Ammonium Chloride Promoted Ugi Four-Component, Five-Center Reaction of α-Substituted α-Isocyano Acetic Acid:  A Strong Solvent Effect

Conditions have been developed for the multicomponent synthesis of di- and tetrapeptide (7) based on the unique reactivity of α-isocyano acetic acid (4 and its α -substituted derivatives) by an Ugi four-component, five-center reaction. Simply mixing 4, a carbonyl compound (aldehyde or ketone, 8), and a secondary amine (9) (ratio:  1:1:2) in toluene in the presence of 1.5 equiv of ammonium chloride afforded the desired product in good to excellent yield as a mixture of two diastereomers.