhshi@
jsnu.edu.cn (Y. Shi).
p
s
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.061

L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
5179
Ph
Sonogashira coupling reaction catalyzed by 2 were conducted
with 1 mol % of 2 in DMSO and K3PO4 as base under aerobic con-
ditions. Under this optimized conditions, the result of reaction
catalyzed by 1 further proved that the complex 2 is more efficient
catalyst than complex 1 (entry 15 vs 17).
To probe the substrate scope of the reaction, many aryl iodides
and bromides were chosen to react with different terminal alkynes
under the optimized conditions. The results were presented in
Table 2. The results showed that the PdeNHC can not only catalyze
the reaction with more reactive aryl iodides, but also can catalyze
Ph
N
N
N
N
Br Pd Br
N
Br Pd Br
N
(2)
(1)
Fig. 1. PdeNHC catalyst.
Table 2
Probe the substrate scope of the Sonogashira reaction catalyzed by 2
interesting to synthesize allyl complex (2) and investigate its cat-
alytic performance in the Sonogashira reaction.9
To prove our hypothesis that 2 would be a better pre-catalyst for
the Sonogashira reaction, we compared the catalytic activity of
1 mol% 2, 2 eq. K3PO4
X
R2
2 eq.
R2
+
R1
DMSO, 100 °C, 1 h
R1
1 eq.
complex
1 and 2 in the reaction of bromobenzene with
Entrya
Aryl halide
R2
Product
3 Yield (%)b
phenylacetylene. The reactions were conducted with 1 mol % 1 or 2
in DMSO and K2CO3 as base under aerobic conditions, which were
the optimized conditions for 1 catalyzed Sonogashira reaction
according to our previous study.8 The results were presented in
Table 1. To our delight, complex 2 gave the higher yield of desired
product than complex 1 did (entry 1 vs 2). The common Pd salts,
such as Pd(OAc)2 and PdCl2 didn’t work at all at the tested condi-
tions (entries 3 and 4).
1
2
3
4
5
Ph
Ph
Ph
Ph
Ph
73 (3a)
81 (3a)
96 (3b)
93 (3c)
94 (3d)
B
I
O2N
Br
Br
O2N
Table 1
Sonogashira coupling reactions under different conditions
F3C
O
F3C
O
Cat., 2 eq Base
+
Br
Sol., 100 °C, 1h
Br
1 eq.
Entry
2 eq.
Yielda (%)
6
7
Ph
Ph
95 (3e)
94 (3f)
Cat. (mol %)
Base
Solvent
OHC
NC
Br
Br
OHC
NC
1
2
3
4
5
6
7
8
1 (1)
2 (1)
PdCl2(1)
Pd(OAc)2(1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (1)
2 (0.5)
1 (1)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
KOH
K3PO4$3H2O
Et3N
K3PO4
K3PO4
K3PO4
DMSO
DMSO
DMSO
DMSO
31
43
0
0
DMF
25
34
30
0
0
0
60
38
62
32
80
48
42
DMSO:H2O¼3:1
DMF:H2O¼3:1
THF
Toluene
Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
Br
8
Ph
Ph
Ph
Ph
96 (3g)
82 (3h)
84 (3i)
86 (3j)
NC
NC
9
10
11
12
13
14
15
16
17
Br
9
F
F
Br
DMSO
DMSO
10
11
F
F
F
F
a
Determined by GCeMS with 1,2,3,4-tetrahydronaphthalene as an internal
standard.
Br
As the solvent normally is a very important parameter de-
termining cross-coupling efficiency, we tested the reaction cata-
lyzed by 2 in different solvents (entries 1 and 5e10). The results
showed that DMSO is the best solvent tested, and relatively low
yield was observed in DMF or a mixed solvent of DMF with water
(3:1). No product was even observed in THF, toluene or dioxane as
solvent at all. Furthermore, the same model systems were used to
evaluate the influence base on the reaction (entries 1 and 11e15).
The results show that among the bases employed, anhydrous K3PO4
is the most suitable base. Stronger bases, such as KOH and Cs2CO3
lead to lower yields even compared to K3PO4$3H2O. Low yield was
observed with organic base, Et3N as well. Reducing the amount of
catalyst to 0.5 mol % would decrease the yield to 48% (entry 16).
Therefore, the optimum reaction conditions for the copper-free
I
12
13
Ph
Ph
78 (3k)
90 (3l)
O
O
Br
O
O
14
Br Ph
91 (3m)
O2N
O2N
(continued on next page)

5180
L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
Table 2 (continued )
Table 3
Hydroarylation of phenylacetylene with arene
Entrya
Aryl halide
R2
Product
3 Yield (%)b
99 (3n)
1 mol% Pd 2
R1
R2
1 eq.
R2
+
TFA, 50 °C, 3 h
R1
15
nBu
O2N
Br
O2N
nBu
1.5 eq.
Entrya
AreH
Alkyne
Product
4 Yield (%)b
91 (4a)
Br
nBu
16
nBu
99 (3o)
1
O2N
O2N
nBu
17
18
19
20
21
22
nBu
99 (3p)
82 (3q)
97 (3r)
95 (3s)
88 (3t)
77 (3u)
F3C
Br
F3C
2
84 (4b)
nBu
Br
nBu
a
Reaction conducted with 1 mmol of phenylacetylene, 1.5 mmol of arene and
0.01 mmol of catalyst 2 in 2 mL of TFA.
b
Isolated yield on average of two runs.
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
F3C
NC
F
Br
Br
F3C
arylation was taken place. Then, we guessed probably the left base
and DMSO would hinder the arylation reaction. Therefore, we tried
the reaction in a two-step one catalyst process. After the comple-
tion of coupling reaction of phenyl iodine with phenylacetylene,
mesitylene and TFA were added into the reaction mixture in which
inorganic salts and DMSO were washed away with saturated brine.
Remarkably, the trans-addition Z-isomer as the only product was
isolated in 89% yield after the mixture was heated at 50 ꢀC for 3 h
(Table 4, entry 1). Therefore, the Pd complex could survive under
two different conditions and successively catalyze the two
reactions.
NC
F
Br
Br
O2N
Br
O2N
23
98 (3v)
The scope and generality of this reaction also have been explored
by the reaction of various aryl halides, alkynes, with several arenes
(Table 4). If the aryl halides have substitute, such as CN, NO2, CHO,
and COMe, the Sonogashira reaction went well, whereas, the alkyne
arylation could not occur. A reasonable explanation is that the un-
saturated bond in these groups deactivated cationic Pd(II) catalytic
species. The reaction is quite general with respect to the internal
alkyne, both arylalkyne and alkylalkyne worked well. It was re-
ported that the yield increased with increasing number of electron
rich substituents on arenes.6c,d,11 It is not so obvious in our catalytic
system and even benzene gave good yields too. Interestingly, the
reaction underwent with a high regio- and stereoselectivity and
yielded the trans-hydroarylation product in high yields; whilst, ei-
ther Z or E isomer was isolated in good selectivity. No Z/E
isomerization of the olefin was observed in this protocol and no
other stereo- or regioisomers were isolated from the reaction mix-
ture. The regio- and stereochemistry of the products were estab-
lished on the basis of chemical shifts in 1H NMR compared with
those of known compounds. The structures (shown in Fig. 2) of (Z)-
3-(2-(3-fluorophenyl)-1-phenylvinyl)-1,2,4,5-tetramethylbenzene
(5e) were further confirmed to be in the Z-configuration by X-ray
crystal structure analysis. The regiochemistry of the products is
dominated by electronic effects of the substituents in alkyne, aryl
group is added to the alkynyl carbon substituted electron rich
phenyl group.
a
Reaction conducted with 0.01 mmol of 2, 1 mmol of aryl halides, 2 mmol of
alkyne and 2 mmol of K3PO4 in 2 mL of DMSO.
b
Isolated yield on average of two runs.
the reaction in good to excellent yield (73%e99%) with less reactive
aryl bromides in the absence of copper co-catalysis. The higher
yield was obtained for aryl bromides with strong electron-
withdrawing group compared to that with weaker electron-
withdrawing group (like entry 3 vs entry 11).
The reaction of aryl bromides with aliphatic alkynes, like 1-
hexyne led better results, compared to that with aromatic al-
kynes (entries 1 and 22 vs entry 18, and entries 4 and 19 vs entry
17). All the reactions tested were very fast, and they can be com-
pleted within 1 h. Unfortunately, the tested reactions of phenyl-
acetylene with phenyl chloride could not proceed under this
conditions.
To develop a practical Sonogashira/hydroarylation reaction, we
tested the catalytic activity of 2 in the hydroarylation of phenyl-
acetylene with mesitylene and 1,2,4,5-tetramethylbenzene in the
first stage of our work.2b,10 The reaction was carried out with
1 mol % of 2 in 2 mL of trifluoroacetic acid (TFA) as solvent at 50 ꢀC
under aerobic atmosphere. To our delight, the reactions occurred
with a highly regioselectivity and completed within 3 h. The steric
hindered Markovnikov product was the only product to be isolated
in high yield, as shown in Table 3.
It is interesting to see if Sonogashira/Hydroarylation of alkyne
can be performed in a two-step one-pot process. After the com-
pletion of the coupling reaction of phenyl iodine with phenyl-
acetylene under optimized conditions, mesitylene and TFA were
added directly to the cooled reaction mixture. Unfortunately, when
the mixture was heated at 50 ꢀC for 3 h, no addition product of
arene to internal alkyne was detected. Firstly we thought the Pd
catalyst may lose the activity, so another 1 mol % of 3a was added
with mesitylene and TFA into the reaction vessel. However, still no
3. Conclusion
Complex 2 showed good catalytic activity in Cu-free Sonoga-
shira coupling reaction and Sonogashira/hydroarylation of alkynes
sequential reaction. All reactions were very fast, the Sonogashira
reaction can be completed within 1 h under aerobic conditions, and
alkyne hydroarylation was only required 3 h. The arylation un-
derwent with a high regio- and stereoselectivity and yielded trans-
hydroarylation product as a sole isomer in high yields.

L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
5181
Table 4
Sonogashira/hydroarylation sequential reaction of alkyne with arene
X
R2
1eq. Ar-H
1 mol% 2, 2eq. K3PO4
remove solvent
R1
+
R2
2 eq.
R1
Ar
DMSO, 100 °C, 1 h
TFA, 50 °C, 3 h
1eq.
Entry
1
Aryl halide
Alkyne
AreH
Product
5 Yield (%)a
Ph
I
89 (5a)
83 (5b)
77 (5c)
65 (5a)
Ph
Br
2
3
4
F3C
F3C
Ph
Br
F
F
Ph
Br
Ph
Ph
Br
Br
5
6
7
73 (5d)
69 (5e)
95 (5f)
F
F
F
F
Ph
I
I
8
9
73 (5g)
F
Br
76 (5h)
F
10
87 (5i)
Br
F3C
F3C
(continued on next page)

5182
L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
Table 4 (continued )
Entry
Aryl halide
Alkyne
AreH
Product
5 Yield (%)a
Br
11
70 (5j)
Ph
Br
12
13
61 (5k)
75 (5l)
Br
F3C
F3C
Ph
Br
14
73 (5m)
62 (5n)
F
F
Ph
Br
15
a
Isolated yield on average of two runs.
Elemental analyses were performed on a EuroVektor Euro EA-300
elemental analyzer. X-ray crystallography was conducted on
a Rigaku Mercury CCD device with graphite-monochromated Mo
ꢀ
Ka
radiation (
l
¼0.71073 A). Absorption correction was performed
using the SADABS program. The structure was solved by directed
methods using the SHELXS-97 program and refined by full-matrix
least squares techniques on F2.
4.2. Catalysis-general procedure
4.2.1. Sonogashira reactions. In a typical run, a 4 mL vial equipped
with a magnetic stirrer bar was charged with a mixture of aryl
halide (1 mmol), alkyne (2 mmol), Pd catalyst (0.01 mmol), K3PO4
(2 mmol), and 2 mL of DMSO in air. The mixture was stirred at
100 ꢀC for 1 h, then cooled to room temperature and brine was
added into it. The resulting mixture was extracted with ethyl ace-
tate three times, and the crude product was obtained by removing
the volatiles. The product was purified by flash column chroma-
tography on silica gel.
Fig. 2. ORTEP structure of complex 5e showing 30% probability ellipsoids; hydrogen
ꢀ
ꢀ
atoms are omitted for clarity. Selected bond lengths (A) and bond angles ( ): C(6)eC(7)
1.495(3), C(7)eC(8) 1.505(3), C(7)eC(18) 1.334(4), C(18)eC(19) 1.480(3), C(6)eC(7)e
C(8) 116.9(2), C(6)eC(7)eC(18) 121.0(2), C(8)eC(7)eC(18) 122.1(2), C(7)eC(18)eC(19)
130.5(2).
4. Experimental
4.1. General
4.2.2. Hydroarylation reactions. After the Sonogashira reaction was
completed, brine was added to cool the reaction mixture. The
resulting solution was extracted with ethyl acetate three times,
and the organic phase was combined. Arene (1 mmol) and TFA
(2 mL) was added to the residue after the volatiles were removed,
and the mixture was stirred at 50 ꢀC for 3 h. After the pH of the
resulting mixture was adjusted by aqueous NaOH solution until
pH reached 11e12, the mixture was extracted with ethyl acetate
three times. The crude product was obtained by removing the
The NHCepalladium complex 2 was prepared according to our
previous reports.8,9 All other reagents were commercially sourced
and were used without further purification. 1H and 13C NMR spectra
were recorded on a Bruker DPX 400 MHz spectrometer at room
temperature and referenced to the residual signals of the solvent.

L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
5183
volatiles and the product was purified by flash column chroma-
tography on silica gel.
2.42 (t, J¼8.0 Hz, 2H), 1.62e1.56 (m, 2H), 1.50e1.45 (m, 2H), 0.95 (t,
J¼8.0 Hz, 3H).
4.2.3. 1,2-Diphenylethyne (3a).1d 1H NMR (CDCl3, 400 MHz):
4.2.19. Hex-1-ynylbenzene (3q).11e 1H NMR (CDCl3, 400 MHz):
d
7.53e7.55 (m, 4H), 7.34e7.36 (m, 6H).
d
7.39 (d, J¼8.0 Hz, 2H), 7.29e7.26 (m, 3H), 2.41 (t, J¼8.0 Hz, 2H),
1.62e1.55 (m, 2H), 1.50e1.45 (m, 2H), 0.95 (t, J¼8.0 Hz, 3H).
4.2.4. 1-Nitro-4-(phenylethynyl)benzene (3b).1d 1H NMR (CDCl3,
400 MHz):
(m, 2H), 7.39e7.40 (m, 3H).
d
8.22 (d, J¼8.0 Hz, 2H), 7.67 (d, J¼4.0 Hz, 2H), 7.55e7.57
4.2.20. 1-Methyl-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene
(3r).11d 1H NMR (CDCl3, 400 MHz):
d
7.60 (d, J¼4.0 Hz, 4H), 7.44 (d,
J¼8.0 Hz, 2H), 7.18 (d, J¼8.0 Hz, 2H), 2.38 (s, 3H).
4.2.5. 1-(Phenylethynyl)-4-(trifluoromethyl)benzene
NMR (CDCl3, 400 MHz):
(3c).11a 1H
d
7.59e7.64 (m, 4H), 7.54e7.59 (m, 2H),
4.2.21. 4-(p-Tolylethynyl)benzonitrile (3s).11h 1H NMR (CDCl3,
7.36e7.38 (m, 3H).
400 MHz):
J¼8.0 Hz, 2H), 2.38 (s, 3H).
d
7.63e7.57 (m, 4H), 7.43 (d, J¼8.0 Hz, 2H), 7.18 (d,
4.2.6. 1-(4-(Phenylethynyl)phenyl)ethanone
(CDCl3, 400 MHz):
7.54e7.56 (m, 2H), 7.36e7.38 (m, 3H), 2.62 (s, 3H).
(3d).11a 1H
NMR
d
7.94 (d, J¼8.0 Hz, 2H), 7.61 (d, J¼8.0 Hz, 2H),
4.2.22. 1-Fluoro-4-(p-tolylethynyl)benzene (3t).11i 1H NMR (CDCl3,
400 MHz):
J¼8.0 Hz, 2H), 7.04 (t, J¼8.0 Hz, 2H), 2.37 (s, 3H).
d
7.52e7.48 (m, 2H), 7.41 (d, J¼8.0 Hz, 2H), 7.16 (d,
4.2.7. 4-(Phenylethynyl)benzaldehyde (3e).1d 1H NMR (CDCl3,
400 MHz):
2H), 7.55e7.57 (m, 2H), 7.37e7.38 (m, 3H).
d
10.02 (s, 1H), 7.87 (d, J¼8.0 Hz, 2H), 7.68 (d, J¼8.0 Hz,
4.2.23. 1-Methyl-4-(phenylethynyl)benzene (3u).11d 1H NMR (CDCl3,
400 MHz):
J¼8.0 Hz, 3H), 7.16 (d, J¼8.0 Hz, 2H), 2.37 (s, 3H).
d
7.53 (d, J¼8.0 Hz, 2H), 7.43 (d, J¼8.0 Hz, 2H), 7.34 (d,
4.2.8. 4-(Phenylethynyl)benzonitrile
400 MHz):
(3f).1d 1H
NMR
(CDCl3,
d
7.59e7.65 (m, 4H), 7.53e7.55 (m, 2H), 7.37e7.39 (m, 3H).
4.2.24. 1-Methyl-4-((4-nitrophenyl)ethynyl)benzene
(3v).11j 1H
NMR (CDCl3, 400 MHz):
2H), 7.45 (d, J¼8.0 Hz, 2H), 7.19 (d, J¼8.0 Hz, 2H), 2.39 (s, 3H).
d
8.21 (d, J¼8.0 Hz, 2H), 7.65 (d, J¼8.0 Hz,
4.2.9. 3-(Phenylethynyl)benzonitrile (3g).11a 1H NMR (CDCl3,
400 MHz):
7.53e7.55 (m, 2H), 7.46 (t, J¼8.0 Hz, 1H), 7.37e7.38 (m, 3H).
d
7.81 (s,1H), 7.74 (d, J¼4.0 Hz,1H), 7.60 (d, J¼8.0 Hz,1H),
4.2.25. 1,3,5-Trimethyl-2-(1-phenylvinyl)benzene (4a).6a 1H NMR
(CDCl3, 400 MHz):
2H), 5.94 (s, 1H), 5.08 (s, 1H), 2.31 (s, 3H), 2.10 (s, 6H).
d
7.26 (d, J¼4.0 Hz, 4H), 7.24-7.22 (m,1H), 6.90 (s,
4.2.10. 1-Fluoro-2-(phenylethynyl)benzene (3h).11b 1H NMR (CDCl3,
400 MHz):
1H), 7.02 (br, 1H).
d
7.51e7.52 (m, 2H), 7.29e7.34 (m, 5H), 7.21 (d, J¼8.0 Hz,
4.2.26. 1,2,4,5-Tetramethyl-3-(1-phenylvinyl)benzene
(4b).6a 1H
NMR (CDCl3, 400 MHz):
1H), 6.96 (s, 1H), 5.96 (s, 1H), 5.05 (s, 1H), 2.23 (s, 6H), 2.03 (s, 6H).
d
7.26 (d, J¼4.0 Hz, 4H), 7.23 (t, J¼4.0 Hz,
4.2.11. 1-Fluoro-3-(phenylethynyl)benzene (3i).11c 1H NMR (CDCl3,
400 MHz):
d 7.48e7.54 (m, 3H), 7.26e7.32 (m, 4H), 7.06e7.12 (m, 2H).
4.2.27. (Z)-2-(1,2-Diphenylvinyl)-1,3,5-trimethylbenzene (5a).2b 1H
4.2.12. 1-Fluoro-4-(phenylethynyl)benzene (3j).11c 1H NMR (CDCl3,
400 MHz):
2H).
NMR (CDCl3, 400 MHz):
d
7.34e7.25 (m, 5H), 7.14 (d, J¼4.0 Hz, 4H),
d
7.50e7.53 (m, 4H), 7.34e7.35 (m, 3H), 7.05 (t, J¼8.0 Hz,
6.97e6.91 (m, 4H), 2.35 (s, 3H), 2.00 (s, 6H).
4.2.28. (Z)-1,3,5-Trimethyl-2-(1-phenyl-2-(4-(trifluoromethyl)phe-
4.2.13. 1-Methoxy-2-(phenylethynyl)benzene
(3k).11d 1H
NMR
nyl)vinyl)benzene (5b). 1H NMR (CDCl3, 400 MHz):
d 7.39e7.28 (m,
(CDCl3, 400 MHz): 7.48e7.51 (m, 3H), 7.40e7.43 (m, 3H), 7.04 (t,
J¼8.0 Hz, 1H), 6.84e6.94 (m, 2H), 3.88 (s, 3H).
d
7H), 7.15 (s,1H), 7.23 (d, J¼8.0 Hz, 2H), 6.94 (s, 2H), 2.36 (s, 3H),1.99 (s,
6H).13C NMR (CDCl3,100 MHz): 142.6,140.9,137.4,135.9,135.4,129.0,
128.7,128.5,128.0,126.5,126.2,125.3,125.2, 21.3,19.8. Anal. Calcd for
C24H21F3 (366.42 g/mol): C, 78.67; H, 5.78. Found: C, 78.24; H, 5.69.
4.2.14. 1-(3-(Phenylethynyl)phenyl)propan-1-one (3l). 1H NMR
(CDCl3, 400 MHz):
d
8.12 (s, 1H), 7.92 (d, J¼8.0 Hz, 1H), 7.70 (d,
J¼8.0 Hz, 1H), 7.55 (dd, J¼8.0 Hz, J¼4.0 Hz, 2H), 7.45 (t, J¼8.0 Hz,
1H), 7.38e7.35 (m, 3H), 3.05e2.99 (m, 2H), 1.24 (t, J¼8.0 Hz, 3H). 13C
NMR (CDCl3, 100 MHz): 154.3, 151.8, 141.6, 138.8, 127.2, 126.4, 125.6,
125.1, 56.1, 49.2, 34.1, 32.1.
4.2.29. (Z)-2-(2-(4-Fluorophenyl)-1-phenylvinyl)-1,3,5-
trimethylbenzene (5c). 1H NMR (CDCl3, 400 MHz):
d 7.32e7.28 (m,
3H), 7.15e7.08 (m, 3H), 7.01e6.94 (m, 6H), 2.36(s, 3H), 2.00 (s, 6H).13C
NMR (CDCl3, 100 MHz): 138.8, 137.4, 137.1, 136.0, 135.8, 129.8, 129.5,
129.3, 127.7, 127.6, 127.1, 126.0, 115.5, 115.3, 21.3, 19.8. Anal. Calcd for
C23H21F (316.41 g/mol): C, 87.31; H, 6.69. Found: C, 86.95; H, 6.48.
4.2.15. 1-Nitro-3-(phenylethynyl)benzene (3m).11a 1H NMR (CDCl3,
400 MHz):
d
8.38 (s, 1H), 8.18 (d, J¼8.0 Hz, 1H), 7.82 (d, J¼8.0 Hz,
1H), 7.56e7.51 (m, 3H), 7.39e7.33 (t, J¼4.0 Hz, 3H).
4.2.30. (Z)-3-(2-(4-Fluorophenyl)-1-phenylvinyl)-1,2,4,5-
tetramethylbenzene (5d). 1H NMR (CDCl3, 400 MHz):
d 7.32e7.27
4.2.16. 1-(Hex-1-ynyl)-4-nitrobenzene (3n).11e 1H NMR (CDCl3,
(m, 3H), 7.11 (t, J¼8.0 Hz, 3H), 6.98 (t, J¼8.0 Hz, 2H), 6.91e6.78 (m,
3H), 2.24 (s, 6H), 1.94 (s, 6H). 13C NMR (CDCl3, 100 MHz): 140.0,
138.7, 137.4, 134.2, 131.7, 130.9, 128.6, 128.3, 127.8, 127.7, 127.0, 126.1,
115.4, 115.2, 20.3, 16.2. Anal. Calcd for C24H23F (330.44 g/mol): C,
87.23; H, 7.02. Found: C, 86.94; H, 7.11.
400 MHz):
d
8.14 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼8.0 Hz, 2H), 2.45 (t,
J¼8.0 Hz, 2H),1.64-1.57 (m, 2H),1.52-1.43 (m, 2H), 0.95 (t, J¼8.0 Hz, 3H).
4.2.17. 1-(Hex-1-ynyl)-3-nitrobenzene (3o).11f 1H NMR (CDCl3,
400 MHz):
d
8.22 (s, 1H), 8.10 (d, J¼8.0 Hz, 1H), 7.67 (d, J¼8.0 Hz,
1H), 7.44 (t, J¼8.0 Hz, 1H), 2.42 (t, J¼4.0 Hz, 2H), 1.63e1.56 (m, 2H),
4.2.31. (Z)-3-(2-(3-Fluorophenyl)-1-phenylvinyl)-1,2,4,5-
1.51e1.45 (m, 2H), 0.95 (t, J¼8.0 Hz, 3H).
tetramethylbenzene (5e). 1H NMR (CDCl3, 400 MHz):
d 7.33e7.24
(m, 5H), 7.10e7.05 (m, 2H), 7.01 (s, 1H), 6.80e6.72 (m, 2H), 6.51 (d,
J¼8.0 Hz, 1H), 2.23 (s, 6H), 1.93 (s, 6H). 13C NMR (CDCl3, 100 MHz):
142.6,141.4,139.8,139.7,138.4,134.3,131.1,129.5,128.6,127.6,126.6,
4.2.18. 1-(Hex-1-ynyl)-4-(trifluoromethyl)benzene (3p).11g 1H NMR
(CDCl3, 400 MHz):
d
7.53 (d, J¼8.0 Hz, 2H), 7.47 (d, J¼8.0 Hz, 2H),

5184
L. Yang et al. / Tetrahedron 69 (2013) 5178e5184
126.3, 124.7, 114.9, 113.9, 20.3, 16.2. Anal. Calcd for C24H23
(330.44 g/mol): C, 87.23; H, 7.02. Found: C, 87.01; H, 7.12.
F
Acknowledgements
We are grateful to the foundation of the National Natural Sci-
ence Foundation of China (Grants 21071121 and 21172188), Sci-
entific Research Foundation (SRF) for the Returned Overseas
Chinese Scholars (ROCS), State Education Ministry (SEM), the
Priority Academic Program Development of Jiangsu Higher Edu-
cation Institutions (PAPD), 333 Project for the Cultivation of High-
level Talents (33GC10002), and Graduate Foundation of Jiangsu
Education Committee (CXLX11_0909) for financial support of this
work.
4.2.32. (Z)-3-(1,2-Diphenylvinyl)-1,2,4,5-tetramethylbenzene
(5f).2b 1H NMR (CDCl3, 400 MHz):
7.34e7.24 (m, 5H), 7.15 (s, 1H),
d
7.11 (d, J¼8.0 Hz, 3H), 7.00 (s, 1H), 6.91 (d, J¼8.0 Hz, 2H), 2.23 (s, 6H),
1.94 (s, 6H).
4.2.33. (Z)-1,2,4,5-Tetramethyl-3-(1-phenylhex-1-enyl)benzene
(5g). 1H NMR (CDCl3, 400 MHz):
d 7.23e7.16 (m, 5H), 6.94 (s, 1H),
6.28 (t, J¼4.0 Hz, 1H), 2.24 (s, 6H), 1.98 (s, 6H), 1.84e1.79 (m, 2H),
1.40e1.35 (m, 2H), 1.30e1.29 (m, 2H), 0.86e0.82 (m, 3H). 13C NMR
(CDCl3, 100 MHz): 141.0, 139.9, 133.5, 132.1, 130.2, 129.5, 128.3,
126.6, 125.9, 31.5, 29.8, 29.4, 22.6, 20.3, 16.4, 14.1. Anal. Calcd for
C22H28 (292.46 g/mol): C, 90.35; H, 9.65. Found: C, 90.03; H, 9.74.
Supplementary data
CCDC 900073 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from
the Cambridge Crystallographic Data Center, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: (þ44)1223-336-33; or e-mail:
deposit@ccdc.cam.ac.uk.
4.2.34. (Z)-2-(1-(3-Fluorophenyl)hex-1-enyl)-1,3,5-trimethylbenzene
(5h). 1H NMR (CDCl3, 400 MHz):
d 7.21e7.15 (m, 1H), 6.96 (d,
J¼8.0 Hz, 1H), 6.91e6.84 (m, 4H), 6.29 (t, J¼8.0 Hz, 1H), 2.32 (s, 3H),
2.04 (s, 6H), 1.89e1.83 (m, 2H), 1.42e1.35 (m, 2H), 1.31e1.26 (m,
2H), 0.85 (t, J¼8.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz): 143.2, 143.1,
137.8, 136.5, 136.2, 135.4, 130.9, 129.7, 129.6, 128.3, 121.3, 113.5,
112.6, 31.5, 29.8, 29.4, 22.7, 21.2, 19.9, 14.1. Anal. Calcd for C21H25
(296.42 g/mol): C, 85.09; H, 8.50. Found: C, 84.78; H, 8.61.
F
References and notes
1. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 50, 4467; (b)
Hundermark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729; (c)
Bakherad, M.; Amin, A. H.; Keivanloo, A.; Bahramian, B.; Raeissi, M. Tetrahedron
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Chem. 2009, 12, 1608; (f) Roy, S.; Plenio, H. Adv. Synth. Catal. 2010, 352, 1014.
2. (a) Gonell, S.; Poyatos, M.; Mata, J. A.; Peris, E. Organometallics 2011, 30, 5985; (b)
Viciu, M. S.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P. Organometallics 2004, 23, 3752.
3. (a) Ren, T. Chem. Rev. 2008, 108, 4185; (b) Negishi, E. I.; Anastasia, L. Chem. Rev.
2003, 103, 1979; (c) Zapf, A.; Beller, M. Top. Catal. 2002, 19, 101; (d) Chinchilla,
4.2.35. (Z)-1,3,5-Trimethyl-2-(1-p-tolyl-2-(4-(trifluoromethyl)phe-
nyl)vinyl)benzene (5i). 1H NMR (CDCl3, 400 MHz):
7.37 (d,
d
J¼8.0 Hz, 2H), 7.24 (s, J¼8.0 Hz, 2H), 7.13 (d, J¼4.0 Hz, 3H), 7.02 (d,
J¼8.0 Hz, 2H), 6.94 (s, 2H), 2.36 (s, 6H), 1.99 (s, 6H). 13C NMR (CDCl3,
100 MHz): 142.5, 141.1, 138.0, 137.9, 137.3, 135.9, 135.5, 129.4, 129.0,
128.5, 126.1, 125.6, 125.2, 21.3, 21.2, 19.8. Anal. Calcd for C25H23F3
(380.45 g/mol): C, 78.93; H, 6.09. Found: C, 78.76; H, 6.15.
ꢁ
R.; Najera, C. Chem. Rev. 2007, 107, 874; (e) Sonogashira, K. J. Organomet. Chem.
2002, 653, 46.
4.2.36. (Z)-1,3,5-Trimethyl-2-(2-phenyl-1-p-tolylvinyl)benzene
4. (a) Fortman, G. C.; Nolan, S. P. Chem. Soc. Rev. 2011, 40, 5151; (b) Diez-Gonzalez,
S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612; (c) Arnold, P. L.; Casely, I.
J. Chem. Rev. 2009, 109, 3599; (d) Enders, D.; Niemeier, O.; Henseler, A. Chem.
Rev. 2007, 107, 5606; (e) Droge, T.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49,
6940; (f) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511; (g) Moore, J. L.;
Rovis, T. Top. Curr. Chem. 2010, 291, 77.
(5j). 1H NMR (CDCl3, 400 MHz):
d
7.22 (d, J¼8.0 Hz, 2H), 7.10 (s, 6H),
6.93 (d, J¼8.0 Hz, 4H), 2.34 (s, 6H), 1.99 (s, 6H). 13C NMR (CDCl3,
100 MHz): 139.8, 138.7, 137.7, 137.2, 136.9, 136.1, 129.3, 128.8, 128.5,
128.3, 127.2, 126.9, 126.0, 21.3, 21.2, 19.9. Anal. Calcd for C24H24
(312.45 g/mol): C, 92.26; H, 7.74. Found: C, 91.97; H, 7.83.
€
ꢁ
5. (a) Gu, S.; Chen, W. Organometallics 2009, 28, 909; (b) Ines, B.; SanMartin, R.;
Churruca, F.; Dominguez, E.; Urtiaga, M. K.; Arriortua, M. I. Organometallics
2008, 27, 2833; (c) Soheili, A.; Albanzeze-Walker, J.; Murry, J. A.; Dormer, P. G.;
Hughes, D. L. Org. Lett. 2003, 5, 4191.
4.2.37. Ethene-1,1,2-triyltribenzene(5k).6d 1H NMR (CDCl3, 400 MHz):
6. (a) Hashimoto, T.; Kutubi, S.; Izumi, T.; Rahman, A.; Kitamura, T. J. Organomet.
Chem. 2010, 696, 99; (b) Choi, D. S.; Kim, J. H.; Shin, U. S.; Deshmukh, R. R.; Song,
C. E. Chem. Commun. 2007, 3482; (c) Yoon, M. Y.; Kim, J. H.; Choi, D. S.; Shin, U.
S.; Lee, J. Y.; Song, C. E. Adv. Synth. Catal. 2007, 349, 1725; (d) Li, R.; Wang, S. R.;
Lu, W. Org. Lett. 2007, 9, 2219; (e) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev.
2002, 102, 1731; (f) Merlic, C. A.; Pauly, M. E. J. Am. Chem. Soc. 1996, 118, 11319.
7. (a) Tsuchimoto, T.; Maeda, T.; Shirakawa, E.; Kawakami, Y. Chem. Commun. 2000,
1573; (b) Song, C. E.; Jung, D.; Choung, S. Y.; Roh, E. J.; Lee, S. Angew. Chem., Int.
Ed. 2004, 43, 6183.
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Dalton Trans. 2012, 41, 5020.
9. Yang, L.; Li, Y.; Chen, Q.; Zhao, J.; Cao, C.; Shi, Y.; Pang, G. Trans. Metal Chem.
2013, 38, 367.
d
7.29 (s, 8H), 7.18 (s, 2H), 7.08 (s, 3H), 7.00 (d, J¼4.0 Hz, 2H), 6.93
(s, 1H).
4.2.38. (E)-1-Methyl-4-(1-phenyl-2-(4-(trifluoromethyl)phenyl)vi-
nyl)benzene (5l). 1H NMR (CDCl3, 400 MHz):
d 7.39e7.32 (m, 6H),
7.23 (d, J¼8.0 Hz, 1H), 7.18e7.13 (m, 4H), 7.07 (t, J¼8.0 Hz, 2H), 6.94
(d, J¼4.0 Hz, 1H), 2.38 (s, 3H). 13C NMR (CDCl3, 100 MHz): 145.1,
143.2, 141.2, 140.1, 138.1, 136.7, 130.3, 129.7, 129.1, 128.3, 128.0, 127.9,
126.4, 125.8, 124.9, 21.4. Anal. Calcd for C22H17F3 (338.37 g/mol): C,
78.09; H, 5.06. Found: C, 77.86; H, 5.15.
10. (a) Glorius, F. Top. Organomet. Chem. 2007, 21, 1; (b) Christmann, U.; Vilar, R.
Angew. Chem., Int. Ed. 2005, 44, 366; (c) Fernandez-Rodriguez, M. A.; Hartwig, J.
F. J. Org. Chem. 2009, 74, 1663; (d) Fernandez-Rodriguez, M. A.; Shen, Q.;
Hartwig, J. F. Chem.dEur. J. 2006, 12, 7782; (e) Fernandez-Rodriguez, M. A.;
Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 2180.
4.2.39. (Z)-2-(2-(4-Fluorophenyl)-1-phenylvinyl)-1,4-
dimethylbenzene (5m). 1H NMR (CDCl3, 400 MHz):
d 7.30e7.23 (m,
3H), 7.14e7.07 (m, 4H), 6.99e6.91 (m, 6H), 2.27 (s, 3H), 1.97 (s, 3H).
13C NMR (CDCl3, 100 MHz): 140.4, 139.3, 137.3, 136.0, 133.3, 130.6,
129.0, 128.6, 128.4, 128.2, 127.9, 127.5, 127.0, 126.6, 115.4, 115.1, 21.1,
19.2. Anal. Calcd for C22H19F (302.38 g/mol): C, 87.38; H, 6.33.
Found: C, 87.16; H, 6.40.
11. (a) Guan, J. T.; Weng, T. Q.; Yu, G. A.; Liu, S. H. Tetrahedron Lett. 2007, 48, 7129;
ꢁ
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(b) Komaromi, A.; Tolnai, G. L.; Novak, Z. Tetrahedron Lett. 2008, 49, 7294; (c)
Bandini, M.; Luque, R.; Budarin, V.; Macquarrie, D. J. Tetrahedron 2005, 61, 9860;
(d) Thakur, K. G.; Jaseer, E. A.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50,
2865; (e) Bakherad, M.; Keivanloo, A.; Bahramian, B.; Hashemi, M. Tetrahedron
Lett. 2009, 50, 1557; (f) Sedelmeier, J.; Ley, S. V.; Lange, H.; Baxendale, I. R. Eur. J.
Org. Chem. 2009, 4412; (g) Shimada, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002,
124, 12670; (h) Rao, M. L. N.; Jadhav, D. N.; Dasgupta, P. Org. Lett. 2010, 12, 2048;
(i) Mino, T.; Shirae, Y.; Saito, T.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71,
9499; (j) Gholap, A. R.; Venkatesan, K.; Pasricha, R.; Daniel, T.; Lahoti, R. J.;
Srinivasan, K. V. J. Org. Chem. 2005, 70, 4869.
4.2.40. (Z)-2-(1,2-Diphenylvinyl)-1,4-dimethylbenzene
NMR (CDCl3, 400 MHz): 7.33e7.22 (m, 5H), 7.13e7.04 (m, 6H), 6.95
(d, J¼8.0 Hz, 3H), 2.26 (s, 3H), 1.98 (s, 3H).
(5n).6d 1H
d