Mechanochemical IMCR and IMCR-post transformation domino strategies: towards the sustainable DOS of dipeptide-like and heterocyclic peptidomimetics

Abstract

A facile mechanochemical Ugi four-component reaction (MC-Ugi-4CR) has been developed for the synthesis of new dipeptide-like products in high yields under solvent-, catalyst-, column-free (SCCF) conditions at room temperature in only three minutes. The scope and versatility of this efficient isocyanide-based multicomponent reaction (IMCR) is demonstrated with the first one-pot diversity-oriented synthesis (DOS) of privileged heterocyclic peptidomimetics (PHPs) such as tri-substituted 2,5-diketopiperazines (DKPs) and α,β-unsaturated-γ-lactams via a sustainable mechanochemical domino strategy that includes IMCR-post transformations in high overall yields and in a total reaction time of only six minutes.