Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 7983 - 7991

Опубликована: Март 28, 2023

Conjugate addition is among the most important synthetic protocols for constructing carbon skeletons and widely used to synthesize natural products drugs. However, asymmetric catalysis studies have mainly focused on stereogenic centers arising from conjugate alkenes. Here, we report first photoinduced cobalt-catalyzed dynamic kinetic reductive reaction that enables formation of heterobiaryls with axial chirality (45 examples, up 91% yield 97% ee). This method features mild conditions, good functional-group tolerance, excellent enantiomeric control. Significantly, large amounts metal waste precious catalysts can be avoided under these conditions. Migration chiral arylcobalt species into alkene might rate-determining step based studies.

Язык: Английский

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Nickel-Catalyzed Enantioselective Reductive Arylation and Heteroarylation of Aldimines via an Elementary 1,4-Addition

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(15), С. 8498 - 8509

Опубликована: Апрель 6, 2023

Nickel catalysts of chiral pyrox ligands promoted enantioselective reductive arylation and heteroarylation aldimines, using directly (hetero)aryl halides sulfonates. The catalytic can also be conducted with crude aldimines generated from condensation aldehydes azaaryl amines. Mechanistically, density functional theory (DFT) calculations experiments pointed to an elementary step 1,4-addition aryl nickel(I) complexes N-azaaryl aldimines.

Язык: Английский

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Enantioselective Reductive (Hetero)Arylation of Cyclic N‐Sulfonyl Imines by Cobalt Catalysis

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(19)

Опубликована: Март 14, 2023

Transition-metal-catalyzed enantioselective addition of aryl organometallic reagents to imines has emerged as one the most powerful tools for formation optically active diarylmethylamines. Here, we report first asymmetric reductive (hetero)arylations using and heteroaryl halides enabled by a chiral cobalt-bisphosphine catalyst. This approach shows good functional group compatibility complements reported strategy without use reagents. Mechanistic investigations supported that aryl-cobalt, instead an arylzinc reagent, was formed in situ this aryl-addition event.

Язык: Английский

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NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of β- or γ-Branched Chiral Aromatic N-Heterocycles

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(40), С. 22122 - 22134

Опубликована: Сен. 25, 2023

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access a library of chiral β- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- atom-economies, generating two kinds products through one synthetic strategy. Furthermore, the possible mechanism extensively investigated using numerous control experiments density functional theory calculations.

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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Enantioselective Reductive Conjugate Alkenylation of α,β-Unsaturated Ketones and Amides via Nickel Catalysis

ACS Catalysis, Год журнала: 2024, Номер 14(8), С. 6228 - 6235

Опубликована: Апрель 10, 2024

Chiral nickel complexes promoted enantioselective reductive alkenylation of a range conjugated enones, using alkenyl bromides, triflates, and tosylates. The neutral condition was compatible with sensitive groups azaheteroaryl rings. Importantly, in products can be readily converted to functionalized alkyl via iron-catalyzed hydrofunctionalization. Some examples asymmetric N-enoyl pyrroles indoles were also included.

Язык: Английский

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Asymmetric reductive arylation and alkenylation to access S-chirogenic sulfinamides

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 15, 2025

The study of the stereochemistry organic sulfur compounds has been ongoing for over a century, with S-chirogenic pharmacophores playing an essential role in drug discovery within bioscience and medicinal chemistry. Traditionally, synthesis sulfinamides featuring stereogenic sulfur(IV) centers involves complex, multistep process that often depends on chiral auxiliaries or kinetic resolution. Here, we introduce effective versatile method synthesizing diverse classes through selective aryl alkenyl addition to sulfinylamines. This is catalysed by nickel cobalt complex under reductive conditions, eliminating need preformed organometallic reagents. facilitates incorporation array halides at position, enabling their integration into various biologically significant pharmacophores. Our detailed mechanistic investigations density functional theory calculations provide insights reaction pathway, particularly highlighting enantiocontrol mode during process. play authors report methodology asymmetric sulfinylamines via common-Earth-metal catalysis.

Язык: Английский

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Chromium‐ and Metal‐Reductant‐Free Asymmetric Nozaki–Hiyama–Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(37)

Опубликована: Июнь 25, 2024

Abstract Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki–Hiyama–Kishi (NHK) reaction is a widely used method for synthesis of alcohols, it suffers drawbacks such as use toxic chromium salts, high amounts metal reductants, poor enantiocontrol. To address these limitations, we present novel approach involving metallaphotoredox‐catalyzed asymmetric NHK production chiral alcohols. This marries (pseudo)halides with aldehydes, leveraging synergistic blend nickel catalyst photocatalyst. innovative technique enables oxidative addition insertion just using nickel, diverging significantly conventional pathway mediated by salts. The adoption this methodology holds immense promise crafting spectrum intricate compounds, particularly those significance pharmaceuticals. Detailed experimental investigations have shed light on metallaphotoredox process, further enhancing our understanding enabling advancements.

Язык: Английский

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Cu-Catalyzed Asymmetric Three-Component Radical Acylarylation of Vinylarenes with Aldehydes and Aryl Boronic Acids

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(47), С. 32235 - 32242

Опубликована: Ноя. 13, 2024

The direct use of readily available aldehydes as acyl radical precursors has facilitated diverse three-component acylative difunctionalization reactions alkenes, offering a powerful route to synthesize β-branched ketones. However, asymmetric alkenes with still remains elusive. Here we report copper-catalyzed acylarylation vinylarenes and aryl boronic acids. This method begins formation from an aldehyde via hydrogen atom transfer. adds the alkene, forming new benzylic that then undergoes enantioselective arylation. A chiral binaphthyl-tethered bisoxazoline ligand is essential for achieving high stereocontrol. strategy enables synthesis range synthetically valuable β,β-diaryl ketones vinylarenes.

Язык: Английский

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10-Step, Gram-Scale Total Synthesis of (−)-Bipinnatin J

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

A concise, scalable total synthesis of (-)-bipinnatin J is disclosed. Commencing from inexpensive starting materials, this marine diterpenoid was fashioned through a convergent enabled by Ni-electrocatalytic decarboxylative cross-coupling taking advantage succinate as an ethylene 2-carbon bridge, unique halogen dance-Zweifel sequence to access trisubstituted furan, Ni-mediated 1,6-conjugate addition, and asymmetric proton transfer.

Язык: Английский

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