Remarkable co-catalysis by copper(I) oxide in the palladium catalyzed cross-coupling of arylboronic acids with ethyl bromoacetate

Article abstract of DOI:10.1039/b111355k

Copper(I) oxide can effectively co-catalyze the Suzuki type cross-coupling reactions of arylboronic acids with ethyl bromoacetate. As an alternative protocol for introducing the methylenecarboxy group into functionalized molecules, this reaction occurs in

Full text of DOI:10.1039/b111355k

Remarkable co-catalysis by copper( ) oxide in the palladium catalyzed
I
cross-coupling of arylboronic acids with ethyl bromoacetate†
Xing-xin Liu and Min-zhi Deng*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Academic
Sinica, 354 Fenglin Lu, Shanghai 200032, P.R. China. E-mail: dengmz@pub.sioc.ac.cn;
Fax: 86-21-64166128; Tel: 86-21-64163300-3425
Received (in Cambridge, UK) 14th December 2001, Accepted 7th February 2002
First published as an Advance Article on the web 22nd February 2002
Copper(
I
) oxide can effectively co-catalyze the Suzuki type
Pd-catalyzed C–C bond formation is one of the most funda-
mental and important reactions in organic synthesis.1 It plays an
important role in a wide range of preparative organic processes,
from the synthesis of natural products2 to suprarmolecular
chemistry and material science.3 The widely used methods are
the palladium-catalyzed coupling reactions of electrophiles
with organomagnesium,4 -zinc,5 -tin,6 -aluminum,7 -zirconium8
and particularly organoboron9 reagents. The coupling reactions
cross-coupling reactions of arylboronic acids with ethyl
bromoacetate. As an alternative protocol for introducing the
methylenecarboxy group into functionalized molecules, this
reaction occurs in the absence of highly toxic thallium
compounds or special ligands and should be convenient and
practical.
Table 2 Cross-coupling of various arylboronic acids with ethyl bromoace-
tate co-catalyzed by Cu2Oa
Scheme 1 The cross-coupling reaction of phenylboronic acid with ethyl
bromoacetate.
Yield (%)b
Entry Arylboronic acid
Product
Ac Bd
85 84
Table 1 The cross-coupling reaction of phenylboronic acid 1 with ethyl
bromoacetate 2a
1
2
1a
1b
2a
T(°C)/ 2b 3b 4b 5b
Entry Catalyst
t(h)
(%) (%) (%) (%)
2b
2c
2d
84 82
85 84
85 83
1c
2c
3d
4d
5d
6
7
8
9
10
11
12
13
14
15
16
Pd(PPh3)4
Ag2O/Pd(PPh3)4
Pd/(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Pd(PPh3)4
80/17
80/17
25/12 19 60
25/12 22 53
80/12
110/15
5
7
65
64
4
6
3
5
4
4
3
3
4
4
3
4
3
3
3
0
0
3
0
0
0
2
3
2
4
6
4
3
2
3
4
2
2
3
2
4
0
2
2
1
3
3
3
4
1c
6
2
65
67
Pd(PPh3)4
80/17 42 46
80/17 44 44
80/17 46 40
80/18 43 41
80/15
80/15
25/15
25/15
80/17
80/17 87
80/17 86
80/17 84 10
80/17 66 29
80/17 42 55
80/17 41 56
1d
CuI/Pd(PPh3)4
Ag2O/Pd(PPh3)4
Ag2CO3/Pd(PPh3)4
Ag2O/PdCl2(dppf)
Ag2O/PdCl2(MeCN)2/(n-Bu)3P
Cu2O
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
Cu2O/Pd(PPh3)4
4
5
4
3
8
70
68
60
68
64
9
5
6
1e
1f
2e
2f
45 63
43 62
17e
18f
19g
20h
21i
8
a All the reactions were carried out using a mixture of phenylboronic acids
(1.1 mmol) and ethyl bromoacetate (1 mmol), 3 equiv. of ancillary catalyst
(except for entries 1, 3, 6, 7, 13), 3.3 equiv. K3PO4·3H2O (entry 15, 1
equiv.), and 3% catalyst (except for entry 13) in 4 ml of toluene under argon
atmosphere. b GC yields based on the amount of ethyl bromoacetate used.
c 1,4-Dioxane as the solvent and KOH as the base. d THF as the solvent.
e K2CO3 as the base. f The amount of Cu2O is 3% mmol. g The amount of
Cu2O is 1% mmol. h The amount of Cu2O is 3% mmol, the amount of
K3PO4·3H2O is 2 equiv. i The amount of Cu2O is 3% mmol, the amount of
K3PO4·3H2O is 1 equiv.
7
8
1g
1h
2g
2h
42 58
46 45
9
1i
2i
65 66
a All the reactions were carried out using a mixture of arylboronic acids (1.1
mmol) and ethyl bromoacetate (1 mmol), 3% mmol of Cu2O, 3.3 mmol base
(based on boronic acids), and 3% mmol Pd(PPh3)4 in 4 ml of toluene at 80
°C under argon atmosphere for 14 ~ 17 h. All the products were identified
by 1H NMR, IR, mass spectral and elemental analysis.† b Isolated yields
based on the amount of ethyl bromoacetate used. c Method A:using
K3PO4.3H2O as base. d Method B: using K2CO3 as base.
Scheme
2 Cross-coupling of various arylboronic acids with ethyl
bromoacetate co-catalyzed by Cu2O.
† Electronic supplementary information (ESI) available: general experi-
mental procedure and NMR, IR, MS and elemental analysis for compounds
2a–i. See http://www.rsc.org/suppdata/cc/b1/b111355k/
622
CHEM. COMMUN., 2002, 622–623
This journal is © The Royal Society of Chemistry 2002

of organoboron compounds have many attractive features (such
as high yields, mild conditions, with many tolerant functional
groups and the ability to remain unaffected in the presence of
water), which make the synthetic process very convenient.
Although the cross-coupling of aryl, alkenyl halides or
triflates with organoboron compounds has been widely de-
scribed, only a few studies to date have explored the coupling of
haloacetate with organoboron compounds.10 In order to expand
the scope of Suzuki type coupling reaction and develop a
convenient and practical method for introducing methylene-
carboxy group into molecules, we studied the cross-coupling
reactions of arylboronic acids with ethyl bromoacetate focusing
on the effects of bases, solvents and catalysts. Herein, we wish
to report our experimental results.
K2CO3 as base is better than K3PO4·3H2O in the coupling
reactions.
In conclusion, we first found that Cu2O effectively co-
catalyzed the Suzuki type coupling reactions of arylboronic
acids with ethyl bromoacetate. Compared with the cross-
coupling conditions reported,10 the reaction does not use highly
toxic thallium carbonate or special ligands such as P(Nap)3, and
should be a convenient and practical method for introducing
methylenecarboxy group into molecules. Further study on the
exact role of Cu2O and the scope of the reaction is currently
underway in our laboratory.
We thank the NNSF of China and the State Key Laboratory
of Organometallic Chemistry for financial support.
Initially, to optimize the coupling conditions, phenylboronic
acid and ethyl bromoacetate were used as the starting materials
(Scheme 1).
Notes and references
It was found that under some conditions, the rate of the
desired cross-coupling reaction is lower than the redox, homo-
coupling reactions of phenylboronic acid and the reductive
reaction of ethyl bromoacetate, which lead to biphenyl 3,
benzene 4, and ethyl acetate 5. The results are summarized in
Table 1.
Table 1 shows that the use of solvent, base and catalyst
(including co-catalyst) plays an import role in the coupling
reactions. It was noticeable that the use of Cu2O as a co-catalyst
dramatically improved the coupling of phenylboronic acid with
ethyl bromoacetate. And 3% equiv. Cu2O is enough and
necessary for accomplishing the desired coupling reaction.
Moreover, the reaction temperature is also important.
Under the optimum conditions above-mentioned, the cou-
pling reactions of various arylboronic acids with ethyl bromoa-
cetate were explored (Scheme 2).
The desired coupling products were obtained in moderate to
good yields. The results are shown in Table 2.
As illustrated in Table 2, the coupling reactions of various
arylboronic acids with ethyl bromoacetate co-catalyzed by
Cu2O can proceed smoothly to give the desired coupling
products in moderate to good yields without using highly toxic
base or special ligands. Interestingly, in some cases, using
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