2-Pyridone synthesis

GUARESKY - THORPE Pyridone Synthesis Synthesis of pyndones from beta diketones and activated amides... 

Marazano and co-workers have also applied the reactions of tryptamine with various Zincke salts, including 115 (Scheme 8.4.39), in the synthesis of pyridinium salts such as 116. This type of product is useful for further conversion to dihydropyridine or 2-pyridone derivatives. For example, in a different study, Zincke-derived chiral pyridinium salts could be oxidized site-selectively with potassium ferricyanide under basic conditions as a means of chiral 2-pyridone synthesis (117 —> 118, Scheme 8.4.40). 

Scheme 8 2-Pyridone synthesis from the reaction of acylketenes and imines...

The alkylation works fine but it turns out to be better to add the aldehyde as an electrophile (cf. the pyridone synthesis on p. 1195) rather than try to reduce an ester to an aldehyde. The other ester is already at the right oxidation level. Notice the use of the NaCl method of decarboxylation (Chapter 26). 

A Ni°-based system related to those already described in connection with syntheses of both cyclobut-enediones and several five-membered heterocycles (Sections 9.4.2.1, 9.4.3.3 and 9.4.3.5) is also capable of catalyzing pyridone synthesis from isocyanates and alkynes. However, the structures found for the isolable metallacyclic intennediates in this system imply a completely different insertion sequence isocyanate first, followed by the two alkynes (Scheme 35). As a consequence, the regiochemistry found in the products of reaction of unsymmetrical alkynes is the reverse of that typical of Co larger substituents end up at positions 4 and 6. Thus, starting wiA the carbonyl carbon of the isocyanate, each carbon-caib-on bond forming event is strongly regioselective for the less-hindered alkyne caibon (equation 46). The... 

Grosche, P., Holtzel, A., Walk, T. B., Trautwein, A. W., Jung, G. Pyrazole, pyridine, and pyridone synthesis on solid support. Synthesis 1999, 1961-1970. 

Heterocycles. While several reports deal with formation of furan derivatives by reaction of 2-diazo-l,3-cyclohexanediones and alkynes which are substituted with electron-withdrawing or electron-donating groups, an a-pyridone synthesis based on an analogous reaction of Af-(a-diazoacyl)amides is applicable to the elaboration of the indolizidine skeleton, and accordingly, a synthesis of ipalbidine. ... 

In a reaction completely analogous to the pyridone synthesis in Scheme 33, 5-nickelafuranones formed from Ni°, an alkyne and carbon dioxide (see Section 9.4.3.3) react with additional alkyne to give 2-py-rones (Scheme Under catalytic conditions this becomes a viable synthesis of the heterocycle be-... 

There have been several reports of the use of cyano-acetamides as C-C-N synthons in pyridone synthesis. The C-C-C component that is required for the formation of a six-membered ring may be either an 0 /3-unsaturated carbonyl compound or a dicarbonyl compound. Alternatively, pyridones have been formed by base-promoted cyclocondensation of cyano-acetamides with a-keto-ketene 5,A -acetals (Scheme 10). ... 

A new pyridone synthesis was developed to form the basis of the second synthesis (Scheme 27) to be announced. This new heterocyclic method involves, in essence, the interaction of a 1,3-dialkoxycarbonylallene with a P-aminocrotonate [in the present context, (95)] or mono-enamine of a 1,3-dicarbonyl... 

Scheme 15 2-Pyridone synthesis using a ring-closing metathesis/oxidation strategy.

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