686
V. Ragoussis, A. Giannikopoulos / Tetrahedron Letters 47 (2006) 683–687
ketone 3 in good yield (73–92%) and high stereoselectiv-
ity (>98%). The trans-geometry was deduced from the
characteristic absorption at 970 cmÀ1 in the IR as well
cyclic or polyfunctional substrates and also in the syn-
thesis of natural products.
1
as by comparison of their H NMR and mass spectra
with those reported in the literature (see Table 1). Minor
amounts (<0.5%) of the corresponding a,b-unsaturated
ketone or (Z)-b,c-unsaturated ketone, as well as the
fully saturated product, were detected by GC–MS
analysis.
Acknowledgement
We thank the University of Athens, Special Research
Account, for supporting this work.
When substrate 2 was obtained by condensation of an
allyl b-acetoacetate and an a-branched aldehyde (entries
b and d), the decarboalkoxylation proceeded in lower
yield (44% and 35%, respectively) and the selectivity of
the reaction was poor. A considerable amount of the
corresponding a,b-unsaturated ketone was present in
the final product. Decarboxylation of substrate 3h,
which contains an aromatic ring (entry h), also needed
forcing conditions and gave, in low yield (35%),
a,b-unsaturated ketone and the reduced ketone in a
1/1 ratio. It must be noted that for the decarboxylation
step, there was no need to separate the E- and Z-isomers
of allyl a-alkenyl-b-ketoesters 2. For example, when the
Z- and E-isomers of substrate 2c were separated by care-
ful column chromatography on silica gel and separately
subjected to the decarboxylation procedure, (E)-6-
methyl-4-hepten-2-one 3c was obtained in the same
yield, and exactly the same purity, in both cases.
References and notes
1. March, J. In Advanced Organic Chemistry, 3rd ed.; John
Wiley and Sons: New York, 1985; pp 564–565.
2. Krapcho, A. P. Synthesis 1982, 893–914, and references
cited therein.
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3416–3417.
4. Tsuji, J. Proc. Jpn. Acad., Ser. B 2004, 80, 349–358.
5. Kourouli, T.; Kefalas, P.; Ragoussis, N.; Ragoussis, V.
J. Org. Chem. 2002, 67, 4615–4618.
6. Jones, G. In Organic Reactions; John Wiley and Sons:
New York, 1967; Vol. 15, pp 204–599.
7. (a) Thomas, F. A.; Thommen, W.; Willhalm, B.; Hag-
aman, W. E.; Wenkert, E. Helv. Chim. Acta 1974, 57,
2055–2061; (b) Wood, F. W.; Shaffer, B. T.; Kubo, A. J.
Chem. Ecol. 1995, 21, 1401–1408; (c) Escoubas, P.; Lajide,
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Gries, G.; Clearwater, J.; Gries, R.; Khaskin, G.; King, S.;
Schaefer, P. J. Chem. Ecol. 1999, 25, 1091–1104.
8. (a) Zhu, J.; Kozlov, M. V.; Philipp, P.; Franke, W.;
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I.; Hulme, N. A. Tetrahedron Lett. 1990, 31, 7513–7516.
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1975, 97, 4825–4836; (b) Banerjee, K. A.; Acevedo, C. J.;
Gonzalez, R.; Rojas, A. Tetrahedron 1991, 47, 2081–2086;
(c) Ito, N.; Etoh, T.; Hagiwara, H.; Kato, M. Synthesis
1997, 153–155; (d) Armesto, D.; Ortiz, M. J.; Agarrabeitia,
A. R.; Martin-Fontecha, M. Org. Lett. 2005, 7, 2687–
2690.
The formation of b,c-unsaturated ketones from allyl a-
alkenyl-b-ketoesters, by palladium catalyzed reductive
decarboxylation, can be explained by the catalytic cycle
presented in Scheme 1.
Oxidative addition of allyl a-alkenyl-b-ketoester 2 to the
palladium(0) species formed in situ from Pd(OAc)2 and
PPh3, affords
a
p-allylpalladium-b-ketocarboxylate
complex 4a initially, which is transformed to p-allylpal-
ladium enolate 4b.3 The a-carbonyl group in p-allylpal-
ladium-b-ketocarboxylate 4b is activated by a chelating
effect. An intramolecular proton transfer of the palla-
dium complex 4b gives 5. Next, p-allylpalladium dieno-
late acid 5 (which cannot be decarboxylated), undergoes
protonation from HCOOH to give b,c-unsaturated keto
acid 6, which is finally decarboxylated to afford b,c-
unsaturated ketone 3 and p-allylpalladium formate.
The latter, after decarboxylation and reductive elimina-
tion of the produced allylpalladium hydride, gives pro-
pene and regenerates the Pd(0) species, which enters a
new catalytic cycle.
10. For recent literature on the subject see: (a) Ma, S.; Yu, S.;
Yin, S. J. Org. Chem. 2003, 68, 8996–9002, and references
cited therein; (b) Cannes, C.; Condon, S.; Durandetti, M.;
Perichon, J.; Nedelec, Y. J. J. Org. Chem. 2000, 65, 4575–
4583; (c) Hantzawa, Y.; Tabuchi, N.; Taguchi, T. Tetra-
hedron Lett. 1998, 39, 6249–6252; (d) Katritzky, R. A.;
Wu, H.; Xie, L. J. Org. Chem. 1996, 61, 4035–4039, and
references cited therein; (e) Chang, S.; Yoon, J.; Brook-
hart, M. J. Am. Chem. Soc. 1994, 116, 1869–1879; (f)
Obora, Y.; Ogawa, Y.; Imai, Y.; Kawamura, T.; Tsuji, J.
J. Am. Chem. Soc. 2001, 123, 10489–10493.
11. (a) Oikawa, Y.; Sugano, K.; Yonemitsu, O. J. Org. Chem.
1978, 43, 2087–2088; (b) Oikawa, Y.; Yoshioka, T.;
Sugano, K.; Yonemitsu, O. Org. Synth. 1985, 63, 198–199.
12. Gilbirt, J. C.; Kelly, T. A. J. Org. Chem. 1988, 53, 449–
450.
In conclusion, the reductive decarboxylation of allyl a-
alkenyl-b-ketoesters by the use of Pd(OAc)2 and PPh3,
followed by the addition of HCOOH/Et3N in THF, pro-
vides an efficient procedure for the preparation of linear
(E)-3-alkenones. The attractive features of this new
approach are: the readily accessible starting materials,
the good yield, the high stereoselectivity of the products
and the operational simplicity of the procedure. The
reaction conditions are mild, preventing the inherent
lability of the double bond undergoing prototropic re-
arrangement to produce conjugated isomeric ketones.
Further studies are underway to apply this reaction in
13. Bandgar, B. P.; Sadavarte, V. S.; Uppalla, L. S. J. Chem.
Res. (S) 2001, 16–17.
14. Cope, A. C.; Hofmann, C. M. J. Am. Chem. Soc. 1941, 63,
3456–3459.
15. (a) Representative experimental procedure and spectral data
for entry c, Table 1; allyl 6-methyl-3-hepten-2-one-3-
carboxylate (2c): To
a mixture of allyl-acetoacetate
(2.28 g, 16 mmol) and isovaleraldehyde (1.45 g,
16.8 mmol) at ice-bath temperature, piperidine (one drop)
was added. The reaction mixture was stirred at 0 ꢁC for
4 h, a saturated aqueous solution of NH4Cl (10 ml) was
added and the total was extracted with diethyl ether