Intramolecular Amination Reaction Research Articles

Iron Corrole-Catalyzed Intramolecular Amination Reactions of Alkyl Azides. Spectroscopic Characterization and Reactivity of [FeV(Cor)(NAd)

As nitrogen analogues of iron-oxo species, high-valent iron-imido species have attracted great interest in the past decades. FeV-alkylimido species are generally considered to be key reaction intermediates in Fe(III)-catalyzed C(sp3)─H bond aminations of alkyl azides but remain underexplored. Here, it is reported that iron-corrole (Cor) complexes can catalyze a wide range of intramolecular C─H amination reactions of alkyl azides to afford a variety of 5-, 6- and 7-membered N-heterocycles, including alkaloids and natural product derivatives, with up to 3880 turnover numbers (TONs) and excellent diastereoselectivity (>99:1d.r.). Mechanistic studies including density functional theory (DFT) calculations and intermolecular hydrogen atom abstraction (HAA) reactions reveal key reactive FeV-alkylimido intermediates. The [FeV(Cor)(NAd)] (Ad = adamantyl) complex is independently prepared and characterized through electron paramagnetic resonance (EPR), resonance Raman (rR) measurement, and X-ray photoelectron spectroscopy (XPS). This complex is reactive toward HAA reactions with kinetic isotope effects (KIEs) similar to [Fe(Cor)]-catalyzed intramolecular C─H amination of alkyl azides.

Electrochemical Dearomative Amination of Phenol Derivatives: Access to Spirooxazolidinones

AbstractAn electrochemical oxidative approach to spirooxazolidinones from phenol derivatives via intramolecular dearomative amination reactions is developed. This reaction proceeds without metal catalysts and external chemical oxidants, and shows broad substrate scope and diverse functional group compatibility. The synthetic utility of this strategy is further exhibited by the gram‐scale synthesis and late‐stage functionalization. By slightly tunning the reaction conditions, the alcohols (1°, 2° and 3°) can be afforded from phenol derivatives, which is a good strategy for the deprotection of para‐methoxyphenyl (PMP) group to recover the alcohol function.magnified image

SYNTHESIS, REACTIVITY AND BIOLOGICAL PROPERTIES OF AMINOPYRAZOLES

In this research a new polyheterocyclic compounds endowed with various biological activities using different aminopyrazoles as starting reagents were sinthesized. We have developed a bibliographic study bearing the interest, the different methods of the synthesis and reactivity of aminopyrazoles. We have used the aminocyanopyrazoles in the preparation of new aromatic heterocycles by carrying out cyclization reactions of the two extracyclic functions amine and nitrile. Some of the obtained compound have shown interesting biological activities and fluorescence properties. We then dealt with the C-4 arylation reactions by activation of the palladium-catalyzed C-H bond of 5-aminopyrazole carrying the cyclopropyl group in the C3 position. This study is then extended to amination reactions. Finally, the synthesis of polyheterocyclic compounds involving intramolecular arylation and amination reactions is reported.

Cascade C–N bond cleavage of amides/intramolecular amination reactions: an atom economical way to α-cabolin-4-ones

A novel one-pot procedure for the synthesis of 2,3-disubstituted α-carbolin-4-ones through successive C–N bond cleavage and intramolecular amination reactions involving a 1,2-acyl migration has been developed.

Intramolecular C(sp₃)-H Bond Amination Strategies for the Synthesis of Saturated N-containing Heterocycles.

The selective functionalization of C(sp³)-H bonds via intramolecular amination reactions represents a very attractive strategy for the construction of saturated N-containing heterocycles (SNHets). Over the past de- cades, the chemical community has devoted its efforts towards expanding the synthetic toolbox with the aim of facilitating access to these key fragments in a controllable, reproducible and efficient manner. This review covers selected examples of the most recent advances in intramolecular C(sp³)-N bond-forming reactions by three main approaches: (1) the Hofmann-Löffler-Freytag (HLF) reaction; (2) transition-metal-catalyzed nitrene C(sp³)-H inser- tion; and (3) transition-metal-catalyzed ligand-assisted C(sp³)-N bond-forming reactions via a reductive elimination step. We will discuss reactivity, selectivity and the major mechanistic insights into these transformations.

Base-Assisted Intramolecular C–N Coupling Reaction from NH2-Bound Cyclopalladated l-Phenylalanine to Indoline-2-carboxylic Acid

The deprotonative intramolecular-amination reaction of phenylalanine-derived palladacycles has been investigated to highlight a facile carbonate-assisted N–H activation before the C–N bond formation. A major counterion effect led to divergent pathways whereby the SPhos-Pd complexes with iodine, triflate, or trifluoroacetate anions were key intermediates to afford access to (S)-2-indolinecarboxylic acid derivatives.

Enantioselective Atropisomeric Anilides Synthesis via Cu-Catalyzed Intramolecular Adjacent C–N Coupling

Catalytically asymmetric synthesis of atropisomeric compounds is an important research area in organic synthesis. However, in comparison with C–C atropisomers, the atropisomers caused by the restricted rotation of C–N single bonds have been given less attention because of the limited methods for accessing these compounds. Herein we report a Cu-catalyzed enantioselective intramolecular Ullmann-type amination reaction for the synthesis of C–N atropisomers. The C–N axial chirality was induced highly efficiently by the intramolecular adjacent C–N cross-coupling. The readily prepared N,N′-(cyclohexane-1,2-diyl)dipicolinamides showed high efficacy and stereoinduction (up to 99% ee).

Engineering Molecular Iodine Catalysis for Alkyl–Nitrogen Bond Formation

An advanced protocol for the intramolecular C–H amination of alkyl groups via amidyl radicals (Hofmann–Loffler reaction) under homogeneous iodine catalysis is reported. This protocol employs common mCPBA as terminal oxidant. It proceeds under mild conditions, with complete chemoselectivity, is compatible with radical intermediates, and allows for the selective intramolecular amination reaction of secondary and tertiary hydrocarbon bonds and is not restricted to benzylic C–H amination. The involvement of an iodine(III) catalyst state in the C–N bond formation derives from selective oxidation at the stage of the corresponding alkyl iodide with mCPBA. Its formation is corroborated by quantum-chemical calculations. This new catalysis thus proceeds within a defined iodine(I/III) catalysis manifold.

Synthesis, structure and N-N bonding character of 1,1-disubstituted indazolium hexafluorophosphate.

1,1-Disubstituted indazolium hexafluorophosphates were synthesized via intramolecular electrophilic amination reactions under mild conditions. The crystal structures were determined and are consistent with the presence of a stable N-N bond, which can be cleaved by hydrogenation. Both experimental and computational studies suggest a covalent bonding character of the N-N bond, with diminished aromaticity of the newly formed pyrazolium ring due to the quaternary ammonium atom (N1), in contrast to the aromatic character of the parent indazole.

A Brønsted acid-promoted asymmetric intramolecular allylic amination of alcohols.

Reported herein is a chiral Brønsted acid-catalyzed asymmetric intramolecular allylic amination reaction, allowing facile access to a range of biologically interesting chiral 2-substituted hydroquinolines in up to 90% yield and with up to 93% ee. Furthermore, a significant effect of an N-protecting group was observed in this asymmetric process.

Pd(II)-catalyzed enantioselective intramolecular oxidative amination utilizing (+)-camphorsulfonic acid

An enantioselective Pd(II)-catalyzed intramolecular oxidative amination reaction was developed utilizing the commercially available chiral X-type ligand (1S)-(+)-camphorsulfonic acid. The Wacker-type cyclization produced chiral indoline products with enantioselectivies up to 45% ee. Electronic structure calculations employing density functional theory support a trans-aminopalladation mechanism.

A practical method, NaOCl-mediated, to prepare thiabendazoles via intramolecular amination reaction

A series of new chlorinated thiabendazoles (6a–m) have been synthesized from readily available anilines and 4-cyanothiazole in moderate to good yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (6f) was confirmed by single-crystal X-ray diffraction. In addition, synthesis of 2-substituted benzimidazoles and 2-phenyl benzothiazole was investigated using our optimized conditions and the outcome is presented herein.

Intramolecular Oxidative Palladium-Catalyzed Amination Involving Double C–H Functionalization of Unactivated Olefins

Intramolecular palladium-catalyzed amination reactions are becoming important tools for the synthesis of various nitrogen-containing­ heterocycles. This account highlights the developments achieved in this field by domino processes in oxidative conditions using unactivated olefins, due to their advantages in terms of step economy and efficiency. These reactions involve the change of oxidation state in the palladium intermediate, requiring the presence of an oxidizing agent to regenerate the catalytic cycle. This kind of additive is essential for the success of the reaction and it can also furnish nucleophilic species that are incorporated into the final product. Reactions can occur at either the intra/intra- or intra/intermolecular level, providing valuable methodologies for the preparation of (poly)heterocyclic scaffolds. Besides, procedures based on the use of strengthened catalytic systems, more recently, disclosed intriguing conditions have enlarged the possibility to modulate the substrate reactivity. Perspectives in this field are directed to the discovery of new reaction conditions, focusing on the employment of oxidatively stable ligands useful for the asymmetric catalysis­.1 Introduction2 Carboamination Reactions2.1 Pd(0)/Pd(II)2.2 Pd(II)/Pd(IV)3 Aminooxygenation Reactions3.1 Pd(0)/Pd(II)3.2 Pd(II)/Pd(IV)4 Diamination Reactions4.1 Pd(0)/Pd(II)4.2 Pd(II)/Pd(IV)5 Aminohalogenation Reactions5.1 Pd(0)/Pd(II)5.2 Pd(II)/Pd(IV)6 Conclusions

Metal- and Reagent-Free Intramolecular Oxidative Amination of Tri- and Tetrasubstituted Alkenes.

A metal- and reagent-free, electrochemical intramolecular oxidative amination reaction of tri- and tetrasubstituted alkenes has been developed. The electrosynthetic method proceeds through radical cyclization to form the key C-N bond, allowing a variety of hindered tri- and tetrasubstituted olefins to participate in the amination reaction. The result is the efficient synthesis of a host of alkene-bearing cyclic carbamates and ureas and lactams.

Phenanthroline-based metal-organic frameworks for Fe-catalyzed Csp3-H amination.

We report here the synthesis of a robust and highly porous Fe-phenanthroline-based metal-organic framework (MOF) and its application in catalyzing challenging inter- and intramolecular C-H amination reactions. For the intermolecular amination reactions, a FeBr2-metalated MOF selectively functionalized secondary benzylic and allylic C-H bonds. The intramolecular amination reactions utilizing organic azides as the nitrene source required the reduction of the FeBr2-metalated MOF with NaBHEt3 to generate the active catalyst. For both reactions, Fe or Zr leaching was less than 0.1%, and MOFs could be recycled and reused with no loss in catalytic activity. Furthermore, MOF catalysts were significantly more active than the corresponding homogeneous analogs. This work demonstrates the great potential of MOFs in generating highly active, recyclable, and reusable earth abundant metal catalysts for challenging organic transformations.

ChemInform Abstract: Towards Uniform Iodine Catalysis: Intramolecular C—H Amination of Arenes under Visible Light.

AbstractA mild protocol is developed for the intramolecular aryl amination reaction using visible light and iodine as catalysts in the presence of a mild hypervalent iodine oxidant.

ChemInform Abstract: An Iridium(I) N‐Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand.

An Iridium(I) N‐Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions

AbstractA chiral iridium(I) N‐heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74–91 %) and excellent enantioselectivities (92–99 % ee). Preliminary mechanistic investigations reveal that the C−H activation occurs at the position ortho to the N‐aryl group of the ligand.

An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand.

ChemInform Abstract: Stereoselective Synthesis of Spirooxindole Derivatives Using an Organocatalyzed Tandem Michael—Michael Reaction.

A highly efficient stereoselective method for the synthesis of functionalized spirooxindole derivatives with three stereogenic centers was realized through an organocatalytic tandem Michael-Michael reaction. By employing (S)-α,α-diphenylprolinol trimethylsilyl ether as the catalyst and N,N'-bis[3,5-bis(trifluoromethyl)phenyl]thiourea as the cocatalyst, the reaction between N-tritylisatylidenemalononitriles and (E)-7-alkyl-7-oxohept-5-enals yields the desired spirooxindole products in good yields (76-95%) and with excellent diastereoselectivities (up to 97 : 3 dr) and enantioselectivities (up to 98% ee), which can be stereoselectively converted into the spiro[indoline-3,8'-isoquinoline] derivative through an intramolecular reductive amination reaction.