Alkylation of 2-phenyl-4-quinolones: synthetic and structural studies

The alkylation of 2-phenyl-4-quinolones was investigated and showed that the N-alkylation versus O-alkylation is highly dependent on whether C-5 is hydroxylated or not. N-Alkylation is favoured by the presence of a 5-hydroxyl group. The synthetic and the NMR structural studies are reported.     

An efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones employing ferric chloride hexahydrate-methanol: synthesis of naturally occurring 4-alkoxy-2-arylquinolines

A simple, inexpensive and efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones has been carried out by employing FeCl₃·6H₂O-methanol under mild conditions. This method has been investigated for the synthesis of an endothelin receptor antagonist, benzofuro[3,2-b]pyridine core structure.     

Synthesis of naturally occurring polyacetylenes via a bis-silylated diyne

A straightforward synthesis of a series of naturally occurring polyacetylenes has been developed, including the montiporynes A and C, possessing cytotoxic activity against several human solid tumor cells, the atractylodin, with antibiotic activity against Escherichia coli, and triynes, which display insecticidal activities, starting from the readily available 1,4-bis(trimethylsilyl)-1,3-butadiyne.     

Synthesis of a naturally occurring nucleopeptide fragment via a phosphotriester approach

The phosphorylating agent 2-chlorophenyl-O,O-bis[1-benzotriazolyl]phosphate has been used for the introduction of a phosphodiester bond between the hydroxyl group of the tyrosine containing dipeptide (H-Ala-Tyr-NH₂) and the 5′-OH of the RNA dimer UpU.     

Convenient synthesis of 1,6,7,8-substituted 2-(3′,4′-substituted-phenyl)-4-quinolones via a 4-ethoxyflavylium salt

Condensation of 2-hydroxyacetophenone with benzaldehyde in the presence of 70% perchloric acid in ethyl orthoformate gave the corresponding 4-ethoxyflavylium perchlorate, which was treated with aqueous ammonia or methylamine solution to afford 1,6,7,8-substituted 2-(3′,4′-substituted-phenyl)-4-quinolone in fair to good yield.     

Direct conversion of 4-amino-2-phenyl-2-oxazolines into either 2-arylimino-1,3-oxazolidine or 2-arylimino-1,3-thiazolidine hydrochlorides

A novel heterocycle-heterocycle inter-conversion is reported. It enables direct and efficient syntheses of either polysubstituted 2-arylimino-1,3-oxazolidine or 2-arylimino-1,3-thiazolidine hydrochlorides by a one-pot treatment of 4-amino-2-phenyl-2-oxazolines with arylisocyanates or arylisothiocyanates, respectively, followed by addition of hydrochloric acid.     

One-pot approach to 2,3-disubstituted-2,3-dihydro-4-quinolones from 2-alkynylbenzamides

Concise and efficient syntheses of various trans-2,3-disubstituted-2,3-dihydro-4-quinolones have been achieved via tandem Hofmann-type rearrangement of 2-alkynylbenzamides, nucleophilic addition of alcohols to the isocyanate intermediates, intermolecular [2+2]-cycloaddition with carbon-carbon triple bonds and aldehydes, and intramolecular aminocyclization of nitrogen of carbamates to the α,β-unsaturated ketones.     

Hypervalent Iodine Oxidation of 2-Aryl-1,2,3,4-tetrahydro-4-quinolones: An Easy Access to 2-Aryl-4-quinolones

Oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones (1a-e) using iodobenzene diacetate in methanolic potassium hydroxide leads to dehydrogenation of 1 thereby providing an easy access to 2-aryl-4-quinolones (2a-e).     

Stereochemistry of addition of vinylacetylene to C2-epimeric trans -2-methyldecahydro-4-quinolones and trans-1,2-dimethyldecahydro-4-quinolones

Conclusions A study was made of the stereochemistry of the addition of vinylacetylene and butylmagnesium halide to the trans-2-methyl- and trans-1,2-dimethyldecahydro-4-quinolones, and the conformations of the vinyl-acetylenic and butyl-substituted alcohols of the decahydroquinoline series that are formed here were established.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2257–2263, October, 1972.n     

Asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones via bifunctional thiourea-mediated intramolecular cyclization

A novel asymmetric preparation of optically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been developed. By installing a sulfonyl group on the nitrogen of the anilines and an ester function on the unsaturated ketones, an intramolecular organocatalytic cyclization took place readily in a stereoselective manner, resulting in the formation of dihydroquinolones with high enantioselectivity.     

Divergent route to access structurally diverse 4-quinolones via mono or sequential cross-couplings

A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.     

A short and divergent route to 2-alkenyl-4-quinolones

2-alkenyl-4-quinolones were accessed via a high-yielding, three-step synthesis starting from 2-methyl-4-quinolones using a one-pot phosphorylation-olefination sequence as the key step and SEM as a convenient protecting group. This protocol tolerates various functional groups and gives the target olefins with complete (E)-selectivity.     

Resolution of 1-phenyl-2-(p-tolyl)ethylamine via diastereomeric salt formation

(S)-1-Phenyl-2-(p-tolyl)ethylamine (S)-1, used for the industrial scale resolution of chrysanthemic acids, was obtained via resolution of the racemate with the hemiphthalate of (S)-isopropylidene glycerol (R)-2. The maximum experimental efficiency [69% yield and >99% e.e. of (S)-1] was achieved by a simple precipitation of (S)-1·(R)-2 from the solution of the 1:1 diastereomeric salt mixture in 93/7 isopropanol/water at saturation of the more soluble (R)-1·(R)-2 salt. Such an experimental efficiency was consistent with 0.79 maximum theoretical resolvability, derived from the solubilities of the two diastereomeric salts, and with DSC data, which indicated that the (S)-1·(R)-2/(R)-1·(R)-2 system is a binary mixture exhibiting an eutectic with composition approximately corresponding to a 0.2 molar ratio of (S)-1·(R)-2.     

A New Route to 2-Aryl-4-quonolones via Thallium(III) p-Tolylsulphonate Mediated Oxidation of 2-Aryl-1,2,3,4-tetrahydro-4-quinolones

Oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones (1a-f) to 2-aryl-4-quinolones (2a-f) using thallium(III) p-tolylsulphonate in refluxing dimethoxyethane has been described. A mechanistic scheme for this new transformation has been proposed.     

A new general approach to 4-substituted-3-halo-2-quinolones

A general procedure for the preparation of 4-substituted-3-halo-2-quinolones (halo = F, Cl, Br) utilizing 2-halo diethylphosphonoacetic acids (halo = F, Cl, Br) and o-aminophenylketones as the starting materials is described. The title compounds are obtained by an intramolecular Horner-Wadsworth-Emmons olefination of halogen-containing N-acyl-o-aminophenylketones. The transformation process is generally applicable under mild conditions.     

Direct conversion of hydroxy aromatic compounds to heteroarylamines via a one-pot smiles rearrangement procedure

8-Hydroxyquinoline ( 9 ) was converted to 8 -aminequinoline ( 10 ) in a one-pot procedure involving alleviation with 2-bromo-2-methylpropionamide ( 2 ) followed by Smiles rearrangement and hydrolysis, in 41% yield. The scope and limitations of this new procedure were explored with additional hydroxyquinolines.     

Sequential Cu-catalyzed amidation-base-mediated camps cyclization: a two-step synthesis of 2-Aryl-4-quinolones from o-halophenones

A direct two-step method for the preparation of 2-aryl- and 2-vinyl-4-quinolones that utilizes a copper-catalyzed amidation of o-halophenones followed by a base-promoted Camps cyclization of the resulting N-(2-ketoaryl)amides is described. With CuI, a diamine ligand, and base as the catalyst system, the amidation reactions proceed in good yields for a range of aryl, heteroaryl, and vinyl amides. The subsequent Camps cyclization efficiently provides the desired 4-quinolones with the conditions that are described.     

Direct conversion of N-methoxy-N-methylamides (Weinreb amides) to ketones via a nonclassical Wittig reaction

[reaction: see text] N-Methoxy-N-methylamides (Weinreb amides) are converted efficiently into ketones by reaction with alkylidenetriphenylphosphoranes and in situ hydrolysis of the product.