Pd-catalyzed decarboxylative couplings of arenecarboxylic acids with aryl iodides

Article abstract of DOI:10.1016/j.tet.2009.04.047

The combination of palladium chloride with BINAP shows high efficiency in the decarboxylative cross-coupling reactions of arenecarboxylic acids with aryl iodides. The reactions proceed smoothly to generate the corresponding biaryl compounds in good to excellent yields.

Full text of DOI:10.1016/j.tet.2009.04.047

Tetrahedron 65 (2009) 4635–4638
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Pd-catalyzed decarboxylative couplings of arenecarboxylic acids
with aryl iodides
,b,
*
Zhiyong Wang a, Qiuping Ding a, Xiaodan He a, Jie Wu a
a Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 March 2009
Received in revised form 10 April 2009
Accepted 14 April 2009
Available online 18 April 2009
The combination of palladium chloride with BINAP shows high efficiency in the decarboxylative cross-
coupling reactions of arenecarboxylic acids with aryl iodides. The reactions proceed smoothly to generate
the corresponding biaryl compounds in good to excellent yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Decarboxylative coupling
Arenecarboxylic acid
Aryl iodide
Palladium chloride
BINAP
1. Introduction
PdCl2 and 60 mol % of highly toxic AsPh3 had to be utilized in the
reaction to obtain respectableyields. Moreover, aryl bromidewas not
Palladium-catalyzed coupling has become a principal method of
forming a C–C bond.1 Recently, the palladium-catalyzed decarboxy-
lative cross-coupling reaction is attracting increasing interest since it
provides an important alternative route for carbon–carbon bond
formation. As highlighted by Baudoin,2 this method has several ad-
vantages over the conventional transition metal-catalyzed cross-
coupling reactions and the direct arylation through C-H activation,
concerning the regioselectivity as well as atom and step economy
issues. Since Nilsson reported the first example for transition-metal
mediated decarboxylative biaryl coupling,3 breakthroughs have
been achieved by Myers,4 Goossen,5 and others6,7 in the de-
velopment of Pd-catalyzed decarboxylative cross-coupling re-
actions. For instance, Myers reported a versatile decarboxylative
Heck-type reaction between arenecarboxylic acids and olefins under
palladium catalysis.4 Goossen and co-workers have described the
efficient preparation of biaryls or ketones via a Pd/Cu co-catalyzed
decarboxylative coupling of arenecarboxylic acids and aryl halides.5
The reactions usually finished in 24 h at 120–170 ꢀC with limited
substrate scope. The group of Forgione and Bilodeau reported Pd-
catalyzed arylation of heteroaromatic carboxylic acids.6d Becht and
Wagner described the decarboxylative couplings of arenecarboxylic
acids with aryl iodides catalyzed by the combination of PdCl2 and
AsPh3 in the presence of Ag2CO3 in DMSO.7a However, 30 mol % of
effective under the conditions. Subsequently, they presented Pd-
catalyzed couplings of arenecarboxylic acids with diaryliodonium
triflates.7d Again, high loading of palladium catalyst (20 mol %) and
ligand was employed. Thus, it is still desired to develop general and
efficient methods for this type of decarboxylative coupling. As part of
a continuing effort in our laboratory for C–C bond formation,8 we
became interested in developing efficient methods via transition
metal-catalyzed decarboxylative coupling of carboxylic acids with
aryl halides. Herein, we disclose our recent efforts for decarboxy-
lative cross-coupling of arenecarboxylic acids with aryl iodides cat-
alyzed by the combination of PdCl2 and BINAP. The reactions usually
finished in 0.5–2 h with good to excellent isolated yields.
2. Results and discussion
Initially, the reaction was conducted using 2-nitrobenzoic acid
1a and 4-iodoanisole 2a as model substrates in the presence of
palladium chloride as catalyst (Table 1). At the outset, various li-
gands were screened in the presence of Ag2CO3 as additive at
150 ꢀC. Gratifyingly, in the presence of S-Phos (10 mol %) this re-
action proceeded smoothly in DMA to afford the corresponding
product 3a in 59% yield (Table 1, entry 1). Further investigation
revealed that the result could be dramatically improved when
BINAP was employed in the reaction (83% yield, Table 1, entry 4). In
addition, this reaction went to completion in less than 2 h. Other
phosphine ligands utilized in this decarboxylative cross-coupling
* Corresponding author. Tel.: þ86 21 5566 4619; fax: þ86 21 6510 2412.
E-mail address: jie_wu@fudan.edu.cn (J. Wu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.047

4636
Z. Wang et al. / Tetrahedron 65 (2009) 4635–4638
Table 1
Table 2 (continued)
Initial studies for Pd-catalyzed decarboxylative coupling of 2-nitrobenzoic acid 1a
and 4-iodoanisole 2a
Entry
Carboxylic acid 1
Aryl iodide 2
Product
Yielda (%)
91
OMe
I
[Pd] (10 mol %)
I
COOH
+
Ligand (10 mol %)
4
1a
3d
Ac
Ag2CO3, solvent
150 °C
MeO
NO2
2d
NO2
3a
I
1a
2a
5
1a
1a
3e
87
PR2
OMe
2e
O
O
PPh2
PPh2
PPh2
PPh2
I
CyJohnPhos: R = Cy
DPEphos
Xantphos
JohnPhos: R = t-Bu
6
7
3f
85
89
Me
Me
CF3
2f
PCy2
OMe
N
N
MeO
I
Me
Me
Cl
Me Me
IMes HCl
1a
1a
3g
Cl
S-Phos
[Pd]
2g
Yielda (%)
I
Entry
Ligand
S-Phos
JohnPhos
CyJohnPhos
BINAP
PCy3
P(o-tolyl)3
DPPP
Solvent
1
2
3
4
5
6
7
8
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
Pd(PPh3)2Cl2
Pd(dppf)Cl2
PdCl2
PdCl2
PdCl2
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMSO
DMF
DMA
59
37
63
83
39
47
49
55
49
52
42
58
52
61
64
61
30
8
9
3h
3i
60
72
Me
MeO
MeO
COOH
NO2
2h
2a
1b
10
11
1b
1b
2b
2d
3j
3k
82
75
DPPF
9
Xantphos
DPEphos
IMesꢁHCl
BINAP
BINAP
BINAP
10
11
12
13
14
15
16
17
OMe
COOH
12
2a
3l
63
OMe
1c
BINAP
BINAP
13
14
1c
1c
2c
2g
3m
3n
76
91
/
a
Isolated yield based on 2-Nitrobenzoic Acid 1a.
F
F
COOH
reaction showed inferior results. Lower yields were observed when
N-heterocyclic carbene9 was used as a replacement (Table 1, entry
11). We also tested other palladium catalysts, and PdCl2 was the
best choice (Table 1, entries 12–14). Reactions in other solvents
(such as DMSO and DMF, Table 1, entries 15 and 16) or at lower
15
2a
3o
75
Cl
1d
COOH
F
16
17
2a
2c
3p
3q
54
41
Table 2
Pd-catalyzed decarboxylative cross-coupling reactions of arenecarboxylic acids 1
with aryl iodides 2
1e
COOH
CO2H
I
PdCl2 (10 mol %)
BINAP (10 mol %)
R2
OMe
1f
R1
R2
+
R1
Ag2CO3 (3.0 equiv)
DMA, 150 °C
0.5-2h
O2N
COOH
3
1
2
18
2c
3r
40
Entry
1
Carboxylic acid 1
Aryl iodide 2
Product
Yielda (%)
83
NO2
1g
COOH
I
3a
3b
a
Isolated yield based on arenecarboxylic acid 1.
NO2
1a
MeO
2a
temperatures (data not shown in Table 1) either occurred to afford
lower conversions, required longer reaction times, or both. In the
absence of ligand or decreasing the amount of palladium catalyst
the yield was diminished. We also tested other additives (such as
CuI, Cu(OAc)2, AgOAc) as replacement of Ag2CO3. However, the
yield could not be improved (data not shown in Table 1).
I
2
3
1a
1a
96
95
2b
I
3c
Having demonstrated the viability of this catalytic strategy we
next investigated the scope of the transformation under the
Me
2c

Z. Wang et al. / Tetrahedron 65 (2009) 4635–4638
4637
preliminary optimized conditions [PdCl2 (10 mol %), BINAP
4. Experimental section
4.1. General method
(10 mol %), Ag2CO3 (3.0 equiv), DMA, 150 ꢀC], and the results are
summarized in Table 2. To assess the impact of the structural and
functional motifs on the reaction we tested a range of linking units
between arenecarboxylic acids 1 and aryl iodides 2. From Table 2, it
was found that for most cases, the reactions furnished the corre-
sponding biaryl compounds 3 in good to excellent yields. For exam-
ple, reaction of 2-nitrobenzoic acid 1a with 1-iodo benzene 2b gave
rise to product 3b in 96% yield (Table 2, entry 2). A similar result was
observed when 1-iodo-4-methylbenzene 2c was employed in the
reaction of 2-nitrobenzoic acid 1a (95% yield, Table 2, entry 3). Ad-
ditionally, for the reactions of 2-nitrobenzoic acid 1a, a range of dif-
ferent groups was tolerated in aryl iodides with different electronic
demands on the aromatic rings involving electron-donating and
electron-withdrawing groups. For instance, reaction of acetyl-
substitutedaryl iodide2dproceeded smoothly, whichgaverise tothe
desired product 3d in good yield (91% yield, Table 2, entry 4). 3-
Substituted aryl iodides, such as 2e or 2f, were also suitable partners
in this process, andthedesired products were furnished in goodyield
(Table 2, entries 5 and 6). When 4-chlorophenyl iodide 2g was
employed in the reaction of 2-nitrobenzoic acid 1a under the standard
conditions, the chloro group in compound 2g was retained during the
transformation, and the product 3g was afforded in 89% yield (Table 2,
entry 7). The aryl iodide bearing ortho-substitution was also employed
in the reaction of 2-nitrobenzoic acid 1a and the desired product 3h
was generated in 60% yield (Table 2, entry 8). Other arenecarboxylic
acids were also examined. Reactions of 4,5-dimethoxy-2-nitrobenzoic
acid 1b or 2,6-dimethoxybenzoic acid 1c with various aryl iodides led
to the corresponding products in good yields (Table 2, entries 9–14).
Fluoro-substituted arenecarboxylic acid 1d reacted with 4-iodoanisole
2a, and gave rise to the biaryl product 3o in 75% yield (Table 2, entry15).
However, only a moderate yield was observed when 2,6-difluoro-
benzoic acid 1e was used in the reaction (54% yield, Table 2, entry 16).
Reaction of 2-methoxybenzoic acid 1f or 3,5-dinitrobenzoic acid 1g
with 1-iodo-4-methylbenzene 2c led to the formation of product 3q or
3r in 41% or 40% yield, respectively (Table 2, entries 17 and 18).
All reactions were performed in reaction tubes under nitrogen
atmosphere. Flash column chromatography was performed using
silica gel (60-Å pore size, 32–63 mm, standard grade). Analytical
thin-layer chromatography was performed using glass plates pre-
coated with 0.25 mm 230–400 mesh silica gel impregnated with
a
fluorescent indicator (254 nm). Thin-layer chromatography
plates were visualized by exposure to ultraviolet light. Organic
solutions were concentrated on rotary evaporators at w20 Torr
(house vacuum) at 25–35 ꢀC. Commercial reagents and solvents
were used as received. Nuclear magnetic resonance (NMR) spec-
tra are recorded in parts per million from internal tetrame-
thylsilane on the
d scale.
General procedure for palladium-catalyzed decarboxylative
cross-coupling reaction of arenecarboxylic acid 1 with aryl iodide 2.
A mixture of arenecarboxylic acid 1 (0.30 mmol), aryl iodide 2
(0.33 mmol, 1.1 equiv), Ag2CO3 (0.90 mmol, 247 mg, 3.0 equiv),
BINAP (0.03 mmol, 19 mg, 0.1 equiv), and PdCl2 (0.03 mmol, 5.3 mg,
0.1 equiv) in DMA (2.0 mL) was stirred at 150 ꢀC under nitrogen for
2 h. After completion of reaction as indicated by TLC, the mixture
was cooled and filtered with Celite (washed with 10 mL of ethyl
acetate). The filtrate was then washed with saturated NH4Cl, dried
with MgSO4, and concentrated under reduced vacuum. The residue
was subsequently purified by flash chromatography on silica gel to
afford product 3.
4.1.1. 40-Methoxy-2-nitrobiphenyl (3a)5b
1H NMR (400 MHz, CDCl3)
d (ppm): 3.83 (s, 3H), 6.94 (d,
J¼8.3 Hz, 2H), 7.24 (d, J¼8.3 Hz, 2H), 7.39–7.44 (m, 2H), 7.57 (t,
J¼7.3 Hz, 1H), 7.80 (d, J¼7.3 Hz, 1H).
4.1.2. 2-Nitrobiphenyl (3b)7d
1H NMR (400 MHz, CDCl3)
d
(ppm): 7.31 (dd, J¼1.9, 7.8 Hz, 2H),
We also examined the palladium-catalyzed decarboxylative cross-
coupling reactions of arenecarboxylic acids with activated aryl bromide
under the standard conditions shown inTable 2 (Scheme 1). Interestingly,
the desired product was also generated, although the yield was low.
7.39–7.48 (m, 5H), 7.60 (t, J¼7.3 Hz, 1H), 7.84 (d, J¼7.8 Hz, 1H).
4.1.3. 40-Methyl-2-nitrobiphenyl (3c)5b
1H NMR (400 MHz, CDCl3)
d (ppm): 2.38 (s, 3H), 7.22–7.24 (m,
4H), 7.41–7.44 (m, 2H), 7.58 (t, J¼7.8 Hz, 1H), 7.81 (d, J¼8.3 Hz, 1H).
Br
CO2H
4.1.4. 40-Acetyl-2-nitrobiphenyl (3d)5b
PdCl2 (10 mol %)
O2N
BINAP (10 mol %)
1H NMR (400 MHz, CDCl3)
d
(ppm): 2.64 (s, 3H), 7.43 (t, J¼8.3 Hz,
+
(1)
(2)
Ag2CO3 (3.0 equiv)
DMA, 150 °C
2h, 35% yield
3H), 7.54 (t, J¼7.3 Hz, 1H), 7.66 (t, J¼7.3 Hz, 1H), 7.93 (d, J¼8.3 Hz,
NO2
Cl
Cl
Br
1H), 7.57 (d, J¼8.3 Hz, 2H).
1a
3g
MeO
4.1.5. 30-Methoxy-2-nitrobiphenyl (3e)10
OMe
PdCl2 (10 mol %)
COOH
BINAP (10 mol %)
1H NMR (400 MHz, CDCl3)
d (ppm): 3.81 (s, 3H), 6.85 (s,1H), 6.88
+
(d, J¼7.8 Hz, 1H), 7.82 (dd, J¼2.4, 8.3 Hz, 1H), 7.32 (t, J¼7.8 Hz, 1H),
7.44 (d, J¼7.3 Hz, 1H), 7.47 (d, J¼7.8 Hz, 1H), 7.59 (t, J¼7.8 Hz, 1H),
7.82 (d, J¼8.3 Hz, 1H).
Ag2CO3 (3.0 equiv)
DMA, 150 °C
2h, 23% yield
OMe
1c
OMe
Cl
Cl
3n
Scheme 1. Pd-catalyzed decarboxylative cross-coupling reactions of arenecarboxylic
acids with aryl bromide.
4.1.6. 20-Nitro-3-trifluoromethylbiphenyl (3f)11
1H NMR (400 MHz, CDCl3)
(d, J¼7.3 Hz,1H), 7.54 (t, J¼8.3 Hz, 2H), 7.59 (s,1H), 7.65 (d, J¼6.3 Hz,
1H), 7.67 (d, J¼6.3 Hz, 1H), 7.94 (d, J¼8.3 Hz, 1H).
d
(ppm): 7.43 (d, J¼7.8 Hz, 1H), 7.48
3. Conclusions
In summary, we have described an efficient method for the
decarboxylative cross-coupling reaction of arenecarboxylic acids
with aryl iodides catalyzed by the combination of PdCl2 and BINAP
in the presence of Ag2CO3 as an additive. The reactions showed high
efficiency and usually finished in 0.5–2 h with good to excellent
isolated yields. Currently, investigations utilizing unactivated aryl
bromides and aryl chlorides as substrates in palladium-catalyzed
decarboxylative cross-coupling reactions of arenecarboxylic acids
are ongoing, and the results will be reported in due course.
4.1.7. 40-Chloro-2-nitrobiphenyl (3g)5b
1HNMR (400 MHz, CDCl3)
d
(ppm):7.24(d, J¼8.3 Hz, 2H), 7.38–7.41(m,
3H), 7.49 (t, J¼7.8 Hz, 1H), 7.61 (dt, J¼0.96, 7.8 Hz,1H), 7.87 (d, J¼7.8 Hz, 1H).
4.1.8. 20-Methyl-2-nitrobiphenyl (3h)12
1H NMR (400 MHz, CDCl3)
d (ppm): 2.10 (s, 3H), 7.09 (d,
J¼7.3 Hz, 1H), 7.20–7.28 (m, 3H), 7.32 (t, J¼7.8 Hz, 1H), 7.51 (t,
J¼7.8 Hz, 1H), 7.63 (t, J¼7.8 Hz, 1H), 7.98 (d, J¼7.8 Hz, 1H).

4638
Z. Wang et al. / Tetrahedron 65 (2009) 4635–4638
4.1.9. 40,4,5,-Trimethoxy-2-nitrobiphenyl (3i)7a
Century Excellent Talents in University (NCET-07-0208) is grate-
fully acknowledged.
1H NMR (400 MHz, CDCl3)
d
(ppm): 3.84 (s, 3H), 3.94 (s, 3H), 3.97 (s,
3H), 6.77 (s, 1H), 6.94 (d, J¼8.3 Hz, 2H), 7.21 (d, J¼8.3 Hz, 2H), 7.51 (s, 1H).
Supplementary data
4.1.10. 4,5-Trimethoxy-2-nitrobiphenyl (3j)7d
1H NMR (400 MHz, CDCl3)
d (ppm): 3.95 (s, 3H), 3.98 (s, 3H),
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2009.04.047.
6.78 (s, 1H), 7.28–7.30 (m, 2H), 7.38–7.42 (m, 3H), 7.55 (s, 1H).
4.1.11. 40-Acetyl-4,5-dimethoxy-2-nitrobiphenyl (3k)
References and notes
Colorless oil. 1H NMR (400 MHz, CDCl3)
d (ppm): 2.64 (s, 3H),
3.96 (s, 3H), 4.00 (s, 3H), 6.76 (s, 1H), 7.39 (d, J¼7.8 Hz, 2H), 7.61 (s,
1. (a) Palladium Reagents and Catalysts; Tsuji, J., 2nd, Ed.; John Wiley & Sons:
Chichester, UK, 2004; (b) de Meijere, A.; Diederich, F. Metal-Catalyzed
Cross-Coupling Reactions, 2nd ed.; John Wiley & Sons: Weinheim, Germany,
2004.
2. Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373.
3. Nilsson, M. Acta Chem. Scand. 1966, 20, 423.
1H), 8.01 (d, J¼8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d (ppm):
26.6, 56.4, 56.5, 107.9, 113.1, 128.3, 128.5, 130.3, 136.2, 140.6, 143.3,
148.4, 152.4, 197.5. MS (EI) m/z 301 (Mþ). Anal. Calcd for C16H15NO5:
C, 63.78; H, 5.02, N, 4.65. Found: C, 63.56; H, 4.95, N, 4.51.
4. (a) Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250;
(b) Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433; (c) Tanaka, D.; Romeril, S. P.;
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4.1.12. 2,40,6-Trimethoxybiphenyl (3l)7a
1H NMR (400 MHz, CDCl3)
d
(ppm): 3.73 (s, 6H), 3.83 (s, 3H),
6.64 (d, J¼8.3 Hz, 2H), 6.95 (d, J¼8.8 Hz, 2H), 7.23–7.29 (m, 3H).
4.1.13. 2,6-Dimethoxy-40-methylbiphenyl (3m)7a
1H NMR (400 MHz, CDCl3)
d (ppm): 2.38 (s, 3H), 3.73 (s, 6H),
6.65 (d, J¼8.3 Hz, 2H), 7.22–7.25 (m, 5H).
4.1.14. 40-Chloro-2,6-dimethoxybiphenyl (3n)7a
1H NMR (400 MHz, CDCl3)
d (ppm): 3.71 (s, 6H), 6.63 (d,
J¼8.8 Hz, 2H), 7.25–7.29 (m, 3H), 7.35 (d, J¼8.3 Hz, 2H).
4.1.15. 2-Chloro-6-fluoro-40-methoxybiphenyl (3o)7a
1H NMR (400 MHz, CDCl3)
d (ppm): 3.85 (s, 3H), 6.99 (d,
J¼8.8 Hz, 2H), 7.06 (t, J¼8.3 Hz, 1H), 7.21–7.31 (m, 4H).
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2409.
4.1.16. 40-Chloro-2,6-difluorobiphenyl (3p)13
1H NMR (400 MHz, CDCl3)
2H), 6.99 (d, J¼8.8 Hz, 2H), 7.19–7.25 (m, 1H), 7.40 (d, J¼8.8 Hz, 2H).
d
(ppm): 3.84 (s, 3H), 6.94 (d, J¼7.8 Hz,
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H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511; (g) Singh, R.; Viciu, M. S.; Kramareva,
N.; Navarro, O.; Nolan, S. P. Org. Lett. 2005, 7, 1829; (h) Grasa, G. A.; Hillier, A.
C.; Nolan, S. P. Org. Lett. 2001, 3, 1077; (i) Viciu, M. S.; Germaneau, R. F.;
Navarro-Fernandez, O.; Stevens, E. D.; Nolan, S. P. Organometallics 2002, 21,
5470.
4.1.17. 40-Methyl-2-methoxybiphenyl (3q)5b
1H NMR (400 MHz, CDCl3)
d (ppm): 2.38 (s, 6H), 3.80 (s, 3H),
6.97 (d, J¼8.8 Hz, 1H), 7.01 (dt, J¼1.0, 7.3 Hz, 1H), 6.97 (d, J¼8.8 Hz,
1H), 7.22 (d, J¼7.8 Hz, 2H), 7.28–7.31 (m, 2H), 7.42 (d, J¼7.8 Hz, 2H).
4.1.18. 40-Methyl-3,5-dinitrobiphenyl (3r)14
1H NMR (400 MHz, CDCl3)
2H), 7.58 (d, J¼7.8 Hz, 2H), 8.75 (d, J¼1.5 Hz, 2H), 8.97 (s, 1H).
d
(ppm): 2.45 (s, 3H), 7.36 (d, J¼7.8 Hz,
10. Cammidge, A. N.; Goddard, V. H. M.; Gopee, H.; Harrison, N. L.; Hughes, D. L.;
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Acknowledgements
Financial support from National Natural Science Foundation of
China (20772018), Shanghai Pujiang Program, and Program for New