Nucleophilic Amination of Aryl Halides with an Azanide Surrogate

Bradley Cooper; Thomas Harris; Ethan Lim; Katherine A. Hooper; George Whitehead; Jonathan R. Carney; Michael James

doi:10.1002/chem.202403952

Nucleophilic Amination of Aryl Halides with an Azanide Surrogate

Bradley Cooper, Thomas Harris, Ethan Lim, Katherine A. Hooper, George Whitehead, Jonathan R. Carney, Michael James

Research output: Contribution to journal › Article › peer-review

Abstract

We report the development of an azanide (−NH2) surrogate which enables the facile conversion of electron-deficient (hetero)aryl halides into primary N-aryl amines under transition-metal-free conditions. The designed amidine reagent is easy to prepare, bench stable, and undergoes facile N-arylation under basic conditions at 40 °C. Intermediate N-aryl amidines are readily cleaved to form N-aryl amines in situ through hydrolysis or base-promoted elimination. The developed surrogate is a safer and more selective alternative to existing anionic N-nucleophiles, such as alkali metal amides or azide salts.

Original language	English
Article number	e202403952
Journal	Chemistry – A European Journal
Volume	31
Issue number	8
Early online date	17 Dec 2024
DOIs	https://doi.org/10.1002/chem.202403952
Publication status	Published - 6 Feb 2025

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title = "Nucleophilic Amination of Aryl Halides with an Azanide Surrogate",

abstract = "We report the development of an azanide (−NH2) surrogate which enables the facile conversion of electron-deficient (hetero)aryl halides into primary N-aryl amines under transition-metal-free conditions. The designed amidine reagent is easy to prepare, bench stable, and undergoes facile N-arylation under basic conditions at 40 °C. Intermediate N-aryl amidines are readily cleaved to form N-aryl amines in situ through hydrolysis or base-promoted elimination. The developed surrogate is a safer and more selective alternative to existing anionic N-nucleophiles, such as alkali metal amides or azide salts.",

author = "Bradley Cooper and Thomas Harris and Ethan Lim and Hooper, \{Katherine A.\} and George Whitehead and Carney, \{Jonathan R.\} and Michael James",

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doi = "10.1002/chem.202403952",

language = "English",

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T1 - Nucleophilic Amination of Aryl Halides with an Azanide Surrogate

AU - Cooper, Bradley

AU - Harris, Thomas

AU - Lim, Ethan

AU - Hooper, Katherine A.

AU - Whitehead, George

AU - Carney, Jonathan R.

AU - James, Michael

PY - 2025/2/6

Y1 - 2025/2/6

N2 - We report the development of an azanide (−NH2) surrogate which enables the facile conversion of electron-deficient (hetero)aryl halides into primary N-aryl amines under transition-metal-free conditions. The designed amidine reagent is easy to prepare, bench stable, and undergoes facile N-arylation under basic conditions at 40 °C. Intermediate N-aryl amidines are readily cleaved to form N-aryl amines in situ through hydrolysis or base-promoted elimination. The developed surrogate is a safer and more selective alternative to existing anionic N-nucleophiles, such as alkali metal amides or azide salts.

AB - We report the development of an azanide (−NH2) surrogate which enables the facile conversion of electron-deficient (hetero)aryl halides into primary N-aryl amines under transition-metal-free conditions. The designed amidine reagent is easy to prepare, bench stable, and undergoes facile N-arylation under basic conditions at 40 °C. Intermediate N-aryl amidines are readily cleaved to form N-aryl amines in situ through hydrolysis or base-promoted elimination. The developed surrogate is a safer and more selective alternative to existing anionic N-nucleophiles, such as alkali metal amides or azide salts.

U2 - 10.1002/chem.202403952

DO - 10.1002/chem.202403952

M3 - Article

SN - 0947-6539

VL - 31

JO - Chemistry – A European Journal

JF - Chemistry – A European Journal

IS - 8

M1 - e202403952

ER -

Nucleophilic Amination of Aryl Halides with an Azanide Surrogate

Abstract

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