Enantioselective Catalysis by the Umpolung of Conjugate Acceptors Involving N-Heterocyclic Carbene or Organophosphine 1,4-Addition

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(10), P. 1190 - 1203

Published: April 24, 2023

ConspectusConjugate acceptors are one of the most common electrophilic functional groups in organic synthesis. While useful a diverse range transformations, their applications largely dominated by reactions from which name is derived (i.e., as an acceptor nucleophiles conjugate position). In 2014, we commenced studies focused on ability to undergo polarity inversion through addition Lewis base catalysts. The first step this process provides enolate, well-developed Rauhut-Currier (RC) and Morita-Baylis-Hillman (MBH) can occur; however, tautomerization provide species β-carbon now act donor also possible. When topic, reaction designs with type species, particularly when accessed using N-heterocyclic carbenes (NHCs), had been reported only handful occasions. Despite lack development, conceptually it was felt that taking advantage switching have number desirable features. Perhaps significant potential reimagine ubiquitous group entirely new synthon, namely, electrophiles position.Our work has catalysis both simple those embedded within more complicated substrates; latter allowed series cycloisomerizations annulation be achieved. cases, possible enantioenriched chiral NHCs or organophosphines catalysts thereby delivering enantioselective approaches novel cyclic molecules. related chemistry either family catalyst, all cases designed take other. addition, fine balance exists between exploit initially formed enolate involve polarity-inverted β-anion. our studies, addressed substrate design, although catalyst control may We consider discussed Account its infancy. Significant challenges remain before broad aim discovering universal approach These broadly relate chemoselectivity substrates bearing multiple functionalities, reliance upon use acceptors, efficiency. To address these challenges, advances design cooperativity likely required.

Language: Английский

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N‐Heterocyclic carbene enabled functionalization of inert C(sp3)‐H bonds via hydrogen atom transfer (HAT) processes

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

Published: Aug. 2, 2024

Abstract Developing methods to directly transform C(sp 3 ) −H bonds is crucial in synthetic chemistry due their prevalence various organic compounds. While conventional protocols have largely relied on transition metal catalysis, recent advancements organocatalysis, particularly with radical NHC catalysis sparked interest the direct functionalization of “inert” for cross C−C coupling carbonyl moieties. This strategy involves selective cleavage generate key carbon radicals, often achieved via hydrogen atom transfer (HAT) processes. By leveraging bond dissociation energy (BDE) and polarity effects, HAT enables rapid diverse )−H substrates, such as ethers, amines, alkanes. mini‐review summarizes progress carbene organocatalytic inert enabled by processes, categorizing them into two sections: 1) C−H involving acyl azolium intermediates; 2) reductive Breslow intermediates.

Language: Английский

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Regiodivergent Organocatalytic Reactions

Catalysts, Journal Year: 2021, Volume and Issue: 11(8), P. 1013 - 1013

Published: Aug. 22, 2021

Organocatalysts are abundantly used for various transformations, particularly to obtain highly enantio- and diastereomeric pure products by controlling the stereochemistry. These applications of organocatalysts have been topic several reviews. emerged as one very essential areas research due their mild reaction conditions, cost-effective nature, non-toxicity, environmentally benign approach that obviates need transition metal catalysts other toxic reagents. Various types including amine catalysts, Brønsted acids, Lewis bases such N-heterocyclic carbene (NHC) cinchona alkaloids, 4-dimethylaminopyridine (DMAP), hydrogen bond-donating gained renewed interest because regioselectivity. In this review, we present recent advances in regiodivergent reactions governed organocatalysts. Additionally, briefly discuss pathways achieving changes conditions solvents, additives, or temperature.

Language: Английский

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Cooperative NHC/Photoredox Catalysis: Three Component Radical Coupling of Aroyl Fluorides, Styrenes and Alcohols

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 364(19), P. 3348 - 3353

Published: July 23, 2022

Abstract Cooperative NHC/photoredox catalysis has emerged as an important research field in recent years. Herein, the use of tertiary alcohols alkyl radical precursors to perform three component coupling with styrenes and aroyl fluorides for preparation α‐arylated aryl ketones is described. Reaction fluoride NHC catalyst provides acyl azolium ion that can be reduced by photoredox corresponding ketyl anion. Oxidatively generated C‐radicals derived from alcohol add styrene derivative subsequent cross adduct delivers after fragmentation targeted ketone. magnified image

Language: Английский

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Construction of N-Polyheterocycles by N-Heterocyclic Carbene Catalysis via a Regioselective Intramolecular Radical Addition/Cyclization Cascade

Organic Letters, Journal Year: 2022, Volume and Issue: 24(25), P. 4615 - 4619

Published: June 22, 2022

N-Polyheterocycles are rapidly accessed by N-heterocyclic carbene (NHC) catalysis through regioselective sequential radical addition/cyclization in the absence of any metals or oxidants. The transformation occurs under mild conditions and enjoys a wide substrate scope with excellent functional group compatibility. Furthermore, gram-scale synthesis is also conducted. Preliminary mechanistic studies reveal potential involvement an NHC cation intermediate.

Language: Английский

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Fluorinated Ketones as Trapping Reagents for Visible-Light-Induced Singlet Nucleophilic Carbenes

Organic Letters, Journal Year: 2021, Volume and Issue: 23(7), P. 2783 - 2789

Published: March 18, 2021

Singlet nucleophilic carbenes (SNCs) containing only one heteroatom donor remain underutilized in chemical synthesis. We recently discovered that visible-light-induced SNC intermediates can be trapped by fluorinated ketones via 1,2-carbonyl addition to afford benzoin-type products. This discovery represents a rare example of reacting with and delivers an efficient, user-friendly, scalable process for accessing tertiary alcohol derivatives driven light circumventing the use exogenous catalysts or additives.

Language: Английский

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N‐Heterocyclic Carbene/Carboxylic Acid Co‐Catalysis Enables Oxidative Esterification of Demanding Aldehydes/Enals, at Low Catalyst Loading

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(36), P. 19631 - 19636

Published: May 19, 2021

Abstract We report the discovery that simple carboxylic acids, such as benzoic acid, boost activity of N‐heterocyclic carbene (NHC) catalysts in oxidative esterification aldehydes. A and efficient protocol for transformation a wide range sterically hindered α‐ β‐substituted aliphatic aldehydes/enals, catalyzed by novel readily accessible N‐Mes‐/N‐2,4,6‐trichlorophenyl 1,2,4‐triazolium salt, acid co‐catalyst, was developed. whole series α/β‐substituted aldehydes/enals hitherto not amenable to NHC‐catalyzed could be reacted at typical catalyst loadings 0.02–1.0 mol %. For benzaldehyde, even 0.005 % NHC proved sufficient: lowest value ever achieved catalysis. Preliminary studies point acid‐induced acceleration acyl transfer from azolium enolate intermediates mechanistic basis observed effect.

Language: Английский

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Combined Power of Organo‐ and Transition Metal Catalysis in Organic Synthesis

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(20)

Published: April 22, 2022

Abstract The combination of organocatalysis with transition metal catalysis is an emerging research area for the scientific community. Various unprecedented transformations that are otherwise inaccessible by individual catalytic systems can be achieved good efficiency and stereocontrolled manner this dual‐catalytic strategy. This Review presents a detailed discussion on recent advances in dual combining catalysis, covering literature last five years. A wide variety combinations metals organocatalysts including aminocatalysts, such as secondary amines more primary amines, Brønsted acid catalysts, especially phosphoric acids based chiral BINOL scaffold N ‐heterocyclic carbene discussed. Considering great contribution domain to organic synthesis, present future potential new exciting field highlighted.

Language: Английский

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NHC-Catalyzed Enantioselective Synthesis of Tetracyclic δ-Lactones by (4 + 2) Annulation of ortho-Quinodimethanes with Activated Ketones

Organic Letters, Journal Year: 2023, Volume and Issue: 25(43), P. 7852 - 7857

Published: Oct. 20, 2023

The N-heterocyclic carbene (NHC)-catalyzed generation of ortho-quinodimethanes (o-QDMs) from 9H-fluorene-1-carbaldehydes followed by the interception with activated ketones resulting in enantioselective synthesis tetracyclic δ-lactones is presented. High diastereoselectivity products, remote C(sp3)-H functionalization, broad substrate scope, and mild reaction conditions are notable features present (4 + 2) annulation.

Language: Английский

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N-Heterocyclic-Carbene-Catalyzed Imine Umpolung for the Cross-Coupling of Quinoxalin-2-ones with Isatins

JACS Au, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

The N-heterocyclic carbene (NHC)-catalyzed umpolung of aldimines using quinoxalin-2-ones for intermolecular reactions is demonstrated. Specifically, NHC-catalyzed cross-coupling with isatins proceeds via the generation aza-Breslow intermediates by addition to C═N moiety quinoxalinones followed interception afford diverse oxindoles in moderate good yields and functional group compatibility. Moreover, detailed mechanistic studies involving isolation characterization imidoyl azoliums (oxidized form intermediates) are provided. Considering significance scaffolds bearing both quinoxalin-2-one oxindole moieties medicine natural products, synthesized molecules employing imine strategy likely find promising applications.

Language: Английский

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