A Three-Component Ugi-Type Reaction of N-Carbamoyl Imines Enables a Broad Scope Primary α-Amino 1,3,4-Oxadiazole Synthesis.

A general synthesis of N-protected primary α-amino 1,3,4-oxadiazoles, from N-carbamoyl imines, N-isocyaniminotriphenylphosphorane (NIITP), and carboxylic acids, is described. Featuring an isocyanide addition reaction with N-carbamoyl imines, this efficient three-component Ugi-type reaction was found to be broad in scope with respect to imine, and carboxylic acid coupling partners. Furthermore, the versatility of this method was demonstrated by α-amino 1,2,4-triazole synthesis, the late-stage functionalization of seven drug molecules, and five divergent derivatizations of a primary α-amino 1,3,4-oxadiazole.