Metal-Free N-Arylation of Secondary Amides at Room Temperature

Abstract

The arylation of secondary acyclic amides has been achieved with diaryliodonium salts under mild and metal-free conditions. The methodology has a wide scope, allows synthesis of tertiary amides with highly congested aryl moieties and avoids the regioselectivity problems observed in reactions with (diacetoxyiodo)benzene.

Sterically Congested 2,6‐Disubstituted Anilines from Direct C−N Bond Formation at an Iodine(III) Center

“…Alternatively, they may engage in direct C−N coupling reactions, even in the absence of a metal promoter, an aspect which has attracted considerable attention from biomedical sciences. Examples include aniline syntheses by the arylation of amides,6a,6b aromatic amines,6c,6d methoxyamines,6e ammonia,6f heterocycles,6g,6h and radical rearrangements 6i. Although aniline syntheses have thus far reached a significant level of generality,7 we observed that there is little synthetic prospect for C−N bond formation in the particular case of 2,6‐disubstituted aniline derivatives 8.…”

Understanding and Exploitation of Neighboring Heteroatom Effect for the Mild N-Arylation of Heterocycles with Diaryliodonium Salts under Aqueous Conditions: A Theoretical and Experimental Mechanistic Study

“…However, we note that further optimization of the conditions for the new substrates is necessary for amplifying the potential of this synthetic strategy. 10,14 or it can be assumed via the iminol tautomer. 16 …”

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…The N-arylation of non-aromatic systems such as alkyl-amides is also possible with the utilization of diaryliodonium salts. Very recently, Olofsson's group reported a metal-free N-arylation method for secondary acyclic amides 25 (23) using diaryliodonium salts and sodium hydride as a base at room temperature (Scheme 12). The methodology has a wide scope regarding the N-arylated products (24), ensures excellent yields, avoids harsh conditions 26 and solves regioselectivity problems observed earlier in this type of transformation.…”

“…The metal-free N-arylation of ortho-acyl anilines (25) for the synthesis of acridine derivatives (26) was recently described by Chen et al 28 The reactions were conducted in 1,2-dichloroethane (DCE) at 130 °C (Scheme 13). The usefulness of transformation was demonstrated on several examples which provided the desired products in good to high yields.…”