Amide bond formation: beyond the dilemma between activation and racemisation

The development of methods for amide bond formation without recourse to typical condensation reagents has become an emerging research area and has been actively explored in the past quarter century. Inspired by the structure of vitamin B12, we have developed a metal-templated macrolactamisation that generates a new wave towards classical macrolactam synthesis. Further, distinct from the extensively used methods with condensation reagents or catalysts based on catalyst/reagent control our metal-catalysed methods based on substrate control can effectively address long-standing challenges such as racemisation in the field of peptide chemistry. In addition, the substrate-controlled strategy demonstrates the feasibility of “remote” peptide bond-forming reaction catalysed by a metal–ligand complex. Moreover, an originally designed hydrosilane/aminosilane system can avoid not only racemisation but also unnecessary waste production. This feature article documents our discovery and application of our original approaches in amide bond formation.