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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Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(48), С. 22140 - 22149

Опубликована: Ноя. 22, 2022

Photocatalysis opens up a new window for carbonyl chemistry. Despite multitude of photochemical reactions compounds, visible light-induced catalytic asymmetric transformations remain elusive and pose formidable challenge. Accordingly, the development simple, efficient, economic systems is ideal pursuit chemists. Herein, we report an enantioselective radical photoaddition to ketones through Lewis acid-enabled photoredox catalysis wherein in situ formed chiral N,N'-dioxide/Sc(III)-ketone complex serves as temporary photocatalyst trigger single-electron transfer oxidation silanes generation nucleophilic species, including primary, secondary, tertiary alkyl radicals, giving various enantioenriched aza-heterocycle-based alcohols good excellent yields enantioselectivities. The results electron paramagnetic resonance (EPR) high-resolution mass spectrum (HRMS) measurements provided favorable evidence stereocontrolled addition process involved this reaction.

Язык: Английский

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Iron^III-catalyzed asymmetric inverse-electron-demand hetero-Diels–Alder reaction of dioxopyrrolidines with simple olefins

Chemical Science, Год журнала: 2024, Номер 15(13), С. 4797 - 4803

Опубликована: Янв. 1, 2024

A highly enantioselective [4 + 2] cycloaddition of a number simple olefins with cyclic hetero-diene dioxopyrrolidines is realized by chiral iron( iii )/ N , ′-dioxide complex catalyst.

Язык: Английский

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Synthesis of Spiro[indoline-pyridine]-dicarboxylates and Substituted Alkylidene Oxindoles by Azomethine Ylides and MBH Carbonates of Isatins

Organic Letters, Год журнала: 2024, Номер 26(19), С. 4117 - 4121

Опубликована: Май 9, 2024

We have developed an efficient protocol for the synthesis of spiro[indoline-pyridine]dicarboxylates and substituted alkylidene oxindoles through [3 + 3] cycloaddition Michael addition individually by azomethine ylides various MBH carbonates isatins. The selective generation cyclic products chain was achieved changing substituents at 3-position oxindoles. features this method include convenient catalysts, mild reaction conditions, broad substrate scopes.

Язык: Английский

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An Overview of Recent Advances in Enantioselective Multicomponent Reactions

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 141768 - 141768

Опубликована: Фев. 1, 2025

Язык: Английский

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Enantioselective Radical Hydroacylation of α,β-Unsaturated Carbonyl Compounds with Aldehydes by Triplet Excited Anthraquinone

ACS Catalysis, Год журнала: 2022, Номер 12(20), С. 12984 - 12992

Опубликована: Окт. 12, 2022

The synthesis of chiral ketones has been a long focus chemistry research. Enantioselective radical hydroacylation, as useful strategy to access various ketones, was restricted the reaction with β-substituted alkenes, in which β-stereocenter generated via stereocontrolled addition prochiral alkene. Herein, we realized highly enantioselective hydroacylation α-substituted α,β-unsaturated carbonyl compounds through direct hydrogen atom transfer presence photocatalyst anthraquinone and N,N′-dioxide/metal complexes. This mild, robust method provided facile wide array α-tertiary stereocenters by using readily available aldehyde reagent. Based on spectroscopy experiments control together DFT calculations, transfer/radical addition/enantioselective reverse sequence proposed.

Язык: Английский

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Cobalt-Catalyzed Asymmetric Dearomative [3 + 2] Annulation of Quinolines, Isoquinolines, and Pyridines

ACS Catalysis, Год журнала: 2023, Номер 13(17), С. 11528 - 11540

Опубликована: Авг. 16, 2023

A highly enantioselective dearomative [3 + 2] annulation of quinolines, isoquinolines, and pyridines with donor–acceptor aminocyclopropanes was achieved. With C1-symmetric imidazoline-pyrroloimidazolone pyridine as the tridentate ligand Co(OTf)2 Lewis acid, diverse chiral indolizidine benzo-fused derivatives were obtained in good yields (up to 98% yield), excellent diastereoselectivities (>20:1 dr), enantioselectivities ee). Mechanistic experiments density functional theory (DFT) calculations revealed that nitrogen acted a bifunctional ligand. The not only coordinated Co(II) salt activate aminocyclopropane via bidentate coordination, but also formed H-bond oxygen atom succinimide moiety fix orientation aminocyclopropane, thus facilitating nucleophilic attack N-heteroaromatics. Additionally, high enantioselectivity reaction governed by steric factors.

Язык: Английский

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Enantioselective anti-Dihalogenation of Electron-Deficient Olefin: A Triplet Halo-Radical Pylon Intermediate

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(8), С. 4808 - 4818

Опубликована: Фев. 16, 2023

The textbook alkene halogenation reaction establishes straightforward access to vicinal dihaloalkanes. However, a robust catalytic method for dihalogenizing electron-deficient olefins in an enantioselective manner is still under development, and its mechanism remains controversial. Herein, we disclose efficient regio-, anti-diastereo-, dibromination, bromochlorination, dichlorination reactions of enones catalyzed by chiral N,N'-dioxide/Yb(OTf)3 complex. With the combination electrophilic halogen halide salts as halogenating agents, array homo- heterodihalogenated derivatives achieved moderate good enantioselectivities. Moreover, DFT calculations reveal that novel triplet halo-radical pylon intermediate probable accounting exclusive regio- anti-diastereoselectivity.

Язык: Английский

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Stereoselective synthesis of fused-, spiro- and bridged heterocycles via cyclization of isoquinolinium salts: a recent update

Organic & Biomolecular Chemistry, Год журнала: 2022, Номер 20(9), С. 1838 - 1868

Опубликована: Янв. 1, 2022

Isoquinoline and its derivatives are ubiquitous in natural alkaloids, synthetic materials pharmaceuticals with a broad spectrum of biological activities. In particular, isoquinolinium salts important organic synthesis because they can serve as building blocks for the rapid construction various condensed heterocyclic systems involving cyclization processes. This review highlights novel stereoselective strategies that emerged last few years (2014-2021) fused-, spiro- bridged heterocycles exploiting bench-stable or situ generated salts. Most reactions described here provide quick access to desired products high stereoselectivity starting from readily available under mild conditions. The potential most transformations was confirmed by gram-scale production target molecules. Some have been useful other bioactive compounds.

Язык: Английский

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Enantioselective [2+2] Cycloaddition of Allenyl Imide with Mono‐ or Disubstituted Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(44)

Опубликована: Сен. 14, 2022

Abstract An efficient catalytic asymmetric [2+2] cycloaddition of allenyl imide and mono‐ or disubstituted alkenes is disclosed. The key feature this method the use bidentate weakly activated less steric hindered alkene pair by utilizing chiral magnesium(II) complex N , N′ ‐dioxide, which could provide through‐space dispersion interactions to orientate arrangement alkene. This protocol allows generation a series axially cyclobutenes four‐membered ring‐containing spirocycles (80 examples) in high yield (up 99 %) with excellent enantioselectivity >99 % ee ), late‐stage modification biologically active molecules as well. Experimental studies DFT calculations revealed that proceeded via stepwise mechanism involving short‐lived zwitterionic intermediate. π‐π interaction between amide moiety ligand was crucial for enantiocontrol.

Язык: Английский

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