Halogenation of fluorinated cyclic 1,3-dicarbonyl compounds: new aspects of synthetic application

In order to elaborate on an approach towards 2-(fluoroacyl)phenols being the superior alternative to the conventional Fries-rearrangement based methodology, the behaviour of cyclic fluorinated 1,3-dicarbonyls in reactions with halogenating agents was examined. The synthetic relevance of the polyhalogenated compounds obtained was demonstrated by the synthesis of several new heterocycles. An aromatization via a halogenation-dehydrohalogenation sequence proved to be a rewarding synthetic route to 2-(fluoroacyl)phenols and previously unknown 3-(fluoroacyl)thiochromones. The structure of one of the synthesized compounds was confirmed by X-ray diffraction analysis.     

Enantioselective palladium-catalyzed addition of 1,3-dicarbonyl compounds to an allene derivative

Enhancing atom economy of the metal‐catalyzed asymmetric allylic alkylation (AAA) shifts from the usual nucleophilic displacement of a leaving group to an addition of a pronucleophile to a double bond. Using 1‐alkoxyallenes as proelectrophiles, the palladium‐catalyzed AAA proceeds with 1,3‐dicarbonyl compounds as pronucleophiles with excellent regioselectivity and enantiomeric excess under optimized conditions. The pH of the medium proved crucial for reactivity/selectivity. By using the more acidic Meldrum's acids, the reactions required a co‐catalytic amount of Brønsted acid, such as trifluoroacetic acid. Single regioisomeric products of 82–99 % ee were obtained. On the other hand, the less acidic 1,3‐diketones failed to react under such conditions. The fact that a less acidic acid like benzoic acid sufficed, suggested the need for general base catalysis as well. Thus, a mixture of triethylamine and benzoic acid proved optimal (ee's 93–99). Employment of the (R,R)‐phenyl Trost ligand gave a product with S configuration. A model to rationalize the results has been developed.     

The synthesis and structure of ferrocenylalkyl onium derivatives of nitrogen-containing heterocyclic compounds

The reactions of hydroxymethylferrocene, -hydroxyethylferrocene, and 1,1-bis(-hydroxyethyl)ferrocene withN-ferrocenylalkyl-substituted benzotriazoles, hexamethylenetetramine, and azaferrocene in the CH₂Cl₂ — 48% aqueous HBF₄ two-phase system affordedN-mono-,N-1,1-ferrocenylene-bis--alkylated, and 1,3-bis-ferrocenylalkylated tetrafluoroborates of the above-mentioned heterocyclic compounds in high yields. An X-ray structural study of 1,3-bis-(ferrocenylmethyl)benzotriazolium tetrafluoroborate confirmed unambiguously the 1,3-arrangement of the ferrocenylmethyl groups in the heterocycle.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 554–558, March, 1995.     

Synthesis and properties of water-soluble 2-aminomethylidene derivatives of 1,3-dicarbonyl compounds

A series of [(2-dimethylamino)ethylamino]methylidene-1,3-dicarbonyl compounds was synthesized for the first time starting from the corresponding 2-ethoxymethylidene derivatives and N,N-dimethylethylenediamine. It was shown that further alkylation of aminomethylidene derivatives with methyl iodide occurs regioselectively at the tertiary nitrogen atom. Quaternization products obtained exhibit high corrosion inhibition of mild steel in hydrochloric acid medium.     

FeCl3-catalyzed alkylation of indoles with 1,3-dicarbonyl compounds: an expedient synthesis of 3-substituted indoles

Indoles undergo smooth alkylation at the 3-position with 1,3-dicarbonyl compounds in the presence of 20 mol % of FeCl₃ under mild reaction conditions to produce a wide range of 3-substituted indoles in excellent yields and with high E-selectivity.     

Synthesis of thieno[3,4-d]pyrimidines by the reactions of 3-amino-4-carbamoylthiophene derivatives with 1,3-dicarbonyl compounds

The reactions of ethyl 3-amino-4-carbamoyl-5-methylthiophene-2-carboxylate with 1,3-dicarbonyl compounds were studied. During the reactions, the corresponding ketone is eliminated to give ethyl 5-methyl-4-oxo-3,4-dihydrothieno[3,4-d]pyrimidine-7-carboxylates.     

1,3-Dipolar cycloaddition in the synthesis of pyrazolyl-substituted nitronyl nitroxides

A new approach to the synthesis of polyfunctional pyrazolyl-substituted nitronyl nitroxides was developed based on the presynthesized pyrazole derivatives prepared by 1,3-dipolar cycloaddition. The structures of the resulting mono-and biradicals were confirmed by X-ray diffraction. Dedicated to Academician A. L. Buchachenko on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2105–2116, September, 2005.     

Ruthenium-catalyzed addition of carboxylic acids or cyclic 1,3-dicarbonyl compounds to propargyl alcohols

Monomeric ruthenium(0) complexes containing redox-coupled dienone ligands were found to catalyze the regio-selective addition of carboxylic acids or cyclic 1,3-dicarbonyl compounds to propargyl alcohols.     

Diacetoxyiodobenzene-mediated oxidative addition of 1,3-dicarbonyl compounds to olefins: an efficient one-pot synthesis of 2,3-dihydrofuran derivatives

A variety of olefins react with -dicarbonyl compounds at 0°C in the presence of diacetoxyiodobenzene to afford highly substituted 2,3-dihydrofuran derivatives in good to excellent yields.     

Strontium triflate catalyzed one-pot condensation of β-naphthol, aldehydes and cyclic 1,3-dicarbonyl compounds

An efficient one-pot condensation of β-naphthol, aldehydes, and cyclic 1,3-dicarbonyl compounds has been achieved with strontium triflate as a catalyst, thus a variety of 8,9,10,12-tetrahydrobenzo[a]xanthen-11-one or 8,9-dihydrobenzo-[f]cyclopenta[b]chromen-10(11H)-one derivatives were prepared in good yields.     

Electrophilic substitution in eleven-vertex metallacarborane 1,2,4-CpCoC2B8H10

Bromination and mercuration of cobaltacarborane 1,2,4-CpCoC₂B₈H₁₀ were investigated. Mercuration under mild conditions (Hg(OCOCF₃)₂ in CH₂Cl₂) afforded the only monomercurated complex containing the mercury atom at position 6. Bromination gave rise to 3-mono-, 6-mono-, or 6,9-disubstituted derivatives depending on the reaction conditions. The mercurated derivative was studied by the X-ray diffraction method.     

Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

A versatile new synthesis of quinolines and related fused pyridines. Part III.

The action of dimethylformamide in phosphorus oxychloride on acylanilides gives 2-chloro-3-substituted quinolines, which may be dechlorinated to give 3-substituted quinolines in good yield. Similarly, N-nitrosodimethylamine in phosphorus oxychloride converts acylanilides into 2-chloro-3-substituted quinoxazolines.     

A facile and convenient one-pot synthesis of polysubstituted thiophenes from 1,3-dicarbonyl compounds in water

A facile and convenient one-pot synthesis of polysubstituted thiophenes 2 and polysubstituted thieno[2,3-b]thiophenes 3 from 1,3-dicarbonyl compounds 1 has been achieved in high yields catalyzed by tetrabutylammonium bromide (TBAB) in the presence of K₂CO₃ in water. TBAB in the aqueous phase can be recycled after the separation of organic products.     

A versatile new synthesis of quinolines and related fused pyridines. Part II.

The conversion of acetanilides to 2-chloroquinoline-3-aldehydes by Vilsmeier reagent proceeds efficiently in POCl₃ solution at 75°. The intermediate, in which the acetyl group has been diformylated, may in some cases be isolated and separately cyclised.     

Stereochemistry of 1,3-diheterocyclanes 4. Molecular and crystal structures of monosubstituted five-membered cyclic sulfites

Racemic and enantiopure cis-and trans-4-(1-naphthyloxy)methyl-2-oxo-1,3,2-dioxathiolanes were studied by X-ray diffraction. The factors responsible for their crystal packings were revealed. The conformation of the exocyclic fragment varies from synclinal to antiperiplanar depending on both the local (cis-trans isomerism of the molecule) and external (homochiral/heterochiral environment) stereochemical factors. Data on the structures of five-membered sulfites in crystals were generalized. It was concluded that the heterocycle has considerable conformational flexibility. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1095–1102, July, 2006.     

Versatile and mild HCl-catalyzed cationic imino Diels-Alder reaction for the synthesis of new tetrahydroquinoline derivatives

A simple, inexpensive, and mild one-pot methodology for the synthesis of novel 4-aryl-3-methyl-1,2,3,4-tetrahydroquinolines derivatives using aqueous HCl as catalyst has been developed. The key step involves the formal inverse-electron-demand [4π⁺ + 2π] cycloaddition reaction of in situ–generated cationic 2-azadienes with arylpropenes (isoeugenol and trans-anethole). Iminium ion intermediates are generated through the condensation between N-benzylanilines and formalin. The products are obtained with good to excellent yields and high trans-diastereoselectivity. Further catalytic hydrogenation (Pd/C) allowed debenzylation to successfully obtain the respective 4-aryl-3-methyl-N-H-tetrahydroquinolines of interest. Recent reports suggest that these compounds could serve as interesting models in pharmacological studies against parasites that cause the most common tropical diseases.     

The unprecedented C-alkylation and tandem C-/O-alkylation of phenanthrolinium salts with cyclic 1,3-dicarbonyl compounds

N-p-Nitrobenzyl- or N-phenacylphenanthrolinium bromides reacted with a series of cyclic 1,3-dicarbonyl compounds in acetonitrile in the presence of triethylamine as base catalyst to give the unprecedented C-alkylated products and tandem alkylated/intramolecular O-alkylated oxazabicyclic compounds according to the structure of cyclic 1,3-dicarbonyl compounds.