Radical Polarity

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Окт. 3, 2024

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence predict effects, the electrophilicity/nucleophilicity >500 radicals has been calculated. This database open-shell species entails frequently encountered synthetic intermediates, including centered at sp

Язык: Английский

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A General Photocatalytic Strategy for Nucleophilic Amination of Primary and Secondary Benzylic C–H Bonds

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(33), С. 18487 - 18496

Опубликована: Авг. 11, 2023

We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp3)-H bonds. A novel amidyl radical precursor organic photocatalyst operate in tandem to transform bonds into carbocations via sequential hydrogen atom transfer (HAT) oxidative radical-polar crossover. The resulting carbocation can be intercepted by variety N-centered nucleophiles, including nitriles (Ritter reaction), amides, carbamates, sulfonamides, azoles, for the construction pharmaceutically relevant C(sp3)-N under unified reaction conditions. Mechanistic studies indicate HAT is radical-mediated operates reductive quenching pathway. These findings establish mild, metal-free, modular protocol rapid diversification library aminated products.

Язык: Английский

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Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer

Molecules, Год журнала: 2023, Номер 28(16), С. 6127 - 6127

Опубликована: Авг. 18, 2023

The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple equivalents for synthons. Hydrogen atom transfer (HAT) is a key method forming alkyl radicals from substrates. Classic reactions, including the Barton nitrite ester reaction Hofmann–Löffler–Freytag reaction, among others, provided early examples HAT. However, recent developments photoredox catalysis electrochemistry have made HAT powerful tool capable introducing wide range functional groups into bonds. Moreover, greater mechanistic insights stimulated development increasingly site-selective protocols. Site-selectivity can be achieved through tuning electron density at certain using additives, judicious choice reagent, solvent system. Herein, we describe latest methods functionalizing C–H/Si–H/Ge–H indirect between 2018–2023, as well critical discussion reagents, aspects, substrate scopes, background contexts

Язык: Английский

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Dual Nickel/Photoredox‐Catalyzed Asymmetric Carbamoylation of Benzylic C(sp³)−H Bonds

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(12)

Опубликована: Янв. 12, 2024

Abstract Radical‐mediated Hydrogen Atom Abstraction of Csp 3 −H bonds has become a powerful tool for the asymmetric functionalization organic feedstocks. Here, we present an synthesis α ‐aryl amides via carbamoylation alkylarenes with isocyanates as electrophiles. The synergistic combination photoredox and chiral nickel‐catalyst, enables use readily available neutral reagents under mild reaction conditions provides straightforward access to pharmacologically relevant motifs in enantiomerically pure form.

Язык: Английский

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Recent Advances in Cyclization Reactions of 1,6‐Enynes

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(6), С. 1220 - 1268

Опубликована: Янв. 22, 2024

Abstract Elaborated molecular architectures, specifically those bearing one or more carbon stereocenters, stand as an important class of carbocyclic and heterocyclic frameworks because they are frequently occurring core structures in numerous natural products biologically active pharmaceutical molecules. Over the past few decades, development versatile synthetic approaches via cascade cyclization reactions 1,6‐enynes for construction a series fused spiro compounds has been focus great deal research initiatives. These synthesis strategies peculiarly fascinating context assembly wide array molecules, products, agrochemicals, functional materials. In this review, recent developments transformations with diverse coupling reagents summarized since 2018, which could be divided into five categories: 1) Introduction; 2) Transition metal catalyzed 1,6‐enynes; 3) Metal‐free 4) Visible‐light‐induced 5) Electrocatalytic 1,6‐enynes.

Язык: Английский

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Unified approaches in transition metal catalyzed C(sp³)–H functionalization: recent advances and mechanistic aspects

Chemical Society Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Direct alteration of unactivated C–H bonds organic building blocks.

Язык: Английский

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Polar Heterobenzylic C(sp³)–H Chlorination Pathway Enabling Efficient Diversification of Aromatic Nitrogen Heterocycles

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(36), С. 19832 - 19839

Опубликована: Авг. 29, 2023

Site-selective radical reactions of benzylic C–H bonds are now highly effective methods for C(sp3–H) functionalization and cross-coupling. The existing methods, however, often ineffective with heterobenzylic in alkyl-substituted pyridines related aromatic heterocycles that prominently featured pharmaceuticals agrochemicals. Here, we report new synthetic leverage polar, rather than radical, reaction pathways to enable the selective chlorination 2- 4-alkyl-substituted other heterocycles. Catalytic activation substrate trifluoromethanesulfonyl chloride promotes formation enamine tautomers react readily electrophilic reagents. resulting heterobenzyl chlorides can be used without isolation or purification nucleophilic coupling reactions. This chlorination–diversification sequence provides an efficient strategy achieve cross-coupling aliphatic amines a diverse collection azoles, among partners.

Язык: Английский

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Late-Stage Isotopic Exchange of Primary Amines

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(44), С. 24367 - 24374

Опубликована: Окт. 27, 2023

Stable isotopes such as 2H, 13C, and 15N have important applications in chemistry drug discovery. Late-stage incorporation of uncommon via isotopic exchange allows for the direct conversion complex molecules into their valuable isotopologues without requiring a de novo synthesis. While synthetic methods exist hydrogen carbon atoms less abundant isotopes, corresponding method accessing 15N-primary amines from naturally occurring 14N-analogues has not yet been disclosed. We report an approach to access 15N-labeled primary late-stage using simple benzophenone imine source. By activating α-1 α-2° Katritzky pyridinium salts α-3° redox-active imines, we can engage alkyl deaminative amination. The imines proceed radical-polar crossover mechanism, whereas are engaged copper catalysis electron donor–acceptor complex. is general variety amines, including multiple compounds, results complete selective labeling.

Язык: Английский

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Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(27), С. 14573 - 14580

Опубликована: Июнь 30, 2023

Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, enantiocontrol. The observed N2:N1 regioselectivity favors the more hindered nitrogen of pyrazole. Experimental DFT studies support a unique mechanism that features five-centered aminocupration.

Язык: Английский

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Accelerated Electrophotocatalytic C(sp³)−H Heteroarylation Enabled by an Efficient Continuous‐Flow Reactor**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(52)

Опубликована: Ноя. 17, 2023

Electrophotocatalytic transformations are garnering attention in organic synthesis, particularly for accessing reactive intermediates under mild conditions. Moving these methodologies to continuous-flow systems, or flow ElectroPhotoCatalysis (f-EPC), showcases potential scalable processes due enhanced irradiation, increased electrode surface, and improved mixing of the reaction mixture. Traditional methods sequentially link photochemical electrochemical reactions, using reactors connected series, yet struggle accommodate transient species. In this study, we introduce a new reactor concept electrophotocatalysis (EPC) that simultaneously utilizes photons electrons. The is designed with transparent employs cost-effective materials. We used technology develop an efficient process electrophotocatalytic heteroarylation C(sp3 )-H bonds. Importantly, same setup can also facilitate purely transformations. This represents significant advancement electrophotocatalysis, providing framework its application complex synthetic

Язык: Английский

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