Room temperature palladium-catalyzed decarboxylative ortho -acylation of acetanilides with α-oxocarboxylic acids

Article abstract of DOI:10.1021/ja105245f

A novel Pd-catalyzed decarboxylative ortho-acylation of acetanilides with α-oxocarboxylic acids is realized at room temperature. This reaction provides efficient access to o-acyl acetanilides under mild conditions.

Full text of DOI:10.1021/ja105245f

Published on Web 08/10/2010
Room Temperature Palladium-Catalyzed Decarboxylative ortho-Acylation of
Acetanilides with r-Oxocarboxylic Acids
Ping Fang, Mingzong Li, and Haibo Ge*
Department of Chemistry and Chemical Biology, Indiana UniVersity Purdue UniVersity Indianapolis,
Indianapolis, Indiana 46202
Received June 15, 2010; E-mail: geh@iupui.edu
Table 1. Optimization of Reaction Conditionsa
Abstract: A novel Pd-catalyzed decarboxylative ortho-acylation
of acetanilides with R-oxocarboxylic acids is realized at room
temperature. This reaction provides efficient access to o-acyl
acetanilides under mild conditions.
Oxidant
(equiv)
Yield
(%)b
Entry
PdX2 (mol %)
Solvents
Transition-metal-catalyzed decarboxylative coupling1 is an
attractive synthetic method for C-C bond formation since it
does not require the use of stoichiometric organometallic
coupling reagents and gives rise to CO2 instead of often toxic
metal compounds. Since the report of a palladium-catalyzed
decarboxylative Heck-type of olefination of benzoic acids by
Meyers,2 extensive studies have been carried out in this area;
representative examples are biaryl coupling by Goossen,3
Forgione,4 and Liu;5 olefination by Satoh6 and Wu;7 alkynylation
by Lee;8 and aryl ketone and ester formation by Goossen3e,9
and Liu.10 Recently, decarboxylative arylation of unactivated
arenes through Pd-catalyzed C-H activation was also devel-
oped.11 It is of note that all of these processes suffer from high
reaction temperature, which reduces their potential application.
Therefore, the development of decarboxylative coupling under
mild conditions is highly desirable.
Inspired by the recent studies in decarboxylative coupling of aryl
halides with potassium R-oxocarboxylates3e,9 and oxalate mo-
noesters,10 we report a room temperature, decarboxylative ortho-
acylation of acetanilides with R-oxocarboxylic acids Via palladium-
catalyzed C-H activation. This new method is complementary to
the directed lithiation/acylation process12 and provides o-acyl
acetanilides, which are important structural units and synthetic
intermediates in biologically active natural products and medicinal
chemistry.13
1c
2
Pd(TFA)2 (10)
Pd(TFA)2 (10)
-
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
air
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
air
O2 (1 atm)
K2S2O8 (2)
BzOOBz (2)
tBuOOBz (2)
Ce(SO4)2 (2)
Oxone (2)
DCM
DCM
DCM
DCM
36
35
0
3d
4e
5
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
Pd(TFA)2 (10)
20
diglyme 93(90f )
6
7
8
9
DME
EtOAc
DCE
82
34
18
o-xylene trace
diglyme 52
diglyme 55
diglyme 65
diglyme 61
diglyme 60
diglyme 38
diglyme 36
diglyme 87
diglyme 75
diglyme trace
10
11
12
13
14
15
16
17
18
19
[Pd(MeCN)4] (BF4)2 (10) (NH4)2S2O8 (2)
Pd(OAc)2 (10)
PdCl2 (10)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2)
(NH4)2S2O8 (1.2) diglyme 85
(NH4)2S2O8 (2.0) diglyme 82
20g Pd(TFA)2 (10)
21h Pd(TFA)2 (5)
a Conditions: 1a (0.3 mmol), 2a (0.6 mmol), PdX2 (0.03 mmol), oxidant
(0.6 mmol), 3 mL of solvent, rt, 12 h unless otherwise noted. b Yields and
conversions are based on 1a, determined by crude 1H NMR using
dibromomethane as the internal standard. c 36 h with 20 mol % AgNO3.
d 36 h, without palladium. e 36 h, without (NH4)2S2O8. f Isolated yield.
g (NH4)2S2O8 (0.36 mmol), 24 h. h Pd(TFA)2 (0.015 mmol), 24 h.
As shown in Table 2, a variety of substituted phenylglyoxylic
acids, including methyl, methoxy, halogen, trifluoromethyl, and
nitro groups, were compatible under the optimal reaction
conditions. Although sterically hindered substrates failed for
Pd(0)/Cu(I)-catalyzed decarboxylative acylation in a previous
report,9a a good yield was obtained in this case (3n). Further-
more, aliphatic R-oxocarboxylic acids were also compatible in
this reaction, giving good to excellent yields (3q-u).
The results of substituted acetanilide (1b-t) compatibility are
presented in Table 3. In general, electron-donating groups
provided higher yields when compared with electron-withdraw-
ing groups at the m- and p-positions (4b-k). Although this
reaction does not work well with strong electron-withdrawing
groups at the m-position, good yields were obtained with
p-substituted compounds (4i-k). Furthermore, m,p-disubstitued
acetanilines also provided good yields (4l-p). Unfortunately,
o-substituted acetanilides failed for the coupling reaction under
the current catalyst system. It is noted that the acetamido group
Early studies showed that decarboxylation of R-oxocarboxylic
acids could be catalyzed by a silver(I) salt with persulfate as
the oxidant at room temperature.14 Thus, our investigation began
with decarboxylative coupling of acetanilide (1a) with phenylg-
lyoxylic acid (2a) in the presence of 10 mol % Pd(TFA)2, 20
mol % AgNO3 and stoichiometric (NH4)2S2O8 in DCM at room
temperature (Table 1, entry 1). To our delight, the desired
product 3a was obtained in 36% yield. Interestingly, it was then
noted that AgNO3 is not required for this reaction.15 Optimization
of the reaction conditions demonstrated that the reaction was
most productive using diglyme as solvent and (NH4)2S2O8 as
oxidant, providing 3a in 93% yield at room temperature with-
in 12
h (entry 5). Further study showed that both
[Pd(MeCN)4](BF4)2 and Pd(OAc)2 are also efficient catalysts for
this reaction while PdCl2 gave only a trace amount of desired
product 3a (entries 17-19). It was also noted that both the
amount of the catalyst and oxidant could be reduced at the
expense of longer reaction time (entries 20 and 21).
9
11898 J. AM. CHEM. SOC. 2010, 132, 11898–11899
10.1021/ja105245f  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Scope of R-Oxocarboxylic Acidsa,b
Acknowledgment. We gratefully acknowledge Indiana Uni-
versity Purdue University Indianapolis for financial support. The
Bruker 500 MHz NMR was purchased using funds from an NSF-
MRI award (CHE-0619254).
Supporting Information Available: Experimental details. This
material is available free of charge via the Internet at http://pubs.acs.org.
References
(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) 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.
(3) (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.;
Linder, C.; Rodriguez, N.; Lange, P. P. Chem.sEur. J. 2009, 15, 9336. (e)
Goossen, L. J.; Zimmermann, B.; Linder, C.; Rodriguez, N.; Lange, P. P.;
Hartung, J. AdV. Synth. Catal. 2009, 351, 2667. (f) Goossen, L. J.;
Rodriguez, N.; Lange, P. P.; Linder, C. Angew. Chem., Int. Ed. 2010, 49,
1111. (g) Goossen, L. J.; Rodr´ıguez, N.; Linder, C.; Zimmermann, B.;
Knauber, T. Org. Synth. 2008, 85, 196.
a Conditions: 1a (0.3 mmol), 2b-u (0.6 mmol), Pd(TFA)2 (0.03
mmol), (NH4)2S2O8 (0.6 mmol), 3 mL of diglyme, rt, 9-36 h. b Isolated
yields based on 1a. c (NH4)2S2O8 (0.36 mmol).
Table 3. Scope of Anilidesa b
,
(4) Forgione, P.; Brochu, M. C.; St-Onge, M.; Thesen, K. H.; Bailey, M. D.;
Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350.
(5) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H. Z.; Liu, L. Angew. Chem.,
Int. Ed. 2009, 48, 9350.
(6) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 12, 592.
(7) Wang, Z. Y.; Ding, Q. P.; He, X. D.; Wu, J. Org. Biomol. Chem. 2009, 7,
863.
(8) (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.
(9) (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.
(10) Shang, R.; Fu, Y.; Li, J. B.; Zhang, S. L.; Guo, Q. X.; Liu, L. J. Am.
Chem. Soc. 2009, 131, 5738.
(11) (a) Cornella, J.; Lu, P. F.; Larrosa, I. Org. Lett. 2009, 11, 5506. (b) Wang,
C. Y.; Piel, I.; Glorius, F. J. Am. Chem. Soc. 2009, 131, 4194. (c) Zhang,
F. Z.; Greaney, M. F. Angew. Chem., Int. Ed. 2010, 49, 2768. (d)
Voutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H. Chem.
Commun. 2008, 6312. (e) Zhou, J.; Hu, P.; Zhang, M.; Huang, S.; Wang,
M.; Su, W. Chem.sEur. J. 2010, 16, 5876. (f) Yu, W.-Y.; Sit, W. N.;
Zhou, Z.; Chan, A. S.-C. Org. Lett. 2009, 11, 3174. (g) Xie, K.; Yang, Z.;
Zhou, X.; Li, X.; Wang, S.; Tan, Z.; An, X.; Guo, C.-C. Org. Lett. 2010,
12, 1564.
(12) (a) Zhang, P. W.; Kern, J. C.; Terefenko, E. A.; Fensome, A.; Unwalla,
R.; Zhang, Z. M.; Cohen, J.; Berrodin, T. J.; Yudt, M. R.; Winneker, R. C.;
Wrobel, J. Bioorg. Med. Chem. 2008, 16, 6589. (b) Hewawasam, P.; Chen,
N.; Ding, M.; Natale, J. T.; Boissard, C. G.; Yeola, S.; Gribkoff, V. K.;
Starrett, J.; Dworetzky, S. I. Bioorg. Med. Chem. Lett. 2004, 14, 1615. (c)
Ubeda, J. I.; Villacampa, M.; Avendano, C. Synlett 1997, 285.
(13) (a) Hirai, K.; Ishiba, T.; Sugimoto, H.; Sasakura, K.; Fujishita, T.; Toyoda,
T.; Tsukinoki, Y.; Joyama, H.; Hatakeyama, H.; Hirose, K. J. Med. Chem.
1980, 23, 764. (b) Mitsch, A.; Wissner, P.; Bohm, M.; Silber, K.; Klebe,
G.; Sattler, I.; Schlitzer, M. Arch. Pharm. 2004, 337, 493. (c) Ogita, H.;
Isobe, Y.; Takaku, H.; Sekine, R.; Goto, Y.; Misawa, S.; Hayashi, H. Bioorg.
Med. Chem. 2002, 10, 3473. (d) Hirai, K.; Fujishita, T.; Ishiba, T.;
Sugimoto, H.; Matsutani, S.; Tsukinoki, Y.; Hirose, K. J. Med. Chem. 1982,
25, 1466.
a Conditions: 1b-t (0.3 mmol), 2a (0.9 mmol), Pd(TFA)2 (0.03
mmol), (NH4)2S2O8 (0.6 mmol), 3 mL diglyme, rt, 7-48 h. b Isolated
yields based on 1. c 2a (0.6 mmol). d In AcOH/THF (1:1, v/v).
is not necessary for this transformation since other amides or
urea also provided good to high yields (4q-t).
Although the reaction mechanism is not clear at this stage, it is
believed that this transformation is initiated by o-palladation of the
acetanilide 1 and subsequent anion exchange with R-oxocarboxylic
acids (Scheme 1). Decarboxylation15b of intermediate II followed
by reductive elimination provides the desired product 3.
Scheme 1. Proposed Catalytic Cycle of Decarboxylative Coupling
(14) (a) Fontana, F.; Minisci, F.; Barbosa, M. C. N.; Vismara, E. J. Org. Chem.
1991, 56, 2866. (b) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I.
Chem. ReV. 1999, 99, 1991.
(15) For selected decarboxylative couplings catalyzed by Pd only, see refs 2, 4,
7, 8, 11d, 11f, and also: (a) Becht, J.-M.; Le Drian, C. Org. Lett. 2008, 10,
3161. (b) Zhang, S. L.; Fu, Y.; Shang, R.; Guo, Q. X.; Liu, L. J. Am.
Chem. Soc. 2010, 132, 638.
In summary, an efficient approach for the direct ortho-acylation
of acetanilides has been developed based on a Pd-catalyzed C-H
activation process at room temperature. This novel method provides
easy access to o-acyl acetanilides under mild conditions.
JA105245F
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