Pd-catalysed decarboxylative Suzuki reactions and orthogonal Cu-based O-arylation of aromatic carboxylic acids

Article abstract of DOI:10.1039/c0cc04104a

Pd-catalysed decarboxylative Suzuki reactions and orthogonal Cu-based O-arylation reactions of aromatic carboxylic acids are reported. The new reactions may provide alternative routes for the synthesis of some biaryls and aromatic carboxylic esters. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c0cc04104a

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Pd-catalysed decarboxylative Suzuki reactions and orthogonal Cu-based
O-arylation of aromatic carboxylic acidsw
Jian-Jun Dai, Jing-Hui Liu, Dong-Fen Luo and Lei Liu*
Received 28th September 2010, Accepted 4th November 2010
DOI: 10.1039/c0cc04104a
Pd-catalysed decarboxylative Suzuki reactions and orthogonal
Cu-based O-arylation reactions of aromatic carboxylic acids are
reported. The new reactions may provide alternative routes for
the synthesis of some biaryls and aromatic carboxylic esters.
By comparison, in our study free carboxylic acids are directly
used and the products are biaryls with a Pd-based catalyst
system and carboxylic esters with a Cu-based catalyst system.
In conception, the new biaryl formation reaction described
here is decarboxylative Suzuki coupling21 whereas the carboxylic
ester formation reaction extends the scope of Chan–Lam
reaction22 to include carboxylic acids as substrates. Moreover,
our observation indicates that the mechanism and outcome
of the decarboxylation reaction may be significantly altered
by changes to the conditions. In the previous work by
Yamashita et al.,21a the combination of Pd and Cu leads to
decarboxylative C–C bond formation between acrylic acids
and aryl boronates. In the present study, when the Cu is
omitted, Suzuki chemistry ensues. When the Pd is omitted,
esterification results.
Recently, the use of readily accessible and stable carboxylic
acids as starting materials for transition metal-catalysed
transformations is a fast growing area of research.1 Of
particular interest are Pd-,2–10 Cu-,11 and Rh12-catalysed
decarboxylative cross-couplings, in which metal-mediated
decarboxylation affords organometal intermediates to participate
in C–C or C-heteroatom bond-forming processes with olefins,2,13
aryl halides (or triflates and tosylates),3–10 and C–H,14 N–H,11c
and S–H15 moieties. Besides decarboxylative coupling,
carboxylic acids can also undergo catalytic addition reactions
with alkynes to produce enol esters.16 Furthermore, through
activation with coupling reagents, carboxylic acids can react
with some metal catalysts to generate acyl–metal intermediates,
which can either be reduced to aldehydes,17 or undergo cross-
coupling with nucleophiles,18 or decarbonylate to generate the
alkyl– or aryl–metal complexes.19
Our work started with the decarboxylative coupling
between 2,4,6-trimethoxybenzoic acid and phenylboronic acid.
It was found that by using Pd(TFA)2/Ag2CO3 the desired
reaction takes place with a yield of 92% (Table 1, entry 1).
The use of other Pd catalysts including Pd(OAc)2, PdCl2,
Pd(CH3CN)4(BF4)2, and Pd(CH3CN)2(OTs)2 and other Ag
salts including AgOAc, Ag2O, Ag3PO4, and AgF2 can also
cause the reaction, but the yields are inferior (see ESIw). Under
the optimized conditions, the scope of the reaction with
In this study we report an observation of orthogonal
Pd- and Cu-based catalyst systems for the reactions between
carboxylic acids and boronic acids. Our study is inspired
by Goossen’s pioneering work on the transition metal-
catalysed transformations of similar reactants.1 In his examples,
carboxylic acids were activated to become carboxylic anhydrides,
and the products were ketones with a Pd-based catalyst
system18 and biaryls with Rh-based catalysts20 (Scheme 1).
Table 1 Pd-catalysed decarboxylative Suzuki coupling of 2,4,6-
trimethoxybenzoic acid with various boronic acidsa
Entry
Ar
3
Yieldb (%)
1
2
3
4
5
6
7
8
Phenyl
para-Tolyl
4-Bromophenyl
4-Phenylphenyl
4-Trifluoromethylphenyl
4-Methoxyphenyl
4-Acetylphenyl
2-Naphthyl
4-Cyanophenyl
4-Ethoxycarbonylphenyl
3-Chlorophenyl
3-Fluorophenyl
3-Methoxyphenyl
3,4-(Methylenedioxy)phenyl
ortho-Tolyl
3,5-Difluorophenyl
3,5-Bis(trifluoromethyl)phenyl
3,5-Dimethylphenyl
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
92
87
95
94
89
72
84
92
72
81
85
97
73
70
32
85
93
95
9
10
11
12
13
14
15
16
17
18
Scheme
1 Transition-metal catalysed transformations between
carboxylic acids and boronic acids.
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical
Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing 100084, China.
E-mail: lliu@mail.tsinghua.edu.cn; Tel: +86 10-62780027
w Electronic supplementary information (ESI) available: Detailed
procedures and compound characterization. See DOI: 10.1039/
c0cc04104a
a
Reaction conditions: 0.2 mmol 2,4,6-trimethoxybenzoic acid, 0.4 mmol
boronic acid, 0.04 mmol Pd(TFA)2, 0.6 mmol Ag2CO3, 1 mL DMSO,
b
120 1C, 10–30 min. Isolated yields.
c
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Chem. Commun., 2011, 47, 677–679 677

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respect to boronic acids was examined. It was found that
boronic acids with a variety of functional groups can be
successfully converted. Both electron-rich and electron-poor
arylboronic acids are good substrates. Steric hindrance at the
ortho position can also be tolerated to some extent (entry 15).
More importantly, the bromo and chloro substitutions (entries
3 and 11) can be well tolerated in the reaction, making possible
additional cross-couplings at the halogenated positions.
Application of the above protocol to other carboxylic acids,
however, encountered some initial difficulties. For instance,
when 2,6-dimethoxybenzoic acid was reacted with 3-methoxy-
phenylboronic acid, the yield only reached ca. 20% because
the oxidative homo-coupling of the boronic acid became
dominant. We proposed that the oxidative homo-coupling
can be minimized by using boronic acids that transmetallate
more slowly. Indeed, when a six-membered boronic acid ester
was used, the yield for the decarboxylative coupling of 2,6-
dimethoxy-benzoic acid increased to 91% (Fig. 1). Similarly,
the yields for the decarboxylative coupling of 2,6-difluoro-
benzoic acid were only 13% with 4-cyanophenylboronic acid
but 67% with its ester. Finally, for a more challenging
substrate (i.e. 2-nitrobenzoic acid) even the use of the diol
ester was insufficient, so that we used the more inert
N-methyliminodiacetic acid (MIDA) boronate.
Table
2
Pd-catalysed decarboxylative Suzuki coupling between
carboxylic acids and boronic acid estersa
The above results indicate that the balance between the
speeds of decarboxylation and transmetallation is critical. For
most of the carboxylic acids, the boronic acid esters of
2,2-dimethylpropane-1,3-diol constitute good coupling partners.
Examination on the scope of the decarboxylative Suzuki
coupling with various carboxylic acids showed that the reac-
tion can tolerate coupling partners with diverse electronic
properties and a variety of functional groups (Table 2).
Again, the reaction can tolerate the bromo and chloro groups
(5d,e, 5u). This particular feature indicates that the decarboxy-
lative Suzuki coupling not only provides an alternative
approach for constructing a C–C bond, but also may increase
the flexibility of designing selective and sequential, multistep
cross-couplings for the synthesis of complex targets.
a
Reaction conditions: 0.2 mmol aryl acid, 0.4 mmol boronic acid
ester, 0.04 mmol Pd(TFA)2, 0.6 mmol Ag2CO3, 1 mL DMSO, 120 1C,
2 h. Isolated yields. 4-Acetylphenylboronic acid MIDA ester was
b
c
d
used. Arylboronic acid was used.
surprised to find out that the Cu catalysts cannot promote
decarboxylation but instead trigger a completely different
reaction mode, i.e. O-arylation between the carboxylic acids
and boronic acids with a high chemoselectivity (Scheme 2).
Interestingly, this reaction mode provides a new, important
example for the Chan–Lam reaction, whose scope for the
formation of C–O bonds was limited to phenol and alcohols
in the previous studies.22 This reaction is also of synthetic
importance, because it provides an alternative approach to
aromatic esters complementary to the esterification of benzoic
acids with phenols through e.g. acyl chlorides.
Having studied the scope of Pd-catalysed decarboxylative
Suzuki coupling, we next tested whether a Cu catalyst system
could also promote the same reaction. Previous work by
Goossen et al. showed that Cu co-catalysts often accelerated
decarboxylation.3 However, in the present study we were
Fig. 1 Balance between the carboxylic acid and boronic acid in
Scheme 2 Orthogonal reactivities observed for the same reactants but
decarboxylative Suzuki couplings.
with different catalyst systems.
c
678 Chem. Commun., 2011, 47, 677–679
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Table 3 Cu-catalysed O-arylation reactions between benzoic acids
and aryl boronic acidsa
G. Deng and L. M. Levy, J. Am. Chem. Soc., 2007, 129, 4824;
(c) L. J. Goossen, B. Zimmermann and T. Knauber, Angew.
Chem., Int. Ed., 2008, 47, 7103; (d) L. J. Goossen, F. Rudolphi,
C. Oppel and N. Rodriguez, Angew. Chem., Int. Ed., 2008, 47,
3043; (e) L. J. Goossen, N. Rodriguez, P. P. Lange and C. Linder,
Angew. Chem., Int. Ed., 2010, 49, 1111.
4 P. Forgione, M.-C. Brochu, M. St-Onge, K. H. Thesen,
M. D. Bailey and F. Bilodeau, J. Am. Chem. Soc., 2006, 128,
11350.
5 (a) A. Maehara, H. Tsurugi, T. Satoh and M. Miura, Org. Lett.,
2008, 10, 1159; (b) M. Miyasaka, A. Fukushima, T. Satoh,
K. Hirano and M. Miura, Chem.–Eur. J., 2009, 15, 3674;
(c) M. Yamashita, K. Hirano, T. Satoh and M. Miura, Org. Lett.,
2010, 12, 592.
6 (a) J. Moon, M. Jeong, H. Nam, J. Ju, J. H. Moon, H. M. Jung and
S. Lee, Org. Lett., 2008, 10, 945; (b) J. Moon, M. Jang and S. Lee,
J. Org. Chem., 2009, 74, 1403.
7 (a) Z. Y. Wang, Q. P. Ding, X. D. He and J. Wu, Org. Biomol.
Chem., 2009, 7, 863; (b) Y. Luo and J. Wu, Chem. Commun., 2010,
46, 3785.
8 (a) R. Shang, Y. Fu, J. B. Li, S. L. Zhang, Q. X. Guo and
L. Liu, J. Am. Chem. Soc., 2009, 131, 5738; (b) R. Shang,
Q. Xu, Y.-Y. Jiang, Y. Wang and L. Liu, Org. Lett.,
2010, 12, 1000; (c) M. Li and H. Ge, Org. Lett., 2010, 12, 3464;
(d) P. Fang, M. Li and H. Ge, J. Am. Chem. Soc., 2010, 132,
11898.
9 J.-M. Becht and C. L. Drian, Org. Lett., 2008, 10, 3161.
10 A. Voutchkova, A. Coplin, N. E. Leadbeater and R. H. Crabtree,
Chem. Commun., 2008, 6312.
11 (a) R. Shang, Y. Fu, Y. Wang, Q. Xu, H.-Z. Yu and L. Liu, Angew.
Chem., Int. Ed., 2009, 48, 9350; (b) M. Yu, D. Pan, W. Jia,
W. Chen and N. Jiao, Tetrahedron Lett., 2010, 51, 1287;
(c) W. Jia and N. Jiao, Org. Lett., 2010, 12, 2000.
12 (a) Z.-M. Sun and P. Zhao, Angew. Chem., Int. Ed., 2009, 48,
6726; (b) Z.-M. Sun, J. Zhang and P. Zhao, Org. Lett., 2010,
12, 992.
13 P. Hu, J. Kan, W. Su and M. Hong, Org. Lett., 2009,
11, 2341.
a
Reaction conditions: 0.2 mmol aryl acid, 0.4 mmol boronic acid, 0.04
mmol Cu(OTf)2, 0.4 mmol Ag2CO3, 1 mL DMSO, 120 1C, 2 h.
Isolated yields. 0.6 mmol phenylboronic acid was used.
b
c
14 (a) C. Wang, I. Piel and F. Glorius, J. Am. Chem. Soc., 2009, 131,
4194; (b) J. Zhou, P. Hu, M. Zhang, S. Huang, M. Wang and
W. Su, Chem.–Eur. J., 2010, 16, 5876; (c) F. Zhang and
M. F. Greaney, Angew. Chem., Int. Ed., 2010, 49, 2768;
(d) J. Zhou, P. Hu, M. Zhang, S. Huang, M. Wang and W. Su,
Chem.–Eur. J., 2010, 16, 5876; (e) M. Zhang, J. Zhou, M. Wang,
W. Su and M. Hong, Chem. Commun., 2010, 46, 5455.
15 Z. Duan, S. Ranjit, P. Zhang and X. Liu, Chem.–Eur. J., 2009, 15,
3666.
Under the optimized conditions with Cu(OTf)2 as catalyst
(see ESIw), the O-arylation reaction can be used to synthesize
various aromatic esters (Table 3). Both electron-rich and
electron-poor aromatic acids can be used. Both electron-rich
and electron-poor boronic acids can also be tolerated. In
addition, vinyl acids (6n, 6o) and heterocyclic acids (6p–r)
are good substrates. Also, the halogen groups can be tolerated
(6c, 6f). Moreover, it is important that vinyl boronic acids
(6s–6u) can participate in the reaction, because aryl enol esters
can be otherwise difficult products to obtain.
16 L. J. Goossen, J. Paetzold and D. Koley, Chem. Commun., 2003,
706.
17 L. J. Goossen and K. Ghosh, Chem. Commun., 2002, 836.
18 (a) L. J. Goossen and K. Ghosh, Angew. Chem., Int. Ed., 2001, 40,
3458; (b) L. J. Goossen and K. Ghosh, Chem. Commun., 2001,
2084; (c) K. Nagayama, I. Shimizu and A. Yamamoto, Chem.
Lett., 2001, 1242; (d) L. J. Goossen, D. Koley, H. L. Hermann and
W. Thiel, J. Am. Chem. Soc., 2005, 127, 11102.
19 (a) M. S. Stephan, A. J. J. M. Teunissen, G. K. M. Verzijl and
J. G. de Vries, Angew. Chem., Int. Ed., 1998, 37, 662;
(b) L. J. Goossen and N. Rodriguez, Chem. Commun., 2004, 724;
(c) L. J. Goossen and J. Paetzold, Angew. Chem., Int. Ed., 2002, 41,
1237; (d) L. J. Goossen and J. Paetzold, Angew. Chem., Int. Ed.,
2004, 43, 1095.
In summary, orthogonal decarboxylative Suzuki coupling
and O-arylation reactions of aromatic carboxylic acids
have been observed with Pd- and Cu-based catalyst systems
respectively. Coupling partners with diverse electronic properties
and many functional groups (in particular, chloro and
bromo groups that are not well tolerated in classical Suzuki
couplings) can be selectively transformed under these con-
ditions. These reactions provide new examples for the use of
carboxylic acids as versatile substrates in transition-metal
catalysed synthesis.
20 L. J. Goossen and J. Paetzold, Adv. Synth. Catal., 2004, 346, 1665.
21 Related, important studies: (a) M. Yamashita, K. Hirano, T. Satoh
and M. Miura, Chem. Lett., 2010, 68; (b) C. Feng and T.-P. Loh,
Chem. Commun., 2010, 46, 4779.
22 (a) D. M. Chan, K. L. Monaco, R.-P. Wang and M. P. Winters,
Tetrahedron Lett., 1998, 39, 2933; (b) P. Y. S. Lam, C. G. Clark,
S. Saubern, J. Adams, M. P. Winters, D. M. T. Chan and
A. Combs, Tetrahedron Lett., 1998, 39, 2941; (c) D. A. Evans,
J. L. Katz, G. S. Peterson and T. Hintermann, J. Am. Chem. Soc.,
2001, 123, 12411; (d) S. V. Ley and A. W. Thomas, Angew. Chem.,
Int. Ed., 2003, 42, 5400; (e) Y. Bolshan and R. A. Batey, Angew.
Chem., Int. Ed., 2008, 47, 2109; (f) R. E. Shade, A. M. Hyde,
J.-C. Olsen and C. A. Merlic, J. Am. Chem. Soc., 2010, 132, 1202.
Notes and references
1 A recent review: L. J. Goossen, N. Rodriguez and K. Goossen,
Angew. Chem., Int. Ed., 2008, 47, 3100.
2 (a) A. G. Myers, D. Tanaka and M. R. Mannion, J. Am. Chem.
Soc., 2002, 124, 11250; (b) D. Tanaka, S. P. Romeril and
A. G. Myers, J. Am. Chem. Soc., 2005, 127, 10323.
3 (a) L. J. Goossen, G. Deng and L. M. Levy, Science, 2006, 313,
662; (b) L. J. Goossen, N. Rodriguez, B. Melzer, C. Linder,
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 677–679 679