Pd-catalyzed oxidative homo-coupling of acrylates and aromatic alkenes for the conjugated diene synthesis

Article abstract of DOI:10.1016/j.tetlet.2018.06.026

We developed a bidentate monoanionic nitrogen ligand that was effective in the Pd-catalyzed oxidative homo-coupling reaction of acrylates and aromatic alkenes. In the presence of Pd(OAc)₂/ligand several conjugated dienes were obtained in good yields with high stereoselectivities.

Full text of DOI:10.1016/j.tetlet.2018.06.026

Accepted Manuscript
Pd-catalyzed oxidative homo-coupling of acrylates and aromatic alkenes for the
conjugated diene synthesis
Ting Zhu, Zhen Li, Fanhua Xiao, Wei-Liang Duan
PII:
S0040-4039(18)30768-8
https://doi.org/10.1016/j.tetlet.2018.06.026
TETL 50064
DOI:
Reference:
Tetrahedron Letters
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Accepted Date:
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6 June 2018
8 June 2018
Please cite this article as: Zhu, T., Li, Z., Xiao, F., Duan, W-L., Pd-catalyzed oxidative homo-coupling of acrylates
and aromatic alkenes for the conjugated diene synthesis, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/
j.tetlet.2018.06.026
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Pd-catalyzed oxidative homo-coupling of
acrylates and aromatic alkenes for the
conjugated diene synthesis
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Ting Zhu, Zhen Li, Fanhua Xiao and Wei-Liang Duan

Tetrahedron Letters
1
Tetrahedron Letters
Pd-catalyzed oxidative homo-coupling of acrylates and aromatic alkenes for the
conjugated diene synthesis
Ting Zhua, Zhen Lib, Fanhua Xiaoa,* and Wei-Liang Duanb,
a School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
b College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We developed a bidentate monoanionic nitrogen ligand that was effective in the Pd-catalyzed
oxidative homo-coupling reaction of acrylates and aromatic alkenes. In the presence of
Pd(OAc)2/ligand several conjugated dienes were obtained in good yields with high
stereoselectivities.
Available online
2017 Elsevier Ltd. All rights reserved.
Keywords:
Pd-catalysis
C−H bond activation
Acrylates
Aromatic alkenes
Conjugated Dienes
———
 Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000;
E-mail addresses: fhxiao@sit.edu.cn (F. Xiao), duanwl@yzu.edu.cn (W.-L. Duan).

2
Tetrahedron Letters
catalyzed oxidative Heck reaction of simple arenes without
directed groups.8 In such work, we found that a bidentate
monoanionic nitrogen ligand 2-OH-1,10-phen/Pd(OAc)2 more
effectively catalyzed the oxidative Heck reaction of arenes than
did 1,10-phen/Pd(OAc)2. We believed that the complex of 2-OH-
1,10-phen with Pd(OAc)2 only contained one acetate anion on the
Pd atom. Given that the binding ability of the acetic anion to Pd
is not strong, a palladium intermediate with a vacant coordination
site can be generated with relative ease and act as a catalyst for
the C−H bond cleavage of simple arenes. On the basis of the
design, we used bidentate monoanionic nitrogen ligands in the
Pd-catalyzed oxidative homo-coupling reaction of acrylates and
aromatic alkenes.
Conjugated diene fragments are widely distributed in many
natural compounds, optical materials and pharmaceuticals.1
Accordingly, diene syntheses attract considerable research
interest. Pd-catalyzed C−H bond activation is a very powerful
tools for C−C bond formation.2 This method provides a
straightforward and atom-economical strategy for synthesizing
compounds. However, simple alkenes are not widely used to
prepare dienes. Given the intrinsically poor activity of the ester
group in coordinating with the metal center, the alkenyl C−H
bond is difficult to activate.3 In 2004, Ishii et al. reported the first
example of the oxidative cross-coupling reaction of acrylates
with vinyl carboxylates under a Pd(OAc)2/HPMoV/O2 system
(Scheme 1a).4 In 2009, Loh et al. developed an efficient method
for the Pd-catalyzed oxidative cross-coupling reaction of simple
olefins with acrylates (Scheme 1b).5 In 2015, Wen et al. reported
the feasibility Pd-catalyzed homodehydrogenation coupling
reaction of aromatic alkenes (Scheme 1c).6 However, in Loh and
Wen's systems, the use of 20 mol% Pd(OAc)2 catalyst achieves
good yields, and decreased Pd(OAc)2 amount to 10 mol%, leads
to relatively low yield. Very recently, Lin and Feng et al.
reported an elegant synthesis of 1,3-dienes from terminal alkenes
via 1,4-palladium migration/Heck sequence.7
Table 1. Optimization of reaction conditions.a
entry
ligand
oxidant
(equiv.)
Ag2CO3 (1.0)
solvent
T
(°C)
140
yieldb
(%)
1
2
/
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
DME
n. p.c
L1
L2
L3
L4
L5
L6
L7
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
AgOAc (1.0)
Ag2CO3 (2.0)
Ag2O (1.0)
140
140
140
140
140
140
140
140
140
140
140
140
150
120
140
140
140
140
21
n. p.
14
75 (72 d)
n. p.
n. p.
n. p.
60
3
4
5
In a previous communication, we reported the palladium-
6
7
8
9
10
11
12
13
14
15
16
17
18
19
66
n. p.
n. p.
15
AgTFA (1.0)
Cu2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
Ag2CO3 (1.0)
55
50
35
CH3CN
DMF
n. p.
9
DMA
27
a All the reactions were conducted with 0.40 mmol of alkenes in 2.0 mL of
solvent. b Yields were determined by 1H NMR analysis of the crude product
using CH2Br2 as the internal standard. c n. p. = no product. d Isolated yields.
To evaluate the feasibility of the homo-coupling reaction, we
chose n-butyl acrylate as the substrate and 5 mol% of Pd(OAc)2
as catalyst (Table 1). First, we used 1.0 equivalent Ag2CO3 as
oxidant in 1,4-dioxane at 140 °C to conduct the reaction without
the ligand, but no product was formed (entry 1). Adding 2-OH-
1,10-phen (L1) led to a 21% product yield (entries 2). By
contrast, the use of 1,10-phen (L2) totally inhibited the progress
of reaction with no formation of the desired product (entry 3).
The 2-OH-1,1'-bipyridine (L3) with a similar structure to that of
L1 exhibited low catalytic activity (14% yield, entry 4).
Interestingly, the use of 2-OH-4,4'-tBu-1,1'-bipyridine (L4)
significantly increased the product yield to 72% (entry 5). We
assumed that the presence of a t-butyl group in L4 can increase
the solubility of the generated Pd/L4 complex relative to that of
Pd/L1 in reaction. Other nitrogen ligands (L5 to L7)9 were also
tested in reaction but did not attain improved results (entries 6–
8). The survey of oxidants showed that silver salt was more
Scheme 1. Pd-catalyzed simple alkenens to form conjugated dienes

Tetrahedron Letters
3
2-
effective than copper salt containing OAc- or CO3 (entries 9–
13). We also found that neither higher nor lower reaction
temperatures were beneficial for the reaction yield (entries 14 and
15). Finally, various solvents, such as DME, CH3CN, and DMF
were screened (entries 16−19), but no further improvement was
achieved.
Table 2. Pd-catalyzed oxidative homo-coupling of acrylatesa, b
aAll the reactions were conducted with 0.40 mmol of alkenes in 2.0 mL of
solvent. bIsolated yields. c140 °C.
aAll the reactions were conducted with 0.40 mmol of alkenes in 2.0 mL of
solvent. bIsolated yields.
Under the obtained optimized conditions, the scope of several
acrylates was investigated (Table 2). Ethyl acrylate, methyl
acrylate, and n-butyl acrylate provided the expected products in
moderate to good yields. However, the reaction of buten-2-one
led to 28% yield. We next examined the reaction of aromatic
alkenes under the reaction conditions in Table 3. The reaction of
styrene provided 51% of the desired product at 140 °C.
Substituents at different positions on the benzene ring (para and
meta positions) was also obtained in good yields. Styrene with
electron-rich t-butyl groups provided the diene product in 73%
yield. However, the arenes bearing electron-deficient substituents
(Cl and F) attained moderate yields (48 and 52% yields).
Moreover, a 1:1 mixture of styrene and n-butyl acrylate were
examined under the reaction, three conjugated dienes were
Scheme 2. Experiments with the mixture of styrene and n-butyl
acrylate
1
formed with the ration of 1:0.35:0.4 (determined by H NMR,
Scheme 2).
Table 3. Pd-catalyzed oxidative homo-coupling of aromatic alkenes.a,b
Scheme 3. Experiments with trans-Styrene-2-d
Mechanistically trans-styrene-2-d was prepared as described
in literature10 and examined under the same reaction conditions
(Scheme 3). Interestingly, only (1E,3E)-1,4-diphenyl-1,3-

4
Tetrahedron Letters
butadiene was obtained with no incorporation of the deuterium
Scheme 3. Proposed catalytic cycle.
atom. Considering our preliminary mechanistic studies and
previous literature, we proposed a possible mechanism (Scheme
3). Pd(OAc)2 coordinated the ligand L4 to form the active
catalyst A. The terminal C–H bond of olefin was cleaved by the
catalyst A to produce the intermediate B. Transmetallation of the
alkenyl group of B into another B molecule then provided the
intermediates C and A. Finally, reductive elimination formed the
diene product and regenerated the active catalyst A in the
presence of silver oxidant. Besides, the mechanism of
intermediate B insertion into the vinyl bond of alkenes, followed
by a β-H elimination step to generate the product, cannot be ruled
out.
In summary, we have developed a bidentate monoanionic
nitrogen ligand L4 and used it in the Pd-catalyzed oxidative
homo-coupling reaction of acrylates and aromatic alkenes to
attain moderate to good yields with high stereoselectivities. This
method potentially enlarges the scope of oxidative coupling
reactions and provides a new route for the synthesis of functional
conjugated dienes.
Acknowledgments
The Natural Science Foundation of China (21472218,
21672183) and Yangzhou University are greatly acknowledged
for funding this work.
6. Wen, Y.-M.; Xie, J.-Y.; Deng, C.-M.; Wu, Y.-L. Synlett 2015, 26, 1755–
1758.
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Highlights




A direct method for the preparation of
conjugated dienes is proposed.
The reaction is proceeded via C-H bond
functionalization of alkenes.
The use of ligand L4 is essential for the
success of reaction.
Both the ester and aryl groups on the
alkenes are tolerated.