Nickel-catalyzed formation of quaternary carbon centers using tertiary alkyl electrophiles

Chemical Society Reviews, Год журнала: 2021, Номер 50(6), С. 4162 - 4184

Опубликована: Янв. 1, 2021

This review provides a comprehensive summary of recent advances in nickel-catalyzed reactions employing tertiary alkyl electrophiles for the construction quaternary carbon centers.

Язык: Английский

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Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(17), С. 9433 - 9438

Опубликована: Янв. 15, 2021

C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. glycosides are extensively investigated as drug candidates applied chemical biology studies. Previously, were derived from lactones, glycals, stannanes, halides, via methods displaying various limitations with respect the scope, functional-group compatibility, practicality. Challenges remain synthesis of nucleosides 2-deoxysugars easily accessible carbohydrate precursors. Herein, we report a cross-coupling method prepare heteroaryl glycosides, including 2-deoxysugars, esters bromoarenes. Activation substrates leverages dihydropyridine (DHP) an activating group followed by decarboxylation generate radical C-O bond homolysis. This strategy represents new means activate alcohols partner. The convenient preparation their exemplifies potential this medicinal chemistry.

Язык: Английский

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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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Aryl Radical Activation of C–O Bonds: Copper-Catalyzed Deoxygenative Difluoromethylation of Alcohols

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(26), С. 9952 - 9960

Опубликована: Июнь 28, 2021

Given their ubiquity in natural products and pharmaceuticals, alcohols represent one of the most attractive starting materials for construction C–C bonds. We report herein first catalytic strategy to harness reactivity aryl radicals activation C–O bonds alcohol-derived xanthate esters, allowing discovery deoxygenative difluoromethylation reaction. Under copper-catalyzed conditions, a wide variety alkyl readily synthesized from alcohol feedstocks, were activated by catalytically generated converted alkyl-difluoromethane via radical intermediates. This scalable protocol exhibits broad substrate scope functional group tolerance, enabling late-stage modification complex pharmaceutical agents. A one-pot has been developed that allows direct use free without purification esters. Mechanistic studies are consistent with hypothesis being formed initiating cleavage generate as key approach represents new cross-coupling partners.

Язык: Английский

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Control of Redox‐Active Ester Reactivity Enables a General Cross‐Electrophile Approach to Access Arylated Strained Rings**

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(33)

Опубликована: Июнь 11, 2022

Strained rings are increasingly important for the design of pharmaceutical candidates, but cross-coupling strained remains challenging. An attractive, underdeveloped, approach to diverse functionalized carbocyclic and heterocyclic frameworks containing all-carbon quaternary centers is coupling abundant strained-ring carboxylic acids with aryl halides. Herein we disclose development a nickel-catalyzed cross-electrophile that couples variety ring N-hydroxyphthalimide (NHP) esters, derived from acid in one step, various heteroaryl halides under reductive conditions. The chemistry enabled by discovery methods control NHP ester reactivity, tuning solvent or using modified

Язык: Английский

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Metal-catalysed C–C bond formation at cyclopropanes

Nature Reviews Chemistry, Год журнала: 2023, Номер 7(8), С. 548 - 560

Опубликована: Май 22, 2023

Язык: Английский

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Radical Deoxyfunctionalisation Strategies**

European Journal of Organic Chemistry, Год журнала: 2022, Номер 2022(26)

Опубликована: Май 10, 2022

Abstract Due to their abundance and readily available synthesis, alcohols provide ideal handles for the selective derivatisation of organic molecules. Radical chemistry offers versatile strategies conversion Csp 3 −O bonds into a wide range −C, −H, or −heteroatom bonds. In these reactions, are derivatised with an activator group which can undergo facile mesolysis generate primary, secondary, tertiary open‐shell species that engage in further transformations. These particularly effective at overcoming steric limitations associated nucleophilic substitution pathways. Despite potential, use radical deoxyfunctionalisation reactions as general strategy synthesis useful complex molecules remains underutilised. this Review, we highlight recent advancements exciting field photocatalysis, transition metal catalysis electrochemistry used initiate processes.

Язык: Английский

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Nickel-Catalyzed Carbonylation of Cyclopropanol with Benzyl Bromide for Multisubstituted Cyclopentenone Synthesis

Organic Letters, Год журнала: 2022, Номер 24(14), С. 2699 - 2704

Опубликована: Апрель 7, 2022

Herein, we reported a Ni-catalyzed carbonylation of cyclopropanol with benzyl bromide to afford multisubstituted cyclopentenone under 1 atm CO. The reaction proceeds through cascade bromides, followed by generation nickel homoenolate from cyclopropanols via β-C elimination 1,4-diketones, which undergoes intramolecular Aldol condensation furnish highly substituted derivatives in moderate good yields. exhibits high functional group tolerance broad substrate scope.

Язык: Английский

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Asymmetric Radical Bicyclization for Stereoselective Construction of Tricyclic Chromanones and Chromanes with Fused Cyclopropanes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(21), С. 11622 - 11632

Опубликована: Май 2, 2023

Asymmetric radical bicyclization processes have been developed via metalloradical catalysis (MRC) to stereoselectively construct chiral chromanones and chromanes bearing fused cyclopropanes. Through optimization of a versatile

Язык: Английский

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Asymmetric Divergent Synthesis of ent-Kaurane-, ent-Atisane-, ent-Beyerane-, ent-Trachylobane-, and ent-Gibberellane-type Diterpenoids

Journal of the American Chemical Society, Год журнала: 2022, Номер 145(1), С. 311 - 321

Опубликована: Дек. 20, 2022

A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations common synthons having ent-kaurane ent-trachylobane cores. The expeditious assembly crucial advanced ent-kaurane- ent-trachylobane-type building blocks is strategically explored through a regioselective diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization the alkene/enone 3-exo-trig alkene/ketone, showing multi-reactivity densely functionalized polycyclic substrates with πC═C πC═O systems in HAT-initiated reactions. Following rapid construction five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, ent-gibberellane-type), could be accessed longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 known γ-substituted cyclohexenone 2, which enantioselective total candol (A1, steps), powerol (A2, 9 sicanadiol (A3, 10 (A4, ent-atisan-16α-ol (A6, trachinol (A8, steps) are achieved for first time.

Язык: Английский

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