4- Pyrones ketones

Carbomethoxy-2-pyrones. Ketone enolates (NaH or LDA) react with 1 with loss of methanol to give 3-carbomethoxy-2-pyrones (2) in generally good yield. The final ring closure can be promoted if necessary by addition of acetic anhydride or TsOH and elevated temperatures. 

The reaction of ketene with the enamine (113) is reported (88) to give l-morpholino-2-acetyl-l-cyclohexene i.e., the enamino ketone expected from acylation of (113). The pyrrolidine enamine (28), however, has been shown to react (73) with excess ketene to give the a-pyrone (124). On the... 

Methanesulfonyl chloride reacts with enamino ketones (104), (e.g., 151) to give good yields of the enol sulfones (e.g., 152). The analogy with ketene addition to form a-pyrones (Section IV.A) is obvious. 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

From the reactions of sulfur and carbon disulfide with cyclic ketone-derived enamines (570-573) 3H-l,2-dithiole-3-thiones were obtained, whereas the addition of carbon disulfide to other enamines gave a-dithio-pyrones (574), through initial dimerization of the enamine. 

The cyclization of 1,3,5-triketones to pyrones will not be discussed here, although this is a related reaction, because pyrones are not true pyrylium salts. Mention will be made, however, of the formation of 2,6-diphenyl-4-pyrone from 1,3-dibenzoylallene this ketone adds secondary amines leading to 3-dialkylamino-l,5-diphenyl-4-penten-l,5-diones, which arc cyclized by hydrogen chloride in acetic acid to 2,6-diphenyl-4-dialkylaminopyrylium chlorides (R = Me and/or Ph) (see Scheme. 5). 

A related reaction is the acylation of yA disuhstituted benzyl ketones to isobenzopyrylium salts the unsubstituted compounds yield 4-pyrones as shown in Section II,D,3,a. Another related acylation converts unsaturated esters into 2-p3U ones, e.g., ethyl, jS-dimethyl-acrylate into 4,6-dimethyl-2-pyrone. ... 

An extension of this synthesis would be the condensation of -keto esters with ketones leading to alkoxypyrylium salts and hence to 2- or 4-pyrones however, attempts at such reactions were unsuccessful. ... 

Balaban, Mateescu, and Nenitzescu, diacylatcd 1,3-diphenyl-2-propanone (213, R =Ph) to 3,5-diphcnyl-4-pyrones (215), the former with acetic and polyphosphorio acids, the latter with acetyl chloride and aluminum chloride. This leaction follows the usual course of ketone acylation, and has been studied in detail several... 

The third synthetic scheme is employed when the phenylthio substituent is in the a-position of the lactone function, which interferes with the cyclization (90JOC5894). Acetylenic ketone 194 (95% yield) is readily transformed to the acetal 195 (with potassium carbonate in methanol) however, under the above conditions neither its hydrolysis nor cyclization to the spiroketal occurs. The spirocyclic pyrone 197 is formed in quantitative yield on treatment of 195 with p-toluenesulfonic acid in a 4 1 THF-H2O mixture at reflux for 12 h. 

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound].423 A... 

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-... 

Cyclopropanes. XI. Pyrones from Nitrocyclopropyl Ketones. J, Amer. 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

The only four- - six-membered ring interconversions of any real synthetic significance are those involving diketene. Base-catalyzed dimerization of diketene is a long-established and efficient method for the preparation of dehydroacetic acid (equation 161), while mild treatment with water in the presence of tertiary amine bases gives 2,6-dimethyl-4-pyrone (equation 162). 1,3-Dioxins are obtained from the acid-catalyzed condensation of diketene with ketones (equation 163). 

Macrocyclic 2-pyrones (113) and (114) are prepared from enamine (115) and ketene (75HCA2409). Reduction of cyano ketone (116) with LAH affords an amino ketone which spontaneously cyclizes to generate a tetrahydropyridine (117) dehydrogenation by palladium on charcoal produces the aromatized phane (118) (71TL671). 

Enamine (235) obtained from cyclic ketones and the acetal of /V-methyl-2-pyrrolidone gave a fused 2-pyrone [83IJC(B)1083]. 2//-Chromenes were obtained from of 3,5-dichlorosalicylaldehyde and enamines (94RRC183) (Scheme 42). The pyran ring is formed by a reaction of aminals of conjugated w-dimethylaminoaldehydes with cyclic /1-dicarbonyl compounds (94IZV285) (Scheme 43). 

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