The 2,5-DKP are heterocyclic peptidomimetics, present in nature with high structural diversity, privileged in the design of new bioactive molecules with potential application in medicinal chemistry, exhibiting anticancer and antimicrobial properties, among others. Conventional synthetic approaches to access DKPs via dipeptide ester cyclization suffer from several disadvantages, for example; low overall yields, use of a large number of reagents and/or drastic reaction conditions, among others. Therefore, in the present work, we report the one-pot synthesis of 2,5-DKP by RMC-I coupled with a cyclic post-transformation process with several advantages over previously reported conventional methods.