Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids: C(sp³)–C(sp³) Cross-Coupling via Radical Sorting

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(14), С. 6185 - 6192

Опубликована: Март 30, 2022

Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, resulting open-shell intermediates can subsequently participate transition metal catalysis. In this report, we describe C(sp3)–C(sp3) cross-coupling of alcohols through dual combination N-heterocyclic carbene (NHC)-mediated deoxygenation hypervalent iodine-mediated decarboxylation. This mild practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array alkyl–alkyl cross-coupled products, including highly congested quaternary carbon centers from corresponding tertiary or acids. We demonstrate applications methodology alcohol C1-alkylation formal homologation, as well late-stage functionalization drugs, natural biomolecules.

Язык: Английский

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Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(13), С. 1637 - 1652

Опубликована: Янв. 23, 2023

Comprehensive Summary Alcohols are among the most accessible functionalities. Catalytic deoxygenative functionalization of alcohols is highly synthetically appealing. While significant progress has been made on reactions with nucleophiles, electrophilic coupling partners remain a real challenge. This manuscript highlights advance in this direction, which mainly achieved by first‐row transition metals. The low‐valent titanium catalyst shown unique reactivity to homolytically cleave C—OH bonds. formed carbon radicals could either undergo reduction give protonation products or couple fragments form C—C chemistry initially realized using stoichiometric amount reagents and later extended catalytic variants. Nickel features variety oxidation states ranging from Ni 0 IV , both two‐electron oxidative addition single‐electron process involved their activation an electrophile. These properties enable nickel catalyze reductive R–X electrophiles. reaction first reported allylic alcohols, then benzylic and, very recently non‐activated alcohols. Recent effort resulted many invaluable methodologies that improve efficiency for construction aliphatic use cobalt copper catalysts not only expands substrate scope these but also shows new selectivity issues.

Язык: Английский

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Alcohols as Alkylating Agents: Photoredox‐Catalyzed Conjugate Alkylation via In Situ Deoxygenation

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(35)

Опубликована: Июнь 21, 2022

The rapid exploration of sp

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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Electrochemically Driven Deoxygenative Borylation of Alcohols and Carbonyl Compounds

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(31), С. 16966 - 16972

Опубликована: Июль 27, 2023

We present a new, unified approach for the transformation of benzylic and allylic alcohols, aldehydes, ketones into boronic esters under electroreductive conditions. Key to our strategy is use readily available pinacolborane, which serves both as an activator electrophile by first generating redox-active trialkylborate species then delivering desired deoxygenatively borylated product. This applicable variety substrates can be employed late-stage functionalization complex molecules.

Язык: Английский

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Ni-catalyzed enantioconvergent deoxygenative reductive cross-coupling of unactivated alkyl alcohols and aryl bromides

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 28, 2024

Abstract Transition metal-catalyzed enantioconvergent cross-coupling of an alkyl precursor presents a promising method for producing enantioenriched C(sp 3 ) molecules. Because alcohol is ubiquitous and abundant family feedstock in nature, the direct reductive coupling aryl halide enables efficient access to valuable compounds. Although several strategies have been developed overcome high bond dissociation energy C − O bond, asymmetric pattern remains unknown. In this report, we describe realization deoxygenative unactivated (β-hydroxy ketone) bromide presence NHC activating agent. The approach can accommodate substituents various sizes functional groups, its synthetic potency demonstrated through gram scale reaction derivatizations into other compound families. Finally, apply our convergent synthesis four β-aryl ketones that are natural products or bioactive

Язык: Английский

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Structural Design of Single‐Atom Catalysts for Enhancing Petrochemical Catalytic Reaction Process

Advanced Materials, Год журнала: 2024, Номер 36(25)

Опубликована: Март 18, 2024

Abstract Petroleum, as the “lifeblood” of industrial development, is important energy source and raw material. The selective transformation petroleum into high‐end chemicals great significance, but still exists enormous challenges. Single‐atom catalysts (SACs) with 100% atom utilization homogeneous active sites, promise a broad application in petrochemical processes. Herein, research systematically summarizes recent progress SACs catalytic reaction, proposes role structural design enhancing performance, elucidates reaction mechanisms conversion processes, reveals high activity origins at atomic scale. Finally, key challenges are summarized an outlook on design, identification appropriate artificial intelligence technology provided for achieving scale‐up process.

Язык: Английский

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Visible-Light-Promoted Desulfurative Alkylation of Alkyl Thianthrenium Salts with Activated Olefins

Organic Letters, Год журнала: 2022, Номер 24(22), С. 4070 - 4074

Опубликована: Июнь 1, 2022

Reactions involving an alkyl radical generated from a primary alcohol by photochemistry are rare and challenging. Herein, we present photocatalyst- metal-free approach that enables the generation of corresponding subsequent C(sp3)-C(sp3) bond formation with activated olefin, via thianthrenium salt/Hantzsch ester electron donor-acceptor complex. This protocol for conversion C-OH to C-C is highly functionality tolerant can successfully be used in late-stage functionalization pharmaceuticals.

Язык: Английский

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Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(15), С. 1783 - 1790

Опубликована: Апрель 10, 2023

Comprehensive Summary Alcohols as among the most widely occurring organic compounds known, deoxygenative transformations of free alcohols partners in radical addition reactions remain formidable challenges with great opportunities to achieve new and useful transformations. Herein, we report a protocol via C—O bond cleavage C—C bond‐forming reaction trifluoromethyl alkenes assisted by titanium reagents strategy, enabling divergent synthesis for functional‐group‐rich organofluorinated high efficiencies. In this transformation, tertiary Ti‐catalysis could be converted alkanes without defluorination acidic conditions, while benzyl are employed Ti‐mediated activation supply gem ‐difluoroalkenes presence base. This is applicable broad range good functional group tolerance variety (including primary, secondary, alcohols), scalable gram level. Remarkably, utility demonstrated several derivatizations late‐stage functionalization drug molecules. The successful applications scale up molecules demonstrate its potential synthetic value discovery settings.

Язык: Английский

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Unlocking HFIP for Fluoroalkylation with Molecular Photoelectrocatalysis

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Despite the increasing interest in radical-based fluoroalkylation techniques, organofluorine compounds bearing partially fluorinated hexafluoroisopropyl group remain extremely scarce due to lack of appropriate reagents. Herein we report an unprecedented photoelectrocatalytic method for C-H hexafluoroisopropylation indoles and tryptophan peptides, utilizing readily available hexafluoro-2-propanol (HFIP) as reagent. In this process, HFIP is converted into radicals, enabling reactions. This study broadens potential applications molecular photoelectrocatalysis, highlighting its capacity enable transformations that are difficult accomplish through traditional electrochemical or photochemical approaches.

Язык: Английский

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