I. Hachiya et al. / Tetrahedron Letters 44 (2003) 2061–2063
2063
Scheme 2.
D. M. A.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K.
J. Am. Chem. Soc. 1994, 116, 6989.
2. Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H.
Tetrahedron 1992, 48, 9111.
3. Staunton, J. In Comprehensive Organic Chemistry; Sammes,
P. G., Ed.; Pergamon Press: Oxford, 1979; Vol. 4, pp.
629–658.
4. Ma, S.; Yin, S.; Li, L.; Tao, F. Org. Lett. 2002, 4, 505 and
references cited therein.
5. Hachiya, I.; Ogura, K.; Shimizu, M. Org. Lett. 2002, 4, 2755.
6. A typical experimental procedure of the reaction of 2-
alkynone with an active methine compound: To 60% NaH
or sodium ethoxide (0.400 mmol) was added a solution of
an active methine compound (0.500 mmol) in 1,4-dioxane
(2.0 mL) and a solution of 2-alkynone (0.200 mmol) in
1,4-dioxane (2.0 mL) successively at room temperature. The
reaction mixture was stirred under reflux for 1 h and then
cooled to room temperature. Brine (10 mL) was added to
quench the reaction. The mixture was extracted with
dichloromethane (15 mL×3). The combined organic layers
were dried over sodium sulfate. The solvents were evapo-
rated in vacuo, and then the residue was purified by
preparative TLC on silica gel to give 2-pyrone and decar-
boxylated 2-pyrone.
7. When dimethyl allylmalonate was used instead of diethyl
allylmalonate, the desired 2-pyrone and its decarboxylated
2-pyrone were obtained in 24 and 6% yields, respectively.
8. For example, the reaction of ethyl 2-methyl-3-oxobutanoate
6 (R=Me) with the imine derived from 3-phenyl-2-propynal
and 4-methoxyaniline gave N-(4-methoxyphenyl)-5-acetyl-
3-methyl-4-phenyl-2-pyridone in 64% yield. The details of
the 2-pyridone synthesis via nucleophilic addition of b-
ketoesters to alkynyl imines will be reported in a full paper.
9. In the case of malonic esters as a nucleophile, it would be
possible to generate cyclobutenone 22. See Ref. 5.
Scheme 3.
In summary, we have found a novel method for 2-
pyrone synthesis by the 1,4-addition of active methine
compounds to 2-alkynone. Although numerous meth-
ods for the synthesis of 2-pyrones are available, in the
present reactions, 3,4,6-trialkyl-5-ethoxycarbonyl or 5-
acetyl-2-pyrones can be easily obtained via a novel
reaction mechanism including cyclobutenoxide interme-
diates because 2-alkynones and active methine com-
pounds such as malonic esters and b-ketoesters,
respectively, are readily available. The synthetic appli-
cation of 2-pyrones is now in progress.
References
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