Iron(iii)-catalyzed mono-, di- and tricyanomethylation of primary amines with diazoacetonitrile: construction of α-amino acetonitriles and asymmetric α-amino succinonitriles†

Abstract

α-Amino nitriles and succinonitriles represent two crucial classes of cyano-containing compounds with significant applications. Herein, we reported for the first time a divergent synthesis of α-amino nitriles and asymmetric α-amino succinonitriles through mono-, di- and tricyanomethylation between primary amines and diazoacetonitrile. This reaction was catalyzed by (TPP)Fe(iii)Cl or PcFe(iii)Cl in either dichloromethane (DCM) alone or a mixed solvent of DCM and acetonitrile at room temperature. The combination of mono- and dicyanomethylation is a new solvent-controlled divergent synthesis approach. Both di- and tricyanomethylation represent novel transformation types in metalloradical catalysis, constructing one C–C bond and multiple (two or three) C–N bonds in one-pot. This approach is distinctly different from the conventional N–H insertion between amines and diazo reagents. Furthermore, the divergent synthesis enables gram-scale preparation of three typical compounds. Mechanistically, monocyanomethylation proceeds via the N–H insertion pathway. For di- and tricyanomethylation, the mechanism involves homodimerization of the iron(iv)–acetonitrile radical, derived from the reaction between diazoacetonitrile and (TPP)Fe(iii)Cl coordinated by bis(amines) or PcFe(iii)Cl. Subsequently, monoamination occurs through the attack of one amine molecule on a carbon atom of the formed C–C bond.