Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

ConspectusN-Heterocycles are essential in pharmaceutical engineering, materials science, and synthetic chemistry. Recently, skeletal editing, which involves making specific point changes to the core of a molecule through single-atom insertion, deletion, or transmutation, has gained attention for its potential modify complex substrates. In this context, insertion nitrogen atoms into carbocycles form N-heterocycles emerged as significant research focus modern chemistry owing novel logic. This distinctive retrosynthetic approach enables late-stage modification molecular skeletons provides different pathway synthesizing multiply substituted N-heterocycles. Nevertheless, atom proven challenging because inherent inertness carbon-based difficulty cleaving C-C bonds. Therefore, selective editing remains growing field Account primarily highlights contributions our laboratory active acknowledges key from other researchers. It is organized two sections based on type carbocycle. The first section explores cycloalkenes. Recent Co-catalyzed oxidative azidation strategies have enabled cyclobutenes, cyclopentenes, cyclohexenes, facilitating synthesis polysubstituted pyridines, been conventionally pyridine cross-coupling. subsequent discovery realm arenes. site-selective stable arenes We developed method intramolecular benzene rings 2-amino biaryls by suppressing competing C-H process using paddlewheel dirhodium catalyst. addition, address issues we employed arenols substrates, could act controlling elements editing. reported Cu-catalyzed arenols, proceeds dearomative azidation/aryl migration process, enabling incorporation Inspired result, recently extended reaction model Fe-catalyst facilitate ring contraction nitrogen-inserted product, achieving carbon-to-nitrogen transmutation arenols. Various polyaromatic effectively undergo desired atom's presenting considerable various applications Account, present an overview achievements reactions, with scopes, mechanistic features, applications. anticipate that will provide valuable insights propel development innovative methodologies both N-heterocycle synthesis.

Язык: Английский

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Reductive Amination of Carbonyl C–C Bonds Enables Formal Nitrogen Insertion

The Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 7, 2024

Given its relevance across numerous fields, reductive amination is one of the oldest and most widely used methods for amine synthesis. As a cornerstone synthetic chemistry, it has largely remained unchanged since discovery over century ago. Herein, we report mechanistically driven development complementary reaction, which reductively aminates C-C σ-bond carbonyls, not carbonyl C-O π-bond, generating value-added linear cyclic 3° amines in modular fashion. Critical to our success were mechanistic insights that enabled us modulate resting state borane catalyst, minimize deleterious disproportionation hydroxylamine nitrogen source, control migratory selectivity key nitrenoid reactive intermediate. Experiments support reaction occurring through amination/reductive Stieglitz cascade, via ketonitrone, can be interrupted under catalyst generate valuable

Язык: Английский

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Molecular Ring Remodeling through C–C Bond Cleavage

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

ConspectusStable and inert C-C bonds form the fundamental framework of organic compounds. Consequently, direct transformations involving bond cleavage present an innovative approach for rapid modification remodeling molecular skeletons. In recent years, concept skeletal editing has garnered widespread attention been significantly developed, providing new opportunities late-stage bioactive molecules, high-value transformation bulk chemicals, a revolution in traditional fragment coupling strategies chemical synthesis. Notable advancements this field have focused on cyclic including ring expansion, contraction, ring-opening reactions, thereby enriching synthetic toolbox available to chemists. However, selective remains formidable challenge, especially complex due high dissociation energy difficulty achieving precise selectivity control. Over past few our group made efforts address these challenges. We demonstrated potential molecule reactions as efficient strategy synthesis molecules.Herein, we two major thematic achieved by group, utilizing cascade activation entropy-driven reconstruction via cleavage. These are characterized mild conditions, accessibility catalysts reagents, exceptional functional compatibility, emerging novel approaches through atom-incorporation mainly nitrogenation, oxygenation, halogenation synthesize pharmaceuticals, natural products, material molecules. (1) Ring expansion reactions: developed that enable insertion C-, N-, O-containing units into rings. methodologies offer practical routes synthesizing amides, amines, lactones, nitrogen-containing heterocycles. (2) Ring-opening enables construction distally difunctionalized frameworks. By transition metal catalysis radical-mediated process, successfully both single C═C double within Furthermore, tackled highly challenging arene (ARO) reaction, enabling stereoselective conjugated systems unsaturation liberation aromatic systems. Mechanistic studies DFT calculations provided critical insights processes. also identified key intermediates involved cleavage, benzyl azide, O-acetyl hydroxylamine, β-azido peroxyl radical, copper bisnitrene, 2-nitrene indazole. findings deepened understanding mechanisms strategy, which further promoted discovery related acyclic substrates.

Язык: Английский

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A novel hydroxytyrosol derivative HT-3 enhances antioxidant and neuroprotective activity through efficient molecular conjugation

Bioorganic Chemistry, Год журнала: 2025, Номер 161, С. 108484 - 108484

Опубликована: Апрель 23, 2025

Язык: Английский

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Copper‐Catalyzed Aromatization‐Driven Ring‐Opening Amination and Oxygenation of Spiro Dihydroquinazolinones

Chemistry - A European Journal, Год журнала: 2024, Номер 30(58)

Опубликована: Авг. 8, 2024

Abstract Mild and inexpensive copper‐catalyzed aromatization‐driven ring‐opening amination oxygenation of spiro dihydroquinazolinones are presented, respectively. These protocols provide facile atom‐economical access to the aminated carbonyl‐containing quinazolin‐4(3 H )‐ones in good yields with functional group compatibility, which difficult obtain by conventional methods. Remarkably, a telescoped procedure involving condensation ring‐opening/functionalization for simple cycloalkanone was found be accessible. Mechanistic studies suggest radical pathway this transformation.

Язык: Английский

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