Pyridones selective synthesis

Aza-Annulation of Enamine Related Substrates with a,b-Unsaturated Carboxylate Derivatives as a Route to the Selective Synthesis of d-Lactams and Pyridones... 

Jiao et al. developed copper-catalyzed diverse constructions of 3,5-diarylpyridines and 2-(lTf)-pyridones through tandem Chichibabin-type cyclization, C(sp )-C(sp ) bond cleavage, and aerobic oxidation with high selectivity. Azide, ceric ammonium nitrate (CAN), and 2-aminopyridine are efficient nitrogen donors in this Cu catalytic system for the selective synthesis of pyridines and pyridones [151] (Scheme 8.81). 

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). 

Vinamidinium salts are important intermediates in the synthesis of heterocycles. The 2-chloro-l,3-bis(dimethylamino)trimethinium hexafluorophosphate salt has been used in the preparation of the highly selective Cox-2 inhibitor etoricoxib (Scheme 1). This method describes a straight-forward preparation of the hexafluorophosphate salt which is a crystalline, thermally and shock-stable, non-hygroscopic solid. The submitters have extensively studied the preparation of vinamidinium salts and demonstrated that the method is applicable to substituted acetic acids that contain an electron-withdrawing group (Table 1)." The annulation reaction is also general and useful for the preparation of pyridines, pyridones and pyridine N-oxides. ... 

A nucleophile-induced ring transformation reaction of 2-pyranones was reported (Scheme 6) to result in a regioselective synthesis of 2-aminopyridines 21 or 2-pyridones 22 <05SL623>. Urea was used to generate ammonia as a nucleophile source. The reaetion of 23 (R=CN) was initially examined under elevated temperatures and solvent-free conditions. This system yielded a mixture of both 21 and the pyridone equivalent of 23, in equal amounts. The reaction conditions were modified to yield 2-aminopyridine 21 selectively as shown in Scheme 6. However, the only reaction found to be selective for 2-pyridone 22 formation is where the cyano group was replaced with an ester, shown in Scheme 6. Compound 24 was converted to pyridone 22 in good yield. 

An elegant new synthesis of polycyclic heteroaromatic compounds via quinone-methide intermediates is illustrated in Scheme 60. The required quinone-methides have also been generated from hydroxy-pyridones and -coumarins, and these have been allowed to react with a wide selection of aromatic amines. ... 

Cheng has published a convenient and synthetically useful alternative method to the NHK reaction for the arylation of aromatic aldehydes in a mild and selective way with nickel(ll) bromide/zinc/dppe mediated protocol for the synthesis of diaryl carbinols. Durandetti reported an electrochemical coupling of aryl halides with aldehydes for the synthesis of diaryl carbinols which was catalytic in chromium and nickel salts. Comins utilized the NHK reaction to prepare 5-(l-hydroxyalkyl)-2,3-dihydro-4-pyridones, which were then explored in reductive, oxidative and substitutive reactions. " The first asymmetric catalytic synthesis of 5y -alk-l-ene-3,4-diols was developed the regio-, diastereo- and enantioselective addition of 3-chloropropenyl pivaloate to aldehydes was made possible by exploiting Salen r(II) species in a catalytic version of the NHK reaction. ... 

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