Carbon nucleophiles, 4-pyrones

Soft carbon nucleophiles other than malonate derivatives follow similar patterns of regioselectivity, as shown by the addition of cyclopentadiene anion (equation 211)>os and the highly acidic 4-hydroxy-6-methyl-2-pyrone (equation 212).393... 

Hydroxy-4-Pyrone Ring-Contractions Solvent Trapping Intramolecular Trapping by Oxygen Nucleophiles Intramolecular Trapping by Carbon Nucleophiles Trapping by [4+3] Cycloaddition ... 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

Pyridones are normally resistant to nucleophilic attack at ring carbon atoms, but the pyrones react rather readily. There is a useful correlation between the position of attack and the hardness or softness of the nucleophile, and the situation for the pyrones is summarized in Schemes 12 and 13. Representative transformations illustrating these concepts are shown in equations (45)-(51). ANRORC reactions are also very common and examples are given in equations (52)—(55). 

Fused benzene rings aid nucleophilic attack on pyridines, pyridinium and pyrylium ions, and pyrones the loss of aromaticity involved in the formation of the initial adduct is less in monobenzo derivatives and still less in linear dibenzo derivatives than in monocyclic compounds. For the same reason, the tendency for this initial adduct to re-aromatize is less for benzopyridines. Fused benzene rings also influence the point of attack by nucleophilic reagents attack rarely occurs on a carbon atom shared with a benzene ring. Thus, in linear dibenzo derivatives, nucleophilic attack is at the y-position (157). 

Recently we have developed a more general approach to molecules exemplified by III. Thus the Diels-Alder cycloaddition of alkyne II and ct-pyrone, followed by aromatization by loss of carbon dioxide, led to the isolation of III (72%) (5). Alkyne II was obtained in high yields, in two steps from dichloroacetylene and triethylphosphite via Arbuzov-type reactions (5). Since the intermediate chloroalkyne phosphonate I was isolable (90%), phosphorus nucleophiles other than triethylphosphite could be used to give unsymmetrical alkyne diphosphoryl species. We have demonstrated this approach by the reaction of I with PhaPOEt and PhP(OEt)2 (5). 

There has been a growing interest in the utilization of CO2 as a potential Cl source for chemicals and fuels to cope with the predictable oil shortage in the near future. Insertion reactions of CO2 into M-H, M-0, M-N, and M-C bonds are well documented, where these reactions are explained in terms of the electrophilicity of CO2 il, 2). Catalytic syntheses of lactones (3-9) and pyrones (10-16) are also established by incorporation of CO2 into dienes and alkynes activated on low-valent metal complexes. Carbon dioxide shows only an electrophilicity under usual reaction conditions, but it exhibits a nucleophilicity upon coordination to low-valent metals because of the intramolecular charge transfer from metals to CO2. Metal-C02 formation may be the key species in electro- and photochemical CO2 reductions. Since the first characterization of [Ni(PCy3)2(T) (C,0)-C02)] (17), a variety of metal... 

Pyrones can in principle add nucleophilic reactants at either C-2 (carbonyl carbon), C-4 or C-6 their reactions with cyanide anion," and ammonia/amines are examples of the latter, whereas the addition of Grignard nucleophiles occurs at carbonyl carbon. 

Pyrones also add Grignard nucleophiles at the carbonyl carbon, C-4 dehydration of the inunediate tertiary alcohol product with mineral acid provides an important route to 4-mono-substituted pyrylium salts." More vigorous conditions lead to the reaction of both 2- and 4-pyrones with two mole equivalents of organometallic reagent and the formation of 2,2-disubstituted-2H- and 4,4-disubstituted-4//-pyrans, respectively." Perhaps surprisingly, hydride (lithium aluminium hydride) addition to 4,6-dimethyl-2-pyrone takes place, in contrast, at C-b." ... 

The regiochemistry of this reaction is consistent with expectation. The more nucleophilic j8-carbon of the enamine bonds to C(2) of the pyrone ring, which is activated by both the C(4) ring carbonyl and the ester substituent. 

The polymerization of carbon suboxide can theoretically be initiated by a ketene like dimerization of the molecule. However, it was shown that the polymerization is induced by trace amounts of nucleophiles, such as water, to give pyrone derivatives, which react with more carbon suboxide to form poly(a-pyrone). Although most reactions of carbon suboxide seem to be initiated by nucleophilic reactions, some cycloaddition reactions of carbon suboxide are known (see Section 3.1.2.2). 

Oxa- and Thia-diazines.—Intramolecular cyclodehydration of phenylglyoxalic acid benzohydrazide [PhC0NHN=C(Ph)C02H] with dicyclohexylcarbodi-imide in THF, or with a mixture of trifluoroacetic acid and trifluoroacetic anhydride, yields 2,5-diphenyl-6-oxo-l,3,4-oxadiazine (359), a synthetically useful diaza-diene. For example, with ynamines, regiospecific cyclo-addition of the nucleophilic /S-carbon of the ynamine with the electrophilic C-2 of the oxazinone yields adduct (360) and hence, by loss of nitrogen, the a-pyrone (361). The annelated a -pyrone (362), from benzyne and the oxadiazinone (359), is itself a diene, and reacts further with the dienophile to give ultimately 9,10-diphenyl-anthracene. 

The photochemical Nazarov reaction is also known, but it has not been broadly used in synthesis. 4-Pyrones have commonly been used as substrates for the photochemical Nazarov. West and co-workers example illustrates this type of reaction (Scheme 19.35). Exposure of pyrone 133 to quartz-filtered ultraviolet (UV) irradiation in methanol solution leads to a 2 3 mixture of cyclopentenones 134 and 135. The two products presumably originate from zwitter-ionic epoxide intermediate 136 that forms through symmetry-allowed disrotatory ring closure from the excited triplet state. Nucleophilic attack by methanol at either of the two positively charged allylic carbon atoms leads to the observed products. This reaction is successful for pyrones that are fused to rings larger than cyclohexane, but it fails... 

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