Novel 2-pyrone synthesis via the nucleophilic addition of active methine compounds to 2-alkynone

Tetrahedron Letters

Volumn 44, Issue 10, 2003, Pages 2061-2063

  Hachiya, Iwao ^a   Shibuya, Hitoshi ^a   Shimizu, Makoto ^a  

^a MIE UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2 ALKYNONE; 2 PYRONE DERIVATIVE; KETONE DERIVATIVE; METHYL GROUP; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; SYNTHESIS;

EID: 0037416902     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00211-9     Document Type: Article

References (12)

1. For examples, see: (a) Chen, K. K.; Kovarikova, A. J. Pharm. Sci. 1967, 56, 1535; (b) Kupchan, S. M.; Moniot, J. L.; Sigel, C. W.; Hemingway, R. J. J. Org. Chem. 1971, 36, 2611; (c) Hayashi, Y.; Yuki, Y.; Matsumoto, T.; Sakan, T. Tetrahedron Lett. 1977, 18, 3637; (d) Prasad, J. V. N. V.; Para. K. S.; Lunney, E. A.; Ortwine, D. F.; Dunbar, J. B., Jr.; Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet, C.; Bhat, T. N.; Liu, B.; Guerin, D. M. A.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K. J. Am. Chem. Soc. 1994, 116, 6989.
2. For examples, see: (a) Chen, K. K.; Kovarikova, A. J. Pharm. Sci. 1967, 56, 1535; (b) Kupchan, S. M.; Moniot, J. L.; Sigel, C. W.; Hemingway, R. J. J. Org. Chem. 1971, 36, 2611; (c) Hayashi, Y.; Yuki, Y.; Matsumoto, T.; Sakan, T. Tetrahedron Lett. 1977, 18, 3637; (d) Prasad, J. V. N. V.; Para. K. S.; Lunney, E. A.; Ortwine, D. F.; Dunbar, J. B., Jr.; Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet, C.; Bhat, T. N.; Liu, B.; Guerin, D. M. A.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K. J. Am. Chem. Soc. 1994, 116, 6989.
3. For examples, see: (a) Chen, K. K.; Kovarikova, A. J. Pharm. Sci. 1967, 56, 1535; (b) Kupchan, S. M.; Moniot, J. L.; Sigel, C. W.; Hemingway, R. J. J. Org. Chem. 1971, 36, 2611; (c) Hayashi, Y.; Yuki, Y.; Matsumoto, T.; Sakan, T. Tetrahedron Lett. 1977, 18, 3637; (d) Prasad, J. V. N. V.; Para. K. S.; Lunney, E. A.; Ortwine, D. F.; Dunbar, J. B., Jr.; Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet, C.; Bhat, T. N.; Liu, B.; Guerin, D. M. A.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K. J. Am. Chem. Soc. 1994, 116, 6989.
4. For examples, see: (a) Chen, K. K.; Kovarikova, A. J. Pharm. Sci. 1967, 56, 1535; (b) Kupchan, S. M.; Moniot, J. L.; Sigel, C. W.; Hemingway, R. J. J. Org. Chem. 1971, 36, 2611; (c) Hayashi, Y.; Yuki, Y.; Matsumoto, T.; Sakan, T. Tetrahedron Lett. 1977, 18, 3637; (d) Prasad, J. V. N. V.; Para. K. S.; Lunney, E. A.; Ortwine, D. F.; Dunbar, J. B., Jr.; Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet, C.; Bhat, T. N.; Liu, B.; Guerin, D. M. A.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K. J. Am. Chem. Soc. 1994, 116, 6989.
5. Afarinkia K., Vinader V., Nelson T.D., Posner G.H. Tetrahedron. 48:1992;9111.
6. Staunton J. Sammes P.G. Comprehensive Organic Chemistry. 4:1979;629-658 Pergamon Press, Oxford.
7. Ma S., Yin S., Li L., Tao F. Org. Lett. 4:2002;505. and references cited therein.
8. Hachiya I., Ogura K., Shimizu M. Org. Lett. 4:2002;2755.
9. 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 evaporated in vacuo, and then the residue was purified by preparative TLC on silica gel to give 2-pyrone and decarboxylated 2-pyrone.
10. 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.
11. 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 β-ketoesters to alkynyl imines will be reported in a full paper.
12. In the case of malonic esters as a nucleophile, it would be possible to generate cyclobutenone 22. See Ref. 5.