LETTER
491
Scandium Triflate Catalyzed Transesterification of Carboxylic Esters
T
ransesterification
i
of
C
ar
c
boxylic
E
st
o
ers le Remme, Katharina Koschek, Christoph Schneider*
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax +49(341)9736599; E-mail: schneider@chemie.uni-leipzig.de
Received 30 November 2006
We started our investigations with the model reaction de-
picted in Scheme 1. Ethyl phenyl acetate (1a) was treated
with Sc(OTf)3 in refluxing methanol and the progress of
the reaction was followed by GC analysis. With 10 mol%
Abstract: The direct transesterification of carboxylic esters is effi-
ciently catalyzed with Sc(OTf)3 (10 mol%) in boiling alcoholic sol-
vent. Methyl, ethyl, isopropyl, and allyl esters were prepared from
a broad range of different substrates in high yields. The application
of microwave irradiation led to significantly reduced reaction times. catalyst full conversion was reached within 10 hours and
the product 2a was isolated in 91% yield. When the cata-
lyst amount was lowered to just 1 mol% the reaction time
rose to 96 hours but the product was still isolated in 95%
yield.8 Thus, although 1 mol% Sc(OTf)3 appeared to be
sufficient for full conversion at elevated temperatures all
further experiments were conducted with 10 mol%
Sc(OTf)3 in refluxing alcoholic solvent in order to reduce
the reaction times to an acceptable level.
Key words: carboxylic esters, catalysis, scandium, transesterifica-
tion
Carboxylic esters are among the most versatile organic
compounds. Accordingly, a broad number of synthetic
procedures have been developed for their preparation.1
Besides the traditional acid-catalyzed reaction of a car-
boxylic acid with an alcohol, the most often utilized meth-
od includes the treatment of an activated carboxylic acid
derivative, which is either prepared in a separate reaction
or formed in situ with an alcohol in the presence of a base.
Alternatively, transesterification reactions have been em-
ployed for the conversion of one ester into another ester.2
Such processes are subject to acid and base catalysis and
are based upon a thermodynamic equilibrium. Among the
most frequently used catalysts are titanium alkoxides de-
veloped by Seebach et al.3 and tetraalkyl distannoxanes
introduced by Otera et al.4 Whereas titanium alkoxides
need to be employed at catalyst loadings of typically 20
mol% or more the distannoxanes are extremely efficient
catalysts even down to 0.05 mol%. Simple Bu2SnO (10
mol%) has been shown by Giannis et al. to be a good
transesterification catalyst as well.5
O
O
Sc(OTf)3
Ph
Ph
OEt
OMe
MeOH, 64 °C
1a
2a
10 mol% Sc(OTf)3, 10 h: 91%
1 mol% Sc(OTf)3, 96 h: 95%
Scheme 1
Using these conditions, various aliphatic carboxylic esters
1 were then converted into the corresponding methyl
esters 2 within 6–12 hours in high yields (Table 1).9
Functional groups such as halogen atoms, cyano, hydrox-
yl, and phosphonyl groups were readily tolerated and suf-
fered no decomposition during the reaction. In fact, some
functionalized esters such as (S)-ethyl mandelate (entry 3)
and ethyl phosphono acetate (entry 8) were among the
most reactive substrates included in this study. Most im-
portantly, chiral centers even adjacent to the ester group
were not affected and completely retained their absolute
configuration. Thus, (S)-methyl mandelate and (R)-meth-
yl b-hydroxy butyrate were obtained in the same ee as the
starting esters (entries 3 and 4). A diester was successfully
converted into the corresponding dimethyl ester in slight-
ly prolonged reaction times presumably due to the
presence of two ester groups (entry 9). Surprisingly, even
esters carrying tertiary amino and Boc-protected amino
groups underwent the Sc(OTf)3-catalyzed transesterifi-
cation reaction albeit in only moderate yields (entries 10–
12). Aromatic and conjugated esters proved to be less
reactive requiring extended reaction times. The product
esters were, however, obtained in good to excellent yields
(entries 13–16).
In 1995 Yamamoto et al. demonstrated the potential of
Sc(OTf)3 to function as an esterification catalyst. They
showed that the reaction of carboxylic acid anhydrides
with alcohols was efficiently catalyzed through Sc(OTf)3
to furnish carboxylic esters in high yields.6 The anhy-
drides employed may be formed in situ from the corre-
sponding acids and para-nitro benzoic acid anhydride and
the esters were obtained with comparable yields. Subse-
quently, Otera discovered that Sc(OTf)3 successfully cat-
alyzed the conversion of N-acyl oxazolidinones into esters
in high yields and short reaction times.7 Since both anhy-
drides and imides constitute reactive carboxylic acid de-
rivatives it was unclear whether regular esters with
attenuated carbonyl activity were suitable substrates for a
Sc(OTf)3-catalyzed transesterification process as well.
SYNLETT 2007, No. 3, pp 0491–0493
Advanced online publication: 07.02.2007
DOI: 10.1055/s-2007-967936; Art ID: G34506ST
© Georg Thieme Verlag Stuttgart · New York
1
5.
0
2.
2
0
0
7
Subsequently, this protocol was extended to the formation
of ethyl, isopropyl and allyl esters, all of which were
formed in good to excellent yields when refluxed with 10