Synthesis Of Nitrogen Heterocycles Research Articles

Synthesis of Nitrogen Heterocycles Utilizing Molecular Nitrogen as a Nitrogen Source and Attempt to Use Air Instead of Nitrogen Gas

Nitrogen fixation using transition metals is a challenging subject. Using a titanium-nitrogen complex, discovered by Yamamoto in 1967, and titanium isocyanate complex, molecular nitrogen could be incorporated into organic compounds to afford various heterocyclic compounds. Furthermore, novel titanium-catalyzed nitrogenation procedure was developed. That is, a THF solution of TiCl 4 or Ti(O i Pr) 4 , and an excess amount of Li and TMSCl was stirred under nitrogen (1 atm) at room temperature overnight and to this solution was added phthalic anhydride. The whole solution was refluxed overnight to afford a phthalimide in over 100 % yield. Using the stoichiometric conditions of the novel nitrogenation, various indole, pyrrole, pyrrolizine, indolizine derivatives and lactams were obtained in good to moderate yields after usual workup. Although the structure of the titanium-nitrogen complex has not been determined yet, the complex is thought to be a mixture of N(TMS) 3 , TiX 2 N(TMS) 2 and XTi=NTMS. Nitrogen in air could be directly fixed using this method, and the natural products, such as monomoline I, lycopodine and pumiliotoxin C, could be synthesized from nitrogen in air as a nitrogen source.

A Ruthenium-Catalyzed, Atom-Economical Synthesis of Nitrogen Heterocycles

The Ruthenium catalyzed, atom-economical domino redox isomerization/cyclization of tethered aminopropargyl alcohols is reported. This process displays a broad scope and functional group tolerance. Furthermore, it presents a novel retrosynthetic disconnection linking simple and easily available, linear propargyl alcohols with added-value nitrogen heterocycles in a single catalytic step.

Microwave activation in the synthesis of nitrogen heterocycles, N-oxides of pyridine series

Oxidation of heterocycles of the pyridine series under conditions of microwave irradiation was studied. It is established that oxidation of pyridine and 4-methylpyridine with hydrogen peroxide results in the corresponding N-oxides, and oxidation of 3-(piperidin-2-yl)pyridine gives δ-oximino-δ-(pyridyl-3-N-oxide)-valeric acid.

ChemInform Abstract: An Efficient Synthesis of Nitrogen Heterocycles by Cp*Ir‐Catalyzed N‐Cycloalkylation of Primary Amines with Diols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

９族金属錯体の水素移動触媒機能を活用する効率的有機合成反応の開発

Development of methodology directed toward environmentally benign molecular transformations is one of the most important subjects in modern synthetic organic chemistry. As a promising method for environmentally benign transformation of organic molecules, we have focused on the transition metal catalyzed Hydrogen Transfer Reactions. Here, we report our recent studies on hydrogen transfer reactions catalyzed by group 9 metal complexes bearing Cp*(η5-pentamethyl-cyclopentadienyl) ligand and their application to organic synthesis, which include (1) Cp*Ir complex-catalyzed oxidation of alcohols, (2) Cp Ir complex-catalyzed transfer hydrogenation of nitrogen heteroaromatics using 2-propanol as a hydrogen donor, (3) Cp Ir complex-catalyzed carbon-nitrogen and carbon-carbon bond formation using alcohols as alkylating reagents, (4) Cp Ir and Cp Rh complex-catalyzed synthesis of nitrogen heterocycles by intra- and intermolecular carbon-nitrogen bond formation.

Chiral N-Acyloxazolidines: Synthesis, Structure, and Mechanistic Insights

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.

Copper(II) Carboxylate-Promoted Intramolecular Carboamination of Alkenes for the Synthesis of Polycyclic Lactams

The copper(II) carboxylate-promoted intramolecular carboamination reactions of variously substituted gamma-alkenyl amides have been investigated. These oxidative cyclization reactions efficiently provide polycyclic lactams, useful intermediates in nitrogen heterocycle synthesis, in good to excellent yields. The efficiency of the carboamination process is dependent upon the structure of the amide backbone as well as the nitrogen substituent.

Copper(II)-Catalyzed Enantioselective Intramolecular Carboamination of Alkenes

The enantioselective oxidative cyclizations of γ-alkenyl arylsulfonamides and a δ-alkenyl arylsulfonamide for the synthesis of nitrogen heterocycles are presented. The reactions are catalyzed by chiral copper(II) complexes, and MnO2 is used as the inexpensive stoichiometric oxidant. A variety of five-membered heterocycles and a tetrahydroisoquinoline have been synthesized in good to excellent yields with good to excellent levels of enantioselectivity. This is the first reported copper-catalyzed enantioselective carboamination of alkenes.

Synthesis of Nitrogen Heterocycles by the Ring Opening of Pyridinium Salts.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Domino Cu‐Catalyzed C—N Coupling/Hydroamidation: A Highly Efficient Synthesis of Nitrogen Heterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

An Efficient Synthesis of Nitrogen Heterocycles by Cp*Ir-Catalyzed N-Cycloalkylation of Primary Amines with Diols

A new efficient method for the N-cycloalkylation of primary amines with diols catalyzed by a Cp*Ir complex have been developed. A variety of five-, six-, and seven-membered cyclic amines are synthesized in good to excellent yields in environmentally benign and atom economical manner with the formation of only water as a coproduct. A large scale synthesis of N-benzylpiperidine and a two-step asymmetric synthesis of (S)-2-phenylpiperidine using (R)-1-phenylethylamine as a starting primary amine have been also achieved.

Synthesis of Nitrogen Heterocycles by the Ring Opening of Pyridinium Salts

Synthesis of Nitrogen Heterocycles by the Ring Opening of Pyridinium Salts

Synthesis of Nitrogen Heterocycles by the Ring Opening of Pyridinium Salts

The century-old ring-opening reaction of pyridinium salts with tethered nucleophiles has been harnessed for a synthesis of substituted indoles and related nitrogen heterocyles. Extension of this method could lead to oxygen- and sulfur-containing heterocycles and carbocycles, as well as to applications in natural product synthesis and medicinal chemistry.

Asymmetric Aza‐Wittig Reactions: Enantioselective Synthesis of β‐Quaternary Azacycles

A hindrance no more: The direct asymmetric synthesis of nitrogen heterocycles containing β-quaternary stereocenters, widely found for example in alkaloids, is highly challenging. The novel approach shown exploits the desymmetrization of prochiral diketo azides to unmask the asymmetric quaternary center, and represents the first reported examples of the asymmetric aza-Wittig reaction.

Solid‐Supported Catalysts for Atom‐Transfer Radical Cyclizations: Assessment of Support Type and Ligand Structure on Catalyst Performance in the Synthesis of Nitrogen Heterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A new approach to the preparation of lanthanide catalysts for the synthesis of 2-propyl-3-ethylquinoline based on the reactions of LnCl3 · 6H2O crystalline hydrates with triisobutylaluminum

A new approach to the preparation of lanthanide catalysts for the synthesis of nitrogen heterocycles (exemplified by 2-propyl-3-ethylquinoline) was developed based on the reactions of LnCl3 · 6H2O crystalline hydrates with alkylaluminums. It was found that the interaction of LnCl3 · 6H2O (Ln = Ce, Pr, Tb, and Eu) with iso-Bu3Al in aromatic solvents (20°C) resulted in the formation of soluble (isobutane and the alumoxane (iso-Bu2Al)2O) and insoluble products (with the empirical formula LnCl3 · xH2O · y(iso-Bu2Al)2O (x = 0.4–0.7; y = 0.04–0.07)). The physiochemical properties of LnCl3 · xH2O · y(iso-Bu2Al)2O were studied, and these compounds were found to be highly efficient catalysts for the reaction of aniline condensation with butyraldehyde to form 2-propyl-3-ethylquinoline.

Solid-Supported Copper Catalysts for Atom-Transfer Radical Cyclizations: Assessment of Support Type and Ligand Structure on Catalyst Performance in the Synthesis of Nitrogen Heterocycles

A range of solid supported pyridinemethanimine 9-11 and polyamine 12-15 ligands have been prepared on silica, polystyrene, and JandaJel supports. The CuCl and CuBr complexes of these supported ligands have been used to assess both the effect of the ligand type and the nature of the support upon a representative range of copper-mediated atom transfer 5-exo-trig 6, 24-25, 5-exo-dig 26, 4-exo-trig 28, and 5-endo-trig 27, 38 radical cyclizations to give nitrogen heterocycles. In addition, the effect of the nature of the support on the stereochemical outcome of the 5-exo cyclization of 25 has been probed. Generally, it was found that the type of support (e.g., polystyrene, silica, or JandaJel) had very little effect upon the efficiency and selectivity of the processes but that the nature of the ligand type immobilized was the important factor. Thus, the 5-exo cyclization of 6 and 24-26 proceeded more rapidly with the PMI ligands 9-11, whereas 4-exo cyclizations 28 and 5-endo radical polar crossover reactions 27 and 38 proceeded more efficiently with the JJ-TEDETA ligand 15. The efficiency of the supported ligands was also compared to their solution counterparts 4 and 5. The reusability of P-PMDETA ligand system 13 was assessed in the cyclization of 6.

Cp*Ir Complex‐Catalyzed Hydrogen Transfer Reactions Directed Toward Environmentally Benign Organic Synthesis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Brønsted Acid-Catalyzed Highly Stereoselective Arene-Ynamide Cyclizations. A Novel Keteniminium Pictet−Spengler Cyclization in Total Syntheses of (±)-Desbromoarborescidines A and C

[reaction: see text] A Brønsted acid-catalyzed highly stereoselective arene-ynamide cyclization is described. These reactions constitute a keteniminium variant of Pictet-Spengler cyclizations, leading to efficient synthesis of nitrogen heterocycles and related alkaloids. Total syntheses of desbromoarborescidines A and C are illustrated here as first applications of this methodology.

Cp*Ir Complex-Catalyzed Hydrogen Transfer Reactions Directed toward Environmentally Benign Organic Synthesis

Catalytic activity of Cp*Ir complexes toward hydrogen transfer reactions are discussed. Three different types of reactions have been developed. The first is Oppenauer-type oxidation of alcohols. This reaction proceeds under quite mild conditions (room temperature in acetone) catalyzed by [Cp*IrCl2]2/K2CO3, and both primary and secondary alcohols can be used as substrates. Introduction of a N-heterocyclic carbene ligand to the catalyst considerably enhances the catalytic activity, and a very high turnover number of 950 has been obtained in the oxidation of 1-phenylethanol. The ­second is the N-alkylation of amines with alcohols. A new effective catalytic system consisting of [Cp*IrCl2]2/K2CO3 for the N-alkylation of primary amines with alcohols has been developed. Synthesis of indoles and 1,2,3,4-tetrahydroquinolines via intramolecular N-alkylation of amino alcohols and synthesis of nitrogen heterocycles via intermolecular N-alkylation of primary amines with diols catalyzed by a Cp*Ir complex have been also achieved. The third is the regio- and chemoselective transfer hydrogenation of quinolines. An efficient method for the transfer hydrogenation of quinolines catalyzed by [Cp*IrCl2]2/HClO4 using 2-propanol as a hydrogen source has been realized. A variety of 1,2,3,4-tetrahydroquinoline derivatives can be synthesized by this method. These results show that Cp*Ir complexes can be useful catalysts for hydrogen transfer ­reactions from the viewpoint of developing environmentally benign organic synthesis.