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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Recent advances in the dearomative functionalisation of heteroarenes

Chemical Science, Journal Year: 2022, Volume and Issue: 13(48), P. 14213 - 14225

Published: Jan. 1, 2022

This Perspective outlines the myriad of products that can be obtained by dearomatisation and functionalization heteroarene substrates. Complex 3D molecules often prepared in one step from simple arene starting materials.

Language: Английский

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Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine–Tetrahydroquinoline Polycycles

Organic Letters, Journal Year: 2022, Volume and Issue: 24(10), P. 2008 - 2013

Published: March 10, 2022

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine–tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- ring-forming efficiency, diverse

Language: Английский

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Recent Advances in the Dearomative Skeletal Editing of Mono-azaarenes

Synthesis, Journal Year: 2023, Volume and Issue: 56(01), P. 55 - 70

Published: Jan. 17, 2023

Abstract Despite its challenges, the skeletal editing of mono-azaarenes (pyridines, quinolines, and isoquinolines) has shown unparalleled synthetic utility in construction complex molecules that are difficult to access by conventional methods. In this short review, we summarize three most recently developed strategies for deconstruction azaarene cores, with a focus on their generality, limitations, mechanistic aspects. Also, application strategy total synthesis some important natural products is discussed. 1 Introduction 2 Skeletal Editing Mono-Azaarenes through Zincke-like Reactions 3 Mono-azaarenes Aza-Buchner 4 via Photoinduced Radical or Energy-Transfer Processes 5 Conclusion

Language: Английский

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Tunable vicinal, geminal diphosphorylation and C–N bond phosphorylation of enaminones toward divergent phosphorylated ketone derivatives

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(42), P. 6383 - 6386

Published: Jan. 1, 2023

The tunable reactions of enaminones with phosphine oxides/phosphonates in the form vicinal- and geminal diphosphorylation, C–N bond phosphorylation have been developed, providing new methods for synthesis divergent phosphorylated molecules.

Language: Английский

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Synthesis spiro and fused chromenes via [4 + 2] cycloaddition of salicyl N-tosylimines and cyclic dienophiles

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1304, P. 137684 - 137684

Published: Feb. 4, 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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A combination of polarity reversal, Diels–Alder cycloaddition and skeletal remodeling to access pyridine-fused nitrones

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(30), P. 4775 - 4778

Published: Jan. 1, 2022

An unprecedented cascade strategy consisting of polarity reversal, normal electron-demand Diels-Alder cycloaddition and skeletal remodeling was developed to construct novel pyridine-fused nitrones in up 82% yield. The key the success umpolung process, which transformed electron-deficient 3-nitropyridinium ring into a reactive, π-extended cyclic nitroalkene, serving as rarely reported hetero-diene participate cycloadditions.

Language: Английский

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Diastereoselective construction of bridged piperidines through an interrupted dearomative reduction

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(57), P. 7964 - 7967

Published: Jan. 1, 2022

An interrupted dearomative reduction strategy was developed to transform planar chalcone-based pyridinium salts into structurally intriguing bridged piperidines in a completely regio- and diastereoselective manner. This reaction proceeded successfully by using cheap easily accessible NaBH4 as the reductant under mild conditions without exclusion of oxygen or use special equipment.

Language: Английский

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Substrate-directed divergent synthesis of fused indole polycycles through Rh(ii)-catalyzed cascade reactions of bis(diazo)indolin-2-ones

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(61), P. 8576 - 8579

Published: Jan. 1, 2022

Herein, we report a substrate-directed diverse synthetic strategy toward two kinds of structurally intriguing fused indole polycycles through Rh( ii )-catalyzed cascade reactions bis(diazo)indolin-2-ones with enaminones.

Language: Английский

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