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

Department of Chemistry

21 Citations (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

Original language	English
Journal	Chemistry: A European Journal
Volume	23
Issue number	4
Pages (from-to)	846-851
Number of pages	6
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.201604098
Publication status	Published - 18 Jan 2017

Keywords

amines
arylation
catalyst-free
nucleophilic substitution
vortioxetine

Access to Document

10.1002/chem.201604098

Cite this

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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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