alpha-cyanation of N-protected cyclic amines was achieved using a direct electrochemical method. Unsubstituted N-protected cyclic amines were easily cyanated at the alpha-position using an undivided cell in high yields; moreover, alpha-cyanation of alpha'-substituted pyrrolidine and alpha'-,beta'- or gamma-substituted piperidines smoothly proceeded in high yield and with high to excellent diastereoselectivity. alpha-Substituted N-cyano-pyrrolidines and -piperidines were also cyanated at the more substituted position (the alpha-position) using a divided cell with high yield and high regioselectivity.

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α'-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α -disubstituted cyclic amines.

No abstract

Electrochemical oxidation of 2-substituted 1-benzyloxycarbonyl- 1,2,3,4-tetrahydropyridines under aqueous conditions using I- as a mediator preferentially afforded 6-substituted 1- benzyloxycarbonyl-2,3-dihydroxypiperidines with a stereochemistry of cis-relationship between the 3-OH and 6- substituent, while the direct electrochemical oxidation resulted in a trans-relationship of the products. Electrochemical method was compared with conventional oxidation such as hydroboration, oxidation by OsO4 and m- chloroperbenzoic acid, all of which predominantly gave products having trans-stereochemistry.

Pyridine derivatives R 0380High Regioselectivity in Electrochemical α-Methoxylation of N-Protected Cyclic Amines. -The reaction is significantly influenced by the protecting group. N-Acyl derivatives are completely transformed into α'-methoxylated compounds. In contrast, N-cyano derivatives cause predominantly α-methoxylation. The regioselectivity can be further improved by lowering the temperature. The products can be subjected to cyanation and allylation to afford 2,2-disubstituted derivatives. Pyrrolidine (X) can be easily converted into pharmaceutically important spiro compounds. -(LIBENDI, S. S.; DEMIZU, Y.; MATSUMURA, Y.; ONOMURA*, O.; Tetrahedron 64 (2008) 18, 3935-3942; Grad. Sch. Biomed. Sci., Nagasaki Univ., Nagasaki 852, Japan; Eng.) -S. Adam 41-145