Cu/Ag-catalyzed double decarboxylative cross-coupling reaction between cinnamic acids and aliphatic acids in aqueous solution

Article abstract of DOI:10.1039/c3ra43144d

A novel double decarboxylative cross-coupling catalyzed by copper and silver has been developed. This method provides a practical approach for the flexible synthesis of alkenes and alkynes from the readily affordable substrates.

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Cu/Ag-catalyzed double decarboxylative cross-coupling reaction
between cinnamic acids and aliphatic acids in aqueous solution
Wen-Peng Mai,* Ge Song, Gang-Chun Sun,* Liang-Ru Yang, Jin-Wei Yuan, Yong-Mei Xiao, Pu Mao
and Ling-Bo Qu
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
A novel double decarboxylative cross-coupling catalyzed by
copper and silver has been developed. This method provides a
practical approach for the flexible synthesis of alkenes and
10 alkynes from the readily affordable substrates.
Carbonꢀcarbon bond formation by transitionꢀmetalꢀcatalyzed
decarboxylative crossꢀcouplings has emerged as an attractive
and important method due to its efficiency, convenience and
environmentally benign properties.1 The method does not use
15 sensitive reagents and is easy to handle. Goossen,2 Larrosa,3
Su,4 Becht,5 and others6 have reported that arene carboxylic
acids could be coupled with a range of substrates, such as aryl
halides, aryl triflates (mesylates), diaryliodonium salts and
unactivated arenes. Myers and others have shown Heck type
20 couplings of benzoic acids with various olefins through
decarboxylative method.7,4bꢀc In addition, other studies such as
50
Scheme 1 Double decarboxylative crossꢀcouplings.
catalyzed double decarboxylative crossꢀcouplings of vinyl or
alkynyl carboxylic acids with alkyl carboxylic acids.
Optimization of the reaction conditions was carried out
using (E)ꢀcinnamic acid (1a) with pivalic acid (2a) as the
55 model substrates. We were pleased to found that the reaction
could proceed in aqueous solution with the presence of a
catalytic amount of Cu(OAc)2 or CuSO4, affording the desired
product 3aa in moderate yields (Table 1, entries 1ꢀ3). CuO
and CuI were evaluated but resulted in low yields using 10%
60 catalyst loading under the same conditions (Table 1, entries 4ꢀ
5). CuCl was ineffective to initiate the decarboxylative
coupling (Table 1, entry 6). To our delight, Cu powder
displayed good catalytic activity in this transformation with
about 70% product yield (Table 1, entries 7ꢀ9). Good yield
65 was also obtained using 5% Cu powder as catalyst when the
temperature was lowered to 90°C (Table 1, entry 10). It was
found that temperature has great influence on the reaction,
only 44% yield was obtained when we performed the reaction
at 65℃ and no product was detected at RT (Table 1, entries
70 11ꢀ12). In addition, no reaction occurred in the absence of
either Cu or AgNO3, it showed that both of the metals were
essential for this transformation (Table 1, entries 13ꢀ14).
Slightly lower product yield was obtained when AgBF4 was
used as catalyst instead of AgNO3 (Table 1, entry 15). We
75 also performed the reaction in Acetone/H2O (1:1), the result
was not good as that we obtained in CH3CN/H2O (1:1) (Table
1, entry 10).
alkynylation,8,6f
acylation,9,2c,6j
esterification10,2bꢀc
and
decarboxylation reaction11,3b have also been investigated in
this area. Despite of the significant advances, these processes
25 still suffer from some drawbacks, such as high temperature
and the need of stoichiometric amount of copper or silver salts.
On the other hand, the substrates are mainly focused on arene
carboxylic acids, which restricts their potential application.
Therefore, the development of decarboxylative couplings that
30 are capable of coupling alkynyl and alkyl carboxylic acids in a
catalytic manner is of considerable interest. Recently, Liu12
and Mao13 reported decarboxylative couplings of cinnamic
acids with alcohols and methyl arenes respectively. Li14
reported decarboxylative alkynylation and fluorination of
35 aliphatic acids under mild conditions. These works greatly
advanced the chemistry of decarboxylative coupling.
Nevertheless, the double decarboxylative crossꢀcoupling has
received much less attention in this field. Larrosa reported the
first example of homocoupling between aromatic carboxylic
40 acids in 2010.15 Afterwards, Tan and Su extended this method
to the crossꢀcoupling of two different aryl carboxylic acids
(Scheme 1, eqn(1ꢀ2)).16 Herein, we describe the first Cu/Agꢀ
With the optimal conditions in hand, the scope of the
substrates was examined. As shown in Table 2, the cinnamic
80 acids with weak electronꢀwithdrawing group could be coupled
with pivalic acid via double decarboxylative processes to give
the crossꢀcoupled products in good yields (Table 2, 3ba-3ea),
School of Chemistry and Chemical Engineering, Henan University
45 of Technology, Lianhua Street, Zhengzhou 450001, China.
Eꢀmail: maiwp@yahoo.com; sungangchun@163.com; Fax:
+86ꢀ371ꢀ67756715; Tel: +86ꢀ371ꢀ67756718
Electronic Supplementary information (ESI) available: See DOI:
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whereas the yield dropped to 29% when (E)ꢀ4ꢀfluorocinnamic
acid was used (Table 2, 3fa). For (E)ꢀ4ꢀmethylcinnamic acid,
tertiary carboxyl group with the primary carboxyl group
35 remained intact which could be further functionalized.
Strangely, the primary carboxylic acids failed to give the
desired products. The reasons were unclear at this stage and
deserve further clarification. However, Nꢀphthaloylglycine (2g)
and 2ꢀ(4ꢀchlorophenoxy)acetic acid (2l) could generate the
40 desired products 3ag and 3al in moderate yields under the
above experimental conditions (Table 2, 3ag-
Table 1 Optimization of reaction conditionsa
Table 2 Cu/Agꢀcatalyzed double decarboxylative crossꢀcoupling of
Entry
1
Catalyst ( mol%)
Cu(OAc)2 (5)
Cu(OAc)2 (10)
CuSO4 (5)
CuO (10)
CuI (10)
CuCl (10)
Cu (10)
Solvent
Yield (%)b
62
T(℃)
110
110
110
110
110
110
110
100
110
90
cinnamic acids with aliphatic acidsa,b
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
2
67
3
55
4
26
5
30
6
n.d
R
7
74
3ha, 40%
R = H, 3aa, 78%
R = o-Cl, 3ea, 82%
8
Cu (10)
71
R = p-Cl, 3ba, 85% R = p-F, 3fa, 29%
R = p-Br, 3ca, 62% R = p-Me, 3ga, 36%
9
Cu (5)
68
78(50c)
d
R = m-Br,
3dac
, 47%R = p-OMe,
3ja
,(0%)
3ab, 89%
10
11
12
13
14
15
Cu (5)
Cu (5)
65
44
Br
Cu (5)
16(rt) CH3CN/H2O (1:1)
n.d
R
R
Cu (0)
90
90
90
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
CH3CN/H2O (1:1)
n.d
R = H, 3ad, 65%
R = Cl, 3bde, 70%
R = H, 3ac, 90%
R = Cl, 3bc, 92%
3dc, 71%
Cu (5)
n.dd
67e
Cu (5)
R
a Reaction conditions: 1a (1.0 mmol), 2a (1.5 mmol), K2S2O8 (1.0 mmol),
CH3CN (3 mL), H2O (3 mL), under air atmosphere, 12 h, 90℃. b Isolated
yield. c Acetone/H2O (1:1) as solvent. d Without AgNO3. e 20% AgBF4 as
catalyst.
5
R = H, 3ae, 82%
R = Cl, 3be, 89%
3af, 73%
3ic, 96%
O
N
O
O
O
it gave the corresponding product in 36% yield. Unfortunately,
O
10 the use of (E)ꢀ4ꢀmethoxycinnamic acid did not furnish any of
the alkenylation product, it only produced the 4ꢀmethoxyꢀ
benzaldehyde in 82% yield (Table 2, 3ja, see ESI). (E)ꢀ3ꢀ
(naphthalenꢀ2ꢀyl)acrylic acid could also afford the desired
product in 40% yield (Table 2, 3ha). Various aliphatic acids
15 were then tested, the double decarboxylative couplings
proceeded smoothly for both secondary and tertiary alkyl
acids. For example, product 3ic was furnished in 96% yield
when 2ꢀ(9Hꢀfluorenꢀ9ꢀylidene)acetic acid coupled with 2ꢀ
ethylhexanoic acid. Other secondary alkyl acids such as
20 cyclobutanecarboxylic acid and 2ꢀethylbutanoic acid also
coupled smoothly to afford the products in high yields (Table
2, 3ae, 3be and 3af). In addition, satisfactory yields were
observed for the more congested tertiary carboxylic acids
although the efficacy was slightly lowered to compare with
25 the secondary congeners (Table 2, 3ad and 3bd). Similarly,
carboxylic acid containing free hydroxyl group, for example,
3ꢀhydroxyꢀ1ꢀadamantanecarboxylic acid was efficiently
transformed into the desired product 3ak in 76% yield while
hydroxy group remained intact. Moreover, the functionalized
30 aliphatic acids, such as 2i, 2j and 2l could also participate in
the transformation affording moderately high yields except for
2h (Table 2, 3ai, 3aj, 3ak and 3ah). It is noteworthy that 2,2ꢀ
dimethylpentanedioic acid (2j) coupled exclusively with the
3age, 35%
3ahe, 21%
3ai, 70%
OH
Cl
OH
O
O
3aje, 49%
3akf,76%
3al, 65%
a Reaction conditions: cinnamic acids (1.0 mmol), alphatic acids (1.5
45 mmol), Cu (5 mol%), AgNO3 (20 mol %), K2S2O8 (1.0 mmol ), CH3CN
(3 mL), H2O (3 mL), 90 ℃, 12 h. b Isolated yield. c At 70℃. d See ESI. e
RT 1 h, then 70℃, 10 h. f 90℃, 5 h.
and 3al). Gemfibrozil is an oral drug used to lower lipid levels.
50 As an application of this protocol, Gemfibrozil could also be
modified to its alkenylation product 3em in 20% yield (eqn
(3)).
55
Having demonstrated the reactivity of cinnamic acids, we
2
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next extended the method to the coupling of alkynyl and alkyl
carboxylic acids. To our delight, effective reaction was
alkanes18 via double decarboxylative crossꢀcouplings of
cinnamic acids or phenylpropiolic acid and aliphatic acids
carried out with the otherwise conditions identical to the 35 which have never been reported before. The reaction could
optimized conditions but just by elevating the reaction
temperature to 110℃, both secondary and tertiary aliphatic
acids underwent high efficient decarboxylative processes with
phenylpropiolic acid to afford the corresponding products
proceed in aqueous solution using catalytic amount of metals
and both substrates are cheap and readily available without
prefunctionalization. Further studies on this transformation
are ongoing in our laboratory.
5
4a’a-4a’c, 4a’f and 4a’k in excellent yields (Scheme 2). This 40 We gratefully acknowledge NSFC (No. 21172055).
reaction provides a new and efficient method for C(sp)−C(sp3)
10 bond formation.17
Notes and references
1
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Cu (5%)
AgNO3 (20%)
COOH HOOC
+
R
R
K2S2O8 (1.0eq)
。
a'
2a-c, 2f
4
CH CN/H O,
45
50
55
60
65
70
75
80
85
90
110 C
3
2
4a'a
4a'c
, 88%
4a'f
, 84%
, 85%
4a'b
, 91%
OH
2
4a'k
, 95%
Scheme 2 Cu/Agꢀcatalyzed double decarboxylative coupling
between phenylpropiolic acid and aliphatic acids.
15
Based on the results of our investigation (See ESI) and
previous studies12ꢀ14, a plausible mechanism is proposed in
Scheme 3. At first, Ag(I) is oxidized to Ag(II) by persulfate and
the latter induces the aliphatic acid to generate alkyl radical.
Afterwards, alkyl radical attacks αꢀposition of cinnamic acid or
20 phenylpropiolic acid to produce intermediate A1 or B1
respectively. Then, A2 and B2 which are produced by A1 and B1
undergo SET process to release CO2 and form product C by the
assistance of Cu(II) (Scheme 3). Aromatic ring in cinnamic acid
or phenylpropiolic acid is very important because it could
25 stabilize the benzyl radical and help the intermediate to finish the
decarboxylative step fast and the final products are relatively
stable under the oxydic conditions.
3
4
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30
Scheme 3 Proposed preliminary mechanism.
11 J. S. Dickstein, C. A. Mulrooney, E. M. O’Brien, B. J. Morgan and
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In summary, we have developed a Cu/Ag bimetallic tandem
catalysis for selective alkenylation or alkynylation of
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