Non-Classical Amide Bond Formation: Transamidation and Amidation of Activated Amides and Esters by Selective N–C/O–C Cleavage

In the past several years, tremendous advances have been made in non-classical routes for amide bond formation that involve transamidation and amidation reactions of activated amides and esters. These new methods enable the formation of extremely valuable amide bonds via transition-metal-catalyzed, transition-metal-free, or metal-free pathways by exploiting chemoselective acyl C–X (X = N, O) cleavage under mild conditions. In a broadest sense, these reactions overcome the formidable challenge of activating C–N/C–O bonds of amides or esters by rationally tackling nN → π*C=O delocalization in amides and nO → π*C=O donation in esters. In this account, we summarize the recent remarkable advances in the development of new methods for the synthesis of amides with a focus on (1) transition-metal/NHC-catalyzed C–N/C–O bond activation, (2) transition-metal-free highly selective cleavage of C–N/C–O bonds, (3) the development of new acyl-transfer reagents, and (4) other emerging methods.

1 Introduction

2 Transamidation of Amides

2.1 Transamidation by Metal–NHC Catalysis (Pd–NHC, Ni–NHC)

2.2 Transition-Metal-Free Transamidation via Tetrahedral Intermediates

2.3 Reductive Transamidation

2.4 New Acyl-Transfer Reagents

2.5 Tandem Transamidations

3 Amidation of Esters

3.1 Amidation of Esters by Metal–NHC Catalysis (Pd–NHC, Ni–NHC)

3.2 Transition-Metal-Free Amidation of Esters via Tetrahedral Intermediates

3.3 Reductive Amidation of Esters

4 Transamidations of Amides by Other Mechanisms

5 Conclusions and Outlook