Regio- and diastereoselective synthesis of α-cyanoamines by anodic oxidation of 6-membered α-silylamines

The electrochemical cyanation of N-benzyl-substituted cyclic six-membered alpha-silylamines including tetrahydroquinoline and piperidine derivatives was studied. The results of these investigations demonstrate that alpha-silylamines are valuable precursors for the preparation of the corresponding alpha-cyanoamines. The TMS group a to the N atom not only governs the chemoselectivity of the iminium formation through a preferential desilylation reaction under the experimental conditions (i.e., amine cation radical desilylation versus deprotonation), it also lowers the oxidation potential of tertiary amines compared to their non-TMS counterparts. Both the stereoselectivity and regioselectivity of the cyanide addition were investigated with 3-methylpiperidine as the model compound. The formation of a single cis diastereoisomer in which the 2-cyano group is axial and the 5-methyl group is equatorial, indicates that the addition of the cyanide anion onto the iminium that the addition of the cyanide anion onto the iminium species is under stereoelectronic control. In addition, the redox reaction involving the intermediate nitrogen-centered cation radical and the cyanide anions played no role, because the alpha-silyl radical has the cyanide anions played no role, because the alpha-silyl radical has such a short lifetime.