Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9045 - 9062

Опубликована: Март 15, 2024

Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite development many methods amine preparation, C(sp3)-rich nitrogen-containing compounds continue pose challenges synthesis. While carbonyl reductive amination (CRA) between ketones and is cornerstone method alkylamine synthesis, it sometimes limited by sterically demanding condensation step dialkyl amines more restricted availability compared aldehydes. We recently reported a "higher-order" variant this transformation, alkylative (CAA), which utilized halogen atom transfer (XAT)-mediated radical mechanism, enabling streamlined complex alkylamines. efficacy visible-light-driven approach, displayed scalability issues, competitive was problem certain substrate classes, limiting applicability. Here, we report change reaction regime that expands CAA platform through realization an extremely broad zinc-mediated reaction. This new strategy enabled elimination CRA, simplified purification, improved scope. Furthermore, harnessed carboxylic acid derivatives as alkyl donors facilitated α-trialkyl tertiary amines, cannot be accessed via CRA. Zn-mediated can carried out at variety scales, from 10 μmol setup microtiter plates high-throughput experimentation, gram-scale medicinally-relevant compounds. believe transformation enables robust, efficient, economical access provides viable alternative current benchmark methods.

Язык: Английский

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Chemical versatility of azide radical: journey from a transient species to synthetic accessibility in organic transformations

Chemical Society Reviews, Год журнала: 2022, Номер 51(6), С. 2255 - 2312

Опубликована: Янв. 1, 2022

This review describes the characteristic features of simple and nascent N-centered azide radical, its unique reactivity in fine chemical synthesis with detailed mechanistic discussions.

Язык: Английский

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Remote and Proximal Hydroaminoalkylation of Alkenes Enabled by Photoredox/Nickel Dual Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(39), С. 17776 - 17782

Опубликована: Сен. 22, 2022

A mild and site-selective hydroaminoalkylation of activated unactivated alkenes via dual photoredox/Ni catalysis is developed. This catalytic strategy enables exclusive access to α-selective products, which complementary previously reported photocatalytic that provides the β-selective products. The chain-walking a Ni–H intermediate toward carbonyl allows for at remote sp3 C–H sites. method tolerates broad substrate scope both amines as well providing streamlined synthesis value-added β-amino acid derivatives from readily available starting materials.

Язык: Английский

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Photocatalyzed Cascade Reactions of Cyclopropanols and α‐Trifluoromethyl‐Substituted Olefins for the Synthesis of Fused gem‐Difluorooxetanes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(44)

Опубликована: Сен. 16, 2022

Fluorinated fused rings are challenging to construct from simple starting materials. Herein, we report the first photocatalyzed cascade reactions of readily available cyclopropanols and α-trifluoromethyl-substituted olefins for synthesis gem-difluorooxetanes. Two three bonds were efficiently constructed in one reaction. The reaction showed broad substrate scope downstream transformations products demonstrated synthetic potential mechanistic study supported presence photoredox catalysis energy transfer catalysis/direct photo-excitation processes.

Язык: Английский

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Hydroaminoalkylation for the Catalytic Addition of Amines to Alkenes or Alkynes: Diverse Mechanisms Enable Diverse Substrate Scope

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(26), С. 11459 - 11481

Опубликована: Июнь 22, 2022

Hydroaminoalkylation is a powerful, atom-economic catalytic reaction for the of amines with alkenes and alkynes. This C–H functionalization allows alkylation using simple or alkynes as alkylating agents. transformation has significant potential transformative approaches in pharmaceutical, agrochemical, fine chemical industries preparation selectively substituted N-heterocycles shows promise materials science synthesis functional responsive aminated materials. Different early transition-metal, late photoredox catalysts mediate hydroaminoalkylation by distinct mechanistic pathways. These insights have resulted development new conditions to realize broad range substrates: activated unactivated, terminal internal, C–C double triple bonds aryl alkyl primary, secondary, tertiary amines, including N-heterocyclic amines. By deploying select specific substrate combinations, control over regioselectivity, diastereoselectivity, enantioselectivity been realized. Key barriers widespread adoption this include air moisture sensitivity transition-metal well heavy dependence on amine protecting directing groups photocatalytic routes. Advances improved catalyst robustness, scope, regio-/stereoselective reactions early- catalysts, catalysis, are highlighted, opportunities further included. perspective that be disruptive strategy from alkenes.

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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Visible Light Photoredox-Catalyzed Decarboxylative Alkylation of 3-Aryl-Oxetanes and Azetidines via Benzylic Tertiary Radicals and Implications of Benzylic Radical Stability

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(10), С. 6476 - 6488

Опубликована: Март 3, 2023

Four-membered heterocycles offer exciting potential as small polar motifs in medicinal chemistry but require further methods for incorporation. Photoredox catalysis is a powerful method the mild generation of alkyl radicals C–C bond formation. The effect ring strain on radical reactivity not well understood, with no studies that address this question systematically. Examples reactions involve benzylic are rare, and their challenging to harness. This work develops functionalization oxetanes azetidines using visible light photoredox prepare 3-aryl-3-alkyl substituted derivatives assesses influence heterosubstitution small-ring radicals. 3-Aryl-3-carboxylic acid suitable precursors tertiary oxetane/azetidine which undergo conjugate addition into activated alkenes. We compare oxetane other systems. Computational indicate Giese additions unstrained acrylates reversible result low yields dimerization. Benzylic part strained ring, however, less stable more π-delocalized, decreasing dimer increasing product Oxetanes show high due Bent's rule rendering irreversible.

Язык: Английский

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Visible-light induced direct C(sp³)–H functionalization: recent advances and future prospects

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(18), С. 5278 - 5305

Опубликована: Янв. 1, 2024

This review summarizes the latest methodological advances in photocatalytic C(sp 3 )–H functionalization, with a particular emphasis on formation of C–P, C–B, C–S bonds, etc ., and some prominent efforts asymmetric C–H functionalization.

Язык: Английский

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Wastewater reuse and pharmaceutical pollution in agriculture: Uptake, transport, accumulation and metabolism of pharmaceutical pollutants within plants

Chemosphere, Год журнала: 2024, Номер 364, С. 143055 - 143055

Опубликована: Авг. 9, 2024

The presence of pharmaceutical pollutants in water sources has become a growing concern due to its potential impacts on human health and other organisms. physicochemical properties pharmaceuticals based their intended therapeutical application, which include antibiotics, hormones, analgesics, antidepressants, is quite diverse. Their wastewater, sewerage water, surface ground even drinking reported by many researchers throughout the world. Human exposure these through or consumption aquatic terrestrial organisms raised concerns about adverse effects, such as endocrine disruption, antibiotic resistance, developmental abnormalities. Once environment, they can persist, undergo transformation, degrade, leading complex mixture contaminants. Application treated compost, manures biosolids agricultural fields introduce environment. As are diverse nature, significant differences observed during uptake accumulation plants. While there have been extensive studies ecosystems, effect land more disparate. now, few reports available plant transportation within between organs. This review summarizes occurrence bodies at range concentrations uptake, accumulation, transport tissues. Research gaps pollutants' specific growth future research scopes highlighted. factors affecting including hydrophobicity, ionization, (pKa, logK

Язык: Английский

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Photocatalytic carboxylation of styrenes with CO2 via C=C double bond cleavage

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION), Год журнала: 2024, Номер 56, С. 74 - 80

Опубликована: Янв. 1, 2024

Язык: Английский

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