2-Pyrone1

[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).


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25. (a) Pirkle, W. H.; McKendry, L. H. TL 1968, 5279. (b) Pirkle, W. H.; McKendry, L. H. JACS 1969, 91, 1179.
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Martin Hulce

Creighton University, Omaha, NE, USA



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