Synthesis of aryl-substituted 1,4-benzoquinone via palladium(II)-catalyzed decarboxylative coupling of arene carboxylate with 1,4-benzoquinone

Article abstract of DOI:10.1055/s-0030-1258033

Various aryl-substituted 1,4-benzoquinone derivatives have been prepared via a palladium-catalyzed decarboxylative cross-coupling of electron-rich aromatic acids with 1,4-benzoquinones. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258033

2352
LETTER
Synthesis of Aryl-Substituted 1,4-Benzoquinone via Palladium(II)-Catalyzed
Decarboxylative Coupling of Arene Carboxylate with 1,4-Benzoquinone
Synthesis of
A
ryl-
a
S
ubstituted
n
1,4-Benzoqu
k
inone ai Zhao, Yuexia Zhang, Jiantao Wang, Huajie Li, Longmin Wu, Zhongquan Liu*
State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou,
Gansu 730000, P. R. of China
Fax +86(931)8915557; E-mail: liuzhq@lzu.edu.cn
Received 28 May 2010
Abstract: Various aryl-substituted 1,4-benzoquinone derivatives
have been prepared via a palladium-catalyzed decarboxylative
cross-coupling of electron-rich aromatic acids with 1,4-benzo-
quinones.
R6
O
R1
R1
O
R2
R3
COOH
R2
R3
Pd(OAc)2
Ag2CO3
O
R6
+
Key words: palladium-catalysis, decarboxylative coupling, C–C
bond formation, arene carboxylate, benzoquinone
DMSO/DMF
120 °C, 3 h
R5
R5
R4
R4
20 examples
yields: 28–83%
O
The development of direct carbon–carbon bond formation
that uses safe, environmentally benign, and low-cost start-
ing materials remains a critical challenge for modern syn-
thetic organic chemists. Recently, some efficient metal-
catalyzed decarboxylative systems have been explored for
C–C bond couplings by using simple carboxylic acids as
the active coupling partners.1 These interesting studies
show that acids can replace both halides and organometal-
lic reagents. An efficient Heck-type reaction which was
believed to be a milestone in palladium-catalyzed decar-
boxylative cross-coupling using ortho-substituted arene
carboxylates alternative to aromatic halides with olefins
was developed by Myers et al.2 On the other hand, carbox-
ylic acids are proved to be efficient surrogates to organo-
metallic reagents in Suzuki–Miyaura coupling reaction.3
Although most of these reactions suffer from limited sub-
strate scope, relatively high additive loading, and high re-
action temperature, it remains very attractive since it
would be safe, convenience, and high selectivities. We
wish to report herein a palladium-catalyzed direct decar-
boxylative coupling of carboxylic acids with 1,4-benzo-
quinone to give various aryl-substituted benzoquinones.
Substituted 1,4-benzoquinone derivatives show versatile
biological activities.4 In the past decades, many methods
have been explored to produce these useful structures.5
However, most of these methods suffer from unstable
starting materials and relatively low selectivities. Taking
advantage of safety, low-cost, and commercial availabili-
ty of carboxylic acids, we successfully accomplished a de-
carboxylative cross-coupling procedure by using arene
carboxylates as the coupling substrates (Scheme 1). To
the best of our knowledge, this is the first example of Pd-
catalyzed synthesis of aryl-substituted benzoquinones via
a direct decarboxylative coupling reaction by using aro-
matic acids and 1,4-benzoquinone.
Scheme 1 Synthesis of aryl-substituted 1,4-benzoquinones using
arene carboxylates and 1,4-benzoquinone
As the initial research, we select 2,4,5-trimethoxybenzoic
acid and 1,4-benzoquinone as standard substrates to opti-
mize suitable conditions for this reaction (Table 1). The
desired decarboxylative coupling product was obtained in
37% yield using 20 mol% of Pd(O2CCF3)2 and 3 equiva-
lents of Ag2CO3 at 120 °C in a mixed solution of 5%
DMSO–DMF (Table 1, entry 1). Interestingly, the isolat-
ed yield of the product increased to 72% by using 20
mol% of Pd(OAc)2 as catalyst (Table 1, entry 2). Howev-
er, the yield was not improved by using other palladium
catalysts (Table 1, entries 3–5) and other additives
(Table 1, entries 6–8). Further investigation of solvent ef-
fect showed that DMF is a more effective solvent
(Table 1, entries 9–12). Decrease of the catalyst and addi-
tive dosage was less efficient (Table 1, entries 13–16). In
the present Pd(II)-catalyzed decarboxylative C–C bond
formation, excess amount of Ag2CO3 was required. It acts
not only as an oxidant which is believed to reoxidize Pd(0)
to Pd(II), but also as a base which might react with car-
boxylic acid to form ArCOOAg followed by transmetala-
tion with Pd(OAc)2(DMSO)2. Other bases such as
Na2CO3, K2CO3, and Cs2CO3 cannot replace the role of
Ag2CO3.
It is seen from Table 2 that aromatic acids bearing elec-
tron-donating groups gave moderate to good yields of the
desired products (Table 2, entries 1–5).6 However, 2,3,4-
trimethoxybenzoic acid only gave 28% yield (Table 2, en-
try 6), it might be attributed to buttressing effect of the
vicinal methoxyl groups. 2,4,6-Trimethyl benzoic acid
gave 43% yield (Table 2, entry 7). The yield of the prod-
uct decreased as the acid bearing an electron-withdrawing
group. For example, 2,6-dimethoxy-3-bromobenzoic acid
and 2-methoxyl-4-amino-5-chlorobenzoic acid gave 36%
and 31% yields of the corresponding products, respective-
SYNLETT 2010, No. 15, pp 2352–2356
x
x
.x
x
.2
0
1
0
Advanced online publication: 12.08.2010
DOI: 10.1055/s-0030-1258033; Art ID: W08510ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Aryl-Substituted 1,4-Benzoquinone
2353
Table 1 Optimization of the Typical Reaction Conditionsa
ly (Table 2, entries 8 and 9). It is noteworthy that some
heterocyclic acids also gave the desired products in 34%
to 52% yields (Table 2, entries 10–12). On the other hand,
1,4-naphthoquinone and some substituted benzoquinones
were investigated as substrates for cross-coupling of aro-
matic acids under the typical conditions (Table 2). Vari-
ous aryl-substituted 1,4-naphthoquinones were obtained
in moderate yields by using electron-rich benzoic acids
and 1,4-naphthoquinone (Table 2, entries 13–16). It is
hard to evaluate the reactivity between 2,4,6-trimethoxyl-
benzoic acid and 2,4,6-trimethylbenzoic acid in this sys-
tem. For arylation of 1,4-benzoquinone, the former
showed higher reactivity than the later (entries 2 and 7),
nevertheless in the case of 1,4-naphthoquinone, 2,4,6-tri-
methoxybenzoic acid showed lower reactivity than 2,4,6-
trimethylbenzoic acid (entries 15 and 16). 2-Methyl-1,4-
benzoquinone and 2-bromo-1,4-benzoquinone gave a
mixture of 5- and 6-aryl-substituted benzoquinones in
moderate yields (entries 17–19).5 No products were ob-
tained using more sterically hindered 2,6-dimethyl 1,4-
benzoquinone (entry 20). Many other experiments show
that at least one electron-donating ortho-positioned group
in the acid is necessary for this reaction. In addition, the
steric effect of benzoquinones is obvious but the electron-
ic effect is not clear which is just opposite to carboxylic
acids.
O
O
MeO
MeO
COOH
MeO
MeO
catalyst
O
+
5% DMSO soln
120 °C, 3 h
OMe
OMe
O
Entry Catalyst
Solvent
Additive
Yield (%)b
1
2
Pd(TFA)2
Pd(OAc)2
DMF
DMF
Ag2CO3
Ag2CO3
37
72
3
4
PdCl2
DMF
Ag2CO3
Ag2CO3
Ag2CO3
AgOAc
53
35
44
44
22
53
35
38
46
53
53
47
36
22
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMF
5
DMF
6
DMF
7
DMF
Cu(OAc)2
Cu2(OH)2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
8
DMF
9
benzene
toluene
DMAc
diglymed
DMF
10
11
12
13e
14f
15g
16h
A possible mechanism of this Pd(II)-catalyzed decarbox-
ylative Heck-type cross-coupling is proposed as followed.
Decarboxylation of the acid which might be catalyzed by
silver(I) salt7 occurs to form an arylsilver intermediate,
which is then transmetalated to give an arylpalladium(II)
intermediate followed by Heck addition to benzoquinone,
and b-hydride elimination gives the C–C bond-coupling
product.
DMF
DMF
DMF
a Reaction conditions: 2,4,5-trimethoxybenzoic acid (0.2 mmol), 1,4-
benzoquinone (0.3 mmol), additive (0.6 mmol), catalyst (0.04 mmol),
DMSO (0.5 mL) in solvent (10 mL), 120 °C, 3 h, unless otherwise
specified.
b Isolated yields.
c DMA = N,N-dimethylacetamide.
d Diglyme = 2-methoxyethyl ether.
e Ag2CO3 (0.4 mmol).
f Ag2CO3 (0.2 mmol).
g Pd(OAc)2 (0.02 mmol).
h Pd(OAc)2 (0.01 mmol).
Table 2 Synthesis of Aryl-Substituted 1,4-Benzoquinone Using Carboxylic Acids with 1,4-Benzoquinonea
Entry
Benzoquinone
Product
Yield (%)b
O
O
OMe
1
83
O
O
O
OMe
O
OMe
2
78
O
O
MeO
OMe
Synlett 2010, No. 15, 2352–2356 © Thieme Stuttgart · New York

2354
Y. Zhao et al.
LETTER
Table 2 Synthesis of Aryl-Substituted 1,4-Benzoquinone Using Carboxylic Acids with 1,4-Benzoquinonea (continued)
Entry
3
Benzoquinone
Product
Yield (%)b
55
O
O
O
OMe
O
O
MeO
OMe
O
4
71
O
OMe
O
O
OMe
OMe
O
5
6
44
28
O
O
O
O
O
OMe
MeO
MeO
O
O
O
O
7
8
43
36
O
O
O
OMe
Br
O
OMe
O
O
O
OMe
Cl
9
31
O
H2N
O
O
O
N
O
10
11
34
52
O
O
O
O
O
O
O
Synlett 2010, No. 15, 2352–2356 © Thieme Stuttgart · New York

LETTER
Synthesis of Aryl-Substituted 1,4-Benzoquinone
2355
Table 2 Synthesis of Aryl-Substituted 1,4-Benzoquinone Using Carboxylic Acids with 1,4-Benzoquinonea (continued)
Entry
12
Benzoquinone
Product
Yield (%)b
39
O
O
S
O
O
O
O
OMe
13
14
63
41
O
O
O
OMe
O
OMe
O
O
MeO
O
O
OMe
OMe
15
16
49
55
O
O
O
MeO
OMe
O
O
O
O
O
O
OMe
OMe
17
18
68
55
O
O
O
O
OMe
OMe
(1:1)
O
O
O
OMe
OMe
O
O
MeO
OMe
MeO
OMe
(1:1)
O
O
O
Br
OMe
Br
OMe
19
20
41
Br
O
O
OMe
O
O
OMe
(1:1)
O
OMe
0
O
MeO
OMe
O
a Reaction conditions: acid (0.2 mmol), 1, 4-benzoquinone (0.3 mmol), Ag2CO3 (0.6 mmol), Pd(OAc)2 (0.04 mmol), DMSO (0.5 mL) in DMF
(10 mL), 120 °C, 3 h, unless otherwise specified.
b Isolated yield.
Synlett 2010, No. 15, 2352–2356 © Thieme Stuttgart · New York

2356
Y. Zhao et al.
LETTER
4824. (f) Becht, J.-M.; Catala, C.; Le Drian, C.; Wagner, A.
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In summary, this work demonstrates a palladium(II)-cata-
lyzed decarboxylative cross-coupling method to prepare
aryl-substituted 1,4-benzoquinone derivatives by using
electron-rich arene carboxylates and 1,4-benzoquinones.
Although electron-rich acid is necessary and hindered
benzoquinone is not effective, carboxylic acids involving
heterocyclic carboxylic acids as substrates, direct cou-
pling with benzoquinone, and short reaction time makes
this procedure attractive. Further investigation including
more efficient catalytic systems and expansion of the sub-
strate scope is under way in our laboratory.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
This project is supported by the Fundamental Research Funds for
the Central Universities (lzujbky-2009-78). We also thank the State
Key Laboratory of Applied Organic Chemistry and Lanzhou Uni-
versity for financial support.
(4) Zhang, B.; Salituro, G.; Szalkowski, D.; Li, Z.; Zhang, Y.;
Royo, I.; Vitella, D.; Diez, M. T.; Pelaez, F.; Ruby, C.;
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J. R.; Heck, J. V.; Smith, R. G.; Moller, D. E. Science 1999,
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References and Notes
(1) For pioneering studies of decarboxylative cross-coupling
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(6) Representative Procedure
2,6-Dimethoxybenzoic acid (36 mg, 0.2 mmol, 1.0 equiv),
1,4-benzoquinone (32 mg, 0.3 mmol, 1.5 equiv), Pd(OAc)2
(9 mg, 0.04 mmol, 0.02 equiv), and Ag2CO3 (165 mg, 0.6
mmol, 3 equiv) were added in DMF (10 mL) and DMSO (0.5
mL). The mixture was heated at 120 °C for 3 h, then was
cooled and poured into EtOAc (50 mL). The mixture was
filtered; the filtrate was washed sequentially with aq HCl
(1 M, 2 × 40 mL) and brine (20 mL), then was dried over
MgSO4, filtered, and concentrated. Chromatographic
separation gave the pure product 1 (40 mg, 0.164 mmol,
83%). 1H NMR (400 MHz, CDCl3): d = 7.33 (t, J = 8.4 Hz,
1 H), 6.85 (d, J = 10.0 Hz, 1 H), 6.81–6.71 (m, 2 H), 6.61 (d,
J = 8.4 Hz, 2 H), 3.73 (s, 6 H). 13C NMR (100 MHz, CDCl3):
d = 187.80, 185.54, 157.80, 142.73, 137.13, 136.32, 135.99,
130.89, 110.03, 103.96, 55.83. MS (EI): m/z (%) = 244 (100)
[M+], 213 (22), 162 (56), 161 (54), 131 (35), 91 (39), 54 (60),
39 (29). ESI-HRMS: m/z calcd for C14H12O4 [M + H]+:
245.0808; found: 245.0803, error: 2.0 ppm.
(d) Gooßen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313,
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Fromm, A. Chem. Commun. 2009, 7173. (b) Cornella, J.;
Sanchez, C.; Banawa, D.; Larrosa, I. Chem. Commun. 2009,
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Lett. 2009, 11, 5710.
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