5.06 – Amides

There have been several major developments in the synthesis of amides since COFGT (1995). First has been the superseding (after several decades) of diimides as the main coupling reagent for amines to carboxylic acids, especially in the synthesis of peptides; although many new reagents have become important, the emergence of the uronium salts is especially notable. Second, the selective hydrolysis of nitriles, histotically quite a tricky process, has received much attention, with a range of Lewis acid and enzymic catalytic methods being developed, the latter often leading to enantio-control. In general, producing amides with high ee has become very important, and a wide range of synthetic methods have been used for the construction of the C/N skeleton, with rearrangement processes continuing to feature strongly. Finally, the use of immobilized reagents and scavengers have been widely reported, especially as amides are so well suited to combinatorial chemistry. Last of all, it is worth noting that the amides fall crudely into two classes—simple bulk amides that are important feed-stocks for the chemical industry, requiring highly efficient, cheap, high throughput procedures; and more complex fine chemicals and target syntheses, for which selectivity and stereocontrol are more important.