182-184 °C). Interestingly, not even a trace of p-fluorophe-
nylglyoxylic acid was obtained from the reaction mixture
(Scheme 2). Although the conceptualization of a novel
Scheme 1. Concept of Glyoxylic Acid Synthesis
Scheme 2
Conceivably, the carboxylation envisioned above would
provide a simple route for the synthesis of value-added
products and in turn open up a potentially useful approach
to the sequestration of CO2,11,12 culpable for the green house
effect and global warming. In this context, it is noteworthy
that the reaction of NHCs and imidazoles with CO2 resulting
in the carboxylates is known in the literature,13 and the latter
have been proposed as carriers of NHCs as well as CO2. NHC-
catalyzed reaction of CO2 with propargylic alcohols and
epoxides leading to carbonates is also known.14 Recently, Zhang
and coworkers have reported the NHC-catalyzed reduction CO2
to methanol.15 Subsequently, while this work was under com-
pletion, the same group reported the NHC-catalyzed reaction
of CO2 with aldehydes leading to carboxylic acids.16
synthesis of phenyl glyoxylic acid did not materialize, the
preparative value of this transformation proceeding under
mild conditions and its mechanistic importance prompted us
to pursue the reaction in some detail.
In a prototype experiment designed to test the validity of
the concept outlined above (Scheme 1), p-fluorobenzaldehyde
(1 equiv) and 1,3-dimesityl-4,5-dihydro-1H-imidazol-3-ium
(SIMes) chloride (0.15 equiv) were taken in THF. After the
addition of DBU (0.2 equiv), the solution was stirred in a
CO2 atmosphere (balloon). After 16 h, the reaction mixture
was quenched with hydrochloric acid (1 N, 5 mL) and
extracted with DCM. The organic layer on usual processing
and chromatography afforded a colorless crystalline solid that
to our surprise was found to be p-fluorobenzoic acid (mp
Subsequent to the preliminary experiments, it was found
that the reaction worked more efficiently when a slow stream
of CO2 was passed through the solution of the aldehyde and
the catalyst for 10 min; the product was obtained in 72%
yield. A number of commonly used NHC catalysts were
screened for assessing their utility in optimizing this reaction,
and the results are summarized in Table 1.
Table 1. Catalyst Screening
(7) (a) Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205.
(b) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004, 126,
14370. (c) He, M.; Bode, J. W. Org. Lett. 2005, 7, 3131. (d) Nair, V.;
Vellalath, S.; Poonoth, M.; Suresh, E. J. Am. Chem. Soc. 2006, 128, 8736.
(e) He, M.; Bode, J. W. J. Am. Chem. Soc. 2008, 130, 418. (f) Chan, A.;
Scheidt, K. A. J. Am. Chem. Soc. 2008, 130, 2740. (g) Philips, E. M.;
Reynolds, T. E.; Scheidt, K. A. J. Am. Chem. Soc. 2009, 130, 2416. (h)
Nair, V.; Sreekumar, V.; Poonoth, M.; Mohan, R.; Suresh, E. Org. Lett.
2006, 8, 507. (i) Nair, V.; Poonoth, M.; Vellalath, S.; Suresh, E.; Thirumalai,
entry
catalyst
condition
yielda (%)
R. J. Org. Chem. 2006, 71, 8964
(8) For a recent review, see: Nair, V.; Vellalath, S.; Babu, B. P. Chem.
Soc. ReV. 2008, 37, 2691
.
1
2
3
4
2a
2b
2c
2d
THF, rt, 10 min
THF, rt, 10 min
THF, rt, 10 min
THF, rt, 10 min
0
61
72
5
.
(9) (a) Harada, K.; Munegumi, T. In ComprehensiVe Organic Synthesis;
Fleming, I., Ed.; Pergamon Press: New York, 1991; Vol. 8, pp 144-145.
(b) Arterburn, J. B.; Pannala, M.; Gonzalaz, A. M.; Chamberlin, R. M.
Tetrahedron Lett. 2000, 41, 7847. (c) Kamochi, Y.; Kudo, T.; Masuda, T.;
Takadate, A. Chem. Pharm. Bull. 2005, 53, 1017. (d) Wang, Z.; La, B.;
Fortunak, J. M.; Meng, X.-J.; Kabalka, G. W. Tetrahedron Lett. 1998, 39,
a Isolated yield. 2a: R ) phenyl. 2b: R ) 2,4,6-trimethylphenyl. 2c: R
) 2,4,6-trimethylphenyl.
5501
.
(10) (a) Taylor, M. B. Cosmet. Dermatol. 1999, 26. (b) Green, B. A.;
Yu, R. J.; Van Scott, E. J. Clin. Dermatol. 2009, 27, 495
.
The reaction was extended to a number of aldehydes, and
the products were characterized by conventional spectro-
scopic methods and by comparison to the data available in
the literature.17,18 The results are presented in Table 2. From
our studies, it was found that in general best results were
obtained when THF was used as the solvent, the exception
being benzaldehyde and 3,4-dimethoxybenzaldehyde which
gave better results in acetonitrile.
(11) For a recent review on biocatalytic carboxylation, see: Glueck,
S. M.; Guemues, S.; Fabian, W. M. F.; Faber, K. Chem. Soc. ReV. 2010,
39, 313
.
(12) (a) Kayaki, Y.; Yamamoto, M.; Ikariya, T. Angew. Chem., Int. Ed.
2009, 48, 4194. (b) Koinuma, H. React. Funct. Polym. 2007, 67, 1129. (c)
Correa, A.; Martin, R. Angew. Chem., Int. Ed. 2009, 48, 6201
.
(13) (a) Voutchkova, A. M.; Feliz, M.; Clot, E.; Eisenstein, O.; Crabtree,
R. H. J. Am. Chem. Soc. 2007, 129, 12834. (b) Holbery, J. D.; Reichert,
W. M.; Tkatchenko, I.; Bouajila, E.; Walter, O.; Tommasi, I.; Rogers, R. D.
Chem. Commun. 2003, 28. (c) Tommasi, I.; Sorrentino, F. Tetrahedron Lett.
2005, 46, 2141.
(14) Zhou, H.; Zhang, W. Z.; Liu, C. H.; Qu, J. P.; Lu, X. B. J. Org.
Chem. 2008, 73, 8039.
(16) Gu, L.; Zhang, Y. J. Am. Chem. Soc. 2010, 132, 914
(17) All of the compounds reported here in are known in the literature;
most of them are commercially available.
.
(15) Riduan, S. N.; Zhang, Y.; Ying, J. Y. Angew. Chem., Int. Ed. 2009,
48, 3322.
2654
Org. Lett., Vol. 12, No. 11, 2010