Pyrones alkylation

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 mass spectrum of 2-pyrone shows an abundant molecular ion and a very prominent ion due to loss of CO and formation of the furan radical cation. Loss of CO from 4-pyrone, on the other hand, is almost negligible, and the retro-Diels-Alder fragmentation pathway dominates. In alkyl-substituted 2-pyrones loss of CO is followed by loss of a hydrogen atom from the alkyl substituent and ring expansion of the resultant cation to the very stable pyrylium cation. Similar trends are observed with the benzo analogues of the pyrones, although in some cases both modes of fragmentation are observed. Thus, coumarins. 

Thiopyrones and selenopyrones can be alkylated more readily than pyrones. Thus 2,6-dimethyl-4/f-pyran-4-thionc (4,6-dimethyl-4-thiopyrone) (23, Y = S) reacts rapidly with methyl iodide yielding a 4-methylmercaptopyrylium iodide (24, Y = S, R = Me, X = I). Many alkylating agents were investigated by King et al. The kinetics of the reaction between 2,6-dimethyl-4-thiopyrone and substituted phenacyl bromides was found to be described by the Hammett... 

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 straightforward construction of substituted pyrone 4 proceeded as follows (see Scheme 6c). Alkylation of the monoanion of 2,4-pentanedione (8) with methyl iodide furnishes 3-methyl-2,4-pentanedione. Conversion of this substance into the corresponding dianion with sodium amide followed by selective carboxylation of the more basic site provides intermediate 7. Pyrone 4 is obtained after cyclization with l,l -carbonyldiimidazole and methylation of the resulting enol with dimethyl sulfate. 

These phenomena can be illustrated by the cycloaddition reactions of fulvenes with electron-deficient a-pyrones. In general, the Diels-Alder reactions of electron-deficient dienes such as 458 with 6-alkyl substituted fulvenes favor addition across one of the endocyclic... 

Similar pyrone complexes were isolated by Semmelhack97a as the products of the reaction between tetracarbonyl[ethoxy(alkyl)carbene]iron(0) complexes and various acetylenes. Vinylketene complexes are proposed as key intermediates in the mechanism of this conversion, which closely matches analogous reactions with cobalt carbenes51 (see Section V,B), while showing crucial differences with the analogous reaction of a chromium carbene (see Section II,B). 

The Deng group identified QN-derived thiourea 121 and QD -derived thiourea 124 to be also efficient promoters of enantio- and diastereoselective Diels-Alder reactions between the 2-pyrone diene 3-hydroxypyran-2-one and the dienophiles fumaronitrile, maleonitrile as well as acrylonitrile, while various C9-hydroxy acylated and alkylated (dihydro)cupreines and (dihydro)cupreidines failed for the same reactions under identical conditions (e.g., 97% yield, 15% ee, 64 36 endoxxo) [289], Catalysts 121 and 124 (5mol% loading), however, produced the corresponding Diels-Alder adducts 1-3 with synthetically useful enantioselectivities (85-... 

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

THE SYNTHESIS OF 2-ALKYL-4-PYRONES FROM MELDRUM S ACID... 

Substituted 7-pyrones are versatile synthetic precursors. There is strong precedent for the metalation4 and bromination5 of the 7-position, which allows 7-pyrones to be used in alkylation and aldol reactions and makes them attractive intermediates in the synthesis of polyacetate and spiroketal containing natural products.6 They can also be used as cycloaddition substrates in the construction of complex polycyclic systems as West has demonstrated.7 Furthermore, 7-pyrones have been used by Wender in an oxidopyrilium-alkene cycloaddition, a key reaction in his synthesis of phorbol.8... 

O-Alkylation of pyridones can be effected with diazomethane 2-pyridone forms 2-methoxypyr-idine. Frequently O- and iV-alkylation occur together 4-pyridone with CH2N2 yields 4-methoxypyridine and l-methyl-4-pyridone. Et30+ and similar active alkylating agents also alkylate the carbonyl oxygen of pyridones and pyrones. 

Alkyl substituents on the pyridone nitrogen atom are usually lost in reactions of this type, but the quaternary salts from /V-substituted acridones can be isolated. Pyrones (with PC15 or POCl3) form... 

Claydon, N., Allan, M., Hanson, J. R., Avent, A.G, Antifungal alkyl pyrones of Trichoderma harzianum. Trans Br Mycol Soc 1987 88 503-13. 

As previously described, ethers can be alkylated photochemically at the carbon alpha to the ether oxygen. In compounds having both an ether and a carbonyl function a "competitive alkylation process may take place. Tetrahydro-y-pyrone can serve as a good model for this "competitive alkylation between a ketone and an ether. This molecule has a ketone function having two methylene groups at its alpha positions, and an ether function having also two adjacent methylenes. When tetrahydro-y-pyrone was left in sunlight with 1-octene the 1 1 adduct was obtained in about 70 % yield. Alkylation occurred at the carbon alpha to the carbonyl function (24) ... 

The construction of the 2,3-dihydrofuran moieties of breviones was reported in which the epoxide and the a-pyrone depicted in the following scheme underwent both C-alkylation and consecutive O-alkylation presumably via rc-allylpalladium complexes <02TL1713>. 

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