A General Three-Component Nozaki–Hiyama–Kishi-Type Reaction Enabled by Delayed Radical-Polar Crossover

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Nozaki–Hiyama–Kishi (NHK) reactions offer a mild approach for the formation of alcohol motifs through radical-polar crossover-based pathways from various radical precursors. However, application multicomponent NHK-type reactions, which allow multiple bonds in single step, has been largely restricted to bulky alkyl precursors, thus limiting their expanded utilization. Herein, we disclose general three-component reaction enabled by delayed crossover, efficiently tolerates plethora precursors that were previously unavailable. This method enables modular assembly versatile homoallylic alcohols feedstock chemicals with excellent chemo-, regio-, diastereo-, and enantioselectivities step. Experimental studies density functional theory (DFT) calculations reveal kinetically favored an allylchromium(III) species is paramount enforcing crossover over direct addition. Finally, straightforward transformations applications products demonstrated, showcasing synthetic utility this method.

Language: Английский

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The Indenyl Effect: Accelerated C−H Amidation of Arenes via Ind*Rh^III Nitrene Transfer Catalysis**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 6, 2023

Investigations into C-H amidation reactions catalysed by cationic half-sandwich d6 metal complexes revealed that the indenyl-derived catalyst [Ind*RhCl2 ]2 significantly accelerated directed ortho of benzoyl silanes using 1,4,2-dioxazol-5-ones. Ring slippage involving a haptotropic η5 to η3 rearrangement indenyl complex proposedly enables ligand substitution at centre proceed via associative, rather than dissociative pathways, leading significant rate and yield enhancements. Intriguingly, this phenomenon appears specific for weakly coordinating carbonyl-based directing groups with no acceleration observed corresponding strongly nitrogen-based groups.

Language: Английский

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Photoinduced copper-catalyzed selective three-component 1,2-amino oxygenation of 1,3-dienes

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(69), P. 10388 - 10391

Published: Jan. 1, 2023

This study presents a highly effective method for the photoinduced copper-catalyzed 1,2-amino oxygenation of 1,3-dienes. synthetic strategy involves dual roles single copper catalyst, which can act as photosensitizer to generate nitrogen radicals and also react with allyl via electron transfer (SET) processes. The produces range quaternary carbon-centered carboxylic esters tertiary ethers high yields excellent regioselectivity under mild reaction conditions.

Language: Английский

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Three-component, stereoselective C–N bond forming alkene difunctionalization

Organic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review discusses emerging strategies in three-component, stereoselective C–N bond-forming alkene difunctionalization, emphasizing mechanistic innovations and their impact on synthetic organic chemistry.

Language: Английский

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Photocatalytic Synthesis of Substituted 2-Aryl Morpholines via Diastereoselective Annulation

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Morpholines are prevalent in medicinal chemistry due to their favorable pharmacokinetic properties and widespread presence FDA-approved drugs. Existing methods for morpholine synthesis often require prefunctionalized or protected reagents, limiting versatility efficiency. Here, we present a photocatalytic, diastereoselective annulation strategy the of morpholines directly from readily available starting materials. This method employs visible-light-activated photocatalyst, Lewis acid, Brønsted acid achieve high yields stereoselectivity. It also provides access diverse substitution patterns, including challenging tri- tetra-substituted morpholines. Mechanistic studies reveal that reaction proceeds through formation radical cation intermediate, with triflic playing critical roles protonating substrate, preserving preventing product oxidation. Beyond morpholines, this is extended piperidines, pyrrolidines, other privileged nitrogen heterocycles. Our findings provide modular approach constructing complex, medicinally valuable scaffolds, advancing both synthetic chemistry.

Language: Английский

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Rhodium‐Catalyzed Enantioselective 1,4‐Oxyamination of Conjugated gem‐Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(37)

Published: June 26, 2023

The incorporation of fluorine atoms in organics improves their bioactivity and lipophilicity. Catalytic functionalization gem-difluorodienes represents one the most straightforward approaches to access fluorinated alkenes. In contrast regular 1,3-dienes that undergo diverse asymmetric di/hydrofunctionalizations, regio- enantioselective oxyamination remains untouched. Herein, we report 1,4-oxyamination gem-difluorodiene by chiral rhodium-catalyzed three-component coupling with readily available carboxylic acid dioxazolone, affording gem-difluorinated 1,4-amino alcohol derivatives. Our protocol exhibits high 1,4-regio- enantioselectivity utility late-stage modification pharmaceuticals natural products. Stoichiometric experiments provide evidences for π-allylrhodium pathway. Related was also realized when trifluoroethanol used as an oxygen nucleophile.

Language: Английский

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Copper-catalyzed 1,4-aminohydroxylation and aminothiolation of 1,3-dienes by carbonyl-assisted migration

Chem Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 101147 - 101147

Published: Oct. 1, 2024

Language: Английский

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An Electron‐Deficient Cp^E Iridium(III) Catalyst: Synthesis, Characterization, and Application to Ether‐Directed C−H Amidation

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 15, 2023

The synthesis, characterization, and catalytic performance of an iridium(III) catalyst with electron-deficient cyclopentadienyl ligand ([CpE IrI2 ]2 ) are reported. [CpE was synthesized by complexation a precursor the CpE [Ir(cod)OAc]2 , followed oxidation, desilylation, removal COD ligand. enabled C-H amidation reactions assisted weakly coordinating ether directing group. Experimental mechanistic studies DFT calculations suggested that high is due to its nature, which accelerates both activation IrV -nitrenoid formation.

Language: Английский

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Aminoalcohol Synthesis through Nonprecious Metal Catalysis: Enantioselective Cu-Catalyzed Reductive Coupling of Aldehydes and Allenamides

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4730 - 4734

Published: June 22, 2023

Herein, we report the development of a Cu-catalyzed aminoallylation aldehyde electrophiles through reductive coupling by circumventing problematic competitive reduction electrophile CuH catalyst. This leads to highly diastereo- and enantioselective process for synthesis chiral 1,2-aminoalcohols containing secondary alcohol substitution. Cleavage N substituents on reaction products was performed, allowing access other diastereomer aminoalcohol, which investigated in context eligulstat.

Language: Английский

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Cobalt/Rhodium-Catalyzed Diversified Amidation of Benzocyclobutenols via C–C Cleavage under Catalyst and Condition Control

Organic Letters, Journal Year: 2023, Volume and Issue: 25(27), P. 5078 - 5083

Published: June 29, 2023

Cobalt(III) and rhodium(III)-catalyzed regio- chemoselective amidation of benzocyclobutenols has been realized using dioxazolone as the amidating reagent to afford three classes C-N-coupled products via β-carbon elimination benzocyclobutenol. The Co(III)-catalyzed coupling initially afforded an isolable o-(N-acylamino)arylmethyl ketone, which could further cyclize corresponding indole derivatives under condition control. In contrast, efficient stepwise diamidation achieved Rh(III) catalyst chemoselectivities are jointly controlled by reactions conditions.

Language: Английский

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