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

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(95), P. 13202 - 13205

Published: Jan. 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.

Language: Английский

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Nickel-Catalyzed Electro-Reductive Cross-Coupling of Aliphatic N-Acyl Imides with Alkyl Halides as a Strategy for Dialkyl Ketone Synthesis: Scope and Mechanistic Investigations

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(19), P. 12315 - 12325

Published: Sept. 27, 2022

The development and in-depth study of a cross-electrophile coupling alkyl N-acyl imides with halides relying on the combination nickel catalysis electrochemistry are described. This methodology takes advantages stability simple access as partners for selective synthesis dissymmetric dialkyl ketones. Noteworthy, developed electrochemical protocol affords to linear ketones when using primary bromides featuring different chain lengths. Mechanistic studies including cyclic voltammetry, stoichiometric reactions, isolation catalytic intermediates provide set fundamental insights into monovalent (bpy)nickel-mediated activation imides. Alkyl react electrogenerated (bpy)Ni(I) species via single-electron oxidation give radicals. N-Acyl shown undergo spontaneous C–N bond oxidative addition at both (bpy)Ni(0) species, leading Ni(II) acyl intermediates. A stable nickel(II) complex has also been isolated fully characterized, its competency is demonstrated. Finally, (bpy)Ni(I)–acyl bromide Overall, these investigations allowed comprehensive mechanistic picture this be assembled.

Language: 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, Journal Year: 2023, Volume and Issue: 88(16), P. 12121 - 12130

Published: July 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.

Language: Английский

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Photocatalytic C–C Bond Cleavage and Fluorosulfonylation of Strained Cycloalkanols for Carbonyl-Containing Aliphatic Sulfonyl Fluorides

Organic Letters, Journal Year: 2023, Volume and Issue: 25(38), P. 7051 - 7056

Published: Sept. 20, 2023

In this report, we present a photocatalytic ring-opening fluorosulfonylation of strained cycloalkanols with sulfur dioxide and NFSI under mild conditions for the synthesis carbonyl-containing aliphatic sulfonyl fluorides. The synthetic potential fluoride products has been examined by diverse transformations, including SuFEx reactions Baeyer-Villiger oxidation reactions. Mechanistic studies demonstrate that reaction operates through radical C-C bond cleavage/SO2 insertion/fluorination cascade process.

Language: Английский

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Ti-Catalyzed Modular Ketone Synthesis from Carboxylic Derivatives and gem-Dihaloalkanes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14884 - 14893

Published: June 26, 2023

Ketones are ubiquitous in organic synthesis. However, the general method to convert widely available carboxylic acids, unactivated esters, and amides into ketones remains elusive. Herein, we describe Ti-catalyzed modular ketone synthesis from derivatives easily accessed gem-dihaloalkanes. Notably, this protocol could achieve direct catalytic olefination of acids. This features a sequence electrophilic transformation good functional group compatibility allows rapid access various functionalized ketones. Preliminary mechanistic studies provide insights reaction pathway support intermediacy plausible alkylidene titanocene gem-bimetallic complexes.

Language: Английский

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Discovery of a Novel Pseudo‐Natural Product Aurora Kinase Inhibitor Chemotype through Morphological Profiling

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: April 3, 2024

Abstract The pseudo‐natural product (pseudo‐NP) concept aims to combine NP fragments in arrangements that are not accessible through known biosynthetic pathways. resulting compounds retain the biological relevance of NPs but yet linked bioactivities and may therefore be best evaluated by unbiased screening methods identification unexpected or unprecedented bioactivities. Herein, various combined with a tricyclic core connectivity via interrupted Fischer indole dearomatization reactions provide collection highly three‐dimensional pseudo‐NPs. Target hypothesis generation morphological profiling cell painting assay guides an chemotype for Aurora kinase inhibition both its relatively 3D structure physicochemical properties being very different from inhibitors. Biochemical characterization indicate phenotype identified corresponds B.

Language: Английский

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Selective Cross‐Ketonization of Carboxylic Acids Enabled by Metallaphotoredox Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(52)

Published: Nov. 1, 2022

Abstract Carboxylic acids are attractive building blocks for synthetic chemistry because they chemically stable, abundant, and commercially available with substantial structural diversity. The process of combining two carboxylic to furnish a ketone is termed ketonization. This potentially valuable transformation that has been underutilized in organic synthesis due the harsh reaction conditions generally required lack selectivity obtained when coupling distinct acids. We report herein metallaphotoredox strategy selectively generates unsymmetrical ketones via cross‐ketonization structurally dissimilar Cross‐selectivity achieved by exploiting divergent reactivity differentially substituted towards critical one‐ two‐electron processes proposed mechanism. method broadly applicable variety functionalized It can also be applied similar steric profile differences their relative rates decarboxylation.

Language: Английский

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The Dowd–Beckwith Reaction: History, Strategies, and Synthetic Potential

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(61)

Published: Aug. 1, 2022

Ring-expansion strategies are valuable synthetic tools that take benefit of existing ring structures and evade the unfavorable enthalpic-and entropic effects arise with end-to-end cyclizations. One potentially important class such reactions is Dowd-Beckwith reaction, ring-expansion ketones via alkoxy radicals. The exciting advancement in this research area starting to show its potential, as demonstrated by applying methodology strategy-level bond formation synthesize complex natural products. This Review aims provide first comprehensive survey development reaction spanning three decades from initial report present day, thus providing readers great detail about contributions organic synthesis. We hope review will further disclose salient features for applications encourage new, more advanced applications.

Language: Английский

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Utilization of methanol for condensation interrupted chemoselective transfer hydrogenation of CC, CO, and CN bonds under low catalyst loading

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(9), P. 2274 - 2286

Published: Jan. 1, 2023

Selective transfer hydrogenation (TH) of unsaturated molecules using methanol is challenging as the in situ generated formaldehyde prone to react with active methylene ( C -methylation) or amine N core desired product.

Language: Английский

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Direct Acylation of Unactivated Alkyl Halides with Aldehydes through N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 16, 2023

Catalytic acylation of organohalides with aldehydes is an ideal strategy for the direct synthesis ketones. However, utilization unactivated alkyl halides in such a transformation remains formidable challenge. In this study, we developed cross-coupling reaction through N-heterocyclic carbene catalysis. With protocol, various ketones could be rapidly synthesized from readily available starting materials under mild conditions. This organocatalytic system was successfully applied late-stage functionalization pharmaceutical derivatives. Mechanistic investigations suggest closed-shell nucleophilic substitution mechanism reaction.

Language: Английский

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