Substituent effects in the mass spectra of benzoyl hetarenes

The mass spectra of several benzoyl hetarenes, of 2-benzoyl pyridines substituted at the phenyl and pyridyl group, respectively, and of phenyl substituted 2-benzoyl pyrroles, have been studied with respect to the formation of benzoyl and hetaroyl ions. A correlation between the intensity of benzoyl ions, relative to molecular ion intensity, and the π-electron density at the substituted carbon atom of the hetarene has been observed for benzoyl hetarenes. The relative intensities of (substituted) benzoyl ions of substituted 2-benzoyl pyridines and 2-benzoyl pyrroles are not easily related to substituent constants of Hammett equations. The relative ionization energies of phenyl substituted 2-benzoyl pyridines, however, and the relative appearance energies of substituted benzoyl ions derived therefrom follow the σ_IP⁺-constant of Bentley and Johnstone and the σ⁺-constants of Brown, respectively.     

Synthesis of 2,3-disubstituted pyrroles and pyridines from 3-halo-1-azaallylic anions.

A new synthesis of 2,3-disubstituted pyrroles and pyridines is described. The reaction of 3-halo-1-azaallylic carbanions, regiospecifically generated from alpha-halogenated ketimines, with omega-iodoazides led to the regiospecific formation of omega-azido-alpha-haloketimines. Treatment of these functionalized imines with tin(II) chloride afforded halogenated five- and six-membered cyclic imines, which were transformed under mild conditions into 2,3-disubstituted pyrroles and pyridines. The stereoselective reduction of 2,3-dialkyl-3-chloro-1-pyrrolines to afford cis-2,3-dialkyl-3-chloropyrrolidines is also reported.     

A convenient approach to the synthesis of 2-(2-aminoethyl)pyrroles and their heterocyclization into hydrogenated pyrrolopyridines and related pyrroloindolizines

2-(2-Aminoethyl)pyrroles and 2-(2-succinimidoethyl)pyrroles were prepared from acetals of ethyl 4-oxoalkanoates via latent vinyl 1,4-dicarbonyl compounds as the key intermediates. The Pictet-Spengler condensation of 2-(2-aminoethyl)pyrroles with aromatic aldehydes gave 4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines in good yields. 4,5,7,8,9,9a-Hexahydro-3H-pyrrolo[2,3-g]indolizines were prepared in a similar way starting from 2-(2-succinimidoethyl)pyrroles.     

Metal free coupling of heteroaryl N-tosylhydrazones and thiols: Efficient synthesis of sulfides

A metal free coupling of heteroaromatic N-tosylhydrazones with thiols is presented. A convenient synthetic route to synthesize heteroaryl N-tosylhydrazones is also showed. Valuable thioethers with pyrroles, pyridines, thieno[2,3-b]pyridines, imidazo[1,2-a]pyridines, and 6H-thieno[2,3-b]pyrroles derivatives were synthesized in good yields. This coupling reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using heteroaryl aldehydes, without the need to isolate the N-tosylhydrazone.     

One-Carbon Ring Expansion of Indoles and Pyrroles: A Straightforward Access to 3-Fluorinated Quinolines and Pyridines

3-Fluorinated quinolines and pyridines are prevalent pharmacophores, yet their synthesis is often challenging. Herein, we demonstrate that dibromofluoromethane as bromofluorocarbene source enables the one-carbon ring expansion of readily available indoles and pyrroles to structurally diverse 3-fluorinated quinolines and pyridines. This straightforward protocol requires only a short reaction time of ten minutes and can be performed under air atmosphere. Preliminary investigations reveal that this strategy can also be applied to the synthesis of other valuable azines by using different 1,1-dibromoalkanes as bromocarbene sources.     

Olefin cross-metathesis for the synthesis of heteroaromatic compounds

The olefin metathesis reaction has underpinned spectacular achievements in organic synthesis in recent years. Arguably, metathesis has now become the foremost choice for a carbon-carbon double bond disconnection. Despite this general utility, de novo routes to heteroaromatic compounds using the cross-metathesis (CM) reaction have only recently emerged as an efficient strategy. This approach allows a convergent union of simple, functionalised, three- to four-carbon olefinic core building blocks, to generate furans, pyrroles and pyridines with a high degree of control of substitution pattern in the product.     

Transformation of 3-formylchromones into pyridines and pyrroles

Interaction of 3-formylchromones with ethyl aminoethanoate provides a novel route to pyridines and pyrroles.     

New C-N and C-C bond forming reactions catalyzed by titanium complexes

Titanium(IV) complexes with two basic dimethylamido ligands can be efficient catalysts for alkyne hydroamination by primary amines. Readily prepared pyrrolyl ligands have proven to be especially useful in generating active catalysts for hydroamination and hydrohydrazination. From these reactions, new methodologies for the synthesis of imines, hydrazones, alpha,beta-unsaturated imines, pyridines, indoles, and pyrroles have developed. In addition, a new reaction that is mechanistically related to hydroamination, alkyne iminoamination, has been discovered. Iminoamination, which is a multicomponent coupling between an amine, alkyne, and isonitrile, provides unsymmetrical alpha, beta-unsaturated beta-iminoamines in a single, titanium-catalyzed step.     

Microwave-assisted preparations of dihydropyrroles from alkenone O-phenyl oximes

Microwave irradiation of alkenone O-phenyl oximes produces iminyl radicals that ring close to yield dihydropyrrole derivatives; pyrroles and pyridines can be obtained from related precursors.     

Cycloaddition reactions of 1-lithio-1,3-dienes with aromatic nitriles affording multiply substituted pyridines, pyrroles, and linear butadienylimines

Fully or partially substituted 1-iodo- or 1-bromo-1,3-dienes could be readily lithiated using t-BuLi or n-BuLi to afford their corresponding 1-lithio-1,3-diene derivatives in quantitative yields. When these in situ generated lithium reagents were treated with organonitriles, depending on the substitution patterns of the butadienyl skeletons, substituted pyridines, pyrroles, and/or linear butadienyl imines were formed in good to excellent yields via N-lithioketimine intermediates. In the cases of 1,2,3,4-tetrasubstituted and 2,3-disubstituted 1-lithio-1,3-dienes, pyridine derivatives or linear butadienyl imines were generally formed depending on the reaction temperatures. When 1,2,3,4-tetrasubstituted 4-halo-1-lithio-1,3-dienes and 1,2-disubstituted 1-lithio-1,3-dienes were treated with organonitriles, pyrrole derivatives or linear butadienyl imines were obtained. Competition between 5-exo and 6-endo cyclization was found to be responsible for the formation of either pyrroles or pyridines. Selective elimination of RLi from the lithiated cyclic N-containing intermediates was observed. The order of elimination was found to be LiCl > Me3SiLi > LiH.     

Facile preparation of various heteroaromatic compounds via azatitanacyclopentadiene intermediates

Coupling of acetylene, nitrile, and a titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, generated new azatitanacyclopentadienes in a highly regioselective manner. Their subsequent reaction with sulfonylacetylene afforded pyridyltitanium compounds, which, upon reaction with electrophiles, gave substituted pyridines virtually as a single isomer. When optically active nitriles were used in this reaction, chiral pyridines were obtained without loss of the enantiopurity. Alternatively, the azatitanacyclopentadiene prepared from an unsymmetrical acetylene reacted with an aldehyde or another nitrile to give furans or pyrroles having four different substituents again in a regioselective manner.     

A new and highly efficient water-soluble copper complex for the oxidation of secondary 1-heteroaryl alcohols by tert-butyl hydroperoxide

The water-soluble copper complex generated in situ from CuCl₂ and 2,2′-biquinoline-4,4′-dicarboxylic acid dipotassium salt (BQC), has been revealed as a highly efficient and selective catalyst for the oxidation of secondary 1-heteroaryl alcohols to the corresponding heteroaromatic ketones with aqueous tert-butyl hydroperoxide, under mild conditions. The catalytic system is compatible with different heterocycles such as pyridines, pyrroles, indoles, thiophens, furans, thiazoles, and imidazoles.     

Cluster analysis of MS- and IR-spectra of pyrazines and related heterocyclic flavour substances

Summary The application of Principal Component Analysis (PCA) on MS- and IR-spectra of 77 substances from a test data set, belonging to 5 different classes of heterocyclic components (pyrazines, pyrroles, pyridines, thiazoles and quinoxalines, Table 1) resulted in a clear separation of the MS-spectral data in distinct clusters and led to the definition of planar classifiers, which were used for the detection of these classes of compounds in the spectral data set of a complex natural matrix. The projection of the GC-MS data of the headspace of opium in the plane of two main variances and the application of the planar classifier for pyrazines/pyrroles resulted in the reduction of the original data set by factor of 30 and allowed more efficient identification of 3 alkylpyrazines and 2 acylsubstituted pyrroles. The PCA of full dimensionality IR-spectra only resulted in less pronounced cluster separation.     

Cycloaddition Reactions of Enamines

This review includes information for around two last decades on cycloaddition reactions of enamines with various agents in order to build carbo- and heterocycles. In addition, the review presents organo-catalytic reactions in which enamines are intermediate products generated in situ. This review covers the synthesis of four, five, six and eight-membered carbocyclic compounds, as well as heterocycles as pyrroles, pyridines, etc.     

Regio‐ and Stereoselective Synthesis of Functionalized Dihydropyridines,Pyridines, and 2H‐Pyrans: Heck Coupling of Monocyclopropanated Heterocycles

A palladium‐catalyzed coupling between aryl halides and monocyclopropanated pyrroles or furans has been developed, leading to valuable six‐membered N‐ and O‐heterocycles. As the key step, a selective cleavage of the non‐activated endocyclic C?C bond of the 2‐heterobicyclo‐[3.1.0]hexane framework is achieved. The developed method offers access to highly functionalized piperidines, pyridines, and pyrans that are challenging to access by traditional methods.     

Heterocyclic amino acids as synthons. Reactions with dicarbonyl compounds

From some alkyl heteroarylglycinates and dicarbonyl compounds various heterocyclic systems are easily accessible. Transformations are described which lead to imidazo[1,5-α]pyridines, heteroaryl-substituted pyrroles, pyrido[1,2-α]pyrazines, pyrido[1,2-α]pyrimidines or quinolizin-4-ones.     

Silylamines in organic synthesis: preparation and some reactions of N,C-dilithiosilylamines

The dimetallation of some olefinic and aromatic N-trimethylsilylamines has been examined. Treatment with a two molar proportion of n-butyllithium gives organodimetallic reagents, which react with trimethylchlorosilane to give N,N,C-tris(trimethylsilyl)amines in 45 to 65% yields. The dianonic reagent obtained from (trimethylsilyl)(allyl)amine reacts with benzoyl chloride, N,N-dimethylformamide, ethyl-2-furylcarboxylate, and benzil to give substituted pyrroles and pyridines.     

Catalytic C-H arylation of SEM-protected azoles with palladium complexes of NHCs and phosphines

[reaction: see text] The synthesis and catalytic evaluation of palladium complexes containing imidazolyl carbene ligand of varying steric and electronic properties is reported. These complexes catalyze the efficient C-H arylation of SEM-protected azole heteroarenes and thus provide a good method for preparation of a wide range of arylated free (NH)-azoles including pyrroles, indoles, imidazoles, and imidazo[1,2-a]pyridines. The reaction is operationally simple; the complexes are insensitive to moisture.     

Facile synthesis of N-aryl pyrroles via Cu(II)-mediated cross coupling of electron deficient pyrroles and arylboronic acids

N-Arylation of electron-deficient pyrroles has been achieved by cross-coupling with arylboronic acids at room temperature in the presence of stoichiometric amounts of copper(II) acetate. The generality of this reaction has been established with variously substituted pyrroles as well as boronic acids. A key intermediate in the synthesis of a matrix metalloprotease inhibitor has been achieved using this methodology.     

Ruthenium-catalysed conversion of 1,4-alkynediols into pyrroles

Various 1,2,5-substituted pyrroles have been synthesised from 1,4-alkynediols using a ruthenium catalysed isomerisation to give the corresponding 1,4-dicarbonyl compounds, which undergo in situ cyclisation to pyrroles in the presence of amine.