Synthetic Methods for Primary Anilines

Abstract

Aryl amines have received significant interest because these compounds widely exist in the structural backbones of ligands, pharmaceuticals, agrochemicals, natural products, and functional materials. In N-arylation reactions, several types of organic electrophile coupling partners such as (pseudo)halides (Ullmann-type and Buchwald–Hartwig couplings) and boronic acids (Chan–Lam coupling) are popular. The main synthetic methods for the preparation of these compounds involving N-arylation utilize aryl halides. Progress has been made with the coupling of arylating reagents which are less expensive than aryl halides, providing both a cost-effective and more efficient reaction route. For example, the process of C–H bond activation/functionalization, a step-efficient and atom-economical transformation, has emerged as a powerful strategy in C–N bond-forming reactions. Moreover, a transition-metal-free method for the N-arylation of amines using an aryne intermediate has been developed. This chapter focuses on recent advances in chemo- and regioselective N-arylation (either on one N-center or on the exocyclic N-site of the ring) or the selective arylation of amino alcohols without additional protection/deprotection using arylating reagents. This chapter provides an overview of arylating reagents for N-arylation reactions found in both basic and applied chemical research. The substrate scope, limitations, reaction mechanism, and chemoselectivity, as well as related control strategies of these reactions, are discussed. To the best of our knowledge, there has been no book about introducing arylating reagents to develop more efficient and environmentally friendly cross-coupling methods for the N-arylation of amines. We believe this critical review will provide necessary background information on the N-arylation of amines.