Cobalt(III)-Catalyzed Enantioselective C–H Functionalization: Ligand Innovation and Reaction Development

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, environmentally friendly 3d metals poses substantial challenges, primarily due variable oxidation states, intricate coordination patterns, limited mechanistic insights. In this Account, we summarize our research endeavors in three types Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, situ-generated octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) Co(II)/chiral phosphoric (CPA) cooperative achieved through strategic ligand design. Our initial objective was achieve functionalization Cp*Co(III) catalysts with external ligands, aiming circumvent laborious preparation CpxCo(III) complexes. To end, developed several CCA incorporating non-covalent interactions (NCIs) a crucial design element. Next, address limitations associated lengthy synthesis Cp-ligated complexes difficulties modification, explored concept situ generation catalysis using commercially available cobalt(II) salts tailor-made ligands. This exploration led two innovative catalytic systems, namely, Co(II)/Salox Co(II)/CCA sequential catalysis. The emerged versatile strategy, demonstrating excellent enantioselectivities across range asymmetric reactions construct various molecules central, axial, planar, inherent chirality. facile single step, along ease further enhances versatility applicability approach. Moreover, successfully applied cobalt/Salox electro- photochemical-catalyzed functionalization, electrons or oxygen traceless oxidant, thereby eliminating need stoichiometric chemical oxidants. Through studies reaction developments, elucidated detailed structure-enantioselectivity relationships which are expected inform future endeavors. Finally, Co(II)/CPA enabled spiro-γ-lactams olefination/asymmetric [4 + 1] spirocyclization. Mechanistically, establishment stereochemistry occurs during cyclization where CPA serves both neutral Brønsted acid, stereoinduction independent cleavage step. We anticipate that insights advancements Account will inspire innovations drive progress metal-catalyzed reactions.

Язык: Английский

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Asymmetric Dearomatization of Indoles through Cobalt‐Catalyzed Enantioselective C−H Functionalization Enabled by Photocatalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Июнь 20, 2024

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger photocatalysis transition-metal-catalyzed asymmetric C-H activation as an efficient sustainable method for construction chiral molecules remains elusive challenging. Herein, we develop cobalt-catalyzed enantioselective enabled by visible-light photoredox catalysis, providing synergistic catalytic strategy dearomatization indoles with high levels enantioselectivity (96 % to >99 ee). Mechanistic studies indicate that excited photocatalyst was quenched divalent cobalt species presence Salox ligand, leading formation catalytically active Co(III) complex. Moreover, stoichiometric reactions cobaltacycle intermediate indole suggest irradiation visible light also play critical role step.

Язык: Английский

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Atroposelective [4+1] Annulation for the Synthesis of Isotopic Isoindolinones Bearing both Central and Axial Chirality

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Isotopically chiral molecules have drawn much attention due to their practical applications in drug discovery. However, existing studies this area are mainly limited centrally and H/D exchange. Herein, we report a phosphoric acid-catalyzed atroposelective [4+1] annulation of ketoaldehydes 1H-indol-1-amines. By means strategy, series D- 18O-labeled atropisomers featuring both central axial chiralities synthesized with high enantioselectivities diastereoselectivities good excellent isotopic incorporation. Experimental density functional theory suggest that the reaction involves sequential condensation, cyclization isomerization cascade, which second step is enantio-determining process.

Язык: Английский

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Synthesis of 3-sulfonylisoindolin-1-ones from olefinic amides and sodium sulfinates via electrooxidative tandem cyclization

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(29), С. 5897 - 5901

Опубликована: Янв. 1, 2024

Sulfonyl groups are motifs that widely found in biologically active compounds and drug molecules, many isolated natural products as well pharmaceuticals contain sulfonyl groups. Herein, we present the synthesis of sulfonyl-substituted isoindolones by a electrochemical oxidative radical cascade cycloaddition reaction olefinic amides with sodium sulfite under oxidant- catalyst-free conditions. Various sulfinates were compatible gave desired yields up to 99%.

Язык: Английский

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Catalytic Asymmetric Barbier Reaction of Ketones with Unactivated Alkyl Electrophiles

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Окт. 3, 2024

The Barbier reaction is a reductive-type addition of an aldehyde or ketone with organic electrophile in the presence terminal metal reductant, providing straightforward and efficient method for carbon-carbon bond formation. This possesses advantage circumventing preparation moisture- air-sensitive organometallic reagents. However, catalytic ketones to construct tetrasubstituted stereogenic centers largely underdeveloped, despite its great potential accessing synthetically challenging chiral tertiary alcohol. Particularly, leveraging unactivated alkyl electrophiles as coupling components still rarely exploited. Herein, we disclose photoredox-assisted cobalt-catalyzed asymmetric alkylative Barbier-type address aforementioned challenges, thereby allowing construction highly congested carbon centers. fragments could be either readily accessible halides redox-active esters generated through decarboxylative pathway. Both types include primary, secondary, ones, thus affording diverse enantioenriched alcohols broad substrate scope. enantioselective protocol applied expedient synthesis core structure

Язык: Английский

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Photo-Promoted carbonylative Difunctionalization of alkenes toward β-Aminoketones

Journal of Catalysis, Год журнала: 2025, Номер unknown, С. 115935 - 115935

Опубликована: Янв. 1, 2025

Язык: Английский

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Nickel(II)/Salox-Catalyzed Enantioselective C–H Functionalization

ACS Central Science, Год журнала: 2025, Номер 11(1), С. 127 - 135

Опубликована: Янв. 2, 2025

Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to distinctive properties. However, the use of cost-effective sustainable divalent C–H activation/asymmetric alkene insertion poses significant challenges due intricate control stereochemistry transformation tetracoordinate C–Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C–H/N–H annulation with oxabicyclic alkenes. This protocol offers straightforward access chiral [2,2,1]-bridged bicyclic compounds bearing four consecutive stereocenters high enantioselectivity (up 96% ee). The development sterically hindered salicyloxazoline (Salox) ligand, TMS-Salox, is key success this protocol. Mechanistic investigations unveiled that Ni(III)-metalacyclic intermediate was formed through situ oxidation achiral organometallic Ni(II) species coordination Salox ligand. process led creation tailored pocket guides approach alkenes, thereby influencing determining stereochemistry.

Язык: Английский

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Asymmetric Synthesis of 3-Substituted Isoindolinones by Direct Alkylation of Chiral N-tert-Butylsulfinyl-isoindolinones

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

A straightforward, versatile, and efficient method for the asymmetric synthesis of 3-substituted isoindolinones is described. In this method, a series (S)-2-(tert-butylsulfinyl)-isoindolin-1-ones were synthesized from corresponding methyl 2-formylbenzoates in two steps with overall yields 71-78%. Deprotonation these compounds using LDA subsequent alkylation resulting carbanions various alkylating agents afforded excellent high diastereomeric ratios. This showcases significant potential broader applications organic medicinal chemistry.

Язык: Английский

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Emerging trends in CO carbonylation

Chem, Год журнала: 2025, Номер unknown, С. 102503 - 102503

Опубликована: Апрель 1, 2025

Язык: Английский

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Enantioselective Cobalt(III)-Catalyzed [4 + 1] Annulation of Benzamides: Cyclopropenes as One-Carbon Synthons

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(18), С. 15041 - 15049

Опубликована: Апрель 28, 2025

A chiral cyclopentadienyl cobalt(III)-catalyzed enantioselective [4 + 1] annulation of N-chlorobenzamides with cyclopropenes is reported. The cobalt catalyst engages in the C-H activation as well promotes C-C bond cleavage cyclopropene, rendering it a one-carbon unit for annulation. reaction efficiently constructs biologically relevant isoindolinones selectivities up to 99:1 er and >20:1 E/Z ratios. cobalt(III) displays unique orthogonal reactivity profile delivering products, whereas its rhodium(III) homologue more classical 2] pattern. Computational studies reveal origin these divergences.

Язык: Английский

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