Palladium-catalyzed intramolecular decarboxylative coupling of arene carboxylic acids/esters with aryl bromides

Article abstract of DOI:10.1002/chem.201103438

Give me a ring? An efficient approach has been developed for the intramolecular decarboxylative coupling of arene carboxylic acids/esters with aryl bromides catalyzed by palladium (see scheme). From a synthetic viewpoint, this method is highly attractive because the catalyst loading is low, the optimized reaction conditions are mild, and the substrate scope is broad. Copyright

Full text of DOI:10.1002/chem.201103438

COMMUNICATION
DOI: 10.1002/chem.201103438
Palladium-Catalyzed Intramolecular Decarboxylative Coupling of Arene
Carboxylic Acids/Esters with Aryl Bromides
Zengming Shen,*[a] Zhenjie Ni,[b] Song Mo,[b] Jing Wang,[b] and Yamin Zhu[a]
The transition-metal-catalyzed decarboxylation of aromat-
ic carboxylic acids has emerged as an exciting strategy in or-
ganic synthesis because it enables the formation of aryl–
metal intermediates by loss of CO2. This process can provide
uct. Since Nilsson reported the first example of transition-
metal-mediated decarboxylative biaryl coupling,[4] break-
throughs have been achieved by the groups of Goossen,[5]
Myers,[6] and others[7–11] in the development of decarboxyla-
tive cross-coupling reactions. Prominent examples include
the bimetallic Pd/Cu-catalyzed intermolecular decarboxyla-
tive coupling of benzoic acids with aryl halides, tosylates or
triflates by Goossen et al.,[5] the palladium-catalyzed decar-
boxylative Heck-type coupling of olefin and arene carboxyl-
ic acids by Myers et al. (for which stoichiometric quantities
of a Ag salt is often required),[6] and the Cu-catalyzed decar-
boxylative coupling of polyfluorobenzoates with aryl halides
by Liu et al.[7a]
To the best of our knowledge, however, the Pd-catalyzed
intramolecular decarboxylative arylation of benzoic acids
with aryl halides has not been well explored. Steglich and
co-workers have reported an intramolecular Heck-type cou-
pling between a tetrasubstituted pyrrole carboxylic acid and
a tethered aryl bromide in the synthesis of lamellarin L/G,
employing a stoichiometric amount of palladium.[12] Recent-
ly, Forgione et al. improved this stoichiometric palladium-
promoted intramolecular reaction to a catalytic system
under microwave irradiation at 1708C, but this reaction was
demonstrated for only two heteroaromatic acids.[9] As a con-
sequence, the development of a general intramolecular de-
carboxylative cross-coupling of benzoic acid with haloarenes
is still a target in organic synthesis. Herein, we wish to
report a concise and efficient protocol for the palladium-cat-
alyzed intramolecular arylation of arene carboxylic acids
with aryl halides through a decarboxylative cross-coupling
pathway under mild conditions [Eq. (3)].
À
unconventional alternatives to perform various types of C
À
C and C heteroatom bond-forming reactions relative to typ-
ical organometallic reagents.[1]
It is known that transition-metal-catalyzed cross-coupling
reactions with organometallic reagents as coupling partners
for the formation of unsymmetrical biaryl compounds, such
as the Suzuki–Miyaura coupling reaction [Eq. (1)], have
proven to be versatile and powerful methods.[2] However,
drawbacks to this reaction still exist, including the limited
commercial availability of some coupling partners or their
tedious preparation and the sensitivity of some organome-
tallic reagents. As an alternative approach, considerable at-
tention has been paid to the investigation of transition-
metal-catalyzed decarboxylative cross-coupling of arene car-
boxylic acids with aryl halides for the synthesis of biaryl
motifs [Eq. (2)].[1]
Carboxylic acids are desirable cross-coupling partners
owing to their prevalence in nature, ease of handling rela-
tive to organometallic reagents, high regioselectivity at the
À
carboxylic acid position relative to that of C H functionali-
zation,[3,10c,11] and the generation of CO2 as the waste prod-
[a] Prof. Dr. Z. Shen, Y. Zhu
School of Chemistry and Chemical Engineering
Shanghai Jiao Tong University
800 DongChuan Road, Shanghai, 200240 (P.R. China)
Fax : (+86)21-54741297
For our initial investigation of the intramolecular decar-
boxylative coupling, we chose the readily available 2-[(2-
E-mail: shenzengming@sjtu.edu.cn
bromobenzyl)oxy]benzoic acid 1a as
(Table 1). Inspired by the Goossen Pd/Cu catalyst system,
we first attempted a combination of Pd(OAc)2 (1 mol%)
a test substrate
[b] M. Sc. Z. Ni, S. Mo, J. Wang
Department of Chemistry, College of Life and Environment Sciences
Shanghai Normal University
AHCTUNGTRENNUNG
and CuI (3 mol%) as the catalyst with 1,10-phenanthroline
as the ligand and K2CO3 as the base in N-methylpyrrolidone
(NMP) at 1708C for 24 h. Pleasingly, a 36% yield of the de-
100 Guilin Road, Shanghai, 200234 (P.R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103438.
Chem. Eur. J. 2012, 18, 4859 – 4865
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4859

Table 1. Screening of reaction conditions.[a]
Tables 2 and 3. We found that ether- and amine-containing
arene carboxylic acids 1 were highly reactive and efficiently
provided the intramolecular decarboxylative coupling prod-
ucts.
For the ether-containing substrates (Table 2), electron-rich
groups (e.g., CH3 and OMe) either on the benzoic acid or
on the haloarene portion of the reagent could smoothly un-
dergo the decarboxylation/coupling process at 758C to ex-
clusively provide the desired products in 88–99% yields
(Table 2, entries 2–4 and 8). However, for the naphthyl-
based acid 1e and electron-deficient substituents (for exam-
Catalyst
([mol%])
Ligand
([mol%])
T
Yield
[%][b]
G
E
[oC]
1
2
3
4
5
CuI (3), Pd
CuI (10)
N
1,10-Phen (5)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
–
170
150
150
150
150
150
120
120
120
75
36
trace
trace
87
22
62
96
97
96
Cu
Pd(OAc)2 (10)
[Pd2A(dba)3] (10)
[Pd(PPh3)4] (10)
(OAc)2 (10)
(OAc)2 (4)
(OAc)2 (4)
(OAc)2 (4)
(OAc)2 (4)
(OAc)2 (4)
A
ACHTUNGTRENNUNG
Table 2. Scope of the biaryl formation.[a]
A
U
6
R
–
7[c]
8[c]
9[c]
10[c]
11[c]
12[c]
Pd
Pd
Pd
Pd
Pd
Pd
N
PPh3 (20)
PPh3 (8)
PCy3 (8)
PCy3 (8)
PPh3 (8)
trace
75
60
96[d]
PPh3 (8)
0
Substrate
Product
T
t
Yield
[%][b]
[a] Reaction conditions: substrate 1a (1 equiv), catalyst, ligand, K2CO3
(1.2 equiv), NMP (0.2m), under a nitrogen atmosphere for 24 h (dba=di-
benzylideneacetone; 1,10-Phen=1,10-phenanthroline). [b] Yield deter-
mined by GC with n-dodecane as the internal standard. [c] Reaction
time: 12 h. [d] Isolated yield.
[oC]
[h]
1
2
75
75
12
12
96
sired compound 6H-benzo[c]chromene (2a) was obtained
under these conditions together with the competing proto-
decarboxylation product (Table 1, entry 1). This observation
indicated that a good yield of 2a could potentially be ach-
ieved by suppressing the formation of the decarboxylative
protonolysis product in an optimized system.
>99
Further investigations showed that catalytic copper alone,
such as CuI or Cu
this reaction (Table 1, entries 2 and 3). Surprisingly, Pd-
ACHTUNGTRENNUNG(OAc)2 (10 mol%) with 1,10-phenanthroline (11 mol%) at
1508C in the absence of a copper catalyst smoothly provided
product 2a in an 87% yield (Table 1, entry 4). Other palla-
ACHTUNGTRENNUNG(OTf)2 (OTf=triflate), could not promote
3
4
5
6
75
75
12
12
7
92
88
98
92
dium complexes, such as [Pd
2ACHTUNGTERNNUG(dba)3] and [PdACHTUGNTERN(NUGN PPh3)4], were
found to be inferior to Pd(OAc)2 (Table 1, entries 5 and 6).
AHCTUNGTRENNUNG
If 1,10-phenanthroline was replaced with PPh3, an excellent
yield (96%) of 2a was obtained at 1208C (Table 1, entry 7).
Decreasing the loading of PdACHTNUTRGNEUNG(OAc)2 from 10 mol% to
4 mol% resulted in full conversion within 12 h (Table 1,
entry 8). Finally, we were pleased to discover that the intra-
molecular decarboxylative coupling reaction could be con-
ducted at a lower temperature (758C). It is interesting that,
120
120
at 758C, Pd
ACHTUNGTRENNUNG
lative coupling process, whereas PdAHCUTNGTRENNUNG
hexyl) shut down the reaction at this temperature (Table 1,
entries 10 and 11). Accordingly, the Pd-catalyzed decarbox-
7
yaltive coupling performed in the presence of PdACTHNUTRGNEUNG(OAc)2
(4 mol%), PPh3 (8 mol%), and K2CO3 (1.2 equiv) in NMP
at 758C for 12 h provided the desired coupling product 2a
exclusively (Table 1, entry 11).
With the optimized reaction conditions in hand, we at-
tempted to extend the scope and generality of this intramo-
lecular decarboxylative coupling reaction, as shown in
7
150
24
–
4860
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 4859 – 4865

Decarboxylative Coupling
COMMUNICATION
83% yield (Table 2, entry 11). Furthermore, we observed
that aryl chloride substrate 1l could also be utilized in the
decarboxylative coupling at 1508C over 3 days to provide
the corresponding product 2a, albeit in a moderate 25%
yield (Table 2, entry 12). This result indicates that the reac-
tivity of the aryl chloride is substantially lower than that of
the corresponding aryl bromide substrate. Unfortunately, al-
kenyl bromide 1m did not lead to the desired coupling
product, due to the formation of 2-(prop-2-yn-1-yloxy)ben-
zoic acid through dehydrobromidation under the reaction
conditions (Table 2, entry 13).
Table 2. (Continued)
Substrate
Product
T
t
Yield
[%][b]
[oC]
[h]
8
9
75
75
21
12
7
96
85
74
The reaction scope is not limited to ether substrates,
amine-containing substrates and heteroaromatic acids are
also tolerated (Table 3). During these studies, a strong de-
pendence on the nitrogen substitution pattern was ob-
10
120
Table 3. Scope of the biaryl formation.[a]
Substrate
Product
T
t
Yield
[oC] [h] [%][b]
11
120
24
83
1
2
3
120
120
120
24
48
72
–
12
13
2a
150
120
72
24
25
–
72
58
[a] Reaction conditions: under
a
nitrogen atmosphere, substrate
(1 equiv), Pd(OAc)2 (4 mol%), PPh3 (8 mol%), K2CO3 (1.2 equiv), NMP
ACHTUNGTRENNUNG
(0.2m). [b] Isolated yield.
4
5
120
120
24
24
–
–
ple, Cl (1 f) and NO2 (1g)), no reaction was observed at
758C. However, upon heating to 1208C, 1e, 1 f, and 1j
smoothly produced the coupling products in high yields (74–
98%; Table 2, entries 5, 6, and 10). Notably, naphthyl-based
acid 1e gave a single coupling product 2e (Table 2, entry 5).
In the report by Fagnou et al., on the other hand, the naph-
thyl substrate with a tethered aryl bromide gave two regioi-
À
someric products through C H bond activation at the a and
b positions on the naphthyl ring.[3d] This case shows that the
decarboxylative coupling has higher regioselectivity for the
À
carboxylic acid position than C H activation. Disappoint-
6
7
120
120
24
24
60
ingly, the strongly electron-withdrawing NO2 group (1g) did
not provide the corresponding product even at 1508C
(Table 2, entry 7). Cl and F atoms were tolerated in biaryl
products 2 f, 2i, and 2j, which provides possible pathways
for further functionalization and applications in organic syn-
thesis (Table 2, entries 6, 9, and 10).
–
In addition to six-membered-ring products, dibenzo-
ACHTUNGTRENNUNG[b,d]furan (2k) was formed under the standard conditions in
Chem. Eur. J. 2012, 18, 4859 – 4865
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4861

Z. Shen et al.
with this substrate either [Eq. (4)]. Thus, in agreement with
our proposal, a suitable coordinating ability of the neighbor-
ing heteroatom appears to be critical for this reaction.
Moreover, we were pleased to find that indole acids 1v–1y
could smoothly undergo the decarboxylative coupling reac-
tion to form the corresponding products 2v–2y in high
yields (Table 3, entries 9–12). The reaction provides a simple
and efficient method to synthesize potentially bioactive
compounds containing an indole framework.[14]
Table 3. (Continued)
Substrate
Product
T
t
Yield
[oC] [h] [%][b]
8
75
28
86
9
10
11
75
120
120
24
60
48
93
79
85
Next, we envisaged that the direct use of esters instead of
carboxylic acids could shorten synthetic sequences if the
ester hydrolysis and cross-coupling could be conducted in
one pot. One challenge in the design of such a process is the
rate match between the hydrolysis/decaryboxylation of the
ester and the oxidative addition of the aryl bromide. Pleas-
ingly, our initial efforts to apply the optimized conditions for
carboxylic acid substrates to ester substrates were successful,
as summarized in Table 4. A 35% yield of 2a formed from
ester 3a was obtained under the standard conditions (Pd-
12
75
48
74
AHCTUNGRTEGNUN(N OAc)2 (10 mol%), 1,10-phenanthroline (11 mol%), and
[a] Reaction conditions: under
a
nitrogen atmosphere, substrate
(1 equiv), Pd(OAc)2 (4 mol%), PPh3 (8 mol%), K2CO3 (1.2 equiv), NMP
(0.2m). [b] Isolated yield.
ACHTUNGTRENNUNG
K2CO3 (1.2 equiv) in NMP at 1508C; Table 4, entry 1). With
this promising preliminary result in hand, different bases
Table 4. Optimization of conditions for the intramolecular decarboxyla-
tive coupling of esters with aryl bromides.[a]
served.[13] Surprisingly, when the ether oxygen was switched
À
for an N H group, substrate 1n did not form the desired
product under the standard conditions, even at 1208C
(Table 3, entry 1). We believe that the electronic and steric
properties of the nitrogen atom may play a pivotal role in
coordinating to the palladium catalyst and controlling the
reaction efficiency. Keeping this hypothesis in mind, we ad-
justed the substituent on the nitrogen atom and discovered
that a methyl (1o) or acetyl group (1p) on the nitrogen
atom efficiently promoted the intramolecular decarboxyla-
tive coupling process (72 and 58% yields, respectively,
Table 3, entries 2 and 3). Interestingly, when the nitrogen
atom has a mesyl group attached to it, none of the corre-
sponding product was observed (Table 3, entry 4). Analo-
gous trends were discovered for substrates 1r–u (Table 3,
entries 5–8).
To further understand the effect of neighboring-group co-
ordination, we subjected compound 1aa, bearing a carbon
atom in place of the oxygen atom, to our standard condi-
tions, which resulted in no observable coupling product
[Eq. (4)]. In addition, we synthesized thioether substrate
1bb, which is considered to have strong coordination ability
with transition metals, and found that no reaction occurred
Pd Loading
[mol%]
Ligand
([mol%])
Base
ACHTUNGTRENN(UNG [equiv])
Yield
[%][b]
G
1
2
3
5
6
7
8
9
10
11
12
13[c]
10
10
10
10
10
10
10
10
10
10
4
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
1,10-Phen (11)
PPh3 (8)
K2CO3 (1.2)
Na2CO3 (1.2)
NaOH (1.2)
KOHACTHNGUTRENNU(G 1.2)
Cs2CO3 (1.2)
tBuOLi (1.2)
tBuOK (1.2)
tBuONa (1.2)
tBuONa (1.2), H2O (5)
tBuONa (1.2), H2O (2)
tBuONa (1.2), H2O (2)
tBuONa (1.2), H2O (2)
35
7
17
12
9
15
21
43
24
45
67
85[d]
4
PPh3 (8)
[a] Reaction conditions: under
a
nitrogen atmosphere, substrate
(1 equiv), catalyst, ligand, base, NMP (0.2m), 1508C, 24 h. [b] Yield deter-
mined by GC with n-dodecane as the internal standard. [c] At 1008C for
15 h. [d] Isolated yield.
4862
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 4859 – 4865

Decarboxylative Coupling
COMMUNICATION
were screened in the reaction and gave low to moderate
yields (Table 4, entries 2–9). It is likely that some moisture
in these systems promoted the reaction, allowing it to occur.
We found that tBuONa with 2 equivalents of H2O and by
using PPh3 as the ligand at 1008C led to the best result and
increased the yield to 85% (Table 4, entry 13). The two
equivalents of H2O were required to promote the in situ hy-
drolysis of the ester.
catalyst loading is low, the optimal reaction conditions are
mild, and the substrate scope is broad. This method could
be used in the synthesis of some biologically active com-
pounds. A representative example is the synthesis of 2-[6-
oxophenanthridin-5ACHTUNRGTNE(NUG 6H)-yl]acetic acid 7, which has been
shown to have some activity in inhibiting aldose reduc-
tase.[15] As shown in Scheme 1, compound 5, prepared by
Next, we subjected substitut-
ed aryl bromide–esters to these
optimized conditions to test this
sequential hydrolysis/decarbox-
ylative coupling reaction. As
shown in Table 5, aromatic
methyl esters containing elec-
tron-donating groups, such as
Scheme 1. Synthesis of biologically active compound 7.
Me and OMe 3b–3d, on the ar-
omatic ring could provide the desired products 2b–2d in
71–90% yields (Table 5, entries 2–4). Notably, phenyl ester
4a was also tolerated in the sequential transformations to
provide biaryl compound 2a in a 71% yield (Table 5,
entry 5).
the condensation of methyl 2-aminobenzoate and 2-bromo-
benzoic acid, reacted with ethyl 2-bromoacetate and then
hydrolyzed under basic conditions to yield compound 6,
containing an aromatic and an aliphatic carboxylic acid in
one molecule. Notably, the aryl bromide preferentially re-
acted with the benzoic acid and not the aliphatic carboxylic
acid to give the desired compound 7 under the standard de-
carboxylative coupling conditions. This selectivity indicates
that an aromatic carboxylic acid is easier to decarboxylate
and has higher reactivity than an aliphatic carboxylic acid.
This conclusion is consistent with the observation that ali-
phatic carboxylic acid 1cc did not react under the Pd-cata-
lyzed coupling conditions.[16]
The intramolecular decarboxylative coupling reaction is
highly attractive from a synthetic point of view in that the
Table 5. Scope of the biaryl formation from esters.[a]
Substrate
Product
Yield
[%][b]
On the basis of the previous investigations into decarbox-
ylative coupling,[5a–b,6,7b–d,9,11c] a possible mechanism is out-
lined in Scheme 2. The highly active Pd0 was generated in
situ from PdII, followed by oxidative addition of the aryl
bromide to the Pd0 catalyst to form arylpalladium interme-
1
85
2
3
4
90
77
71
5
71
[a] Reaction conditions: under
(1 equiv), Pd(OAc)2 (4 mol%), PPh3 (8 mol%), tBuONa (1.2 equiv),
H2O (2 equiv), NMP (0.2m), 1008C. [b] Isolated yield.
a
nitrogen atmosphere, substrate
ACHTUNGTRENNUNG
Scheme 2. Proposed mechanism for the decarboxylative biaryl synthesis.
Chem. Eur. J. 2012, 18, 4859 – 4865
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4863

Z. Shen et al.
3120; d) N. Rodrꢂguez, L. J. Goossen, Chem. Soc. Rev. 2011, 40,
5030–5048.
[2] For reviews, see: a) Handbook of Organopalladium Chemistry for
Organic Synthesis (Ed.: E.-I. Negishi), Wiley, New York, 2002,
Chapter 3, pp. 215–1119, and references therein; b) N. Miyaura, A.
Suzuki, Chem. Rev. 1995, 95, 2457–2483.
[3] a) L.-C. Campeau, M. Parisien, M. Leblanc, K. Fagnou, J. Am.
Chem. Soc. 2004, 126, 9186–9187; b) M. Parisien, D. Valette, K.
Fagnou, J. Org. Chem. 2005, 70, 7578–7584; c) L.-C. Campeau, P.
Thansandote, K. Fagnou, Org. Lett. 2005, 7, 1857–1860; d) L.-C.
Campeau, M. Parisien, A. Jean, K. Fagnou, J. Am. Chem. Soc. 2006,
128, 581–590; e) W. Liu, H. Cao, J. Xin, L. Jin, A. Lei, Chem. Eur.
J. 2011, 17, 3588–3592; f) H. Li, C.-L. Sun, M. Yu, D.-G. Yu, B.-J.
Li, Z.-J. Shi, Chem. Eur. J. 2011, 17, 3593–3597; g) T. Harayama, A.
Hori, Y. Nakano, T. Akiyama, H. Abe, Y. Takeuchi, Heterocycles
2002, 58, 159–164; h) D. E. Ames, A. Opalko, Tetrahedron 1984, 40,
1919–1925; i) P. H. Bernardo, K.-F. Wan, T. Sivaraman, J. Xu, F. K.
Moore, A. W. Hung, H. Y. K. Mok, V. C. Yu, C. L. L. Chai, J. Med.
Chem. 2008, 51, 6699–6710.
diate A, which likely coordinates to Pd through both the
carboxylate and ether oxygen atoms, forming intermedia-
te B. Decarboxylation then occurs with extrusion of CO2 to
give cyclobiarylpalladium intermediate C. It is worth noting
that the coordinating ability of the ether oxygen atom in the
substrate may help stabilize intermediate B and facilitate
the decarboxylation reaction.[13] Reductive elimination of in-
termediate C provides the desired product and regenerates
the Pd0 catalyst. A detailed mechanistic investigation is cur-
rently underway in our laboratory.
In summary, we have achieved an efficient protocol for
forming biaryl compounds through palladium-catalyzed in-
tramolecular decarboxylative coupling of arene carboxylic
acids with aryl bromides. In contrast to the system reported
by Goossen et al., only a single catalytic metal is required.
This practical and convenient method has broad substrate
scope, produces high yields under mild conditions, and is
complementary to that of the intermolecular decarboxyla-
tive coupling reaction under Pd/Cu-cocatalyzed conditions.
Furthermore, decarboxylative coupling from the ester in-
stead of the carboxylic acid has also been shown to smooth-
ly yield intramolecular biaryl coupling products.
[4] a) M. Nilsson, Acta. Chem. Scand. 1966, 20, 423–426; b) M. Nilsson,
Acta. Chem. Scand. 1968, 22, 1998–2002.
[5] a) L. J. Goossen, G. Deng, L. M. Levy, Science 2006, 313, 662–664;
b) L. J. Goossen, N. Rodriguez, B. Melzer, C. Linder, G. Deng,
L. M. Levy, J. Am. Chem. Soc. 2007, 129, 4824–4833; c) L. J. Goos-
sen, B. Zimmermann, T. Knauber, Angew. Chem. 2008, 120, 7211–
7214; Angew. Chem. Int. Ed. 2008, 47, 7103–7106; d) L. J. Goossen,
N. Rodriguez, C. Linder, J. Am. Chem. Soc. 2008, 130, 15248–
15249; e) L. J. Goossen, F. Rudolphi, C. Oppel, N. Rodriguez,
Angew. Chem. 2008, 120, 3085–3088; Angew. Chem. Int. Ed. 2008,
47, 3043–3045; f) L. J. Goossen, B. Zimmermann, C. Linder, N. Ro-
driguez, P. P. Lange, J. Hartung, Adv. Synth. Catal. 2009, 351, 2667–
2674; g) L. J. Goossen, C. Linder, N. Rodriguez, P. P. Lange, Chem.
Eur. J. 2009, 15, 9336–9349; h) L. J. Goossen, C. Linder, N. Rodri-
guez, P. P. Lange, Angew. Chem. 2010, 122, 1129–1132; Angew.
Chem. Int. Ed. 2010, 49, 1111–1114; i) L. J. Goossen, P. Mamone, C.
Oppel, Adv. Synth. Catal. 2011, 353, 57–63.
[6] a) A. G. Myers, D. Tanaka, M. R. Mannion, J. Am. Chem. Soc. 2002,
124, 11250–11251; b) D. Tanaka, A. G. Myers, Org. Lett. 2004, 6,
433–436; c) D. Tanaka, S. P. Romeril, A. G. Myers, J. Am. Chem.
Soc. 2005, 127, 10323–10333.
[7] a) R. Shang, Y. Fu, Y. Wang, Q. Xu, H.-Z. Yu, L. Liu, Angew.
Chem. 2009, 121, 9514–9518; Angew. Chem. Int. Ed. 2009, 48, 9350–
9354; b) R. Shang, Y. Jiang, Q. Xu, Y. Wang, L. Liu, Org. Lett. 2010,
12, 1000–1003; c) R. Shang, Y. Fu, J. B. Li, S. L. Zhang, Q. X. Guo,
L. Liu, J. Am. Chem. Soc. 2009, 131, 5738; d) R. Shang, Z.-W. Yang,
Y. Wang, S.-L. Zhang, L. Liu, J. Am. Chem. Soc. 2010, 132, 14391–
14393.
Experimental Section
General procedure for intramolecular decarboxylative arylation: Synthe-
sis of 6H-benzo[c]chromene (2a): Under a nitrogen atmosphere, a mix-
ture of PdACHTUNGTRENNUNG(OAc)2 (4 mol%, 0.9 mg), PPh3 (8 mol%, 2.1 mg), 1a
(0.1 mmol, 30 mg), and K2CO3 (0.12 mmol, 17 mg) was dissolved in NMP
(0.5 mL). The reaction system was stirred at 758C and monitored by
TLC. Upon completion, the mixture was poured into aqueous HCl (1 n,
5 mL), and extracted with ethyl acetate (3ꢁ15 mL). The combined or-
ganic layers were dried over anhydrous Na2SO4, filtered, and the volatiles
were removed in vacuo. The residue was purified by column chromatog-
raphy (ethyl acetate/petroleum ether), yielding 2a (96%) as a yellow oil.
1H NMR (400 MHz, CDCl3) d=5.02 (s, 2H), 6.91 (dd, J=8.1, 1.2 Hz,
1H), 6.96 (dt, J=7.5, 1.2 Hz, 1H), 7.05 (d, J=7.4 Hz, 1H), 7.12–7.20 (m,
2H), 7.28 (t, J=7.6 Hz, 1H), 7.60 (d, J=7.7 Hz, 1H), 7.64 ppm (dd, J=
7.7, 1.6 Hz, 1H); IR (KBr): n˜ =3179, 1484, 1400, 1244, 1120, 1017, 755,
688 cmÀ1; MS (EI): m/z: 182 [M]+, 181, 152, 127, 115, 91, 76.
[8] Z. Duan, S. Ranjit, P. Zhang, X. Liu, Chem. Eur. J. 2009, 15, 3666–
3669.
[9] a) P. Forgione, M.-C. Brochu, M. St-Onge, K. H. Thesen, M. D.
Bailey, F. Bilodeau, J. Am. Chem. Soc. 2006, 128, 11350–11351; b) F.
Bilodeau, M.-C. Brochu, N. Guimond, K. H. Thesen, P. Forgione, J.
Org. Chem. 2010, 75, 1550–1560.
Acknowledgements
This work was supported by the National Natural Sciences Foundation of
China (20852004, 20902058), the Shanghai Pujiang Program
(09J1408100), the Shanghai Education Committee (ssd09018) and the
Shanghai Jiao Tong University (“SMC Rising Star Project” and present
funding).
[10] For selected other examples of decarboxylative coupling reactions,
see: a) J.-M. Becht, C. Catala, C. Le Drian, A. Wagner, Org. Lett.
2007, 9, 1781–1783; b) J.-M. Becht, C. L. Drian, Org. Lett. 2008, 10,
3161–3164; c) A. Voutchkova, A. Coplin, N. E. Leadbeater, R. H.
Crabtree, Chem. Commun. 2008, 6312–6314; d) A. Maehara, H.
Tsurugi, T. Satoh, M. Miura, Org. Lett. 2008, 10, 1159–1162; e) M.
Miyasaka, A. Fukushima, T. Satoh, K. Hirano, M. Miura, Chem.
Eur. J. 2009, 15, 3674–3677; f) P. Hu, J. Kan, W. Su, M. Hong, Org.
Lett. 2009, 11, 2341–2344; g) Z. Fu, S. Huang, W. Su, M. Hong, Org.
Lett. 2010, 12, 4992–4995; h) F. Zhang, M. F. Greaney, Org. Lett.
2010, 12, 4745–4747; i) Y. Luo, J. Wu, Chem. Commun. 2010, 46,
3785–3787; j) Z.-M. Sun, P. Zhao, Angew. Chem. 2009, 121, 6854–
6858; Angew. Chem. Int. Ed. 2009, 48, 6726–6730; k) Z.-M. Sun, J.
Zhang, P. Zhao, Org. Lett. 2010, 12, 992–995; m) R. Shang, Z.
Huang, L. Chu, Y. Fu, L. Liu, Org. Lett. 2011, 13, 4240–4243; n) C.-
F. Yang, J.-Y. Wang, S.-K. Tian, Chem. Commun. 2011, 47, 8343–
Keywords: arenes · aryl halides · arylation · carboxylic acid ·
cross-coupling · decarboxylation · intramolecular reactions
[1] For recent reviews, see: a) A. Zapf, Angew. Chem. 2003, 115, 5552–
5557; Angew. Chem. Int. Ed. 2003, 42, 5394–5399; b) O. Baudoin,
Angew. Chem. 2007, 119, 1395–1397; Angew. Chem. Int. Ed. 2007,
46, 1373–1375; c) L. J. Goossen, N. Rodriguez, K. Goossen, Angew.
Chem. 2008, 120, 3144–3164; Angew. Chem. Int. Ed. 2008, 47, 3100–
4864
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 4859 – 4865

Decarboxylative Coupling
COMMUNICATION
8345; o) D. Yang, D. Zhao, L. Mao, L. Wang, R. Wang, J. Org.
Chem. 2011, 76, 6426–6431; p) J. Hu, N. Zhao, B. Yang, G. Wang,
L.-N. Guo, Y.-M. Liang, S.-D. Yang, Chem. Eur. J. 2011, 17, 5516–
5521; q) H. Zhao, Y. Wei, J. Xu, J. Kan, W. Su, M. Hong, J. Org.
Chem. 2011, 76, 882–893; r) M. Yamashita, K. Hirano, T. Satoh, M.
Miura, Adv. Synth. Catal. 2011, 353, 631–636; s) F. A. Arroyave,
J. R. Reynolds, Org. Lett. 2010, 12, 1328–1331; t) X.-C. Huang, F.
Wang, Y. Liang, J.-H. Li, Org. Lett. 2009, 11, 1139–1142.
[13] For some representative examples relating to the chelating effect,
see: a) G. Liu, X. Lu, J. Am. Chem. Soc. 2006, 128, 16504–16505;
b) Z. Shen, P. K. Dornan, H. A. Khan, T. Woo, V. M. Dong, J. Am.
Chem. Soc. 2009, 131, 1077–1091; c) M. Imai, M. Tanaka, S.
Nagumo, N. Kawahara, H. Suemune, J. Org. Chem. 2007, 72, 2543;
d) C.-H. Jun, C. W. Moon, D.-Y. Lee, Chem. Eur. J. 2002, 8, 2422,
and references therein.
[14] a) A. Scopton, T. R. Kelly, J. Org. Chem. 2005, 70, 10004–10012;
b) G. A. Kraus, T. Wu, Tetrahedron 2005, 61, 9502–9505; c) T.
Komoda, S.-I. Nakatsuka, Heterocycl. Commun. 2003, 9, 119–122.
[15] a) J. DeRuiter, B. E. Swearingen, V. Wandrekar, C. A. Mayfield, J.
Med. Chem. 1989, 32, 1033–1038;
[11] a) C. Wang, I. Piel, F. Glorius, J. Am. Chem. Soc. 2009, 131, 4194–
4195; b) J. Cornella, P. Lu, I. Larrosa, Org. Lett. 2009, 11, 5506–
5509; c) K. Xie, Z. Yang, X. Zhou, X. Li, S. Wang, Z. Tan, X. An,
C.-C. Guo, Org. Lett. 2010, 12, 1564–1567; d) P. Fang, M. Li, H. Ge,
J. Am. Chem. Soc. 2010, 132, 11898–11899; e) M. Li, H. Ge, Org.
Lett. 2010, 12, 3464–3467; f) F. Zhang, M. F. Greaney, Angew.
Chem. 2010, 122, 2828–2831; Angew. Chem. Int. Ed. 2010, 49, 2768–
2771; g) J. Lindh, P. J. R. Sjçberg, M. Larhed, Angew. Chem. 2010,
122, 7899–7903; Angew. Chem. Int. Ed. 2010, 49, 7733–7737.
b) J. DeRuiter, R. A. Davis, V. G.
Wandrekar, C. A. Mayfield, J.
Med. Chem. 1991, 34, 2120–2126.
[16] Compound 1cc did not give the
corresponding product under the
standard conditions.
[12] a) C. Peschko, C. Winklhofer, W. Steglich, Chem. Eur. J. 2000, 6,
1147–1152; b) A. Heim, A. Terpin, W. Steglich, Angew. Chem. 1997,
109, 158–159; Angew. Chem. Int. Ed. Engl. 1997, 36, 155–156.
Received: November 2, 2011
Revised: February 16, 2012
Published online: March 15, 2012
Chem. Eur. J. 2012, 18, 4859 – 4865
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4865