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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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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Direct use of methanol instead of formaldehyde or paraformaldehyde: Acceptorless dehydrogenative coupling for the synthesis of arylhydrazones catalyzed by a metal–ligand iridium bifunctional catalyst

Journal of Catalysis, Journal Year: 2024, Volume and Issue: 438, P. 115685 - 115685

Published: Aug. 3, 2024

Language: Английский

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Dearomative cyclization of pyridines/isoquinolines with cyclopropenones: access to indolizinones and benzo-fused indolizinones

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(27), P. 4051 - 4054

Published: Jan. 1, 2023

Dearomatization reactions provide a rapid approach to construct complicated molecules that are difficult synthesize by traditional methods from simple aromatic compounds. Herein, we report an efficient dearomative [3+2] cycloaddition reaction of 2-alkynyl pyridines with diarylcyclopropenones, leading the synthesis densely functionalized indolizinones in moderate good yields under metal-free conditions. In addition, this strategy can also be employed cyclization isoquinolines access variety benzo-fused indolizinones. Density functional theory (DFT) calculations revealed appropriate substituent at 2-position pyridine is crucial dearomatization process.

Language: Английский

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Metal-free three-component tandem cyclization for modular synthesis of 2,3-dihydrobenzothiazin-4-ones

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(7), P. 2021 - 2026

Published: Jan. 1, 2024

The first three-component cyclization reaction of benzo[ c ][1,2]dithiol-3-ones based on S–S bond cleavage is disclosed herein.

Language: Английский

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Iridium-catalyzed reductive β-alkylation of (iso)quinoline derivatives by an in situ enone-trapping strategy

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(22), P. 4516 - 4520

Published: Jan. 1, 2024

Here, we report an iridium-catalyzed reductive β-alkylation of (iso)quinolinium salts with β-chloro ketones, which offers important complement to the synthesis functionalized (iso)tetrahydroquinolines.

Language: Английский

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Skeletal editing of benzodithiol-3-ones for the assembly of benzo[d][1,3]oxathiin-4-ones

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(18), P. 4979 - 4985

Published: Jan. 1, 2024

A novel skeletal editing of benzodithiol-3-ones via swapping from S atom to C–O entities is developed herein, which provides a robust route assemble benzo[ d ][1,3]oxathiin-4-ones in decent yields by utilizing aldehydes as cyclization partners.

Language: Английский

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Ruthenium-Catalyzed Interrupted Transfer Hydrogenation: An Approach for Reductive Functionalization of Quinolinium and Napthyridinium Salts

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(18), P. 13167 - 13178

Published: Sept. 11, 2024

Until now, a myriad of effective approaches have emerged for the functionalization

Language: Английский

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Six-membered ring systems: pyridines and benzo derivatives

Progress in heterocyclic chemistry, Journal Year: 2023, Volume and Issue: unknown, P. 383 - 425

Published: Jan. 1, 2023

Language: Английский

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A Regiodivergent Dearomative Trifunctionalization of Quinolinium Salts to Access Fused Tetrahydroquinoline Polycycles

Organic Letters, Journal Year: 2024, Volume and Issue: 26(34), P. 7144 - 7148

Published: Aug. 19, 2024

Dearomative trifunctionalization of quinolinium salts is one the most straightforward approaches to access biologically relevant multisubstituted tetrahydroquinolines. However, research in this field still its infancy. Here, we report a base-controlled regiodivergent dearomative strategy for transforming quinoliniums into two kinds structurally intriguing tetrahydroquinoline polycycles through one-pot three-component cascade annulation. The key situ generation "Nu–E–Nu" trifunctional reagent that can precisely identify matched reactive sites quinoliniums.

Language: Английский

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