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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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 Reductive (Hetero)Arylation of Cyclic N‐Sulfonyl Imines by Cobalt Catalysis

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(19)

Опубликована: Март 14, 2023

Transition-metal-catalyzed enantioselective addition of aryl organometallic reagents to imines has emerged as one the most powerful tools for formation optically active diarylmethylamines. Here, we report first asymmetric reductive (hetero)arylations using and heteroaryl halides enabled by a chiral cobalt-bisphosphine catalyst. This approach shows good functional group compatibility complements reported strategy without use reagents. Mechanistic investigations supported that aryl-cobalt, instead an arylzinc reagent, was formed in situ this aryl-addition event.

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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Cobalt‐Catalyzed Asymmetric Remote Borylation of Alkyl Halides

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

Опубликована: Июнь 2, 2023

Abstract Enantioselective functionalization of racemic alkyl halides is an efficient strategy to assemble complex chiral molecules, but remains one the biggest challenges in organic chemistry. The distant and selective activation unreactive C−H bonds has received growing interest as it enables rapid generation molecular complexity from simple building blocks. Here, we reported a cobalt‐catalyzed remote borylation (pseudo)halides (alkyl−X, X=I, Br, Cl, OTs) with pinacolborane (HBpin) presented robust approach for valuable secondary organoboronates halides. This migration reaction compatible primary, secondary, tertiary bromides, offering direct access broad range alkylboronates. extension this catalytic system aryl was also demonstrated. Preliminary mechanistic studies revealed that involved radical pathway.

Язык: Английский

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Strategies for Carbon Electrophile Addition to Carbonyls and Imines by Cobalt Catalysis

European Journal of Organic Chemistry, Год журнала: 2023, Номер 26(45)

Опубликована: Окт. 16, 2023

Abstract The addition of carbon electrophiles to carbonyls and imines has emerged as a valuable strategy for the construction C−C bonds. merger this concept with sustainable cobalt catalysis yielded numerous innovative methodologies. Remarkable functional group tolerance selectivity have been observed in many cases, providing reliable methods bond construction. cobalt‐catalyzed additions carbonyls, carboxylic acid derivatives described review include earliest reports, such Takai‐Utimoto Co/Cr co‐catalyzed their progression, well modern variants, exemplified by recent Co/photoredox protocols. systematic appraisal provides clearer perspective inspiration its further development.

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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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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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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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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