Amination Of Arenes Research Articles

Organocatalytic Electrophilic Arene Amination: Rapid Synthesis of 2-Quinolones.

For decades, the synthesis of 2-quinolones, a crucial structural motif in pharmaceuticals and agrochemicals, has relied heavily on costly noble metal complexes and structurally complex ligands. Despite considerable efforts from synthetic chemists, a mild, metal-free, environmentally friendly, and cost-effective approach has remained elusive. This study introduces a robust, metal-free synthetic platform that leverages an innovative organoiodine-catalyzed electrophilic arene C(sp2)-H amination strategy to efficiently produce a wide range of new and modifiable 2-quinolones. Moreover, this study allows ready synthetic access to novel 8-aryl-substituted 2-quinolones, uncovering new chemical spaces with significant potential for medicinal applications.

Organocatalytic Atroposelective C‐H Amination of Arenes with Indolines

An atroposelective synthesis of axially chiral N‐arylindolines has been established by organocatalytic nucleophilic amination of arenes with 7‐substituted indolines, providing a straightforward way to achieve the expected C‐N atropisomers in good yields (up to 95%) with good to excellent enantioselectivities (up to 97% ee) from readily available starting materials. Furthermore, axially chiral N‐arylindole derivatives could be prepared upon oxidative aromatization of the corresponding N‐arylindolines.

Photocatalytic Direct Para‐Selective C−H Amination of Benzyl Alcohols: Selectivity Independent of Side Substituents

AbstractAminoarenes are important molecules for broad applications in nearly all modern industries that involve chemicals. Direct and site‐selective C−H bond amination of arenes provides the most efficient and convenient method to prepare aminoarenes. A main challenge is to selectively install the amino group (or other functional groups) to the distal para‐carbon of arenes (especially multi‐substituted arenes) during the C−H bond functionalization events. Herein, we address this problem by designing a new strategy via a sequential radical dearomatization/radical amination/rearomatization process for para‐selective amination of benzyl alcohols. The para‐selectivity of our reaction is completely independent of the electronic and steric properties of the other substituents of the arene substrates. Aminoarenes with many substituents (up to full substitution) and diverse substitution patterns, including those difficult to synthesize previously, could be readily prepared using our protocols. Further exploration of the current strategy shall lead to other challenging C−H functionalization of arenes.

Photocatalytic Direct Para-Selective C-H Amination of Benzyl Alcohols: Selectivity Independent of Side Substituents.

Aminoarenes are important molecules for broad applications in nearly all modern industries that involve chemicals. Direct and site-selective C-H bond amination of arenes provides the most efficient and convenient method to prepare aminoarenes. A main challenge is to selectively install the amino group (or other functional groups) to the distal para-carbon of arenes (especially multi-substituted arenes) during the C-H bond functionalization events. Herein, we address this problem by designing a new strategy via a sequential radical dearomatization/radical amination/rearomatization process for para-selective amination of benzyl alcohols. The para-selectivity of our reaction is completely independent of the electronic and steric properties of the other substituents of the arene substrates. Aminoarenes with many substituents (up to full substitution) and diverse substitution patterns, including those difficult to synthesize previously, could be readily prepared using our protocols. Further exploration of the current strategy shall lead to other challenging C-H functionalization of arenes.

Amination of Arenes Using Blue Light and Lewis Acids

Amination of Arenes Using Blue Light and Lewis Acids

Visible-Light Photocatalytic C-H Amination of Arenes Utilizing Acridine-Lewis Acid Complexes.

This report describes the development of a visible-light photocatalytic system for C(sp2)-H amination that leverages in situ-generated photocatalysts. We demonstrate that the combination of acridine derivatives and Lewis acids forms potent photooxidants that promote the C-H amination of electronically diverse arenes upon irradiation with visible-light (440 nm). A first-generation photocatalyst composed of Sc(OTf)3 and acridine effects the C-H amination of substrates with oxidation potentials ≤ +2.5 V vs SCE with pyrazole, triazole, and pyridine nucleophiles. Furthermore, the simplicity and modularity of this system enable variation of both Lewis acid and acridine to tune reactivity. This enabled the rapid identification of two second-generation photocatalysts (derived from (i) Al(OTf)3 and acridine or (ii) Sc(OTf)3 and a pyridinium-substituted acridine) that catalyze a particularly challenging transformation: C(sp2)-H amination with benzene as the limiting reagent.

Metal-free meta-Selective C–H Amination of Arenes

Metal-free meta-Selective C–H Amination of Arenes

Recent Advance in Electrochemical C(sp2)—H Amination of Arenes

Recent Advance in Electrochemical C(sp²)—H Amination of Arenes

Organo-initiator enabled undirected C–H amination of arenes

An undirected metal-free C–H amination protocol was presented, showcasing the integration of a novel organo-initiator.

Recent advances in electrochemical C–N bond formation via C–H/N–H activation with hydrogen evolution

Electroorganic synthesis is a powerful sustainable tool for achieving greener and more efficient chemical processes across various industries. By adhering to the principles of green chemistry, atom economy, and resource efficiency, electroorganic synthesis can play a pivotal role in addressing environmental concerns and promoting a more sustainable future for chemical production. This review focuses on the latest advancements in the emerging application of electrochemistry in C-N bond formation through C-H/N-H cross-coupling. The first part of the review describes the electrochemical amination of arenes using metal catalysis (Cu, Co, Ni) with directing groups on the arene moiety. The next section addresses the same type of electrochemical C-N bond formation on arenes without directing groups, which represents a more general strategy enabling the synthesis of anilines and various heterocyclic-bound arenes in high yields. Further developments on benzylic systems are also discussed. This is followed by developments in the combination of photocatalysis and electrochemistry to activate C-H bonds in arenes, alkanes, and benzylic systems, including the use of flow reactor configurations for these reactions.

Advancing Meta-Selective C-H Amination through Non-Covalent Interactions.

Regioselective C-H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C-H amination of arenes, overcoming the long-standing requirement for a redundant directing group. The remarkable advancements in functional group accommodation for precise regiochemical control were achieved through the discovery of an unprecedented organo-initiator and the strategic utilization of non-covalent interactions. This protocol has been successfully applied in the concise synthesis and late-stage derivatization of drug molecules, which would have been otherwise challenging to achieve.

Organocatalytic aromatization-promoted umpolung reaction of imines.

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization. The attachment of strongly electron-withdrawing groups to imines could enhance the umpolung reactivity by both electronegativity and aromatic character, enabling the direct amination of (hetero)arenes with good efficiencies and stereoselectivities. Additionally, the application of chiral Brønsted acid catalyst furnishes (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines via dearomative amination from N-electrophilic aromatic precursors. Control experiments and density functional theory calculations suggest an ionic mechanism for the umpolung reaction of imines. This disconnection expands the options to forge C-N bonds stereoselectively on (hetero)arenes, which represents an important synthetic pursuit, especially in medicinal chemistry.

Photocatalytic C–H Amination of Arenes by a Ruthenium Complex on Faujasite-Type Zeolite

Photocatalytic C–H Amination of Arenes by a Ruthenium Complex on Faujasite-Type Zeolite

Copper-catalyzed primary amination of arene C[sbnd]H bond with hydroxylamine derivative

A novel methodology for the primary amination of aromatic C(sp2)-H bond utilizing hydroxylamine derivative as ammonia surrogates has been developed. With a cost-effective and convenient copper oxide, a variety of aromatic primary amines were synthesized without external oxidant with moderate to good yields under the mild conditions. This amination exhibits excellent functional group tolerance, wide substrate scope, the use of readily available substrates, and a facile work-up procedure. Furthermore, the late-stage modification of drug-like small molecules with complex structures was also allowed.

Photoinduced Arene C−H Amination with Ammonia: A Practical and Regioselective Strategy for Primary Amines

AbstractIntroducing the primary amino group into aromatic ring is one of the most important study issues in organic chemistry, particularly for the pharmaceuticals and agrochemicals chemistry. Herein, we describe a photoinduced direct C−H amination of arenes with ammonia via the site‐selective C−H thianthrenation that forms a new C−N bond with excellent regioselectivity. The reaction is carried out under mild conditions, and with a wide range of functional group tolerance, such as sensitive −Cl, −Br, and −OH groups which are poorly tolerated in conventional approaches. Moreover, the synthetic utility of our amination protocol has been confirmed through late‐stage modification and gram‐scale synthesis of complex drug‐like molecules.

Intermolecular Dearomative 1,2-Amination/Carbonylation via Nucleophilic Addition of Simple Amines to Arene π-Bonds.

The incorporation of the privileged amino functionality is of paramount importance in organic synthesis. In contrast to the well-developed amination methods for alkenes, the dearomative amination of arenes is largely underexplored due to the inherently inert reactivity of arene π-bonds and selectivity challenges. Herein, we report an intermolecular dearomative aminofunctionalization via direct nucleophilic addition of simple amines to chromium-bound arenes. This multicomponent 1,2-amination/carbonylation reaction enables rapid access to complicated alicyclic compounds containing amino and amide functionalities from benzene derivatives under CO-gas-free conditions, which also represents the first application of nitrogen-based nucleophiles in η6-coordination-induced arene dearomatizations.

I(III)-Mediated Arene C–H Amination Using (Hetero)Aryl Nucleophiles

Herein, we report the metal-free oxidative C-H amination of arenes via a "heterocyclic group transfer" reaction from an I(III) N-HVI reagent. N-Heterocycles serve as oxidatively masked amine nucleophiles, and the resulting N-arylpyridinium salts are inert to further oxidation. The reaction proceeds under mild conditions, and mechanistic studies indicate the intermediacy of an arene radical cation. Derivatizations of the resulting pyridinium salts to diverse aryl amine scaffolds are demonstrated.

Copper-catalyzed amination of arene

<p indent="0mm">Aromatic amines are widely used in the fields of natural products, pharmaceutical chemistry and materials science, thus the new methods of metal-catalyzed C–N bond coupling for constructing aromatic amines always have always been the focus of attention of chemists and the scientific community. Copper, as a catalyst for the amination of arenes, has attracted extensive attention due to its unique catalytic performance and variety of oxidation states. In this review, the recent progress in the construction of aromatic compounds C(sp²)–N catalyzed by copper is reviewed, and the reaction mechanisms of representative amination reactions are briefly described.

Photoelectrocatalytic C–H amination of arenes

Reported herein is an organocatalyzed photoelectrochemical C(aryl)–H amination reaction for direct access to anilides from easily available and stable arenes and carbamates without the need for sacrificial oxidants.

Ortho-Selective amination of arene carboxylic acids via rearrangement of acyl O-hydroxylamines.

Direct amination of arene C-H bonds is an attractive disconnection to form aniline-derived building blocks. This transformation presents significant practical challenges; classical methods for ortho-selective amination require strongly acidic or forcing conditions, while contemporary catalytic processes often require bespoke directing groups and/or precious metal catalysis. We report a mild and procedurally straightforward ortho-selective amination of arene carboxylic acids, arising from a facile rearrangement of acyl O-hydroxylamines without requiring precious metal catalysts. A broad scope of benzoic acid substrates are compatible and the reaction can be applied to longer chain arene carboxylic acids. Mechanistic studies probe the specific requirement for trifluoroacetic acid in generating the active aminating agent, and suggest that two separate mechanisms may be operating in parallel in the presence of an iron catalyst: (i) an iron-nitrenoid intermediate and (ii) a radical chain pathway. Regardless of which mechanism is followed, high ortho selectivity is obtained, proposed to arise from the directivity (first) or attractive interactions (second) arising with the carboxylic acid motif.