title: Mechanism and Scope of Base-Controlled Catalyst-Free N-Arylation of Amines with Unactivated Fluorobenzenes.
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.
authors.affiliation: Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Borch Jacobsen
authors.affiliation: Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Meldal
authors.affiliation: Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
authors.forename: Frederik
authors.identifier: http://orcid.org/0000-0001-5098-7198
authors.initials: F
authors.lastname: Diness
keywords: amines; arylation; catalyst-free; nucleophilic substitution; vortioxetine