Diastereoselective α-alkoxylation of lactamide N-alkyl groups via intramolecular formation of oxonium ions as the key intermediate

Abstract

Stereoselective introduction of an alkoxy group to the amine unit of lactamide derivatives, under electrochemical oxidation conditions, was investigated based upon the assumption that a cyclic oxonium ion can be formed between the alkoxy substituent on the chiral center and a carbocation generated at the α-position of N-alkyl substituents. With N-monosubstituted lactamides, diastereoselectivity in the N-α-alkoxylated product was not observed. With N,N-disubstituted lactamides, however, the selectivity appeared though in low ratios (≈2.2). Requisite factors that govern the stereoselectivity, i.e. nucleophilicity of both internal and external nucleophiles and substitution on amine units, were also examined.