ORGANIC
LETTERS
2009
Vol. 11, No. 9
2035-2037
Transition-Metal-Free Carboxylation of
Organozinc Reagents Using CO2 in DMF
Solvent
Koji Kobayashi and Yoshinori Kondo*
Graduate School of Pharmaceutical Sciences, Tohoku UniVersity,
Aramaki-aza aoba 6-3, Aoba-ku, Sendai 980-8578, Japan
Received March 13, 2009
ABSTRACT
An efficient process for the carboxylation of functionalized organozinc reagents with CO2 under transition-metal-free conditions was developed
by employing DMF solvent in the presence of LICl.
The reaction of nucleophiles with carbon dioxide is one of
the most important processes for fixation of CO2.1 Highly
reactive nucleophiles such as organolithiums and organo-
magnesium reagents have been used for the reaction with
CO2, which is a relatively less reactive electrophile. Transi-
tion-metal-catalyzed addition reaction of carbon nucleophiles
toward CO2 has attracted attention, and recently some
important progress has been made toward the carboxylation
of organozinc compounds and organoboron compounds.2
Oshima et al.2a and Dong et al.2b independently reported
nickel- and palladium-catalyzed carboxylation of organozinc
reagents with CO2, and these methods provided a new access
to various functionalized aryl and alkyl carboxylic acids. The
use of transition-metal catalysts seemed to be essential for
the carboxylation of organozinc compounds in the reports,
but we are pleased to report a simple transition-metal-free
process by employing a polar aprotic solvent, DMF.
Organozinc reagents have been widely used as soft
nucleophiles in organic synthesis, and the control of the
nucleophilicity is highly important for desired selective
transformations.3 Various methods have been utilized for
promoting the reactivity of organozinc compounds, and
conventionally ate complexation or transmetalation has been
employed.3 On the other hand, solvent is one of the most
important parameters in organic reaction. The solvent effects
of organometallic reactions have been studied from various
viewpoints,4 not only on the improvement of solubility of
metal salt but also on the change of the oligomeric complex
structures, on acceleration of the reaction, and on the reaction
selectivity. These effects are considered to depend on the
physicochemical nature of solvents (polarity, donor number,
and acceptor number, etc.). Therefore, it is an attractive
research subject to investigate the relationship between the
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2365–2387. (b) Arakawa, H.; Aresta, M.; Armor, J. N.; Barteau, M. A.;
Beckman, E. J.; Bell, A. T.; Bercaw, J. E.; Creutz, C.; Dinjus, E.; Dixon,
D. A.; Domen, K.; DuBois, D. L.; Eckert, J.; Fujita, E.; Gibson, D. H.;
Goddard, W. A.; Goodman, D. W.; Keller, J.; Kubas, G. J.; Kung, H. H.;
Lyons, J. E.; Manzer, L. E.; Marks, T. J.; Morokuma, K.; Nichoras, K. M.;
Periana, R.; Que, L.; Rostrup-Nielson, J.; Sachtler, W. M. H.; Schmidt,
L. D.; Sen, A.; Somorjai, G. A.; Stair, P. C.; Stults, B. R.; Tumas, W.
Chem. ReV. 2001, 101, 953–996. (c) Gibson, D. H. Chem. ReV. 1996, 96,
2063–2095. (d) Behr, A. Angew. Chem., Int. Ed. Engl. 1988, 27, 661–678.
(2) (a) Ochiai, H.; Jang, M.; Hirano, K.; Yorimitsu, H.; Oshima, K. Org.
Lett. 2008, 10, 2681–2683. (b) Yeung, C. S.; Dong, V. M. J. Am. Chem.
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N. Org. Lett. 2008, 10, 2697–2700. (d) Ukai, K.; Aoki, M.; Takaya, J.;
Iwasawa, N. J. Am. Chem. Soc. 2006, 128, 8706–8707.
(3) Knochel, P.; Jones, P. Organozinc Reagents; Oxford University Press:
Oxford, 1999.
(4) (a) Rutherford, J. L.; Collum, D. B. J. Am. Chem. Soc. 2001, 123,
199–202. (b) Majewski, M.; Nowak, P. Tetrahedron Lett. 1998, 39, 1661–
1664. (c) Winkle, M. R.; Ronald, R. C. J. Org. Chem. 1982, 47, 2101–
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818–820.
10.1021/ol900528h CCC: $40.75
Published on Web 04/01/2009
2009 American Chemical Society