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 are two important classes of cyano-containing compounds with extremely significant application value. Herein, we firstly reported the divergent synthesis for preparing α-amino nitriles and asymmetric α-amino succinonitriles via the developed mono-, di- and tricyanomethylation between primary amines with diazoacetonitrile catalyzed by (TPP)Fe(III)Cl or PcFe(III)Cl in sole dichloromethane (DCM) or the mixed solvent of DCM and acetonitrile at room temperature. Within the divergent synthesis, the combination of the mono- and dicyanomethylation is a new example around solvent control divergent synthesis; both of the di- and tricyanomethylation represent a novel type of transformation in the field of metalloradical catalysis, which can construct one C−C bond & two or three C−N bonds in one-pot and are totally different from the conventional N−H insertion between amines with diazo reagents; additionally, the divergent synthesis can be used for the gram-scale preparation of three typical compounds. For the proposed mechanism, the monocyanomethylation proceeds by the N−H insertion pathway; while for the di- and tricyanomethylation, the homodimerization of iron(III)−acetonitrile radical derived from the reaction between diazoacetonitrile and (TPP)Fe(III)Cl coordinated by bis(amines) or PcFe(III)Cl is involved, and the attack of one amine molecule toward one carbon on the formed C−C bond (monoamination) is followed.