Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope DOI
Marvin Kischkewitz, Bruno Marinič, Nicolas Kratena

et al.

Angewandte Chemie, Journal Year: 2022, Volume and Issue: 134(27)

Published: May 13, 2022

Abstract Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition‐metal‐free conditions as well rhodium catalysis with very low catalyst loadings (0.01 mol %) uses inexpensive formic acid terminal reductant. A wide range electrophiles, including enones, imides, unsaturated esters sulfones, β‐nitro styrenes aldehydes are intercepted by in situ formed enamine species forming large variety substituted tetrahydro(iso)quinolines. Electrophiles incorporated at C‐3 C‐4 position quinolines isoquinolines respectively, providing access to substitution patterns which not favoured electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited facilitate three types annulation reactions, giving rise complex polycyclic products formal [3+3] [4+2] cycloaddition.

Language: Английский

Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines DOI Creative Commons
Marcos Escolano, Daniel Gaviña, G. Alzuet

et al.

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

Citations

56
Recent advances in the dearomative functionalisation of heteroarenes DOI Creative Commons
Nicolas Kratena, Bruno Marinič, Timothy J. Donohoe

et al.

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

Citations

53
Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities DOI

Sha Hu,

Jiong Chen,

Jin-Xu Cao

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 136, P. 106549 - 106549

Published: April 20, 2023

Language: Английский

Citations

21
Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope DOI
Marvin Kischkewitz, Bruno Marinič, Nicolas Kratena

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(27)

Published: May 13, 2022

Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition-metal-free conditions as well rhodium catalysis with very low catalyst loadings (0.01 mol %) uses inexpensive formic acid terminal reductant. A wide range electrophiles, including enones, imides, unsaturated esters sulfones, β-nitro styrenes aldehydes are intercepted by in situ formed enamine species forming large variety substituted tetrahydro(iso)quinolines. Electrophiles incorporated at C-3 C-4 position quinolines isoquinolines respectively, providing access to substitution patterns which not favoured electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited facilitate three types annulation reactions, giving rise complex polycyclic products formal [3+3] [4+2] cycloaddition.

Language: Английский

Citations

25
Metal and Activating Group Free C-4 Alkylation of Isoquinolines via a Temporary Dearomatization Strategy DOI Creative Commons

Aaron J. Day,

Timothy C Jenkins, Marvin Kischkewitz

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(4), P. 614 - 618

Published: Jan. 23, 2023

A simple method for the C-4 alkylation of isoquinolines is described using benzoic acid as a nucleophilic reagent and vinyl ketones an electrophile. The reaction shows tolerance substitution at C-3, C-5-C-8 positions well allowing some variation ketone electrophiles. products contain carbonyl that can act synthetic handle further manipulations giving esters, amines, or alkyl products.

Language: Английский

Citations

7
The Construction of Highly Substituted Piperidines via Dearomative Functionalization Reaction DOI Creative Commons
Miao Hu, Hao Ding, William DeSnoo

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Oct. 20, 2023

Nitrogen heterocycles play a vital role in pharmaceuticals and natural products, with the six-membered aromatic aliphatic architectures being commonly used. While synthetic methods for N-heterocycles are well-established, synthesis of their functionalized analogues, particularly piperidine derivatives, poses significant challenge. In that regard, we propose stepwise dearomative functionalization reaction construction highly decorated derivatives diverse functional handles. We also discuss challenges related to site-selectivity, regio- diastereoselectivity, provide insights into mechanism through mechanistic studies density theory computations.

Language: Английский

Citations

7
Unveiling Novel Synthetic Pathways through Brook Rearrangement DOI

Mohamed Agbaria,

Nwar Egbaria,

Zackaria Nairoukh

et al.

Synthesis, Journal Year: 2024, Volume and Issue: 56(16), P. 2483 - 2498

Published: Jan. 30, 2024

Abstract The Brook rearrangement is a valuable synthetic tool that facilitates the controlled construction of complex molecules. Conventionally, it generates carbanion intermediates utilized in subsequent functionalization reactions. In this review, we will explore recent advancements extend beyond traditional Specifically, highlight its involvement unusual bond cleavage, annulation reactions, and dearomatization efforts. novelty underscored by showcasing most applications. 1 Introduction 2 Novel Synthetic Pathways Involving Rearrangement 2.1 C–C C–X Bond Formation 2.2 Cleavage 2.3 Stereodefined Substituted Silyl Enol Allenol Ethers 2.4 Annulation Reactions 2.5 Dearomatization 3 Applications 4 Conclusion

Language: Английский

Citations

2
Metal-free transfer hydrogenation/cycloaddition cascade of activated quinolines and isoquinolines with tosyl azides DOI
Suman Yadav,

Ruchir Kant,

Malleswara Rao Kuram

et al.

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(46), P. 7088 - 7091

Published: Jan. 1, 2023

The difficulty in isolating cyclic enamines emanating from their intrinsic instability has impeded exploration cycloaddition reactions. Here, we achieved a metal-free domino reaction providing quinoline and isoquinoline-derived amidines by the of azides with situ generated via dearomatization.

Language: Английский

Citations

5
Microwave‐assisted Rhodium(I)‐Catalyzed C8‐Regioselective C−H Alkenylation and Arylation of 1,2,3,4‐Tetrahydroquinolines with Alkenyl and Aryl Carboxylic Acids DOI Creative Commons
Haoqiang Zhao,

Qi Zeng,

Ji Yang

et al.

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(8), P. 1820 - 1826

Published: Feb. 7, 2024

Abstract Rh(I)‐catalyzed C8‐selective C−H alkenylation and arylation of 1,2,3,4‐tetrahydroquinolines with alkenyl aryl carboxylic acids under microwave assistance have been realized. Using [Rh(CO) 2 (acac)] as the catalyst Piv O acid activator, undergo decarbonylative a wide range acids, affording C8‐alkenylated or arylated 1,2,3,4‐tetrahydroquinolines. This method enables synthesis that would otherwise be difficult to access by means conventional protocols. Moreover, this catalytic system also works well in acids. The activity strongly depends on choice N ‐directing group, readily installable removable ‐(2‐pyrimidyl) group being optimal. pathway is elucidated mechanistic experiments.

Language: Английский

Citations

1
Iridium-catalyzed reductive β-alkylation of (iso)quinoline derivatives by an in situ enone-trapping strategy DOI

Yan-Ping Sun,

Jianjie Chen,

Min Zhang

et al.

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

Citations

1