Elusive metal-free primary amination of arylboronic acids: synthetic studies and mechanism by density functional theory

Abstract

Herein, we disclose the first metal-free synthesis of primary aromatic amines from arylboronic acids, a reaction that has eluded synthetic chemists for decades. This remarkable transformation affords structurally diverse primary arylamines in good chemical yields, including a variety of halogenated primary anilines that often cannot be prepared via transition-metal-catalyzed amination. The reaction is operationally simple, requires only a slight excess of aminating agent, proceeds under neutral or basic conditions, and, importantly, can be scaled up to provide multigram quantities of primary anilines. Density functional calculations reveal that the most likely mechanism involves a facile 1,2-aryl migration and that the presence of an ortho nitro group in the aminating agent plays a critical role in lowering the free energy barrier of the 1,2-aryl migration step.

Figure 1

Approaches to primary aromatic amines from aryl halides and aromatic boronic acids/derivatives.

Figure 2

1,2-Aryl migration transition state. (Bond lengths in Å)

Scheme 1

Hydroxylation and Amination of Arylboronic Acids via Leaving-Group-Initiated 1,2-Aryl Migration

Scheme 2

Primary Amination of Arylboronic Acids on a Gram-Scale Using Aminating Agent DPH (8).