Electrosynthesis of α‐Aminonitriles: Anodic Cyanation of N‐Substituted Tetrahydroquinolines and N‐Phenylpiperidines

Abstract

AbstractThe electrochemical cyanation of N‐alkyl‐substituted cyclic six‐membered amines including N‐alkyl‐1,2,3,4‐tetrahydroquinoline and N‐phenylpiperidine derivatives has been investigated. The reaction gives the corresponding α‐aminonitriles and was carried out at a graphite felt anode percolated with a methanolic solution of the amine, containing six equivalents of sodium cyanide per mol of substrate, and lithium acetate as the supporting electrolyte. In the case of N‐substituted tetrahydroquinolines 1a–f, cyanation occurs regioselectively at the ring and the position of substitution depends on the nature of the N‐alkyl substituent. The stereoselectivity of the cyanide addition was investigated using various 3‐methyltetrahydroquinolines 8a–c as substrates. In all cases, the major stereoisomers 9a–c possess a cis configuration in which the 2‐cyano group has an axial disposition and the 3‐methyl group is equatorial. In a similar fashion, various N‐phenylpiperidines substituted at the ring by either one or two methyl groups were oxidized. In all the selected amines the introduction of the cyanide group occurs stereospecifically in the position α to the nitrogen atom. The cis or trans relative configuration of the cyanated compounds is discussed separately for each substrate. It is noteworthy that in all cases the cyano group was in an axial position.