desirable for the synthesis of diverse esters. Moreover, the
transesterification of esters is more advantageous than the
condensation reaction of carboxylic acids with alcohols due to
handling ease and high stability of esters as well as their high
solubility in most organic solvents.5 Because the transesterifi-
cation is an equilibrium reaction, it is difficult to attain high
conversions. The following methods have been used to force
the reaction toward the product side: (i) use of excess amounts
of either of the reactants,6 (ii) use of an enol ester as a reactant,
accompanied by the formation of the corresponding aldehyde
or ketone,7 and (iii) removal of the resulting lower alcohol by
molecular sieves8 or continuous distillation. The last approach
is the most ideal method, and several catalytic transesterifications
at high temperature using esters of lower alcohols were
developed using this approach.3,9 Moreover, Otera et al. recently
reported transesterification at room temperature promoted by a
fluorous distannoxane catalyst in a fluorous biphase system.9m
There is great demand, however, for the development of a
versatile transesterification under mild and harmless conditions
to produce highly functionalized compounds such as pharma-
ceutical agents and so on.
Transesterification of Various Methyl Esters
Under Mild Conditions Catalyzed by
Tetranuclear Zinc Cluster
Takanori Iwasaki, Yusuke Maegawa, Yukiko Hayashi,
Takashi Ohshima,* and Kazushi Mashima*
Department of Chemistry, Graduate School of Engineering
Science, Osaka UniVersity, Toyonaka,
Osaka 560-8531, Japan
ohshima@chem.es.osaka-u.ac.jp;
ReceiVed March 19, 2008
Recently, we developed a direct conversion of carboxylic
acids, esters, and lactones with ꢀ-amino alcohols to oxazolines
catalyzed by a µ-oxo-tetranuclear zinc cluster Zn4(OCOCF3)6O
(1) (Figure 1),10a in which zinc ions act cooperatively, similar
to aminopeptidase11 and efficient multimetallic catalysts.12
A new catalytic transesterification promoted by a tetranuclear
zinc cluster was developed. The mild reaction conditions
enabled the reactions of various functionalized substrates to
proceed in good to high yield. A large-scale reaction under
solvent-free conditions proceeded with a low E-factor value
(0.66), indicating the high environmental and economical
advantage of the present catalysis.
(4) (a) Manabe, K.; Sun, X. M.; Kobayashi, S. J. Am. Chem. Soc. 2001,
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Soc. 2005, 127, 4168. (d) Sakakura, A.; Nakagawa, S.; Ishihara, K. Tetrahedron
2005, 62, 422. (e) Sakakura, A.; Nakagawa, S.; Ishihara, K. Nat. Protoc. 2007,
2, 1746.
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1969, 34, 2032. (b) Masaki, Y.; Tanaka, N.; Miura, T. Chem. Lett. 1997, 55. (c)
Ranu, B. C.; Dutta, P.; Sarkar, A. J. Org. Chem. 1998, 63, 6027. (d) Ranu,
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879.
Esterification is one of the most general and important
reactions in organic synthesis because of the ubiquity of esters
in various biologically active natural products and drugs.1
Common synthetic routes to esters include condensation reac-
tions of carboxylic acids with alcohols and reactions with highly
reactive acylating reagents such as acyl halides and acid
anhydrides. These methods require stoichiometric amounts of
the condensation reagent or base, resulting in the formation of
greater than stoichiometric amounts of unwanted chemical
waste.2–4 In terms of atom-economy and environmental con-
cerns, the catalytic transesterification of esters, especially methyl
and ethyl esters, with higher and/or functionalized alcohols is
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Sakaguchi, S. J. Org. Chem. 1996, 61, 3088. (b) Orita, A.; Mitsutome, A.; Otera,
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Chem. 1999, 64, 9063. (d) Shirae, Y.; Mino, T.; Hasegawa, T.; Sakamoto, M.;
Fujita, T. Tetrahedron Lett. 2005, 46, 5877. (e) Bosco, J. W. J.; Agrahari, A.;
Saikia, A. K. Tetrahedron Lett. 2006, 47, 4065. (f) Bosco, J. W. J.; Saikia, A. K.
Chem. Commun. 2004, 1116.
(8) (a) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett. 2002, 4, 3583.
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Weidmann, B.; Zueger, M. Synthesis 1982, 138. (b) Schultheiss-Reimann, P.;
Kuntz, H. Angew. Chem., Int. Ed. Engl. 1983, 22, 63. (c) Otera, J.; Yano, T.;
Kawabata, A.; Nozaki, H. Tetrahedron Lett. 1986, 27, 2383. (d) Waldmann, H.;
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A. S. J. Org. Chem. 1998, 63, 1058. (i) Krasik, P. Tetrahedron Lett. 1998, 39,
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10.1021/jo800625v CCC: $40.75
Published on Web 06/10/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 5147–5150 5147