A mild, efficient and general method for the synthesis of trialkylsilyl (Z)-4-oxo-2-alkenoates and γ-hydroxybutenolides

Article abstract of DOI:10.1055/s-1998-1574

2-Trialkylsilyloxyfurans react rapidly with dimethyldioxirane at -78°C to provide trialkylsilyl (Z)-4-oxo-2-alkenoates whose hydrolysis delivers γ-hydroxybutenolides with high efficiency; a short synthesis of a naturally occurring monoterpene γ-hydroxybutenolide (4) is reported.

Full text of DOI:10.1055/s-1998-1574

January 1998
SYNLETT
31
A Mild, Efficient and General Method for the Synthesis of Trialkylsilyl
(Z)-4-Oxo-2-alkenoates and γ-Hydroxybutenolides
1
John Boukouvalas* and Nicolas Lachance
Département de Chimie, Université Laval, Québec (Québec), Canada G1K 7P4
Received 15 October 1997
Abstract. 2-Trialkylsilyloxyfurans react rapidly with dimethyldioxirane
at -78 °C to provide trialkylsilyl (Z)-4-oxo-2-alkenoates whose
hydrolysis delivers γ-hydroxybutenolides with high efficiency; a short
synthesis of a naturally occurring monoterpene γ-hydroxybutenolide (4)
is reported.
provides pure silyl ester 2 in usually quantitative yield (entries 1-7).
Hydrolysis of 2 to γ-hydroxybutenolide 3 can be conveniently
performed in the same flask on exposure to 10-30 equiv. of water and
Amberlyst-15 for 1-12 h at room temperature. After filtration, drying
(MgSO ) and evaporation, the residue is washed with pentane to furnish
4
3 which can be further purified by recrystallization (in the case of
solids) or flash chromatography.
The γ-hydroxybutenolide unit is a key structural feature of the potent
2
analgesic and antiinflammatory agent manoalide and many other
3
4
natural and unnatural products of biomedical importance. Moreover,
Importantly, selective oxidation of the siloxyfuran moiety in substrates
containing olefin groups can be achieved with equally high efficiency
by using 1 equiv. of dioxirane at -78°C. Central to the success of this
procedure is the comparatively high reactivity of the electron-rich
siloxyfuran towards dimethyldioxirane, and also the ability to control
γ-hydroxybutenolides and their acyclic derivatives, namely (Z)-4-oxo-2-
5
alkenoates, are widely used as multifunctional building blocks in the
5,6
7
laboratory and the chemical industry. Among existing methods for
5c,8
preparing γ-hydroxybutenolides,
the most popular rely on
15
photosensitized oxygenation of furans bearing
a
hydrogen or
precisely the amount, temperature and rate of addition of the oxidant.
9,10
trialkylsilyl group at the α−position.
However, the requisite furans
Thus, 5-geranyl-2-triisopropylsilyloxyfuran 1i, which contains two
trisubstituted olefin groups, was cleanly transformed into the
corresponding silyl ester 2i and γ-hydroxybutenolide 3i (entry 7, Table
1).
are not always easy to prepare and their photooxygenation often
11
4a
proceeds with modest efficiency, especially on a large scale.
We report here a new, highly efficient synthesis of γ-hydroxy-
butenolides and trialkylsilyl (Z)-4-oxo-2-alkenoates from the readily
12
available 2-trialkylsilyloxyfurans. The essence of our approach is the
capacity of siloxyfurans to undergo rapid oxidative cleavage upon
13
treatment with dimethyldioxirane (cf. 1→2, Scheme 1). Plausible
intermediates include the epoxides A-B and zwitterion C, all of which
would be expected to undergo facile decomposition, even at
13b,c
temperatures below -78 °C.
Subsequent hydrolysis of the so
obtained (Z)-4-oxo-2-alkenoates 2a,b affords γ-hydroxybutenolide 3 in
high yield.
Furthermore, it is perfectly feasible to effect hydroxylation of the
butenolide ring without purification of intermediates. A demonstration
is provided by the straightforward synthesis of γ-hydroxybutenolide 4,
an unnamed natural product isolated from the aerial parts of Boltonia
Scheme 1
17
18
asteroides (Scheme 2). Thus, Negishi coupling of the easily
12a
19
The generality of this methodology is demonstrated by the entirely
prepared bromobutenolide 6
with the homoallylzinc compound 7
regioselective construction of a variety of substituted triisopropylsilyl
provided lactone 8 which underwent sequential silylation, oxidation and
hydrolysis to give 4 in an unoptimized yield of 80% after purification by
flash chromatography. Again, no epoxidation of the olefin moiety had
occurred, as judged by the high field H and C NMR spectra of the
crude reaction product.
12,14
(Z)-4-oxo-2-alkenoates and γ-hydroxybutenolides (Table 1).
The
procedure entails treatment of a dichloromethane solution of siloxyfuran
1
13
1 (0.1-0.2 M) with 1-1.1 equiv. of dimethyldioxirane in acetone (0.03-
15
0.08 M) for 0.5-1 h at 0 or -78 °C. Evaporation of the solvents

32
LETTERS
SYNLETT
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Scheme 2
In conclusion, we have described a new, entirely regioselective method
for constructing γ-hydroxy-butenolides and trialkylsilyl (Z)-4-oxo-2-
alkenoates with diverse substitution patterns. The method is distinctly
mild and efficient and promises to be widely useful.
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yields(84-99%) from the coresponding α,β or β,γ-butenolides
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Acknowledgement. We thank the Natural Sciences and Engineering
Research Council of Canada (NSERC) for financial support and a
postgraduate scholarship to N.L.
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