Investigation of the Configurational Stabilities of Chiral Isocyanoacetates in Multicomponent Reactions

Isocyanoacetates are uniquely reactive compounds characterized by an ambivalent isocyano functional group and an enolizable alpha-carbon. It is widely believed that chiral alpha-substituted isocyanoacetates are configurationally unstable in some synthetically useful isocyanide-based multicomponent reactions. Herein, we demonstrate that chiral isocyanoacetates can be used with minimal to negligible epimerization in a variety of canonical Ugi four-component condensations as well as Joullie-Ugi three-component condensations, reactions that are particularly useful for constructing complex peptide structures in a single synthetic operation.