Nickel-Catalyzed Ligand-Controlled Selective Reductive Cyclization/Cross-Couplings

Accounts of Chemical Research, Год журнала: 2023, Номер 56(5), С. 515 - 535

Опубликована: Янв. 23, 2023

ConspectusThe use of quaternary stereocenters during lead candidate optimization continues to grow because improved physiochemical and pharmacokinetic profiles compounds with higher sp3 fraction. Pd-catalyzed redox-neutral alkene difunctionalization involving carbopalladation alkenes followed by nucleophilic-trapping σ-alkyl-palladium intermediates has been developed as an efficient method construct stereocenters. However, the low chemoselectivity air sensitivity organometallic nucleophiles, well their availability accessibility, limit scope application this elegant strategy. Recently, Ni-catalyzed reductive cross-coupling evolved into a privileged strategy easily valuable C(sp3)-C bonds. Despite great progress, enantioselective coupling C(sp3) electrophiles still relies on activated or functionalized alkyl precursors, which are often unstable require multiple steps prepare. Therefore, via selective cyclization/cross-coupling was developed. This not only offers robust practical alternative for traditional but also provides strategic complementarity electrophiles. In Account, we summarize latest results from our laboratory topic. These findings mainly include explorations in modulating enantioselectivity cyclization mode cyclization/cross-couplings.We will first discuss chiral heterocycles focus effects ligands, reductants, additives roles cross-coupling. A wide range have explored, including aryl halides, vinyl alkynyl gem-difluoroalkenes, CO2, trifluoromethyl alkenes, cyano The synthetic potential approach demonstrated synthesis biologically active natural products drug molecules. Second, detail how tune steric nickel catalysts modifying bipyridine ligands regiodivergent cyclization/cross-couplings. Specifically, bidentate favors exo-selective cyclization/cross-coupling, while carboxylic acid-modified ligand permits endo-selective cyclization/cross-coupling. We show activate amide substrate altering electronic properties substituents nitrogen, thereby enabling nucleophilic addition halides carbonyls. Further investigation led tunable cyclization/cross-couplings (addition carbonyl vs 7-endo-cyclization) divergent pharmacologically important 2-benzazepine frameworks. Finally, serendipitously discover that changing oxidation state can control migratory aptitude different groups, thus providing switchable skeletal rearrangement transformation is high value it represents conceptually unprecedented new C-C bond activation. Thus, Account summarizes methods allow formation using variety insight relationship between structure, substrate, selectivity.

Язык: Английский

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Interrogating the Mechanistic Features of Ni(I)-Mediated Aryl Iodide Oxidative Addition Using Electroanalytical and Statistical Modeling Techniques

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(15), С. 8689 - 8699

Опубликована: Апрель 4, 2023

While the oxidative addition of Ni(I) to aryl iodides has been commonly proposed in catalytic methods, an in-depth mechanistic understanding this fundamental process is still lacking. Herein, we describe a detailed study using electroanalytical and statistical modeling techniques. Electroanalytical techniques allowed rapid measurement rates for diverse set iodide substrates four classes catalytically relevant complexes (Ni(MeBPy), Ni(MePhen), Ni(Terpy), Ni(BPP)). With >200 experimental rate measurements, were able identify essential electronic steric factors impacting through multivariate linear regression models. This led classification mechanisms, either three-center concerted or halogen-atom abstraction pathway based on ligand type. A global heat map predicted was created shown applicable better reaction outcome case Ni-catalyzed coupling reaction.

Язык: Английский

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Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

Chemical Reviews, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Язык: Английский

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Nickel-Catalyzed Three-Component Alkylacylation of Alkenes Enabled by a Photoactive Electron Donor–Acceptor Complex

Organic Letters, Год журнала: 2022, Номер 24(22), С. 3938 - 3943

Опубликована: Май 23, 2022

An electron donor-acceptor complex-enabled, nickel-catalyzed three-component net-reductive 1,2-alkylacylation of alkenes is developed. This conjunctive reductive acyl cross-coupling process obviates the use an exogenous photocatalyst and a stoichiometric metal-based reductant, affording various synthetically useful 1,3-dicarbonyl compounds in good yields with broad substrate scope excellent functional group tolerance. Both alkyl electrophiles are derived from highly abundant readily accessible carboxylic acids, making catalytic 1,2-dicarbofunctionalization more general sustainable.

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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Nickel-Catalyzed Asymmetric Cross-Electrophile trans-Aryl-Benzylation of α-Naphthyl Propargylic Alcohols

ACS Catalysis, Год журнала: 2023, Номер 13(10), С. 6795 - 6803

Опубликована: Май 3, 2023

Herein, we report a nickel-catalyzed asymmetric three-component trans-dicarbofunctionalization of β-substituted α-naphthyl propargylic alcohols using readily available aryl and benzyl halides as the coupling partners under reductive conditions. This cross-electrophile strategy enables synthesis various axially chiral allylic bearing tetrasubstituted olefinic unit in complete regio- E selectivity, well high enantiocontrol. Relying on hydroxyl group functional handle, such structural motifs are successfully derivatized into diverse functional-group-rich alkenes.

Язык: Английский

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Nickel-Catalyzed Hydrocarbamoylation of Alkenes with Isocyanates

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

The hydrocarbamoylation of alkenes with isocyanates is a promising method for synthesizing amides. However, applying this strategy to more inert, simple alkenes, such as styrenes, α-olefins, and internal poses significant challenges. Here, we report the first nickel-catalyzed isocyanates, facilitated by triethoxysilane reduce nickelacycle intermediates. By switching ligands─including 6,6′-dimethyl-2,2′-bipyridine N-heterocyclic carbene─this efficiently produces amides from diverse array including gaseous olefins.

Язык: Английский

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Synthesis of Multisubstituted Allenes via Nickel-Catalyzed Cross-Electrophile Coupling

ACS Catalysis, Год журнала: 2021, Номер 11(21), С. 13355 - 13362

Опубликована: Окт. 19, 2021

In this context, we report the successful application of a cross-electrophile strategy in synthesis multisubstituted allenes. Under catalysis nickel, reductive cross-coupling between propargyl carbonates and organoiodides provides an entry to prepare tri- or tetrasubstituted allenes without employing any pregenerated organometallics. Furthermore, also prove be suitable allenylating agents nickel-catalyzed asymmetric aryl-allenylation aryl-iodide-tethered unactivated alkenes, furnishing variety chiral benzene-fused cyclic compounds bearing quaternary allenyl-substituted stereogenic center highly enantioselective manner.

Язык: Английский

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Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

RSC Advances, Год журнала: 2024, Номер 14(21), С. 14539 - 14581

Опубликована: Янв. 1, 2024

The synthesis of dihydrobenzofuran scaffolds bears pivotal significance in the field medicinal chemistry and organic synthesis. These heterocyclic hold immense prospects owing to their significant pharmaceutical applications as they are extensively employed essential precursors for constructing complex frameworks. Their versatility importance make them an interesting subject study researchers scientific community. While exploring synthesis, have unveiled various novel efficient pathways assembling core. In wake extensive data being continuously reported each year, we outlined recent updates (post 2020) on methodological accomplishments employing catalytic role several transition metals forge functionalities.

Язык: Английский

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Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(11), С. 7741 - 7746

Опубликована: Май 14, 2024

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade undergoes a sequence oxidative addition, unsaturated bond migration, carbonyl insertion, nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines aliphatic could proceed smoothly in this transformation under one atm CO.

Язык: Английский

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