Radical Reactions with N-Heterocyclic Carbene (NHC)-Derived Acyl Azoliums for Access to Multifunctionalized Ketones

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8270 - 8293

Published: May 13, 2024

As one of the most important key intermediates, NHC-bound acylazolium-based ionic transformations have been intensively explored in past two decades. With expeditious development NHC-catalyzed radical recent years, acylazolium chemistry has reached another level, with number relevant publications increasing significantly. However, a summary focused on acylations NHC-derived acyl azoliums classified according to mechanistic difference not reported. Such detailed classification and deep analysis provide opportunities for better understanding history trend this field. In review, reactions N-heterocyclic carbene (NHC)-derived are systematically introduced. The achievements challenges within area also summarized discussed at end.

Language: Английский

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Photoinduced Electron Transfer from Xanthates to Acyl Azoliums: Divergent Ketone Synthesis via N‐Heterocyclic Carbene Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 12, 2023

Considering the prevalence of alcohols and carboxylic acids, their fragment cross-coupling reactions could hold significant implications in organic synthesis. Herein, we report a versatile method for synthesizing diverse range ketones from acid derivatives via N-heterocyclic carbene (NHC) catalysis. Mechanistic investigations revealed that photoexcited xanthates acyl azoliums undergo single electron transfer (SET) under photocatalyst-free conditions, generating NHC-derived ketyl radicals alkyl radicals. These open-shell intermediates subsequently radical-radical reaction, yielding valuable ketones. Furthermore, this approach can be employed three-component involving alkenes enynes, resulting structurally cross-coupled The unified strategy offers unique opportunity coupling derivatives, accommodating functional groups even complex settings.

Language: Английский

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Light‐Driven Enantioselective Carbene‐Catalyzed Radical‐Radical Coupling

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Oct. 17, 2023

Abstract An enantioselective carbene‐catalyzed radical‐radical coupling of acyl imidazoles and racemi c Hantzsch esters is disclosed. This method involves the an N‐heterocyclic carbene‐derived ketyl radical a secondary sp 3 ‐carbon allows access to chiral α‐aryl aliphatic ketones in moderate‐to‐good yields enantioselectivities without any competitive epimerization. The utility this protocol highlighted by late‐stage functionalization various pharmaceutical compounds further demonstrated transformation enantioenriched products biologically relevant molecules. Computational investigations reveal carbene controls double‐facial selectivity alkyl radicals, respectively.

Language: Английский

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Mesoionic Carbene‐Catalyzed Formyl Alkylation of Aldehydes

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

Published: April 18, 2023

Ketones are among the most useful functional groups in organic synthesis, and they commonly encountered a broad range of compounds with various applications. Herein, we describe mesoionic carbene-catalyzed coupling reaction aldehydes non-activated secondary even primary alkyl halides. This metal-free method utilizes deprotonated Breslow intermediates derived from carbenes (MICs), which act as super electron donors induce single-electron reduction mild has substrate scope tolerates many groups, allows to prepare diversity simple ketones well bio-active molecules by late-stage functionalization.

Language: Английский

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Carbene‐Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp³)−H Bonds

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

Published: April 5, 2023

The development of catalyst-controlled methods for direct functionalization two distinct C-H bonds represents an appealing approach C-C formations in synthetic chemistry. Herein, we describe organocatalytic straightforward acylation C(sp3 )-H employing readily available aldehyde as "acyl source" involving dehydrogenative coupling aldehydes with ether, amine, or benzylic bonds. developed method affords a broad range ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential the oxidative radical N-heterocyclic carbene catalysis to give ketyl and ) through rarely explored intermolecular hydrogen atom transfer pathway, rendering acylative high efficiency metal- light-free catalytic Moreover, prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.

Language: Английский

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Organocatalytic C−H Functionalization of Simple Alkanes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(45)

Published: Sept. 21, 2023

The direct functionalization of inert C(sp3 )-H bonds to form carbon-carbon and carbon-heteroatom offers vast potential for chemical synthesis therefore receives increasing attention. At present, most successes come from strategies using metal catalysts/reagents or photo/electrochemical processes. use organocatalysis this purpose remains scarce, especially when dealing with challenging C-H such as those simple alkanes. Here we disclose the first organocatalytic functionalization/acylation completely unfunctionalized Our approach involves N-heterocyclic carbene catalyst-mediated carbonyl radical intermediate generation coupling alkanes (through corresponding alkyl intermediates generated via a hydrogen atom transfer process). Unreactive are widely present in fossil fuel feedstocks, commercially important organic polymers, complex molecules natural products. study shall inspire new avenue quick these under light- metal-free catalytic conditions.

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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Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5580 - 5596

Published: Feb. 12, 2024

Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, mechanism and wavelength-dependent efficiency of transformation have remained unclear. In work, we increased electron richness nitrogen in azacycles improve light absorption strengthen critical intramolecular hydrogen bonding while enabling direct installation photoreactive handle. As result, broadly expanded substrate scope, including underexplored electron-rich previously unsuccessful now achieved. The significantly improved yields diastereoselectivities facilitated reaction rate, kinetic isotope effect (KIE), quenching studies, addition determination quantum yields. Guided by these propose revised ET/PT contraction, which is additionally corroborated computational characterization lowest-energy excited states through time-dependent DFT. at wavelengths longer than those strongly absorbed was investigated rate measurements, revealed red shift photochemical action plot relative absorbance. elucidated mechanistic photophysical details effectively rationalize empirical observations, additive effects, were poorly understood. Our findings not only demonstrate enhanced synthetic utility shed but may also offer valuable guidance understanding reactivity related systems.

Language: Английский

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Visible light-mediated NHC and photoredox co-catalyzed 1,2-sulfonylacylation of allenesviaacyl and allyl radical cross-coupling

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(4), P. 1047 - 1055

Published: Jan. 1, 2023

Visible light-mediated NHC and photoredox co-catalyzed radical 1,2-sulfonylacylation of allenes via cross-coupling between an allyl NHC-stabilized acyl radical.

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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