Greener Methods for Amide Bond Synthesis

The amide bond is an important linkage ubiquitous in nature and technology found in many small molecules and materials. Formation of amide bonds is most easily accomplished via condensation at high temperatures using amines and carboxylic acids, but peptide coupling agents are pervasively used to form amides under milder conditions. While these coupling agents are robust synthetic reagents, they are generally used in super stoichiometric amounts which can be disadvantageous due to their sensitizing nature and lack of atom economy. This chapter presents a brief survey of "greener" methods to form amides via the catalytic use or release of small benign molecules such as H2 or H2O. Both heterogenous and homogenous catalytic systems will be discussed. We will group catalytic methods by which functional moieties (e.g., alcohol, aldehyde, nitrile, azide, and acid homologs) are used as starting materials for the reaction. We hope to inform the reader of the broad scope of "green" amide bond-forming reactions which can be used in lieu of canonical peptide coupling reagents.