[504-31-4]  · C4H4O2  · 2-Pyrone  · (MW 96.08)

(diene for cycloadditions2 and inverse electron demand cycloadditions;3 used in the synthesis of cyclobutadiene4)

Physical Data: mp 8-9 °C; bp 206-209 °C (slight dec), 102-103 °C/20 mmHg; d204 1.200 g cm-3; n20D 1.530.

Solubility: miscible with H2O.

Form Supplied in: liquid; available in 95-98% purity commercially.

Preparative Methods: can be prepared in 66-70% chemical yield by pyrolytic decarboxylation of coumalic acid on copper turnings at 650 °C.5 Alternatively, the dihydro analog, 5,6-dihydro-2H-pyran-2-one, can be prepared by acid-catalyzed condensation of vinylacetic acid and Formaldehyde.6 Allylic bromination followed by dehydrobromination provides 2-pyrone in overall chemical yields of ca. 18%.

Handling, Storage, and Precautions: decomposes upon heating.

General Considerations.

2-Pyrone and its analogs (see 3-Hydroxy-2-pyrone, 2-Pyridone) find use in cycloaddition reactions, providing bicyclolactone adducts which can be elucidated into a variety of highly functionalized cyclohexadienes and benzenes. This pyranone reacts with a wide variety of standard dienophiles, including Maleic Anhydride,7 Dimethyl Acetylenedicarboxylate,8 fumarates,9 Methyl Vinyl Ketone,10 and acrylates.9,10 Under typical thermal conditions the bicyclolactone intermediate is not isolated; in situ decarboxylation leads to cyclohexadiene or benzene products. In the former case, a second equivalent of dienophile may undergo cycloaddition with the initial product, leading to 2:1 adducts from tandem cycloaddition.11 High pressure cycloaddition conditions may alter this outcome (eq 1).7,9

This approach has been used to prepare barrelene10 and other molecules of interesting topologies.12 A two-step, intramolecular version of this tandem cycloaddition using an unactivated double dienophile (eq 2)13a represents a convergent approach to polycyclic compounds of interest in natural products synthesis.13,14

When itaconic anhydride is used as dienophile and the resultant adduct decarboxylated, the interesting toluene tautomer 5-methylene-1,3-cyclohexadiene is produced;15 similarly, use of benzocyclobutene as the dienophile, followed by in situ decarboxylation, provides a route to chemically and theoretically interesting benzocyclooctatriene.16 With benzoquinones as dienophiles, substituted 2-pyrones provide strategic diene subunit synthons in anthraquinone synthesis.17 Alkyne dienophiles always result in o-disubstituted benzene products,8,18 with rare exception.19 [4 + 2] Cycloaddition reactions using cyclopropanes20 and nitrosobenzene21 have been reported, as have [4 + 2], [3 + 4], and [3 + 2] cycloadditions using a 1,1-/1,3-dipole cyclopropenone acetal.22

Thermal or high pressure dimerizations for the most part lead to polymerization.23 At very high (625 °C) temperatures, rearrangement by reversible electrocyclic ring opening to provide intermediate ketene aldehydes can be observed.24 On the other hand, photosensitized dimerization of 2-pyrone yields a mixture of the expected exo dimers (1) and (2).25 Direct irradiation of 2-pyrone in ether leads to bicyclo[2.2.0]pyran-2-one (3),26 the direct precursor to cyclobutadiene via photodecarboxylation (eq 3).27

Nucleophilic addition reactions of 2-pyrone can be complex; benzylthiolate, cysteine, cysteine methyl ester, and N-acetylcysteine all give complex mixtures of products when reacted with 2-pyrone.28 Grignard reagents undergo 1,2-additions to the carbonyl moiety,29 as do alkoxides.30 Metal hydrides can provide either 1,2-addition or 1,6-addition.31 Reaction with ammonia affords 2-pyridone; Diazomethane32 and cyanide attack at C-6 (eq 4).33

Electrophilic substitutions of 2-pyrones are possible.1 In the case of bromination or chlorination, 3-halo-2-pyrones form by means of sequential halogenation-dehydrohalogenation, rather than by direct electrophilic substitution.34 3-Bromo-2-pyrone itself undergoes metal-halogen exchange with Lithium Dimethylcuprate, resulting in 3-cuprio-2-pyrone.35 This organocopper reagent, which is the least nucleophilic of those reported in the literature, has properties reminiscent of organocopper reagents derived from a-bromoacrolein and a-bromoacrylates (see Lithium (3,3-Diethoxy-1-propen-2-yl)(phenylthio)cuprate).

1. Staunton, J. In Comprehensive Organic Chemistry; Barton, D. H. R.; Ollis, W. D., Eds.; Pergamon: New York, 1979; Vol. 4, p 629.
2. Posner, G. H.; Nelson, T. D.; Kinter, C. M.; Johnson, N. JOC 1992, 57, 4083.
3. Meier, H.; Molz, T.; Merkle, U.; Echter, T.; Lorch, M. LA 1982, 914.
4. Maier, G. AG(E) 1988, 27, 309.
5. Zimmerman, H. E.; Grunewald, G. L.; Paufler, R. M. OSC 1973, 5, 982.
6. Nakagawa, M.; Saegusa, J.; Tonozuka, M.; Obi, M.; Kiuchi, M.; Hino, T.; Ban, Y. OSC 1988, 6, 462.
7. Effenberger, F.; Ziegler, T. CB 1987, 120, 1339.
8. Ziegler, T.; Layh, M.; Effenberger, F. CB 1987, 120, 1347.
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10. Zimmerman, H. E.; Grunewald, G. L.; Paufler, R. M.; Sherwin, M. JACS 1969, 91, 2330.
11. Ho, T.-L. Tandem Organic Reactions; Wiley: New York, 1992; p 146.
12. (a) Akhtar, I.; Atkins, R. J.; Fray, G. I.; Geen, G. R. T 1980, 36, 3033. (b) Sasaki, T.; Manabe, T.; Nishida, S. JOC 1980, 45, 476. (c) Paquette, L. A.; Broadhurst, M. J. JOC 1973, 38, 1893.
13. (a) Swarbrick, T. M.; Markó, I. E.; Kennard, L. TL 1991, 32, 2549. (b) Markó, I. E.; Seres, P.; Swarbrick, T. M.; Staton, I.; Adams, H. TL 1992, 33, 5649.
14. Krantz, A.; Lin, C. Y. JACS 1973, 95, 5662.
15. Kopecky, K. R.; Lau, M.-P. JOC 1978, 43, 525.
16. Barton, J. W.; Lee, D. V.; Shapherd, M. K. JCS(P1) 1985, 1407.
17. Jung, M. E.; Lowe, J. A. CC 1978, 95.
18. (a) Ishikawa, M.; Sakamoto, H.; Kanetani, F.; Minato, A. OM 1989, 8, 2767. (b) Echter, T.; Meier, H. CB 1985, 118, 182. (c) Molz, T.; König, P.; Goes, R.; Gauglitz, G.; Meier, H. CB 1984, 117, 833. (d) Newkome, G. R.; Roper, J. M.; Robinson, J. M. JOC 1980, 45, 4380. (e) Reed, J. A.; Schilling, C. L., Jr.; Tarvin, R. F.; Rettig, T. A.; Stille, J. K. JOC 1969, 34, 2188. (f) Ervin, A. B.; Seyferth, D. JACS 1967, 89, 952.
19. Seyferth, D.; Blank, D. R.; Ervin, A. B. JACS 1967, 89, 4794.
20. Anastassiou, A. G.; Libsch, S. S.; Griffith, R. C. TL 1973, 3103.
21. Becker, Y.; Bronstein, S.; Eisenstadt, A.; Shvo, Y. JOC 1976, 41, 2496.
22. (a) Boger, D. L.; Brotherton, C. E. JACS 1986, 108, 6695. (b) Boger, D. L.; Brotherton, C. E. T 1986, 42, 2777.
23. Pirkle, W. H.; Eckert, C. A.; Turner, W. V.; Scott, B. A.; McKendry, L. H. JOC 1976, 41, 2495.
24. Pirkle, W. H.; Seto, H.; Turner, W. V. JACS 1970, 92, 6984.
25. (a) Pirkle, W. H.; McKendry, L. H. TL 1968, 5279. (b) Pirkle, W. H.; McKendry, L. H. JACS 1969, 91, 1179.
26. (a) Arnold, B. R.; Brown, C. E.; Lusztyk, J. JACS 1993, 115, 1576. (b) Corey, E. J.; Streith, J. JACS 1964, 86, 950.
27. (a) Cram, D. J.; Tanner, M. E.; Thomas, R. AG(E) 1991, 30, 1024. (b) Chapman, O. L.; McIntosh, C. L.; Pacansky, JACS 1973, 95, 614. (c) Lin, C. Y.; Krantz, A. CC 1972, 1111.
28. Jones, J. B.; Middleton, H. W. CJC 1970, 48, 3819.
29. (a) Gomper, R.; Christman, O. CB 1961, 94, 1784. (b) Gomper, R.; Christman, O. CB 1961, 94, 1795.
30. Bland, N.; Thorpe, J. F. JCS 1912, 101, 1557.
31. (a) Morgan, L. R., Jr. JOC 1962, 27, 343. (b) Vogel, G. CI(L) 1962, 268. (c) Yamada, K.; Mishizaka, M.; Hirata, Y. BCJ 1961, 34, 1873.
32. Fried, J.; Elderfield, R. C. JOC 1941, 6, 577.
33. Vogel, G. JOC 1965, 30, 203.
34. Pirkle, W. H.; Dines, M. JOC 1969, 34, 2239.
35. Posner, G. H.; Harrison, W.; Wettlaufer, D. G. JOC 1985, 50, 5041.

Martin Hulce

Creighton University, Omaha, NE, USA

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