Benzylic C–H Esterification with Limiting C–H Substrate Enabled by Photochemical Redox Buffering of the Cu Catalyst

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(17), P. 9434 - 9440

Published: April 21, 2023

Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, with peroxide-based oxidants often require excess substrate. Here, we report photochemical to overcome this limitation by using Cu/2,2'-biquinoline catalyst that supports benzylic esterification limiting Mechanistic studies indicate blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state CuII CuI, which activates the peroxide generate an alkoxyl radical hydrogen-atom-transfer species. This "photochemical redox buffering" introduces unique sustain activity of Cu catalysts in reactions.

Language: Английский

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A General Photocatalytic Strategy for Nucleophilic Amination of Primary and Secondary Benzylic C–H Bonds

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(33), P. 18487 - 18496

Published: Aug. 11, 2023

We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp3)-H bonds. A novel amidyl radical precursor organic photocatalyst operate in tandem to transform bonds into carbocations via sequential hydrogen atom transfer (HAT) oxidative radical-polar crossover. The resulting carbocation can be intercepted by variety N-centered nucleophiles, including nitriles (Ritter reaction), amides, carbamates, sulfonamides, azoles, for the construction pharmaceutically relevant C(sp3)-N under unified reaction conditions. Mechanistic studies indicate HAT is radical-mediated operates reductive quenching pathway. These findings establish mild, metal-free, modular protocol rapid diversification library aminated products.

Language: Английский

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Intermolecular Enantioselective Benzylic C(sp³)−H Amination by Cationic Copper Catalysis**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(24)

Published: April 14, 2023

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3 )-H functionalization by hydrogen-atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods intermolecular amination remain elusive. Herein, we report cationic copper catalytic system with peroxide an oxidant. This mild, straightforward method can be used to transform array feedstock alkylarenes and amides into high enantioselectivities, it good functional group tolerance broad substrate scope. More importantly, synthesize bioactive molecules, including drugs. Preliminary mechanistic studies indicate that reaction involves radicals generated transfer.

Language: Английский

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Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer

Molecules, Journal Year: 2023, Volume and Issue: 28(16), P. 6127 - 6127

Published: Aug. 18, 2023

The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple equivalents for synthons. Hydrogen atom transfer (HAT) is a key method forming alkyl radicals from substrates. Classic reactions, including the Barton nitrite ester reaction Hofmann–Löffler–Freytag reaction, among others, provided early examples HAT. However, recent developments photoredox catalysis electrochemistry have made HAT powerful tool capable introducing wide range functional groups into bonds. Moreover, greater mechanistic insights stimulated development increasingly site-selective protocols. Site-selectivity can be achieved through tuning electron density at certain using additives, judicious choice reagent, solvent system. Herein, we describe latest methods functionalizing C–H/Si–H/Ge–H indirect between 2018–2023, as well critical discussion reagents, aspects, substrate scopes, background contexts

Language: Английский

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Desymmetrization–Addition Reaction of Cyclopropenes to Imines via Synergistic Photoredox and Cobalt Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 18892 - 18898

Published: July 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

Language: Английский

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Visible-light induced direct C(sp³)–H functionalization: recent advances and future prospects

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(18), P. 5278 - 5305

Published: Jan. 1, 2024

This review summarizes the latest methodological advances in photocatalytic C(sp 3 )–H functionalization, with a particular emphasis on formation of C–P, C–B, C–S bonds, etc ., and some prominent efforts asymmetric C–H functionalization.

Language: Английский

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Dual Nickel/Photoredox‐Catalyzed Asymmetric Carbamoylation of Benzylic C(sp³)−H Bonds

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 12, 2024

Abstract Radical‐mediated Hydrogen Atom Abstraction of Csp 3 −H bonds has become a powerful tool for the asymmetric functionalization organic feedstocks. Here, we present an synthesis α ‐aryl amides via carbamoylation alkylarenes with isocyanates as electrophiles. The synergistic combination photoredox and chiral nickel‐catalyst, enables use readily available neutral reagents under mild reaction conditions provides straightforward access to pharmacologically relevant motifs in enantiomerically pure form.

Language: Английский

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Recent advances in C(sp³)–N bond formation via metallaphoto-redox catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(50), P. 6340 - 6361

Published: Jan. 1, 2024

In this review, the state-of-the-art advances in radical-involved C(sp 3 )–N bond formation via metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.

Language: Английский

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Polar Heterobenzylic C(sp³)–H Chlorination Pathway Enabling Efficient Diversification of Aromatic Nitrogen Heterocycles

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(36), P. 19832 - 19839

Published: Aug. 29, 2023

Site-selective radical reactions of benzylic C–H bonds are now highly effective methods for C(sp3–H) functionalization and cross-coupling. The existing methods, however, often ineffective with heterobenzylic in alkyl-substituted pyridines related aromatic heterocycles that prominently featured pharmaceuticals agrochemicals. Here, we report new synthetic leverage polar, rather than radical, reaction pathways to enable the selective chlorination 2- 4-alkyl-substituted other heterocycles. Catalytic activation substrate trifluoromethanesulfonyl chloride promotes formation enamine tautomers react readily electrophilic reagents. resulting heterobenzyl chlorides can be used without isolation or purification nucleophilic coupling reactions. This chlorination–diversification sequence provides an efficient strategy achieve cross-coupling aliphatic amines a diverse collection azoles, among partners.

Language: Английский

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Regio- and Enantioselective Nickel-Catalyzed Ipso- and Remote Hydroamination Utilizing Organic Azides as Amino Sources for the Synthesis of Primary Amines

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

Published: Oct. 23, 2024

Primary amines serve as key synthetic precursors to most other

Language: Английский

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