C O M M U N I C A T I O N S
Table 1. Esterification Reaction between an Equimolar Mixture of
Carboxylic Acids and Alcohols Catalyzed by 1ba
Figure 3. Preparation of 3b and its recovery and reuse.
catalyzed cross-coupling of 4-bromopolystyrene resin cross-linked
with 2% divinyl benzene (11, 2.71 mmol Br/g, 200-400 mesh)10
with 2,4,6-trimethylaniline in 75% yield.11 3b was then readily
prepared in 97% yield by treating 12 with C6F5SO3H. On the
contrary, an immobilized catalyst could not be prepared from 12
and TfOH since 3b decomposed with superacidic TfOH. 3b was
recovered by filtration and reused as the catalyst more than 10 times
for the direct ester condensation reaction of 4 with octanol, and
activity loss was not observed for the recovered catalyst.
In conclusion, the hydrophobic effect of bulky diarylammonium
sulfonates activated the esterification reaction, and steric hindrance
suppressed the dehydrative elimination of secondary alcohols to
produce alkenes. Thus, we achieved direct, catalytic ester condensa-
tion of carboxylic acids with an equimolar amount of primary
alcohols without solvents at room temperature. In addition, the
immobilization of bulky diarylammonium pentafluorobenzene-
sulfonate on a polymer support provided an efficient atom-
economical esterification catalyst that could be easily recovered
and reused.
a Unless otherwise noted, a solution of carboxylic acids (2 mmol) and
alcohols (2 mmol) in heptane (4 mL) was heated at 80 °C in the presence
of 1b (1 mol %). Yield of alkenes is shown in parentheses. b 1b (5 mol %)
was used. c 1b (10 mol %) was used at 115 °C.
Table 2. Esterification Reaction without Solvents and Heatinga
a A mixture of carboxylic acids (2 mmol) and alcohols (2.2 mmol) was
stirred at room temperature in the presence of 1b (1 mol %).
preferentially activated less-hindered carboxylic acids rather than
secondary alcohols.
To explore the generality and scope of the selective esterification
catalyzed by 1b (1 mol %) at 80 °C, the condensation was examined
with an equimolar mixture of various structurally diverse carboxylic
acids and alcohols (Table 1). 2-Unsubstituted carboxylic acids,
2-monosubstituted carboxylic acids, and sterically demanding 2,2-
disubstituted carboxylic acids were smoothly condensed to produce
the corresponding esters. R,â-Unsaturated carboxylic acids and
benzoic acids were also transformed into the corresponding esters.
2-Alkoxycarboxylic acids and 2-unsubstituted carboxylic acids were
very reactive substrates, probably due to the favorable chelation
between the substrates and 1b. 4-Oxopentanoic acid was selectively
esterified without a protecting ketone moiety. 1b was adaptable
for acid-sensitive alcohols, such as benzyl alcohol, allylic alcohols,
propargylic alcohols, and secondary alcohols. In particular, it is
noteworthy that the esterification with sterically demanding alcohol
8 proceeded to give the desired esters in good yield with less than
5% of alkenes. Although Lewis acidic metal salts such as Hf(IV)
and Zr(IV) were not adapted to 1,2-diols due to tight chelation with
metal ions,4c these diols were also esterified in high yield by 1b.
Relatively less reactive aryl alcohols and 1-adamantanol were also
esterified in high yields.
Ester condensation reactions with relatively more reactive
primary alcohols proceeded even at room temperature (22 °C)
without solvents (Table 2). Most carboxylic acids were esterified
with 1.1 equiv of methanol in good yield in the presence of 1 mol
% of 1b. 1-Octanol was also reactive. As far as we know, this is
the first example of an ultimate green esterification process.
One major problem associated with using soluble catalysts lies
in the recovery of the catalyst from the reaction medium. A simple
solution is to immobilize the catalyst on a polymeric matrix.9 Figure
3 describes the preparation of immobilized catalyst 3b. 4-(N-
Mesitylamino)polystyrene resin (12) was prepared by palladium-
Acknowledgment. Financial Support for this project has been
provided by JSPS KAKENHI(15205021), the 21st Century COE
Program “Nature-Guided Materials Processing” of MEXT, Shorai
Foundation for Science and Technology, the Ogasawara Foundation
for the Promotion of Science & Engineering, and the Noguchi
Fluorous Project of the Noguchi Institute.
Supporting Information Available: Experimental procedures, full
characterization of new compounds. This material is available free of
References
(1) Otera, J. Esterification; Wiley-VCH: Weinheim, Germany, 2003.
(2) Manabe, K.; Sun, X.-M.; Kobayashi, S. J. Am. Chem. Soc. 2001, 123,
10101.
(3) Xiang, J.; Orita, A.; Otera, J. AdV. Synth. Catal. 2002, 344, 84.
(4) (a) Ishihara, K.; Ohara, S.; Yamamoto, H. Science 2000, 390, 1140. (b)
Ishihara, K.; Nakayama, M.; Ohara, S.; Yamamoto, H. Synlett 2001, 1117.
(c) Ishihara, K.; Nakayama, M.; Ohara, S.; Yamamoto, H. Tetrahedron
2002, 58, 8179. (d) Nakayama, M.; Sato, A.; Ishihara, K.; Yamamoto, H.
AdV. Synth. Catal. 2004, 346, 1275.
(5) Wakatsugi, K.; Misaki, T.; Yamada, K.; Tanabe, Y. Tetrahedron Lett.
2000, 41, 5249.
(6) For the measurement of pKa in CD3CO2D, see: Rode, B. M.; Engelbrecht,
A.; Schantl, J. Z. Physik. Chem. (Leipzig) 1973, 253 (1-2), 17. The pKa
values of diarylammonium sulfonates could not be estimated due to their
low solubility.
(7) For the values of H0, see: Habel, W.; Sartori, P. J. Fluorine Chem. 1982,
20, 559. The acidity of C6F5SO3H may be moderated by an intramolecular
electrostatic interaction between H+ and o-F.
(8) For the activation of [Ph2NH2]+[OTf]- in fluorous media, see: Gacem,
B.; Jenner, G. Tetrahedron Lett. 2003, 44, 1391. In contrast, 1b and 2b
were not activated by fluorous media because of their sufficient
hydrophobicity.
(9) Lei, M.; Ma, C.; Wang Y.-G. Chinese J. Chem. 2001, 19, 1309.
(10) Purchased from TCI, Co., Ltd., Japan.
(11) Vyskocil, S.; Jaracz, S.; Smrina, M.; St´ıcha, M.; Hanus, V.; Pola´sek, M.;
Kocovsky, P. J. Org. Chem. 1998, 63, 7727.
JA050223V
9
J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005 4169