2,5-Bis(2-(diphenylphosphino)phenyl)-1,3,4-oxadiazole ligands and their Cu(I) complexes for Sonogashira coupling reaction

Article abstract of DOI:10.1002/aoc.3124

Two diphosphane ligands - 2,5-bis(2-(diphenylphosphino)-5-R)phenyl)-1,3,4- oxadiazole (L1, R = H, L2, R = OMe) and their binuclear complexes, L1Cu and L2Cu, were prepared and characterized. The molecular structures of L1Cu and L2Cu, as perchlorate salts,

Full text of DOI:10.1002/aoc.3124

Full Paper
Received: 9 August 2013
Revised: 21 December 2013
Accepted: 24 December 2013
Published online in Wiley Online Library: 14 February 2014
(wileyonlinelibrary.com) DOI 10.1002/aoc.3124
2,5-Bis(2-(diphenylphosphino)phenyl)-1,3,4-
oxadiazole ligands and their Cu(I) complexes
for Sonogashira coupling reaction
Cai-Xia Lina,b, Jia-Fang Zhua, Qing-Shan Lia, Li-Hua Aoa, Yan-Juan Jina,
Feng-Bo Xua*, Fang-Zhong Hua* and Yao-Feng Yuana,b*
Two diphosphane ligands – 2,5-bis(2-(diphenylphosphino)-5-R)phenyl)-1,3,4-oxadiazole (L1, R = H, L2, R = OMe) and their
binuclear complexes, L1Cu and L2Cu, were prepared and characterized. The molecular structures of L1Cu and L2Cu, as
perchlorate salts, were established by X-ray crystallography, which showed them to be binuclear complexes with each Cu
atom tetrahedrally coordinated by two P atoms and two N atoms. The ligands and their Cu(I) complexes catalyzed
Sonogashira coupling reactions of iodobenzene with phenylacetylene in the presence of K2CO3 under Pd-free conditions.
Coupling reactions catalyzed by L1 or L2 with Cu(MeCN)4ClO4 in situ exhibited better yields than those by the corresponding
Cu(I) complexes L1Cu or L2Cu. Detailed studies showed L1 or L2 with Cu(MeCN)4ClO4 to be suitable catalysts for the coupling
reaction of terminal alkynes and aryl halides. The coupling reactions of aryl iodides with electron-withdrawing groups showed
better results. Copyright © 2014 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: Sonogashira coupling; diphosphane ligands; Cu(I) complexes; Pd-free conditions
K2CO3 as base and PEG400 as solvent.[30] It is noteworthy that suit-
Introduction
able ligands are usually required for good coupling efficiency.[6,31]
Transition metal-catalyzed cross-coupling reactions have been
widely used in organic synthesis in academic and industrial
laboratories.[1–6] Among them, the coupling reaction between
terminal alkynes with aryl or vinyl halides (Sonogashira reaction)
is commonly utilized for the synthesis of compounds having C
(sp2)―C(sp) bonds, which are frequently employed in areas of
natural products, pharmaceuticals, biologically active molecules,
liquid crystalline materials, conducting polymers and molecular
organic materials.[7–11] Based on the enormous number of
applications of coupling in synthetic chemistry, developing new
catalysts for the Sonogashira coupling reaction has always been
of great interest to chemists.[6,12] Traditionally, the Sonogashira
coupling reaction is carried out using phosphane-ligated
palladium complexes together with CuI as co-catalyst in the pres-
ence of large amounts of amines as base or solvent, which are
economically and environmentally malignant.[13–18] Investigating
catalysts using a cheaper metal[19–26] instead of the expensive
noble metal palladium and developing greener protocols[12,27,28]
for the Sonogashira cross-coupling reaction remains a challenge.
In recent years, some copper-based catalysts have proved
effective for this transformation.[19–22] For example, the combina-
tion of CuI and PPh3 using potassium hydroxide[19]/potassium
carbonate[20] as base has been used for the coupling of aryl
iodides and terminal alkynes in water. The CuBr/rac-BINOL(1-(2-
hydroxynaphthalen-1-yl)-naphthalen-2-ol) system can catalyze
coupling reactions between terminal alkynes and aryl halides.[29]
Moreover, octahedral and rod-like CuI nanocrystals combined
with PPh3 have been used as catalysts for the cross-coupling
reaction of 4-iodoanisole and phenylacetylene in the presence of
In view of diphosphane ligands and their metal complexes having
been widely applied in catalytic chemistry for many years,[32–35] in
this paper two diphosphane ligands containing nitrogen donor
groups – 2,5-bis(2′-(diphenylphosphino)phenyl)-1,3,4-oxadiazole
(L1) and 2,5-bis(2-(diphenylphosphino)-5-methoxy)phenyl)-1,3,4-
oxadiazole (L2) and their binuclear Cu(I) complexes, L1Cu and
L2Cu – as their perchlorate salts, were synthesized and charac-
terized. The catalytic applications of L1 or L2/Cu(MeCN)4ClO4
as well as L1Cu and L2Cu were studied for their effectiveness
as catalysts in coupling reactions between terminal alkynes
and aryl halides.
Experimental
General Procedures
All reactions were carried out under a dry argon atmosphere
using standard Schlenk techniques unless stated otherwise. The
*
Correspondence to: Feng-Bo Xu, Fang-Zhong Hu and Yao-Feng Yuan, State Key
Laboratory and Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, People’s Republic of China. Email: xufb@nankai.edu.cn;
fzhu@nankai.edu.cn; yaofeng_yuan@fzu.edu.cn
a State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, People’s Republic of China
b Department of Chemistry, Fuzhou University, Fuzhou 350108, People’s Republic
of China
Appl. Organometal. Chem. 2014, 28, 298–303
Copyright © 2014 John Wiley & Sons, Ltd.

Diphosphane ligands/Cu(I)-catalyzed Sonogashira coupling
solvents were purified by standard methods. Flash chromatogra-
phy was performed using 200–300 mesh silica gel with the
indicated solvent system according to standard techniques.
Analytical thin-layer chromatography was performed on pre-
coated, glass-backed silica gel plates. The melting points were
determined with an X-4 binocular microscope melting-point
apparatus (Beijing Tech Instruments Co., Beijing, China) without
correction. Electrospray (ESI) mass spectra were obtained on a
Finnigan LCQ spectrometer. High-resolution mass spectra were
obtained on a Varian QFT-ESI mass spectrometer. 1H, 13C{1H}
and 31P{1H} NMR spectra were recorded on a Bruker AV400/300
spectrometer. Chemical shifts (δ) are reported in ppm relative to
the internal standard tetramethylsilane. J values are given in
Hz. Additionally, N,N′-bis(2-bromobenzoyl)hydrazine 3a, N,N′-
bis(2-bromo-5-methoxybenzoyl)hydrazine 3b and intermediate
4a were synthesized according to the literature.[36]
of desiccant, the solvent was evaporated to yield a crude
product, which was recrystallized using CH2Cl2–petroleum ether
(1:2, v/v) to afford a yellow solid of pure L1. Yield 0.57 g, 37%; m.
p. 83–85 °C. 31P NMR (162 MHz, CDCl3): δ À7.04 (s). 1H NMR
(400 MHz, CDCl3): δ 7.76–7.73 (m, 2H, C3―H), 7.36–7.28 (m,
24H, protons of C4, C6 and PPh2), 7.02–6.99 (m, 2H, C5―H). 13
C
NMR (100 MHz, CDCl3): δ 164.4 (C7), 138.2 (d, JC–P = 27.2 Hz, C2),
136.9 (d, JC–P = 11.0 Hz, C1), 134.7 (C4), 134.0 (d, JC–P = 20.4 Hz,
C2′, C6′, C2″ and C6″), 130.9 (C4′ and C4″), 130.0 (d, JC–P = 4.1 Hz,
C3 and C5), 128.8 (C1′ and C1″), 128.6 (d, JC–P = 7.4 Hz, C3′, C5′,
C3″ and C5″), 128.2 (d, JC–P = 24.0 Hz, C6). HRMS (ESI) calcd for
C38H29N2OP+2, [M + H+]: 591.1755. Found: 591.1752. Anal. Calcd
for C38H28N2OP2: C, 77.28; H, 4.78; N, 4.74%. Found: C, 77.54; H,
4.75; N, 4.79%.
Synthesis of 2,5-bis(2-(diphenylphosphino)5-methoxyphenyl)-1,3,4-oxadiazole L2
8
Synthesis of 2,5-bis(2-bromo-5-methoxy-phenyl)-1,3,4-oxadiazole 4b
O
O
4
3
2
8
5
O
O
O
4
1
1
6
7
3
N
N
5
2
6'
O
P
P
5'
4'
1''
7
6
2''
3''
4''
1'
2'
N
N
Br
Br
6''
3'
4b
5''
L2
A solution of N,N′-bis(2-bromo-5-methoxybenzoyl)hydrazine
3b (4.00 g, 8.73 mmol) in POCl3 (28 ml) was refluxed for 20 h. After
cooling to room temperature, the reaction mixture was dripped
into ice water slowly with agitation and a white precipitate was
formed. After filtration, the crude solid was washed with water
and dried under vacuum, and the pure 4b was obtained by
recrystallization with CH2Cl2–petroleum ether (1:1, v/v). Yield
1.66 g, 43%; m.p. 107–108 °C. 1H NMR (400 MHz, CDCl3): δ 7.65
(d, 2H, JH–H = 8.8 Hz, C6―H), 7.59 (d, 2H, JH–H = 2.6 Hz, C3―H),
6.97 (dd, 2H, JH–H = 8.8 Hz, 2.6 Hz, C5―H), 3.87 (s, 6H, C8―H).
13C NMR (100 MHz, CDCl3): δ 164.0 (C7), 158.8 (C4), 135.5 (C2),
125.5 (C6), 119.4 (C5), 116.3 (C3), 111.9 (C1), 55.8 (C8). HRMS
(ESI) calcd for C16H12Br2N2O3Na+, [M + Na+]: 462.9092. Found:
462.9080. Anal. Calcd for C16H12Br2N2O3: C, 43.67; H, 2.75; N,
6.37%. Found: C, 43.53; H, 2.54; N, 6.59%.
L2 was prepared using an analogous procedure as for L1. Yield
54%; m.p. 212–214 °C. 31P NMR (162 MHz, CDCl3): δ À9.53 (s). H
1
NMR (400 MHz, CDCl3): δ 7.46 (m, 2H, C3―H), 7.30–7.28 (m, 20H,
protons of PPh2), 6.97–6.89 (m, 4H, protons of C5 and C6), 3.77
(s, 6H, C8―H). 13C NMR (100 MHz, CDCl3): δ 164.5 (C7), 159.9
(C4), 137.6 (d, JC–P = 11.5 Hz, C1), 136.5 (C2), 133.8 (d, JC–
P = 20.0 Hz, C2′, C6′, C2″ and C6″), 129.8 (d, JC–P = 26.5 Hz, C6),
128.6 (C3′, C5′, C3″ and C5″), 128.5 (C4′ and C4″), 128.4 (d, JC–
P = 11.5 Hz, C1′ and C1″), 117.6 (C3), 114.8 (d, JC–P = 4.9 Hz, C5),
55.5 (C8). HRMS (ESI) calcd for C40H33N2O3P+2, [M + H+]: 651.1966.
Found: 651.1966. Anal. Calcd for C40H32N2O3P2: C, 73.84; H, 4.96;
N, 4.31%. Found: C, 73.94; H, 4.87; N, 4.31%.
Synthesis of complex L1Cu
2+
4
3
Synthesis of 2,5-bis(2-(diphenylphosphino)phenyl)-1,3,4-oxadiazole L1
-
2ClO4
5
2
O
3'
2'
1'
7
4
3
6
1
4'
5'
N
N
N
PPh2
PPh2
5
P
2
O
6'
6''
1''
Cu
PPh2
Cu
6
7
1
N
N
6'
5''
2''
P
P
5'
4'
N
1''
2''
3''
4''
L1
1'
4'' 3''
O
2'
6''
3'
5''
L1Cu
Under argon atmosphere, to a mixture of 2,5-bis(2-bromophenyl)-
1,3,4-oxadiazole 4a (1.00 g, 2.63 mmol) in THF (50 ml) was added n-b
utyllithium (2.63 ml, 2.3 M, 6.05mmol) dropwise at À78 °C. The
resulting mixture was stirred at the same temperature for 0.5 h.
Chlorodiphenylphosphane (1.04 ml, 5.79 mmol) was then dripped
into the mixture. The resulting mixture was stirred at À78 °C for 1 h,
and then warmed to room temperature and stirred overnight. The
solvent was removed under the protection of argon and the
resulting residue was dissolved in CH2Cl2 (20 ml). The mixture
was washed with water (10 ml) and the organic layer was
separated and dried over anhydrous Na2SO4. After separation
Under argon atmosphere, L1 (135.7 mg, 0.23 mmol) was
dissolved in degassed CH2Cl2 (30 ml) and then Cu(CH3CN)4ClO4
(76 mg, 0.23 mmol) was added. The resulting mixture was stirred
for 1 h and then recrystallized using CHCl3–hexane (1:1, v/v) to
obtain a yellow solid. Yield 67.8 mg, 39%; m.p. 220–222 °C. 31P
1
NMR (162 MHz, CDCl3): δ À6.49 (s). H NMR (400 MHz, CDCl3): δ
8.32 (d, 4H, JH–H = 7.3 Hz, C3―H), 7.75 (t, 4H, JH–H = 7.3 Hz,
C4―H), 7.52 (t, 4H, JH–H = 7.3 Hz, C5―H), 7.20–6.91 (m, 44H,
protons of C6 and PPh2). 13C NMR (100 MHz, CD3CN): δ 163.6
(C7), 134.9 (C2), 133.0 (C1), 132.5 (C4), 132.2 (d, JC–P = 2.3 Hz, C3
and C5), 131.2 (C4′ and C4″), 130.9 (C1′ and C1″), 130.3 (d, JC–
Appl. Organometal. Chem. 2014, 28, 298–303
Copyright © 2014 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

Cai-Xia Lin et al.
P = 15.6 Hz, C2′, C6′, C2″ and C6″), 128.8 (d, JC–P = 5.6 Hz, C3′, C5′,
C3″ and C5″), 125.7 (C6). HRMS (MALDI) calcd for C38H28N2CuOP+2,
crystals. Diffraction intensity data were collected at 293(2) K on a
Rigaku Saturn724 CCD diffractometer using Mo-Kα radiation
(0.71073 Å). Data reduction and absorption corrections were
[M À 2ClOÀ]/2: 653.0973. Found: 653.0951.
4
performed using CrystalClear.[37,38] All the structures were solved
Synthesis of complex L2Cu
[39]
using direct methods
and refined by full-matrix least-squares
on F2.[40] For the structure of L1Cu, the ClOÀ4 anion is disordered
over two sites of equal weight. In addition, badly disordered
unresolved solvent molecules were present. Similar problems were
encountered for L2Cu. Accordingly, only the basic features of the
molecular structures are discussed herein; more details are avail-
able online as supporting information. Despite the fact that crystals
of L1Cu and L2Cu have been grown in other mixed-solvent sys-
tems, better-quality data sets could not be obtained.
8
2+
-
O
O
2ClO4
4
3
2
5
O
3'
7
2'
1'
6
1
4'
5'
N
N
N
PPh2
PPh2
P
6'
6''
1''
Cu
PPh2
Cu
5''
2''
N
4'' 3''
O
O
O
Results and Discussion
L2Cu
Synthesis and Characterization of Diphosphane Ligands, L1,
L2 and binuclear complexes L1Cu, L2Cu
Complex L2Cu was prepared using an analogous procedure as for
L1Cu. Yield 31%; m.p. 220–222 °C. 31P NMR (162 MHz, CDCl3): δ À8.15
(s). 1H NMR (400 MHz, CDCl3): δ 7.89 (s, 4H, C3―H), 7.24–7.10 (m, 8H,
C6―H and C5―H), 7.00–6.91 (m, 40H, protons of PPh2), 4.04 (s, 12H,
C8―H). 13C NMR (100 MHz, CDCl3): δ 164.8 (C7), 161.7 (C4), 137.3 (C2),
133.0 (d, JC–P =8.0Hz, C1), 130.3 (C4′ and C4″), 129.3 (C6), 128.9 (d, JC–
P =4.8Hz, C3′, 5′, 3″ and C5″), 127.8 (d, JC–P = 9.0Hz, C1′ and C1″),
122.3 (d, JC–P =15.7Hz, C2′, C6′, C2″ and C6″), 118.9 (C3), 117.1 (d,
As shown in Scheme 1, 2-bromo-5-R-benzoic acid 1 (1a, R = H; 1b,
R = OMe) was reacted with SOCl2 to yield corresponding acid
chlorides 2a and 2b in high yield, which were then treated with
hydrazine hydrate to give hydrazide 3a and 3b, respectively.[36]
Hydrazides 3a and 3b were treated with phosphoryl trichloride
at refluxing temperature, eliminating an H2O molecule to produce
the oxadiazole intermediates 4a[36] and 4b, in moderate yield.
Compounds 4a and 4b were then treated with chlorodiphenylp
hosphane and n-butyllithium to obtain the corresponding ligands
2,5-bis(2-(diphenylphosphino)-5-R-phenyl)-1,3,4-oxadiazoles L1 and
L2 (L1, R= H; L2, R = OMe), respectively. Ligands L1 and L2 were
reacted with equimolar amounts of Cu(MeCN)4ClO4 to yield the
corresponding dinuclear Cu(I) complexes L1Cu and L2Cu, respec-
tively (Scheme 2).
J
C–P = 2.4 Hz, C5), 56.4 (C8). HRMS (ESI) calcd for C40H32CuN2O3P+2, [M
2ClOÀ4 ]/2: 713.1184. Found 713.1181.
General Procedure for Cu(I)-Catalyzed Coupling Reaction of
Aryl Halides and Arylacetylenes
Under an argon atmosphere, a Schlenk reaction tube was charged
with aryl halide (0.50 mmol), arylacetylene substrate (0.55 mmol),
K2CO3 (207 mg, 1.50 mmol), catalysts (5mol% Cu(I) salt with 5 mol
% ligand or 2.5mol% Cu(I) complex) and dioxane (5ml). After the
mixture was stirred at reflux temperature for 16 h, the solvent was
evaporated under reduced pressure and the residue was purified
by flash column chromatography on silica gel to give the product.
All NMR data of coupling products are listed online as supporting
information.
In the 31P NMR spectra of L1 and L2, the signals appeared at
À7.04 and À9.53 ppm, respectively, and these were shifted down-
field to À6.50 and À8.15 ppm, respectively, for L1Cu and L2Cu.
X-Ray Crystallographic Studies of Complexes
As outlined in the Experimental section, the structure analyses
of L1Cu and L2Cu were less than optimal. Accordingly, only
rudimentary information concerning the nature of the very
similar cations is included herein. As shown in Fig. 1, the
molecular structure of binuclear Cu(I) complex L1Cu features two
bidentate bridging bis(diphenylphosphino) ligands and the N2P2
donor defines a distorted tetrahedral coordination geometry.
The molecule is formed about a central and planar six-
membered Cu2N4 ring. Through the chelation of L1 via P
and N atoms to Cu, four distorted six-membered rings
X-Ray Structure Determinations
Diffusion of diethyl ether into the CHCl3 and DMF solutions, respec-
tively, of complexes L1Cu and L2Cu produced yellow single
NH2NH2.H2O
O
Br
Br
O
THF, 0 o
C
SOCl2
H
R
R
N
N
Br
comprising Cu, P, N and three C atoms were formed in each
binuclear complex.
R
COOH
R
H
Br
COCl
1a, R = H
1b, R = OMe
3a, R = H
3b, R = OMe
2a, R = H
2b, R = OMe
Catalytic Activity Study
The coupling reaction between iodobenzene 5a (102.0 mg,
0.50 mmol) and phenylacetylene 6a (56.1 mg, 0.55 mmol)
with K2CO3 (206.9 mg, 1.5 mmol) in dioxane (5 ml) was cho-
sen as the model reaction to identify the catalytic effects of
the ligands and their Cu(I) complexes. As shown in Table 1,
when using ligand L1 or L2 as catalysts the reaction afforded
trace product (Table 1, entries 1 and 2). Similarly, a low yield
was obtained while the reaction was performed in the
1. n-BuLi, -78 o
2. PPh2Cl, -78 o
C
R
R
R
R
POCl3
reflux
C
O
O
N
N
N
N
PPh2
Ph2P
Br
Br
L1 R = H, yield 37%
L2 R = OMe, yield 54%
4a, R = H, yield 59%
4b, R = OMe, yield 43%
Scheme 1. The synthesis of ligands L1 and L2.
wileyonlinelibrary.com/journal/aoc
Copyright © 2014 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 298–303

Diphosphane ligands/Cu(I)-catalyzed Sonogashira coupling
2+
R
R
presence of Cu(MeCN)4ClO4 without any ligands (Table 1, entry 3).
When either Cu(I) complex L1Cu or L2Cu was used as cata-
lyst, the reaction gave the desired product in 65% and 73%
yield, respectively (Table 1, entries 4 and 5). When the reac-
tion was catalyzed by L1 or L2 with Cu(MeCN)4ClO4, in situ,
the coupling product was obtained in higher yields of 92%
and 99%, respectively (Table 1, entries 6 and 7). The above re-
sults implied that the diphosphane molecules with cuprous
salt in situ catalyzed the coupling reaction more effectively
than the formed Cu(I)–diphosphane complexes. The results
may reflect coordination saturation of the Cu(I) atoms in
L1Cu and L2Cu. When the complexes were applied as cata-
lysts for the coupling reaction, there needs be an
elimination process first to provide a coordination site for
the phenylacetylene to form copper(I) acetylides. However,
when using ligands L1, L2 with Cu(I) salts in situ, the Cu(I) would
directly complex with the large amounts of phenylacetylene to
form copper(I) acetylides.[22,31]
O
N
N
N
N
PPh2
PPh2
Cu
Cu(MeCN)4
ClO4
CH2Cl2
-
2ClO4
Cu
L1, L2
PPh2
PPh2
O
R
R
L1 Cu, R = H, yield 39%
L2 Cu, R = OMe, yield 31%
Scheme 2. The synthesis of dinuclear Cu(I) complexes L1Cu and L2Cu.
Next, the optimal reaction conditions were estimated by inves-
tigating the effects of the species of copper salts, solvents, bases,
the amount of catalysts and reaction temperature on the model
coupling reaction between iodobenzene 5a and phenylacetylene
6a. It was found that when applying Cu(MeCN)4ClO4 as copper
salt, K2CO3 as base, dioxane as solvent and refluxing temperature
as reaction temperature the reaction afforded product in the
highest yield of 92% (supporting information, Tables S1–S3).
When 3 mol% of catalyst was used, a yield of 67% was obtained
for the coupling reaction. An amount of 5 mol% of catalyst was
found to be optimal for the reaction and >90% yields could be
obtained. When 10 mol% catalyst was used in the reaction the
yield did not increase obviously (Table S4).
With the optimized reaction conditions in hand, the coupling
reactions of a variety of aryl iodides 5 and three terminal aryl
alkynes 6a–c were carried out with L1 or L2 and Cu(MeCN)
4ClO4 as catalysts. In order to avoid possible noble metal contam-
ination,[41] all reactions were performed in carefully cleaned flasks
with clean stirring bars. Moreover, the catalysts used in the cou-
pling reaction were treated carefully to confirm the high purity
of the Cu(I) salts. For example, Cu(MeCN)4ClO4 was recrystallized
many times and investigated by atomic absorption spectroscopy
(AAS) until the indicated Pd content was less than 5 ppb.
As shown in Table 2, the yields of the catalytic coupling
reaction with L2 in the presence of Cu(MeCN)4ClO4 were higher
than those catalyzed by L1 with Cu(MeCN)4ClO4. In addition,
the aryl iodides carrying election-withdrawing groups consis-
tently gave the desired products in higher yields than the aryl
iodides with electron-donating groups. Taking L1, for example,
for p-nitroiodobenzene and o-nitroiodobenzene, the coupling
yields were both 99% (Table 2, entries 2 and 3). However, the
compounds p-chloroiodobenzene, p-methoxyiodobenzene and
p-methyliodobenzene were coupled with phenylacetylene 6a to
give 7d–f only in moderate yields (Table 2, entries 4–6). Notably,
o-aminoiodobenzene, containing the electron-donating amino
group, reacted with 6a to give the product in 91% yield (Table 2,
entry 7), indicating that the ortho substituent of the aryl iodides
has a great influence on cross-coupling under the reaction condi-
tions employed. For the coupling reactions of aryl iodides 5a–g
and 4-methoxyphenylacetylene 6b (Table 2, entries 8–13), p-nit
roiodobenzene, o-nitroiodobenzene and o-aminoiodobenzene
gave good results (Table 2, entries 9, 10 and 13). While iodoben-
zene, p-chloroiodobenzene and p-methoxyiodobenzene were
reacted with 4-methoxyphenylacetylene, only undesirable yields
Figure 1. Molecular structure of centrosymmetric L1Cu; hydrogen
atoms; anions and solvent of crystallization omitted for clarity. Symmetry
operation a: 1-x, 2-y, 1-z.
Table 1. Catalysts screeninga
catalyst
dioxane, K2CO3
I
reflux
+
5a
6a
7a
Entry
Catalyst
Yield (%)b
1
2
3
4
5
6
7
L1 (5 mol%)
L2 (5 mol%)
Trace
Trace
13
Cu(MeCN)4ClO4 (5 mol%)
L1Cu (2.5 mol%)
65
L2Cu (2.5 mol%)
73
L1 (5 mol%), Cu(MeCN)4ClO4 (5 mol%)
L2 (5 mol%), Cu(MeCN)4ClO4 (5 mol%)
92
99
aReaction conditions: iodobenzene (102.0 mg, 0.50 mmol), pheny
lacetylene (56.1 mg, 0.55 mmol), K2CO3 (206.9 mg, 1.5 mmol), solvent
(5 mL), 16 h.
bYield of isolated product is based on iodobenzene.
Appl. Organometal. Chem. 2014, 28, 298–303
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Cai-Xia Lin et al.
Table 2. L/Cu(MeCN)4ClO4-catalyzed Sonogashira couplinga
R2
Cu(MeCN)4ClO4
(5 mol%)
L1/L2 (5 mol%)
dioxane, K2CO3
reflux
X
+
R2
R1
5
6
R1
7
Entry
5
X
R1
6
R2
Product
L1 yield (%)b
L2 yield (%)b
1
5a
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
H
6a
H
H
7a
7b
7c
92
99
99
42
73
78
91
72
91
95
54
36
82
80
86
90
52
44
52
87
21
70
64
6
99
99
99
54
83
85
99
77
99
99
62
48
89
85
94
99
56
52
59
95
34
78
72
11
Trace
2
5b
5c
5d
5e
5f
p-NO2
o-NO2
p-Cl
6a
6a
6a
6a
6a
6a
6b
6b
6b
6b
6b
6b
6c
6c
6c
6c
6c
6c
6c
6a
6a
6a
6a
6a
3
H
4
H
7d
7e
7f
5
p-OMe
p-CH3
o-NH2
H
H
6
H
7
5 g
5a
5b
5c
5d
5e
5 g
5a
5b
5c
5d
5e
5f
H
7 g
7e
7 h
7i
8
p-OMe
p-OMe
p-OMe
p-OMe
p-OMe
p-OMe
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
H
9
p-NO2
o-NO2
p-Cl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
7j
p-OMe
o-NH2
H
7 k
7 l
7b
7 m
7n
7o
7 h
7p
7q
7a
7b
7c
p-NO2
o-NO2
p-Cl
p-OMe
p-CH3
o-NH2
H
5 g
5 h
5i
Br
Br
Br
Br
Cl
p-NO2
o-NO2
p-Cl
H
5j
H
5 k
5 l
H
7d
7c
o-NO2
H
Trace
aReaction conditions: Cu(MeCN)4ClO4 (8.2mg, 0.025 mmol, 5 mol%), 5 mol%L1/L2, aryl halide (0.50mmol), arylacetylene (0.55 mmol), K2CO3
(206.9mg, 1.5mmol), dioxane (5ml), 16h.
bIsolated yield is based on aryl iodide (average of two runs).
of 72%, 54% and 36%, respectively (entries 8, 11 and 12), were
obtained. In coupling reactions between aryl iodides 5a–g and
p-nitrophenylacetylene 6c, those with electron-withdrawing
iodides, i.e. 5b–c, also furnished products in good yields (Table 2,
entries 15 and 16). The yields of the coupling for aryl iodides 5d–f
with electron-donating groups were moderate (Table 2, entries
17–19). When aryl bromides or chlorides were coupled with
substituted phenylacetylene 6, lower activity was achieved com-
pared with the reaction with aryl iodides (Table 2, entries 22–25).
For example, p-nitrobromobenzene and o-nitrobromobenzene
were treated with phenylacetylene to furnish 7b and 7c in yields
of 70% and 64%, respectively (Table 2, entries 22 and 23), and
bromobenzene or p-chlorobromobenzene treated with phen
ylacetylene gave the coupling products in very low yields (Table 2,
entries 21 and 24). For the aryl chloride, only trace product can be
obtained in the catalytic reaction (Table 2, entries 25).
From the above results, it can be concluded that in the pres-
ence of Cu(MeCN)4ClO4 L2, with an electron-donating methoxy
group, is more useful for catalyzing the coupling reaction be-
tween aryl halides and arylacetylenes than L1. Based on the
reported mechanisms of Sonogashira reaction catalyzed by palla-
dium and copper,[22,28,31,42–44] the possible mechanism of in situ
Cu(I)-catalyzed Sonogashira coupling reactions under Pd-free
conditions is possibly a ligand-accelerated catalytic process, as
proposed by Bolm et al.[22,31] The Cu(I) salt might first react with ex-
cess phenylacetylene in the presence of large amounts of base to
form copper(I) acetylides, then react with the oxadiazole-bridged
phosphane ligand to generate a highly electron-rich acetylide com-
plex that is able to react with the aryl halide to give the coupling
products (Scheme 3).
Intriguingly, when o-iodophenol was treated with phenyla
cetylene in the L1/L2 and Cu(MeCN)4ClO4 in situ catalytic system,
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Appl. Organometal. Chem. 2014, 28, 298–303

Diphosphane ligands/Cu(I)-catalyzed Sonogashira coupling
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Conclusions
In summary, two ligands – 2,5-bis(2′-(diphenylphosphino)phenyl)-
1,3,4-oxadiazole (L1) and 2,5-bis(2-(diphenylphosphino)-5-me
thoxy)phenyl)-1,3,4-oxadiazole (L2) – and their Cu(I) complexes
(L1Cu and L2Cu) were synthesized and characterized. The L1 or
L2/Cu(MeCN)4ClO4 and the Cu(I) complexes can catalyze the
Sonogashira coupling reaction under Pd-free conditions between
aryl halides and terminal aryl alkynes. The reactions were highly
dependent on the substituents in the aryl halides, arylacetylenes
and ligands. The coupling reaction of electron-deficient aryl
iodides and arylacetylenes catalyzed by L1/L2 in the presence
of Cu(MeCN)4ClO4 furnished products in excellent yields,
while less reactive aryl bromides gave low yields. Further
modification on the ligands and their catalytic activity for
Sonogashira cross-coupling reactions will be the subject of
future investigations.
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Acknowledgments
We thank the National Natural Science Foundation of China (Nos
21172114, 20772060 and 21172036), National Key Technology
Research and Development Program (No. 2011BAE06B03-12)
and Tianjin Natural Science Foundation (No. 11JCYBJC14200) for
financial support.
Supporting Information
Additional supporting information may be found in the online
version of this article at the publisher’s web-site.
Appl. Organometal. Chem. 2014, 28, 298–303
Copyright © 2014 John Wiley & Sons, Ltd.
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