6- Aryl-2-pyrones

When 27 was irradiated in the presence of bromine in 1,2-dichIoroethane solution at -78°C, the rrans-dibromide (30) was formed quantitatively (69JOC2239) (Scheme 18). Sulfuryl chloride, usually a source of chlorine radicals, gave the 3,5-dichloro derivative with 6-phenyl-2-pyrone (63JGU3361). Reaction of 6-aryl-2-pyrones with iodine monochloride in carbon tetrachloride or acetic acid gave 3-iodo products in around 70% yields. Iodine in peracetic acid gave the same products in only 50% yields... 

The cycloadditions of 5-aryl-2-pyrone 21 and 6-aryl-2-pyrone 24 with vinylene carbonate 22 further demonstrate the importance of the substitution pattern of the 2-pyrone (Scheme 7) <00TL4955 00TL7583>. While the cycloaddition of 21 furnished the cycloadduct 23, the reaction of 24 with vinylene carbonate could not be arrested at the cycloadduct stage and only... 

Scheme 7. Diels-Alder cycloadditions of 5-aryl-2-pyrone and 6-aryl-2-pyrone...

The highly substituted 6-aryl-2-pyrones 28 react with acetophenones 29 in a stepwise base-induced formal cycloaddition reaction. The reaction proceeds via a sequential Michael and aldol reaction in the presence of an alkali metal hydroxide. In this case, the formal cycloadduct 31 extrudes CO2, providing the diene 32, which subsequently undergoes dehydration to afford aromatic products 33 (Scheme 9) <03TL3363>. 

Scheme 9. Formal stepwise cycloadditions of 6-aryl-2-pyrones 28...

The reaction doe.s not involve dehydrogenation and may also be applied (with low yield) to aliphatic acid chlorides. The reaction with aryl isocj anates proceeds analogously to the reaction with ketenes leading through a-ketoiminoketenes to atylimino-4-pyrones, identical to those obtained by Bardone-Gaudemar and described at the end of Section II,B,2,a (see Scheme 6). 

Structurally related to the triarylmethanes is the xanthene chromogen (1.30), in which two of the aryl nuclei are linked by an oxygen atom to form a pyrone ring. Similar terminal groupings (amino, hydroxy, or both) are usually present. Xanthene dyes have mainly... 

The synthesis of pyrone derivatives attracted attention due to their synthetic potential. In an illustrative example Cho and co-workers studied the Suzuki-coupling of 3,5-dibromo-2-pyrone with arylboronic acids (8.9.). Under regular conditions the aryl group is introduced selectively into the more electron deficient 3-position, while in the presence of an equimolar amount of copper(I) iodide the coupling is diverted selectively into the 5-position (N.B. drop of the reaction temperature from 50 °C to ambient temperature negated the effect of copper and led to 3-arylation). The way copper effects the coupling is still unclear, but it was successfully used in the preparation of a range of 5-aryl-2-pyrons.17... 

Except in one case, all reactions of 2-pyrones with nucleophiles use alkyl or aryl magnesium halides. 

Lee, J.-H. Kim, W.-S. Lee, Y. Y. Cho, C.-G. Stille couplings of 3-(trimethylstannyl)-5-bromo-2-pyrone for the syntheses of 3-aryl-5-bromo-2-pyrones and their ambident dienyl character. Tetrahedron Lett. 2002, 43, 5779— 5782. 

The 4-hydroxy-2H-pyran-2-one moiety is a key structural feature in a recently discovered new class of non-peptidic HIV protease inhibitors. Therefore, the synthetic methodologies were extended to allow the functionalization of commercially available chemicals. Direct arylation of the pyrone ring at the C-3 and C-5 positions had not been reported until the re-... 

The reaction of thioenol aryl ethers with 1,3-diketones mediated by Ag2C03 on Celite leads to a facile construction of medium- and large-sized ring-substituted furans (Equation 36) <20000L1387>. This method has been exploited in syntheses of dibenzofurans, coumestans, and 4-pyrones. 

The isomeric 6-hydroxy-2-pyrone (glutaconic anhydride) and its 4-methyl analog (47) react similarly with aryldiazonium salts and on hydrolysis with dilute alkali or acid the hydrazones (48) are transformed into l-aryl-6-oxo-l,6-dihydro-3-pyridazinecarboxylic acids or their 4-methyl analogs (49) in variable yields (28-74%). 

In fact, by chromatography on basic alumina, only the corresponding pyrroles 8 and pyrones 9 were obtained and separated the regioisomeric ratio depending on the nature of the aryl substituent56-60. 

We have developed a stable CAB 2 (R = aryl) complex that can be prepared in situ by mixing tartaric acid derivative and arylboronic acid at room temperature. In contrast with 2, R = H, which is both air- and moisture-sensitive, the B-alkylated catalyst 2, R = aryl or alkyl, is stable and can be stored in closed containers at room temperature (Eq. 39). A solution of the catalyst (20 mol %) is effective in catalyzing the hetero Diels-Alder reaction of aldehydes with a Danishefsky diene to produce dihydro-pyrone derivatives of high optical purity (up to 98 % ee) (Eq. 40) [39]. The extent of asymmetric induction is largely dependent on the structure of the boronic acid. In general, bulky phenylboronic acid (R = 2,4,6-Me3CeH2, o-MeOC6H4) results in excellent asymmetric induction. 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

The reactions of amidines or guanidines with a-functionalized carbonyl compounds continue to be utilized for the synthesis of imidazoles. Thus, the mixed anhydride of acetic and chloroacetic acids reacts with symmetrical diarylguanidines to give l-aryl-2-arylaminoimidazolin-4-ones, and there is competitive formation of imidazoles and pyrimidines in the reaction of benzamidine with 3-bromobenzo-4-pyrones (18). Imidazoles are minor products, but are favored in nonpolar solvents. The use of a-dicarbonyl compounds with guanidine gives 2-amino-4-hydroxy-4-methyl-4//-imid-azoles, which give excellent yields of 2-aminoimidazoles on catalytic hydrogenation. " ... 

In most reactions of 2-pyrones, alkyl or aryl Grignard halides have been used. The best results have been achieved for 4,6-disubstituted 2-pyrones because of the general stability of 2,2,4,6-tetrasubstituted 2//-pyrans. Thus,... 

The Pd-catalyzed carbonylation of aryl halides (cf Section 2.1.2) occurs with high turnover numbers and reaction rates in SCCO2 as the solvent using standard precursor complexes and commercially available phosphine or phosphite ligands [30]. The generally better performance of the phosphite-based catalysts was attributed to their better solubility in the reaction mixture, but the formation of Pd carbonyl complexes was also mentioned as a possibility. The [Ni(cod)2]/dppb system (dppb = l,4-bis(diphenylphosphino)butane) was investigated in an early study as a catalyst for the synthesis of pyrones from alkynes and CO2 under conditions beyond the critical data of carbon dioxide [31]. Replacing dppb with PMcs results in a system with better solubility and catalytic performance, albeit catalyst deactivation remains a problem [3 c, 15]. 

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