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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Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles

Chemical Science, Год журнала: 2024, Номер 15(30), С. 12026 - 12035

Опубликована: Янв. 1, 2024

A 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction 5-7-membered ( E )-1,2-difluorovinyl azacycles is developed.

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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Cobalt-Catalyzed Asymmetric Reductive Alkenylation and Arylation of Heterobiaryl Tosylates: Kinetic Resolution or Dynamic Kinetic Resolution?

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(49), С. 26747 - 26755

Опубликована: Ноя. 29, 2023

Herein, we report a cobalt-catalyzed atroposelective reductive cross-coupling of racemic heterobiaryl tosylates with C(sp2)–X type electrophile. Both aryl and alkenyl halides are competent precursors for this reaction, providing variety heterobiaryls as the products in highly enantioselective manner high functionality tolerance. The related asymmetric arylation alkenylation discovered to proceed divergent mechanisms. reaction pathway changes from kinetic resolution (KR) when bromides iodides bearing strong electron-withdrawing substitution on para-position employed starting materials an enantioconvergent transformation via dynamic KR configurationally labile cobaltacycles relatively electron-rich used. change mechanisms turns out arise relative rates two competing elementary steps, which epimerization cyclic Co(I) intermediates their trapping by coupling electrophiles C(sp2)-type oxidative addition.

Язык: Английский

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CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles

Chemical Science, Год журнала: 2024, Номер 15(23), С. 8888 - 8895

Опубликована: Янв. 1, 2024

A highly efficient method achieves precise construction of alkyl chiral centers at remote C3-positions in five-membered S/O-heterocycles via cobalt-catalyzed asymmetric hydroalkylation heterocyclic alkenes.

Язык: Английский

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A General Enantioselective α-Alkyl Amino Acid Derivatives Synthesis Enabled by Cobalt-Catalyzed Reductive Addition

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

Опубликована: Сен. 12, 2024

Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications biochemistry, medicinal and materials science. Herein, we report cobalt-catalyzed aza-Barbier reaction of dehydroglycines unactivated alkyl halides to afford α-amino esters high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use moisture-, air-sensitive organometallic reagents, stoichiometric chiral auxiliaries, enabling conversion variety primary, secondary, even tertiary α-alkyl-amino under mild conditions, thus leading broad functional group tolerance. The expedient access biologically active motifs demonstrates practicality this by reducing number synthetic steps enhancing efficiency.

Язык: Английский

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Cobalt-Catalyzed Chemoselective π–σ–π-Type Tandem Reductive Coupling to Access Isoquinolines via Carbocobaltation of Nitriles

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 1596 - 1606

Опубликована: Янв. 14, 2025

Transition metal-catalyzed reductive coupling chemistry has been recognized as a powerful tool for the synthesis of diverse organic molecules. However, despite enormous progress in this field, there is no precedent tandem widely accessible nitriles with electrophiles that contain σ- and π-type (σ/π-type) electrophilic functional groups simultaneously. Herein, we have established unique cobalt catalysis system, enabling chemoselective coupling/tandem cyclization reaction aryl halides (Br, Cl, I) bearing carbonyl moiety variety aryl, alkenyl, alkyl via carbocobaltation unknown yet. The protocol allows modular structurally isoquinolines wide substrate scope (>60 examples), good functionalities tolerance, chemoselectivity.

Язык: Английский

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Enantioselective Heck/Tsuji−Trost reaction of flexible vinylic halides with 1,3-dienes

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

Опубликована: Янв. 22, 2025

Abstract The enantioselective domino Heck/cross-coupling has emerged as a powerful tool in modern chemical synthesis for decades. Despite significant progress relative rigid skeleton substrates, the implementation of asymmetric cascades highly flexible haloalkene substrates remains challenging and long-standing goal. Here we report an efficient Heck/Tsuji−Trost reaction vinylic halides with 1,3-dienes enabled by palladium catalysis. Specifically, Heck insertion stereodetermining step to form ƞ 3 allyl complex situ trapping nucleophiles enable Heck/etherification formal (4 + 2) cycloaddition manner. Engineering Sadphos bearing androgynous non-C 2 -symmetric chiral sulfinamide phosphine ligands are vital component achieving excellent catalytic reactivity enantioselectivity. This strategy offers general, modular divergent platform rapidly upgrading feedstock dienes various value-added molecules is expected inspire development other Heck/cross-couplings.

Язык: Английский

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Cross-Electrophile Coupling to Form Sterically Hindered C(sp²)–C(sp³) Bonds: Ni and Co Afford Complementary Reactivity

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

Опубликована: Март 7, 2025

The formation of sterically hindered C(sp2)-C(sp3) bonds could be a useful synthetic tool but has been understudied in cross-electrophile coupling. Here, we report two methods that couple secondary alkyl bromides with aryl halides contain C-X bonds: 1) ortho-substituted nickel catalysts and 2) di-ortho-substituted iodides cobalt catalysts. Stoichiometric experiments deuterium labeling studies show [Co] is better than [Ni] for oxidative addition Ar-I radical capture/reductive elimination steps arenes. For both metals, Ar-H side products observed reactions low-yielding appear to arise from Ar• hydrogen-atom transfer the solvent. While origins differences scope are not yet understood, these demonstrate previously unknown complementarity between

Язык: Английский

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Nickel‐Catalyzed Asymmetric Reductive 1,4‐ and 1,5‐Dicarbofunctionalization^†

Chinese Journal of Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Comprehensive Summary Herein, we present the first examples of asymmetric reductive 1,4‐dicarbofunctionalization 1,3‐dienes and 1,5‐dicarbofunctionalization vinylcyclopropanes, which proceed under catalysis a chiral nickel/bis‐imidazoline complex using alkyl halides aryl iodides or alkenyl bromides as electrophilic coupling partners. In these highly enantioselective transformations operating in radical relay mechanism, C(sp 3 )‐ 2 )‐type carbo‐moieties are respectively installed on terminal internal position with newly formed olefinic unit high E ‐selectivity.

Язык: Английский

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