COMMUNICATIONS
CCl
was hydrolyzed with aqueous NaOH (4n)/THF at room temperature for
h to furnish polymeric [(C CH SnO] (2) (93%). Treatment of 2
5 mmol) with aqueous HCl (4n; 6.5 mmol) in acetone at room temper-
4 6 2 2 2 2
at room temperature for 3 h gave (C F13CH CH ) SnBr (96%), which
A Mild and Effective Method for the
Transesterification of Carboxylic Acid Esters**
2
(
6
F
13CH
2
2
)
2
n
Patrick Baumhof, Ralph Mazitschek, and
Athanassios Giannis*
119
2 2
ature for 24 h afforded 1a in 85% yield: m.p. 90 ± 918C (CH Cl ); Sn
NMR ([D
6
]acetone): d � 178.3, � 202.5; elemental analysis: calcd for
C
64
H
32Cl
4
F
104
O
2
Sn : C 22.44, H 0.94; found: C 22.58, H 0.54.
4
Transesterification is one of the most important trans-
formations in organic synthesis.[ The most important meth-
ods, besides acid or base catalysis, employ titanium tetraalk-
Fluorous biphasic transesterification: A mixture of ethyl 3-phenylpropio-
nate(356 mg, 2.0 mmol), 1-octanol (260 mg, 2.0 mmol), and 1a (171 mg,
1]
0.1 mmol) in FC-72 (4.0 mL) was added to a test tube. The test tube was
placed in a stainless-steel pressure bottle and heated at 1508C for 16 h. The
reaction mixture was then cooled to room temperature and toluene (5 mL)
was added. The FC-72 layer was washed with toluene (2 Â 1 mL) and the
combined toluene solution was evaporated to afford pure octyl 3-phenyl-
propionate (525 mg, 2.0 mmol). The FC-72 solution was used in the next
reaction.
[2]
[3]
[4]
oxides, complex tin compounds, indium iodide, or
enzymes.[ During a dibutyltin oxide-mediated selective
O-methylation of compound 1a, we observed the formation
of methyl ester 1b as a side product (Scheme 1). Interestingly,
5]
Received: April 17, 2001 [Z16946]
[
[
[
1] J. Otera, Chem. Rev. 1993, 93, 1449.
2] B. M. Trost, Science 1991, 254, 1471.
3] J. Otera, T. Yano, A. Kawabata, H. Nozaki, Tetrahedron Lett. 1986, 27,
2383.
[4] J. Otera, S. Ioka, H. Nozaki, J. Org. Chem. 1989, 54, 4013.
[5] J. Otera, N. Dan-oh, H. Nozaki, J. Org. Chem. 1991, 56, 5307.
[6] J. Otera, N. Dan-oh, H. Nozaki, J. Chem. Soc. Chem. Commun. 1991,
Scheme 1. Dibutyltin oxide catalyzed transesterification of ethyl ester 1a
into methyl ester 1b.
1742.
[
[
[
7] J. Otera, N. Dan-oh, H. Nozaki, Tetrahedron 1993, 49, 3065.
8] A. Orita, A. Mitsutome, J. Otera, J. Org. Chem. 1998, 63, 2420.
9] A. Orita, K. Sakamoto, Y. Hamada, A. Mitsutome, J. Otera,
Tetrahedron 1999, 55, 2899.
neither elimination nor epimerization at the stereogenic
center adjacent to the ester moiety was observed. Previous
attempts to obtain methyl ester 1b by using various acids and
bases always led either to complete epimerization or to the
[
[
10] A. Orita, T. Ito, Y. Yasui, J. Otera, Synlett 1999, 1927.
11] J. Otera in Advances in Detailed Reaction Mechanism, Vol. 3 (Ed.:
J. M. Coxon), JAI, Greenwich, 1994, p. 167.
decomposition of 1a. Furthermore, Ti(OMe) was not suitable
4
for this purpose owing to its insolubility in methanol.[
2]
[
[
12] T. Horv a th, Acc. Chem. Res. 1998, 31, 641.
The significance of the observed side product encouraged
us to optimize this reaction and to investigate the scope and
limitations of this method. Several simple as well as highly
functionalized aliphatic and aromatic esters were treated with
catalytic amounts of dibutyltin oxide (1 ± 10 mol%) in differ-
ent alcohols as solvents. The isolated derivatives correspond-
ed to the product of transesterification with the alcohol that
was used as solvent (Table 1). The reaction conditions are
very mild and thus the method is tolerant of several functional
groups, for example, acetals, ketals, aliphatic bromides, b-
ketoesters, and enol ethers. Most significantly, free hydroxy,
phenolic, and even amino groups do not affect the reaction.
The potential scope of this method was clear from the
treatment of 4a with dibutyltin oxide in methanol to afford
the desired derivative 4b in an excellent yield (Table 1,
entry 4).[ We suppose that the tert-butyl ester moiety in 4a is
first transformed into the methyl ester, which is then attacked
intramolecularly by the free amino group to afford the final
product 4b. To exclude the possibility that the amide was
13] D. P. Curran, Angew. Chem. 1998, 110, 1230; Angew. Chem. Int. Ed.
1998, 37, 1174.
[
[
[
[
14] E. G. Hope, A. M. Stuart, J. Fluorine Chem. 1999, 100, 75.
15] B. Bucher, D. P. Curran, Tetrahedron Lett. 2000, 41, 9617.
16] J. Otera, T. Yano, K. Nakashima, R. Okawara, Chem. Lett. 1984, 2109.
17] T. Yano, K. Nakashima, J. Otera, R. Okawara, Organometallics 1985,
4
, 1501.
[
[
[
[
[
18] S. P. Chavan, P. K. Zubaidha, S. W. Dantale, A. Keshavaraja, A. V.
Ramaswamy, T. Ravindranathan, Tetrahedron Lett. 1996, 37, 233.
19] B. S. Balaji, M. Sasidharan, R. Kumar, B. Chanda, Chem. Commun.
1996, 707.
20] D. E. Ponde, V. H. Deshpande, V. J. Bulbule, A. Sudalai, A. S. Gajare,
J. Org. Chem. 1998, 63, 1058.
21] B. M. Reddy, V. R. Reddy, B. Manohar, Synth. Commun. 1999, 29,
1235.
22] The quantitative recovery of the catalyst without depression of the
activity is apparent: the reaction shown in Table 1, entry 2 was
repeated and gave >99% yield (GC) and 98 ± 100% recovery of the
catalyst in every run. For further supporting evidence, see ref. [24].
23] Zhuꢁs conventional transesterification was carried out in refluxing
flourocarbon solvents in a Dean ± Stark trap. The product ester (67 ±
6]
[
[
8
7% yield) was readily separated from the solvent but the catalyst,
Ti(OiPr) , remained in the organic layer: D.-W. Zhu, Synthesis 1993,
53.
4
9
24] The reaction in Table 2, entry 1 was repeated 20 times. The GC yield
was constantly >99% each time, and 91% of the catalyst was
recovered after the 20th run, indicative of virtually no loss and no
deactivation of the catalyst during the repetition.
[
*] Prof. Dr. A. Giannis, P. Baumhof, R. Mazitschek
Institut für Organische Chemie der Universität Karlsruhe
Richard-Willstätter-Allee 2, 76128 Karlsruhe (Germany)
Fax : (49)721-608-7652
E-mail: giannis@ochhades.chemie.uni-karlsruhe.de
[**] P.B. and R.M. are grateful to the Land Baden-Württemberg for a
scholarship from the Landesgraduiertenförderung.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
3672
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4019-3672 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 19