Metal-free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

• Published in: Angewandte Chemie International Edition Vol. 55; no. 51; pp. 15812 - 15815
• Main Authors: Sandtorv, Alexander H., Stuart, David R.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 19-12-2016; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: alicyclic amines; amination; hypervalent iodine reagents; metal-free synthesis; nucleophilic aromatic substitution; hypervalent iodine reagents; metal-free synthesis; alicyclic amines; amination; nucleophilic aromatic substitution
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201610086

A mild and metal‐free approach to C−N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso‐substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal‐free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal‐free C−N coupling reactions.
A new challenger: Aryl amines are synthesized in a metal‐free reaction between unsymmetrical aryl(2,4,6‐trimethoxyphenyl)iodonium salt electrophiles and alicyclic amine nucleophiles. Yields and scope exceed those of the classical SNAr approach. The reaction conditions are mild and lead to highly regiospecific substitution of the iodonium moiety in the iodonium reagents.