Mechanism and Scope of Base-Controlled Catalyst-Free N-Arylation of Amines with Unactivated Fluorobenzenes

Christian Borch Jacobsen; Morten Peter Meldal; Frederik Diness

doi:10.1002/chem.201604098

Mechanism and Scope of Base-Controlled Catalyst-Free N-Arylation of Amines with Unactivated Fluorobenzenes

Christian Borch Jacobsen, Morten Peter Meldal, Frederik Diness

Kemisk Institut

21 Citationer (Scopus)

Abstract

A general method for transition metal-free N-arylation of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple two-step synthesis of the antidepressant Vortioxetine

Originalsprog	Engelsk
Tidsskrift	Chemistry: A European Journal
Vol/bind	23
Udgave nummer	4
Sider (fra-til)	846-851
Antal sider	6
ISSN	0947-6539
DOI	https://doi.org/10.1002/chem.201604098
Status	Udgivet - 18 jan. 2017

Adgang til dokumentet

10.1002/chem.201604098

Citationsformater

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abstract = "A general method for transition metal-free N-arylation of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple two-step synthesis of the antidepressant Vortioxetine",

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author = "Jacobsen, {Christian Borch} and Meldal, {Morten Peter} and Frederik Diness",

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AB - A general method for transition metal-free N-arylation of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple two-step synthesis of the antidepressant Vortioxetine

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KW - arylation

KW - catalyst-free

KW - nucleophilic substitution

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