4-Pyrones condensation

Dimethyl-4-pyrone condenses with aromatic aldehydes at a methyl" and can be lithiated and thereby substituted." ... 

Pyrones and 2-pyrones ° condense with aromatic aldehydes at 2- and 6-methyl groups and 2,6-dimethyl-... 

For the preparation of 4-substituted coumarins, a phenol may be condensed with ethyl acetoacetate under the influence of sulphuric acid. Thus resorcinol (II) readily undergoes this condensation (which is represented diagrammatically above) to give 7-hydroxy-4-methyl-coumarin (III). Note that the coumarins, like all 2 pyrones, are systematically lactones. 

The Pechmaim reaction has found extensive appHcations for the synthesis of numerous coumarin derivatives (39). Coumarin derivatives substituted in the pyrone ring can be obtained by condensing phenol with beta-ketoesters. For example, 4-methylcoumarin (3) is obtained with ethyl acetoacetate... 

Wizinger and co-workers found that 2,6-diphenyl-4-pyrone or 4,0-diphenyl-2-pyrone react with A , Y-dimethylaniline in the presence of POCI3 and PCI 5, yielding triarylpyrylium salts 29 and 30, respectively. With the same condensing agents, the above authors reacted... 

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. ... 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

Condensation, of triphenylphosphine with chloroform, 45, 33 Coumalic acid, decarboxylation of, apparatus for, 46,102 to give a-pyrone, 46,101 purification of, 46,102 Coumarilic acid, 46, 29 COUMARONE, 46, 28... 

Methylcarbazole reacted with 2,6-dimethyl-4-pyrone in the presence of phosphorus oxychloride generating the pyrylium salt 170. Xanthydrol and thiaxanthydrol condensed with carbazole and 9-methylcarbazole under acid catalysis and sulfuric acid oxidation to give the colored salts 171 (X = O or S) the process has been used for the colorimetric determination of carbazole. ... 

PKSs are characterized by their ability to catalyze the formation of polyketide chains from the sequential condensation of acetate units from malonate thioesters. In plants they produce a range of natural products with varied in vivo and pharmacological properties. PKSs of particular note include acridone synthase, bibenzyl synthase, 2-pyrone synthase, and stilbene synthase (STS). STS forms resveratrol, a plant defense compound of much interest with regard to human health. STS shares high sequence identity with CHS, and is considered to have evolved from CHS more than once. ° Knowledge of the molecular structure of the CHS-like enzymes has allowed direct engineering of CHS and STS to alter their catalytic activities, including the number of condensations carried out (reviewed in Refs. 46, 51, 52). These reviews also present extensive, and superbly illustrated, discussions of CHS enzyme structure and reaction mechanism. 

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). 

The Lewis acid-mediated condensation reaction of a,/3-unsaturated carboxylic acids with 4-hydroxy-2-pyrones has been utilized to prepare Fleischmann s a,a-bispyrone 2 and Praill s a,7-bispyrone 3 and confirm their assignments <2000TL1901>. 

The condensation of 6-substituted 4-hydroxypyrones with 1-cyclohexenecarboxaldehydes in the presence of L-proline gives the initial 1,2-addition addition product of the pyrone with the aldehydes, followed immediately by a 67t-electrocyclic process to give substituted oxopyrano[4,3-/ ][l]benzopyrans <1997JOC6888>. 

The cumulation reactions, which start from carboxylic acids and esters usually lead to the formation of pyrone derivatives. Methyl (Z)-3-iodoacrylate and 3-hexyne gave, for example, 5,6-diethyl-2-pyrone in acceptable yield (4.38.). Inclusion of the acrylate into a six membered ring starting from ethyl 2-bromocyclohexen-l-carboxylate, led to a condensed ring system, giving a partially reduced isocoumarin derivative.50... 

Schulte and coworkers (62AP801) have prepared a number of 3-propargyl-4-hydroxy-2-pyrone derivatives (210) by condensation of /3-dicarbonyl compounds (208) with propargyl-malonyl chloride (209). On heating (210) with zinc carbonate, ring closure took place to give the corresponding furo[3,2-c]pyrone derivatives (211 Scheme 40). 

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