meta-Selective Radical Acylation of Electron-rich Arenes DOI Creative Commons
Yamato Goto,

Masaki Sano,

Yuto Sumida

et al.

Published: April 27, 2023

meta-Selective functionalisation of electron-rich arenes provides a non-traditional route to organic synthesis. In classical electrophilic aromatic substitution electron-donating group-pendant arenes, occurs according ortho- and para-orientation. There have been numerous efforts overcome this selectivity, various synthetic methods developed, mainly based on transition metal catalysis. Here, we show new N-heterocyclic carbene photoredox cocatalysis for meta-selective acylation arenes. This approach proceeds without the directing groups or steric factors required in catalysis, resulting precisely opposite regioselectivity from conventional approaches such as Friedel–Crafts acylation. The catalytic system involves sequence single electron oxidation an arene followed by radical–radical coupling between ketyl radical cation. protocol will lead expeditious synthesis molecules that commonly require multiple steps rare metals promotes construction libraries biologically active molecules.

Language: Английский

ortho-Selective Dearomative [2π + 2σ] Photocycloadditions of Bicyclic Aza-Arenes DOI

Roman Kleinmans,

Subhabrata Dutta,

Kristers Ozols

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(22), P. 12324 - 12332

Published: May 26, 2023

Dearomative photocycloadditions are valuable chemical transformations, serving as an efficient platform to create three-dimensional molecular complexity. However, the photolability of original addition product especially within context ortho cycloadditions often causes undesired consecutive rearrangements, rendering these cycloadducts elusive. Herein, we report ortho-selective intermolecular photocycloaddition bicyclic aza-arenes including (iso)quinolines, quinazolines, and quinoxalines by utilizing a strain-release approach. With bicyclo[1.1.0]butanes coupling partners, this dearomative [2π + 2σ] cycloaddition enables straightforward construction C(sp3)-rich bicyclo[2.1.1]hexanes directly connected N-heteroarenes. Photophysical experiments DFT calculations revealed origin selectivity indicate that, in originally proposed energy transfer or direct excitation pathways, chain reaction mechanism is operative depending on conditions.

Language: Английский

Citations

124
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

58
N-heterocyclic carbene- and organic photoredox-catalysed meta-selective acylation of electron-rich arenes DOI
Yamato Goto,

Masaki Sano,

Yuto Sumida

et al.

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(11), P. 1037 - 1045

Published: Aug. 3, 2023

Language: Английский

Citations

30
Recent Advances in Dearomative Partial Reduction of Benzenoid Arenes DOI

De‐Hai Liu,

Jiajia Ma

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 14, 2024

Abstract Dearomative partial reduction is an extraordinary approach for transforming benzenoid arenes and has been well‐known many decades, as exemplified by the dehydrogenation of Birch hydroarylation Crich addition. Despite its remarkable importance in synthesis, this field experienced slow progress over last half‐century. However, a revival observed with recent introduction electrochemical photochemical methods. In Minireview, we summarize advancements dearomative arenes, including dihydrogenation, hydroalkylation, arylation, alkenylation, amination, borylation others. Further, intriguing utilization synthesis natural products also emphasized. It anticipated that Minireview will stimulate further arene transformations.

Language: Английский

Citations

13
Photochemical dearomative skeletal modifications of heteroaromatics DOI Creative Commons
Peng Ji, Kuaikuai Duan, Menglong Li

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(12), P. 6600 - 6624

Published: Jan. 1, 2024

Dearomatization has emerged as a powerful tool for rapid construction of 3D molecular architectures from simple, abundant, and planar (hetero)arenes. The field evolved beyond simple dearomatization driven by new synthetic technology development. With the renaissance photocatalysis expansion activation mode, last few years have witnessed impressive developments in innovative photochemical methodologies, enabling skeletal modifications dearomatized structures. They offer truly efficient useful tools facile highly complex structures, which are viable natural product synthesis drug discovery. In this review, we aim to provide mechanistically insightful overview on these innovations based degree alteration, categorized into dearomative functionalization editing, highlight their utilities.

Language: Английский

Citations

13
Synthesis of Collidine from Dinitrogen via a Tungsten Nitride DOI

Lukas Eberle,

Joachim Ballmann

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 7979 - 7984

Published: March 15, 2024

The synthesis of pyridines from dinitrogen in homogeneous solution is known to be challenging considering that an N2 cleavage step needs combined with two N–C coupling steps. Herein, a tungsten complex bearing tailor-made 2,2′-(tBu2As)2-substituted tolane ligand scaffold was shown split afford the corresponding nitride, which not case for (iPr2As)2-substituted derivative. former nitride then reacted 2,4,6-trimethylpyrylium triflate, led formation oxo complex, along collidine. Over course this reaction, O atom pyrylium starting material replaced N via hitherto unprecedented skeletal editing process.

Language: Английский

Citations

12
Uncanonical Semireduction of Quinolines and Isoquinolines via Regioselective HAT-Promoted Hydrosilylation DOI
Chao Hu,

Cuong Vo,

Rohan R. Merchant

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 25 - 31

Published: Dec. 22, 2022

Heterocycles are the backbone of modern medical chemistry and drug development. The derivatization "an olefin" inside aromatic rings represents an ideal approach to access functionalized saturated heterocycles from abundant building blocks. Here, we report operationally simple, efficient, practical method selectively hydrosilylated reduced N-heterocycles bicyclic aromatics via a key diradical intermediate. This is expected facilitate complex heterocycle functionalizations that enable novel medicinally relevant scaffolds.

Language: Английский

Citations

28
N-Sulfonylation of azoles with sulfonyl hydrazides enabled by electrocatalysis DOI
Cheng Huang, Kang Chen, Zhihong Liu

et al.

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(15), P. 8706 - 8710

Published: Jan. 1, 2024

We report an electrochemical strategy for N -sulfonylation of azoles with sulfonyl hydrazides via radical–radical cross-coupling.

Language: Английский

Citations

5
Dearomative dimerization of quinolines and their skeletal rearrangement to indoles triggered by single-electron transfer DOI

Eugene Yew Kun Tan,

Alireza Dehdari,

Amirah S. Mat Lani

et al.

Chem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

5
Catalyst‐Free Photooxidative N‐Acylation of Azoles with Aldehydes DOI

Nianfeng Gong,

Zelin Zhao,

David James Young

et al.

Chemistry - A European Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract A catalyst‐free photochemical N‐acylation of azoles with aldehydes has been developed using inexpensive BrCCl 3 as the oxidant. This transition‐metal‐ and photocatalyst‐free amidation proceeded efficiently a wide variety substrates to give corresponding N‐acylazoles, including for late modification pharmaceutically active molecules, on gram‐scale.

Language: Английский

Citations

0