Decarboxylative acylation of arenes with α-oxocarboxylic acids via palladium-catalyzed C-H activation

Article abstract of DOI:10.1021/ol1012857

(Equation Presented). An efficient palladium-catalyzed decarboxylative acylation of unactivated arenes with α-oxocarboxylic acids is reported. This method provides a novel access to aryl ketones.

Full text of DOI:10.1021/ol1012857

ORGANIC
LETTERS
2010
Vol. 12, No. 15
3464-3467
Decarboxylative Acylation of Arenes
with r-Oxocarboxylic Acids via
Palladium-Catalyzed C-H Activation
Mingzong Li and Haibo Ge*
Department of Chemistry and Chemical Biology, Indiana UniVersity Purdue UniVersity
Indianpolis (IUPUI), Indianapolis, Indiana 46202
geh@iupui.edu
Received June 3, 2010
ABSTRACT
An efficient palladium-catalyzed decarboxylative acylation of unactivated arenes with r-oxocarboxylic acids is reported. This method provides
a novel access to aryl ketones.
Transition-metal-catalyzed decarboxylative coupling has
attracted considerable attention in recent years.1 This
method avoids the preparation and use of stoichiometric
organometallic reagents and produces CO2 as the waste
instead of often toxic metal salts. Representative examples
include Pd/Cu-catalyzed decarboxylative coupling of
benzoic acids with aryl halides or surrogates by Goossen,2
palladium-catalyzed decarboxylative Heck-type of olefi-
nation and biaryl coupling of aromatic carboxylic acids
by Meyers3 and Forgione,4 and Cu-catalyzed decarboxyl-
ative coupling of potassium polyfluorobenzoates with aryl
iodides or bromides by Liu.5 Recent studies showed that
alkenyl6 or alkynyl7 carboxylic acids, R-oxocarboxylate2f,8
and potassium oxalate monoesters9 could also undergo
decarboxylative coupling with aryl halides, and thus product
diversity was improved.
Transition-metal-catalyzed cross-coupling directed by
either electronic effects or directing groups is also of
contemporary interest since this method does not require
the prefunctionalization of substrates and is economically
advantageous.10 Inspired by recent studies in this area,11
decarboxylative coupling of aromatic carboxylic acids with
unactivated arenes has also been achieved.12 However,
transition-metal-catalyzed decarboxylative acylation on
aromatic sp2 C-H bonds is rare. Based on the success of
(1) (a) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373. (b) Goossen,
L. J.; Goossen, K.; Rodriguez, N.; Blanchot, M.; Linder, C.; Zimmermann,
B. Pure Appl. Chem. 2008, 80, 1725. (c) Goossen, L. J.; Rodriguez, N.;
Goossen, K. Angew. Chem., Int. Ed. 2008, 47, 3100.
(2) (a) Goossen, L. J.; Deng, G. J.; Levy, L. M. Science 2006, 313,
662. (b) Goossen, L. J.; Rodriguez, N.; Melzer, B.; Linder, C.; Deng, G. J.;
Levy, L. M. J. Am. Chem. Soc. 2007, 129, 4824. (c) Goossen, L. J.;
Rodriguez, N.; Linder, C. J. Am. Chem. Soc. 2008, 130, 15248. (d) Goossen,
L. J.; Rodr´ıguez, N.; Linder, C.; Zimmermann, B.; Knauber, T. Org. Synth.
2008, 85, 196. (e) Goossen, L. J.; Linder, C.; Rodriguez, N.; Lange, P. P.
Chem.sEur. J. 2009, 15, 9336. (f) Goossen, L. J.; Zimmermann, B.; Linder,
C.; Rodriguez, N.; Lange, P. P.; Hartung, J. AdV. Synth. Catal. 2009, 351,
2667. (g) Goossen, L. J.; Rodriguez, N.; Lange, P. P.; Linder, C. Angew.
Chem., Int. Ed. 2010, 49, 1111.
(5) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H. Z.; Liu, L. Angew.
Chem., Int. Ed. 2009, 48, 9350.
(6) (a) Wang, Z. Y.; Ding, Q. P.; He, X. D.; Wu, J. Org. Biomol. Chem.
2009, 7, 863. (b) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org.
Lett. 2010, 12, 592.
(7) (a) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung, H. M.;
Lee, S. Org. Lett. 2008, 10, 945. (b) Kim, H.; Lee, P. H. AdV. Synth. Catal.
2009, 351, 2827. (c) Moon, J.; Jang, M.; Lee, S. J. Org. Chem. 2009, 74,
1403.
(3) (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.; Myers, A. G. J. Am. Chem. Soc. 2005, 127,
10323.
(8) (a) Goossen, L. J.; Rudolphi, F.; Oppel, C.; Rodriguez, N. Angew.
Chem., Int. Ed. 2008, 47, 3043. (b) Goossen, L. J.; Zimmermann, B.;
Knauber, T. Angew. Chem., Int. Ed. 2008, 47, 7103
(9) Shang, R.; Fu, Y.; Li, J. B.; Zhang, S. L.; Guo, Q. X.; Liu, L. J. Am.
Chem. Soc. 2009, 131, 5738.
.
(4) Forgione, P.; Brochu, M. C.; St-Onge, M.; Thesen, K. H.; Bailey,
M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350.
10.1021/ol1012857  2010 American Chemical Society
Published on Web 07/12/2010

C-H activation on 2-phenylpyridine and other nitrogen-
containing substrates,10f herein we describe the first
palladium-catalyzed decarboxylative acylation of unac-
tived arenes with R-oxocarboxylic acids via C-H activa-
tion.
(7.5/1.5/1, v/v/v), providing the desired product (3a) in
61% yield with a high conversion (88%, entry 1).
13
It is important to note that both Pd(TFA)2 and Ag2CO3
are required for this coupling reaction; no desired product
could be obtained in the absence of either of these two
reagents (entries 2 and 3). Further study showed that both
Pd(MeCN)2Cl2 and Pd(PhCN)2Cl2 could efficiently cata-
lyze the reaction (entries 6 and 7), whereas Pd(OAc)2 and
PdCl2 gave relatively lower yields (entries 4 and 5).
Encouraged by these results, the effect of different silver(I)
salts on this reaction was examined, and it turned out that
the optimal results could be produced with 3 equiv of
Ag2O in the presence of Pd(PhCN)2Cl2 as a catalyst (entry
9). Next, the amount of Ag2O was reduced by the addition
of a co-oxidant, and a moderate yield of 3a was obtained
with 1 equiv of Ag2O and 2 equiv of K2S2O8 (entry 11).
Further optimization demonstrated that the coupling yield
could be raised to 84% with 2 equiv of Ag2O and 1 equiv
of K2S2O8 in 12 h (entry 13). It should be noted that
K2S2O8 is required for obtaining a high yield since 2 equiv
of Ag2O alone gave 71% yield (entry 14).
Table 1. Optimization of Reaction Conditionsa
Ag(I) salt
(equiv)
co-oxidant
(equiv)
yield convn
entry
PdX2
(%)b
(%)b
1
Pd(TFA)2
Ag2CO3 (3)
Ag2CO3 (3)
61
0
0
59
66
72
73
69
79
88
<1
<10
81
86
89
89
91
96
54
97
67
98
87
2c
3d Pd(TFA)2
4
5
6
7
8
9
PdCl2
Pd(OAc)2
Pd(MeCN)2Cl2 Ag2CO3 (3)
Pd(PhCN)2Cl2 Ag2CO3 (3)
Pd(PhCN)2Cl2 AgOAc (3)
Pd(PhCN)2Cl2 Ag2O (3)
Ag2CO3 (3)
Ag2CO3 (3)
The substituent effects of phenylglyoxylic acid on this
reaction were then studied (Table 2). It was noticed that
p-substituted electron-donating groups provided good to
high yields (3b and 3c), whereas the strong electron-
withdrawing group CF3 gave a moderate yield (3g).
Interestingly, high yields were obtained with p-fluoro (3d),
p-chloro (3e) and p-bromo (3f) substituted phenylglyoxylic
acids, although it is not surprising that halogens were
tolerated under the reaction conditions. Further investiga-
tion showed that electronic properties do not affect the
o-substituted phenylglyoxylic acids since both electron-
donating groups and electron-withdrawing groups gave
good to high yields (70-95%, 3h-k). With a sterically
hindered substrate, a modest yield was obtained (3l), and
it is noteworthy that Pd/Cu(I)-catalyzed decarboxylative
acylation of aryl bromide gave <5% yield with this
substrate in a previous report.8a In addition, aliphatic
R-oxocarboxylic acids also provide moderate to good
yields of desired products (3o and 3p).
10 Pd(PhCN)2Cl2 Ag2O (1)
11 Pd(PhCN)2Cl2 Ag2O (1)
12 Pd(PhCN)2Cl2 Ag2O (1)
(NH4)2S2O8 (2) 38
K2S2O8 (2)
Oxone (2)
57
40
13e Pd(PhCN)2Cl2 Ag2O (2) K2S2O8(1)
84(81)f
71
14 Pd(PhCN)2Cl2 Ag2O (2)
a Reaction conditions: 2 equiv of 2a, 10 mol % PdX2, Ag(I) salt (quantity
noted), co-oxidant (quantity noted), 1,4-dioxane/HOAc/DMSO (7.5/1.5/1,
v/v/v, c ) 0.1 M), 120 °C, 16 h unless otherwise noted. b Yields and
conversions are based on 1a, determined by crude 1H NMR using
dibromomethane as the internal standard. c Without palladium. d Without
Ag(I) salt. e 12 h. f Isolated yield.
Our investigation started with decarboxylative coupling
of 2-phenylpyridine (1a) with phenylglyoxylic acid (2a)
in the presence of 10 mol % Pd(TFA)2 with 3 equiv of
Ag2CO3 as a decarboxylative reagent and oxidant (Table
1). Solvent screening showed that optimal results could
be obtained with a mixture of 1,4-dioxane/AcOH/DMSO
The results of substituted 2-phenylpyridines (1b-p)
compatibility studies are presented in Table 3. As ex-
pected, a series of functional groups including methyl,
methoxyl, chloro, trifluoromethyl, and acetyl on the phenyl
ring were compatible under the optimal reaction condi-
tions, and the desired products were produced in good to
high yields (4b-n). Interestingly, there does not appear
to be an electronic effect on this substrate since both
electron-donating groups and electron-withdrawing groups
at the o-, m-, and p-positions worked efficiently with the
exception of p-CF3, which gave a moderate yield (4l).
Furthermore, benzo[h]quinoline10f worked extremely well
to give 4o in 95% yield. Acylation of 4,4-dimethyl-2-
(10) For some recent reviews, see: (a) Kakiuchi, F.; Kochi, T. Synthesis
2008, 3013. (b) Li, B. J.; Yang, S. D.; Shi, Z. J. Synlett 2008, 949. (c)
Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009,
48, 9792. (d) Chen, X.; Engle, K. M.; Wang, D. H.; Yu, J. Q. Angew. Chem.,
Int. Ed. 2009, 48, 5094. (e) Colby, D. A.; Bergman, R. G.; Ellman, J. A.
Chem. ReV. 2010, 110, 624. (f) Lyons, T. W.; Sanford, M. S. Chem. ReV.
2010, 110, 1147.
(11) (a) Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, A. H. M.;
Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. J. Am. Chem. Soc. 2002,
124, 1586. (b) Chen, X.; Hao, X. S.; Goodhue, C. E.; Yu, J. Q. J. Am.
Chem. Soc. 2006, 128, 6790. (c) Chiong, H. A.; Daugulis, O. Org. Lett.
2007, 9, 1449.
(12) (a) Voutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H.
Chem. Commun. 2008, 6312. (b) Cornella, J.; Lu, P. F.; Larrosa, I. Org.
Lett. 2009, 11, 5506. (c) Wang, C. Y.; Piel, I.; Glorius, F. J. Am.
Chem. Soc. 2009, 131, 4194. (d) Yu, W. Y.; Sit, W. N.; Zhou, Z. Y.; Chan,
A. S. C. Org. Lett. 2009, 11, 3174. (e) Zhang, F. Z.; Greaney, M. F. Angew.
Chem., Int. Ed. 2010, 49, 2768. (f) Xie, K.; Yang, Z. Y.; Zhou, X. J.; Li,
X. J.; Wang, S. Z.; Tan, Z.; An, X. Y.; Guo, C. C. Org. Lett. 2010, 12,
1564.
(13) (a) Chen, X.; Goodhue, C. E.; Yu, J. Q. J. Am. Chem. Soc. 2006,
128, 12634. (b) Giri, R.; Maugel, N.; Li, J. J.; Wang, D. H.; Breazzano,
S. P.; Saunders, L. B.; Yu, J. Q. J. Am. Chem. Soc. 2007, 129, 3510.
Org. Lett., Vol. 12, No. 15, 2010
3465

Table 2. Scope of R-Oxocarboxylic Acidsa
Table 3. Scope of 2-Phenylpyridinesa
a Reaction conditions: 2 equiv of 2b-p, 10 mol % Pd(PhCN)2Cl2, 2
equiv of Ag2O, 1 equiv of K2S2O8, 1,4-dioxane/HOAc/DMSO (7.5/1.5/1,
v/v/v, c ) 0.1 M), 120 °C, 12 h unless otherwise noted. b Yields isolated
based on 1a. c 3 equiv of Ag2O, without K2S2O8. d 16 h.
phenyl-4,5-dihydrooxazole14 also gave a modest yield of
product 4p.
a Reaction conditions: 2 equiv of 2a, 10 mol % Pd(PhCN)2Cl2, 2 equiv
of Ag2O, 1 equiv of K2S2O8, 1,4-dioxane/HOAc/DMSO (7.5/1.5/1, v/v/v,
c ) 0.1 M), 120 °C, 12 h unless otherwise noted. b Isolated yields based
on 1. c 16 h.
In summary, an efficient approach for the direct
acylation of the aromatic sp2 C-H bond based on a Pd/
(14) (a) Chen, X.; Li, J. J.; Hao, X. S.; Goodhue, C. E.; Yu, J. Q. J. Am.
Chem. Soc. 2006, 128, 78. (b) Giri, R.; Liang, J.; Lei, J. G.; Li, J. J.; Wang,
D. H.; Chen, X.; Naggar, I. C.; Guo, C. Y.; Foxman, B. M.; Yu, J. Q.
Angew. Chem., Int. Ed. 2005, 44, 7420.
Ag bimetallic system has been developed. This novel
method allowed for the decarboxylative cross-coupling of
3466
Org. Lett., Vol. 12, No. 15, 2010

unactivated arenes with both aromatic and aliphatic
R-oxocarboxylic acids.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data (MS, HRMS, NMR) for all
newly identified compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We gratefully acknowledge Indiana
University Purdue University Indianapolis for financial
support. The Bruker 500 MHz NMR was purchased using
funds from an NSF-MRI award (CHE-0619254).
OL1012857
Org. Lett., Vol. 12, No. 15, 2010
3467