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

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Enantioselective C–H bond functionalization under Co(iii)-catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(25), P. 3354 - 3369

Published: Jan. 1, 2024

Enantioselective C–H functionalization relies on 4d and 5d metals, but with their depletion, sustainable alternatives using 3d metals are crucial.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: June 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.

Language: Английский

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A Dual Cobalt‐Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides via C−H Activation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: June 19, 2024

Abstract In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C−H bonds amides and subsequent migratory insertion π‐bonds present in indole as reactive partner, achieve syn ‐selective tetrahydro‐5 H ‐indolo[2,3‐ c ]isoquinolin‐5‐one derivatives with excellent yields enantiomeric excesses up to >99 %. The developed operates without metal oxidant, relying solely on oxygen oxidant employing an organic dye photocatalyst irradiation. Control experiments stoichiometric studies elucidate reversible nature enantiodetermining activation step, albeit not being rate‐determining. This study only expands horizon cobalt‐catalyzed bond functionalization, but also showcases potential synergy between cobalt photoredox catalysis enabling synthesis complex molecules.

Language: Английский

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Solvent‐Controlled Enantiodivergent Construction of P(V)‐Stereogenic Molecules via Palladium‐Catalyzed Annulation of Prochiral N‐Aryl Phosphonamides with Aromatic Iodides

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(41)

Published: July 9, 2024

In this work, we describe an efficient and modular method for enantiodivergent accessing P(V)-stereogenic molecules by utilizing the catalytic atroposelective Catellani-type C-H arylation/desymmetric intramolecular N-arylation cascade reaction. The enantioselectivity of protocol was proved to be tuned polarity solvent, thus providing a wide range both chiral enantiomers in moderate good yields with excellent enantiomeric excesses. Noteworthy is that strategy developed herein represents unprecedented example solvent-dictated inversion compounds.

Language: Английский

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

ACS Central Science, Journal Year: 2025, Volume and Issue: 11(1), P. 127 - 135

Published: Jan. 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.

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

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Chiral Osmium(II)/Salox Species Enabled Enantioselective γ‐C(sp³)−H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(20)

Published: March 19, 2024

Abstract Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp 3 )−H functionalization, among which Os(II)/Salox species is found be most efficient for precise stereocontrol in realizing amidation. As exemplified by enantioenriched pyrrolidinone synthesis, such tailored catalyst efficiently enables an intramolecular site‐/enantioselective amidation γ‐position dioxazolone substrates, benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording corresponding γ‐lactam products with good er values (up 99 : 1) diverse functionality (>35 examples). The unique performance advantage developed system terms catalytic energy profile induction has further clarified integrated experimental computational studies.

Language: Английский

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Solvent‐Controlled Enantiodivergent Construction of P(V)‐Stereogenic Molecules via Palladium‐Catalyzed Annulation of Prochiral N‐Aryl Phosphonamides with Aromatic Iodides

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(41)

Published: July 9, 2024

Abstract In this work, we describe an efficient and modular method for enantiodivergent accessing P(V)‐stereogenic molecules by utilizing the catalytic atroposelective Catellani‐type C−H arylation/desymmetric intramolecular N ‐arylation cascade reaction. The enantioselectivity of protocol was proved to be tuned polarity solvent, thus providing a wide range both chiral enantiomers in moderate good yields with excellent enantiomeric excesses. Noteworthy is that strategy developed herein represents unprecedented example solvent‐dictated inversion compounds.

Language: Английский

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Chiral Osmium(II)/Salox Species Enabled Enantioselective γ‐C(sp³)−H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(20)

Published: March 19, 2024

Abstract Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp 3 )−H functionalization, among which Os(II)/Salox species is found be most efficient for precise stereocontrol in realizing amidation. As exemplified by enantioenriched pyrrolidinone synthesis, such tailored catalyst efficiently enables an intramolecular site‐/enantioselective amidation γ‐position dioxazolone substrates, benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording corresponding γ‐lactam products with good er values (up 99 : 1) diverse functionality (>35 examples). The unique performance advantage developed system terms catalytic energy profile induction has further clarified integrated experimental computational studies.

Language: Английский

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