Vicinal dianions of diethyl α-aroylsuccinates: A general synthetic route to α-aroyl- and α-arylidene-γ-butyrolactones

Article abstract of DOI:10.1016/S0040-4039(03)01622-8

Vicinal dianions derived from diethyl α-aroylsuccinates were found to react with carbonyl compounds β-regioselectively to afford α-aroyl-γ-butyrolactones, which were converted into α-arylidene-γ-butyrolactones by reduction with H₂/Pd-C followed

Full text of DOI:10.1016/S0040-4039(03)01622-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6717–6720
Vicinal dianions of diethyl a-aroylsuccinates: a general synthetic
route to a-aroyl- and a-arylidene-g-butyrolactones
Manat Pohmakotr,* Laddawan Sampaongoen, Arisara Issaree, Patoomratana Tuchinda and
Vichai Reutrakul
Department of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand
Received 29 May 2003; revised 14 June 2003; accepted 27 June 2003
Abstract—Vicinal dianions derived from diethyl a-aroylsuccinates were found to react with carbonyl compounds b-regioselectively
to afford a-aroyl-g-butyrolactones, which were converted into a-arylidene-g-butyrolactones by reduction with H2/Pd–C followed
by elimination employing methanesulfonyl chloride in pyridine. The method provides a general and convenient route to a-aroyl-
and a-arylidene-g-butyrolactones.
© 2003 Elsevier Ltd. All rights reserved.
Carbonꢀcarbon bond forming reactions based on the
reactions of dianions are of interest, because high regio-
and stereoselectivities towards electrophiles have been
achieved.1 Among these dianions, the vicinal dianions
of succinic acid derivatives were extensively demon-
strated to be useful reagents for the preparation of
various classes of compounds.2 In the course of our
study on using succinic acid derivatives as versatile
building blocks for synthesis of some natural products
containing the g-butyrolactone nucleus including lig-
nans, we have recently reported the syntheses of
( )-lichesterinic acid, ( )-phaseolinic acid, ( )-nephro-
mopsinic acid and ( )-dihydroprotolichesterinic acid by
making use of the vicinal dianion derived from triethyl
ethanetricarboxylate.3 In continuation of our above
results, we wish to report herein the reactions of vicinal
dianions of a-aroylsuccinic esters with carbonyl com-
pounds. It could be envisaged that these vicinal dian-
ions would react with carbonyl compounds b-
regioselectively to provide a-aroyl-g-butyrolactones,
which would be useful as the precursors for many
synthetic manipulations. In this communication, the
preparation of a-arylidene-g-butyrolactones4 from a-
aroyl-g-butyrolactones is also reported.
The vicinal dianion 2a was readily generated by treat-
ment of a-benzoylsuccinic ester 1a5 with lithium diiso-
propylamide (LDA, 2.1 equiv.) in tetrahydrofuran
(THF) at −78°C for 1 h. The reaction of the vicinal
dianion 2a with benzaldehyde (1.1 equiv.) in the pres-
ence of ZnCl2 (1.1 equiv.) at −78°C for 2 h, followed by
slowly warming up to rt overnight afforded the
expected a-aroyl-g-butyrolactone 3a in 74% yield as a
mixture of diastereomers after quenching with 2N HCl.
The formation of g-butyrolactone 3a revealed that the
vicinal dianion 2 combined with benzaldehyde regiose-
lectively at the b-carbon to furnish the b-hydroxy
adduct which underwent lactonisation upon acidic
Scheme 1.
Keywords: dianions; diethyl a-aroylsuccinates; a-arylidene-g-butyrolactones; a-aroyl-g-butyrolactones.
* Corresponding author. Tel.: 066-02-2015158; fax: 066-02-6445126; e-mail: scmpk@mahidol.ac.th
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01622-8

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work-up. Exclusive b-regioselectivities of the vicinal
dianion 2a with other aromatic aldehydes and isobu-
tyraldehyde, as well as acetone and cyclohexanone (Table
1, entries 1–3 and 10–12) were observed (Scheme 1).
Moderate to good yields of the corresponding g-butyro-
lactones 3 as diastereomeric mixtures were obtained. The
reactions of vicinal dianions 2b and 2c with aromatic
aldehydes under the same conditions gave moderate
yields of g-butyrolactones 3 as mixtures of diastereomers
(Table 1, entries 4–9). The 3,4-trans-4,5-cis-isomer (TC-
isomer) of g-butyrolactones 3a–i could be obtained in
pure form by preparative thin-layer chromatography
(silica gel). The relative stereochemistries of the TC-iso-
mer of 3a was concluded from NOE experiments.6
Table 1. Preparation of a-aroyl-g-butyrolacones 3 and a-arylidene-g-lactones 5

M. Pohmakotr et al. / Tetrahedron Letters 44 (2003) 6717–6720
6719
Scheme 2.
Having obtained functionalized g-butyrolactones 3 in
an efficient way, we next demonstrated the synthetic
utility of these g-butyrolactones as precursors for syn-
theses of a-arylidene-g-butyrolactones 5. These syn-
thetic transformations could be simply accomplished by
successive reduction and elimination reactions. Thus,
TC-3a was subjected to a catalytic hydrogenation (H2/
Pd–C/EtOAc) to furnish alcohol 4a as a 90:10 mixture
of diastereomers, which was further treated with
methanesulfonyl chloride in pyridine at rt for 3 h
followed by heating at 60°C for 1 h to give E-benzyli-
dene-g-butyrolactone 5a in 60% overall yield (Scheme
2). As shown in Table 1, compounds 5b–i were pre-
pared in good overall yields as E-isomers.7 The expla-
nation for the formation of the E-isomer as the sole
product could be due to the fact that elimination of the
initially formed mesylate group of compound 4 pro-
ceeded via an E2-elimination followed by a conjugate
addition–elimination of pyridine to the initially formed
a-arylidene-g-butyrolactones to lead to the thermody-
namically more stable E-isomer. An E1cb mechanism
may also be responsible for these results. The cis-stere-
ochemistry at C-4 and C-5 was confirmed by the NOE
experiments of compound 3h.8
2002, 41, 176–178; (b) Kende, A. S.; Mendoza, J. S.;
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5. a-Aroylsuccinic esters 1 were prepared by reacting a-
N,N-dimethylaminonitriles derived from aromatic alde-
hydes with diethyl fumarate in ethanol employing NaOEt
as a base followed by hydrolysis of the resulting adducts
with CuSO4.9 Alternatively, these compounds could also
be achieved by conjugate addition of aromatic aldehydes
to diethyl fumarate catalysed by Stetter’s catalyst [3-ben-
zyl-5-(2-dihydroxy-ethyl)-4-methylthiazolium chloride] in
ethanol at 80°C for 15 h.10
In summary, we have shown that the vicinal dianions
derived from a-aroylsuccinic esters react with carbonyl
compounds regioselectively at the b-carbon in the pres-
ence of ZnCl2 to furnish a-aroyl-g-butyrolactones in
moderate yields. These compounds could be used as
useful precursors for the preparation of a-arylidene-g-
butyrolactones. Thus, our method described herein pro-
vides
butyrolactones.
a general synthetic route to a-arylidene-g-
Acknowledgements
We thank the Thailand Research Fund for financial
support (BRG/22/2544) to M.P. and the award of a
Senior Research Scholar to V.R. Thanks are also made
to the Higher Education Development Project: Post-
graduate Education and Research Program in Chem-
istry for support. We are grateful to Professor Paul
Knochel, LMU, Munich, Germany, for the HRMS and
CHN determination of some compounds.
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