ORGANIC
LETTERS
2
005
Vol. 7, No. 22
047-5050
N-Alkyl-4-boronopyridinium Halides
versus Boric Acid as Catalysts for the
5
Esterification of
Acids
r-Hydroxycarboxylic
Toshikatsu Maki, Kazuaki Ishihara,*,† and Hisashi Yamamoto*,‡
†
Graduate School of Engineering, Nagoya UniVersity, Furo-cho, Chikusa,
Nagoya 464-8603, Japan, and Department of Chemistry, The UniVersity of Chicago,
5735 South Ellis AVenue, Chicago, Illinois 60637
ishihara@cc.nagoya-u.ac.jp; yamamoto@uchicago.edu
Received August 25, 2005
ABSTRACT
Boric acid is a highly effective catalyst for the dehydrative esterification reaction between equimolar mixtures of
r-hydroxycarboxylic acids
and alcohols. In contrast, N-methyl-4-boronopyridinium iodide (2a) is a more effective catalyst than boric acid for the similar esterification in
excess alcohol. A heterogeneous catalyst, such as N-polystyrene-bound 4-boronopyridinium chloride, is also an effective catalyst and can be
recovered by filtration.
In 1996, we found that the dehydrative condensation of
equimolar mixtures of carboxylic acids and amines proceeds
under azeotropic reflux conditions with the removal of water
in less-polar solvents, such as toluene and xylene, in the
presence of benzeneboronic acids 1 bearing electron-with-
drawing groups at the m- or p-positions, such as 3,4,5-tri-
fluorobenzeneboronic acid (1a) and 3,5-bis(trifluoromethyl)-
pyridinium chloride (2b), were effective as cationic catalysts
for amide condensation in polar solvents, such as anisole,
acetonitrile, N-methylpyrrolidinone (NMP), and ionic liquid.2
Unfortunately, these boronic acids were much less effective
for the esterification of simple carboxylic acids because an
alkoxyborane species was preferentially produced rather than
1
a
the desired acyloxyborane species. In 2004, however,
Houston et al. reported that boric acid (B(OH) , 10-20 mol
1
benzeneboronic acid (1b). We also found that N-alkyl-4-
3
boronopyridinium halides 2, such as 4-borono-N-methylpy-
ridinium iodide (2a) and N-polystyrene resin-bound 4-borono-
%) was effective as a catalyst for the chemoselective esteri-
fication of R-hydroxycarboxylic acids with excess alcohol
as solvents even at ambient temperature (Scheme 1).3 This
,4
†
Nagoya University.
The University of Chicago.
‡
(2) (a) Ohara, S.; Ishihara, K.; Yamamoto, H. The 77th Spring Meeting
of Chemical Society of Japan, 2000. (b) Ishihara, K.; Yamamoto, H. Jpn.
Kokai Tokkyo Koho JP 2001-270939 (2001-10-02), Application: JP
2000-87495 (2000-03-27). (c) Maki, T.; Ishihara, K.; Yamamoto, H.
Org. Lett. 2005, 7, 5043.
(3) Houston, T. A.; Wilkinson, B. L.; Blanchfield, J. T. Org. Lett. 2004,
6, 679.
(
1) (a) Ishihara, K.; Ohara, S.; Yamamoto, H. J. Org. Chem. 1996, 61,
4
2
2
1
1
196-4197. (b) Ishihara, K.; Ohara, S.; Yamamoto, H. Macromolecules
000, 33, 3511-3513. (c) Ishihara, K.; Ohara, S.; Yamamoto, H. Org. Synth.
002, 79, 176-185. (d) Maki, T.; Ishihara, K.; Yamamoto, H. Synlett 2004,
355-1358. (e) Ishihara, K.; Kondo, S.; Yamamoto, H. Synlett 2001, 1371-
374.
1
0.1021/ol052061d CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/05/2005