Lithium perchlorate as an efficient catalyst for selective transesterification of β-Keto esters essentially under neutral conditions

Article abstract of DOI:10.1055/s-2001-16033

Lithium perchlorate catalysed efficient transesterification of β-keto esters has been carried out, which affords various esters under almost neutral conditions.

Full text of DOI:10.1055/s-2001-16033

1338
LETTER
Lithium Perchlorate as an Efficient Catalyst for Selective Transesterification
of -Keto Esters Essentially Under Neutral Conditions
B. P. Bandgar,* V. S. Sadavarte, L. S. Uppalla
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Nanded-431 606, India
Fax 0091-2462-29245; E-mail: bandgar_bp@yahoo.com
4 April 2001
tentiality of the reaction. We report here lithium
Abstract: Lithium perchlorate catalysed efficient transesterifica-
perchlorate as a neutral catalyst for selective and practical
transesterification of -keto esters (Scheme).
tion of -keto esters has been carried out, which affords various es-
ters under almost neutral conditions.
After scanning through different catalysts (Table 2), we
found that lithium perchlorate worked remarkably well.
Treatment of butyl/ ethyl/ methyl -keto ester with alco-
hols along with a catalytic amount of lithium perchlorate
in toluene at 100 °C afforded -keto esters in excellent to
good yields. Various alcohols (primary, secondary, tertia-
ry, benzylic, allylic and propargylic) underwent smooth
transesterification reactions. Even less reactive trityl alco-
hol afforded the corresponding -keto ester in moderate
yield (Table 1, entry 7) which is otherwise often problem-
atic in acid catalyzed reactions or failed to undergo trans-
esterification with Ti(OEt)4.4e It should be pointed out that
transesterification of -keto esters with unsaturated alco-
hols is rather difficult as it is offset by facile decarboxylat-
ed rearrangement.12 The superiority of this procedure can
be clearly visualized in transesterifications leading to the
synthesis of -keto esters with an aromatic moiety in good
yields (Table 1, entries 9-12). In this connection it should
be mentioned that a recent literature report13 which de-
scribes the synthesis of alkyl -keto esters employing a tin
based super acid catalyst, failed with aromatic substrates.
It is also clear from Table 1 that the conversion of ethyl es-
ter to higher homologue appears to be efficient by this
procedure (Table 1, entry 1) in excellent yield. It is impor-
tant to note that chiral integrity of (–)-menthol is main-
tained under these reaction conditions (chiral alcohol is
recovered by base hydrolysis of ester and its optical rota-
tion is checked, Table 1, entry 5). It is noteworthy to men-
tion that the reaction appears to be specific only for
transformation of -keto esters. Other esters like -keto
esters, -keto esters as well as normal esters failed to un-
dergo the reaction (Table 1, entries 13-17).
Key words: transesterification, -keto ester, lithium perchlorate,
catalyst
-Keto esters represent an important class of organic
building blocks1 and are used for efficient synthesis of a
number of complex natural products. Transesterification,
one of the useful and important methods of ester synthesis
has wide applications both in academic and industrial
research2 and in general, it is accelerated by protic acids,3
Lewis acids3 and basic catalysts.3 More recently, various
catalysts have been reported to effect transesterifica-
tion.3,4 Most of the reported methods of transesterification
of -keto esters are not general and are equilibrium driven
reactions where usage of an excess of one of the reactants
is mandatory to obtain good yields. Toxic and expensive
DMAP5 catalyzed transesterification required a large
amount of catalyst whereas tertiaryl butyl acetoacetate6 is
restricted to tertiary butyl esters, thus lacking generality.
Distannoxanes7 gave good yields of -keto esters; howev-
er the catalysts are difficult to prepare. Although many
methods are available for the preparation of alkyl ben-
zoylacetates, there are few reports4a,4d on the synthesis
of -keto esters which are required for the synthesis
of lignans including podophyllotoxin. -Disubstituted
-keto ester enolates underwent efficient 1,3-ester shift
under basic conditions.8 Very few examples are reported
on transesterification of -keto esters with propargylic
alcohols2,9 even though several of the reported methods
were effective with allylic alcohols. Transesterification of
simple esters with stoichiometric amounts of iron(III)
perchlorate10 is also reported without selectivity towards
-keto esters.
In conclusion we have demonstrated that lithium perchlo-
rate is an excellent catalyst for transestrification of -keto
esters essentially under neutral conditions besides en-
abling an easy work-up. The effectiveness of this protocol
is manifested in its selectivity towards -keto esters
whereas other esters are found to be unreactive under
these reaction conditions.
In recent years lithium perchlorate and lithium perchlorate
in diethyl ether (LPDE) have gained a lot of importance
as versatile reagents for effecting organic transformations
under neutral conditions.11 Thus, the development of a
new method which allows transesterification under essen-
tially neutral conditions should heighten the synthetic po-
Scheme
Synlett 2001, No. 8, 1338–1340 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Lithium Perchlorate as an Efficient Catalyst for Selective Transesterification
1339
Table 1 Lithium perchlorate catalyzed transesterification of -keto esters
Synlett 2001, No. 8, 1338–1340 ISSN 0936-5214 © Thieme Stuttgart · New York

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B. P. Bandgar et al.
Table 1 continued
LETTER
a) Yields of pure isolated products. b) Products are characterised by their spectral analysis.
Table 2 Catalytic effect on transesterification of ethyl acetoacetate (5 mmol) with n-butanol (5 mmol)
a) Yields of pure isolated products. b) Products are characterised by their spectral analysis.
Typical procedure: Methyl 3-(3,4,5-trimethoxyphenyl)-3-oxo
propionate (5 mmol), cinnamyl alcohol (5 mmol) and lithium per-
chlorate (1 mmol) in toluene (20 mL) was heated to 100 °C in a
round bottom flask with distillation condenser to remove methanol.
After completion (TLC) the reaction mixture was cooled, filtered
and the filtrate was concentrated and chromatographed on SiO2
(hexane-ethyl acetate, 9:1) to afford (E)-3-phenyl-2-propenyl 3-
(3,4,5-trimethoxyphenyl)-3-oxopropanoate as a colourless liquid in
excellent yield.
(3) Kumar, P.; Pande, R. K. Synlett 2000, 2, 251 and references
cited therein.
(4) (a) Balaji, B. S.; Sasidharan, M.; Kumar, R.; Chanda, B.
Chem. Commun. 1996, 707; (b) Ranu, B. C.; Dutta, P.; Sarkar,
A. J. Org. Chem. 1998, 63, 6027; (c) Reddy, B. M.; Reddy, V.
R.; Manohar, B. Synth. Commun. 1999, 29, 1235; (d) Balaji,
B. S.; Chanda B. M. Tetrahedron 1998, 54, 13227; (e) Krasik,
P. Tetrahedron Lett. 1998, 39, 4223; (f) Fukuzawa, S.; Hongo,
Y. Tetrahedron Lett. 1998, 39, 3521.
(5) Taber, D. F.; Amedio, Jr. J. C.; Patle, Y. K. J. Org. Chem.
1985, 50, 3618.
(6) Witzeman, J. S.; Nottingham, W. D. J. Org. Chem. 1991, 56,
1713.
(7) Otera, J.; Danoh, N.; Nozaki, H. J. Org. Chem. 1991, 56,
5301.
(8) Habi, A.; Gravel, D. Tetrahedron Lett. 1994, 35, 4315.
(9) Mottet, C.; Hamelin, O.; Garavel, G.; Depres, J.; Green A. E.
J. Org. Chem. 1999, 64, 1380.
Yield: (77%); IR (neat) cm-1: 3322, 1734, 1699; 1H NMR: = (200
MHz, CDCl3): 7.5-7.3 (m, 5H), 7.39 (s, 1H), 7.23 (s, 1H), 6.75 (d,
J = 15 Hz, 1H), 6.30-6.20 (m, 1H) 4.8 (dd, J = 6 and 1.2 Hz, 2H),
4.05, 3.89 (s, 9H), [3.88, 5.5, 12.1] (s, 2H); 13C NMR : = (50
MHz, CDCl3): 191, 167, 153, 143, 135, 134, 130, 128, 128, 126,
122, 106, 86, 65, 60, 56, 45; Anal. Calcd. for C21 H22 O6 (370.41): C,
68.10; H, 5.99. Found: C, 67. 90; H, 5.55
(10) Kumar, B.; Kumar, H.; Parmar, A. Ind. J. Chem. B 1993, 32,
292.
(11) Babu, B. S.; Balsubramanian, K. K. Tetrahedron Lett. 1998,
39, 9287 and references cited therein.
Acknowledgement
VSS thanks CSIR, New Delhi for Jr. Research Fellowship.
(12) (a) Carrol, M. F. J. Am. Chem. Soc. 1940, 704; (b) Kimel, W.;
Cope, A. C. J. Am. Chem. Soc. 1943, 65, 1992.
(13) Chavan, S. P.; Zubaidha, P. K.; Dantale, S. W.; Keshavaraja,
A.; Ramaswami, A. V. Ravindranathan, T. Tetrahedron Lett.
1996, 37, 233.
References and Notes
(1) Benetti, S.; Ramagnoli, R.; De Risi, C.; Spalluto, G.; Zanirato,
V. Chem. Rev. 1995, 95, 1065.
(2) (a) Fujoita, T.; Tanak, M.; Norimine, Y.; Suemunc, H. J. Org.
Chem. 1997, 62, 3824; (b) Shapiro, G.; Marli M. J. Org.
Chem. 1997, 62, 7096.
Article Identifier:
1437-2096,E;2001,0,08,1338,1340,ftx,en;D04501ST.pdf
Synlett 2001, No. 8, 1338–1340 ISSN 0936-5214 © Thieme Stuttgart · New York