Radical NHC Catalysis

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(19), P. 11984 - 11999

Published: Sept. 19, 2022

Radical/radical cross-coupling reactions represent an efficient and straightforward approach for the construction of chemical bonds accordingly have drawn increasing attention over past decades. In order to achieve synthetically useful transformations, a persistent radical should be coupled with transient in accordance effect (PRE). However, known radicals outnumber by far types free radicals, which limits widespread application PRE, until today. Thus, development between has been focus, meanwhile transition-metal catalysis successfully implemented artificially prolong lifetimes, allowing their utilization formal radical/radical cross-couplings. Complementary research field recently uncovered that organocatalytically generated NHC-derived ketyl are type catalytically radicals. NHC-catalyzed transformations aldehydes carboxylic acid derivatives enabled disclosure ever-increasing number interesting reactions, different from traditional ionic processes, offering otherwise inaccessible activation modes. These discoveries opened door NHC organocatalysis manipulation reactions. Due its obvious potential synthetic organic chemistry, it is timely provide perspective on this emerging field.

Language: Английский

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Single-electron carbene catalysis in redox processes

Trends in Chemistry, Journal Year: 2022, Volume and Issue: 4(4), P. 277 - 290

Published: Feb. 11, 2022

Language: Английский

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Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 23, 2022

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile a precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized precursors two-component coupling. Herein, an N-heterocyclic catalyzed decarboxylative carboxylic acids imidazoles disclosed, in which the are directly used precursors. could also be generated situ by reaction acid with CDI thus furnishing formally two acids. In addition, successfully extended three-component using alkene third partner via relay process. mild conditions, operational simplicity, use reacting partners make our powerful strategy construction complex ketones from readily available starting materials, late-stage modification natural products medicines.

Language: Английский

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Organic Photoredox-Catalyzed Silyl Radical Generation from Silylboronate

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(13), P. 7804 - 7810

Published: June 16, 2022

A visible-light-driven silyl radical generation method from silylboronates has been developed. The activation of with a catalytic amount mild base promoted the single-electron oxidation process to form radicals. Facile single electron transfer for borate readily occurred without hydrogen atom hydrosilane in presence various photoredox catalysts. Combining this protocol radical-mediated N-heterocyclic carbene catalysis enabled acylsilylation alkenes via relay generation. Furthermore, recent advanced methods synthesis significantly improved utility process.

Language: Английский

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A light-driven enzymatic enantioselective radical acylation

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 74 - 78

Published: Dec. 18, 2023

Language: Английский

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Critical Assessment of the Reducing Ability of Breslow‐type Derivatives and Implications for Carbene‐Catalyzed Radical Reactions**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(51), P. 26783 - 26789

Published: Oct. 15, 2021

Abstract We report the synthesis of acyl azolium salts stemming from thiazolylidenes C NS , triazolylidenes TN mesoionic carbenes MIC and generation their corresponding radicals enolates, covering about 60 Breslow‐type derivatives. This study highlights role additives in redox behavior these compounds unveils several critical misconceptions radical transformations aldehyde derivatives under N‐heterocyclic carbene catalysis. In particular, reducing ability enolates has been dramatically underestimated case biomimetic . contrast with previous electrochemical studies, we show that catalytic intermediates can transfer electrons to iodobenzene within minutes at room temperature. Enols derived are not previously claimed super electron donors, although enolate powerful agents.

Language: Английский

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Remote C(sp³)−H Acylation of Amides and Cascade Cyclization via N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(15)

Published: Feb. 3, 2022

Abstract The direct functionalization of inert C(sp 3 )−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote acylation amides and cascade cyclization through radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, diversity nitrogen‐containing substrates, including simple linear aliphatic carbamates ortho ‐alkyl benzamides, can be successfully applied to this system. With established protocol, over 120 examples functionalized δ‐amino ketones isoquinolinones with diverse substituents were easily synthesized up 99 % yield mild conditions. robustness generality strategy further highlighted by successful unactivated late‐stage modification pharmaceutical molecules. Then, asymmetric control radical reaction was attempted proven feasible newly designed chiral thiazolium catalyst, moderate enantioselectivity obtained at current stage. Preliminary mechanistic investigations several reactions, KIE experiments, computational studies shed light on mechanism.

Language: Английский

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Photoredox cooperative N-heterocyclic carbene/palladium-catalysed alkylacylation of alkenes

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 30, 2022

Three-component carboacylation of simple alkenes with readily available reagents is challenging. Transition metal-catalysed intermolecular works for strained ring or directing groups. Herein, we develop a photoredox cooperative N-heterocyclic carbene/Pd-catalysed alkylacylation aldehydes and unactivated alkyl halides to provide ketones in good yields. This multicomponent coupling reaction features wide scope alkenes, broad functional group compatibility free exogenous photosensitizer external reductant. In addition, series chlorinated cyclopropanes one two vicinal quaternary carbons obtained when chloroform carbon tetrachloride used as the halide. The involves radicals from ketyl under carbene/Pd catalysis.

Language: Английский

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N-Heterocyclic Carbene-Photocatalyzed Tricomponent Regioselective 1,2-Diacylation of Alkenes Illuminates the Mechanistic Details of the Electron Donor–Acceptor Complex-Mediated Radical Relay Processes

ACS Catalysis, Journal Year: 2021, Volume and Issue: 12(1), P. 285 - 294

Published: Dec. 15, 2021

Progress in the development of photocatalytic reactions requires a detailed understanding mechanisms underpinning observed reactivity, yet mechanistic details many systems, especially those that involve electron donor–acceptor complexes, have remained elusive. We report herein and combined computational study alkene 1,2-diacylation enables regioselective installation two different acyl groups, establishing direct, tricomponent access to 1,4-diketones, key intermediates heterocyclic medicinal chemistry. The studies revealed central role complex formed from an N-heterocyclic carbene (NHC) catalyst-derived intermediate transfer reagent, providing description structural electronic factors determining characteristics photoinduced charge-transfer process mediates transformation. in-depth investigation also illuminated roles other radical donors relevant catalytic activities carbenes reactions.

Language: Английский

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Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(49), P. 22767 - 22777

Published: Nov. 24, 2022

There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation trisubstituted alkenes. Different from photoredox single electron transfer deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with prochiral C-centered radical. This operationally simple method provides a straightforward access variety pyrroline oxazolidinone heterocycles vicinal stereocenters (77 examples, up >19:1 d.r.). Electrochemical studies acyl thiazolium salts support our reaction design highlight reducing ability Breslow-type derivatives. A detailed computational analysis this organocatalytic system suggests that radical–radical coupling is rate-determining step, π–π stacking interaction between radical intermediates subtly controls diastereoselectivity.

Language: Английский

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