CH‐Functionalization of Heterocycles with the Formation of C−O, C−N, C−S/Se, and C−P Bonds by Intermolecular Addition of Heteroatom‐Centered Radicals

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(11), P. 1714 - 1755

Published: April 12, 2023

Abstract In the last decade, free radicals have found a wide application in functionalization of unsaturated compounds, such as alkenes, alkynes, and arenes, via free‐radical addition to carbon‐carbon π‐bonds. these processes, intermolecular attack on aromatic substrates represents challenge due relatively high resistance π‐system reactions comparison alkene C=C bonds. The heterocycles is especially interesting diversity their structures chemical properties well importance for medicinal chemistry, agrochemistry, materials science. Addition C‐centered widely known Minisci‐type well‐reviewed. this paper, we summarized main achievements less explored group processes: by heteroatom‐centered (O‐, N‐, S‐/Se‐, P‐radicals) with emphasis papers published after 2010. Literature analysis revealed strong trend towards usage electrochemistry photoredox‐catalysis generation recent years. remaining fundamental problem field lack experimental support proposed mechanisms frequent existence several plausible reaction pathways. progress mechanistic studies can significantly improve prediction optimal conditions depending structure.

Language: Английский

---

Relay C–H Functionalization Enables De Novo Synthesis of Pyridines and Pyridones

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(9), P. 5795 - 5807

Published: April 13, 2023

The realization of sequential and controllable C–H functionalization in one step can maximize the utilization bonds to rapidly create valuable scaffolds dramatically increase atom functional group utilization. In this work, we describe an iron-catalyzed relay proto col that enables de novo synthesis a wide range pyridines pyridones. This transformation involves three-fold (two Csp3–H Csp2–H) allows simultaneous generation three chemical two rings step. reaction features operational simplicity, broad substrate scope (>70 examples), good compatibility, suitability derivation some bioactive molecules. Various control kinetic isotope effect experiments were performed understand mechanism. DFT investigations support interesting imine α-carbon radical addition/1,5-hydrogen transfer/homolytic aromatic substitution cascade process.

Language: Английский

---

Photocatalytic Decarboxylative [3 + 2] and [4 + 2] Annulation of Enynals and γ,σ-Unsaturated N-(Acyloxy)phthalimides by NaI/PPh₃ Catalysis

Organic Letters, Journal Year: 2021, Volume and Issue: 23(20), P. 7839 - 7844

Published: Sept. 28, 2021

A practical and eco-friendly strategy for the radical-mediated decarboxylative [3 + 2] [4 annulation of enynals γ,σ-unsaturated N-(acyloxy)phthalimides through photoactivation an electron donor-acceptor (EDA) complex has been developed. wide range primary, secondary, tertiary alkyl N-hydroxyphthalimide (NHP) esters can be used as suitable substrates synthesis fused ketones without any transition-metal catalysts or oxidants. This protocol features a broad substrate scope, excellent selectivity, clean reaction conditions.

Language: Английский

---

Synthesis of Stable N–H Imines with a Benzo[7,8]indolizine Core and Benzo[7,8]indolizino[1,2-c]quinolines via Copper-Catalyzed Annulation of α,β-Unsaturated O-Acyl Ketoximes with Isoquinolinium N-Ylides

Organic Letters, Journal Year: 2022, Volume and Issue: 24(21), P. 3828 - 3833

Published: May 23, 2022

A copper-catalyzed annulation of α,β-unsaturated O-acyl ketoximes with isoquinolinium N-ylides has been developed for the concise synthesis stable N-H imines a benzo[7,8]indolizine core. When β-(2-bromoaryl)-α,β-unsaturated are used as starting materials, cascade cyclization occurs to afford benzo[7,8]indolizino[1,2-c]quinolines.

Language: Английский

---

Microwave-Promoted Synthesis of 1-Tetralones via Iminyl Radical-Mediated 1,5-Hydrogen Atom Transfer

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Microwave irradiation of O-phenyloximes produces 1-tetralones via N-O homolysis, 1,5-hydrogen atom transfer (HAT), and cyclization a radical intermediate onto an aromatic ring. The HAT step is facilitated by coordination Lewis acid InCl3·H2O to iminyl radical. reaction rapid exhibits broad substrate scope. A larger scale transformation can be performed using conventional heating instead microwave irradiation.

Language: Английский

---

Functionalized Oxindole Construction via a Cyano Migration and Cyclization Relay Strategy

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

A visible-light-induced trifunctionalization of unactivated alkenes for building functionalized oxindoles through a radical cyano migration strategy is reported. This transformation employs tandem alkene sulfonylation-initiated migration/cyclization cascade process. features stable and easily accessible substrates, mild reaction conditions, metal-free catalysts, the capability late-stage functionalization.

Language: Английский

---

Ceria–Zirconia-Supported Pt as an Efficient Catalyst for the Sustainable Synthesis of Hydroxylamines and Primary Amines via the Hydrogenation of Oximes Under Ambient Conditions

Molecules, Journal Year: 2025, Volume and Issue: 30(9), P. 1926 - 1926

Published: April 26, 2025

Amines and hydroxylamines are essential compounds in the synthesis of pharmaceuticals other functionalized molecules. However, primary amines particularly remains a challenging task. The most common way to obtain involves reduction substances containing C-N bonds, such as nitro compounds, nitriles, oximes. Among these, oximes readily accessible substrates easily derived from ketones aldehydes. much harder reduce compared nitriles. catalytic heterogeneous hydrogenation often requires harsh conditions catalysts with high precious metal loadings, while hard be obtained by this method. In work, we showed that Pt supported on porous ceria–zirconia solid solution enables selective atom-efficient both through oximes, achieving yields up 99% under ambient reaction “green” THF:H2O solvent system. activity 1% Pt/CeO2-ZrO2 catalyst (TOF > 500 h−1) is due low-temperature hydrogen activation nanoparticles formation hydride, Pt-H. strong influence electron-donating electron-withdrawing groups aromatic implies nucleophilic attack hydridic electrophilic carbon protonated

Language: Английский

---

C(sp3)−H bond functionalization of oximes derivatives via 1,5−hydrogen atom transfer induced by iminyl radical

Chinese Chemical Letters, Journal Year: 2021, Volume and Issue: 33(3), P. 1199 - 1206

Published: Aug. 19, 2021

Language: Английский

---

Polysubstituted Indole Synthesis via Palladium/Norbornene Cooperative Catalysis of Oxime Esters

Organic Letters, Journal Year: 2022, Volume and Issue: 24(2), P. 484 - 489

Published: Jan. 3, 2022

Polysubstituted indoles are prevalent in pharmaceuticals, agrochemicals, and organic materials. Presented herein is the fact that polyfunctionalized can be efficiently constructed from easily accessible oxime esters aryl iodides, involving a palladium/norbornene synergistic synthesis. The reaction enabled by unique class of electrophiles cooperative catalysis, which derived simple ketone. broad substrate scope high functional group tolerance could make this method attractive for synthesis polysubstituted indoles.

Language: Английский

---

Radical Alkene-Trifluoromethylation-Triggered Nitrile Insertion/Remote Functionalization Relay Processes: Diverse Synthesis of Trifluoromethylated Azaheterocycles Enabled by Copper Catalysis

Organic Letters, Journal Year: 2022, Volume and Issue: 24(4), P. 1110 - 1115

Published: Jan. 26, 2022

A copper-catalyzed alkene-trifluoromethylation-triggered nitrile insertion/remote functionalization relay process has been achieved, in which "interrupted" remote 1,n-difunctionalizations of alkenes with insertion can deliver iminyl radical intermediates instead C-based radicals, followed by subsequent 1,n-HAT to furnish corresponding functionalization. This protocol enables a straightforward approach streamline the assembly structurally diverse trifluoromethylated azaheterocycles.

Language: Английский

---