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

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 1122 - 1246

Published: Jan. 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.

Language: Английский

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Iridium supported on porous polypyridine-oxadiazole as high-activity and recyclable catalyst for the borrowing hydrogen reaction

Green Chemistry, Journal Year: 2022, Volume and Issue: 24(6), P. 2602 - 2612

Published: Jan. 1, 2022

Porous polypyridine-oxadiazole supported iridium catalysts (PPO-Ir) revealed high catalytic activity for the reaction of dimethyl-6-aminouracil (including 1,3-dimethylbarbituric acid, 2-aminobenzylamine) with alcohols.

Language: Английский

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Reductive Functionalization of Pyridine-Fused N-Heteroarenes

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(5), P. 795 - 813

Published: Feb. 23, 2024

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which important for the development medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing thermodynamic stability, kinetic inertness, and lone electron pair–induced catalyst deactivation N-heteroarenes, limited strategies (e.g., C–H activation/functionalization, electrophilic substitution, Minisci reaction) are available realize synthetic purpose maintain aromaticity final products. Moreover, relevant transformations have limitations such as needing harsh reaction conditions, requiring preinstallation specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, poor selectivity. Herein, considering that imines, enamines, radicals, cyclic amines generated during reduction precise transformation these reductive intermediates offers fundamental basis developing tandem reactions. Our group revealed slow rate, synergistic catalysis, controlled electroreduction effective fulfilling functionalization N-heteroarenes. Thus, we established series new methods provide diverse construction modalities functionalized N-heterocycles. The striking features include high efficiency, atom economy, use readily accessible feedstocks in absence flammable pressurized H2 gas, alongside promising potential obtained N-heterocyclic present study would be appealing fields organic chemistry, biomedical functional materials. This Account describes application dearomatization substrate-activating reaction-initiating modes summarizes via alkylation, arylation, annulation at nitrogen, α, β, other remote carbon sites achieved over past 8 years. Details regarding reactions their plausible mechanisms perspectives discussed. We hope our contributions this field will aid further tackle intractable challenges area.

Language: Английский

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Diastereoselective construction of cage-like and bridged azaheterocycles through dearomative maximization of the reactive sites of azaarenes

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 8(2), P. 204 - 211

Published: Oct. 29, 2020

A highly diastereoselective multicomponent dearomative multifunctionalization of N-alkyl activated azaarenes with 1,5-diazapentadienium salts has been developed to access structurally rigid and synthetically challenging cage-like bridged azaheterocycles.

Language: Английский

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Porous cross-linked polymer copper and iridium catalyzed the synthesis of quinoxalines and functionalized ketones under solvent-free conditions

Materials Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 5(21), P. 7861 - 7872

Published: Jan. 1, 2021

Two innovative porous cross-linked polymers (PCP–BTA–Ir and PCP–BTA–Cu) exhibited high catalytic activity towards the synthesis quinoxalines.

Language: Английский

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Hexafluoroisopropanol-Mediated Intramolecular Ring-Opening Cyclization of Indolyl-N-Tethered Epoxides: Tether-Length-Controlled Synthesis of 1,7- and 1,2-Fused Indoles

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 86(12), P. 8274 - 8285

Published: June 1, 2021

Despite having the capability to construct benzo-fused heterocycles in complete atom economy and high chemo-, regio-, enantio-, diastereoselectivities, intramolecular Friedel-Crafts epoxide arene cyclization (IFCEAC) remains underutilized organic synthesis. The wide adaptation of this powerful Csp2-Csp3 bond-forming reaction, therefore, requires a broad understanding substrate scope better impact heterocycle Along line, we investigated applicability IFCEAC for synthesis 1,7- 1,2-fused indoles. In article, report results our systematic investigation into limitations first examples hexafluoro-2-propanol (HFIP)-mediated readily accessible indolyl-N-tethered epoxides. We observed that nature position indole substituents tether length separating these two reacting moieties have strong effects on cyclization. This mild transition-metal-free protocol delivered pyrrolo[3,2,1-ij]quinolin-5-ols moderate good yields from substrates bearing both methylene linker connects an electron-rich carbocyclic ring. Notably, reactions required presence π-activating aryl substituent carbon atom. Interestingly, replacing with ethylene unit resulted regioswitching, which corresponding tetrahydropyrido[1,2-a]indol-8-ols yields. could also successfully extend methodology pyrrolyl-N-tethered epoxides very high-yielding tetrahydroindolizin-7-ols.

Language: Английский

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Transfer hydrogenation of N-heteroarenes with 2-propanol and ethanol enabled by manganese catalysis

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(24), P. 6901 - 6908

Published: Jan. 1, 2021

A convenient well-defined manganese catalyzed transfer hydrogenation of N-heteroarenes using 2-propanol and ethanol as hydrogen sources is developed. DFT calculations support an outer sphere mechanism.

Language: Английский

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Ruthenium-Catalyzed Hydrogen Evolution o-Aminoalkylation of Phenols with Cyclic Amines

Organic Letters, Journal Year: 2020, Volume and Issue: 22(12), P. 4781 - 4785

Published: June 3, 2020

Herein, we present a ruthenium-catalyzed new hydrogen evolution ortho-aminoalkylation of phenolic derivatives with cyclic amines as the coupling agents. The developed cross-coupling reaction offers practical platform for direct access to variety functionalized phenols features good substrate and functional group compatibility, readily available catalyst system feedstocks, no need additional sacrificial oxidants, high atom efficiency.

Language: Английский

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Sc(OTf)₃-Mediated One-Pot Synthesis of 2,3-Disubstituted Quinolines from Anilines and Epoxides

The Journal of Organic Chemistry, Journal Year: 2020, Volume and Issue: 85(10), P. 6741 - 6746

Published: April 22, 2020

Here, we report the first synthesis of 2,3-disubstituted quinolines from anilines and aromatic or aliphatic epoxides. This reaction utilizes Sc(OTf)3 as a Lewis acid TEMPO an oxygen scavenger. A wide variety highly substituted were obtained with moderate to excellent yields (up 96%).

Language: Английский

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Recent Applications of Quinolinium Salts in the Synthesis of Annulated Heterocycles

SynOpen, Journal Year: 2022, Volume and Issue: 06(02), P. 86 - 109

Published: April 25, 2022

Abstract Quinoline derivatives are frequently found in natural products and biologically active compounds; however, construction of quinoline fused polyheterocycles is a challenging goal synthetic organic chemistry. In this regard, quinolinium salts meet the demand to great level, as they can be synthesized readily employed effectively for rapid condensed heterocyclic core. The present review focuses on recent (2015–2021) applications different salts, which react with suitable partners access diverse annulated products. Most reactions discussed here involve easily available starting materials, operationally simple, offer high atom-efficiency, environmentally benign. Mechanistic aspects representative transformations have also been highlighted better understand reaction pathways. 1 Introduction 2 Annulation Involving N-Alkyl Quinolinium Salts 2.1 Reaction Alkenes 2.2 Alkynes/Arynes 2.3 Phenolic Compounds 2.4 Cyclic/Acyclic Diketones 2.5 Amines/Cyclic Amines 2.6 Enamines 2.7 Isocyanoacetates 2.8 Cyclopropanes 2.9 Ring Expansion Reactions 3 Zwitterionic Tosylates 3.1 3.2 Allenes/Ketenes 3.3 Aldehyde-Amino Acid (Azomethine Ylide) 3.4 Sulfonium 3.5 Diazoacetate 4 Thiolates 4.1 4.2 Sulfenes 4.3 Arynes 5 N-Oxides 5.1 Diynes Ynones 5.2 Lactonization Acrylate 6 N-Iminoquinolinium 6.1 Allenoates 6.2 Hydroxymethylallyl Carbonate 7 Miscellaneous Cyclizations 8 Conclusions

Language: Английский

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