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

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(48), P. 22140 - 22149

Published: Nov. 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.

Language: 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, Journal Year: 2024, Volume and Issue: 26(19), P. 4117 - 4121

Published: May 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.

Language: Английский

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

Chemical Science, Journal Year: 2024, Volume and Issue: 15(13), P. 4797 - 4803

Published: Jan. 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.

Language: Английский

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

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(20), P. 12984 - 12992

Published: Oct. 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.

Language: Английский

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

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(17), P. 11528 - 11540

Published: Aug. 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.

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(8), P. 4808 - 4818

Published: Feb. 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.

Language: Английский

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

Organic & Biomolecular Chemistry, Journal Year: 2022, Volume and Issue: 20(9), P. 1838 - 1868

Published: Jan. 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.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 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.

Language: Английский

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Mg(OTf)₂ as an Excellent Catalyst for the Reductive Depolymerization and Methanolysis of Polyesters and Polycarbonates

Advanced Sustainable Systems, Journal Year: 2024, Volume and Issue: unknown

Published: May 15, 2024

Abstract The use of alkaline earth‐abundant metal catalysts as alternatives to transition in the depolymerization plastic waste is a very important research area. In this work, first method described for conversion polyesters into value‐added compounds catalyzed by magnesium catalyst. It demonstrated that commercially available, inexpensive and air‐stable, earth catalyst Mg(OTf) 2 efficiently promotes reductive several using pinacolborane (HBpin) reducing agent with good excellent yields. This also remains active at least 12 consecutive polycaprolactone (PCL) reactions yields between 89% 81%. efficient polycarbonate poly(bisphenol A carbonate) (PC.BPA). Furthermore, it found successfully catalyzes methanolysis polycarbonates moderate temperature

Language: Английский

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