Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines

Chemical Reviews, Год журнала: 2024, Номер 124(3), С. 1122 - 1246

Опубликована: Янв. 2, 2024

Dearomatization reactions have become fundamental chemical transformations in organic synthesis since they allow for the generation of three-dimensional complexity from two-dimensional precursors, bridging arene feedstocks with alicyclic structures. When those processes are applied to pyridines, quinolines, and isoquinolines, partially or fully saturated nitrogen heterocycles formed, which among most significant structural components pharmaceuticals natural products. The inherent challenge lies low reactivity heteroaromatic substrates, makes dearomatization process thermodynamically unfavorable. Usually, connecting event irreversible formation a strong C–C, C–H, C–heteroatom bond compensates energy required disrupt aromaticity. This aromaticity breakup normally results 1,2- 1,4-functionalization heterocycle. Moreover, combination these subsequent tandem stepwise protocols allows multiple heterocycle functionalizations, giving access complex molecular skeletons. aim this review, covers period 2016 2022, is update state art nucleophilic dearomatizations showing extraordinary ability dearomative methodology indicating their limitations future trends.

Язык: Английский

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Indolizine Synthesis through Annulation of Pyridinium 1,4‐Thiolates and Copper Carbenes: A Predictive Catalysis Approach

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(5), С. 760 - 766

Опубликована: Фев. 8, 2023

Abstract Predictive catalysis was applied to the reaction of pyridinium 1,4‐zwitterionic thiolates with a copper carbene. Theoretical calculations were first performed determine suitability their annulation and make predictions about performance different salts, diazo species, derivatives. With in hand, experimental conditions optimized, scope assessed, precision evaluated. Yields up 90% obtained for synthesis indolizine scaffolds reactivity metal magnified image

Язык: Английский

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Temperature‐Dependent Regiodivergent Synthesis of Functionalized Maleimides and Itaconimides via in‐situ Generated Pyridinium Ylide

European Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Abstract We report a temperature‐dependent regiodivergent synthetic strategy for the construction of functionalized maleimides and itaconimides using in‐situ generated pyridinium ylides. This approach enables efficient access to both regioisomeric products under mild straightforward reaction conditions. A variety salts with different aromatic alkyl groups were successfully used N ‐aryl ‐alkyl succinimides demonstrating broad substrate compatibility. The practicality scalability this methodology confirmed through scale‐up experiments, which maintained high yields reproducibility.

Язык: Английский

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Asymmetric Three-Component Reaction of Enynal with Alcohol and Imine as An Expeditious Track to Afford Chiral α-Furyl-β-amino Carboxylate Derivatives

ACS Catalysis, Год журнала: 2022, Номер 12(22), С. 14185 - 14193

Опубликована: Ноя. 4, 2022

Herein, we report an achiral dirhodium complex and chiral phosphoric acid cooperatively catalyzed asymmetric three-component reaction of enynal with alcohol imine, affording α-furyl-β-amino carboxylates in good to high yields generally excellent stereoselectivity. The successful introduction as a carbene precursor this provides expeditious track prepare furan derivatives adjacent quaternary tertiary stereocenters. starting materials are stable readily available, the method features 100% atom economy bond-formation efficiency. This is highly enantioselective gem-difunctionalization metal generated situ from enynal. These products could be smoothly converted polycyclic frameworks drug-conjugated through different cycloaddition reactions.

Язык: Английский

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Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis

Chemical Science, Год журнала: 2023, Номер 14(15), С. 4134 - 4142

Опубликована: Янв. 1, 2023

Highly selective assembly of 2,3-fused indolizines was achieved via a cascade allylation/Friedel–Crafts type reaction with Cu/Ir catalysis. This protocol furnishes stereodivergent synthesis chiral bearing three stereogenic centers excellent results.

Язык: Английский

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In silico reaction screening with difluorocarbene for N-difluoroalkylative dearomatization of pyridines

Nature Synthesis, Год журнала: 2022, Номер 1(10), С. 804 - 814

Опубликована: Авг. 8, 2022

Abstract Quantum chemical calculations are mainly regarded as a method for mechanistic studies in organic chemistry, whereas their use the simulation of unknown reactions could greatly assist reaction development. Here we report strategy developing multicomponent on basis results computational simulations. In silico screening with difluorocarbene using artificial force induced suggested that cycloadditions between an azomethine ylide and variety coupling partners would proceed to generate corresponding α,α-difluorinated N -heterocyclic compounds. The predicted was successfully realized experimentally, leading -difluoroalkylative dearomatization pyridines involving pyridinium ylide-mediated 1,3-dipolar cycloaddition diverse range electrophiles such aldehydes, ketones, imines, alkenes alkynes. Moreover, performance be explained by comparing energy barrier desired pathway competitive undesired pathway, which also identified search.

Язык: Английский

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Synthesis of 5-Fluoro-dihydroindolizines from Pyrrole-2-acetic Acids and Trifluoromethyl Alkenes via Dual C–F Bond Cleavage in a CF₃ Group

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(7), С. 4801 - 4812

Опубликована: Март 17, 2022

Herein, we describe the synthesis of 5-fluoro-dihydroindolizines via dual C–F bond cleavage in a trifluoromethyl group. The photocatalytic defluorinative coupling pyrrole-2-acetic acids and α-trifluoromethyl alkenes cleaved first bond, providing gem-difluoroalkenes bearing an unprotected pyrrole motif. Subsequently, intramolecular SNV reaction closed ring by forming C–N concomitantly with second bond. Using indole-2-acetic as substrates, reactions also allow assembly 6-fluoro-dihydropyrido[1,2-a]indoles.

Язык: Английский

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Recent advances in the cyclization reactions of pyridinium 1,n-zwitterions (n = 4 and 5): scope and mechanism

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(11), С. 2813 - 2829

Опубликована: Янв. 1, 2023

This review summarizes the recent advances in cyclization reactions involving pyridinium 1, n -zwitterions ( = 4 and 5) highlights applications of efficient construction heterocycles.

Язык: Английский

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Evaluation of Pyrazolyl‐Indolizine Derivatives as Antimicrobial Agents: Synthesis, In vitro, In silico ADMET and Molecular Docking Studies

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(8)

Опубликована: Май 28, 2024

Herein, we report analogues of s-indacene by the synthesis novel indolizine derivatives. Using chloroform as an appropriate solvent, sixteen derivatives pyrazolyl-indolizine (4--19) were prepared reaction 3-(dimethylamino)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (1) with hydrazonoyl chloride (2) in presence triethylamine good to excellent yields. We used NMR spectra, IR, mass spectrometry, well elemental analyses prove chemical structures and purity synthesized compounds 4-19. Among all tested 5, 9, 13 19 had a potent antimicrobial efficiency against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aerginousea, Sallmonella typhemerium, Candida albicans. Furthermore, significant increase lipid peroxidation (LPO) toward Gram-negative bacteria, aeruginosa when treated compound 9 was observed, while remarkably increased cell membrane oxidation Salmonella typhimurium. Additionally, utilized docking studies silico methods evaluate drug-likeness, physicochemical properties, ADMET profiles compounds. The results molecular simulation revealed that displayed decreased binding energy interacting active sites important enzymes, including Sterol 14-demethylase C. albicans, Dihydropteroate synthase S. LasR P. aeruginosa, Glucosamine-6-phosphate typhimurium, Gyrase B B. subtilis.

Язык: Английский

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Recent advances in the global ring functionalization of 7-azaindoles

Chemical Communications, Год журнала: 2020, Номер 56(79), С. 11749 - 11762

Опубликована: Янв. 1, 2020

The 7-azaindole building block has attracted considerable interest in the field of drug discovery current portfolio.

Язык: Английский

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