Heteroaromatic annulation studies on 2-[bis(methylthio)methylene]-1,3-indanedione: efficient routes to indenofused heterocycles

2-[Bis(methylthio)methylene]-1,3-indanedione has been shown to be a useful three carbon 1,3-dielectrophilic synthon for the highly efficient regiospecific synthesis of a variety of indenofused five- and six-membered heterocycles via heteroaromatic annulation. The methodology has been further elaborated to the corresponding N,S-acetals leading to amino substituted heterocycles, thus providing further point of diversity in the newly synthesized heterocyclic frameworks. Further, the facile access to cytotoxic indeno[2,1-c]quinolin-7-ones and the novel polycyclic heteroaromatics demonstrates the versatility of heteroaromatic annulation protocol via α-oxoketene-S,S-acetal in generating novel biologically important polycyclic heteroaromatics.     

An advantageous synthesis of new indazolone and pyrazolone derivatives

The synthesis of new indazolone and pyrazolone derivatives starting from methyl anthranilate type substrates is presented. This general approach constitutes a novel and advantageous alternative for the synthesis of the target heterocycles, which implies the use of the environmentally friendly oxidizer PIFA. The synthetic design includes the oxidation of N-arylamides by the hypervalent iodine reagent to the corresponding N-acylnitrenium ions, which can be intramolecularly trapped by an amine moiety to furnish the title compounds by formation of a new N-N single bond.     

Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol

Aza variant of intramolecular catalytic, asymmetric nucleophile-catalyzed, aldol lactonization (NCAL) reaction has been explored to synthesize β-lactone fused nitrogen heterocycles as aza sugars’ precursors by employing achiral amino acids. The utility of these bicyclic β-lactones is presented by the formal synthesis of aza sugars, (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol.     

An efficient microwave-assisted solvent-free synthesis of pyrido-fused ring systems applying the tert-amino effect

Significant improvements in the synthesis of pyrido-fused heterocycles were observed when performing the reaction under solvent-free conditions, applying the tert-amino effect as the key ring closure methodology. An unexpected cyclization of ortho-(1′-azacycloalkyl)benzaldehydes has been studied in water and on solid support.     

Synthesis of novel dipyrazolo[3,4-b:3,4-d]pyridines and study of their fluorescence behavior

A convenient route was successfully developed for the synthesis of novel heterocycles such as pyrazolo[3,4-h][1,6]naphthyridine and dipyrazolo[3,4-b:3,4-d]pyridine (DPP) from pyrazolo[3,4-b]pyridine in good yield. The DPP derivatives synthesized were further studied for their fluorescence properties.     

An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.     

Synthesis and reactivity of N-aryl substituted N-heterocyclic silylenes

The synthesis of two N-aryl substituted 2-silaimidazolidenes 9a, b by metal-reduction of the appropriate silicon(IV) heterocycles is reported. Structural as well as spectroscopic data obtained for the N-aryl substituted N-heterocyclic silylenes (NHSi) are very close to those obtained previously for their N-alkyl substituted counterparts. NHSis 9a, b are used as starting materials for the synthesis of a series of dichalcogenadisiletanes 19-24 and for of a mono silylene tungsten complex 29. The reactivity studies revealed only marginally differences between the N-aryl substituted NHSis 9a, b and previously described N-alkyl substituted silylenes.     

Mechanism of the heterocyclization of vic-alkynylanthra- and vic-alkynylnaphthoquinone diazonium salts

On the basis of experimental data and of quantum-chemical calculations, a principal scheme for the mechanism of cyclization of vic-alkynylanthra- and vic-alkynylnaphthoquinone diazonium salts resulting in the formation of 5- and 6-membered heterocycles is proposed. Within the framework of the new notions of the reaction mechanism, a possibility of controlling the formation of condensed pyrazole or pyridazine rings is demonstrated.     

Lewis acid catalyzed intramolecular halo-arylation of tethered alkenes using N-halosuccinimide (NXS) as the halogen source: a general method for the synthesis of chromanones, chromans, quinolones, tetrahydroquinolines and tetralins

Lewis acid catalyzed intramolecular halo-arylation of tethered alkenes was performed using N-halosuccinimide (NXS) as the halogen source. Among the Lewis acids investigated, Sm(OTf)₃ was found to be the best catalyst. This catalytic process provides a general method for the regio- and stereoselective synthesis of annulated arene heterocycles and carbocycles such as 2-chromanones, chromans, 2-quinolones, tetrahydroquinolines and tetralins possessing a halo-functionality.     

Synthesis and characterization of benzo[c]thiophene analogs incorporating benzo[b]thiophene/1-hexylindole/benzo[b]furan

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating heterocycles such as benzo[b]thiophene/1-hexylindole/benzo[b]furan and thiophene units is described. Optical and electrochemical studies of the benzo[c]thiophene analogs are also reported.     

Synthesis and characterization of fluorene tethered benzo[c]thiophene/benzo[c]selenophene analogs

Synthesis of 9,9-dialkyl/diarylfluorene based benzo[c]thiophene/benzo[c]selenophenes is presented. The synthesis of benzo[c]thiophene analogs is also realized with fluorene containing one or two thiophene units. The optical and electrochemical studies of fluorenyl benzo[c]heterocycles are correlated with their structures.     

Synthesis of condensed heterocycles via cyclopropylimine rearrangement of cyclopropylazoles

Thermal cyclopropylimine rearrangement of cyclopropylazoles into condensed heterocycles and factors affecting the regioselectivity and conversion are reported. A method of conducting the reaction in the absence of solvents is developed. A series of 2-cyclopropylazoles, including novel examples, is synthesized and their transformations into the corresponding condensed heterocyclic compounds (2,3-dihydro-1H-pyrroles and 6,7-dihydro-5H-pyrrolo[2,1-b]thiazolium salts) are studied.     

Amine nucleophilic addition to nitroalkene as a new practical approach for the synthesis of fully substituted isoxazoline-N-oxide

The secondary amine nucleophilic addition to the nitroalkene was used to generate the active nitronate intermediate, followed by the sequential addition to aldehyde and ylide, giving the fully substituted isoxazoline-N-oxide in one-pot fashion. Mechanistic studies revealed the equilibrium nature of the diene intermediates, which provide the foundation for the asymmetric synthesis of this interesting heterocycles.     

Copper fluorapatite catalyzed N-arylation of heterocycles with bromo and iodoarenes

Copper exchanged fluorapatite (CuFAP) is an effective heterogeneous catalyst for N-arylation of heterocycles with bromo- or iodoarenes using K₂CO₃ as base. N-Arylated products were isolated in good to excellent yields, demonstrating the versatility of the reaction.     

A novel direct N-alkenylation of nitrogen-containing heterocycles with magnesium alkylidene carbenoids

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio nitrogen-containing heterocycles (e.g., indole, indazole, phenothiazine, and phenoxazine) gave N-alkenylated products in moderate to good yields. The intermediate of this reaction was found to be the alkenyl anion, which could be trapped with iodoalkanes using CuI as a catalyst to give the heterocycles having fully substituted alkenes on the nitrogen. The alkenyl anion intermediate could be trapped also with benzoyl chloride and phenyl isocyanate. This reaction offers a quite novel and direct N-alkenylation of nitrogen-containing heterocycles.     

Optically active aziridine esters by nucleophilic addition of nitrogen heterocycles to a chiral 2H-azirine-2-carboxylic ester

Chiral enriched ethyl 3-methyl-2H-azirine-2-carboxylate acts as an efficient alkylating agent for a variety of five-membered aromatic nitrogen heterocycles.     

New and efficient RCM in pyridinic series: synthesis of 2H-dihydropyrano- or 2,3H-dihydrooxepino[3,2-b]pyridines

A new and very efficient route to polycyclic heterocycles with isosteric replacement of benzene by pyridine is reported. This strategy involving the RCM reaction in pyridinic series as a keystep allows us to prepare 2H-dihydropyrano- or 2,3H-dihydrooxepino[3,2-b]pyridines 1 and 2 in very good overall yields (47% and 44%, respectively).     

Oxidative addition of N-aminophthalimide to thiophene and selenophene: the first example of a 5-thia(seleno)-3,7-diazatricyclo[4.1.0.0]heptane system

The first examples of condensed saturated heterocycles containing a central tricyclic bisaziridine core were obtained by oxidative addition of N-aminophthalimide to thiophene and selenophene. Their structures and spectral features are described.     

An expedient domino three-component [3+2]-cycloaddition/annulation protocol: regio- and stereoselective assembly of novel polycyclic hybrid heterocycles with five contiguous stereocentres

A novel three-component strategy for the efficient synthesis of unprecedented polycyclic hybrid heterocycles comprising fused, bridged, and spiro rings with five contiguous stereocentres in a regio- and stereoselective manner is described. This transformation proceeds via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of sarcosine/thiazolidine-4-carboxylic acid and acenaphthoquinone to a series of 2-[arylmethylidene]-3,4-dihydro-1(2H)-acridinones and concomitant annulation through an intramolecular aldol-type reaction.     

Preparation, characterization, and cycloaddition reaction of the heterocumulenes attached directly to azulenes. An efficient strategy for the preparation of azulene-substituted heterocycles

Preparation and cycloaddition reaction of novel azulene-substituted N-sulfinylamines 1 and 2 are reported. The influence of the -NSO group on the UV-vis and NMR spectra of the azulene ring to which it is bonded is discussed. X-ray crystal analysis of 1 revealed the syn-configuration and the twisted structure of the N-sulfinylamine moiety. The synthetic utility of 1 and 2 have been explored by the cycloaddition reaction to afford novel azulene-substituted heterocycles under high-pressure conditions. We also described herein the synthesis and some properties of related 2-azulenylisothiocyanate.