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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 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.

Language: Английский

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Asymmetric reductive arylation and alkenylation to access S-chirogenic sulfinamides

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 15, 2025

The study of the stereochemistry organic sulfur compounds has been ongoing for over a century, with S-chirogenic pharmacophores playing an essential role in drug discovery within bioscience and medicinal chemistry. Traditionally, synthesis sulfinamides featuring stereogenic sulfur(IV) centers involves complex, multistep process that often depends on chiral auxiliaries or kinetic resolution. Here, we introduce effective versatile method synthesizing diverse classes through selective aryl alkenyl addition to sulfinylamines. This is catalysed by nickel cobalt complex under reductive conditions, eliminating need preformed organometallic reagents. facilitates incorporation array halides at position, enabling their integration into various biologically significant pharmacophores. Our detailed mechanistic investigations density functional theory calculations provide insights reaction pathway, particularly highlighting enantiocontrol mode during process. play authors report methodology asymmetric sulfinylamines via common-Earth-metal catalysis.

Language: Английский

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

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(7)

Published: Jan. 2, 2024

Abstract 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.

Language: Английский

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Catalytic Asymmetric Barbier Reaction of Ketones with Unactivated Alkyl Electrophiles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 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

Language: 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, Journal Year: 2024, Volume and Issue: 136(25)

Published: Jan. 22, 2024

Abstract 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.

Language: Английский

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Synergistically Activating Nucleophile Strategy Enabled Organocatalytic Asymmetric P-Addition of Cyclic Imines

Chemical Science, Journal Year: 2024, Volume and Issue: 15(30), P. 12017 - 12025

Published: Jan. 1, 2024

An attractive organocatalytic asymmetric addition of P-nucleophiles with cyclic N -sulfonyl imines by phosphonium salt catalysis has been disclosed, offering a facile way to phosphorus-containing benzosultams in high yields and stereoselectivities.

Language: Английский

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Cobalt-Catalyzed Enantioselective Reductive Addition of Ketimine with Cyclopropyl Chloride to Construct the Chiral Amino Esters Bearing Cyclopropyl Fragments

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(22), P. 6311 - 6318

Published: Jan. 1, 2024

Co-catalyzed asymmetric reductive addition of ketimine with cyclopropyl chloride has been realized to access diverse chiral amino esters bearing fragments broad functional group tolerance and excellent enantioselectivities.

Language: Английский

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Catalyst‐Free, Air‐Mediated C(sp²)−H Alkylation of Cyclic Aldimines with Alkylboronic Acids

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4544 - 4549

Published: Nov. 22, 2023

Abstract The air mediated radical alkylation of cyclic aldimines via autoxidation alkylboronic acids has been realized under mild reaction conditions. By simply heating with acid using as sole oxidant, this protocol provides a catalyst‐free access to variety alkylated 21–91% yields. Preliminary mechanistic studies suggest that pathway might be involved in the reaction.

Language: Английский

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Reductive Metal-Catalyzed Coupling as an Alternative to the Use of Stoichiometric Organometallic Reagents in Carbonyl and Imine Additions

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Nickel‐Catalyzed Enantioselective Carbonyl Addition of Aryl Chlorides and Bromides to Aldehydes

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(47)

Published: June 7, 2024

Abstract The Ni‐catalyzed enantioselective addition reaction of aryl halides to aldehydes was studied with cyanobis(oxazoline) as chiral ligands and Mn reductant. Aryl heteroaryl bromides reacted phenyl aldehyde at room temperature produce dibenzyl alcohols in 16–99 % yields 53–92 ees. Moreover, the coupling chloride a variety aryl, alkyl demonstrated presence cyanobis(oxazoline)/Ni(II) 60 °C generally high moderate enantioselectivities.

Language: Английский

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