Visible light induced cross-coupling synthesis of asymmetrical heterobiaryls using Pd/CeO2 nanocomposite photocatalyst

Article abstract of DOI:10.1016/j.cclet.2018.01.002

A simple, mild and green approach has been developed for the synthesis of asymmetrical heterobiaryls under the irradiation of visible light without any oxidants and promoting reagents through using Pd/CeO₂ nanocomposite photocatalyst. This method can tolerate considerable functional groups such as electron-donating groups and electron-withdrawing groups through C–C cross-coupling. Moreover, we obtain the products with moderate yields in an efficient way. Finally, a plausible mechanism is proposed.

Full text of DOI:10.1016/j.cclet.2018.01.002

Accepted Manuscript
Title: Visible light induced cross-coupling synthesis of
asymmetrical heterobiaryls using Pd/CeO2 nanocomposite
photocatalyst
Authors: Yanqin Ge, Pinhui Diao, Xu Chen, Nannan Zhang,
Guo Cheng
PII:
DOI:
Reference:
S1001-8417(18)30002-0
https://doi.org/10.1016/j.cclet.2018.01.002
CCLET 4392
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
13-11-2017
8-12-2017
2-1-2018
Please cite this article as: Yanqin Ge, Pinhui Diao, Xu Chen, Nannan Zhang,
Guo Cheng, Visible light induced cross-coupling synthesis of asymmetrical
heterobiaryls using Pd/CeO2 nanocomposite photocatalyst, Chinese Chemical
Letters https://doi.org/10.1016/j.cclet.2018.01.002
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Communication
Visible light induced cross-coupling synthesis of asymmetrical heterobiaryls using
Pd/CeO2 nanocomposite photocatalyst
Yanqin Ge1, Pinhui Diao1, Xu Chen, Nannan Zhang, Guo Cheng
College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China
Graphical abstract
A simple, mild and green approach has been developed for the synthesis of asymmetrical heterobiaryls under the irradiation
of visible light without any oxidants and promoting reagents through using Pd/CeO2 nanocomposite photocatalyst. This method
tolerates considerable functional groups such as electron-donating groups and electron-withdrawing groups through C-C cross-
coupling.
ABSTRACT
A simple, mild and green approach has been developed for the synthesis of asymmetrical heterobiaryls under the irradiation of visible light without
any oxidants and promoting reagents through using Pd/CeO2 nanocomposite photocatalyst. This method can tolerate considerable functional groups
such as electron-donating groups and electron-withdrawing groups through C-C cross-coupling. Moreover, we obtain the products with moderate
yields in an efficient way. Finally, a plausible mechanism is proposed.
Keywords: Visible light, Nanocomposite photocatalyst, Pd/CeO2, C-C cross-coupling, Mild condition
Asymmetrical heterobiaryls are extremely important motifs in semiconductor, liquid crystal materials, and drug development [1, 2].
Consequently, a number of methods have been reported for the synthesis of the asymmetrical heterobiaryls [3, 4]. Particularly, in
recent decades, different kinds of efficient ways to synthesize the asymmetrical heterobiaryls have been developed. The traditional
ways focus on direct cross-coupling using transition-metal, such as Suzuki [5], Stille [6], Negishi [7], etc. However, these methods
have many disadvantages, the use of plenty of metal organic precursors and high temperature. After those reactions, there will be a
large number of metal wastes generate, which were hard to deal with and harmful to the environment. As a consequence, exploring a
convenient, novel, green and sustainable approach for cross-coupling synthesis is a highly desirable and challenging task.
Recently, scientists have repeatedly found that organic transformation induced by visible-light has shown its innately continuous and
green chemistry [8-14]. What is more, visible light photoredox catalyst also has received much attention in the organic synthesis [15-
23]. It can be used to induce visible-light-triggered reactions as most organic compounds do not absorb visible light. Pd NPs is a kind
of catalyst which has been widely applied in the organic reactions [24-27] due to their advantages of high stability, reusability and low
toxicity. However, there are only rare studies about using it as catalyst under visible light irradiation in the organic synthesis until now.
Pd NPs supported catalyst (Pd/CeO2, Pd/ZrO2) is a new kind of photocatalyst, it has been used in our laboratory for years [28]. As we
all know, under the visible-light irradiation, the excited electron on the metal Pd(0) surface can inject into the chemical antibonding
orbital directly, then induce the reaction started because of chemically adsorbed molecules [29, 30]. To our knowledge, Pd/CeO2
induces the cross-coupling for the synthesis of asymmetrical heterobiaryls has not been reported yet. Fortunately, we disclose a mild
and highly efficient, visible-light promoted protocol for the synthesis of heterobiaryls from aryl halide and bromo aromatic
heterocyclic compound derivatives without using external reductants. A series of asymmetrical heterobiaryls can be conveniently
generated in an efficient and scalable fashion.
The Pd/CeO2 was prepared via a simple impregnation-reduction process using PdCl2, lysine and NaBH4 as starting materials (detail
see Supplementary information).
The prepared 3 wt% Pd/CeO2 was characterized by TEM, Pd nanoparticle size distribution, UV–vis, XRD and XPS. First, as can be
seen from the TEM image (Fig. 1A), the Pd nanoparticles disperse equally on the surface of the CeO2. Fig. 1B shows that the average
———
 Corresponding author.
E-mail address: guocheng@njtech.edu.cn (C. Guo).
1 These two authors contributed equally to this project.

particle diameter of the metal palladium nanoparticles is < 7 nm and dispersed on the surface of the CeO2 evenly. Moreover, UV–vis
spectra (Fig. 2A) shows that the light absorption of Pd/CeO2 is stronger than CeO2 both in the UV and visible range, suggesting that the
enhanced light absorption arises from the dispersion of Pd nanoparticles on the CeO2 surface. It is obvious that the diffraction peaks of
the Pd/CeO2 could correspond to the pure CeO2 entirely from Fig. 2B, indicating that the structure of CeO2 remained unchanged after
the metal NPs were loaded, which may be account of the metal content is inferior to the detection limit and/or the crystallinity of the
surface metal NPs is poor. As seen from Fig. 2C, we find that the XPS spectra of Pd 3d exhibits two signal peaks at 336.01 and 341.41
eV, which are attributed to the Pd0 species. From XPS analysis, it can be deduced that the Pd0 species are predominant in the
composites. XPS analysis also shows that the Pd content on the surface of CeO2 was about 2.75 %, which is almost identical with the
theoretical content of Pd (3 %).
Initial investigation was conducted by employing reacts 1 with 2 in the presence of 3 wt% Pd/CeO2 as a photoredox catalyst, K3PO4
as the base and DMA as the solvent under the irradiation of an incandescent light (0.79 W/cm2) (with a glass filters to cut off the
irradiation below a certain value of wavelength) at 60 oC for 24 h, resulting in 81% yield of the target product 3 (Table 1, entry 6). As
shown in Table 1, the application of 2 wt% and 4 wt% Pd provided 72% and 60% yield respectively (Table 1, entries 7, 8), and 5 wt%
Pd gave only a small amount (Table 1, entry 9). Pd NPs is nanoparticles of nonplasmonic transition metals, we then turn to choose 3
wt% Au/ZrO2, which has been well demonstrated to have localized surface plasmon resonance (LSPR) [13, 14], but it only give a 40%
yield of the target product (Table 1, entry 1). Then we screen kinds of other photocatalysts (Table 1, entries 2−5), when 3 wt% Pd/TiO2
and Au/TiO2 were used as the photoredox catalyst, we achieved quite low yields, 13%, 12% respectively (Table 1, entries 2 and 4). The
use of Pd/ZrO2 or Au/CeO2 as the photoredox catalyst has no improvement in the transformation (Table 1, entries 3 and 5). The use of
CeO2 as a catalyst led to a 7% yield of product, this result shows that the CeO2 support itself has a very limited contribution to the
catalytic activity of the photocatalyst (Table 1, entry 10). Then, different solvents were also evaluated for this conversion (Table 1,
entries 11-15), and those prove DMA was facilitated the reaction effectively. In order to improve the yield of the target product,
different bases were tested, including K2CO3, KOAc, KOH, Na2CO3 and NaOAc. The results promoted us to use K3PO4 to conduct this
reaction (Table 1, entries 16-19). It is important to note that visible light and catalyst are essential in the reaction (Table 1, entry 20).
1
In the optimal conditions, we turned to study the scope and generality of this method and all the products were characterized by H
NMR. As shown in Table 2, we can see that the most yields in the dark of target products were <10%. All of those show that the
visible-light acts a conclusive role. From Table 2 we can see that varies substituent group, like electron-donating groups and electron-
withdrawing groups on the substrates 1 and 2 worked well in the reaction to give the corresponding products with moderate to good
yields. This implied that the electronic effect had little influence on the reaction. Regardless of differences in the electronic and steric
properties of substrates 1, they afford the desired product in good yields range from 60% to 82% with the reactant 2 unchanged (Table
2, 3a-3h). We also choose three kinds of different bromo-aromatic heterocyclic (pyridine, furan, thiophene) to explore the practicality
of our reaction conditions with the reactant 1 unchanged. To our delight we receive quite satisfactory consequence, as shown in Table 2
(3i-3u). Compared to furan and thiophene, pyridine has a lower yield. But we can still obtain the yield above 55%. From those, we can
conclude that the reaction conditions bear different aromatic heterocyclic and their substrates. What's more, from the Table 2, we can
see the reaction bears the chemical reactivity of aryl iodine better than bromine.
As shown in Fig. S1a (Supporting information) we can know that at the early stage of the reaction process, the yield of 3 has a big
increase. And, the yield increased slowly from the twentieth hour. When the reaction time ranged from 24 h to 36 h, the same target
product was obtained and slight increase. So we choose 24 h as the best choice reaction time finally.
The advantages of heterogeneous catalysts exist in their easy separation, good stability and fantastic recyclability. As expected, the
recycled photocatalyst showed good reusability and only slight decrease in its activity after five cycles, which was reveled on Fig. S1b
(Supporting information).
According to the previous literatures [28, 31, 32], under visible light irradiation, Pd nanoparticles can absorb the energy of incident
light to make the ground state bound electrons on the surface of the metal reach its excitation, which could occur energy level transition
to transferred to a higher energy level orbit become the exciting electrons, named photo-induced electrons. It can enhance the catalytic
performance of photocatalyst obviously. What's more, Pd (0) d10 complex has a long-life time excited state (three-line excited state) in
solution state [33-35], and the increase of charge density on the metal palladium surface also makes the metal interact more closely
with the reactants in the reaction system. Moreover, as to our reaction system, the key step is the process of dehalogenation, and our
photocatalyst due to the photoredox electron shuttling, it could avoid using external reductants, offering a promising bond-forming
strategy [36]. Based on the results above, we accounted out a photoredox cycle and the C–C cross-coupling events product was
strongly favored due to the Fischer–Ingold persistent radical effect (PRE) [37, 38]. The PRE is a general principle that explains the
highly specific formation of the cross-coupling product (R1 – R2) between two radicals R1 and R2, when one species is persistent (long
lived) and the other is transient. During the initial step, the concentrations of both radicals are very low (usually <10-7 mol/L), which
enables the homo-coupling of transient radical and the cross-coupling of two different radicals is unfavorable. After this period, the

increasing of two different radicals concentration steers the reaction subsequently to follow a single pathway, that is, the cross reaction
[39].
A plausible mechanism of the photocatalytic cross-coupling is illustrated in Fig. 3. Under the visible light irradiation, the
concentrated energetic electrons can transfer to the halogen atom from the Pd atoms to facilitate the cleavage of C–X bonds to form an
Ar–Pd–X complex A and Het-Pd-Br complex B. Next, the intermediates Ar-Pd-Het C generates in situ from the complexs A and B on
the surface of Pd NPs. The final product D can be achieved by reductive elimination, and the Pd active sites can be returned to the
initial states.
In summary, we have developed a novel and environmental benign process for the synthesis of asymmetrical heterobiaryls through
cross-coupling by using the visible-light-mediated catalyst Pd/CeO2. In contrast to previous work, the tolerances of substrates are good.
Moreover, further studies on the application of recycle photochemical based on earth abundant metals for other organic transformations
in progress in our laboratory.
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35
30
25
20
15
10
5
B
0
2
3
4
5
6
7
8
9
Particle size (nm)
Fig. 1. (A) TEM image of the 3wt% Pd/CeO2. (B) Pd nanoparticle size distribution of the 3wt% Pd/CeO2.
10
8
1.0
(111)
A
B
C
(220)
336.01 eV
540 nm
(311)
(222)
(200)
0.8
0.6
0.4
0.2
0.0
3 wt% Pd/CeO2
Pd/CeO2
(400)
341.41 veV
6
4
CeO2
20
2
CeO2
0
300
400
500
600
700
800
10
30
40
50
60
70
330 332 334 336 338 340 342 344 346
Binding energy (eV)
2/degree
Wavelength (nm)
Fig. 2. (A) UV–vis spectra of pure CeO2 (black), 3 wt% Pd/CeO2 (red). (B) The X-ray diffraction patterns for pure 3 wt% Pd/CeO2 (blue) and
CeO2 (black). (C) X-ray photoelectron spectra (XPS) of 3 wt% Pd/CeO2.
Fig. 3. Proposed mechanism for synthesize of asymmetrical heterobiaryls.

Table 1
Optimization of the reaction conditions. a
Entry Catalyst b
Solvent Base
3%wt Au/ZrO2 DMA K3PO4
Yield c(%)
40
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
3%wt Pd/TiO2 DMA
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
13
79
12
46
81
72
60
35
7
35
62
71
3%wt Pd/ZrO2 DMA
3%wt Au/TiO2 DMA
3%wt Au/CeO2 DMA
3%wt Pd/CeO2 DMA
2%wt Pd/CeO2 DMA
4%wt Pd/CeO2 DMA
5%wt Pd/CeO2 DMA
CeO2
DMA
3%wt Pd/CeO2 EtOH
3%wt Pd/CeO2 THF
3%wt Pd/CeO2 CH3CN K3PO4
3%wt Pd/CeO2 DMSO
3%wt Pd/CeO2 DMF
3%wt Pd/CeO2 DMA
3%wt Pd/CeO2 DMA
3%wt Pd/CeO2 DMA
3%wt Pd/CeO2 DMA
3%wt Pd/CeO2 DMA
K3PO4
K3PO4
K2CO3
KOH
73
79
60
60
NaOH
53
NaOAc 71
K3PO4
n.rd, n.re
20d e
a
Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), catalyst (80 mg), solvent (5 mL), base 0.45 mmol, irradiation under incandescent light
(0.79 W/cm2) at 60 oC under air for 24 h, n.r. = no reaction.
b The metal-loading (m/m) 100 mg photocatalyst contain 3 mg metal-loading.
c HPLC yield.
d No light.
e No catalyst.

Table 2
Results of photosynthesis of asymmetrical heterobiaryls of substituted 1 and 2.
Entry
1 (R1)
X1
2 (R2)
3
Yield a (%)
hʋb
Dark
X = I (Br) 2-MeO
2-COCH3
S (n = 1) 2-COCH3
3a
3b
3c
3d
3e
3f
70% (61%) 6% (trace)
69% (63%) 5% (5%)
79% (65%) 6% (4%)
79% (69%) 9% (4%)
83% (71%) 8% (5%)
70% (68%) 7% (5%)
81% (78%) 9% (5%)
3-MeO
4-NO2
4-MeO
4-COCH3
4-COOCH3
4-Br
3g
3h
X = I
65%
71%
60%
80%
64%
72%
76%
5%
6%
4-I
X = Br
X = I
4-Br
trace
10%
trace
trace
4%
4-COOCH3 S (n = 1) 2-CHO
3i
2-CH3
2-COOH
2-COPh
3j
3k
3l
2-COOC2H5 3m 83%
11%
6%
6%
O (n = 1) 2-CHO
2-COOCH3
2-COOH
N (n = 2) 2-CH3
3n
3o
3p
3q
3r
3s
3t
78%
82%
73%
55%
63%
59%
68%
64%
5%
trace
trace
trace
3%
2-COCH3
2-COOH
2-CHO
2-COOC2H5 3u
trace
a Isolated yield.
b The yield in bracket is of 3 when X=Br of reactant 1.