Deacylative Thiolation by Redox‐Neutral Aromatization‐Driven C−C Fragmentation of Ketones

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(15)

Опубликована: Фев. 17, 2023

Herein we report the development of deacylative thiolation diverse methyl ketones. The reaction is redox-neutral, and heavy-metal-free, which provides a new way to introduce thioether groups site-specifically unactivated aliphatic positions. It also features excellent functional group tolerance broad substrate scope, thus allowing late-stage derivatization. process benefits from efficient condensation between activation reagent ketone substrates, triggers aromatization-driven C-C fragmentation rapid radical coupling with thiosulfonates. Experimental computational mechanistic studies suggest involvement chain pathway.

Язык: Английский

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Photocatalytic C–C Bond Azidation and Cyanation of Acyclic Ketones via a Pro-aromatic Intermediate

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Herein, we report a formal C–C bond azidation and cyanation of unactivated aliphatic ketones using commercially available tosyl azide cyanide, respectively. A visible-light-mediated organophotocatalyst enables radical ketone-derived pro-aromatic dihydroquinazolinones (under mostly redox-neutral conditions) as supported by preliminary mechanistic studies. These metal-free scalable protocols can be used to synthesize tertiary, secondary, primary alkyl azides nitriles with good functional group tolerance postsynthetic diversification the group, including bioconjugation.

Язык: Английский

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Ketone-derived 2,3-dihydroquinazolinones inN-heteroarene C–H alkylationviaC–C bond scission under oxidative metal catalysis

Chemical Communications, Год журнала: 2022, Номер 58(95), С. 13202 - 13205

Опубликована: Янв. 1, 2022

A silver-catalysed oxidative sp2 C-H alkylation of N-heteroarenes with ketone-derived 2,3-dihydroquinazolinones at room temperature is developed. The combination a metal catalyst and perdisulfate oxidant promotes the rarely explored thermal activation pre-aromatic 2,3-dihydroquinazolinone to generate an alkyl radical, supported by mechanistic studies. In addition broad scope, good functionality tolerance, late stage functionalization APIs, synthesis novel Papaverine analogue, utilization N-heteroarene bond ketone as non-trivial radical source represents salient feature this method.

Язык: Английский

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Photocatalytic Alkylation/Arylative Cyclization of N-Acrylamides of N-Heteroarenes and Arylamines with Dihydroquinazolinones from Unactivated Ketones

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(16), С. 12121 - 12130

Опубликована: Июль 29, 2023

We describe a visible-light photoredox-catalyzed alkylation/arylative cyclization of N-acrylamides─from 2-arylindoles, 2-arylbenzimidazoles, or N-substituted anilines─with ketone-derived dihydroquinazolinones, accessing indolo- and benzimidazolo[2,1-a]isoquinolines 2-oxindoles. The consecutive incorporation alkyl- aryl-carbogenic motifs across C=C bond via formal cleavage ketone α-C-C arene C-H bonds leads to the formation five- six-membered rings, with an all-carbon quaternary stereocenter. This dicarbofunctionalization elaborates aromatization-driven radical C-C functionalization unactivated aliphatic ketones construct diverse cyclic structures functionality tolerance.

Язык: Английский

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Catalytic asymmetric deuterosilylation of exocyclic olefins with mannose-derived thiols and deuterium oxide

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(5), С. 1182 - 1190

Опубликована: Янв. 1, 2023

Metal-free, photoinduced asymmetric deuterosilylation of exocyclic olefins has been achieved using a mannose-derived thiol catalyst.

Язык: Английский

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Bidirectional Elongation Strategy Using Ambiphilic Radical Linchpin for Modular Access to 1,4-Dicarbonyls via Sequential Photocatalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(37), С. 20344 - 20354

Опубликована: Июль 25, 2023

Organic molecules that can be connected to multiple substrates by sequential C-C bond formations utilized as linchpins in multicomponent processes. While they are useful for rapidly increasing molecular complexity, most of the reported linchpin coupling methods rely on use organometallic species strong carbon nucleophiles form bonds, which narrows functional group compatibility. Here, we describe a metal-free, radical-mediated approach using formyl-stabilized phosphonium ylide multifunctional under visible-light photoredox conditions. The present method uses ambiphilic character ylide, serves both nucleophilic and an electrophilic carbon-centered radical source. stepwise controllable generation these intermediates allows photocatalysis involving two mechanistically distinct additions, initiated same photocatalyst one pot with high tolerance. methodology enables bidirectional assembly electronically differentiated alkene fragments thus offers rapid modular access 1,4-dicarbonyl compounds versatile synthetic intermediates.

Язык: Английский

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Methyl Ketones as Alkyl Halide Surrogates: A Deacylative Halogenation Approach for Strategic Functional Group Conversions

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(38), С. 21096 - 21103

Опубликована: Сен. 15, 2023

Alkyl halides are versatile precursors to access diverse functional groups (FGs). Due their lability, the development of surrogates for alkyl is strategically important complex molecule synthesis. Given stability and ease derivatization inherent in common ketones, here we report a deacylative halogenation approach convert various methyl ketones corresponding chlorides, bromides, iodides. The reaction driven by forming an aromatic byproduct, i.e., 1,2,4-triazole, which N′-methylpicolinohydrazonamide (MPHA) employed form prearomatic intermediate halogen atom-transfer (XAT) reagents used quench radical intermediate. efficient yielding primary secondary from wide range with broad FG tolerance. It also works natural-product-derived fluoro-containing substrates. In addition, one-pot conversions other FGs annulations alkenes alkynes through realized. Moreover, unusual iterative homologation iodides demonstrated. Finally, mechanistic studies reveal intriguing double XAT process iodination reaction, could have implications beyond this work.

Язык: Английский

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Photoinduced C−O Bond Formation through C−C Bond Cleavage of Alcohols by Suppressing Alcohol Oxidation

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(7), С. 1595 - 1605

Опубликована: Фев. 3, 2024

Abstract Herein, we present a photoinduced deconstructive alkoxyamination of alkyl alcohols catalyzed by iron salts. This transformation involves the initiation alkoxy radicals through chlorine radical‐induced radical formation, followed β ‐scission and trapping resulting carbon with 2,2,6,6‐tetramethylpiperidin‐1‐yl (TEMPO). reaction exhibits broad substrate scope (40 examples), including primary secondary that are prone to oxidation combination TEMPO iron. Mechanistic investigations have revealed enhanced coordination chloride ion center inhibits OH process, thereby enabling tolerance alcohols.

Язык: Английский

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Direct excitation strategy for deacylative couplings of ketones

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Июль 24, 2024

Abstract The homolysis of chemical bonds represents one the most fundamental reactivities excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike contemporary radical‐generating mechanisms, direct excitation homolyze and produce aliphatic carbon‐centered visible remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation homolytic C−C bond cleavage release alkyl without external photocatalysts. Spectroscopic computational analysis reveal unique optical structural features DHPQs, rationalizing their faster kinetics radical generation than a structurally similar but visible‐light transparent precursor. Such capability allows DHPQ facilitate wide range Ni‐metallaphotoredox couplings with aryl, alkynyl acyl halides. Other catalytic non‐catalyzed alkylative transformations DHPQs are also feasible various acceptors. We believe this work would be broad interest, aiding synthetic planning simplified operation expanding reach photocatalyst‐free approaches cutting‐edge research.

Язык: Английский

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Photoinduced Radical Cyclization of 1,6‐Diynes: Rapid Access to Highly Substituted Carbocyclic and Heterocyclic Compounds

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(7), С. 1012 - 1019

Опубликована: Март 7, 2023

Abstract We have developed photoinduced sulfonyl radical‐triggered cyclization of 1,6‐dynes without metals, oxidants, or additives. During the reaction, three new bonds are formed (−SO 2 −C, C−C, and C−I/C−Se−) under mild conditions, with excellent selectivity. The conversion is temporally atomically economical easy to handle even on a gram scale. Detailed mechanistic studies showed that reaction proceeds via radical pathway. Subsequent synthetic transformations products produced various substituted compounds. Importantly, we observed an unprecedented selective C−C single bond cleavage boronic acid insertion Suzuki conditions. magnified image

Язык: Английский

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