Cobalt‐Catalyzed Enantioselective Reductive α‐Chloro‐Carbonyl Addition of Ketimine to Construct the β‐Tertiary Amino Acid Analogues

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(25)

Опубликована: Янв. 22, 2024

β-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, efficient asymmetric synthesis this motif still remains a significant challenge. Herein, we disclose cobalt-catalyzed enantioselective reductive addition reaction ketimine using α-chloro carbonyl compound as radical precursor, providing expedient access to diverse array enantioenriched β-quaternary analogues. This protocol exhibits outstanding enantioselectivity broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out possibility Reformatsky-type confirm involvement species stereoselective process. The synthetic utility has been demonstrated through rapid assembly iterative oligopeptide, showcasing its versatile platform for late-stage modification drug candidates.

Язык: Английский

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Mechanism and Origin of Stereoselectivity for the NHC-Catalyzed Desymmetrization Reaction for the Synthesis of Axially Chiral Biaryl Aldehydes

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(5), С. 3133 - 3142

Опубликована: Фев. 15, 2024

Organocatalytic desymmetrization reaction is a powerful tool for constructing axial chirality, but the theoretical study on origin of stereoselectivity still lags behind even now. In this work, N-heterocyclic carbene (NHC)-catalyzed biaryl frameworks synthesis axially chiral aldehydes has been selected and theoretically investigated by using density functional theory (DFT). The fundamental pathway involves several steps, i.e., desymmetrization, formation Breslow oxidation, esterification, NHC regeneration. processes have identified as stereoselectivity-determining rate-determining steps. Further weak interaction analyses proved that C–H···O hydrogen bond C–H···π interactions are responsible stability key stereoselective transition states. This research contributes to understanding nature NHC-catalyzed reactions compounds.

Язык: Английский

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Enantioselective synthesis of molecules with multiple stereogenic elements

Chemical Society Reviews, Год журнала: 2024, Номер 53(22), С. 11165 - 11206

Опубликована: Янв. 1, 2024

This review explores the fascinating world of molecules featuring multiple stereogenic elements, unraveling different strategies designed over years for their enantioselective synthesis.

Язык: Английский

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Nickel-Catalyzed Enantioselective Reductive Arylation of Common Ketones

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(19), С. 12895 - 12900

Опубликована: Май 2, 2024

A nickel complex of chiral bisoxazolines catalyzed the stereoselective reductive arylation ketones in high enantioselectivity. range common acyclic and cyclic reacted without aid directing groups. Mechanistic studies using isolated a bis(oxazoline) (L)Ni(Ar)Br revealed that Mn reduction was not needed, while Lewis acidic titanium alkoxides were critical to ketone insertion.

Язык: Английский

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Visible-Light-Induced Redox-Neutral Difunctionalization of Alkenes and Alkynes

Chemical Communications, Год журнала: 2024, Номер 60(72), С. 9659 - 9691

Опубликована: Янв. 1, 2024

The twelve principles of green chemistry illuminate the pathway in direction sustainable and eco-friendly synthesis, marking a fundamental shift synthetic organic paradigms. In this realm, harnessing power visible light for difunctionalization various skeletons without employing any external oxidant or reductant, specifically termed as redox-neutral difunctionalization, has attracted tremendous interest from chemists due to its low cost, easy availability environmentally friendly nature contrast traditional metal-catalyzed difunctionalizations. This review presents an overview recent updates on visible-light-induced reactions with literature coverage up May 2024.

Язык: Английский

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Enantioselective Rhodium‐Catalyzed C−H Arylation Enables Direct Synthesis of Atropisomeric Phosphines

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(8)

Опубликована: Янв. 6, 2024

Atropisomeric phosphines hold considerable significance in asymmetric catalysis, yet their synthesis presents a formidable challenge owing to intricate multistep procedures. In this context, groundbreaking methodology has been presented for preparation. This innovative approach entails an atroposelective rhodium-catalyzed C-H activation employing aryl and heteroaryl halides, chelated by P(III) center. The essence of strategy lies its ability directly construct chiral phosphine ligands single step, thereby exhibiting exceptional efficiency terms atom redox economy. Illustrative examples serve demonstrate the immense potential situ-formed catalysis. Mechanistic experiments have further provided invaluable insights into transformation.

Язык: Английский

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Atroposelective Synthesis of Axially Chiral Diaryl Ethers by N-Heterocyclic-Carbene-Catalyzed Sequentially Desymmetric/Kinetic Resolution Process

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(6), С. 4067 - 4073

Опубликована: Фев. 23, 2024

We describe herein an N-heterocyclic-carbene-catalyzed atroposelective synthesis of axially chiral diaryl ethers. Through a sequentially enantioselective desymmetric process and kinetic resolution process, the products could be constructed in good yields with excellent enantiopurities. Both alcohols phenols were compatible this catalytic system. The carboxylic acids derived from esters proven to potential ligands for asymmetric synthesis, example, Rh(III)-catalyzed C–H functionalization.

Язык: Английский

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Cobalt‐Catalyzed Enantioselective Alkenylation of Aldehydes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(33)

Опубликована: Май 31, 2024

Catalytic enantioselective alkenylation of aldehydes with easily accessible alkenyl halides promoted by a chiral cobalt complex derived from newly developed tridentate bisoxazolinephosphine is presented. Such processes represent an unprecedented reaction pathway for catalysis and general approach that enable rapid construction highly diversified enantioenriched allylic alcohols containing 1,1-, 1,2-disubstituted trisubstituted alkene as well axial stereogenicity in up to 99 % yield : 1 er without the need preformation alkenyl-metal reagents. DFT calculations revealed origin enantioselectivity.

Язык: Английский

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Visible Light‐Mediated Cobalt and Photoredox Dual‐Catalyzed Asymmetric Reductive Coupling for Axially Chiral Secondary Alcohols^†

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(23), С. 3253 - 3260

Опубликована: Июль 20, 2023

Comprehensive Summary Secondary alcohols bearing both axial and central chirality comprise attractive biological activity exhibit excellent chiral induction in asymmetric reactions. However, only very limited catalytic approaches were developed for their synthesis. We herein describe visible light‐mediated cobalt‐catalyzed reductive Grignard‐type addition of aryl iodides with axially prochiral biaryl dialdehydes leading to the direct construction secondary alcohols. Preliminary mechanistic studies indicate that efficient kinetic recognition diastereomers might occur improve stereoselectivity, which open a new avenue challenging cascade multiple elements. This protocol features enantio‐ diastereoselectivity, green mild conditions, simple operation, broad substrate scope, providing modular platform synthesis

Язык: Английский

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Direct Evidence for Excited Ligand Field State-based Oxidative Photoredox Chemistry of a Cobalt(III) Polypyridyl Photosensitizer

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(38), С. 20786 - 20791

Опубликована: Сен. 13, 2023

Increasing interest in sustainable chemistry coupled with the quest to explore new reactivity has spurred research on first-row transition metal complexes for potential applications a variety of settings. One more active areas is photoredox catalysis, where synthetically tunable nature their electronic structures provides rich palette options tailoring desired chemical transformation. Understanding mechanism excited-state critical informed development next-generation catalysts, which turn requires information concerning propensity excited states engage electron or energy transfer processes. Herein we provide direct evidence highly oxidizing lowest-energy ligand-field (LF) state d6-low-spin Co(III) photosensitizer [Co(4,4′-Br2bpy)3]3+ (where 4,4′-Br2bpy 4,4′-dibromo-2,2′-bipyridine). The redox associated LF complex was bracketed by performing bimolecular quenching studies using series simple organic donors. Time-resolved absorption spectroscopy confirmed dynamic process attributed reductive chromophore. Analysis Stern–Volmer plots each chromophore-quencher pair revealed limiting value Ered* ∼ 1.25 V vs Fc/Fc+ metal-centered state, significantly stronger than that commonly employed metal-based agents such as [Ru(bpy)3]2+ (Ered* = 0.32 Fc/Fc+) and [Ir(ppy)2(bpy)]+ 0.27 Fc/Fc+). These results suggest this class chromophores could find utility requiring activation oxidatively resistant substrates catalysis.

Язык: Английский

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