Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(12), С. 3110 - 3129

Опубликована: Янв. 1, 2023

This review focuses on the very recent advances (from 2020 to beginning of 2023) in enantioselective catalytic reactions for construction oxa-quaternary stereocenters.

Язык: Английский

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Nickel-catalyzed direct stereoselective α-allylation of ketones with non-conjugated dienes

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 22, 2023

The development of efficient and sustainable methods for the construction carbon-carbon bonds with simultaneous stereoselective generation vicinal stereogenic centers is a longstanding goal in organic chemistry. Low-valent nickel(0) complexes which promote α-functionalization carbonyls leveraging its pro-nucleophilic character conjunction suitable olefin acceptors are scarce. We report Ni(0)NHC catalyst selectively converts ketones non-conjugated dienes to synthetically highly valuable α-allylated products. directly activates α-hydrogen atom carbonyl substrate transferring it acceptor. transformation creates adjacent quaternary tertiary diastereoselective enantioselective manner. Computational studies indicate ability trigger ligand-to-ligand hydrogen transfer process from ketone substrate, setting selectivity process. shown selective functionalization α-C-H bond groups by opens up new opportunities exploit 3d-metal catalysis access chiral building blocks.

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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Tunable Thiazolium Carbenes for Enantioselective Radical Three-Component Dicarbofunctionalizations

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

Опубликована: Дек. 10, 2024

Asymmetric N-heterocyclic carbene (NHC) organocatalysis is a cornerstone of synthetic organic chemistry. The emerging concept single-electron NHC catalysis broadened the scope C–C bond-forming reactions, facilitating synthesis variety attractive racemic compounds. However, development effective and selective chiral catalysts for asymmetric radical-mediated reactions has been challenging. In this report, we introduce family highly tunable thiazolium carbenes with three distinct positions broad electronic steric modulation featuring bulky flanking groups. We demonstrate catalytic efficacy these in an enantioselective SET-type three-component acyl-difluoroalkylation olefins using range aldehydes difluoroalkyl bromides. This method provides straightforward access to diverse set β-difluoroalkylated α-chiral ketones (65 examples) up 87% yield excellent enantioselectivities >99:1 er. utility methodology further outlined by enantio- diastereoselective late-stage modifications pharmaceutically relevant compounds twofold orthogonal acyl-difluoroalkylations linchpin reagents.

Язык: Английский

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Scalable synthesis of (±)-gregatin A via a 1,3-dipolar cycloaddition strategy

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A 6-step gram-scale synthesis of the fungal polyketide gregatin is described. This features an intermolecular 1,3-dipolar cycloaddition, a N–O bond cleavage and subsequent cascade cyclization.

Язык: Английский

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Chiral ruthenium complex/Ph ₂ P(2-furyl)–catalyzed asymmetric nucleophilic addition of aryl aldehyde hydrazones to simple ketones

Science Advances, Год журнала: 2025, Номер 11(12)

Опубликована: Март 21, 2025

An efficient synthesis of chiral tertiary alcohols through asymmetric nucleophilic addition reaction aldehyde hydrazones to simple ketones (especially aryl/methyl ketones) has been well established. Aryl aldehydes could be used as latent benzyl carbanion equivalents via reductive polarity reversal. The key the success was combination an achiral monophosphine ligand Ph 2 P(2-furyl) with a diamine derivative, which enhanced enantioselectivity and reactivity. Density functional theory calculations revealed hydrogen bond interactions between ligand, base anion, combined induce desired enantioselectivity. Moreover, further synthetic transformation high chirality transfer also demonstrated.

Язык: Английский

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Enantioselective macrocyclization via catalytic metallic dipole relay

Nature Catalysis, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

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Enantioselective acyl-trifluoromethylation of olefins by bulky thiazolium carbene catalysis

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

Опубликована: Апрель 7, 2025

Abstract Enantioenriched α -chiral β -fluorinated ketones are valuable structural motifs with application in several fields. The recently emerged concept of NHC-catalyzed radical acyl-trifluoromethylation olefins offers a rapid route to construct racemic single step. Due the lack competent chiral NHC catalysts constructing these molecules an enantioselective manner remains unmet challenge. Herein, we report family thiazolium carbenes having bulky flanking groups and offering three distinct positions broad steric electronic tunability. display so far unmatched enantioselectivities for acyl-trifluoromethylations simple unactivated wide variety aldehydes Togni’s reagent. method provides enantioenriched -trifluoromethylated high yields excellent up 98:2 er. A potential applicability this methodology is demonstrated through enantio- diastereoselective late-stage functionalizations pharmaceutical compounds.

Язык: Английский

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Dynamic Kinetic Asymmetric Hydroacylation: Racemization by Soft Enolization

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

Опубликована: Апрель 29, 2025

We report a dynamic kinetic asymmetric transformation (DyKAT) of racemic aldehydes by Rh-catalyzed hydroacylation acrylamides. This intermolecular generates 1,4-ketoamides with high enantio- and diastereoselectivity. DFT experimental studies provide mechanistic insights reveal an unexpected pathway for aldehyde racemization. Our study represents pioneering resolution contributes to the growing field stereoconvergent catalysis featuring C-C bond construction.

Язык: Английский

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One‐Pot Synthesis of Chiral Succinate Dehydrogenase Inhibitors and Antifungal Activity Studies

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Abstract In this work, a series of novel chiral succinate dehydrogenase inhibitors (SDHIs) are synthesized through one‐pot Rh‐catalyzed asymmetric hydrogenation‐condensation strategy. This method exhibits high efficiency (up to 1000 Ton, 94% yield over two steps), stereoselectivity 99% ee), and broad substrate scope (68 examples in total), providing superior pathway for the synthesis such fungicides. Mechanistic studies indicate that amino group at 2‐position phenyl ring acts as an activating group, enhancing reactivity control reaction. Furthermore, these molecules exhibit broad‐spectrum highly effective antifungal biological activity. Notably, enantiomers show significant differences both vitro vivo fungi‐inhibiting experiments. Especially, ( S )‐ 5f showcases activity against Botrytis cinerea (EC 50 = 0.48 µ m ) is much higher than its R enantiomer 36.7 ). Molecular docking calculations, molecular dynamic simulation, enzyme assays, ligand‐target interaction experiments demonstrate (ΔG MM‐PBSA −18.86 kcal mol −1 , K D 6.04 inhibits more effectively −13.01 8.5 Moreover, have significantly different effects on spore germination destruction fungal phenotype.

Язык: Английский

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