Nucleophilic Carbene and HOAt Relay Catalysis in an Amide Bond Coupling:  An Orthogonal Peptide Bond Forming Reaction

A catalyzed internal redox process provides a route from α-reducible aldehydes and amines to α-reduced amides. The chemistry is catalyzed by nucleophilic carbenes and common peptide cocatalysts such as HOBt and HOAt in a relay fashion. The transformation proceeds in excellent yields using a variety of primary and secondary alkyl and aryl amines. The aldehyde component may be varied from haloaldehydes to epoxy and aziridino aldehydes as well as enals. The latter three substrates provide for a waste-free amide bond forming reaction.