I(III)-Mediated Arene C–H Amination Using (Hetero)Aryl Nucleophiles

Motsch, Bill; Kaur, Jasjit Y; Wengryniuk, Sarah E.

doi:10.1021/acs.orglett.3c00809

Cited by 7 publications

(7 citation statements)

References 45 publications

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“…Nucleophilic activation of the pyridinium can also be achieved by generation of in situ hypervalent iodine ( N -HVI) reagents (Scheme B) . With a broad tolerance to electronic nature of the pyridine (electron-poor and -rich), a range of aryl ethers were coupled to form N -aryl ether pyridinium salts in good yields.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

Carson,

Liu,

Kozlowski

2024

J. Org. Chem.

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Herein, we describe a dual photocatalytic system to synthesize phenol−pyridinium salts using visible light. Utilizing both electron donor−acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C−N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (S N Ar) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol−pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

Carson,

Liu,

Kozlowski

2024

J. Org. Chem.

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“…An established way of synthesizing N -(hetero)arylpiperidines is via their corresponding pyridinium salts, − with Zincke ring-opening and ring-closing chemistry being closely associated with this strategy (Figure B). In the first stage, pyridines react with 2,4-dinitro chlorobenzene to form N -arylpyrdinium salts; subsequent reactions with anilines form the target pyridinium ion through ring-opened azatriene intermediates. , Metal-catalyzed hydrogenation reactions can provide access to piperidines and influence the stereochemical outcome. , Furthermore, pyridinium salts are reactive electrophiles and undergo addition reactions that substitute the carbon framework of the heterocycle.…”

Section: Introductionmentioning

confidence: 99%

“…Direct approaches that form N -arylpyridiniumsvia radical ions or ionic cross-coupling reactions are highly promising. Controlling regioselectivity and expanding the scope of the pyridine partner are the remaining challenges for those processes. − …”

Section: Introductionmentioning

confidence: 99%

A General Strategy for N-(Hetero)arylpiperidine Synthesis Using Zincke Imine Intermediates

Selingo,

Greenwood,

Andrews

et al. 2023

J. Am. Chem. Soc.

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Methods to synthesize diverse collections of substituted piperidines are valuable due to the prevalence of this heterocycle in pharmaceutical compounds. Here, we present a general strategy to access N-(hetero)arylpiperidines using a pyridine ring-opening and ring-closing approach via Zincke imine intermediates. This process generates pyridinium salts from a wide variety of substituted pyridines and (heteroaryl)anilines; hydrogenation reactions and nucleophilic additions then access the N-(hetero)arylpiperidine derivatives. We successfully applied highthroughput experimentation (HTE) using pharmaceutically relevant pyridines and (heteroaryl)anilines as inputs and developed a one-pot process using anilines as nucleophiles in the pyridinium salt-forming processes. This strategy is viable for generating piperidine libraries and applications such as the convergent coupling of complex fragments.

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“…Traditional methods for nondirected aromatic C–H amination rely on a sequential nitration/reduction/alkylation process, which suffers from limitations in site selectivity and substrate compatibility. Consequently, researchers have explored several alternative approaches utilizing transition metal catalysis, ,, stoichiometric reactive reagents, and, in the past decade, novel photocatalytic methods , to enhance selectivity and expand substrate scope.…”

mentioning

confidence: 99%

Site-Selective Electrochemical Arene C–H Amination

Alvarez,

Stewart,

Ullah

et al. 2024

J. Am. Chem. Soc.

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Here we present the discovery and development of a highly selective aromatic C−H amination reaction. This electrochemical strategy involves a cathodic reduction process that generates highly electrophilic dicationic N-centered radicals that can efficiently engage in aromatic C−H functionalization and channel the regioselectivity of the aromatic substitution. The nitrogenradical cation−pi interaction with arenes used throughout nature leads to a charge transfer mechanism, with subsequent aromatic C−N bond formation. This electrochemical process generates aryl DABCOnium salts in excellent yields and regioselectivities (single regioisomer in most cases). The scope of the reaction on arene is broad where various functionalities such as aryl halides (bromides, chlorides, fluorides), carbonyls (ketones, esters, imides), sulfonamides, and heteroarenes (pyridines, bipyridines, and terpyridines) are well tolerated. Moreover, we disclose the synthetic utility of the aryl DABCOnium salt adducts leading to the direct access of diverse aryl piperazines and the chemoselective cleavage of the exocyclic aryl C(sp 2 )−N bond over electrophilic C(sp 3 )−N + bonds via photoredox catalysis to afford synthetically useful aryl radicals that can engage in aryl C−C and C−P bond formation.

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I(III)-Mediated Arene C–H Amination Using (Hetero)Aryl Nucleophiles

Cited by 7 publications

References 45 publications

Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

A General Strategy for N-(Hetero)arylpiperidine Synthesis Using Zincke Imine Intermediates

Site-Selective Electrochemical Arene C–H Amination

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