C O M M U N I C A T I O N S
Table 3. Carboxylation of Phenylacetic Acid Derivativesa,b
can be applied to the carboxylation of vinylic C-H bonds. We
have also characterized by X-ray crystallography the first cyclo-
metalation complex formed from carboxylic acids.
Acknowledgement. We thank The Scripps Research Institute
and the U.S. National Science Foundation (NSF CHE-0615716)
for financial support, the Camille and Henry Dreyfus Foundation
for a New Faculty Award, and A. P. Sloan Foundation for a
Fellowship.
Supporting Information Available: Experimental procedure and
characterization of all new compounds. This material is available free
a Run using 10 mol % Pd(OAc)2, 2 equiv of Ag2CO3, 2 equiv of
NaOAc, 1 atm of CO, dioxane, 150 °C, 18 h. b Isolated yields. c Isolated
as the corresponding anhydrides. d Run with 1 equiv of K2HPO4 added.
NMR yield in absence of K2HPO4 is given in parenthesis.
References
(1) (a) Handbook of Organopalladium Chemistry for Organic Synthesis;
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Y.; Takaki, K.; Taniguchi, Y Synlett 1996, 591-599. For the carboxylation
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alkylation of phenyl acetic acids using oxazoline as auxiliary,12
direct functionalization of phenyl acetic acids via six-membered
palladacycles has not been achieved to date. This method provides
a convenient route for the preparation of 1,3-dicarboxylic acids.
We are pleased to find that the ꢀ-vinyl C-H bond in R,ꢀ-
unsaturated carboxylic acid 24 is also carboxylated selectively to
give cis-1,2-dicarboxylic acid 24a in 68% yield.13 This reaction
protocol could be very useful in the synthesis of natural products
containing a succinic acid/anhydride moiety.14
(3) For the carbonylation of C-H bonds by other metals, see: (a) Mori, Y.;
Tsuji, J. Tetrahedron 1971, 27, 3811–3819. (b) Kunin, A. J.; Eisenberg,
R. J. Am. Chem. Soc. 1986, 108, 535–536. (c) Moore, E.; Pretzer, W. R.;
O’Connell, J. H.; LaBounty, L.; Chou, L.; Grimmer, S. S. J. Am. Chem.
Soc. 1992, 114, 5888–5890. (d) Choi, J.-C.; Kobayashi, Y.; Sakakura, T.
J. Org. Chem. 2001, 66, 5262–5263. (e) Funk, J. K.; Yennawar, H.; Sen,
A. HelV. Chim. Acta 2006, 89, 1687–1695. (f) Imoto, S.; Uemura, T.;
Kakiuchi, F.; Chatani, N. Synlett 2007, 170–172.
(4) Orito, K.; Horibata, A.; Nakamura, T.; Ushito, H.; Nagasaki, H.; Yuguchi,
M.; Yamashita, S.; Tokuda, M. J. Am. Chem. Soc. 2004, 126, 14342–14343.
(5) Yu, W.-Y.; Sit, W. N.; Lai, K.-M.; Zhou, Z.; Chan, A. S. C. J. Am. Chem.
Soc. 2008, 130, 3304–3306.
(6) For the amide-directed ortho-lithiation/CO2 insertion process for carbox-
ylation, see: Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew.
Chem., Int. Ed. 2004, 43, 2206–2225.
(7) (a) 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, 3510–3511. (b) Mei, T.-S.;
Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 5215–
5219.
(8) For other works on carboxyl-directed C-H bond activation, see: (a) Kao,
L.-C.; Sen, A. J. Chem. Soc., Chem. Commun. 1991, 1242–1243. (b) Miura,
M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998,
63, 5211–5215. (c) Dangel, B. D.; Johnson, J. A.; Sames, D. J. Am. Chem.
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2006, 47, 1375–1379. (e) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am.
Chem. Soc. 2007, 129, 9879–9884. (f) Ueura, K.; Satoh, T.; Miura, M. J.
Org. Chem. 2007, 72, 5362–5367. (g) Maehara, A.; Tsurugi, H.; Satoh,
T.; Miura, M. Org. Lett. 2008, 10, 1159–1162.
(9) Decouzon, M.; Ertl, P.; Exner, O.; Gal, J.-F.; Maria, P.-C. J. Am. Chem.
Soc. 1993, 115, 12071–12078.
(10) Mart´ın-Matute, B.; Mateo, C.; Ca´rdenas, D. J.; Echavarren, A. M.
Chem.sEur. J. 2001, 7, 2341–2348.
We have also characterized an intermediate C-H insertion
complex in order to gain insight into the catalytic process. Treatment
of sodium carboxylate 1b with Pd(OAc)2 in CH2Cl2 or dioxane at
100 °C gives a cyclopalladated intermediate whose structure is
consistent with 1c by 1H and 13C NMR (Scheme 1).15 This complex
is insoluble in organic solvents other than DMSO. Palladacycle 1c
was also converted into a more soluble tetrameric palladacycle 1d
by stirring it with Ph3P in CH2Cl2 at 24 °C under N2. The structure
of 1d was then characterized by X-ray crystallography, thus
confirming 1c as the first isolated C-H insertion intermediate from
simple carboxylic acids.16 A suspension of palladacycle 1c in
dioxane or CH2Cl2 also reacts stoichiometrically with CO at room
temperature to produce the anhydride 1f quantitatively, possibly
via the intermediate 1e. Under the catalytic conditions, the anhydride
1f is finally hydrolyzed in situ in the presence of base and traces
of water to give the dicarboxylic acid 1a.17
In summary, we have developed the first Pd(II)-catalyzed reaction
protocol for the direct carboxylation of benzoic and phenylacetic
acid derivatives to form dicarboxylic acids. The reaction conditions
(11) Phenylacetic and R-methyl phenylacetic acids give <10% products.
(12) Chen, X.; Li, J.-J.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 78–79.
(13) For a recent example of vinylic C-H bond activation, see: (a) Lu, J.; Tan,
X.; Chen, C. J. Am. Chem. Soc. 2007, 129, 7768–7769. (b) The R-aryl
ring is necessary for the vinyl C-H carboxylation. Carboxylation at the
ortho-aryl C-H bond was not observed.
Scheme 1. Formation and Characterization of Palladacycle 1c
(14) (a) Kar, A.; Argade, N. P. J. Org. Chem. 2002, 67, 7131–7134. (b) Chen,
X.; Zheng, Y.; Shen, Y. Chem. ReV. 2007, 107, 1777–1830.
(15) Palladacycles are usually observed in dimeric or trinuclear forms in absence
of external ligands: (a) Reference 2g. (b) Giri, R.; Liang, J.; Lei, J.-G.; Li,
J.-J.; Wang, D.-H.; Chen, X.; Naggar, I. C.; Guo, C.; Foxman, B. M.; Yu,
J.-Q Angew. Chem., Int. Ed. 2005, 44, 7420–7424.
(16) For the synthesis of a similar complex from o-halobenzoic acids, see: (a)
Fernandez-Rivas, C.; Cardenas, D. J.; Martin-Matute, B.; Monge, A.;
Gutierrez-Puebla, E.; Echavarren, A. M. Organometallics 2001, 20, 2998–
3006. (b) Nagayama, K.; Kawataka, F.; Sakamoto, M.; Shimizu, I.;
Yamamoto, A. Bull. Chem. Soc. Jpn. 1999, 72, 573–580.
(17) Evidence for in situ hydrolysis under catalytic conditions is as follows: (a)
early termination of the reaction of 1 gave a mixture of anhydride 1f and
dicarboxylic acid 1a. (b) In a separate experiment, the anhydride 1f was
converted into dicarboxylic acid 1a under the catalytic conditions.
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