ORGANIC
LETTERS
2005
Vol. 7, No. 7
1331-1333
Ytterbium Triflate-Promoted Tandem
One-Pot Oxidation Cannizzaro Reaction
−
of Aryl Methyl Ketones
Massimo Curini,* Francesco Epifano, Salvatore Genovese,
M. Carla Marcotullio, and Ornelio Rosati
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica,
Via del Liceo, 06123 Perugia, Italy
Received January 20, 2005
ABSTRACT
Ytterbium triflate was shown to be an effective catalyst in promoting the synthesis of either isopropyl esters or free
r
-hydroxy-arylacetic acids
from substituted aromatic glyoxals and aryl methyl ketones, respectively. The reaction to provide acids starting from differently substituted
ketones was carried out by an environmentally friendly method using an aqueous medium as a solvent and giving the adducts in 78
yield without any further purification after the usual workup.
−99%
The Cannizzaro reaction is one of the oldest processes
described in synthetic organic chemistry.1 It is conventionally
promoted by strong bases such as stoichiometric amounts
of alkali metal hydroxides at high temperatures. Moreover,
requiring drastic conditions, the Cannizzaro reaction is of
limited use and scope, except when performed as an
intramolecular process. In particular, when carried out using
aryl glyoxals as starting materials, the intramolecular Can-
nizzaro reaction becomes one of the most efficient routes
for the synthesis of mandelic acid and other substituted
R-hydroxy-arylacetic acids that are important synthons of
many natural and semisynthetic biologically active com-
pounds such as prostaglandins,2 â-lactams,3,4 vanillic acid
metabolites,5 and homatropine.6 Recently, new methods have
been developed using Lewis acids as catalysts instead of
“traditional” Brønsted bases to promote the intramolecular
Cannizzaro reaction for the synthesis of mandelic acid
derivatives. The use of catalytic quantities of a Lewis acid
would in fact decrease competitive side reactions that
frequently occur when the process is carried out in a strong
basic medium. Until now, only one method has been reported
to efficiently promote the synthesis of R-hydroxy-arylacetic
esters from the corresponding glyoxals: recently Morken and
co-workers7 described the use of 10 mol % Cr(ClO4)2
hexahydrate as a catalyst in 2-propanol/dichloroethane as a
solvent for 24 h at room temperature to obtain isopropyl
R-hydroxy-aryl acetates in 40-84% yield. Notably, other
Lewis acids such as Cu(II), Fe(III), Li+, Mg2+, Al3+, Y3+
and other transition metal salts gave no reaction or their
catalyzed processes were limited by conditions requiring high
temperature and more than 20% loading and by the occur-
rence of several side reactions.8 Although the one reported
by Morken and co-workers represents an effective method
for converting glyoxals into mandelate ester derivatives, the
(1) For a review, see: Geissman, T. A. Org. React. 1944, 2, 94-113.
(2) Miersch, O.; Kramell, R.; Parthier, B.; Wasternack, C. Phytochemistry
1999, 50, 353-361.
(3) Hoover, J. R. E.; Dunn, G. L.; Jakas, D. R.; Lam, L. L., Taggart, J.
J.; Guarini, J. R.; Phillips, L. J. Med. Chem. 1974, 17, 34-41.
(4) Nishihata, T.; Takahagi, H.; Yamamoto, M.; Tomida, M.; Rytting,
J. H.; Higuchi, T. J. Pharm. Sci. 1984, 73, 109-113.
(5) Yoshioka, M.; Yoshida, A.; Ichihashi, Y.; Saito, H. Chem Pharm.
Bull. 1985, 33, 2145-2148.
(7) Russell, A. E.; Miller, S. P.; Morken, J. P. J. Org. Chem. 2000, 65,
8381-8383.
(8) (a) Maruyama, K.; Murakami, Y.; Yoda, K.; Mashino, T.; Nishinaga,
A. J. Chem. Soc., Chem. Commun. 1992, 1617-1618. (b) Jin, S. J.; Arora,
P. K. Sayre, L. M. J. Org. Chem. 1990, 55, 3011-3018. (c) Okuyama, T.;
Kimura, K.; Fueno, T. Bull. Chem. Soc. Jpn. 1982, 55, 2285-2286.
(6) El Nimr, A. E.; Salama, H. A.; Khalil, R. M.; Kassem, M. A.
Pharmazie 1983, 38, 728-730.
10.1021/ol050125e CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/01/2005