Light-Driven N-Heterocyclic Carbene Catalysis Using Alkylborates

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(21), P. 12886 - 12892

Published: Oct. 8, 2021

Radical–radical coupling, the selective reaction between two different radical species, has contributed to methodology for connecting bulky units. Light-driven N-heterocyclic carbene (NHC) organocatalysis is recognized as a state-of-the-art enabling radical–radical coupling. The catalytic process involves forming an acyl azolium intermediate from NHC catalyst and donor, followed by single electron reduction of this key intermediate, which largely dependent on photoredox catalyst. We designed catalysis in direct photoexcitation borate form high reducing agent facilitated event. produces alkyl transfer accomplish This protocol enables cross-coupling alkylborates imidazoles addition relay-type alkylacylations alkenes with imidazoles, affording ketones broad scope.

Language: Английский

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Suzuki-type cross-coupling of alkyl trifluoroborates with acid fluoride enabled by NHC/photoredox dual catalysis

Chemical Science, Journal Year: 2022, Volume and Issue: 13(9), P. 2584 - 2590

Published: Jan. 1, 2022

An acylative Suzuki-type cross-coupling of alkyl trifluoroborates and acid fluorides was developed by merging NHC organocatalysis with photoredox catalysis. A broad spectrum ketones could be facilely synthesised under mild reaction conditions.

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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Combined Photoredox and Carbene Catalysis for the Synthesis of α-Amino Ketones from Carboxylic Acids

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(4), P. 2522 - 2531

Published: Feb. 4, 2022

α-Amino ketone moieties are present in many pharmacologically active molecules, but their synthesis is challenging. Herein, we report a mild, operationally simple method for direct acylation of α-amino C(sp3)–H bonds from carboxylic acids via the merger carbene and photoredox catalysis. Specifically, cross-coupling reactions between wide range acids, class feedstock chemicals, readily available N-alkyl anilines by means single-electron N-heterocyclic catalysis combined with photocatalysis provided access to structurally diverse ketones. The features broad substrate scope compatible array functional groups. To demonstrate potential applications method, subjected one products further transformations.

Language: Английский

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Synthesis of Cyclohexanones by a Tandem Photocatalyzed Annulation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(16), P. 7030 - 7037

Published: March 22, 2022

The rapid synthesis of cyclic scaffolds is high importance to the chemistry community. Strategies for convergent substituted carbocycles and heterocycles remain underexplored despite plethora applications that these motifs have in pharmaceutical materials industries. Reported herein a tandem carbene photoredox-catalyzed process cycloalkanones via formal [5 + 1] cycloaddition. Featuring two distinct photoredox cycles novel α-oxidation benzylic ketones, this reaction offers mild approach construct contiguous C-C bonds eliminates need strong bases or expensive metal catalysts. utility method highlighted through various product diversification reactions allow access range important scaffolds.

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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Oxidative Radical NHC Catalysis: Divergent Difunctionalization of Olefins through Intermolecular Hydrogen Atom Transfer

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 9, 2022

Oxidative N-heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one most important activation strategies for NHC-catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as external single-electron oxidant realize divergent difunctionalization olefins. The key success this chemistry is catalytic generation oxygen radicals that could trigger intermolecular hydrogen atom transfer activate inert C-H bonds, thereby enabling productive relay process. With protocol, commonly used general chemicals serve precursors allow efficient synthesis value-added products in a straightforward and cost-effective manner. Preliminary mechanistic investigations, including control experiments DFT calculations, shed light on organocatalytic reaction mechanism.

Language: Английский

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Enantioselective functionalization at the C4 position of pyridinium salts through NHC catalysis

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

Published: April 1, 2022

Abstract A catalytic method for the enantioselective and C4-selective functionalization of pyridine derivatives is yet to be developed. Herein, we report an efficient asymmetric β-pyridylations enals that involve N-heterocyclic carbene (NHC) catalysis with excellent control over enantioselectivity pyridyl C4-selectivity. The key strategy precise stereocontrol involves enhancing interactions between chiral NHC-bound homoenolate pyridinium salt in presence hexafluorobenzene, which effectively differentiates two faces radical. Room temperature sufficient this transformation, reaction efficiency further accelerated by photo-mediation. This methodology exhibits broad functional group tolerance enables facile access a diverse range enantioenriched β-pyridyl carbonyl compounds under mild metal-free conditions.

Language: Английский

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