Pd(ii)-catalyzed decarboxylative allylation and Heck-coupling of arene carboxylates with allylic halides and esters

Article abstract of DOI:10.1039/c0ob00696c

This work demonstrates an alternative method to prepare allylated arenes and aryl-substituted allylic esters via catalytic decarboxylative C-C bond formation using aromatic carboxylic acids and allylic halides and esters.

Full text of DOI:10.1039/c0ob00696c

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Pd(II)-catalyzed decarboxylative allylation and Heck-coupling of arene
carboxylates with allylic halides and esters†
Jiantao Wang,a Zili Cui,b Yuexia Zhang,a Huajie Li,a Long-Min Wua and Zhongquan Liu*a
Received 8th September 2010, Accepted 12th November 2010
DOI: 10.1039/c0ob00696c
This work demonstrates an alternative method to prepare
allylated arenes and aryl-substituted allylic esters via cat-
alytic decarboxylative C–C bond formation using aromatic
carboxylic acids and allylic halides and esters.
allylation could be also involved in this path. In path B, a polarity
reversing attack gives the desired allylic arenes which might involve
a transmetallation between an aryl metal intermediate formed
by electrophilic aromatic substitution and an allylic partner.
Although these methods are usually practical to prepare allylated
arenes, most of them suffer from complex mixture of products
(Friedel–Crafts aromatic allylation) and usage of organometallic
reagents which might be relatively high-cost and low stability.
Taking advantage of high stability, low-cost and commercial
availability of arene carboxylates, we successfully accomplished
a palladium-catalyzed decarboxylative arene allylation by using
simple aryl carboxylic acids and allylic halides (Scheme 1,
path C).4
As the initial research, we chose 2,4,5-trimethoxybenzoic acid
and allylic bromide as standard substrates to optimize suitable
conditions for this reaction (Table 1). It was found that the solvent,
catalysts, and additives affect the reaction efficiency critically.
The desired allylic arene was obtained in 62% yield under the
conditions: 20 mol% Pd(OAc)2, 3 eq. Ag2CO3, 5% DMSO/toluene
(v/v), 110 ◦C, 2 h (entry 1). The investigation of solvent effect
showed that toluene was a more effective solvent (entries 2–6).
However, increase of the dosage of DMSO to 20% v/v of solvent
gave only 49% yield of the product (entry 7). No products were
detected without DMSO in this system (entry 8). Other silver salts
as additives gave relatively low yields (entries 9–11). Addition of
20 mol% Cu2O used as a co-catalyst gave a slightly higher yield of
the product (entry 12). Reduction of the amount of Ag2CO3 gave
relatively lower yields (entries 13). The yields of the desired product
decreased to 45%, 55% and 55% by using 20 mol% of Pd(TFA)2,
20 mol% of PdCl2 and 10 mol% of Pd(OAc)2 respectively (entries
14–16). A 46% yield of allylated arene was formed when the
reaction was carried out at 80 ◦C (entry 17). Interestingly, the yields
increased appreciably to 75% and 89% by reducing the dosage of
Cu2O to 5 mol% and 1 mol% respectively (entries 18 and 19). An
80% yield of the product was obtained by using 10 mol% Pd(OAc)2
(entry 20). However, reducing the amount of Pd(OAc)2 to 5 mol%
resulted only 54% yield of the desired product (entry 21).
The development of more efficient protocols for C–C bond
formation that use low-cost, safe and environmentally benign
starting materials remains a critical challenge for organic chemists.
Recently, metal-catalyzed decarboxylative couplings show that
simple carboxylic acids seem to be efficient surrogates for
both halides and organometallics.1 Many efficient protocols to
construct C–C bonds via palladium-catalyzed decarboxylative
couplings have been developed by Myers,2 Gooßen,3 Tunge,4
Miura,5 and others.6 Although most of these systems suffer from
limited substrate scope, relatively high temperature and/or over-
loading additives, catalytic decarboxylative C–C bond formation
remains very attractive since carboxylic acids are stable, easily
available and relatively environmentally benign. We wish to report
herein a palladium-catalyzed decarboxylative allylation of arenes
by using arene carboxylates and allylic halides.
Allylic aromatic compounds show versatile biological activi-
ties in natural products.7 Additionally, they also represent an
important class of organic intermediates in complex molecule
synthesis due to the versatility of olefin transformations. In the
past decades, two fundamental methods have been explored to
construct the allylic arenes (Scheme 1).8 In path A, an aromatic
nucleophile attacks an allyl electrophile to give the allylated arene.
Traditional acid/Lewis acid catalyzed Friedel–Crafts aromatic
Scheme 1 Synthesis of allylic aromatic compounds.
As depicted in Table 2, various arene carboxylates and allylic
halides were tested as substrates for the coupling reaction under
the typical conditions. The corresponding (E)-a-coupled allylic
arenes were obtained as major products. Reaction of allylic
iodide with 2,4,6-trimethoxylbenzoic acid gave a very low yield
of the product (entry 1). Electron-rich arene carboxylates gave
high to excellent yields of the corresponding products except for
aState Key Laboratory of Applied Organic Chemistry and Department of
Chemistry, Lanzhou University, Lanzhou 730000, P. R. China. E-mail:
liuzhq@lzu.edu.cn; Fax: +86-931-8915557; Tel: +86-931-8912280
bDepartment of Chemistry and Biology, Gannan Normal University,
Ganzhou, Jiangxi 341000, P. R. China
† Electronic supplementary information (ESI) available: Experimental
details, characterisation data and spectra. See DOI: 10.1039/c0ob00696c
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Table 1 Optimization of the typical reaction conditionsa
Table 2 Palladium-catalyzed decarboxylative allylation of arenesa
Entry Catalyst (mol%)
Additive (eq.) Solvent
Yield (%)b
Entry
1
Allylic halide
Product
Yield (%)b
12
1
2
3
4
5
6
7
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Ag2CO3 (3) Toluene
Ag2CO3 (3) Benzene
Ag2CO3 (3) DCE
Ag2CO3 (3) Dioxane
Ag2CO3 (3) DMF
Ag2CO3 (3) DMSO
Ag2CO3 (3) Toluene
62
36
54
56
trace
0
2
3
4
90
88
70
49
(20% DMSO)
Ag2CO3 (3) Toluene
(0% DMSO)
Toluene
8
Pd(OAc)2 (20)
15
9
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)/Cu2O (20) Ag2CO3 (3) Toluene
Pd(OAc)2 (20)/Cu2O (20) Ag2CO3 (1) Toluene
Pd(TFA)2 (20)/Cu2O (20) Ag2CO3 (3) Toluene
Ag2SO4 (3)
Ag2O (3)
AgOAc (6)
31
39
47
67
49
45
55
55
46
75
89
80
54
10
11
12
13
14
15
16
17c
18
19
20
21
Toluene
Toluene
PdCl2 (20)/Cu2O (20)
Ag2CO3 (3) Toluene
Pd(OAc)2 (10)/Cu2O (20) Ag2CO3 (3) Toluene
Pd(OAc)2 (20)/Cu2O (20) Ag2CO3 (3) Toluene
Pd(OAc)2 (20)/Cu2O (5) Ag2CO3 (3) Toluene
5c
6
28
60
Pd(OAc)2(20)/Cu2O (1) Ag2CO3(3)
Toluene
Toluene
Ag2CO3 (3) Toluene
Pd(OAc)2(10)/Cu2O (1) Ag2CO3(3)
Pd(OAc)2 (5)/Cu2O (1)
a Reaction conditions: 2,4,5-trimethoxybenzoic acid (0.1 mmol), allylic
bromide (0.2 mmol), 5% DMSO/solvent (v/v), 110 ◦C, 2 h, unless
otherwise noted. b Yield determined by GC with nitrobenzene as internal
standard. c The reaction was carried out at 80 ◦C.
7
8
27
48
2,4-dimethoxylbenzoic acid (entries 2–5). The desired allylated
arene was also obtained in good yield using halogen-substituted
benzoic acid (entry 6). Although the yield was low, heterocyclic
carboxylic acid was also an effective substrate (entry 7). Various
alkyl-substituted allylic chlorides were proved to be effective
coupling partners (entries 8–11). 1-Bromo-2-butene and aryl-
substituted allylic halide gave low yields of the product (entries 12
and 13). A 33% yield of the desired product was obtained by using
halide branched allylic halide such as 1, 2-dibromo-2-propene
(entry 14). Although only electron-rich aromatic carboxylic acids
bearing at least one ortho substituted group are effective substrates,
the features of direct decarboxylative arene allylation using
carboxylic acids and allylic halides, relatively few side products
and short reaction time make this procedure very attractive.
In the Tsuji–Trost reaction, allylic halides and allylic
esters act as effective coupling partners. However, the direct
decarboxylative Heck-type coupling products were formed by
using aromatic carboxylic acids and allylic carboxylic esters
under similar conditions (Table 3). Various arene carboxylates
and allylic carboxylic esters were investigated as substrates for
the direct decarboxylative Heck-type coupling. Our experiments
show that aromatic carboxylic acids with at least one ortho
substituent are effective substrates (entries 1–6). It is noteworthy
that polyfluorobenzoic acids give relatively low yields of the
desired products (entries 7–9). Various allylic carboxylic esters
have been proved to be effective coupling partners (entries
10–13). A competing Heck coupling would occur between
the allylic and the acrylic double bonds (entries 12 and
13). However, the C–C bond formation only took place at the
9c
30
10
11
90 (E/Z = 1.8/1)d
82 (E/Z = 1.6/1)d
12c
13c
14c
17
27
33
a Reaction conditions: acid (0.3 mmol), allylic halide (0.6 mmol), 10 mol%
Pd(OAc)2, 1 mol% Cu2O, 3 eq. Ag2CO3, 5% DMSO/toluene (v/v), 110 ◦C,
2 h. b Isolated yields. c 20 mol% Pd(OAc)2. d The E- and Z-isomers are
confirmed by NOE experiments.
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Table 3 Palladium-catalyzed decarboxylative Heck coupling of aromatic
Table 3 (Contd.)
carboxylic acids with allylic estersa
Entry
14
Allylic ester
Product
Yield (%)b
86 (8/1/1)
Entry
1
Allylic ester
Product
Yield (%)b
70 (16/8/1)
a Reaction conditions: acid (0.5 mmol), allylic ester (1.0 mmol), 10 mol%
Pd(OAc)2, 1 mol% Cu2O, 3 eq. Ag2CO3, 5% DMSO/dioxane (v/v), 110 ◦C,
2 h. b Isolated yields, the isomers are confirmed by GC-MS, the ratios of
2
3
4
5
95 (10/2/1)
90 (8/2/1)
80 (20/4/1)
42 (14/2/1)
1
the isomers are determined by H NMR, and the E- and Z-isomers are
confirmed by NOE experiments. c Only one compound was obtained.
position of the terminal allylic C C bond alternative to the other
one. This suggests that another C C bond could be tolerated
in the allylic substrate. In addition, an allylic ether is also an
effective coupling partner in this system (entry 14). A very low yield
(21%) of the product was obtained without Cu2O in the reaction
of 2,4,6-trimethoxybenzoic acid with allylic acetic ester under
the typical conditions. This suggests that catalytic Cu2O in this
system is very important to form the desired product smoothly.
It is very interesting that a g-coupled product was formed in
moderate yield using (Z)-1,3-dichloro-2-butene as allylic coupling
partner (Scheme 2). A possible mechanism was demonstrated
as following. Decarboxylation of aromatic acid and Pd would
generate intermediate 1, then proceed via a Heck-like addition
to form intermediate 2 followed by elimination of PdL2(OAc)Cl
as an alternative to PdL2(OAc)H to give product 3 rather than
4. Therefore, the mechanism for the decarboxylative allylation
might be similar to that proposed by Myers.2 Carboxyl exchange
between palladium acetate and arene carboxylic acid followed
by decarboxylation forms an arylpalladium intermediate which
should be the rate-determining step, then olefin insertion followed
by b-halide elimination to give the corresponding allylic arene.
This procedure might be present as a potentially interesting topic
that draws further attention. While in the decarboxylative Heck-
type coupling with allylic ester and ether, a b-hydride elimination
would occur to give aryl-branched allylic esters and/or ether.
Further studies on the mechanism in details involving the role
of Cu2O are ongoing.
6
7
52c
26 (16/2/1)
8
9
41 (15/3/1)
33 (20/3/1)
10
11
62 (5/1/4)
90 (8/2/1)
12
13
95 (6/1/1)
80 (6/1/1)
Scheme 2 An insight into the possible mechanism.
In summary, this work demonstrates an alternative method
to prepare allylated arenes and aryl-substituted allylic esters via
catalytic decarboxylative C–C bond formation using aromatic
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carboxylic acids and allylic halides and esters. The mechanism
for the decarboxylative allylation might involve a Heck-like
addition of Ar-PdL2(OAc) to the double bond followed by
elimination of PdL2(OAc)Cl or PdL2(OAc)Br. Although one ortho
substituent in the electron-rich arene carboxylic acid is necessary,
the organometallic-reagent free, short reaction time, and relatively
high chemoselectivity features make this system attractive. Further
investigation of this procedure is underway in our laboratory.
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