Palladium catalysed β-selective oxidative Heck reaction of an electron-rich olefin

Article abstract of DOI:10.1039/c3cc47045h

A palladium catalysed oxidative β-arylation of an electron-rich olefin is described. The reaction was under mild conditions; meanwhile, additives and directing groups are not needed. Various arylboronic acids worked well under the standard conditions.

Full text of DOI:10.1039/c3cc47045h

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Palladium catalysed b-selective oxidative Heck
reaction of an electron-rich olefin†
Lingkui Meng,‡a Chao Liu,‡a Wei Zhang,a Chao Zhoua and Aiwen Lei*ab
Cite this: Chem. Commun., 2014,
50, 1110
Received 14th September 2013,
Accepted 25th October 2013
DOI: 10.1039/c3cc47045h
www.rsc.org/chemcomm
A palladium catalysed oxidative b-arylation of an electron-rich olefin
is described. The reaction was under mild conditions; meanwhile,
additives and directing groups are not needed. Various arylboronic
acids worked well under the standard conditions.
The Heck reaction has become one of the most important tools
for constructing aryl substituted alkenes since the 1960s.1
Electron-deficient olefins applied in the Heck reaction generally
generate highly regioselective linear b-arylated products, while for
electron-rich olefins a mixture of both a,b-arylated regio-isomeric
products is generally obtained.2 Recently, much effort has been
applied to solve this problem, for instance, diphosphine ligands,
ionic liquids and alcohol additives have shown high efficiency
in the formation of a-regioselective products for electron rich
olefins.2d,3 Oxidative Heck reactions using arylboronic acids as
nucleophiles have also shown high efficiency in obtaining highly
regioselective a-arylated electron rich olefins.2b,c
Fig. 1 Alternative olefin insertion pathways.
Scheme 1 Formation of b-arylated vinyl acetate.
not easy to obtain.5 Thus, it is highly desirable to establish a
Although directing-group-assisted b-selective Heck reactions of catalytic system for b-arylated vinyl esters synthesis from com-
electron rich olefins have been achieved in the past years, few mercially available simple olefins under mild conditions.
reports have focused on establishing an efficient catalytic system
This work was started by testing various electron-rich olefins
for the b-arylation of electron rich olefins without a directing to react with arylboronic acids (see details in ESI†). HOAc was
group.3a,4 The major reason is the electrical properties of the two initially chosen as solvent to inhibit homocoupling of arylboronic
olefin carbons, which highly influence the olefin insertion step of a acids 1.6 Fortunately, after testing several electron-rich olefins,
Heck reaction (Fig. 1). Therefore, it is a big challenge to establish vinyl acetate was found to be able to convert to the b-arylation
an a-selective Heck reaction system with an electron-deficient product in 23% yield. This promising result encouraged us to
olefin and a b-selective Heck reaction system with a simple further investigate this b-selective oxidative Heck reaction.
electron-rich olefin. Herein, we report an oxidative b-selective
After screening multiple conditions, only the co-solvent was
Heck reaction for the electron rich olefin vinyl acetate (Scheme 1). found to highly influence the yield of the b-arylation product.
b-Arylated vinyl esters, with their hydrolysates, are important When DMSO was applied as co-solvent, the yield increased to 51%
building blocks. Although b-arylated vinyl esters can be easily (Table 1, entry 1), while other co-solvents had an adverse effect on
generated from a-arylated aldehydes, a-arylated aldehydes are the b-arylation reaction with only a small amount of b-arylation
product obtained (Table 1, entries 2–6). Subsequently, other acids
were also tested. When HOAc was replaced by TFA, no b-arylation
product could be obtained; this might be due to hydration of vinyl
acetate in the strongly acidic environment or the decomposition
of arylboronic acid (Table 1, entry 7). The amount of HOAc also
a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072,
Hubei, P. R. China. E-mail: aiwenlei@whu.edu.cn; Tel: +86-27-68754672
b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University,
Nanchang 330022, Jiangxi, P. R. China
had an effect on the yield of the desired product. A lower loading
of HOAc led to a decreased yield whereas no desired product was
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc47045h
‡ These authors contributed equally to this work.
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Table 1 Solvent effect on the b-selective oxidative Heck reactiona
Table 2 Scope of arylboronic acids for b-selective oxidative Heck reaction
with vinyl acetatea
Entry
Sol. 1
Sol. 2
1/2a
Yieldb (%)
Entry
1
Substrate
Yieldb (%)
63
Product
1
2
3
4
5
6
7
8
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
TFA
DMSO
DMF
1,4-Dioxane
MeCN
THF
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
1/20
1/20
1/20
1/20
1/20
1/20
1/20
1/20
1/20
1/20
1/5
51
12
12
9
2
6
n.d.
n.d.
54
61e
47
36
2
24
49
64
64
76
77
86
76
45
—
9c
10d
11
12
HOAc
HOAc
HOAc
HOAc
3
1/1
a
The reaction was carried out with 1 (1 eq., 68 mg, 0.5 mmol), 2a,
Pd(OAc)2 (5 mol%, 5.6 mg, 0.025 mmol), BQ (1,4-benzoquinone, 1.2 eq.,
64.8 mg, 0.6 mmol), in sol. 1/sol. 2 (1 mL/1 mL), at 50 1C, for 12 h.
4
b
c
d
e
GC yield. Sol. 1/sol. 2 (1.5 mL/0.5 mL). 60 1C. Isolated yield.
5
observed in the absence of HOAc, along with high yields of biaryl
by-products (Table 1, entry 8). Lowering the amount of DMSO
seemed to have little effect on the yield of b-arylation product (Table 1,
entry 9), while lowering the amount of vinyl acetate decreased the yield
of b-arylation product (Table 1, entries 11 and 12). Higher temperature
was found to increase the yield of b-arylation product. When the
reaction was carried out at 60 1C, the best result of b-arylation product
was obtained respectively (Table 1, entry 10).
With the optimized condition established, the scope of the
arylboronic acids for this palladium catalysed b-arylation reac-
tion was examined for a number of arylboronic acids (Table 2).
Moderate to good yields were obtained. Halogens (F, Cl, Br and I)
were all well tolerated, thus allowing additional transformation of
the initial b-arylation products (3d–f, 3k). In addition, both electron-
rich and electron-deficient arylboronic acids were compatible
under the current conditions (3b, 3h–j, 3l–m). It is noteworthy that
higher yields of the corresponding product could be generated with
electron-poor arylboronic acids (3g–j, 3l). Furthermore, aldehyde,
ketone, ester and cyan groups also went smoothly and gave the
corresponding products in good yields (3g–i, 3l).
6
7
8
9
10
11
67
75
12
Next, the substrate scope of arylboronic acids with regard to the
vinyl acetate moiety was examined. Prop-1-en-2-yl acetate 2b also
coupled with arylboronic acids (Table 3). When (4-chlorophenyl)-
boronic acid was applied to couple with 2b the b-arylation product
could be obtained in up to 92% yield (Table 3, entry 1). Aryl groups
a
The reaction was carried out with 1 (1 eq., 0.5 mmol), 2a (20 eq.,
10 mmol), Pd(OAc)2 (5 mol%, 5.6 mg, 0.025 mmol), BQ (1.2 eq.,
64.8 mg, 0.6 mmol), in 1 mL HOAc and 1 mL DMSO, at 60 1C, for 12 h.
b
Isolated yield.
bearing an electron-donating substituent were also well tolerated of oxidant were studied. Kinetic data showed that the concen-
under the current reaction conditions; when (4-(tert-butyl)phenyl)- tration of oxidant had little influence on the reaction rate; this
boronic acid was applied a 74% yield of b-arylation product could indicated that oxidation of Pd(0) to Pd(II) was not the rate limiting
be isolated (Table 3, entry 2).
step for this reaction (see ESI†). Then the relationships of reaction
The coupling product of arylboronic acids with prop-1-en-2-yl rate with the concentration of arylboronic acid and palladium
acetate was the acetate protected 1-arylpropan-2-one. This indicated catalyst were also studied (Fig. 2 and 3). These results showed that
that this b-arylation reaction could be a precursor for 1-arylpropan- the concentrations of arylboronic acid and palladium catalyst all
2-one synthesis. Arylboronic acid 1h was tested for the corre- have an influence on the reaction rate of this b-arylation process.
sponding 1-arylpropan-2-one synthesis and 1-arylpropan-2-one Therefore we may come to the conclusion that the transmetalation
was found to be generated in 63% in two steps (Scheme 2).
Furthermore, kinetic experiments were conducted by using
step might be the rate limiting step for this reaction (see ESI†).
This oxidative Heck reaction proceeds under acidic condi-
operando IR. Firstly, the relations of reaction rate vs. the concentration tions, which usually makes the corresponding Pd catalyst more
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Table 3 Scope of arylboronic acids for b-selective oxidative Heck reaction
electron-deficient. In the proposed catalytic cycle, Pd species I
is the key intermediate for generating the selectivity (see ESI†).
Usually, for a-selectivity, the phenyl migration to the a-position
dominates. However, in this case, as the Pd center is electron-
deficient, migration of the electron-rich phenyl group from
the Pd center is prohibited. Moreover, deprotonation at the
b-position to generate intermediate III (path A) or reductive
elimination at the b-position to generate intermediate II would
also be possible (path B) (see ESI†).
In summary, we have demonstrated the first b-selective
oxidative Heck reaction between arylboronic acid and vinyl acetate.
Various substituted arylboronic acids were found to be suitable for
the synthesis of important building block b-arylated vinyl acetates.
In addition, the reaction conditions are mild, and no ligand or base
were needed. Operando IR experiments showed that the trans-
metalation step might be the rate limiting step for this reaction.
This work was supported by the 973 Program (2012CB725302),
the National Natural Science Foundation of China (21390400,
21025206, 21272180 and 21302148), and the Research Fund
for the Doctoral Program of Higher Education of China
(20120141130002) and the Program for Changjiang Scholars
and Innovative Research Team in University (IRT1030).
with prop-1-en-2-yl acetatea
Entry
1
Substrate
Yieldb (%)
Product
92
74
2
a
The reaction was carried out with 1 (1 eq., 0.5 mmol), 2b (20 eq.,
10 mmol), Pd(OAc)2 (5 mol%, 5.6 mg, 0.025 mmol), BQ (1.2 eq.,
64.8 mg, 0.6 mmol), in 1 mL HOAc and 1 mL DMSO, at 60 1C, for 12 h.
b
Isolated yield.
Scheme 2 Synthesis of 1-arylpropan-2-one through b-arylation reaction
of vinyl acetate.
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1112 | Chem. Commun., 2014, 50, 1110--1112
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