Sequential One‐Pot Synthesis of Dipeptides through the Transient Formation of CDI‐ N ‐Protected α‐Aminoesters

The synthesis of dipeptides through a sequential one‐pot procedure from commercially available protected amino acids is described. The transformation relies on the use of in situ generated transiently CDI‐protected α‐amino esters (CDI, e.g. N , N′ ‐carbonyldiimidazole). In addition of being a highly atom‐economical process, the couplings take place under very mild and neutral conditions without adding a base to the reaction medium. This protocol provides a concise and less costly route to dipeptide derivatives (12 examples, up to 87% yield) and is compatible with commonly used N ‐urethane protecting groups. Moreover, no epimerization was detected even when sensitive Boc‐Cys(Bn)−OH was used.