The ligand and base-free Pd-catalyzed oxidative Heck reaction of arylboronic acids and olefins

Article abstract of DOI:10.1039/c2ob25462j

Highly effective Pd-catalyzed Heck-type oxidative couplings between arylboronic acids and terminal olefins were reported. It is noteworthy that such reactions could be carried out in the absence of the base and the ligand.

Full text of DOI:10.1039/c2ob25462j

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The ligand and base-free Pd-catalyzed oxidative Heck reaction of arylboronic
acids and olefins†
Peng Sun, Yan Zhu, Hailong Yang, Hong Yan, Linhua Lu, Xiang Zhang and Jincheng Mao*
Received 2nd March 2012, Accepted 24th April 2012
DOI: 10.1039/c2ob25462j
acid with methyl acrylate in acetic acid at 110 °C in the presence
of Ag2O in air to obtain a 40% yield of the product after 18 hours
(Table 1, entry 1). In the absence of Ag2O, only trace amounts of
the product was obtained (entry 2). Then we tested a range of
hydrogen acceptors for the purpose of optimizing the reaction.
Usual oxidants such like K2S2O8 and Ag2CO3 provided lower
yields of desired product (entries 3–4). Only when BQ (1,4-ben-
zoquinone) and DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)
Highly effective Pd-catalyzed Heck-type oxidative couplings
between arylboronic acids and terminal olefins were
reported. It is noteworthy that such reactions could be
carried out in the absence of the base and the ligand.
Recently the oxidative variant of the Heck reaction1 has received
considerable attention. After first reported by Dieck and Heck2
and further development of Cho and Uemura,3 various catalytic
systems have been developed to simplify this methodology.4
Notably Jung and co-workers, who have done a series of
wonderful pioneering work in this area, firstly reported a base-
free version of oxidative Heck, which has brought oxidative
Heck to a new age.5 Xiao and co-workers6 developed an oxygen
and base-free method for the olefination of arylboronic acids.
However, the reported methods required Pd complex, ligands as
well as oxygen.7 Therefore, based on our interest in coupling
reactions,8 we aim to develop an oxygen, ligand and base-free
catalytic system for the oxidative coupling of olefins and phenyl-
boronic acids (Scheme 1).9
Table 1 Screening catalytic conditions in oxidative Heck coupling
between phenylboronic acid and methylacrylatea
Entry
Pd cat. (mol%)
Oxidant Solvent
T (°C) Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
PdCl2 (2)
Ag2O
—
K2S2O8 AcOH
Ag2CO3 AcOH
AcOH
AcOH
110
110
110
110
110
110
110
90
70
90
90
90
40
Trace
<5
<5
54
84
NR
82
73
62
NR
69
47
Trace
Trace
Trace
Trace
16
89
99
92
99
It was suggested that Pd(II)-catalysed oxidative Heck reactions
require a regeneration of the Pd(II) step. We wish to get the
H–Pd–X intermediate intercepted by hydrogen acceptors.
We initially examined our hypothesis by treating phenylboronic
BQ
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
DMSO
DMF
DDQ
TBHP
DDQ
DDQ
DDQ
9
10
11
12
13
14c
15
16
17
18
19d
20e,f
21e,g
22e,h
23e,h,i
24e,h,j
Pd(PPh3)2Cl2 (2) DDQ
Pd(dba)2 (2)
Pd/C (2)
DDQ
DDQ
—
90
90
90
90
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
PEG-400 90
Dioxane 90
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
90
90
90
90
90
90
90
Scheme 1 Pd-catalyzed oxidative coupling between arylboronic acids
and olefins.
62
96
46
25e,h,j,k Pd(OAc)2 (2)
a Catalytic conditions: Phenylboronic acid (0.5 mmol), methylacrylate
(3.0 mmol), oxidant (1.0 equiv), additive, solvent (3 mL), 70–110 °C,
18–30 h, air. b Isolated yield based on phenylboronic acid. c In oxygen
atmosphere. d 4 equiv of Ac2O as the additive. e 5 equiv of Ac2O as the
additive. f 30 h. g 24 h. h 27 h. i 0.5 equiv DDQ. j In Ar. k 4 equiv DDQ.
Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry, Chemical Engineering and Materials Science, Soochow
University, Suzhou 215123, P.R. China. E-mail: jcmao@suda.edu.cn
†Electronic supplementary information (ESI) available: Experimental
details and copies of HRMS and NMR spectra of product. See DOI:
10.1039/c2ob25462j
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Table 2 Pd-catalyzed Heck coupling between methylacrylate and
Table 2 (Contd.)
various arylboronic acidsa
Entry
15
ArB(OH)2
Product
Yieldb (%)
35
Entry
1
ArB(OH)2
Product
Yieldb (%)
99
16
62
2
3
4
5
42
56
92
60
a Reaction conditions: Aryl boronic acid (0.5 mmol), methylacrylate
(3.0 mmol), DDQ (1.0 equiv), Ac2O (5 equiv), AcOH (3 mL), 27 h,
90 °C, air. b Isolated yield based on arylboronic acid (average of two
runs).
dropped to 73% (entry 9). We next tested a series of palladium
catalysts (entries 10–13). The use of other Pd sources gave lower
yields or even led to no formation of the expected product.
Therefore we believe that DDQ plays a quite vital role in our cat-
alytic system. The control reaction indicated that only a trace of
product could be obtained in the absence of DDQ even in an
oxygen atmosphere (entry 14). It was supposed that the H–Pd–
OAc intermediate might react with acetic acid and DDQ to better
release Pd(OAc)2. Then, several commonly-used solvents,
including DMF, DMSO, PEG-400 and dioxane were investigated
in the study, but the reactions performed poorly on those (entries
15–18). Acetic anhydride was used as the additive in order to
trap the hydrogen atom from the H–Pd–OAc intermediate. 4
equiv of acetic anhydride affords the desired product with a yield
of 89% (entry 19), 5 equiv of Ac2O would achieve almost quan-
titative transformation when the reaction time was increased to
30 hours (entry 20). A slightly decreased yield of 92% was
obtained when the reaction time was reduced to 24 hours (entry
21). An excellent yield of 99% was obtained when the reaction
was conducted for 27 hours (entry 22). Under the same con-
ditions, only 0.5 equiv of DDQ afforded a decreased yield (62%,
entry 23). The reaction performed in argon atmosphere also
acquired a good result (96%, entry 24). In addition, excessive
DDQ without air gave a much lower yield (46%, entry 25).
With the optimized protocol in hand, we then set out to inves-
tigate the scope and limitations of this oxidative coupling reac-
tion. The results are shown in Table 2. Different substituents and
different substituting sites on the benzene ring were tested under
our standard conditions, and most of the substrates could achieve
moderate to good yields. We found that electron-rich phenyl-
boronic acids (Table 2, entries 2–3, 9–11) as well as electron-
deficient phenylboronic acids (entries 4–8) all proceed smoothly.
Ortho-substituted phenylboronic acids were also examined, and
less amount of product was obtained in the view of steric hin-
drance effect (entries 8, 10–11). O-formyl phenylboronic acid
could only afford only trace of product, since the formyl group
may have a poisoning effect on the Pd-catalyst through coordi-
nating to it. The two isomers of naphthylboronic acid were then
investigated in the reaction (entries 12–13): 1-naphthylboronic
6
38
7
8
51
Trace
9
84
75
25
10
11
12
45
13
14
77
49
were used as oxidants, the reactions were performed smoothly
(54% yield for BQ and 84% yield for DDQ, respectively)
(entries 5–6). When TBHP (tert-butyl hydroperoxide) was
employed as the oxidant, no formation of the product was
observed (entry 7). Decrease of the temperature to 90 °C led to
slightly lower yield of 82% (entry 8) and at 70 °C the yield
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Table 3 Pd-catalyzed Heck coupling between phenylboronic acid and
various terminal olefinsa
Entry
1
Olefin
Product
Yieldb (%)
99
2
3
4
5
6
65
78
89
61
99
Scheme 2 Oxidative coupling between methylacrylate and organo-
boron or organosilicon-based reagents.
Scheme 3 Oxidative coupling between α-methylacrylate and phenyl-
boronic acid using Pd(OAc)2/DDQ/Ac2O/AcOH system.
7
8
69
99
Scheme 4 Oxidative coupling between α-methylstyrene and phenyl-
boronic acid using Pd(OAc)2/DDQ/Ac2O/AcOH system.
both the 4-methyl and 4-chloro styrenes afforded the desired
product almost quantitatively (entries 8–9).
9
99
Subsequently, the scope of other boron- and silicon-based
reagents was examined under the optimized conditions and most
of them obtained good to excellent yields (Scheme 2). Potassium
phenyltrifluoroborate gave a higher yield of 90% while for coup-
lings of 2-phenyl-1,3,2-benzodioxaborole or sodium tetraphenyl-
borate were 54% and 56%, respectively. To our delight,
phenyltrimethoxysilane could also achieve a 67% yield, which
demonstrates that our methodology was not only well-applied
for organoboron reagents but also for organosilicons.
a Reaction conditions: Phenylboronic acid (0.5 mmol), olefin
(3.0 mmol), DDQ (1.0 equiv), Ac2O (5 equiv), AcOH (3 mL), 27 h,
90 °C, air. b Isolated yield based on phenylboronic acid (average of two
runs).
We next set out to test the regioselectivity of our methodology
by treating phenylboronic acid and α-substituted olefins
(Schemes 3 and 4). α-Methylacrylate and α-methylstyrene were
chosen to study regioselectivity of the reaction. As shown, the
hydrogen-migrating products were major in both, with the ratio
of 1.78 : 1 and 2.23 : 1. In addition, the conversion of α-methyla-
crylate was almost quantitative despite the steric hindrance pro-
vided by the α-methyl group.10
acid afforded the desired product with 45% yield, which was
lower than its isomer (77%). When heteroarylboronic acids were
used, the reaction could also proceed smoothly and the desired
heteroaryl olefins were acquired in moderate yields between 35%
and 49% (entries 14–15). 4-(1-Naphthyl)phenylboronic acid
could also participate in the coupling successfully, affording the
desired product in yield of 62% (entry 16).
We here wish to disclose a plausible mechanism (Fig. 1)
which was proposed on the basis of results reported by
others.6,7a,11,12 First, Pd(II) catalyst reacts with phenylboronic
acid to form an aryl-Pd(II) species I, which subsequently coordi-
nates to the olefin to form a Pd(II) intermediate II. This inter-
mediate will undergo an insertion to the olefin to give an
intermediate III. After elimination of β-hydrogen, a Pd-hydride
species H–Pd–OAc will be released to give the desired product,
and then it would form a Pd(0)-DDQ species IV, which stabilizes
We next applied our methodology to the coupling between
phenylboronic acid and various olefins (Table 3). Under the opti-
mized conditions, various acrylates affords the desired product in
yield between 65% and 99% (entries 1–4). Acryl acid and acryl-
amide was then studied: acryl acid could achieve almost full con-
version while the yield for acrylamide decreased to 61% (entries
5–6). We then extended our protocol to the coupling of phenyl-
boronic acid and various styrenes. Under the standard con-
ditions, the yield of styrene was reduced to 69% (entry 7) while
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Notes and references
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we assume that the leaving group of B(OH)2 could be stabilized
initially by the acetic anhydride and finally by DDQ due to its
oxophility. A species V are supposed to be released. The VI
species was detected by MS after reaction, which might be
supportive.
In summary, we have disclosed that in the aerobic catalytic
system of Pd(OAc)2-DDQ-Ac2O-AcOH, the olefination of phe-
nylboronic acids could be well achieved. Many different types of
substituted substrates are tolerated. It is noteworthy that various
organoboronic reagents and an organosilicon reagent could also
be used to afford the desired product. The regioselectivity of this
protocol was also examined. Efforts are underway to extend this
methodology to other types of olefins and aryl reagents.
We are grateful to the grants from International S&T
Cooperation Program of Jiangsu Province (BZ2010048), the
Scientific Research Foundation for the Returned Overseas
Chinese Scholars, State Education Ministry, the Priority Aca-
demic Program Development of Jiangsu Higher Education Insti-
tutions, and the Key Laboratory of Organic Synthesis of Jiangsu
Province.
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