Catalytic synthesis of (E)-a,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene

Article abstract of DOI:10.3762/bjoc.5.3

A practical and high yielding synthesis of a,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene was developed.

Full text of DOI:10.3762/bjoc.5.3

Catalytic synthesis of (E)-α,β-unsaturated esters from
aldehydes and 1,1-diethoxyethylene
Rubén Manzano1, Lidia Ozores1, Andreas Job2, Lars Rodefeld3
and Benjamin List*,1
Preliminary Communication
Open Access
Address:
Beilstein Journal of Organic Chemistry 2009, 5, No. 3.
1Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1,
45470 Mülheim an der Ruhr, Germany, 2Saltigo GmbH, 51369
Leverkusen, Germany and 3Bayer CropScience AG, 40789 Monheim,
Germany
doi:10.3762/bjoc.5.3
Received: 19 December 2008
Accepted: 26 January 2009
Published: 30 January 2009
Email:
Benjamin List* - list@mpi-muelheim.mpg.de
Editor-in-Chief: J. Clayden
* Corresponding author
© 2009 Manzano et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
1,1-diethoxyethylene; α,β-unsaturated esters
Abstract
A practical and high yielding synthesis of α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene was developed.
Introduction
A number of reactions transforming aldehydes into α,β-unsatur- and reliably high (E)-stereoselectivities (Scheme 1, eq 4).
ated esters have been developed and especially Wittig reaction Although previously attempted under thermal conditions with
variants are widely used [1]. A general problem with these poor success, our catalytic reaction is entirely new [25].
approaches, however, is their unsatisfactory atom economy
resulting in significant by-product formation (Scheme 1, eq We reasoned that the reaction of readily available and inex-
1–2). Alternatives have been suggested but a solution that is pensive ketene diethyl acetal [26] or ketene dimethyl acetal
both as general and efficient as the Wittig procedures and satis- (available from Aldrich) with aldehydes upon treatment with a
factory with respect to the demand for atom economy is still suitable reagent or catalyst could readily lead to the corres-
needed [2-22]. We have recently developed a new approach ponding unsaturated ester and ethanol or methanol as the only
based on the Knoevenagel condensation of readily available and by-product. The use of ketene dialkyl acetals for organic trans-
inexpensive malonate half esters with aldehydes which leads to formations is infrequent [27]. To the best of our knowledge,
the formation of water and CO2 as the only by-products they have been employed in [2+2] cycloadditions [28-30],
(Scheme 1, eq 3) [23,24]. Here we describe as a new approach, Diels-Alder processes [31] and reactions with alcohols [32] and
the boronic acid-catalyzed condensation of ketene dialkyl acetal N-formyl imines [33], to afford orthoesters and N-formyl-β-
with aldehydes to furnish α,β-unsaturated esters in good yields aminoesters respectively.
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Beilstein Journal of Organic Chemistry 2009, 5, No. 3.
Scheme 1: Conversions of aldehydes into α,β-unsaturated esters.
Results and Discussion
Cinnamaldehyde, as an example of an unsaturated aldehyde
Initial experiments revealed that Brønsted acids such as acetic gave the desired product in 83% yield (entry 6). The unsatur-
acid indeed catalyze the newly designed transformation. After ated esters derived from branched aliphatic aldehydes were isol-
screening various catalysts and different reaction conditions, we ated in 80–89% yield (entries 7–8). Even α-unbranched, linear
found that boronic acids [34], especially 2,4,5-trifluorophenyl- aldehydes furnished the expected product (entries 9–10).
boronic acid, proved to be quite active catalysts of the condens- However, in these cases, the yields are slightly lower (61–64%).
ation of benzaldehyde with ketene diethyl acetal (Table 1). In addition, 1,1-dimethoxyethylene has also been tested and was
Brønsted acids are also effective but this particular boronic acid, found to give the corresponding methyl esters analogously.
which possesses both Lewis acidity and Brønsted acidity, was
the most active catalyst and gave the highest yields of the Despite the absence of any supporting evidence, we envision a
corresponding α,β-unsaturated ester. The optimized procedure plausible mechanism that explains the peculiar effectiveness of
involved the slow addition of 1,1-diethoxyethylene to benzalde- boronic acids as catalysts (Scheme 2). Accordingly, the boronic
hyde in the presence of a catalytic amount (5 mol%) of 2,4,5- acid functions as a Lewis acid activating the aldehyde but also
trifluorophenylboronic acid at 50 °C in MTBE, affording the
corresponding α,β-unsaturated ester in 98% yield as the pure
Table 2: Olefination of different aldehydes.
(E)-isomer.
The procedure proved general and both aromatic as well as
aliphatic aldehydes can be utilized (Table 2). For aromatic alde-
hydes the yields are typically very high (93–98%, entries 1–5).
Table 1: Selected results for catalyst screening.
Entry
R
Yielda
1
2
3
4
5
6
7
8
9
10
p-MeO-Ph
Ph
94
98
97
93
97
83
89
80
64
61
p-Br-Ph
1-naphthyl
p-MePh
PhCH=CH
Cy
Entry
Catalyst
Yielda
1
2
3
4
5
2,4,5-C6H2F3-B(OH)2
B(OH)3
98
71
86
86
82
p-TsOH·H2O
C6F5-B(OH)2
CF3CO2H
iPr
n-C4H9
n-C6H13
aYield of isolated product
aYield of isolated product
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Beilstein Journal of Organic Chemistry 2009, 5, No. 3.
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A solution of benzaldehyde (500 mg, 4.7 mmol) and 2,4,5-
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was prepared. After heating the reaction mixture to 50 °C, a
solution of ketene diethyl acetal (4 equiv) in MTBE (2.5 mL)
was added dropwise over 2 h, and the reaction was stirred at the
same temperature for 12 h. The solvent was removed under
vacuum, and the crude material was purified by flash chromato-
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Acknowledgments
Generous support from the Max-Planck-Society, and the Fonds
der Chemischen Industrie is gratefully acknowledged. R.M.
thanks the Ministerio de Ciencia e Innovación for a predoctoral
fellowship (FPU).
doi:10.1002/adsc.200505196
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