4-Pyridones 5,6-dihydro- from

The enantioselective (76-90% ee) formation of the dihydro-y-pyridones 113 from various imines 112 (R = Ph, 3,5-xylyl or 3-pyridyl) and Danishefsky s diene 4 in the presence of 4 A molecular sieves and one equivalent of a catalyst prepared from triphenyl... 

In a study of the Lewis-acid catalyzed formation of optically active dihydro-j -pyridones 118 from the imines 117 (R = Ts. Ph. Bn or CO2L11 and the diene 4 in the presence of chiral Lewis acids, it was found that only the tosyl compound reacted diastereoselectively,... 

Access to piperidines through the intermediacy of 4-piperidones continues as a useful concept. A simple, diastereoselective route to 2,3,6-trisubstituted 2,3-dihydro-4-pyridones 218 from linear diketoester 219, aryl aldehydes, and ammonium acetate has been developed <05TL5511> (Scheme 63). 

Base for Deprotonation of Heteroatom-Hydrogen (X-H) Bonds. The deprotonation of heteroatom-hydrogen bonds with KHMDS constitutes a key step in diverse methods for the preparation of heterocycles. A cyclization of 3,4-dihydro-2-pyridones derived from (S)-phenylglycinol... 

N-Condensed 3,4-dihydro-2-pyridone ring from 0-alkyllactims... 

Gycloisomerization of cyanoketones 3,4-Dihydro-2-pyridone ring from 7-cyanoketones... 

The fluoboric acid-catalyzed aza-Diels-Alder reaction of aldimine and Danishefsky s diene proceeds smoothly to afford dihydro-4-pyridones in high yields [90] (Equation 4.16). Unstable aldimines generated from aliphatic aldehydes can be prepared in situ and allowed to react under one-pot reaction conditions. This one-pot Bronsted acid-catalyzed three-component aza-Diels-Alder reaction affords the adducts in good to high yields. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

The procedure described here for the preparation of succinimide silver salt is a modification of one reported for the formation of the silver derivative of maleimide. The alkylation step is modeled after the procedure of Comstock and Wheeler/ who prepared 2-ethoxypyrrolin-5-one in unspecified 3deld, and is an improvement over a later procedure developed in the laboratories of the submitters/ The general scheme has been successfully applied to the preparation of a variety of 2-ethoxypyrrolin-5-ones (Table 1) as well as 6-ethoxy- and 6-propoxy-4,5-dihydro-2(3H)-pyridone from the corresponding five- and six-membered cyclic imides/... 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

In Scheme 6.230, the multistep synthesis of 2,3-dihydro-4-pyridones is highlighted [411]. The pathway described by Panunzio and coworkers starts from a dioxin-4-one precursor, which is readed with 2 equivalents of benzyl alcohol under solvent-free microwave conditions to furnish the corresponding /1-diketo benzyl esters. Subsequent treatment with 1 equivalent of N,N-dimethylformamide dimethyl acetal (DMFDMA), again under solvent-free conditions, produces an enamine, which is then cyclized with an amine building block (1.1 equivalents) to produce the desired 4-pyridinone produds. All microwave protocols were conducted under open-vessel conditions using power control. 

The action of the valine derivatives 87 on the diene 86 under EtAlCU catalysis resulted in a mixture of cycloadducts 88, which on hydrolysis with aqueous methanolic sodium carbonate furnished a mixture of the dihydro-2-pyridones 89 and 90 and the esters 91 and 92. In the case of imines derived from aliphatic aldehydes, e.g. 87 (R = Pr), all four types of product were isolated, whereas imines from aromatic aldehydes, 87 (R = Ph, 3-CIC6H4 etc.), gave only the esters 91 and 92 (equation 55). All products were formed in yields of 64-84% and in high de49. 

Reduction of o /i-unsatin-ated lactams, S,6-dihydro-2-pyridones, with lithium aluminum hydride, lithium alkoxyaluminum hydrides and alane gave the corresponding piperidines. 5-Methyl-5,6-dihydro-2-pyridone (with no substituent on nitrogen) gave on reduction with lithium aluminum hydride in tetrahydrofuran only 9% yield of 2-methylpiperidine, but l,6-dimethyl-5,6-dihydro-2-pyridone and 6-methyl-l-phenyl-5,6-dihydro-2-pyridone afforded 1,2-dimethylpiperidine and 2-methyl-1-phenylpiperidine in respective yields of 47% and 65% with an excess of lithium aluminum hydride, and 91% and 92% with alane generated from lithium aluminum hydride and aluminum chloride in ether. Lithium mono-, di- and triethoxyaluminum hydrides also gave satisfactory yields (45-84%) [7752]. 

This same sequence, however, has been used successfully to prepare (60) [67]. Conversion of (65a, R = NH2) to the corresponding pyridone (65b, R = OH) was accomplished with isoamyl nitrite-H2S04. Arylation of (64) with (65b, R = OH) yielded (66b, R = OH) from which (60) was obtained as described (vide supra). Catalytic reduction of (60) then gave the 7,8-dihydro derivative (69). 

In a departure from the biomimetic catecholamide-based siderophores, Raymond s group have turned to derivatives of l-hydroxy-2(I//)-pyridone a structure which can be regarded as a cyclic hydroxamic acid264. Unlike hydroxamate siderophores, l,5-bis[l,2-dihydro-l-hydroxy-2-oxo-pyridin-6-yl)carbonyl]-l,5-diazaheptane (33) rapidly removes iron from transferrin. 

A solution of 1 eq. of the tert-butyl ester of 7-aminocephalosporanic acid and 1 eq. of dicyclohexylcarbodiimide in 100 ml of methylene chloride/DMF (1 1) is cooled to 0°C. The mixture is combined with 1 eq. of 3,5-dichloro-4-pyridone-l-acetic acid after 5 min the ice bath is removed and the mixture agitated for another 30 min at 25°C. The thus-formed urea is filtered off and the filtrate filtered over silica gel (eluent ethyl acetate/1% methanol). The solvent is concentrated by evaporation, and the thus-obtained tert-butyl ester of 7-(3,5-dichloro-l,4-dihydro-4-oxo-l-pyridylacetamido)cephalosporanic acid is crystallized from ether. 

Irradiation of a tert-butyl alcohol solution of 6-ethoxy-4,5-dihydro-2(3H> pyridone (14) under conditions similar to those described for 12 gives two products, tert-butyl N-(ethoxyethylidene)carbamate (27) in 15% yield and glutarimide in 23% yield18. There is no indication of formation of the cyclobutyl analogue of 13. In aprotic solvent, ethoxyvinyl isocyanate (28) and glutarimide (29) are the major photoproducts formed. The gaseous byproducts from the irradiation of 6-propoxy-... 

Related co-cyclotrimerizations of two alkyne molecules with limited isocyanates have also been achieved using cobalt and nickel catalysts. With respect to intramolecular versions, two examples of the cobalt(I)-catalyzed cycloaddition of a,m-diynes with isocyanates have been reported to afford bicyclic pyri-dones only in low yields, although 2,3-dihydro-5(lff)-indolizinones were successfully obtained from isocyanatoalkynes and several silylalkynes with the same cobalt catalysis [19]. On the other hand, the ruthenium catalysis using Cp RuCl(cod) as a precatalyst effectively catalyzed the cycloaddition of 1,6-diynes 21 with 4 equiv. of isocyanates in refluxing 1,2-dichloroethane to afford bicyclic pyridones 25 in 58-93% yield (Eq. 12) [20]. In this case,both aryl and aliphatic isocyanates can be widely employed. 

Akiyama et al. have reported that the cycloaddition of 102 to imines is effectively accelerated by 10 mol% of a Bronsted acid such as HBF4 in aqueous media, affording dihydro-4-pyridones in good to high yield (Scheme 10.109) [295]. This catalytic system is applicable to three-component synfhesis of dihydro-4-pyridones from aldehydes, anilines, and 102. The three-component coupling can be achieved efficiently in water without any organic solvent by using SDS as surfactant. 

The same strategy has been used to prepare trans bicyclic enones. The protected C5 phosphonylated aldehyde is obtained in 84% yield by a CuBr SMe2-mediated Michael addition of the Grignard reagent derived from 4-chlorobutyraldehyde diethyl acetal to a 5-phosphonylated 2,3-dihydro-4-pyridone in THF. Subsequent room-temperature hydrolysis of the acetal using aqueous oxalic acid in THF affords a near-quantitative yield of the crude aldehyde, which undergoes an intramolecular Homer-Wadsworth-Emmons reaction under treatment with Et3N/LiCl in THF at room temperature (89%). ... 

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