Ni^II-Catalyzed Enantioselective Anti-Markovnikov Hydrophosphination of Unactivated Alkynes

ACS Catalysis, Год журнала: 2023, Номер 13(10), С. 6994 - 7001

Опубликована: Май 9, 2023

A mechanism-inspired, reaction mode-controlled enantio- and regioselective anti-Markovnikov hydrophosphination of unactivated alkynes was accomplished by NiII catalysis. Alkenyl phosphine products could be obtained with high regio- enantioselectivity easily derivatized to structurally diverse chiral compounds. Mechanistic studies on both Ni0-catalyzed Markovnikov addition NiII-catalyzed have been carried out combining experimental computational methods. In the Ni0 system, an allyl nickel complex as catalyst resting state whose structure unambiguously determined single-crystal XRD analysis. sequential hydrometallation, ligand exchange, reductive elimination mechanism elucidated corroboratively DFT calculations. cationic secondary serves active catalyst. migratory insertion protonation sequence operative accomplish hydrophosphination.

Язык: Английский

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Cobalt‐Catalyzed Asymmetric Aza‐Nozaki–Hiyama–Kishi (NHK) Reaction of α‐Imino Esters with Alkenyl Halides

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(7)

Опубликована: Янв. 2, 2024

Chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi (NHK) reaction represents one of the most powerful approaches for formation chiral carbon-heteroatom bond. However, construction sterically encumbered tetrasubstituted stereocenter through NHK still posts a significant challenge. Herein, we disclose cobalt-catalyzed aza-NHK ketimine with alkenyl halide to provide convenient synthetic approach manufacture enantioenriched α-vinylic amino acid. This protocol exhibits excellent functional group tolerance 99 % ee in cases. Additionally, this asymmetric reductive method is also applicable aldimine access trisubstituted stereogenic centers.

Язык: Английский

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Desymmetrization–Addition Reaction of Cyclopropenes to Imines via Synergistic Photoredox and Cobalt Catalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(28), С. 18892 - 18898

Опубликована: Июль 5, 2024

Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated synthesis series chiral functionalized cyclopropanes with high yield, enantioselectivity, diastereoselectivity (44 examples, up 93% yield >99% ee). A possible mechanism involving cyclopropene desymmetrization Co-H species imine addition Co-alkyl was proposed. study provides novel route important extends frontier metallaphotoredox

Язык: Английский

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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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Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 6, 2024

Abstract General, catalytic and enantioselective construction of chiral α,α -dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed anti- Markovnikov alkene hydroalkylation via the remote stereocontrol for synthesis other N -heterocycles. This asymmetric C(sp 3 )−C(sp ) coupling features high flexibility in introducing diverse set alkyl groups at α -position The utility this methodology has been demonstrated by late-stage functionalization drug molecules, bioactive natural products functional materials, identification class molecules exhibiting anti-apoptosis activities UVB-irradiated HaCaT cells. Ligands play vital role controlling reaction regioselectivity. Changing ligand from bi-dentate L6 tridentate L12 enables CoH-catalyzed hydroalkylation. Mechanistic studies disclose that involves migratory insertion process while MHAT process.

Язык: Английский

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Stereoselective Synthesis of Trisubstituted Alkenes via Copper Hydride-Catalyzed Alkyne Hydroalkylation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(32), С. 17557 - 17563

Опубликована: Авг. 4, 2023

Alkenes are ubiquitous in organic chemistry, yet many classes of alkenes remain challenging to access by current synthetic methodology. Herein, we report a copper hydride-catalyzed approach for the synthesis Z-configured trisubstituted with high stereo- and regioselectivity via alkyne hydroalkylation. A DTBM-dppf-supported Cu catalyst was found be optimal, providing substantial increase product yield compared reactions conducted dppf as ligand. DFT calculations show that DTBM substitution leads acceleration hydrocupration through combined ground transition state effects related preventing dimerization enhancing catalyst–substrate dispersion interactions, respectively. Alkyne hydroalkylation successfully demonstrated methyl larger alkyl tosylate electrophiles produce variety (hetero)aryl-substituted moderate yields complete selectivity Z stereochemically configured products. In formation key C–C bond, computational studies revealed direct SN2 pathway alkylation vinylcopper intermediate situ-formed iodides.

Язык: Английский

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Dimeric Manganese‐Catalyzed Hydroalkenylation of Alkynes with a Versatile Silicon‐Based Directing Group

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(31)

Опубликована: Июнь 7, 2023

Herein, we present a manganese-catalyzed, branched-selective hydroalkenylation of terminal alkynes, under mild conditions through facile installation versatile silanol as removable directing group. With an alkenyl boronic acid the coupling partner, this reaction produces stereodefined (E,E)-1,3-dienes with high regio-, chemo- and stereoselectivity. The protocol features such room temperature air atmosphere, while maintaining excellent functional group compatibility. resulting 1,3-dienesilanol products serve building blocks, removal allows for synthesis both branched 1,3-dienes downstream reactions, well stereoselective construction linear (E,E,E)- or (E,E,Z)-1,3,5-trienes. In addition, Diels-Alder cycloaddition can smoothly selectively deliver silicon-containing pentasubstituted cyclohexene derivatives. Mechanistic investigations, in conjunction DFT calculations, suggest bimetallic synergistic activation model to account observed enhanced catalytic efficiency good regioselectivity.

Язык: Английский

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Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 28, 2024

1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization two with both syn- and anti-selectivity in one catalyst system is undeveloped proves be significant challenge. Herein, we report Nickel-catalyzed four-component reaction 1,3-dienes using terminal alkynes, aryl boroxines, perfluoroalkyl iodides, wherein the forms three new C-C bonds single vessel serve as modular strategy excellent chemoselectivity, good regioselectivity exclusive stereoselectivity. Control experiments reveal plausible mechanism DFT calculations explain cause for formation this unusual reaction. Furthermore, successfully incorporate biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases diversity molecular scaffolds brings more potential values medicinal chemistry, synthetic utility our protocol further demonstrated by late-stage transformations.

Язык: Английский

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Enantioselective alkene hydroalkylation overcoming heteroatom constraints via cobalt catalysis

Nature Synthesis, Год журнала: 2024, Номер 3(9), С. 1134 - 1144

Опубликована: Июль 10, 2024

Язык: Английский

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Bifunctional iron-catalyzed alkyne Z-selective hydroalkylation and tandem Z-E inversion via radical molding and flipping

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 4, 2024

The challenging synthesis of thermodynamic-unfavored cis-olefins through catalytic cross-coupling reactions requires the synergistic interaction substrate-activating units and configuration-regulating catalysts. Successfully hitting these two birds with one stone, we herein develop a convenient photoredox access to Z-alkenes from alkynes light alkanes bifunctional iron-catalyzed system possessing both C(sp

Язык: Английский

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